Imaging of Diseases of the Chest, 5Th Edition

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Imaging of

Diseases of the Chest F I F T H

E D I T I O N

David M Hansell MD FRCP FRCR Professor of Thoracic Imaging Department of Radiology Royal Brompton Hospital London UK

David A Lynch MD

Division of Radiology National Jewish Medical and Research Center Denver Colorado USA

H Page McAdams MD Associate Professor of Radiology Department of Radiology Duke University Medical Center Durham North Carolina USA Alexander A Bankier MD

Professor of Radiology Department of Radiology Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA

MOSBY an imprint of Elsevier Limited First Edition 1990 Second Edition 1995 Third Edition 2000 Fourth Edition 2005 Fifth Edition 2010 © 2010, Elsevier Limited. All rights reserved. The right of David M Hansell, David A Lynch, H Page McAdams and Alexander A Bankier to be identified as authors of this work has been asserted by them in accordance with the Copyright, Designs and Patents Act 1988. The Fleischner glossary appears courtesy of RSNA. © RSNA, 2008. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL and Remy J. Fleischner Society: Glossary of Terms for Thoracic Imaging. Radiology 2008; 246: 697–722. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Rights Department: phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; e-mail: [email protected]. You may also complete your request on-line via the Elsevier website at http://www.elsevier.com/ permissions. ISBN: 978-0-7234-3496-2 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Hansell, David M.   Imaging of diseases of the chest. – 5th ed. /   1. Chest–Imaging. 2. Chest–Diseases–Diagnosis.   I. Title II. Lynch, D. A. III. McAdams, H. Page. IV. Bankier, A. A.   617.5′40754-dc22   ISBN-13: 9780723434962 Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress Notice Medical knowledge is constantly changing. Standard safety precautions must be followed, but as new research and clinical experience broaden our knowledge, changes in treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current product information provided by the manufacturer of each drug to be admini­ stered to verify the recommended dose, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on experience and know­ ledge of the patient, to determine dosages and the best treatment for each individual patient. Neither the Publisher nor the author assume any liability for any injury and/or damage to persons or property arising from this publication. The Publisher Printed in China Last digit is the print number: 9  8  7  6  5  4  3  2  1

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PREFACE This book has been written to provide radiologists, physicians, and thoracic surgeons with a onevolume account of chest imaging, primarily in the adult patient. An attempt has been made to present an integrated review of the appearances encountered in diseases of the lung, pleura and mediastinum using the various imaging techniques available in a modern imaging department. From the preface to the first edition (1990) We have again tried to meet the objectives set by our predecessors all of whom have retired since the first edition was published twenty years ago. Alex Bankier has kindly agreed to join us in our endeavors to bring this new edition up-to-date. As with previous editions, the clinical and pathologic features of different diseases are provided in varying degrees of detail with more in-depth coverage given to rarer and less well understood conditions. There are new sections on emerging diseases, such as the surfactant deficiency disorders, but we are aware that current understanding of some of these conditions is incomplete and that inevitably their nomenclature and classification will change over the coming years. References have been refreshed but the temptation to discard references simply because they are old has been resisted. Classic descriptions, notably elucidations of fundamental radiographic signs, have been retained. Apart from paying tribute to the legacy of earlier writers, many of these meticulous studies have not been bettered. In line with current publishing aesthetics there are splashes of color that we hope will enliven the largely black and white contents. As an aide memoire, and to promote some degree of standardization in the descriptive language used in chest radiology, the latest version of the Fleischner Society’s glossary of terms for thoracic imaging is reproduced in its entirety. We hope that this new edition will be a useful resource and will provide more or less complete answers for anyone involved with thoracic imaging. David M Hansell David A Lynch H Page McAdams Alexander A Bankier 2010

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ACKNOWLEDGEMENTS Imaging of Diseases of the Chest is essentially the fruit of the labors of the current and previous authors but thanks are due to the contributors of subsections which have survived several editions. Our admiration and gratitude is freely given to our dedicatee Peter Armstrong who was the inspiration and driving force behind the first and subsequent editions of Imaging of Diseases of the Chest. We have tried our best to emulate his lucid writing style. As with previous editions our secretaries and helpers, Anne-Marie Henry, Tanya Mann, Nancy Williams, and Mary Anne Hansell have rendered superb assistance in many ways and in so doing have enabled us to meet what sometimes seemed to be impossible deadlines. We would also like to thank innumerable colleagues and visitors to our departments who have, without knowing it, refined our thinking and improved the presentation of our material. We are grateful to Herb Kressel, Editor of Radiology, for allowing us to reproduce the Fleischner Society’s glossary of terms for thoracic imaging. Our publishers, notably Joanne Scott, Jess Thompson, and Michael Houston of Elsevier Mosby, have steered us through the production process with their usual calm efficiency and have given us encouragement when it was needed. Our wives, Mary Anne, Anne, Emma and Francesca have once again shown great forbearance in allowing us to complete the task of updating Imaging of Diseases of the Chest. David M Hansell David A Lynch H Page McAdams Alexander A Bankier 2010

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DEDICATION To our families and Dedicated to Peter Armstrong, senior author of earlier editions

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CHAPTER

1

Technical considerations

CONVENTIONAL CHEST RADIOGRAPHY Technique Extraradiographic views Portable chest radiography Limitations of conventional chest radiography DIGITAL CHEST RADIOGRAPHY Radiographic data acquisition Image processing Image display Novel applications Computer-aided diagnosis COMPUTED TOMOGRAPHY General considerations Acquisition parameters Radiation dose Measurement of radiation dose Technical factors influencing dose delivery Dose reduction in chest CT Image reconstruction Multiplanar reconstructions Surface shaded display

The chest radiograph remains the prime imaging investigation in respiratory medicine and the basic technique has changed little over the past 100 years. Of all the cross-sectional imaging techniques, computed tomography (CT) has had the greatest impact on diagnosis of lung and mediastinal disease, while magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography have complementary roles in specific clinical situations. Refinements to CT scanning protocols, notably since the widespread introduction of multidetector CT (MDCT), have led to a substantial increase in the total number of performed CT examinations. Subsequent increases in radiation burden delivered by diagnostic imaging have become a focus of public interest, and the ongoing refinement of means to reduce patient irradiation has become a priority.

CONVENTIONAL CHEST RADIOGRAPHY Technique The standard views of the chest are the erect posteroanterior (PA) and lateral projections. The PA chest radiograph is taken at near total lung capacity (inspiratory film) with the patient positioned such that the medial ends of the clavicle are equidistant from the spinous process of the thoracic vertebra at that level. The scapulae are held as far to the side of the chest as possible by rotating the patient’s shoulders forward and placing the backs of the patient’s wrists on the iliac crests. A chest radiograph obtained near residual volume (expiratory film) can substantially change the appearance of the mediastinal contour, as well as giving the misleading impression of diffuse lung disease (Fig. 1.1). Even on a correctly exposed

Maximum intensity projections Minimum intensity projections Intravenous contrast enhancement Window settings Indications and protocols Special techniques HRCT for parenchymal disease CT technique for airways diseases POSITRON EMISSION TOMOGRAPHY General considerations Examination technique Indications RADIONUCLIDE IMAGING Perfusion scanning Ventilation scanning MAGNETIC RESONANCE IMAGING Technical considerations Applications

film, just under half the area of the lungs is obscured by overlying structures.1 Furthermore, many technical factors, notably the kilovoltage and film–screen combination used, determine how well lung detail is seen. The steep S-shaped dose–response curve of conventional radiographic film–screen combinations makes it impossible to obtain perfect exposure of the most radiolucent and radiodense parts of the chest in a single radiograph. Methods of overcoming this shortcoming have included the use of high-kilovoltage (above 120  kV) techniques,2 asymmetric screen–film combinations,3 ‘trough’ or more complex filters,4 and sophisticated scanning equalization radiographic units.5 High-kilovoltage radiographs have several advantages over lowkilovoltage films. Because the coefficients of X-ray absorption of bone and soft tissue approach each other at high kilovoltage, the bony structures no longer obscure the lungs to the same degree as on low-kilovoltage radiographs. Furthermore, the better penetration of the mediastinum with high-kilovoltage techniques allows greater detail of the large airways to be seen. At high kilovoltage, exposure times are shorter, so that structures within the lung tend to be sharper. Although scattered radiation is greater with high kilovoltage, the use of a grid causes a net reduction of imagedegrading scattered radiation compared with a low-kilovoltage, nongrid technique. With a high-kilovoltage technique, an air gap of 15 cm in depth is often used, instead of a grid to disperse the scattered radiation; this is as effective as a grid, and the radiation dose to the patient is similar for the two techniques.6 To counteract the unwanted magnification and penumbra effects of interposing an air gap, the focus–film (or anode-to-image) distance is increased to approximately 4  m. Although high-kilovoltage radiographs are preferable for routine examination of the lungs and mediastinum, low-kilovoltage radiographs provide excellent detail of unobscured

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Chapter 1 • Technical Considerations

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Fig. 1.1  A, Normal chest radiograph of an individual breathholding at full inspiration. B, By comparison, at full expiration the mediastinum appears abnormally widened and there is the appearance of a diffuse increase in lung density.

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Fig. 1.2  Lateral decubitus view. A, Erect frontal chest radiograph shows blunting of the left costophrenic angle (arrow), potentially caused by pleural effusion. B, Lateral decubitus view confirms pleural effusion by showing that some of the pleural fluid gravitates along the left lateral chest wall (arrows). lung because of the better contrast between lung vessels and surrounding aerated lung. Moreover, calcified lesions, such as pleural plaques, and small pulmonary nodules,7 are particularly well demonstrated on low-kilovoltage films.

Extraradiographic views The frontal and lateral projections suffice for most clinical indications. Other radiographic views are becoming much less frequently requested because of the ready availability of CT. Nevertheless, an additional view may occasionally solve a particular clinical problem quickly and in a cost-effective manner. The lateral decubitus view is not, as its name implies, a lateral view. It is a frontal view taken with a horizontal beam, with the patient

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lying on his or her side. Its main purpose is to demonstrate the mobility of fluid in the pleural space. If a pleural effusion is not loculated, it gravitates to the dependent part of the pleural cavity (Fig. 1.2). If the patient lies on his or her side, the fluid layers between the chest wall and the lung edge. Because the ribs, unlike the diaphragm, are always identifiable, comparison of a standard frontal view with a lateral decubitus view is a reliable way of recognizing unloculated pleural fluid. A lateral shoot through radiograph may be used to advantage to show a small anterior pneumothorax in recumbent patients in intensive care.8 The lordotic view is now rarely used, but is included here for completeness. It is performed by angling the X-ray beam 15° cranial either by positioning the patient upright and angling the beam up or by leaving the beam horizontal and leaning the patient backward. The lung apices are thereby better penetrated, and are

Conventional Chest Radiography

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Fig. 1.3  Use of the lordotic view. A, Selective view of the apex shows a small opacity projected over the anterior end of the left first rib. B, Lordotic view confirms that the opacity is intrapulmonary, rather than part of the calcified costochondral cartilage.

free from the superimposed clavicle and first rib. The lordotic view may be useful for distinguishing a focal pulmonary opacity from incidental calcification of the costochondral junctions (Fig. 1.3). With the exception of identifying rib fractures and confirming the presence of a rib lesion, oblique views of the thorax are rarely required.

Portable chest radiography Portable or mobile chest radiography has the obvious advantage that the examination can be performed without moving the patient to the radiology suite. In many centers, the proportion of portable to departmental chest radiographs has increased over time. However, portable radiography has a number of disadvantages. The shorter focus–film distance results in undesirable magnification. High-kilovoltage techniques cannot be used because portable machines are unable to deliver the high kilovoltage and because accurately aligning the X-ray beam with a grid is difficult. Furthermore, the maximum milliamperage is severely limited, necessitating long exposure times with the risk of significant blurring of the image. Portable lateral radiographs with conventional film radiography are even less likely to be successful because of the long exposure times. Radiation exposure of nearby patients and staff is a further caveat. Positioning of bed-bound patients is difficult, and the resulting radiographs often show half-upright or rotated subjects. Even in the so-called erect position with the patient sitting up, the chest is rarely as vertical as it is in a standing patient. More important, the patient is unable to take a deep breath when propped up in bed. Many patients cannot be moved to the radio­ logy department and the improved quality of digital portable radiographs, notably flat panel detectors, represents a substantial improvement.

Limitations of conventional chest radiography The chest constitutes a large part of the body and an image of the chest needs to encompass at least 40  cm. This large field-of-view imposes constraints on the image receptor, because the receptor must provide consistent and uniform response over the entire field.

This field-of-view also increases the contribution of scattered radiation that can decrease image quality.9 The wide latitude of X-ray transmission through the thorax imposes a limit on the visualization of subtle abnormalities. For a typical X-ray beam used in chest radiography, regional variations in transmission through the thorax can range over two orders of magnitude.9 Ideally, an imaging system should have enough latitude to capture and effectively display the diagnostically meaningful part of the X-ray transmission. Coverage of such wide latitude, however, can limit depiction of subtle low-contrast lesions. Maintaining wide latitude while preserving the visibility of low-contrast features is thus a particular challenge.9,10 The combination of high X-ray photon energy, a thick body part, and a large field-of-view results in a substantial amount of scattered radiation. This can account for 95% of the detected X-ray flux in the mediastinum and up to 70% in the lung in radiographs acquired without a grid.11 Scattered radiation degrades contrast and increases image noise. The contribution of scattered radiation to image noise is not correctable.9 Conventional chest radiography involves the projection of a three-dimensional structure onto a two-dimensional image. Anatomic structures can therefore overlie each other, sometimes referred to as anatomic noise.9 Anatomic noise can reduce the detectability of lesions. The projection of ribs is of particular concern for detection of lung nodules, because the ribs overlie about 75% of the area of the lungs. Moreover, a substantial portion of the lungs is projected over the heart and parts of the diaphragm.9 The influence of anatomic noise on the detectability of lung nodules has been extensively studied several decades ago.12,13 More recently, Samei et al.14 demonstrated that anatomic noise is far more important than quantum noise in limiting the detectability of lung nodules. Perceptual and cognitive processes are of particular importance in chest radiography because of the complexity of the tasks and the confounding effect of technical and anatomic parameters.9 Perceptual errors can occur at both the visual and the cognitive level. Incompleteness of the search task may contribute to about 55% of missed lesions. These errors occur when the observer fails to look at the location of the lesion12,15 or when he or she does not fix their eyes on this territory for a dwell time of at least 0.3 second.16 Cognitive errors account for 45% of missed lesions and can occur when the fixation time on a potential abnormality exceeds the above limit but the reader fails to call the nodule pathologic.12

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Chapter 1 • Technical Considerations

DIGITAL CHEST RADIOGRAPHY Radiographic data acquisition Digital chest radiography is expected to completely replace analog technology in the near future. There are several compelling reasons for the transition from analog to digital techniques. The decoupling of acquisition and display functions of the acquisition device in digital radiography makes it possible to optimize either of those functions independently. The availability of image data in electronic form makes it possible to post-process the image for optimal display and to display the images on viewing workstations. The electronic format also makes it possible to safely archive the data using less space and fewer resources for storage. Digital images can be distributed widely and copies can be made available to multiple viewers. Finally, acquisition and processing units can be integrated into one system.9 Computed radiography (CR) was one of the first commercial digital imaging techniques17 and is still the most common technology for acquiring digital chest radiographs. The technology is based on photostimulable properties of barium halide phosphors. After exposure of a phosphor cassette to X-rays, the cassette is transported to a computed radiography reader device that scans the cassette with a laser beam. The laser releases the energy locally deposited by X-rays on the screen and causes the screen to fluoresce. The released light is used to form the image after it is collected by a light guide, digitized, and associated with the geometric location of the laser beam at the time of stimulation.9 While CR has the largest number of installations in digital radiography, its disadvantages in terms of image quality per unit dose and suboptimal workflow have encouraged the development of flat-panel detector technology. Flat-panel detectors are made of thin layers of amorphous silicon thin-film transistors (TFTs) deposited on a piece of glass. The TFT layer is coupled with an X-ray absorptive layer. Indirect flat-panel detectors use a phosphor screen to convert the X-rays to light photons, which are detected by the photodiode array associated with the TFT layer and converted to a charge deposited in the capacitors associated with each TFT.18,19 Direct flat-panel detectors use a photoconductor layer that converts the X-ray energy directly to charge, which is subsequently directed to the collecting TFTcapacitor array through the application of a strong electric field.20 After exposure, the charge on the capacitors is collected line by line and pixel by pixel by using the associated grid and data lines, thereby forming the raw digital image data for processing and display.9 Charge-coupled device (CCD) and complementary metal-oxide semiconductor (CMOS) cameras use an alternative technology for the acquisition of digital chest radiographs. With these detectors, the X-ray energy is first converted to light within a phosphor layer. The light is then directed to a single or a multitude of CCD or CMOS cameras that detect the light image and form the radiograph.21 An important component of these detectors is the coupling of the phosphor layer and the camera. Because most CCD and CMOS sensors are limited in size, it is necessary to minify the original light image generated on the phosphor screen so that it can be captured by the camera. This is accomplished by using either a fiberoptic coupler or a lens system. In either case there is a loss of efficiency, since only a small fraction of the light photons generated by the phosphor are detected by the camera(s). Consequently, the inherent efficiency of these detectors is limited.9 A recent development takes advantage of slot-scan technology to reduce the amount of scattered radiation on digital chest radiographs.22 The detector consists of a cesium iodide scintillation layer fiberoptically coupled to a series of linear CCDs. With no antiscatter grid in place, a narrow-fan X-ray beam synchronized with the movement of the detector assembly scans the chest. Image data are continuously read from the CCDs as the patient is scanned by using

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the time-integration method.23,24 After scanning, the image data are processed for optimal display. The advantage of this technology is superior scatter rejection with little effect on the detection of primary radiation. This can enhance the effective detection efficiency of the imaging system.9

Image processing Prior to display, digital images commonly undergo a series of processing steps. These processes can be divided into preprocessing and post-processing. Image preprocessing consists of correction and scaling. The first type of processing includes image corrections for detector defects or nonuniformities often present on raw digital images. The second type of preprocessing includes reduction of the full dynamic range of the raw image to the range of perception capability of the human eye.9 Post-processing is commonly divided into three types: • Gray-scale processing involves the conversion of detector signal values to display values. The display intensities of an image are changed by means of either a look-up table or windowing and leveling. • Edge enhancement aims to enhance fine details within the image by manipulating the high-frequency content of the radiograph, using a variant of the unsharp masking technique in which a blurred version of the image is formed, and a fraction of the resultant image is subtracted from the original image. • Multifrequency processing involves an even more flexible manipulation of multiple portions of the frequency spectrum. The image is initially decomposed into multiple frequency components, and the component images are then weighted and added back together. If the processing parameters are set optimally, the resultant image can compress the overall dynamic range of the image while at the same time enhance local contrast.9

Image display Soft-copy display is the optimal way of viewing digital chest radiography. The conventional method of displaying digital radiographs has been on cathode-ray tubes, which still dominate the market.25 Active-matrix liquid-crystal displays are rapidly replacing cathode-ray tubes.26–28 The advantages of liquid-crystal displays include improved resolution, reduced weight, smaller form factor, reduced reflection, improved bit depth, and improved luminance range, although disadvantages in terms of limited viewing angle and structured noise may be practically relevant.29,30 Another recent trend has been the increased acceptance of color monitors, some of which have shown acceptable technical performance for radiographic applications.31 The use of color monitors offers the advantage of being able to accommodate applications other than image viewing on the same device, with workflow and multitasking advantages.9 Color monitors also make it possible to take advantage of color for viewing multidimensional chest images on the same display. It is thus expected that color liquid-crystal displays will gradually replace monochrome monitors in clinical practice.9

Novel applications Digital chest radiography lends itself the development of new techniques to improve the detection of subtle lesions. These techniques include algorithms typically coupled with methodological innovations that use imaging physics to improve lesion conspicuity. Three notable novel applications are dual-energy imaging, temporal subtraction imaging, and digital tomosynthesis. All of these techniques are implemented by using a conventional chest radiography system coupled with a digital imaging receptor.9 Whether they will be widely adopted remains to be seen.

Digital Chest Radiography Dual-energy subtraction imaging is used to generate images of two independent tissue types, most commonly bone and soft tissue. The dual-energy technique distinguishes bone from soft tissue by using the known energy dependence of X-ray attenuation in soft tissue and in bone. By means of photoelectric absorption, calcified structures attenuate more heavily than soft tissue structures. Therefore, the contrast of calcium diminishes with increases in beam energy more than does the contrast between soft tissues. Thus, the image obtained at the lower energy will show a larger fraction of contrast from bone than from soft tissue. These two images may be combined such that the soft tissue and calcium components can be isolated. Typically, an image containing only calcified structures and an image containing only soft tissue structures are generated.

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Dual-energy subtraction radiography can improve lung nodule conspicuity by eliminating overlying anatomic noise from the bones (Figs 1.4 and 1.5). The technique can also be used to better demonstrate calcium in lesions.32–36 Temporal subtraction techniques aim to selectively enhance areas of interval change by subtracting the patient’s previous radiograph from the current radiograph.37 The quality of the difference image strongly depends on the success of two-dimensional registration and warping of the two radiographs, so that the variations in patient positioning can be minimized.38,39 The difference image is uniformly gray in areas of no change, whereas areas that stand out on the gray background indicate interval change (Fig. 1.6). Several studies40–42 have shown that temporal subtraction improves the

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Fig. 1.4  Dual-energy subtraction. A, Frontal chest radiograph shows possible left lung nodule (arrow). B, Bone subtracted image shows no evidence of nodule. C, Soft tissue subtracted image shows nodular opacity consistent with callus from healing rib fracture (yellow arrow). Note motion-induced artifact along the left heart border (red arrow). (Courtesy of H Page McAdams, Durham, NC, USA.)

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Chapter 1 • Technical Considerations

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Fig. 1.5  Dual-energy subtraction. A, Frontal chest radiograph shows right lung nodule (arrow) in a TB-exposed patient. B, Soft tissue subtracted image confirms that the nodule is calcified (arrow) and thus likely to represent granuloma. (Courtesy of H Page McAdams, Durham, NC, USA.)

visual perception of subtle abnormalities. A 20% reduction in the average reading time with temporal subtraction was also noted.9,43 Digital tomosynthesis can produce an unlimited number of section images at arbitrary depths from a single set of acquisition images.44 During motion of the X-ray tube, a series of projection radiographs are acquired, and the anatomy at different depths in the patient changes orientation in the projection images owing to parallax. These projection images are then shifted and added to bring into focus objects in a predefined plane. By varying the amount of shift, different plane depths can be reconstructed (Fig. 1.7). Objects outside of the focus plane are blurred. Currently, chest imaging with tomosynthesis is one of the areas receiving the most clinical and research interest.9,44

Reports about the accuracy of this technique vary substantially, and direct comparison between studies is not possible. All proposed approaches, however, struggle to maintain a clinically acceptable sensitivity level while reducing the number of falsepositive detections. Several studies nevertheless show that CAD can assist radiologists in improving their overall detection rate for lung nodules.48–51 Moreover, laboratory observer studies have shown promising results for applications designed to determine the malignant potential of pulmonary nodules.40,52 CAD techniques have also been applied to the detection and differentiation of interstitial lung disorders, with varying success.53–56 Finally, less fully explored CAD applications include the detection of cardiomegaly,57 pneumothorax,58,59 interval changes,60 and tuberculosis.61

Computer-aided diagnosis Computer-aided detection (CAD) and computer-aided diagnosis (CADx) systems rely on combinations of image-processing, patternrecognition, and artificial intelligence techniques. The application of CAD and CADx analysis in chest radiography has followed a traditional model of first detecting and then characterizing potential abnormalities.45,46 Image-processing algorithms are applied to identify regions of interest that appear suspicious according to predefined clinical expectations. Image feature analysis then seeks to determine the morphologic and textural characteristics of candidate regions. Finally, feature-based decision analysis provides a definitive assessment of candidate regions.9 The majority of CAD applications involve the detection of pulmonary nodules.47 Typically, morphology-based image processing is applied to detect nodular-appearing structures, while more detailed morphologic and texture analyses eliminate falsepositive nodule-like structures (Figs 1.8–1.10). The final decision is made by applying a linear classifier, a neural network, or a rulebase algorithm that merges the image findings into a final binary decision.9

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COMPUTED TOMOGRAPHY CT relies on the same physical principles as conventional radiography: the absorption of X-rays by tissues with constituents of differing atomic number. With multiple projections and computed calculations of radiographic density, differences in X-ray absorption can be displayed in a cross-sectional format. The basic components of a CT machine are an X-ray tube and an array of X-ray detectors opposite the tube. The signal from the X-ray detectors is reconstructed by a computer. The speed with which a CT scanner acquires a single sectional image depends on the time the anode takes to rotate around the patient. Volumetric (formerly referred to as spiral or helical) CT has altered the clinical CT imaging protocols developed in the 1990s.62 The basic principle of volumetric CT entails moving the patient into the CT gantry at a constant rate while data are continuously acquired, often within a single breathhold.63,64 The resulting ‘corkscrew’ of information is then reconstructed, most frequently as a contiguous set of axial images, similar to conventional single-slice

Computed Tomography

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Fig. 1.6  Temporal subtraction. A, Current radiograph shows subtle lingular opacity. B, The opacity was not present on the previous radiograph. C, Temporal subtraction image emphasizes the new opacity. (Courtesy of Heber MacMahon, Chicago, IL, USA.) CT sections. To achieve this, interpolation is needed because direct reconstruction results in nonorthogonal images of nonuniform thickness. Continuous volume CT scanning has several advantages: (1) rapid scan acquisition in one or two breathholds; (2) reduced volume of contrast needed for optimal opacification of vessels, for example the pulmonary arteries; (3) no misregistration between sections obtained in one acquisition, thus improving detection of small structures; and (4) potential for multiplanar or three-dimensional reconstructions.65–68

The advent of MDCT technology has revolutionized the diagnostic potential of CT by definitively transforming CT from an axial cross-sectional technique into a true three-dimensional technique that allows for arbitrary selection of section planes and volumetric display of the acquired data (Figs 1.11–1.13). Most importantly, MDCT permits shorter acquisition times and greater anatomic coverage.69 The potentially huge number of images routinely generated by clinical protocols, however, represent a challenge in terms of efficient interpretation and the logistics of image storage

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Chapter 1 • Technical Considerations

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Fig. 1.7  Digital tomosynthesis. A, Tomosynthesis image shows left lung nodule overlying a rib (arrow). B, Presence of subpleural nodule is confirmed by CT (arrow). (Courtesy of H Page McAdams, Durham, NC, USA.)

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Fig. 1.8  Computer-aided detection (CAD). A, Frontal chest radiograph shows three lung nodules, all of which are successfully detected by CAD shown in B. While two of the nodules are easy to see (yellow circles), one nodule (red circle) is more difficult to detect due to an overlying rib.

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Computed Tomography

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Fig. 1.9  Computer-aided detection (CAD). A, Frontal chest radiograph shows three lung nodules detected by CAD shown in B. The three nodules (yellow circles) are relatively easy to see. CAD also highlights one false-positive nodule (red circle), in fact corresponding to calcified costochondral cartilage of the first rib.

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Fig. 1.10  Computer-aided detection (CAD). A, Chest radiograph shows a lung nodule correctly identified by CAD shown in B (yellow circle), despite being directly adjacent to the lower margin of the first rib.

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Chapter 1 • Technical Considerations

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Fig. 1.11  Aortic aneurysm. A, Chest radiograph shows enlarged and tortuous aorta (arrows) in a patient with chest pain. B, Surface shaded reconstructions of emergency CT show large aneurysm of the aortic arch and the descending aorta (arrow).

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Fig. 1.12  A, Surface shaded reconstruction of the aorta shows asymptomatic variant of left common carotid artery arising from the brachiocephalic trunk (arrow). B, Normal origin of the vessel (arrow) is shown in a different patient.

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Computed Tomography

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Fig. 1.13  Aortic dissection. A, Curved array reformat shows intima (arrows) in a patient with aortic dissection. B, Surface shaded display in the same patient shows the intima membrane in its entire length (arrows).

and transmission. The technique of volumetric MDCT scanning of the thorax continues to be refined, and the full potential of acquiring and analyzing data in a truly volumetric manner is still to be realized.70,71

General considerations The CT image is composed of a matrix of picture elements (pixels). There are a fixed number of pixels within the picture matrix so that the size of each pixel varies according to the diameter of the circle to be scanned. The smaller the scan circle size, the smaller the area represented by a pixel and the higher the spatial resolution of the final image. In practical terms the field-of-view size should be adjusted to the size of area of interest, usually the thoracic diameter of the patient. Depending on the field-of-view size, the pixel size varies between 0.3 mm and 1 mm across. By selecting a specific area of interest, the operator can achieve an even increased spatial resolution for that region (targeted reconstruction of the raw data). In a clinical context, targeted reconstruction is used only when the finest morphologic detail is required. Sometimes there is a marked difference in the appearance of CT images acquired on different scanners. This is the result of differences in the software reconstruction algorithms that ‘smooth’ the image to a greater or lesser extent by averaging the density of neighboring pixels. Smoothing is used to reduce the conspicuity of image noise and improve contrast, but it has the drawback of reducing the definition of fine structures. The lung is a highcontrast environment, and smoothing here is less necessary than in other parts of the body. Higher spatial resolution algorithms, which make image noise more conspicuous, are generally more desirable, and it has been recommended that they should be applied to both standard thick sections and high-resolution CT (HRCT).72,73

Acquisition parameters Although a single CT section appears as a two-dimensional image, it has a third dimension of depth. Thus each pixel has a volume, and the three-dimensional element is referred to as a voxel. The average radiographic density of tissue within each voxel is calculated, and the final CT image consists of a representation of the numerous voxels in the section. The single attenuation value of a voxel represents the average of the attenuation values of all the structures within the voxel. The thicker the section, the greater the chance of different structures being included within the voxel and so the greater the averaging that occurs. The most obvious way to reduce this ‘partial volume’ or ‘volume averaging’ effect is to use thinner sections (Fig. 1.14). The entire thorax is now usually examined with contiguous sections. MDCT has brought section thickness down to a range of 0.75–2.5  mm. Additional dedicated thin sections are sometimes required to clarify partial volume effects or to study areas of anatomy that are oriented obliquely to the plane of scanning. Specific examples of the use of thin sections to display differential densities, which would otherwise be lost because of the partial volume effect, is the demonstration of small foci of fat within a hamartoma, or of calcifications within a pulmonary nodule. Thin sections of 1–1.5 mm thickness are also used to study the fine morphologic detail of the lung parenchyma (HRCT). Apart from the evaluation of diffuse lung disease, when sampling of a few parts of the lung (traditionally with sections taken at 10–30  mm intervals) is adequate, contiguous section scanning is necessary to allow accurate interpretation in most clinical situations. For volumetric CT scanning, consideration needs to be given to the speed of table travel, volume of interest, duration of scanning (usually within one breathhold), and reconstruction interval. Pitch is defined as the distance traveled by the table per gantry revolution

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Chapter 1 • Technical Considerations

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Fig. 1.14  Influence of section thickness. A, Chest radiograph shows reticular opacities in the right lung base (arrows). B, Transverse 8 mm thick CT section confirms abnormalities but does not allow detailed morphologic analysis.

divided by the section thickness (collimation). A potential source of confusion arises from the two definitions of pitch used in the context of MDCT: it should be remembered that either the section thickness or the total z-axis length of the detector array may be used. The latter definition is most frequently quoted in the literature.69 It should also be emphasized that definitions of acquisition parameters and protocols for MDCT may, because of unique detector array designs, be specific to a given manufacturer. A typical pitch of 1 describes the situation, assuming a gantry revolution in 1 second, in which the table travels at 10 mm/s with 10 mm collimation. During a 10-second breathhold, 10 cm in longitudinal axis will be covered. If the travel speed is increased to 20  mm/s, the pitch will be increased to 2 and twice the distance will be covered. In general, the useful range of pitch for thoracic work is between 1 and 2.74 When detection of small pulmonary nodules is the primary aim, a pitch of less than 1.5 is recommended.75 Conversely, when radiation dose is a major consideration, scanning at a higher pitch reduces the radiation burden to the patient.76–78 Although the spatial resolution of volumetric CT in the transaxial plane is nearly comparable to conventional CT, there is some image degradation because of broadening of the slice profile, inherent in all volumetric CT; this results in additional partial volume averaging in the longitudinal (z-) axis.79 The faster the table feed, the broader the slice profile will be. The use of a 180° interpolation algorithm produces a slice profile close to the nominal section thickness, although this causes a slight increase in image noise.69,80 Greatly increased z-axis resolution is a feature of MDCT with isotropic imaging (identical resolution in all planes) being the ultimate

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goal being pursued by manufacturers.69 This goal has now been reached. A higher pitch and increased section thickness together enable greater coverage at the expense of increased partial volume effects. However, this can be partly ameliorated by reducing the reconstruction increment, thus producing a larger number of overlapping images.81,82 The ability to retrospectively reconstruct axial images with considerable overlap by choosing a small reconstruction interval is a major advantage of MDCT.69

Radiation dose The introduction of MDCT has increased the clinical indications for CT, and thus increased the total number of CT examinations performed and the anatomic coverage of CT examinations. This has led to a substantial overall increase of radiation dose delivered by diagnostic CT. The issue of increased delivery of radiation is compounded by the fact that younger and thus more radiation-sensitive patients are being scanned with increasing frequency (e.g. for suspected pulmonary embolism), as well as the trend to recruit (per definition) asymptomatic individuals for CT screening studies. The resulting public concerns have stimulated the publication of guidelines for maximum dose levels administered by CT. The European Guideline for Quality in Computed Tomography EUR 16262 defines such dose levels for all organs. Guidelines specifically designed for CT of the chest have been published by the Fleischner Society.83 This brief discussion of the topic will focus on the factors that determine

Computed Tomography Table 1.1 Parameters frequently used in the calculation of dose Parameter

Abbreviation

Comment

CT Dose Index

CTDI

Integral under the dose profile of a CT section

Weighted CT Dose Index

CTDIw

Average radiation dose across the diameter of a phantom

Volume CT Dose Index

CTDIvol

Corresponds to CTDIw corrected by the pitch factor. Indicates average local dose to a patient within the scan volume. Allows for direct comparison of the radiation dose from different scan parameter settings, even between scanners

Dose–length product

DLP

Effective dose

E

Corresponds to CTDIvol multiplied by the length of the scan. At identical CTDIvol, scans covering longer anatomical areas will deliver more dose than those covering shorter areas Computed parameter used to estimate the radiation risk to the patient. Does not provide precise radiation risk for the individual patient, but is rather an index of risk for a particular scanner and examination

C

Fig. 1.14  Continued C, Transverse 1 mm thick CT section shows generalized ground-glass opacities, traction bronchiectasis (arrow) and a subtle microcystic pattern (circle) in a patient later diagnosed with nonspecific interstitial pneumonia.

dose delivery in clinical chest CT, and on the relationship between radiation dose and image quality.

Measurement of radiation dose Several methods are currently in use to quantify the delivery of ionizing radiation to the patient. The fact that there are several methods attests to the complexity of the issue, and may also present an obstacle to the understanding of radiation dose assessment. The most important parameters for radiation dose assessment, together with brief explanations, are summarized in Table 1.1.

Box 1.1  Technical factors influencing dose delivery from CT • • • • • • •

Scanner geometry Focal spot tracking Geometric efficiency Detector efficiency Electronic noise Noise filtering Tube current modulation

Focal spot tracking Slightly widening the pre-patient collimation (‘over-beaming’) was used in early MDCT units to compensate for subtle alterations of the focal spot size during the tube rotation. Over-beaming has now been replaced by focal-spot-tracking that adjusts the collimator setting and is a standard feature in latest generation scanners.

Technical factors influencing dose delivery

Geometric efficiency

Dose delivery and image quality are substantially influenced by scanner technology. The following parameters are of practical importance (Box 1.1).

The geometric efficiency of a detector is determined by the amount of radiation that reaches the detector relative to the amount of radiation that leaves the patient. Geometric efficiency depends on the width, spatial orientation, absorption of the septa separating detectors, and width of the dose profile in the z-direction.

Scanner geometry To decrease the centrifugal forces of the tube during rotation, manufacturers tend to move the tube closer to the isocenter of the scanner. At fixed mAs settings, this substantially increases patient dose, notably the skin entry dose.

Detector efficiency Solid-state detectors have an up to 30% higher quantum yield than older xenon gas detectors. Using solid-state detectors, the same

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Chapter 1 • Technical Considerations image noise can thus be achieved with considerably lower dose than using xenon detectors.

Electronic noise The amplifiers of the detector system are responsible for a constant level of noise. The smaller the detector signal, the more important the electronic noise becomes. This is particularly noticeable in obese patients, low-dose protocols, and in thin-section imaging.

Noise filtering Noise filtering works on the raw data and averages the signal from neighboring detector elements if the signal from these detectors drops too low. Averaging influences only a small portion of the projectional data.

Tube current modulation Tube current modulation is based on the substantial differences in diameter between the AP and the lateral diameters of the body cross-section as well as widely differing attenuations inherent in thoracic imaging. As attenuation follows an exponential function, small changes in diameter will cause major differences in attenuation. Different technical solutions are currently applied to modulate the mA according to the maximum and minimum patient size as determined by the scanogram. In chest CT, dose modulation allows for dose reductions of up to 30% without loss of image quality, depending on the habitus of the individual patient.

Dose reduction in chest CT The concept of reduced tube current for chest CT was introduced in 1990 by Naidich et  al.,84 who demonstrated acceptable image quality for assessment of the lung parenchyma with tube current settings of 20 mAs compared with a standard setting of 250 mAs. While the resulting images were adequate for assessing lung parenchyma, they showed increased noise and resulting marked degradation of image quality. The authors noted that such low-dose techniques were most suited for the assessment of children and potentially for screening patients at high risk for lung cancer. These recommendations have indeed been implemented and further studied in lung cancer screening programs,85–87 and low-dose protocols now feature in most lung cancer screening trials.88 Similar dose reduction strategies have been applied to HRCT of the lungs. No substantial differences in the depiction of lung parenchymal structures were seen between low-dose (40 mAs) and highdose (400  mAs) thin-section CT images.89 Ground-glass opacities, however, were difficult to assess on low-dose images because of increased image noise. Therefore, it has been recommended that 200 mAs should be used for initial thin-section CT and lower doses (i.e. 40–100 mAs) should be used for follow-up CT examinations.83 The relationship between radiation exposure and image quality on both mediastinal and lung windows has been evaluated on conventional 10  mm collimation chest CT images.90 Although the findings showed a consistent increase in image quality with higher radiation exposure, they did not show a remarkable difference in the detection of mediastinal or lung parenchymal abnormalities between 20  mAs and 400  mAs. The authors concluded that adequate image quality could be consistently obtained in average-sized patients by using tube currents of 100–200 mAs. The authors noted that to further evaluate the effect of reduced radiation dose on diagnostic accuracy in chest CT, comparison of complete chest CT studies at a variety of radiation exposures in a large number of patients is needed. They also acknowledged that such a study could not be performed in patients because of the unacceptable radiation dose that would result from multiple CT examinations at differing radiation exposures. Additionally, the variable effect of motion artifacts on repeated scanning make comparisons difficult.83

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A practical method for evaluating the effect of reduced radiation dose on image quality is computer simulation.91 The technique consists of obtaining a diagnostic CT with a standard dose and then modifying the raw scan data by adding Gaussian-distributed random noise to simulate the increased noise associated with reduced radiation exposure. The raw scan data are then reconstructed using the same field-of-view and reconstruction algorithm as the high-dose reference scan. In a validation trial, experienced chest radiologists were unable to distinguish simulated reduced dose CT images from real reduced dose CT images.91 Computer simulation of noise allows investigators to determine the effect of dose reduction on diagnostic accuracy without exposing patients to radiation unnecessarily. In addition, the simulated images are in exact registration with the original images, eliminating artifacts due to volume averaging or motion. In chest CT, this technique has been used to evaluate the effect of dose reduction in CT angiograms performed for suspected pulmonary embolism,77 and in expiratory CT examinations performed to detect air-trapping.92

Image reconstruction The recent proliferation of MDCT has led to an increase in the creation of images in planes or volumes other than the traditional transverse images (Fig. 1.15). What follows is a brief discussion of the reconstruction capabilities of modern CT scanners as applied to chest imaging. More detailed technical background information is provided in the specialized literature.93

Multiplanar reconstructions Quint et  al.94 evaluated CT images from lung transplant patients using 3  mm collimation, pitch of 1, and a 1.5  mm reconstruction interval and found axial images were 91% accurate in the detection of bronchial stenoses. By comparison, viewing the axial images with multiplanar reconstructions (sagittal and coronal) improved accuracy, marginally, to 94%. However, observers found it easier to identify mild stenoses on the multiplanar images, highlighting the difficulty of accurately assessing luminal caliber on sequential axial images. Multiplanar reconstructions also depict the lengths of stenotic segments more clearly due to the orientation of the section along the long axis of the airway.

Surface shaded display Improvements in computing power and speed have led to the replacement of shaded surface display renditions with threedimensional volume rendering. Volume rendering converts the volume of information acquired by MDCT into a simulated threedimensional form that surpasses the technique of surface shaded display,95 which is limited by threshold voxel selection. The volumerendered three-dimensional image is the computed sum of voxels along a ray projected through the dataset in a specific orientation, thus using all the MDCT data to form the final image (Fig. 1.16). The volume-rendering technique assigns a continuous range of values to a voxel, allowing the percentage of different tissue types to be reflected in the final image while maintaining three-dimensional spatial relationships. Remy-Jardin et al.67 compared overlapping axial CT images with volume-rendered bronchographic images for the detection of airway abnormalities and identification of lesion morphology. Findings on the volume-rendered images were concordant but added no complementary value to those on the transverse CT images in half of the cases. However, volumerendered images provided supplemental information in a third and could correct potential interpretative errors from viewing only transverse CT images in 5%. The most alluring technique to be applied to airway imaging is ‘virtual bronchoscopy’ (VB). These images are obtained using volume-rendering techniques that allow internal rendering of the tracheobronchial tree, producing an appearance similar to that seen

Computed Tomography

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Fig. 1.15  Surface shaded display. In a patient with recurrent pulmonary embolism, coronal CT images show tortuous and slightly enlarged bronchial arteries (arrows). Surface shaded display depicts the anatomical course of these arteries (purple) and allows an improved three-dimensional impression.

by a bronchoscopist. Adequate images can be obtained even with low (50 mA) tube currents.96 Studies using this technique have nevertheless revealed several limitations. Summers et al.97 used virtual bronchoscopy to assess 14 patients with a variety of airway abnormalities. They found that, overall, 90% of segmental bronchi that were measurable at CT could be measured at VB. However, of the total bronchi expected to be visible, only 82% could be evaluated at VB and only 76% of segmental bronchi were demonstrated compared with 91% and 85%, respectively, for multiplanar CT images. Axial CT and the ‘virtual’ images were of similar accuracy in estimating the maximal luminal diameter and cross-sectional area of the central airways. These authors used 3 mm sections, pitch of 2, a field-of-view of 26 cm or less and 1 mm reconstruction intervals. Virtual bronchoscopy demonstrates stenoses of the central airways (proved with fiberoptic bronchoscopy) in most cases,98,99 but, in one study,98 all the stenoses demonstrated by VB were also shown on

the transverse images. In addition, evaluation of the length of the stenoses and surrounding tissues required simultaneous display of multiplanar reformations. The use of airway stents for benign and malignant stenotic disease provides another potential, but limited, use for volumerendering techniques. As stents require frequent follow-up, MDCT of the airway offers an easier way to monitor cases until adjustment requires direct intervention.100 From experience so far it seems that, for many central airways diseases, MDCT does not have a greater sensitivity than conventional transaxial images, but it does confer advantage in describing spatial relationships of airway disease, particularly in communicating this information to clinicians.101 Another potential application of volume-rendering techniques is the curved planar reformation. A curved structure, such as an airway, can be electronically ‘starched’ into a straight structure and, thereby, made amenable to objective geometric quantification.102

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Chapter 1 • Technical Considerations

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Maximum intensity projections One of the early reported limitations of HRCT for the assessment of diffuse infiltrative lung disease was the perception that micro­ nodules were more reliably distinguished from blood vessels on standard collimation sections.103,104 The problem of making this distinction has probably been overstated in the past. However, with MDCT, it is possible to acquire volumetric data rapidly; the entire thorax can be imaged with a high-resolution technique in 17 seconds using a pitch of 6, 1.0  mm detectors, and a rotation time of 0.5 seconds;105 maximum intensity projection (MaxIP) images have been advocated as an additional tool in the evaluation of diffuse infiltrative lung diseases; the diagnostic benefit of MaxIP postprocessing for the detection of larger nodules, for example pulmonary metastases, is unequivocal.106 Remy-Jardin and colleagues107

16

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Fig. 1.16  A, Surface shaded display in a patient with right aortic arch. B, The heart has been removed from the image and the trachea (blue) added. C, The image has been rotated to create a lateral view.

compared conventional CT (1  mm and 8  mm collimation) with MaxIP images (sliding slabs of 3 mm, 5 mm, and 8 mm thickness generated from volumetric CT performed at the level of the region of interest) in patients with a suspicion of micronodular infiltration. MaxIP images showed micronodular disease involving less than 25% of the lung when conventional CT was inconclusive and better defined the profusion and distribution of micronodules when they were identified on conventional images. However, in patients with normal 1 mm and 8 mm images, sliding-thin-slab MaxIPs did not reveal additional lung abnormalities. Bhalla et  al.108 used MaxIP reconstruction in 20 patients with known diffuse lung disease and found two main advantages over thin-section CT: more precise identification of nodules and more accurate characterization of suspected nodule distribution (perivascular versus centrilobular). The technique is not widely used routinely in the context of diffuse lung

Computed Tomography disease, largely because in most cases of suspected interstitial lung disease a standard HRCT technique will have been used (Fig. 1.17).

Intravenous contrast enhancement

Minimum intensity projections

Because of the high contrast on CT between vessels and surrounding air in the lung, as well as between vessels and surrounding fat within the mediastinum, intravenous contrast enhancement is needed only for specific clinical indications. The exact timing of the injection of contrast medium depends most on the time the scanner takes to acquire data. With MDCT scanning, the circulation time of the patient becomes an important factor. However, general guidance about the time of arrival of contrast medium from the antecubital vein to various structures is possible.110 In normal individuals arrival time in the superior vena cava is 4 seconds, pulmonary arteries 7 seconds, ascending aorta 11 seconds, descending aorta 12 seconds, and inferior vena cava 16 seconds. With the advent of increasingly rapid scanners, however, these rules of thumb have become less reliable, and the risk persists that the rapid scanner will ‘overtake’ the inflow of contrast material, i.e. the scanner acquisi-

The contrast between normal and low-attenuation lung parenchyma in patients with constrictive obliterative bronchiolitis or emphysema may be subtle on inspiratory HRCT images and imageprocessing techniques such as minimum intensity projections (MinIPs) can improve the conspicuity of such regional density differences108,109 (Figs 1.17 and 1.18). In a study by Fotheringham et  al.,109 MinIP images showed good correlation with pulmonary function tests and had the lowest observer variation when compared with inspiratory and expiratory images. Window settings for the interpretation of MinIP slabs have not been standardized; window widths of 350–500 Hounsfield Units (HU) and a window level of −750 to −900  HU have been used in the few studies that have investigated this technique.

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B

Fig. 1.17  Minimum and maximum intensity projections. A, Coronal CT image in a patient with emphysema (arrows). The extent of emphysematous destruction becomes more apparent on the minimum intensity projection B, while the maximum intensity projection C, allows better visualization of the vascular structures.

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Chapter 1 • Technical Considerations

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tion will be faster than the patient’s circulation time of the injected contrast. To overcome this potential problem, techniques have been developed that allow individually tailored contrast injection protocols based on the injection of a test bolus.111,112 An easier and more practical solution employs ‘bolus-tracking’ software. By placing a region-of-interest in a vessel supplying an area of diagnostic interest, the radiologist can determine the level of vascular enhancement that must be achieved before the CT unit will start to scan. The use of the ‘bolus-tracking’ technology can be further improved by a saline flush injected immediately after the contrast material at an identical flow rate. Because the spontaneous flow in the injected vein is indeed often slower than the injection rate, the inflow of contrast material slows down once the injection is completed. This can lead to a premature decrease in contrast in either the pulmonary artery or the aorta. A saline flush overcomes this by ‘pushing’ the contrast material forwards, thereby stabilizing the vascular contrast plateau. Finally, the saline flush technique helps to overcome potential inter-patient variability of vascular enhancement caused by differences in cardiac output. Ideally, the time from contrast arrival to peak enhancement in either the pulmonary artery or the aorta should last as long as the injection time, but it tends to end earlier in patients with a high cardiac output and last longer in patients with a low cardiac output.

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B

Fig. 1.18  Minimum intensity projection. A, Coronal CT image in a patient with emphysema shows minimal emphysematous lesions in the right upper lobe (yellow arrows). B, Lesions are better seen on minimum intensity projection. As further sections are added to the projection C, visualization of emphysema is further improved and lesions in the left hemithorax previously not clearly seen (red arrows) become apparent. The contrast medium rapidly diffuses out of the vascular space into the extravascular space, so that opacification of the vasculature following a bolus injection quickly declines and nonvascular structures such as lymph nodes steadily increase in density over time. Because of these dynamics, there is a time at which a solid structure may have exactly the same density as an adjacent vessel. The timing and duration of the contrast medium infusion must therefore be taken into account when interpreting a contrast-enhanced CT examination. Rapid scanning protocols with automated injectors improve contrast enhancement of vascular structures at the expense of enhancement of solid lesions because of the rapidity of scanning. With MDCT scanning it is possible to achieve good opacification of all the thoracic vascular structures with a total dose of less than 100  mL contrast (iodine content of 150–350  mg/mL) at a rate of about 2 mL/s.113 Some CT scanners generate streak artifact centered on the highdensity bolus of contrast, usually as it passes through the superior vena cava. This beam-hardening artifact may be troublesome if it obscures detail in the adjacent pulmonary arteries, particularly in patients being investigated for pulmonary embolism. One solution is to reduce the iodine concentration and use a high volume of dilute contrast at an increased flow rate.114 A reduction in both the streak artifact and amount of contrast needed can also be achieved

Computed Tomography Table 1.2 Parameters that will influence planning of the contrast injection protocol* Parameter

Abbreviation

Unit

Contrast volume Flow rate Scan delay Saline flush Position of region-of-interest for bolus triggering Concentration of contrast material Osmolarity of contrast material Viscosity

V F D N X

mL mL/s s mL –

C

mg iodine/ mL

O V

osmol/L kP

*V, F, and D are key parameters for planning of injection protocols, while C, O, and V are specific for a given manufacturer’s product. N and X can be determined by the radiologist.

by the above described saline flush.115 One protocol recommended for general thoracic CT scanning is 100  mL of 150  mg iodine/mL (300  mg iodine/mL diluted 50 : 50) injected at a rate of 2.5  mL/s after a 25-second delay.116 However, Loubeyre et al.117 have shown that satisfactory enhancement of the hilar vasculature can be obtained with a more modest amount of contrast (60 mL of 250 mg iodine/mL at 3 mL/s). For the examination of inflammatory lesions, it may be necessary to delay scanning by at least 30 seconds to allow contrast to diffuse into the extravascular space. Each injection protocol must be carefully tailored to the clinical problem, and no single ideal protocol exists. Moreover, the injection protocol will depend on a variety of parameters (summarized in Table 1.2). These parameters should ideally be documented on the images, as their combination and interaction can have important implications for image interpretation. Consideration must be given to the consequences of accidental extravasation of contrast medium: the flow rate used, within reason, is not predictive of the likelihood of extravasation.118 Nevertheless large volumes (more than 100 mL) introduced into the soft tissues of the forearm by an automated power injector may be associated with severe complications, including compartment syndrome and tissue necrosis; in the event of extravasation of a large volume of contrast, urgent surgical advice should be sought.119

Window settings (Box 1.2) The average density of each voxel is measured in Hounsfield Units; these units have been arbitrarily chosen so that zero is water density and −1000 is air density. The range of Hounsfield Units encountered in the thorax is wider than in any other part of the body, ranging from aerated lung (approximately −800 HU) to ribs (+700 HU). The operator uses two variables to select the range of densities to be viewed: window width and window center or level. The window width determines the number of Hounsfield Units to be displayed. Any densities greater than the upper limit of the window width are displayed as white, and any below the limit of the window are displayed as black. Between these two limits the densities are displayed in shades of gray. The median density of the window chosen is the center or level, and this center can be moved higher or lower at will, thus moving the window up or down through the range. The narrower the window width, the greater the contrast discrimination within the window. No single window setting can depict this wide range of densities on a single image. For this reason, thoracic work requires at least two sets of images, usually to demonstrate the lung parenchyma and the soft tissues of the mediastinum. Furthermore, it may be necessary for the operator to adjust the window settings to improve the demon-

Box 1.2  Window settings* • Soft tissues, mediastinum, chest wall: center 40 HU, width 300–500 HU • Lung parenchyma: center −600 HU, width 1500 HU • HRCT: center −500 to −800 HU, width 1300–1600 HU *Approximate recommendations – optimized settings will depend on scanner type, display modus, viewing conditions, and personal preference.

stration of a particular abnormality. Standard window widths and centers for thoracic CT vary between institutions, but some generalizations can be made: for the soft tissues of the mediastinum and chest wall a window width of 300–500 HU and a center of +40 HU are appropriate. For the lungs a wide window of approximately 1500 HU or more at a center of approximately −600 HU is usually satisfactory.120 For skeletal structures the widest possible window setting at a center of 30  HU is best. Allowing observers to adjust window settings, compared with images at fixed window settings, does not appear to improve performance in terms of identifying fine lung structures or detecting diffuse lung disease.121 The window settings have a profound influence on the visibility and apparent size of normal and abnormal structures. The most accurate representation of an object is achieved if the value of the window level is halfway between the density of the structure to be measured and the density of the surrounding tissue.122,123 For example, the diameter of a pulmonary nodule, measured on soft tissue settings appropriate for the mediastinum, will be grossly underestimated.124 When inappropriate window settings are used, smaller structures are proportionately more affected than larger structures. The optimal window settings for the post-processed data, for example MinIP images or three-dimensional volumerendered images, cannot be prescribed and are largely a matter of observer preference. In the context of HRCT, the window settings have a substantial effect on both the appearance of the lungs and the apparent dimensions of, for example, the thickness of bronchial walls.125,126 Alterations of the window settings may sometimes make detection of parenchymal abnormalities impossible in cases of a subtle increase or decrease in attenuation of the lung parenchyma. Although no absolute window settings can be given because of machine variation and individual preferences, uniformity of window settings from patient to patient will aid consistent interpretation of the lung images. In general, a window level of −500 to −800 HU and a width of between 1300 HU and 1600 HU is usually satisfactory. Modifying the window settings for particular tasks is often desirable; for example, when searching for pleuro-parenchymal abnormalities in asbestos-exposed individuals, a wider window of up to 2000 may be useful. Conversely, a narrower window width of approximately 600  HU may usefully emphasize the subtle density differences encountered in patients with emphysema or small airways disease.

Indications and protocols There is no single protocol which can be recommended for every clinical eventuality without being prohibitively excessive in terms of radiation dose, time taken, or data acquired. The optimal protocol is one that makes a difference to patient outcome by providing clinically relevant information at the lowest possible radiation dose. There is a constant tension between the desire for a comprehensive examination and the unnecessary exposure of the patient to ionizing radiation.83 Moreover, the advent of MDCT has led to a multiplication of specialized protocols that are described in the current reference literature.127 Despite its obvious benefits, MDCT encourages indiscriminate ‘catch-all’ protocols, a problem that is exacerbated by unfocused clinical requests. Attempts to contain, and, wherever possible, reduce, the radiation dose of a CT examination

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Chapter 1 • Technical Considerations Box 1.3  Clinical indications for CT of the chest

Abnormal chest radiograph • • • • •

Further evaluation of mediastinal or pleural mass Lung cancer staging Characterization of diffuse lung disease Assessment of thoracic aortic dissection Workup of patients with severe emphysema considered for lung volume reduction surgery

Normal chest radiograph • Identification of cryptic diffuse lung disease (HRCT) • Detection of pulmonary metastases from known extrathoracic malignancy • Demonstration of pulmonary embolism • Investigation of hemoptysis (e.g. endobronchial lesion or subtle bronchiectasis) • Investigation of patients with biochemical or endocrinologic evidence of disease that might be related to a small intrathoracic tumor (e.g. thymoma or bronchial carcinoid)

should be a constant consideration when planning examination protocols.83,128 Indications for CT can be broadly divided into situations in which CT elucidates an abnormality shown on a plain chest radiograph and those in which the chest radiograph appears normal but cryptic disease is suspected. These indications are summarized in Box 1.3.

Special techniques HRCT for parenchymal disease Three factors significantly improve the spatial resolution of CT images of the lung: narrow scan collimation, a high spatial resolution reconstruction algorithm, and a small field-of-view.129 Other aspects that affect the final image, over which the user has no control, include the X-ray focal spot size, the geometry and array of detectors, and the frequency of data sampling and scan acquisition time.130 Narrow collimation of the X-ray beam reduces volume averaging within the section and so increases spatial resolution compared with standard collimation.131,132 Collimation of between 0.5 mm and 1.5  mm can be used.132–134 Reducing the section thickness below 0.5  mm will yield no further improvement in spatial resolution. Differences between 1.5  mm and 3  mm collimation are probably insignificant for the detection of small structures,132 but subtle regional variations in the density of the lung parenchyma are more easily appreciated with thinner collimation images. Narrow section collimation has a marked effect on the appearance of the lungs, notably the vessels and bronchi: the branching vascular pattern seen particularly in the mid-zones on standard 10 mm sections has a more nodular appearance on narrow sections, because shorter segments of the obliquely running vessels are included in the plane of section. Another effect of narrow collimation is an apparent increase in the diameter of vessels that course parallel with the plane of section. This is due to the elimination of the partial volume effect of air surrounding the rounded surface of the vessel encountered in standard width sections. Interspacing between each section is usually 1 cm or 2 cm. Studies have shown that wider intervals do not have a deleterious effect on diagnosis in a wide spectrum of interstitial lung diseases;135,136 a more minimalist approach might entail images being obtained at the level of the arch, tracheal carina, and 2 cm above the right hemi­ diaphragm. In practice, however, even experienced radiologists need the reassurance that confirmatory or ancillary features are not being missed by keeping the interspace distance to 3 cm or less. The application of MDCT to HRCT has implications in terms of image quality, novel image presentation (reformats), and radiation

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burden. Schoepf et al.137 acquired scans with 1 mm collimation with MDCT and reconstructed 5  mm contiguous and 1.25  mm HRCT sections from the original data. Image quality of the 5 mm ‘fused’ images was significantly superior to the 5  mm single detector CT images, and the 1.25 mm images were of similar quality to conventional HRCT (1 mm sections acquired at 10 mm increments) using single detector CT. For the patient in whom such a comprehensive examination is required, this may be an appropriate and useful technique. However, for the majority of patients being evaluated for suspected interstitial lung disease, conventional HRCT remains an adequate examination. A standard HRCT examination yields approximately 30 transverse images; a protocol involving the reconstruction of 5  mm contiguous sections and 1.25  mm sections at 10  mm increments (from a MDCT volumetric set acquired with 1  mm detector collimation) would produce approximately 90 images. In an attempt to reduce the number of images that need to be interrogated using this protocol, Remy Jardin et al.138 evaluated the diagnostic accuracy of coronal thin sections as an alternative to transaxial HRCT scans. Reconstructions in the coronal plane result in fewer images and diagnostic accuracy was similar to that of conventional transaxial HRCT.138 Not surprisingly, coronal reformations produced from ‘isotropic’ data obtained from volumetric 0.5 mm collimation acquisitions can be of high quality.133 The issue of dose with respect to MDCT is an important one. Volumetric imaging of the chest with 1 mm collimation entails an effective dose of between 6.4 mSv and 7.8 mSv even when a relatively low dose (70 mAs) is used. This is considerably higher than the effective dose of a conventional (1.5  mm at 10  mm intervals) HRCT which is approximately 0.98 mSv (140 kVp and 175 mAs). It has been estimated that the mean skin radiation dose delivered with HRCT using 1.5 mm sections at 20 mm intervals is 6% of that of conventional 10  mm contiguous scanning protocols.139 A study of the differences of the more meaningful parameter of effective radiation dose has shown that a standard HRCT protocol (1.5 mm sections at 10  mm intervals) delivers an approximately 6.5 times less effective dose than a conventional single detector CT (10 mm contiguous sections); the effective dose from a standard HRCT (0.98  mSv) is about 12 times that of a PA and lateral chest radiograph.140 It is possible to reduce the milliamperage of an HRCT examination by up to 10-fold and still obtain comparably diagnostic images.89 Such low-dose techniques result in a considerable increase in image noise and subtle parenchymal abnormalities, such as early emphysema or ground-glass opacification, may be obscured. Lee et al.135 compared relatively low- (80 mAs) and high-dose (340 mAs) HRCTs and found no difference in diagnostic accuracy in 50 patients with chronic diffuse infiltrative lung disease. Taking these options into account, one approach might be to use 80–90 mAs for the initial HRCT and to use the lower dose (40–50 mAs) for subsequent follow-up. The type and characteristics of the software algorithm used to reconstruct the CT image is as crucial as the chosen section width. In conventional body CT, images are reconstructed with a medium or relatively low spatial frequency algorithm designed to smooth the image and so reduce the visibility of image noise and improve contrast resolution. In HRCT, a high spatial frequency algorithm is used which takes advantage of the inherently high-contrast environment of the lung. The high spatial frequency algorithm (also known as the edge-enhancing, sharp, or formerly ‘bone’ algorithm) reduces image smoothing and makes structures visibly sharper, but simultaneously increases image noise.129,132 More than any other manipulation in HRCT technique, it is the combination of section thickness and the unique reconstruction algorithm of a particular CT scanner that determine the final appearance of the lung image; occasionally, the variations in appearances of images obtained on different CT scanners make comparisons difficult. Several artifacts can be consistently identified on HRCT images, but they do not usually degrade the diagnostic content. The most frequently encountered artifact is a streaking appearance due to patient motion. Even with millisecond scan acquisition, movement of the lung due to cardiac motion sometimes causes degradation of

Computed Tomography image quality of the adjacent lingula and, to a lesser extent, the middle lobe. Pulsation artifacts take the form of high-density linear streaks, usually arising from the heart border. Another manifestation of movement is a ‘star’ pattern centered on pulmonary vessels,141 and these vessels may show a superficial resemblance to bronchiectatic airways in cross-section.142 Sometimes the oblique fissure is seen as two fine lines in parallel.129 This artifact is due to linear structures being scanned in different positions after the gantry has turned through 180°. Although the double fissure artifact is unlikely to cause misdiagnosis, ‘double vessels’ may occasionally resemble bronchiectasis.142 Some scanners are capable of prospective ECGgating. Schoepf et al.143 subjectively assessed image quality and the presence of motion artifacts on ECG-gated versus non-ECG-gated HRCT sections. While ECG-gating clearly reduces artifacts adjacent to the heart, it has not yet been determined whether ECG-gating actually improves the diagnostic accuracy of HRCT. The larger the patient, the more conspicuous the image noise because of increased X-ray absorption by the patient. Image noise or quantum mottle takes the form of granular streaks arising from high-attenuation structures and is particularly evident in the posterior lung adjacent to the vertebral column. Image noise rarely interferes with diagnosis and, while the problem can be counteracted by increasing the kVp and mA settings, the reduction in noise is, except in the largest patients, barely perceptible. The phenomenon of aliasing results in a fine streak-like pattern radiating from sharp, high-contrast interfaces. The severity of the aliasing artifact is related to the geometry of the CT scanner and particularly the spacing of the detectors and scan collimation; unlike quantum mottle, aliasing is independent of the radiation dose. Aliasing and quantum mottle are most prominent in the paravertebral regions and often parallel the pleural surface.129 These artifacts are exaggerated by the non-smoothing high spatial resolution reconstruction algorithm but do not mimic normal anatomic structures and are rarely severe enough to obscure important detail in the lung parenchyma. When early interstitial fibrosis is suspected, HRCT scans are often performed in the prone position to prevent potential confusion with the increased opacification seen in the dependent posterobasal segments of many normal individuals scanned in the supine position (Fig. 1.19). The increased density seen in the posterior dependent lung in the supine position will disappear in normal individuals

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when the scan is repeated at the same anatomic level with the patient in the prone position. The physiologic mechanism of the increased opacification in the dependent lung in normal individuals is not fully understood and has been ascribed to gravity-dependent perfusion144 and/or relative atelectasis of the dependent lung.145 Prone sections are mandatory in patients with suspected diffuse lung disease and a normal or near-normal chest radiograph, but are unnecessary if the chest radiograph is clearly abnormal.146

CT technique for airways diseases Bronchiectasis The simplest and most widely used technique for patients with suspected bronchiectasis remains narrow collimation (l.0–1.5 mm) sections every 10  mm from lung apex to base with images reconstructed using a high spatial frequency reconstruction algorithm.147,148 Potential advantages of volumetric CT include improved detection of subtle bronchiectasis missed between HRCT sections, reduced motion artifact, various post-processing reformats (Figs 1.20 and 1.21), and seamless reconstruction of oblique airways.149,150 In a study which compared HRCT with volumetric CT for the detection of bronchiectasis, Lucidarme et al.151 showed that the detection rate of bronchiectasis with volumetric CT (3 mm collimation, pitch of 1.6; 24-second breathhold) was superior to a standard HRCT protocol (1.5  mm collimation at 10  mm intervals). Furthermore, interobserver agreement was superior with the volumetric CT protocol. However, the radiation burden to patients using the volumetric CT protocol was 3.4 times greater than that of conventional HRCT. In another study that compared HRCT with volumetric CT (5 mm collimation, pitch of 1; 40-second breathhold), volumetric CT with 5 mm section thickness was not as sensitive as HRCT.152 More recently, Remy-Jardin et al.153 have shown that in terms of diagnostic accuracy there are no important differences between 3 mm and 1 mm reconstructed images acquired with MDCT; the implication being that there could be a modest radiation saving if 3 mm sections were acquired from 4 × 2.5  mm detectors (rather than 4 × 1  mm detectors necessary for 1 mm reformations). Yi et al.154 investigated the effects of radiation dose on volumetric acquisitions and concluded that a tube current of 70  mA or higher provided image quality comparable to standard (170 mA) HRCT images; neverthe-

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Fig. 1.19  Supine and prone sections. In this patient with suspected diffuse lung disease, A, the supine CT image shows bilateral subpleural opacities (arrows). B, The opacities disappear with the patient in the prone position (arrows).

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less, the radiation dose of the volumetric protocol is considerably higher (five times) than that of HRCT. Whether or not such volumetric acquisitions are necessary for the majority of patients with suspected bronchiectasis remains open, although the ability of these datasets to provide coronal and other reformats appears to have diagnostic advantages155 (Fig. 1.21). Variations in window settings have a marked effect on the apparent thickness of bronchial walls.125 Narrow window settings will also alter the apparent bronchial diameter, unless the measurement of the diameter is made between points in the ‘center’ of the bronchial walls.156 In the context of suspected bronchiectasis, a window level of between −400 and −950 HU and a width of between 1000 HU and 1600 HU have been widely recommended.157–159 A more liberal recommendation about the appropriate window level for the accurate evaluation of bronchial wall thickness has been reported in a study by Bankier et al.125 that correlated thin-section CT with planimetric measurements of inflation-fixed lungs. For the accurate estimation of bronchial wall thickness the authors suggest that, irrespective of the chosen window width, the window center should be between −250  HU and −700  HU, and that within this range bronchial wall thickness is not appreciably affected. Window

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Fig. 1.20  Various forms of post processing: minimum intensity projection A, shows subtle bilateral bronchiectasis (arrows). Curved array reformats B, C, also show mucus plug (red arrow) and extension of the pathology to the pleural surface (yellow arrow). width should be greater than 1000 HU (a narrower window width will cause a spurious appearance of bronchial wall thickening); the suggested window width range lies between 1000  HU and 1400 HU.125

Small airways disease HRCT is currently regarded as the imaging method of choice for the detection of small airways disease. Standard HRCT technique is satisfactory for demonstrating constrictive obliterative bronchiolitis and diffuse panbronchiolitis. The former requires attention to appropriate contrast resolution to demonstrate sometimes subtle regional attenuation differences caused by air-trapping (mosaic attenuation pattern). The latter is more dependent on adequate spatial resolution to depict the small branching structures that characterize exudative panbronchiolitis (tree-in-bud pattern).160 In this context a suggested HRCT protocol is 1–1.5  mm collimation sections every 10  mm from apices to costophrenic angles with the patient breathholding at full inspiration.161 Care should be exercised when choosing window widths as minor differences in lung attenuation may be visible only when narrow window widths are used.162

Computed Tomography

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Fig. 1.21  A, B, Curved array reformat shows large broncholith (arrow) on A, bone and B, lung window setting.

Expiratory CT The necessity of the routine acquisition of expiratory CT sections is controversial. The regional inhomogeneity of the lung density is accentuated and small or subtle areas of air-trapping may be revealed on CT performed at end-expiration163,164 (Figs 1.22 and 1.23). Expiratory CT may sometimes be helpful in differentiating between the three main causes of a mosaic pattern (infiltrative lung disease, small airways disease, and occlusive pulmonary vascular disease) which may be problematic on inspiratory CT.120,165 A fewer number of expiratory than inspiratory HRCT sections (e.g. at 30 mm or 40 mm intervals) are usually obtained. Although expiratory images almost invariably make regional inhomogeneity more conspicuous, and occasionally reveal the presence of air-trapping not suspected on the inspiratory images, in most patients with clinically significant small airways disease the mosaic pattern is already apparent on inspiratory images. Dynamic studies in which sections are obtained in rapid succession at a given level during forced expiration may improve the conspicuity and apparent extent of air-trapping.166 A study that compared low-dose (40 mA) dynamic expiratory CT with the more conventional end-expiratory CT technique demonstrated that the density changes were significantly greater with the dynamic technique.167 In specific circumstances, for example the surveillance of lung transplant patients when the early detection of small airways dysfunction may be important, dynamic expiratory lowdose thin-section CT may be indicated. Each dynamic sequence (acquired at the level of the arch, carina, and 2 cm above the right hemidiaphragm) is obtained as a 6-second cine-acquisition with no table movement.

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Fig. 1.22  Transverse CT section through the left lower lobe shows A, normal lung attenuation in inspiration and B, relatively uniform increased attenuation in expiration in a healthy individual.

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Fig. 1.23  Air-trapping in a patient after right lung transplantation for emphysema. A, Inspiratory CT section shows comparable attenuation of both lungs. B, Expiratory section shows attenuation increase in the transplanted right lung with small paracardiac areas of air-trapping (arrows) and absence of attenuation increase in the emphysematous left lung.

Central airways disease The near-isotropic volume datasets that can be acquired with MDCT and advances in volume-rendering software have made routine three-dimensional airway imaging possible. Transverse imaging currently remains widely used for the evaluation of the central airways despite several limitations including underestimation of subtle bronchial stenoses, difficulties in depicting complex three-dimensional relationships of the airways, and inadequate representation of the airways that lie obliquely to the axial plane.67,101 Two-dimensional multiplanar and three-dimensional reconstruction images aid assessment of a wide variety of airway diseases.168–170

CT angiography The most common indication for CT angiography (CTA) is suspected acute pulmonary embolism. However, CTA is useful in a series of other suspected abnormalities involving the thoracic vasculature, such as malformations, chronic thromboembolic disease, aortic disease, or venous pathologies. Precontrast acquisitions are required only in patients with suspected bleeding and mural hematoma in aortic dissection. In suspected pulmonary embolism, the scan range will usually cover the range between the aortic arch and the diaphragm. To minimize potential motion artifacts introduced by breathing, the preferred scan direction is caudocranial. In MDCT, scan length is not a limiting factor (Fig. 1.24). Preferably, the scan should be acquired at full inspiration. If this is not possible because the patient is dyspneic, quiet breathing must be achieved. With 8- and 16-row MDCT units, anatomic coverage of the entire thorax can be achieved in 4–5 seconds. The contrast injection protocol will depend on individual patient factors and on the scanner technology used. In general, a bolus-tracking technique should be used, and moderate volumes of contrast material injected with a relatively high flow (3–5  mL/s) and chased by a saline flush are preferable. Tube current settings provide a relatively large flexibility for dose reduction,77 which is of particular interest in pregnant women suspected of having acute pulmonary embolism. The precise role of CTA in the workup of pulmonary embolism has been recently summarized in an interdisciplinary recommendation171 and is considered more fully in Chapter 7.

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POSITRON EMISSION TOMOGRAPHY General considerations Imaging with positron emission tomography (PET) is playing an increasingly important role in the assessment of malignant disease. PET imaging with the fluorine-18 (18F)-labeled glucose analog 18 F-fluorodeoxyglucose (FDG) is a recent addition to the imaging of cancer. FDG uptake is not specific for cancer, but the increased transport of glucose into malignant cells and upregulation of enzymatic activity resulting in increased tracer uptake is well established. Tracer uptake can be objectively quantified by measuring the standard uptake value (SUV). PET can thereby provide an accurate separation of normal physiologic uptake from pathologic uptake, however, with limited spatial resolution. There have therefore been many attempts to ‘fuse’ the functional imaging information obtained with PET and the morphologic information obtained with CT. The recent availability of combined PET-CT scanners is the result of a hardware-oriented approach to image fusion. Current manufacturer designs combine a CT and a PET scanner within a single system. Although the scanner externally appears as a single device, there is little internal mechanical integration.172

Examination technique The typical PET-CT examination starts after injection of 10–15 mCi of FDG and an uptake period of 1 hour, after which the patient is positioned on the scanner bed. First, a topogram is acquired. The anatomic range to be scanned is then defined on the topogram. To minimize the mismatch between CT and PET, a respiration protocol must be used. A reasonably good match is generally obtained if the CT images are acquired with partial expiration, and the PET images with shallow breathing. After completion of the CT acquisition, the bed is advanced into the PET field-of-view, and PET data are acquired over the same range as the CT scan. CT and PET image reconstruction occurs in parallel, allowing the calculation of attenuation-correction factors to be performed during the PET acquisition. Attenuation correction is necessary because attenuation values are energy dependent, i.e. the correction factors derived from a CT

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Fig. 1.24  Pulmonary embolism. A, Transverse CT section shows bilateral emboli (arrows). B, C, Coronal and D, E, sagittal curved array reformats show entire craniocaudal extent of individual emboli (arrows).

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Chapter 1 • Technical Considerations scan at mean photon energy of 70 keV must be scaled to the PET energy of 511 keV. Once the acquisition for the first bed position is completed, reconstruction of PET images starts. Within several minutes of the conclusion of the PET acquisition, attenuation-corrected and reconstructed PET images that are automatically coregistered with the CT image by accounting for the axial shift between the CT and the PET fields-of-view are available for analysis.172

Indications By far the most frequent indication for PET-CT in the context of chest imaging is the assessment for suspected or proven malignancy. Promising results for PET-CT have been reported for pulmonary nodules larger than 1 cm, for hilar and mediastinal lymph node staging, for staging and restaging of nonsmall cell lung cancer, and for the detection of distant metastases173–178 (Figs 1.25–1.27). Less favorable results have been reported for the assessment of smaller pulmonary nodules, for ground-glass nodules, for carcinoid tumors, and for small cell lung cancer.179,180 The diagnostic performance of PET-CT for each of these entities are discussed in detail in the relevant chapters.

RADIONUCLIDE IMAGING Diagnostic scintigraphy involves simultaneous imaging of the distributions of pulmonary blood-flow and alveolar ventilation. The  Q scan). The combined study is called a ventilation/perfusion ( V main clinical indication for this technique in the evaluation of pulmonary embolism.

Perfusion scanning Perfusion lung imaging is performed by the intravenous injection of a radiotracer which is trapped in the lung on first pass. There are two available classes of tracer: first, microparticles of human protein labeled with technetium-99m (Tc-99m) which microembolize in the lung vascular bed; and, secondly, radioactive inert gases, which, because of their low aqueous solubility, rapidly enter alveolar gas following intravenous injection. The latter approach is essentially obsolete for clinical purposes. The clinical diagnosis of pulmonary embolism is routinely based on particles of macroaggregated human serum albumin (MAA), which have a size range of 10–

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Fig. 1.25  PET-CT. A, CT shows large right lung mass (arrows). B, PET image shows strong FDG uptake of the lesion (arrows). C, Fused image confirms that lesion and uptake overly (yellow arrows), while the adjacent parenchymal consolidation shows no uptake (red arrow).

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100  µm (radiolabeled microspheres of albumin, which had a narrower size range, are no longer commercially available). In patients with an anatomic right-to-left shunt, there is a theoretical risk of systemic tissue ischemia as a result of vessel occlusion from the larger shunted particles, so some departments use a smaller dose for such patients. The risk, however, is negligible. Similarly, in patients with pulmonary hypertension, there is a risk of further occlusion of an already depleted vascular bed. However, the number of capillaries (normally 300 million) far outnumbers the number of particles administered (200 000–500 000), thus even in pulmonary vascular disease, there is a wide safety margin. The particles are biodegradable and have a biological half-time in the lung of 6–8 hours. The Tc-99m elutes from the particles faster than this, and by 24 hours most of the remaining activity is visible in the gut and kidneys. Provided the particles mix completely in the blood prior to microembolization, the distribution of radioactivity is proportional to the distribution of pulmonary blood flow. Not only is photon emission itself a random event but so is the distribution of the particles. A distribution of radioactivity which is proportional to the distribution of pulmonary blood flow is, therefore, also dependent on the injection of a sufficiently large number of particles as well as the amount of injected radioactivity.181 A Tc-99m lung perfusion scan gives an effective radiation dose equivalent of 1 mSv/100 MBq. The usual imaging dose is 75 MBq (about 2 mCi). Since the material is ‘sticky’, injection through long

Fig. 1.26  PET-CT. A, CT shows right lung mass (arrows). B, PET image shows strong FDG uptake by the mass (arrows). C, Fused image confirms that mass and uptake coincide (arrows). lines should be avoided because a considerable fraction is likely to be retained in the line.

Ventilation scanning Two classes of agents are available for ventilation imaging: the radioactive inert gases xenon-133 and krypton-81m (Xe-133, Kr-81m) and the radiolabeled aerosols. Worldwide, Xe-133 used to be the most widely used inert gas for imaging ventilation but now aerosols are more frequently used. The ultra-short-lived inert gas Kr-81m is probably the optimal agent for ventilation imaging, but it is expensive and has limited availability. Because of the very short half-life of Kr-81m, the technique of Kr-81m imaging is fundamentally different from that of xenon imaging. With continuing inhalation the distribution of radioactivity increasingly reflects regional lung volume. Eventually the wash-in rate becomes equal to the wash-out rate, and during this equilibrium phase the image portrays regional lung volume. After inhalation of the gas has been terminated, the equilibrium phase is followed by the wash-out phase. Regions of air-trapping within the lung then become evident as areas of increased count rate. Although this dynamic approach may give useful information, particularly regarding air-trapping, it can be conveniently performed in only one projection, usually the posterior. This is a disadvantage because,

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owing to its low energy, Xe-133 (80  keV) has to be administered before Tc-99m (140 keV), that is, at a time when the location of any perfusion abnormalities, if present, is not known. Nevertheless, wash-in images acquired during limited periods of inhalation can be obtained in multiple projections, such as posterior and both posterior obliques.182 Alternatively, the lungs can be imaged in these three projections during the wash-out phase, since regional hypoventilation is often associated with air-trapping. Xe-127 has a higher energy (203  keV) than Tc-99m and so can be administered following perfusion imaging in a selected projection, namely the one that best shows any perfusion defects, a significant advantage over Xe-133.183 Because of its very short half-life of 13 seconds, Kr-81m (190 keV) effectively gives information only for wash-in studies since it has decayed by the time it is exhaled. Perfusion and ventilation images can be obtained without moving the patient, either in sequence by alternating the photopeak settings on the gamma camera between Kr-81m and Tc-99m, or simultaneously by dual photon acquisition. For the sequential approach, switching off the Kr-81m supply prevents ‘down-scatter’ of the higher energy photons of Kr-81m into the Tc-99m window. Residual gas clears rapidly, mainly by radioactive decay, and does not therefore interfere with the Tc-99m images. Kr-81m is ideal for physiologic studies of the lung because of its ability to provide moment-to-moment (real-time) information on

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Fig. 1.27  PET-CT in a patient with suspicious lung nodules. A, CT image shows the larger (yellow arrow) and a smaller (red arrow) nodule in the right lung. B, PET shows single focus of uptake (arrow). C, Fused image confirms that uptake corresponds to the smaller nodule (arrow). regional ventilation and its facility for single photon emission computed tomography (SPECT).184 Aerosol ventilation imaging has become popular largely because of technical improvements in the delivery systems and reduction in aerosol particle size. Aerosols are generally made from Tc-99m diethylenetriaminepentaacetic acid (DTPA). Their administration requires the cooperation of the patient, who is asked to breathe through a mouthpiece, with a nose clip in place, for several minutes. Most users give the aerosol before the administration of Tc-99m MAA, although some give it after, only to patients with abnormal perfusion scans. If they are given in close succession, some form of image subtraction may be necessary. As with Kr-81m, images can be acquired in multiple projections, facilitating comparison with the subsequent perfusion images. Aerosols also provide the opportunity of SPECT. The regional distribution of radioactivity depicts regional ventilation at the instant of inhalation. In this respect, aerosol imaging is similar to Tc-99m MAA perfusion imaging in that distribution of agent is ‘frozen’ at the time of administration, unlike Kr-81m, which continuously and dynamically depicts the distribution of ventilation as the patient breathes the gas. The value of Kr-81m imaging is underlined by patients shown to have an unstable distribution of ventilation (that is, different from one projection to another). This may give rise to diagnostic confusion but is difficult to detect with any other ventilation agent. Unstable

Magnetic Resonance Imaging ventilation has been noted particularly in children,185 and may be posture dependent. It calls into question the reliability of injecting MAA in the supine position and administering the ventilation agent in the erect position. Another type of aerosol available is an agent called ‘Technegas’. This is an ultrafine dispersion of Tc-99m-labeled carbon particles generated by combustion of pertechnetate, a 2500 °C in a graphite crucible in an atmosphere of 100% argon within the Technegas ‘generator’. This agent gives ventilation images with a quality approaching that of Kr-81m,186 but is otherwise similar to the conventional DTPA aerosols in terms of convenience and availability. Once the generator has been purchased ventilation imaging can be performed immediately on request. Deposition of particles in the central airways, which is a problem with conventional DTPA aerosols, particularly in patients with chronic lung disease, appears to be less with the Technegas because of the smaller particle size. As with Tc-99m DTPA aerosols, subtraction of the Technegas signal from the subsequent perfusion signal (or vice versa) may be necessary. Movement of gas in the peripheral airways, beyond the sixteenth generation of airway,187 is by molecular diffusion, at a rate that is inversely proportional to molecular size. Aerosol particles are therefore presumably deposited mainly in distal airways rather than alveoli, although their kinetic energy may carry them into the alveolar sac. The Tc-99m DTPA complex then dissolves in alveolar fluid and diffuses across the distal airway epithelium into the pulmonary circulation. This rate of transfer of hydrophilic solutes such as Tc-99m DTPA across the alveolar–capillary barrier is proportional to the permeability of the barrier and inversely proportional to solute molecular size and to alveolar fluid volume.188 In normal nonsmoking subjects, Tc-99m DTPA clears from the lung by this route with a half-time of about 80 minutes. By the time the perfusion scans are performed, activity is often already visible in the renal collecting systems, especially in smokers. It is also usually visible, as swallowed activity, in the upper gastrointestinal tract as a result of particle deposition in the mouth, and in the proximal airways of patients with chronic lung disease as a result of particle deposition caused by turbulent airflow. Larger particles tend to be deposited in the proximal airways, and it is toward the elimination of this problem that the technical improvements in aerosol production and delivery have largely been aimed.  Q lung scanA minimum of four views is recommended for V ning: anterior, posterior, and both posterior obliques. Occasionally, laterals and anterior obliques may also be useful. SPECT may have  Q lung scanning, particularly when ventilation imaging a rule in V is performed with Kr-81m184 or Technegas.189 If clinically relevant,  Q lung imaging should be performed with little hesitation in V pregnant women because of the obvious undesirability of anti­ coagulation in such circumstances. The radiation dose to the fetus is small, especially if Kr-81m is used for ventilation imaging. Perfusion-only lung imaging may be adequate, provided the patient is a nonsmoker, has a normal chest radiograph, and has no history of chronic lung disease. Reducing the injected dose to less than about 40 MBq provides an opportunity for follow-up scan, although for statistical reasons the number of particles injected should not be reduced.181 Tc-99m is excreted in breastmilk,190 so nursing mothers should express their milk and save it for 2 days from the time of injection to allow radionuclide physical decay.

MAGNETIC RESONANCE IMAGING Technical considerations MRI of the lung poses some unique challenges, particularly the consequences of cardiac and respiratory movement and the extremely low proton density of normal lung. The large tissue–air interface of the lung induces susceptibility artifacts that affect mag-

netic field homogeneity and lead to signal loss from intravoxel phase dispersion of spins in lung parenchyma.191 An experimental technique which circumvents this rapid decay in signal has been reported.192 With the numerous imaging sequences, gating techniques, and planes of sections available to the radiologist, no single protocol can be prescribed for a thoracic MRI examination; more than any other imaging investigation in the chest, the protocol needs to be tailored to the clinical question to be answered. For example, the MRI examination of suspected pulmonary embolism will be different in virtually every detail from an examination of the diaphragm. An appreciation of the factors that affect the signal-to-noise ratio (SNR) is crucial when considering the method of obtaining optimal magnetic resonance (MR) images of the thorax. In MRI, signal intensity is proportional to the volume of tissue within a voxel. Because background noise is constant through the entire tissue volume, the voxel size in MRI needs to be larger than in CT to maintain a tolerable SNR. The same consideration applies to section thickness, as section width is directly related to SNR. The field-of-view has a profound effect on SNR. Although the field-of-view should be equivalent in size to the region of interest, SNR decreases dramatically below a field-of-view of 30 cm because of the reduction in pixel size inherent in decreasing the field-ofview (halving the field-of-view reduces the pixel size by fourfold and therefore the SNR by the same factor). The SNR can be increased by increasing the number of radiofrequency excitations and averaging the signal from each pixel. Doubling the number of radiofrequency excitations entails doubling the scanning time for what is only a modest increase in SNR; for this reason it is rarely employed. MR images are degraded by periodic respiratory and cardiovascular motion. The result is blurring of the image and superimposition of ghost images. At higher magnetic fields, degradation of the image by motion is more marked and the ghost images are more obvious because of the higher SNR. Artifacts from cardiovascular motion are minimized by synchronizing the acquisition of the images to a certain point in the cardiac cycle by electrocardiographic triggering. Such gating increases the scan time by approximately 15% while markedly improving image quality.193 Artifact from the movement of normal breathing cannot be countered by gating simply because the respiratory cycle is too long and a basic gating technique would require extremely long examination times.194 Many data acquisition and processing techniques, including averaging, rephasing, and reordering of phase encoding (ROPE)195 and navigator196 techniques, have been developed to overcome this problem. None is ideal, but fast scan techniques with acquisition within one breathhold have been reported.197 Rapid breathhold MRI has been successfully applied to cardiac studies.198 For lung imaging, however, this technique suffers from the susceptibility artifacts encountered with gradient echo imaging. Fast spin-echo (FSE), also called turbo spin-echo (TSE), imaging uses a multiecho spin-echo sequence that changes the phase-encode gradient for each of the echoes, which allows the acquisition of multiple lines of k-space within a given repetition time. This considerably reduces the total imaging time, compared with an ordinary spin-echo sequence. The dominant image contrast is determined by the echo times of the low-order k-space acquisitions (low-order phase-encoding steps give global image contrast; highorder phase-encoding steps give edge detail). Therefore, by changing the k-space coverage and changing which echo the low k-space acquisitions are acquired over, it is possible to change the effective echo time and produce images with different T1 or T2 weightings. On T2-weighted (long effective echo time) FSE images, fat signal appears bright due to the T1-weighting from signals acquired at shorter echo times. To pre-empt this, fat saturation is sometimes used for clinical imaging. MR angiography is most commonly performed using contrastenhanced gradient echo techniques. Imaging of structures located in areas with physiologic motion (thorax and abdomen) is commonly performed using rapid imaging during a breathhold (typically 15 seconds). However, this may be difficult in a patient with

29

Chapter 1 • Technical Considerations lung disease. In addition, as patients are required to breathhold reproducibly at the same diaphragm position, slice misregistration can occur. This refers to imaging artifact caused by imperfect alignment of individual image slices. In addition to the reproducibility problem, the signal-to-noise ratio and spatial resolution are inherently low because of the limited acquisition time of a single breathhold. In recent years, respiratory monitoring has become possible using an MR navigator echo, which tracks the diaphragm position in real time and uses this information to gate image data acquisition. The navigator echo can also be used for sophisticated and intelligent phase-encode ordering.196 Newly introduced parallel MRI techniques appear to open a new window of opportunity for MRI of the lung, with the potential for improving both temporal and spatial resolution.199–202 Available studies, however, are still restricted to technical feasibility, and clinical applications are sparse.203–206

Applications The most significant advantage of MRI over other cross-sectional imaging is its excellent contrast resolution of soft tissues, it also has the benefit of not using ionizing radiation. This makes MRI an interesting technique for physiologic studies of the lung.207–212 There are specific instances in which MRI is traditionally considered a

useful problem-solving technique; these include the identification of mediastinal or chest wall invasion by tumor,213–216 the differentiation between solid and vascular hilar masses,126,217 the demonstration of diaphragmatic abnormalities,218 and the assessment of mediastinal disease in patients with treated lymphoma219–221 (Fig. 1.28). There is interest in the role of MR angiography for the diagnosis of pulmonary embolism, either by direct demonstration of intravascular thrombus222–225 or by decreased signal areas representing underperfused lung on gadolinium-enhanced MRI.226 The most common clinical indications for MRI examinations of the thorax are listed in Table 1.3. High spatial resolution imaging with MRI is technically possible, but there is a trade-off between resolution on one hand and signalto-noise ratio and acquisition time on the other. The relatively poor spatial resolution of MRI remains an obstacle to its more widespread use in thoracic imaging. For example, the spurious appearance of small clusters of lymph nodes in the mediastinum, which appear as a single mass, prevents the routine application of MRI to the staging of bronchogenic carcinoma. However, faster spin-echo techniques improve contrast and spatial resolution by reducing been developed to evaluate the lung parenchyma,196,227–229 but there are considerable difficulties in motion artifact compared with standard T2-weighted images. Some specialized imaging sequen­ ces, protocols, and mapping techniques (Fig. 1.29) have been shown to obtain an adequate signal from lung parenchyma.212,230

B A

Fig. 1.28  A, Chest radiograph shows widening of the right paratracheal stripe (arrows). B, CT confirms presence of a lesion (arrow), but streak artifacts degrade the image. C, T2-weighted MR image confirms by high signal intensity that the lesion is cystic (arrow). The final diagnosis after surgery was a mesodermal cyst.

30

C

Magnetic Resonance Imaging

A

B

C

D

Fig. 1.29  T1-maps in a normal volunteer, A, B; a patient with emphysema, C, D; and a patient with diffuse pulmonary fibrosis, E, F.

31

Chapter 1 • Technical Considerations

E

F

Fig. 1.29  Continued Maps are calculated for both inspiration (A, C, E) and expiration (B, D, F). Compared with the normal volunteer, reduced overall T1 is seen in the patient with emphysema, while T1 is substantially increased in the patient with pulmonary fibrosis.

Table 1.3 Potential clinical indications for MRI of the thorax Organ

Suspected pathology

Aorta

Dissection Aneurysm Aortitis Coarctation Malformations Assessment for radiofrequency ablation Pulmonary hypertension Vasculitis Malformations Pulmonary embolism Superior sulcus (‘Pancoast’) tumors Malignant chest wall invasion Thyroid tumors Lymphoma Teratoma Neurogenic tumors

Veins Pulmonary arteries

Lung parenchyma Mediastinum

More recently, various inhaled agents for imaging the airspaces of the lung have been investigated.231–234 Hyperpolarized noble gases, specifically helium-3, have been used to demonstrate ventilated parts of the lung.209,235–248 In addition, xenon gas, which rapidly crosses lipid membranes, has the potential to be used for imaging the lung interstitium.231 More recently, ventilation imaging has been performed using oxygen as a paramagnetic contrast agent with inversion recovery sequence (IR) or multiple IR sequences,208,210 and perfusion imaging has been successfully demonstrated using arterial spin labeling (ASL). Combining oxygen-enhanced and ASL methods yields an MR technique to correlate ventilation and perfusion.211 Nevertheless, the generation of dedicated contrast agents is complex and so these techniques remain in the experimental domain.

REFERENCES 1. Chotas HG, Ravin CE. Chest radiography: estimated lung volume and projected area obscured by the heart, mediastinum, and diaphragm. Radiology 1994;193:403–404. 2. Revesz G, Shea FJ, Kundel HL. The effects of kilovoltage on diagnostic accuracy in chest radiography. Radiology 1982;142: 615–618. 3. Swensen SJ, Gray JE, Brown LR, et al. A new asymmetric screen-film combination for conventional chest radiography:

32

evaluation in 50 patients. AJR Am J Roentgenol 1993;160:483–486. 4. Peppler WW, Zink F, Naimuddin S, et al. Patient-specific beam attenuators. In: Proceedings of the Chest Imaging Conference. Madison, WI, 1987: 64–78. 5. Vlasbloem H, Schultze Kool LJ. AMBER: A scanning multiple-beam equalization system for chest radiography. Radiology 1988;169:29–34.

6. Trout ED, Kelley JP, Larson VL. A comparison of an air gap and a grid in roentgenography of the chest. AJR Am J Roentgenol 1975;124:404–411. 7. Kelsey CA, Moseley RD, Mettler FA, et al. Comparison of nodule detection with 70-kVp and 120-kVp chest radiographs. Radiology 1982;143:609–611. 8. Morgan RA, Owens CM, Collins CD, et al. The improved detection of pneumothoraces in critically ill patients with lateral

References shoot-through digital radiography. Clin Radiol 1993;48:249–252. 9. McAdams HP, Samei E, Dobbins J 3rd, et al. Recent advances in chest radiography. Radiology 2006;241:663–683. 10. Ravin CE, Chotas HG. Chest radiography. Radiology 1997;204:593–600. 11. Floyd CE Jr, Baker JA, Lo JY, et al. Measurement of scatter fractions in clinical bedside radiography. Radiology 1992;183: 857–861. 12. Kundel HL, Nodine CF, Carmody D. Visual scanning, pattern recognition and decision-making in pulmonary nodule detection. Invest Radiol 1978;13:175–181. 13. Kundel HL, Revesz G, Toto L. Contrast gradient and the detection of lung nodules. Invest Radiol 1979;14:18–22. 14. Samei E, Flynn MJ, Eyler WR. Detection of subtle lung nodules: relative influence of quantum and anatomic noise on chest radiographs. Radiology 1999;213:727–734. 15. Kundel HL. Peripheral vision, structured noise and film reader error. Radiology 1975;114:269–273. 16. Carmody DP, Nodine CF, Kundel HL. An analysis of perceptual and cognitive factors in radiographic interpretation. Perception 1980;9:339–344. 17. Sonoda M, Takano M, Miyahara J, et al. Computed radiography utilizing scanning laser stimulated luminescence. Radiology 1983;148:833–838. 18. Samei E, Flynn MJ. An experimental comparison of detector performance for direct and indirect digital radiography systems. Med Phys 2003;30:608–622. 19. Siewerdsen JH, Antonuk LE, el-Mohri Y, et al. Empirical and theoretical investigation of the noise performance of indirect detection, active matrix flat-panel imagers (AMFPIs) for diagnostic radiology. Med Phys 1997;24:71–89. 20. Zhao W, Rowlands JA. Digital radiology using active matrix readout of amorphous selenium: theoretical analysis of detective quantum efficiency. Med Phys 1997;24: 1819–1833. 21. Yaffe MJ, Rowlands JA. X-ray detectors for digital radiography. Phys Med Biol 1997; 42:1–39. 22. Samei E, Saunders RS, Lo JY, et al. Fundamental imaging characteristics of a slot-scan digital chest radiographic system. Med Phys 2004;31:2687–2698. 23. Holdsworth DW, Gerson RK, Fenster A. A time-delay integration charge-coupled device camera for slot-scanned digital radiography. Med Phys 1990;17:876–886. 24. Mainprize JG, Ford NL, Yin S, et al. A slot-scanned photodiode-array/CCD hybrid detector for digital mammography. Med Phys 2002;29:214–225. 25. Uffmann M, Prokop M, Kupper W, et al. Soft-copy reading of digital chest radiographs: effect of ambient light and automatic optimization of monitor luminance. Invest Radiol 2005;40:180–185. 26. Balassy C, Prokop M, Weber M, et al. Flat-panel display (LCD) versus highresolution gray-scale display (CRT) for chest radiography: an observer preference study. AJR Am J Roentgenol 2005;184: 752–756. 27. Oschatz E, Prokop M, Scharitzer M, et al. Comparison of liquid crystal versus cathode ray tube display for the detection

of simulated chest lesions. Eur Radiol 2005;15:1472–1476. 28. Scharitzer M, Prokop M, Weber M, et al. Detectability of catheters on bedside chest radiographs: comparison between liquid crystal display and high-resolution cathode-ray tube monitors. Radiology 2005;234:611–616. 29. Badano A, Flynn MJ, Martin S, et al. Angular dependence of the luminance and contrast in medical monochrome liquid crystal displays. Med Phys 2003;30: 2602–2613. 30. Badano A, Gagne RM, Jennings RJ, et al. Noise in flat-panel displays with subpixel structure. Med Phys 2004;31:715–723. 31. Averbukh AN, Channin DS, Flynn MJ. Assessment of a novel, high-resolution, color, AMLCD for diagnostic medical image display: luminance performance and DICOM calibration. J Digit Imaging 2003; 16:270–279. 32. Hartman TE. Dual-energy radiography. Semin Roentgenol 1997;32:45–49. 33. Kamimura R, Takashima T. Clinical application of single dual-energy subtraction technique with digital storage-phosphor radiography. J Digit Imaging 1995;8:21–24. 34. Kelcz F, Zink FE, Peppler WW, et al. Conventional chest radiography vs dual-energy computed radiography in the detection and characterization of pulmonary nodules. AJR Am J Roentgenol 1994;162:271–278. 35. Kido S, Ikezoe J, Naito H, et al. Clinical evaluation of pulmonary nodules with single-exposure dual-energy subtraction chest radiography with an iterative noise-reduction algorithm. Radiology 1995;194:407–412. 36. Oestmann JW, Greene R, Rhea JT, et al. ‘Single-exposure’ dual energy digital radiography in the detection of pulmonary nodules and calcifications. Invest Radiol 1989;24:517–521. 37. Kano A, Doi K, MacMahon H, et al. Digital image subtraction of temporally sequential chest images for detection of interval change. Med Phys 1994;21:453–461. 38. Ishida T, Ashizawa K, Engelmann R, et al. Application of temporal subtraction for detection of interval changes on chest radiographs: improvement of subtraction images using automated initial image matching. J Digit Imaging 1999;12:77–86. 39. Ishida T, Katsuragawa S, Nakamura K, et al. Iterative image warping technique for temporal subtraction of sequential chest radiographs to detect interval change. Med Phys 1999;26:1320–1329. 40. Abe H, MacMahon H, Engelmann R, et al. Computer-aided diagnosis in chest radiography: results of large-scale observer tests at the 1996-2001 RSNA scientific assemblies. RadioGraphics 2003;23:255–265. 41. Kakeda S, Nakamura K, Kamada K, et al. Improved detection of lung nodules by using a temporal subtraction technique. Radiology 2002;224:145–151. 42. Okazaki H, Nakamura K, Watanabe H, et al. Improved detection of lung cancer arising in diffuse lung diseases on chest radiographs using temporal subtraction. Acad Radiol 2004;11:498–505. 43. Difazio MC, MacMahon H, Xu XW, et al. Digital chest radiography: effect of

temporal subtraction images on detection accuracy. Radiology 1997;202:447–452. 44. Dobbins JT 3rd, McAdams HP, Godfrey DJ, et al. Digital tomosynthesis of the chest. J Thorac Imaging 2008;23:86–92. 45. Doi K. Overview on research and development of computer-aided diagnostic schemes. Semin Ultrasound CT MR 2004; 25:404–410. 46. MacMahon H. Advanced image processing and computer-aided diagnosis: are we there yet? J Thorac Imaging 2008;23:75–76. 47. van Ginneken B, ter Haar Romeny BM, Viergever MA. Computer-aided diagnosis in chest radiography: a survey. IEEE Trans Med Imaging 2001;20:1228–1241. 48. MacMahon H, Engelmann R, Behlen FM, et al. Computer-aided diagnosis of pulmonary nodules: results of a large-scale observer test. Radiology 1999;213:723–726. 49. Marten K, Grillhosl A, Seyfarth T, et al. Computer-assisted detection of pulmonary nodules: evaluation of diagnostic performance using an expert knowledgebased detection system with variable reconstruction slice thickness settings. Eur Radiol 2005;15:203–212. 50. Marten K, Seyfarth T, Auer F, et al. Computer-assisted detection of pulmonary nodules: performance evaluation of an expert knowledge-based detection system in consensus reading with experienced and inexperienced chest radiologists. Eur Radiol 2004;14:1930–1938. 51. Shiraishi J, Abe H, Engelmann R, et al. Effect of high sensitivity in a computerized scheme for detecting extremely subtle solitary pulmonary nodules in chest radiographs: observer performance study. Acad Radiol 2003;10:1302–1311. 52. Shiraishi J, Abe H, Engelmann R, et al. Computer-aided diagnosis to distinguish benign from malignant solitary pulmonary nodules on radiographs: ROC analysis of radiologists’ performance – initial experience. Radiology 2003;227:469–474. 53. Abe H, Ashizawa K, Li F, et al. Artificial neural networks (ANNs) for differential diagnosis of interstitial lung disease: results of a simulation test with actual clinical cases. Acad Radiol 2004;11:29–37. 54. Ashizawa K, Ishida T, MacMahon H, et al. Artificial neural networks in chest radiography: application to the differential diagnosis of interstitial lung disease. Acad Radiol 1999;6:2–9. 55. Ashizawa K, MacMahon H, Ishida T, et al. Effect of an artificial neural network on radiologists’ performance in the differential diagnosis of interstitial lung disease using chest radiographs. AJR Am J Roentgenol 1999;172:1311–1315. 56. Monnier-Cholley L, MacMahon H, Katsuragawa S, et al. Computer-aided diagnosis for detection of interstitial opacities on chest radiographs. AJR Am J Roentgenol 1998;171:1651–1656. 57. Nakamori N, Doi K, MacMahon H, et al. Effect of heart-size parameters computed from digital chest radiographs on detection of cardiomegaly. Potential usefulness for computer-aided diagnosis. Invest Radiol 1991;26:546–550. 58. Abe K, Doi K, MacMahon H, et al. Computer-aided diagnosis in chest radiography. Preliminary experience. Invest Radiol 1993;28:987–993.

33

Chapter 1 • Technical Considerations 59. Sanada S, Doi K, MacMahon H. Image feature analysis and computer-aided diagnosis in digital radiography: automated detection of pneumothorax in chest images. Med Phys 1992;19: 1153–1160. 60. Ko JP, Betke M. Chest CT: automated nodule detection and assessment of change over time – preliminary experience. Radiology 2001;218:267–273. 61. van Ginneken B, Katsuragawa S, ter Haar Romeny BM, et al. Automatic detection of abnormalities in chest radiographs using local texture analysis. IEEE Trans Med Imaging 2002;21:139–149. 62. Zeman RK, Baron RL, Jeffrey RB Jr, et al. Helical body CT: evolution of scanning protocols. AJR Am J Roentgenol 1998;170: 1427–1438. 63. Kalender WA, Seissler W, Klotz E, et al. Spiral volumetric CT with single-breathhold technique, continuous transport, and continuous scanner rotation. Radiology 1990;176:181–183. 64. Vock P, Soucek M, Daepp M, et al. Lung spiral volumetric CT with single breathhold technique. Radiology 1990;176: 864–867. 65. Lawler LP, Fishman EK. Multi-detector row CT of thoracic disease with emphasis on 3D volume rendering and CT angiography. RadioGraphics 2001;21: 1257–1273. 66. Ravenel JG, McAdams HP, Remy-Jardin M, et al. Multidimensional imaging of the thorax: practical applications. J Thorac Imaging 2001;16:269–281. 67. Remy-Jardin M, Remy J, Artaud D, et al. Volume rendering of the tracheobronchial tree: clinical evaluation of bronchographic images. Radiology 1998;208:761–770. 68. Salvolini L, Bichi SE, Costarelli L, et al. Clinical applications of 2D and 3D CT imaging of the airways – a review. Eur J Radiol 2000;34:9–25. 69. Prokop M. General principles of MDCT. Eur J Radiol 2003;45(suppl 1):S4–S10. 70. Rubin GD. Data explosion: the challenge of multidetector-row CT. Eur J Radiol 2000; 36:74–80. 71. Rubin GD, Napel S, Leung AN. Volumetric analysis of volumetric data: achieving a paradigm shift. Radiology 1996;200: 312–317. 72. Hopper KD, Kasales CJ, Mahraj R, et al. Routine use of a higher order interpolator and bone algorithm in thoracic CT. AJR Am J Roentgenol 1996;167:947–949. 73. Zwirewich CV, Terriff B, Müller NL. High-spatial-frequency (bone) algorithm improves quality of standard CT of the thorax. AJR Am J Roentgenol 1989;153: 1169–1173. 74. Paranjpe DV, Bergin CJ. Spiral CT of the lungs: optimal technique and resolution compared with conventional CT. AJR Am J Roentgenol 1994;162:561–567. 75. Wright AR, Collie DA, Williams JR, et al. Pulmonary nodules: effect on detection of spiral CT pitch. Radiology 1996;199: 837–841. 76. Rubin GD, Napel S. Increased scan pitch for vascular and thoracic spiral CT. Radiology 1995;197:316–317. 77. Tack D, De Maertelaer V, Petit W, et al. Multi-detector row CT pulmonary angiography: comparison of standard-dose

34

and simulated low-dose techniques. Radiology 2005;236:318–325. 78. Tack D, Gevenois PA. Radiation dose in computed tomography of the chest. JBR-BTR 2004;87:281–288. 79. Brink JA, Heiken JP, Balfe DM, et al. Spiral CT: decreased spatial resolution in vivo due to broadening of section-sensitivity profile. Radiology 1992;185:469–474. 80. Polacin A, Kalender WA, Marchal G. Evaluation of section sensitivity profiles and image noise in spiral CT. Radiology 1992;185:29–35. 81. Buckley JA, Scott WW Jr, Siegelman SS, et al. Pulmonary nodules: effect of increased data sampling on detection with spiral CT and confidence in diagnosis. Radiology 1995;196:395–400. 82. Kasales CJ, Hopper KD, Ariola DN, et al. Reconstructed helical CT scans: improvement in z-axis resolution compared with overlapped and nonoverlapped conventional CT scans. AJR Am J Roentgenol 1995;164:1281–1284. 83. Mayo JR, Aldrich J, Müller NL. Radiation exposure at chest CT: a statement of the Fleischner Society. Radiology 2003;228: 15–21. 84. Naidich DP, Marshall CH, Gribbin C, et al. Low-dose CT of the lungs: preliminary observations. Radiology 1990;175:729–731. 85. Henschke CI, McCauley DI, Yankelevitz DF, et al. Early lung cancer action project: overall design and findings from baseline screening. Lancet 1999;354:99–105. 86. Itoh S, Ikeda M, Arahata S, et al. Lung cancer screening: minimum tube current required for helical CT. Radiology 2000; 215:175–183. 87. Swensen SJ. CT screening for lung cancer. AJR Am J Roentgenol 2002;179:833–836. 88. Ravenel JG, Costello P, Silvestri GA. Screening for lung cancer. AJR Am J Roentgenol 2008;190:755–761. 89. Zwirewich CV, Mayo JR, Müller NL. Low dose high resolution CT of lung parenchyma. Radiology 1991;180:413– 417. 90. Mayo JR, Hartman TE, Lee KS, et al. CT of the chest: minimal tube current required for good image quality with the least radiation dose. AJR Am J Roentgenol 1995; 164:603–607. 91. Mayo JR, Whittall KP, Leung AN, et al. Simulated dose reduction in conventional chest CT: validation study. Radiology 1997; 202:453–457. 92. Bankier AA, Schaefer-Prokop C, De Maertelaer V, et al. Air trapping: comparison of standard-dose and simulated low-dose thin-section CT techniques. Radiology 2007;242:898–906. 93. Dalrymple NC, Prasad SR, Freckleton MW, et al. Informatics in radiology (infoRAD): introduction to the language of threedimensional imaging with multidetector CT. RadioGraphics 2005;25:1409–1428. 94. Quint LE, Whyte RI, Kazerooni EA, et al. Stenosis of the central airways: evaluation by using helical CT with multiplanar reconstructions. Radiology 1995;194: 871–877. 95. Kauczor HU, Wolcke B, Fischer B, et al. Three-dimensional helical CT of the tracheobronchial tree: evaluation of imaging protocols and assessment of suspected stenoses with bronchoscopic

correlation. AJR Am J Roentgenol 1996;167: 419–424. 96. Choi YW, McAdams HP, Jeon SC, et al. Low-dose spiral CT: application to surface-rendered three-dimensional imaging of central airways. J Comput Assist Tomogr 2002;26:335–341. 97. Summers RH, Feng DH, Holland SM, et al. Virtual bronchoscopy: segmentation method for real-time display. Radiology 1996;200:857–862. 98. Ferretti GR, Knoplioch J, Bricault I, et al. Central airway stenoses: preliminary results of spiral-CT-generated virtual bronchoscopy simulations in 29 patients. Eur Radiol 1997;7:854–859. 99. Fleiter T, Merkle EM, Aschoff AJ, et al. Comparison of real-time virtual and fiberoptic bronchoscopy in patients with bronchial carcinoma: opportunities and limitations. AJR Am J Roentgenol 1997;169: 1591–1595. 100. Lawler LP, Corl FM, Haponik EF, et al. Multidetector row computed tomography and 3-dimensional volume rendering for adult airway imaging. Curr Probl Diagn Radiol 2002;31:115–133. 101. Naidich DP, Gruden JF, McGuinness G, et al. Volumetric (helical/spiral) CT (VCT) of the airways. J Thorac Imaging 1997;12: 11–28. 102. Hoffman EA, Clough AV, Christensen GE, et al. The comprehensive imaging-based analysis of the lung: a forum for team science. Acad Radiol 2004;11:1370–1380. 103. Mathieson JR, Mayo JR, Staples CA, et al. Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of CT and chest radiography. Radiology 1989; 171:111–116. 104. Remy-Jardin M, Degreef JM, Beuscart R, et al. Coal worker’s pneumoconiosis: CT assessment in exposed workers and correlation with radiographic findings. Radiology 1990;177:363–371. 105. Dawn SK, Gotway MB, Webb WR. Multidetector-row spiral computed tomography in the diagnosis of thoracic diseases. Respir Care 2001;46:912–921. 106. Gruden JF, Ouanounou S, Tigges S, et al. Incremental benefit of maximum-intensityprojection images on observer detection of small pulmonary nodules revealed by multidetector CT. AJR Am J Roentgenol 2002;179:149–157. 107. Remy-Jardin M, Remy J, Gosselin B, et al. Sliding thin slab, minimum intensity projection technique in the diagnosis of emphysema: histopathologic-CT correlation. Radiology 1996;200:665–671. 108. Bhalla M, Naidich DP, McGuinness G, et al. Diffuse lung disease: assessment with helical CT – preliminary observations of the role of maximum and minimum intensity projection images. Radiology 1996;200:341–347. 109. Fotheringham T, Chabat F, Hansell DM, et al. A comparison of methods for enhancing the detection of areas of decreased attenuation on CT caused by airways disease. J Comput Assist Tomogr 1999;23:385–389. 110. Naidich DP, Webb WR, Müller NL, et al. Principles and techniques of thoracic CT and MR. In: Computed tomography and magnetic resonance of the thorax. Philadelphia: Lippincott-Raven, 1999:14–15.

References 111. Fleischmann D, Hittmair K. Mathematical analysis of arterial enhancement and optimization of bolus geometry for CT angiography using the discrete fourier transform. J Comput Assist Tomogr 1999;23:474–484. 112. Fleischmann D, Rubin GD, Bankier AA, et al. Improved uniformity of aortic enhancement with customized contrast medium injection protocols at CT angiography. Radiology 2000;214:363–371. 113. Loubeyre P, Debard I, Nemoz C, et al. Using thoracic helical CT to assess iodine concentration in a small volume of nonionic contrast medium during vascular opacification: a prospective study. AJR Am J Roentgenol 2000;174:783–787. 114. Rubin GD, Lane MJ, Bloch DA, et al. Optimization of thoracic spiral CT: effects of iodinated contrast medium concentration. Radiology 1996;201:785– 791. 115. Hopper KD, Mosher TJ, Kasales CJ, et al. Thoracic spiral CT: delivery of contrast material pushed with injectable saline solution in a power injector. Radiology 1997;205:269–271. 116. Leung AN. Spiral CT of the thorax in daily practice: optimization of technique. J Thorac Imaging 1997;12:2–10. 117. Loubeyre P, Debard I, Nemoz C, et al. High opacification of hilar pulmonary vessels with a small amount of nonionic contrast medium for general thoracic CT: a prospective study. AJR Am J Roentgenol 2002;178:1377–1381. 118. Federle MP, Chang PJ, Confer S, et al. Frequency and effects of extravasation of ionic and nonionic CT contrast media during rapid bolus injection. Radiology 1998;206:637–640. 119. Bellin MF, Jakobsen JA, Tomassin I, et al. Contrast medium extravasation injury: guidelines for prevention and management. Eur Radiol 2002;12: 2807–2812. 120. Stern EJ, Frank MS, Godwin JD. Chest computed tomography display preferences. Survey of thoracic radiologists. Invest Radiol 1995;30:517–521. 121. Maguire WM, Herman PG, Khan A, et al. Comparison of fixed and adjustable window width and level settings in the CT evaluation of diffuse lung disease. J Comput Assist Tomogr 1993;17:847–852. 122. Baxter BS, Sorenson JA. Factors affecting the measurements of size and CT number in computed tomography. Invest Radiol 1981;16:337–341. 123. Koehler PR, Anderson RE, Baxter B. The effect of computed tomography viewer controls on anatomical measurements. Radiology 1979;130:189–194. 124. Harris KM, Adams H, Lloyd DCF, et al. The effect on apparent size of simulated pulmonary nodules of using three standard CT window settings. Clin Radiol 1993;47: 241–244. 125. Bankier AA, Fleischmann D, Mallek R, et al. Bronchial wall thickness: appropriate window settings for thin- section CT and radiologic-anatomic correlation. Radiology 1996;199:831–836. 126. Webb WR, Gamsu G, Stark DD, et al. Magnetic resonance imaging of the normal and abnormal pulmonary hila. Radiology 1984;152:89–94.

127. Prokop M. Lungs and tracheobronchial system. In: Prokop M, Galanski M (eds). Spiral and multislice computed tomography of the body. Stuttgart: Thieme, 2003:279–373. 128. Schindera ST, Nelson RC, Yoshizumi T, et al. Effect of automatic tube current modulation on radiation dose and image quality for low tube voltage multidetector row CT angiography phantom study. Acad Radiol 2009. [Epub ahead of print] 129. Mayo JR, Webb WR, Gould R, et al. High-resolution CT of the lungs: an optimal approach. Radiology 1987;163: 507–510. 130. Mayo JR. High resolution computed tomography: technical aspects. Radiol Clin North Am 1991;29:1043–1049. 131. Murata K, Khan A, Herman PG. Pulmonary parenchymal disease: evaluation with high-resolution CT. Radiology 1989;170:629–635. 132. Murata K, Khan A, Rojas KA, et al. Optimization of computed tomography technique to demonstrate the fine structure of the lung. Invest Radiol 1988;23:170–175. 133. Honda O, Johkoh T, Yamamoto S, et al. Comparison of quality of multiplanar reconstructions and direct coronal multidetector CT scans of the lung. AJR Am J Roentgenol 2002;179:875–879. 134. Webb WR, Müller NL, Naidich DP. Technical aspects of HRCT. In: Webb WR, Müller NL, Naidich DP (eds). Highresolution CT of the lung. Philadelphia: Lippincott, Williams & Wilkins, 2000:1–21. 135. Lee KS, Primack SL, Staples CA, et al. Chronic infiltrative lung disease: comparison of diagnostic accuracies of radiography and low- and conventionaldose thin-section CT. Radiology 1994;191: 669–673. 136. Leung AN, Staples CA, Müller NL. Chronic diffuse infiltrative lung disease: comparison of diagnostic accuracy of high-resolution and conventional CT. AJR Am J Roentgenol 1991;157:693–696. 137. Schoepf UJ, Bruening RD, Hong C, et al. Multislice helical CT of focal and diffuse lung disease: comprehensive diagnosis with reconstruction of contiguous and high-resolution CT sections from a single thin-collimation scan. AJR Am J Roentgenol 2001;177:179–184. 138. Remy-Jardin M, Campistron P, Amara A, et al. Usefulness of coronal reformations in the diagnostic evaluation of infiltrative lung disease. J Comput Assist Tomogr 2003;27:266–273. 139. Mayo JR, Jackson SA, Müller NL. High-resolution CT of the chest: radiation dose. AJR Am J Roentgenol 1993;160: 479–481. 140. van der Bruggen-Bogaarts BA, Broerse JJ, Lammers JW, et al. Radiation exposure in standard and high-resolution chest CT scans. Chest 1995;107:113–115. 141. Kuhns LR, Borlaza G. The ‘twinkling star’ sign: an aid in differentiating pulmonary vessels from pulmonary nodules on computed tomograms. Radiology 1980;135: 763–764. 142. Tarver RD, Conces DJ, Godwin JD. Motion artifacts on CT simulate bronchiectasis. AJR Am J Roentgenol 1988;151:1117–1119. 143. Schoepf UJ, Becker CR, Bruening RD, et al. Electrocardiographically gated thin-section

CT of the lung. Radiology 1999;212: 649–654. 144. Cailes JB, Du Bois RM, Hansell DM. Density gradient of the lung parenchyma on CT in patients with lone pulmonary hypertension and systemic sclerosis. Acad Radiol 1996;3:724–730. 145. Morimoto S, Takeuchi N, Imanaka H, et al. Gravity-dependent atelectasis: radiologic, physiologic and pathologic correlation in rabbits on high-frequency oscillation ventilation. Invest Radiol 1989;24:522– 533. 146. Volpe J, Storto ML, Lee K, et al. Highresolution CT of the lung: determination of the usefulness of CT scans obtained with the patient prone based on plain radiographic findings. AJR Am J Roentgenol 1997;169:369–374. 147. Grenier P, Lenoir S, Brauner M. Computed tomographic assessment of bronchiectasis. Semin USCTMRI 1990;11:430–441. 148. Hansell DM. Bronchiectasis. Radiol Clin North Am 1998;36:107–128. 149. Engeler CE, Tashjian JH, Engeler CM, et al. Volumetric high-resolution CT in the diagnosis of interstitial lung disease and bronchiectasis: diagnostic accuracy and radiation dose. AJR Am J Roentgenol 1994; 163:31–35. 150. Grenier P, Beigelman C, Remy-Jardin M, et al. Spiral CT of the bronchial tree. In: Remy-Jardin M, Remy J (eds). Spiral CT of the chest. Berlin: Springer-Verlag, 2000: 185–199. 151. Lucidarme O, Grenier P, Coche E, et al. Bronchiectasis: comparative assessment with thin-section CT and helical CT. Radiology 1996;200:673–679. 152. van der Bruggen-Bogaarts BAHA, van der Bruggen HMJG, van Waes PFGM, et al. Assessment of bronchiectasis: comparison of HRCT and spiral volumetric CT. J Comput Assist Tomogr 1996;20:15–19. 153. Remy-Jardin M, Amara A, Campistron P, et al. Diagnosis of bronchiectasis with multislice spiral CT: accuracy of 3–mm-thick structured sections. Eur Radiol 2003;13:1165–1171. 154. Yi CA, Lee KS, Kim TS, et al. Multidetector CT of bronchiectasis: effect of radiation dose on image quality. AJR Am J Roentgenol 2003;181:501–505. 155. Sung YM, Lee KS, Yi CA, et al. Additional coronal images using low-milliamperage multidetector-row computed tomography: effectiveness in the diagnosis of bronchiectasis. J Comput Assist Tomogr 2003;27:490–495. 156. Desai SR, Wells AU, Cheah FK, et al. The reproducibility of bronchial circumference measurements using computed tomography. Br J Radiol 1994;67:257–262. 157. Grenier P, Cordeau MP, Beigelman C. High-resolution computed tomography of the airways. J Thorac Imaging 1993;8: 213–229. 158. Kang EY, Miller RR, Müller NL. Bronchiectasis: comparison of preoperative thin-section CT and pathologic findings in resected specimens. Radiology 1995;195: 649–654. 159. Seneterre E, Paganin F, Bruel JM, et al. Measurement of the internal size of bronchi using high resolution computed tomography (HRCT). Eur Respir J 1994;7:596–600.

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Chapter 1 • Technical Considerations 160. Hansell DM. Small airways diseases: detection and insights with computed tomography. Eur Respir J 2001;17: 1294–1313. 161. Miller WT Jr, Kotloff RM, Blumenthal NP, et al. Utility of high resolution computed tomography in predicting bronchiolitis obliterans syndrome following lung transplantation: preliminary findings. J Thorac Imaging 2001;16:76–80. 162. Stern EJ, Frank MS. Small-airways disease of the lungs: findings at expiratory CT. AJR Am J Roentgenol 1994;163:37–41. 163. Arakawa H, Webb WR, McCowin M, et al. Inhomogeneous lung attenuation at thin-section CT: diagnostic value of expiratory scans. Radiology 1998;206:89–94. 164. Lucidarme O, Coche E, Cluzel P, et al. Expiratory CT scans for chronic airway disease: correlation with pulmonary function test results. AJR Am J Roentgenol 1998;170:301–307. 165. Arakawa H, Niimi H, Kurihara Y, et al. Expiratory high-resolution CT: diagnostic value in diffuse lung diseases. AJR Am J Roentgenol 2000;175:1537–1543. 166. Lucidarme O, Grenier PA, Cadi M, et al. Evaluation of air trapping at CT: comparison of continuous-versus suspended-expiration CT techniques. Radiology 2000;216:768–772. 167. Gotway MB, Lee ES, Reddy GP, et al. Low-dose dynamic expiratory thin-section CT of the lungs using a spiral CT scanner. J Thorac Imaging 2000;15:168–172. 168. Boiselle PM, Reynolds KF, Ernst A. Multiplanar and three-dimensional imaging of the central airways with multidetector CT. AJR Am J Roentgenol 2002;179:301–308. 169. Boiselle PM, Ernst A. Tracheal morphology in patients with tracheomalacia: prevalence of inspiratory lunate and expiratory ‘frown’ shapes. J Thorac Imaging 2006;21: 190–196. 170. Boiselle PM, Lee KS, Lin S, et al. Cine CT during coughing for assessment of tracheomalacia: preliminary experience with 64-MDCT. AJR Am J Roentgenol 2006;187:W175–177. 171. Remy-Jardin M, Pistolesi M, Goodman LR, et al. Management of suspected acute pulmonary embolism in the era of CT angiography: a statement from the Fleischner Society. Radiology 2007;245: 315–329. 172. Blodgett TM, Meltzer CC, Townsend DW. PET/CT: form and function. Radiology 2007;242:360–385. 173. Buscombe J, O’Rourke E. Is 18F FDG PET-CT cost effective in lung cancer? Expert Rev Anticancer Ther 2007;7:471– 476. 174. De Wever W, Stroobants S, Verschakelen JA. Integrated PET/CT in lung cancer imaging: history and technical aspects. JBR-BTR 2007;90:112–119. 175. De Wever W, Vankan Y, Stroobants S, et al. Detection of extrapulmonary lesions with integrated PET/CT in the staging of lung cancer. Eur Respir J 2007;29:995–1002. 176. Kim YK, Lee KS, Kim BT, et al. Mediastinal nodal staging of nonsmall cell lung cancer using integrated 18F-FDG PET/CT in a tuberculosis-endemic country: diagnostic efficacy in 674 patients. Cancer 2007; 109:1068–1077.

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177. Pauls S, Buck AK, Hohl K, et al. Improved non-invasive T-staging in non-small cell lung cancer by integrated 18F-FDG PET/ CT. Nuklearmedizin 2007;46:9–14, quiz N11–12. 178. Yi CA, Lee KS, Kim BT, et al. Efficacy of helical dynamic CT versus integrated PET/ CT for detection of mediastinal nodal metastasis in non-small cell lung cancer. AJR Am J Roentgenol 2007;188:318–325. 179. Fischer BM, Mortensen J, Langer SW, et al. A prospective study of PET/CT in initial staging of small-cell lung cancer: comparison with CT, bone scintigraphy and bone marrow analysis. Ann Oncol 2007;18:338–345. 180. Kim BT, Lee KS, Shim SS, et al. Stage T1 non-small cell lung cancer: preoperative mediastinal nodal staging with integrated FDG PET/CT – a prospective study. Radiology 2006;241:501–509. 181. Heck LL, Duley JW Jr. Statistical considerations in lung imaging with 99mTc albumin particles. Radiology 1974;113: 675–679. 182. Diffey BL, Gibson CJ, Scott LE. A new technique for xenon–133 ventilation imaging in the diagnosis of pulmonary embolism. Br J Radiol 1986;59:1179–1184. 183. Nimmo MJ, Merrick MV, Millar AM. A comparison of the economics of xenon 127, xenon 133 and krypton 81m for routine ventilation imaging of the lungs. Br J Radiol 1985;58:635–636. 184. Wiener C, McKenna WJ, Myers MJ. Lung ventilation is reduced in patients with cardiomegaly in the supine but not the prone position. Am Rev Respir Dis 1990;141:150–155. 185. Peters AM, Gordon I, Kaiser AM. Spontaneous abrupt changes in the distribution of ventilation: scintigraphy. Br J Radiol 1988;62:536–543. 186. James JM, Lloyd JJ, Leahy BC, et al. 99Tcm-Technegas and krypton-81m ventilation scintigraphy: a comparison in known respiratory disease. Br J Radiol 1992;65:1075–1082. 187. West JB. Uptake and delivery of the respiratory gases. In: West JB (ed). Physiological basis of medical practice. Baltimore: Williams & Wilkins, 1985: 546–571. 188. O’Doherty MJ, Peters AM. Pulmonary technetium-99m diethylene triamine penta-acetic acid aerosol clearance as an index of lung injury. Eur J Nucl Med 1997;24:81–87. 189. Lemb M, Oei TH, Sander U. Ventilationperfusion lung SPECT in the diagnosis of pulmonary thromboembolism using Technegas. Eur J Nucl Med 1989;14:422. 190. Mountford PJ, Coakley AJ. A review of the secretion of radioactivity in human breast milk: data, quantitative analysis and recommendations. Nucl Med Commun 1989;10:15–27. 191. Bergin CJ, Glover GH, Pauly JM. Lung parenchyma: magnetic susceptibility in MR imaging. Radiology 1991;180:845–848. 192. Alsop DC, Hatabu H, Bonnet M, et al. Multi-slice, breathhold imaging of the lung with submillisecond echo times. Magn Reson Med 1995;33:678–682. 193. Mark AS, Winkler ML, Peltzer M, et al. Gated acquisition of MR images of the thorax: advantages for the study of the hila

and mediastinum. Magn Reson Imaging 1987;5:57–63. 194. Lewis C, Prato FS, Drost DJ, et al. Comparison of respiratory triggering and gating techniques for the removal of respiratory artifacts in MR imaging. Radiology 1986;160:803–810. 195. Bailes DR, Gilderdale DJ, Bydder GM, et al. Respiratory ordered phase-encoding (ROPE): a method for reducing respiratory motion artifacts in MR imaging. J Comput Assist Tomogr 1985;9:835–838. 196. Schmidt MA, Yang GZ, Keegan J, et al. Non-breath-hold lung magnetic resonance imaging with real-time navigation. MAGMA 1997;5:123–128. 197. Moody AR, Bolton SC, Horsfield MA. Optimization of a breath-hold magnetic resonance gradient echo technique for the detection of interstitial lung disease. Invest Radiol 1995;30:730–737. 198. Edelman RR, Manning W, Burstein D, et al. Coronary arteries: breath-hold MR angiography. Radiology 1991;181:641– 643. 199. Arnold JF, Kotas M, Pyzalski RW, et al. Potential of magnetization transfer MRI for target volume definition in patients with non-small-cell lung cancer. J Magn Reson Imaging 2008;28:1417–1424. 200. Arnold JF, Morchel P, Glaser E, et al. Lung MRI using an MR-compatible active breathing control (MR-ABC). Magn Reson Med 2007;58:1092–1098. 201. Oechsner M, Pracht ED, Staeb D, et al. Lung imaging under free-breathing conditions. Magn Reson Med 2008. 202. Pracht ED, Fischer A, Arnold JF, et al. Single-shot quantitative perfusion imaging of the human lung. Magn Reson Med 2006;56:1347–1351. 203. Ohno Y, Koyama H, Nogami M, et al. Postoperative lung function in lung cancer patients: comparative analysis of predictive capability of MRI, CT, and SPECT. AJR Am J Roentgenol 2007;189:400–408. 204. Ohno Y, Koyama H, Nogami M, et al. Whole-body MR imaging vs. FDG-PET: comparison of accuracy of M-stage diagnosis for lung cancer patients. J Magn Reson Imaging 2007;26:498–509. 205. Ohno Y, Koyama H, Nogami M, et al. STIR turbo SE MR imaging vs. coregistered FDG-PET/CT: quantitative and qualitative assessment of N-stage in non-small-cell lung cancer patients. J Magn Reson Imaging 2007;26:1071–1080. 206. Ohno Y, Koyama H, Onishi Y, et al. Non-small cell lung cancer: whole-body MR examination for M-stage assessment – utility for whole-body diffusion-weighted imaging compared with integrated FDG PET/CT. Radiology 2008;248:643–654. 207. Bankier AA, Storey P, Mai VM, et al. Gravity-dependent signal gradients on MR images of the lung in supine and prone positions: a comparison with isogravitational signal variability. J Magn Reson Imaging 2006;23:115–122. 208. Chen Q, Levin DL, Kim D, et al. Pulmonary disorders: ventilation-perfusion MR imaging with animal models. Radiology 1999;213:871–879. 209. de Lange EE, Mugler JP 3rd, Brookeman JR, et al. Lung air spaces: MR imaging evaluation with hyperpolarized 3He gas. Radiology 1999;210:851–857.

References 210. Mai VM, Chen Q, Bankier AA, et al. Multiple inversion recovery MR subtraction imaging of human ventilation from inhalation of room air and pure oxygen. Magn Reson Med 2000;43:913–916. 211. Mai VM, Liu B, Polzin JA, et al. Ventilation-perfusion ratio of signal intensity in human lung using oxygenenhanced and arterial spin labeling techniques. Magn Reson Med 2002;48: 341–350. 212. Mayo JR, MacKay A, Müller NL. MR imaging of the lungs: value of short TE spin-echo pulse sequences. AJR Am J Roentgenol 1992;159:951–956. 213. Bergin CJ, Healy MV, Zincone GE, et al. MR evaluation of chest wall involvement in malignant lymphoma. J Comput Assist Tomogr 1990;14:928–931. 214. Brown L, Aushenbaugh G. Masses of the anterior mediastinum: CT and MRI findings. AJR Am J Roentgenol 1991;157: 1171–1180. 215. Heelan RT, Demas BE, Caravelli JF, et al. Superior sulcus tumors: CT and MR imaging. Radiology 1989;170:637–641. 216. Padovani B, Mouroux J, Seksik L, et al. Chest wall invasion by bronchogenic carcinoma: evaluation with MR imaging. Radiology 1993;187:33–38. 217. Glazer GM, Gross BH, Aisen AM, et al. Imaging of the pulmonary hilum: a prospective comparative study in patients with lung cancer. AJR Am J Roentgenol 1985;145:245–248. 218. Mirvis SE, Keramati B, Buckman R, et al. MR imaging of traumatic diaphragmatic rupture. J Comput Assist Tomogr 1988;12: 147–149. 219. Glazer HS, Lee JKT, Levitt RL, et al. Radiation fibrosis: differentiation from recurrent tumor by MR imaging. Radiology 1985;156:721–726. 220. Nyman R, Rehn S, Glimelius B, et al. Magnetic resonance imaging for assessment of treatment effects in mediastinal Hodgkin’s disease. Acta Radiol 1987;28:145–151. 221. Webb WR. MR imaging of treated mediastinal Hodgkin disease. Radiology 1989;170:315–316. 222. Gupta A, Frazer CK, Ferguson JM, et al. Acute pulmonary embolism: diagnosis with MR angiography. Radiology 1999; 210:353–359. 223. Ley S, Kauczor HU, Heussel CP, et al. Value of contrast-enhanced MR angiography and helical CT angiography in chronic thromboembolic pulmonary hypertension. Eur Radiol 2003;13: 2365–2371.

224. Meaney JFM, Weg JG, Chenevert TL, et al. Diagnosis of pulmonary embolism with magnetic resonance angiography. N Engl J Med 1997;336:1422–1427. 225. Oudkerk M, van Beek EJ, Wielopolski P, et al. Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism: a prospective study. Lancet 2002;359: 1643–1647. 226. Amundsen T, Kvaerness J, Jones RA, et al. Pulmonary embolism: detection with MR perfusion imaging of lung – a feasibility study. Radiology 1997;203:181–185. 227. Bergin CJ, Glover GM, Pauly J. Magnetic resonance imaging of the lung parenchyma. J Thorac Imaging 1993;8: 12–17. 228. Bergin CJ, Pauly JM, Macovski A. Lung parenchyma: projection reconstruction MR imaging. Radiology 1991;179:777–781. 229. Müller NL, Mayo JR, Zwirewich CV. Value of MR imaging in the evaluation of chronic infiltrative lung diseases: comparison with CT. AJR Am J Roentgenol 1992;158: 1205–1209. 230. McFadden RG, Carr TJ, Wood TE. Proton magnetic resonance imaging to stage activity of interstitial lung disease. Chest 1987;92:31–39. 231. Albert MS, Cates GD, Driehuys B, et al. Biological magnetic resonance imaging using laser-polarized 129Xe. Nature 1994; 370:199–201. 232. Edelman RR, Hatabu H, Tadamura E, et al. Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging. Nat Med 1996;2:1236–1239. 233. MacFall JR, Charles HC, Black RD, et al. Human lung air spaces: potential for MR imaging with hyperpolarized He-3. Radiology 1996;200:553–558. 234. Thomas SR, Gradon L, Pratsinis SE, et al. Perfluorocarbon compound aerosols for delivery to the lung as potential 19F magnetic resonance reporters of regional pulmonary pO2. Invest Radiol 1997;32: 29–38. 235. Kauczor HU, Hofmann D, Kreitner KF, et al. Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging. Radiology 1996;201: 564–568. 236. Salerno M, Altes TA, Brookeman JR, et al. Rapid hyperpolarized 3He diffusion MRI of healthy and emphysematous human lungs using an optimized interleaved-spiral pulse sequence. J Magn Reson Imaging 2003;17:581–588.

237. Altes TA, Mata J, de Lange EE, et al. Assessment of lung development using hyperpolarized helium-3 diffusion MR imaging. J Magn Reson Imaging 2006;24: 1277–1283. 238. Altes TA, Powers PL, Knight-Scott J, et al. Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings. J Magn Reson Imaging 2001;13: 378–384. 239. Altes TA, Rehm PK, Harrell F, et al. Ventilation imaging of the lung: comparison of hyperpolarized helium-3 MR imaging with Xe-133 scintigraphy. Acad Radiol 2004;11:729–734. 240. de Lange EE, Altes TA, Patrie JT, et al. The variability of regional airflow obstruction within the lungs of patients with asthma: assessment with hyperpolarized helium-3 magnetic resonance imaging. J Allergy Clin Immunol 2007;119:1072–1078. 241. Salerno M, Altes TA, Mugler JP 3rd, et al. Hyperpolarized noble gas MR imaging of the lung: potential clinical applications. Eur J Radiol 2001;40:33–44. 242. Salerno M, Brookeman JR, de Lange EE, et al. Hyperpolarized 3He lung imaging at 0.5 and 1.5 Tesla: a study of susceptibilityinduced effects. Magn Reson Med 2005;53: 212–216. 243. Salerno M, de Lange EE, Altes TA, et al. Emphysema: hyperpolarized helium 3 diffusion MR imaging of the lungs compared with spirometric indexes – initial experience. Radiology 2002;222: 252–260. 244. van Beek EJ, Wild JM, Kauczor HU, et al. Functional MRI of the lung using hyperpolarized 3-helium gas. J Magn Reson Imaging 2004;20:540–554. 245. Cai J, Altes TA, Miller GW, et al. MR grid-tagging using hyperpolarized helium-3 for regional quantitative assessment of pulmonary biomechanics and ventilation. Magn Reson Med 2007;58: 373–380. 246. Cai J, Miller GW, Altes TA, et al. Direct measurement of lung motion using hyperpolarized helium-3 MR tagging. Int J Radiat Oncol Biol Phys 2007;68: 650–653. 247. Mata J, Altes T, Knake J, et al. Hyperpolarized 3He MR imaging of the lung: effect of subject immobilization on the occurrence of ventilation defects. Acad Radiol 2008;15:260–264. 248. Mugler JP 3rd, Wang C, Miller GW, et al. Helium-3 diffusion MR imaging of the human lung over multiple time scales. Acad Radiol 2008;15:693–701.

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CHAPTER

2

The normal chest

AIRWAYS AND LUNGS Central airways Pulmonary hila Lung parenchyma The pleura Fissures Accessory fissures Incomplete fissures (Inferior) pulmonary ligaments MEDIASTINUM Normal mediastinum Mediastinal blood vessels Esophagus Thymus Mediastinal spaces Pretracheal space Aortopulmonary window Subcarinal space Right paratracheal space and posterior tracheal space

This chapter describes the normal anatomy of the airways, lungs, mediastinum, and diaphragm, as demonstrated on chest radiography (Figs 2.1–2.3), computed tomography (CT), and magnetic resonance imaging (MRI).

AIRWAYS AND LUNGS Central airways The trachea1,2 is a tube which, in children and young adults, passes downward and backward close to the midline (Fig. 2.4) and has sufficient flexibility to adapt to body position. In adults, the aorta may cause a recognizable impression and, in infants and young children, the brachiocephalic artery may indent the trachea. In older individuals, the intrathoracic trachea deviates slightly to the right to accommodate the left-sided arch. With unfolding and ectasia of the aorta, the trachea deviates more to the right as it descends into the chest and may also bow forward. In a CT study of 50 normal individuals, the midpoint of the trachea in the thorax lay between 1.6 cm to the right and 0.7 cm to the left of the midline.3 The trachea has 16–20 incomplete C, U, or horseshoe-shaped cartilage rings which can give the trachea a corrugated outline. Calcification of the cartilage rings is a common normal finding after the age of 40 years, increasing in frequency with the age of the individual;4 in one study, it was seen on CT in 50% of subjects in their seventh and eighth decades.5 The incidence of visible tracheal calcification on chest radiography is very small; it was less than 1% in a series of 5000 inpatients, most of whom were women over 70 years.6 In cross-section, the trachea is usually round, oval, or oval with a flattened posterior margin, the posterior margin being formed by

Anterior junction Posterior junction and paraspinal areas Retrocrural space Mediastinal and hilar lymph nodes Normal lymph node size Normal mediastinal contours on plain chest radiographs, frontal view Left mediastinal border Right mediastinal border Anterior junction Posterior junction and azygoesophageal recess Paraspinal lines Lateral view Mediastinum above the aortic arch Trachea and retrotracheal area Retrosternal line Inferior vena cava DIAPHRAGM AND CHEST WALL

the fibromuscular membrane. It may occasionally show other configurations such as a square or inverted pear shape.4,7,8 The trachea enters the thorax 1–3 cm above the level of the suprasternal notch and the intrathoracic portion is 6–9  cm in length.8 The range of tracheal diameters in adults on chest radiography in men is 13– 25 mm in coronal plane, and 13–27 mm in sagittal plane; in women the diameters are 10–21  mm in coronal plane, and 10–23  mm in sagittal plane.9 On CT, which allows precise assessment of diameters and cross-sectional areas without magnification, the mean transverse diameter is 15.2  mm (SD 1.4) for women and 18.2  mm (SD 1.2) for men, the lower limit of normal being 12.3  mm for women and 15.9 mm for men.10 The diameters in the growing child and young adult have been documented by Griscom and Wohl.11 In addition to sex and age differences, it is probable there are interracial differences in the diameter and configuration of the trachea.12 Cross-sectional areas can also be measured: the mean is 194  mm2 (SD 35) in women and 272 mm2 (SD 33) in men. The normal crosssectional area on forced expiration is considerably less than on full inspiration: in 10 normal male volunteers the cross-sectional area dropped from a mean of 280  mm2 (SD 50.5) at full inspiration to 178 mm2 (SD 40.2) at end-expiration.13 The major change is forward movement or invagination of the posterior wall of the trachea, leading to a marked reduction in the anteroposterior diameter14–18 (Fig. 2.5). The trachea divides into the two mainstem bronchi at the carina at approximately the level of T5. The left main bronchus extends up to twice as far as the right main bronchus before giving off its upper lobe division, the left main bronchus is approximately 50 mm long and the right main bronchus is approximately 25 mm long. In children the angles are symmetric, but in adults the right mainstem bronchus has a steeper angle than the left. The range of subcarinal angles is wide;19 in one survey they varied between 35° and 90.5° (mean 60.8°, SD 11.8°).20 Abnormalities of angle can, therefore, only

39

Chapter 2 • The Normal Chest

A

B

Fig. 2.1  Radiograph of a normal chest in the A, posteroanterior and B, left lateral projection.

A

B

Fig. 2.2  A, Frontal and B, lateral chest radiographs of a healthy woman. Note mild pectus excavatum on the lateral image (arrows).

40

Airways and Lungs

B

A

Fig. 2.3  Radiographs of a healthy elderly man obtained in A, inspiration and B, expiration. Note that on B, the lung volumes are smaller, the lung bases are less translucent, and the diameter of the cardiac silhouette is relatively enlarged.

be diagnosed by right–left comparisons, not by absolute measurement. The lobar and segmental branching pattern is shown in Fig. 2.6 and the branching pattern of the airways beyond the segmental bronchi is shown diagrammatically in Fig. 2.7. The walls of the segmental bronchi are invisible on chest radiography except when seen end-on as ring shadows. They are, however, clearly seen on CT, particularly on thin contiguous sections.21 The CT anatomy of central airways has been described in the literature.8,22–24 The reader is also referred to a number of detailed articles concerning the CT appearance of the segmental and subsegmental airways: upper lobes,25–28 lower lobes,29,30 and lingular segments.25 Variations in bronchial anatomy,31–34 particularly those affecting segmental and subsegmental airways, are fairly common, but are rarely clinically relevant (Fig. 2.8). However, they can be confusing to bronchoscopists searching for landmarks. There are two kinds of anomalous airways: (i) displaced, in which a standard airway arises from an unusual site; and (ii) supernumerary. Displaced airways are much commoner than supernumerary ones. Ghaye et al.35 have written a detailed, illustrated review including an analysis of their experience of both types of variants on CT examination. Anomalous bronchi can be well shown by thin-section multidetector CT (MDCT) with three-dimensional reconstructions, or by MRI.33,36 The reported variations are: • Tracheal bronchus, also known as bronchus suis, is an anomaly in which either a segment of the right upper lobe or the entire right upper lobe bronchus originates from the trachea rather than the main bronchus (Fig. 2.8). Tracheal bronchus is found in 0.5–3% of bronchoscopies.37,38 A tracheal bronchus arises from the lateral wall of the trachea,35,39,40 usually within a few centimeters of the mainstem take-off. It is much more common on the right side and is usually a displaced apical segmental bronchus, but it may be supernumerary supplying the apical segment, a displaced upper lobe airway, or even a supernumerary upper lobe airway.41 When a tracheal bronchus is a displaced upper lobe airway, the more distal trachea is narrowed.42 The anomaly is usually clinically inapparent, but occasionally the orifice is

• •

•

•

narrow41,43,44 or the airway is bronchiectatic,41,43 which may lead to recurrent distal pneumonia and abscess formation. Apical cyst formation in the lung supplied by a tracheal bronchus is also described.45 There may be a common origin of the right upper and middle lobe bronchi.46 An accessory cardiac bronchus is a supernumerary bronchus arising from the medial aspect of the right main bronchus or the bronchus intermedius proximal to the origin of the right superior (apical) segmental airway of the lower lobe. It usually passes downward and medially toward the heart, paralleling the bronchus intermedius. It is either blind-ending, in which case it may have a nodule of nonaerated lung tissue at its tip, or supplies a small ventilated ‘lobule’.47,48 Most patients are asymptomatic; however, an accessory cardiac bronchus may be associated with local infection49 or hemoptysis. Ghaye et  al.35 found a frequency of accessory cardiac bronchus of 0.08% in 17 500 consecutive patients. The diameter of the accessory bronchus ranged from 4  to 14  mm, and the length ranged from 4  to 23 mm. The simultaneous occurrence of an accessory cardiac and tracheal bronchus has been reported.48,50,51 Lateral inversion of right- and left-sided airways occurs in situs inversus. With situs ambiguus the airway has either a bilateral right-sided or left-sided configuration. Such anomalies are strongly associated with serious congenital heart disease.52,53 Isolated cases of the so-called bridging bronchus have been described.54 In this condition, the right lower lobe bronchus arises from the left main bronchus and crosses or ‘bridges’ the mediastinum to reach the right lung (Fig. 2.9). This anomaly is exceedingly rare.

Pulmonary hila Understanding the appearances of the normal hila requires an appreciation of the anatomy of the major bronchi, hilar blood

41

Chapter 2 • The Normal Chest

A

B

C

A

Fig. 2.4  Volumetric CT images of the trachea. A, Minimal intensity projections show the trachea in its entire course. B, Surface shaded display shows the relation between trachea and lungs. C, Surface shaded display of the trachea alone shows lobar and segmental bronchial anatomy to advantage.

B

Fig. 2.5  CT images of the trachea in A, inspiration and B, expiration. In inspiration, the trachea has a near rounded appearance. In expiration, the posterior wall of the trachea bulges inward (arrow).

42

Airways and Lungs

A

B

C

D

E

F

Fig. 2.6  Divisions of the bronchial tree shown by bronchography. A, Right bronchial tree, anteroposterior view. B, Right bronchial tree, right posterior oblique view. C, Right bronchial tree, lateral view. D, Left bronchial tree, AP view. E, left bronchial tree, left posterior oblique view. F, Left bronchial tree, lateral view.

43

Chapter 2 • The Normal Chest

LUL apicoposterior segment (B1+2)

RUL apical segment (B1) RUL posterior segment (B2)

LUL anterior segment (B3)

RUL anterior segment (B3)

Lingular superior segment (B4)

RLL superior segment (B6)

LLL superior segment (B6)

ML lateral segment (B4)

Lingular inferior segment (B5)

ML medial segment (B5)

LLL anterior medial basal segment (B7+8)

RLL anterior basal segment (B8) RLL lateral basal segment (B9)

LLL lateral basal segment (B9)

RLL posterior basal segment (B10)

A

LLL posterior basal segment (B10)

RLL medial basal segment (B7)

RUL apical segment (B1) RUL anterior segment (B3) ML medial segment (B5)

RUL posterior segment (B2) RLL superior segment (B6) RLL medial basal segment (B7)

ML lateral segment (B4) RLL anterior basal segment (B8)

RLL posterior basal segment (B10) RLL lateral basal segment (B9)

B

LUL apicoposterior segment (B1+2) LUL anterior segment (B3) LLL superior segment (B6)

Lingular superior segment (B4) Lingular inferior segment (B5)

LLL posterior basal segment (B6)

LLL anterior basal segment (B7+8) LLL lateral basal segment (B9)

C

Fig. 2.7  Diagram of branches of airways beyond the segmental bronchi. A, AP view. B, Lateral view of right bronchial tree. C, Lateral view of left bronchial tree. RUL, right upper lobe; RLL, right lower lobe; ML, middle lobe; LUL, left upper lobe; LLL, left lower lobe.

44

Airways and Lungs

A

B

Fig. 2.8  CT images of right upper lobe bronchus arising from the trachea. A, Transverse CT image shows high take-off of the bronchus from the trachea (arrow). B, Coronal reconstruction clearly shows the tracheal bronchus (arrow).

Fig. 2.9  Bridging bronchus in a child with recurrent right lower lobe pneumonia. CT shows the bronchus (black arrow) arising from the left lung and crossing the mediastinum to supply the right lower lobe. (Case courtesy of N L Müller, Vancouver, BC, Canada.)

vessels (Figs 2.10 and 2.11),24,55–57 and hilar lymph nodes,58,59 and their relationship to one another on cross-sectional imaging (Fig. 2.12). Connective tissue does not contribute significantly to the bulk of the hila, and the small amount of fat between the vessels is, for practical purposes, visible only on CT and MRI. The following points of anatomy should be remembered: • The right main bronchus has a more vertical course than the left main bronchus and the right upper lobe bronchus arises more proximally than the left upper lobe bronchus. • The right mainstem bronchus and its divisions into the right upper lobe bronchus and bronchus intermedius are outlined posteriorly by lung so that the posterior wall of these portions of the bronchial tree is seen as a thin stripe on lateral chest radiographs (Fig. 2.13), except for a focal nodule, representing a small draining pulmonary vein in some 5% of normal subjects.60 This region is, therefore, an important area in which to look for masses, such as lymphadenopathy. On the left side the lower lobe artery intervenes between the lung and the bronchial tree, and only a small tongue of lung can invaginate between the left lower lobe artery and the descending aorta to contact the posterior wall of the left mainstem bronchus (Fig. 2.12).61

• The right pulmonary artery passes anterior to the major bronchi to reach the lateral aspect of the bronchus intermedius and right lower lobe bronchus, whereas the left pulmonary artery arches over the left main bronchus and left upper lobe bronchus to descend posterolateral to the left lower lobe bronchus. • The pulmonary veins are similar on the two sides. The superior pulmonary veins are the anterior structures in the upper and mid-hilum on both sides, and the inferior pulmonary veins run obliquely forward beneath the divisions of each lower lobe artery to enter the left atrium. Because the central portions of the pulmonary arteries are so differently organized on the two sides, the relationship between the major veins and arteries differs. On the right, the superior pulmonary vein is separated from the central bronchi by the lower division of the right pulmonary artery, whereas on the left, the superior pulmonary vein is separated from the lower division of the left pulmonary artery by the bronchial tree. • On chest radiographs, the transverse diameter of the lower lobe arteries prior to their segmental divisions can be measured with reasonable accuracy. These arteries should normally be 9–16 mm in diameter (Fig. 2.14). The large round shadow seen on lateral and oblique views of the right hilum is a combination of the right pulmonary artery and the superior pulmonary vein. The combined shadows of these two vessels may be sufficiently large to be confused with a mass. • Normally there are no large vessels traversing the angle between the middle and the lower lobe bronchi on the right, or the angle between the upper and lower lobe bronchi on the left, on lateral or oblique plain chest radiographs. Therefore, a rounded shadow larger than 1 cm in either of these angles is likely to be a mass rather than a normal vessel.62 • Normal hilar lymph nodes are not recognizable on chest radiography, but are identifiable on contrast-enhanced CT as triangular or linear soft tissue densities.58 The normal range of size of hilar lymph nodes has not yet been fully established, but Remy-Jardin et al.58 suggested a short-axis figure of up to 3 mm, except around the left lower lobe artery where the diameter may be somewhat larger in healthy individuals. The shape of the hila on CT is important when trying to assess the normality of lymph nodes. In normal subjects, the interfaces with the lungs are concave except at the sites of blood vessels.59 • A collection of fat between the bifurcation of the right pulmonary artery as it exits the mediastinum, lying anterolateral to the bronchus intermedius, may be confused with lymphadenopathy if this anatomic variant is not recognized.63 The major

45

Chapter 2 • The Normal Chest

A

C

46

B

Fig. 2.10  Pulmonary arteries and veins shown by pulmonary angiography. A, Anteroposterior view of pulmonary arteries. B, AP view of pulmonary veins in the same patient. C, Lateral view of pulmonary arteries (different patient). LPA, Left pulmonary artery; RPA, right pulmonary artery.

Airways and Lungs

A

C

B

D

Fig. 2.11  Diagrammatic illustration of the hilar structures. A, Frontal view. B, Right hilum: oblique view. C, Left hilum: oblique view. D, A lateral radiograph with the position of the central pulmonary arteries and veins drawn in. The left and right pulmonary arteries are indicated by dotted lines (the left lies posterior to the right). The inferior pulmonary veins are similar on the two sides and are superimposed (only one is drawn in). The right superior pulmonary vein is on a more anterior plane than the left superior pulmonary vein.

47

Chapter 2 • The Normal Chest

BCT LCCA

LSA

A

B

Thy

AA

Tr

AZ

D

C

AA

MPA LSPV

RPA

LPA

RMB

DA E

LMB

F

Fig. 2.12  (A–J) CT sections at representative levels of the mediastinum. BCT, brachiocephalic trunk; LCCA, left common carotid artery; LSA, left subclavian artery; Thy, thymus; AA, ascending aorta; Az, azygos vein; Tr, trachea; MPA, main pulmonary artery; RPA, right pulmonary artery; LPA, left pulmonary artery; DA, descending aorta; LSPV, left superior pulmonary vein; RMB, right main bronchus; LMB, left main bronchus; RMLB, right middle lobe bronchus; Ling B, lingula bronchus; LLLB, left lower lobe bronchus; RLLB, right lower lobe bronchus; RLA, right lobe artery; LLA, left lobe artery.

48

Airways and Lungs

RMLB Ling B

RLLB G

H

Segm branches of RLA and RLLB I

LLLB

Segm branches of LLA and LLLB

J

Fig. 2.12  Continued

49

Chapter 2 • The Normal Chest

B

A

Fig. 2.13  A, A lateral radiograph of normal pulmonary hila. The yellow arrow points to the posterior wall of the right main bronchus, and the red arrows point to the posterior wall of bronchus intermedius. B, Lateral view in a patient with lymphangitis carcinomatosa shows thickening of the tissues posterior to bronchus intermedius (arrows).

difficulty is that the fat in question may be combined in the same CT section as horizontal portions of the adjacent right pulmonary artery and appear to be of soft tissue rather than fat density, due to partial volume artifact.

Lung parenchyma The segmental bronchi divide into progressively smaller airways until, after 6–20 divisions, they become bronchioles. The bronchioles divide, and the last of the purely conducting airways are known as the terminal bronchioles. Beyond the terminal bronchioles lie the acini, the gas-exchange units of the lung. The entire airway down to the terminal bronchiole can be demonstrated on a well-filled bronchogram. The bronchopulmonary segments are based on the divisions of the bronchi and can be identified with reasonable accuracy by CT.23,27 The boundaries between segments are complex in shape; the segments have been likened to the pieces of a three-dimensional jigsaw puzzle. With the rare exception of accessory fissures, the segments are not delimited by septa. Although processes such as atelectasis, pneumonia, or edema may predominate in one segment or another, these processes never conform precisely to the whole of just one segment, since collateral air drift occurs from adjacent segments. In other words, it is unusual to see visible evidence of precise segmental boundaries. The pulmonary blood vessels (Fig. 2.10) are responsible for the branching linear markings within the lungs. It is not possible to distinguish arteries from veins in the outer two-thirds of the lungs on chest radiography. More centrally, the orientation of the arteries

50

and veins differs: the inferior pulmonary veins draining the lower lobes run more horizontally, and the lower lobe arteries more vertically. In the upper lobes, the arteries and veins show a similar gently curving vertical orientation, but the upper lobe veins (when not superimposed on the arteries) lie lateral to the arteries and can sometimes be traced to the main venous trunk, the superior pulmonary vein, even on chest radiographs. The diameter of the blood vessels beyond the hilum varies according to the patient’s position. On films taken with the patient in the upright position, the diameter of both the arteries and veins increases gradually from apex to base; for comparisons of diameter to be valid, the measurements must be made equidistant from the hilum. These changes in vessel size correlate with physiologic studies of perfusion, which show that in an erect subject there is a gradation of blood flow increasing from apex to base, a difference that is less marked when supine. Although general statements regarding differences in regional blood vessel size can be made, meaningful measurements of individual peripheral pulmonary vessels are difficult to make on plain chest radiographs, since it is not possible to know whether the vessel being measured is an artery or a vein or what degree of magnification has been used. The following measurements are suggested for upright chest films: • The artery and bronchus of the anterior segment of either or both upper lobes are frequently seen end-on. The diameter of the artery is usually slightly less than the diameter of the bronchus (4–5 mm).60 • Woodring64 measured the visible bronchi and immediately adjacent arteries in the upper and lower half of the chest in

Airways and Lungs

A

Round

Oval

Crescentic

Triangular

B

Fig. 2.15  Intrapulmonary lymph nodes. A, Typical locations of intrapulmonary lymph nodes in relation to the pulmonary lobule and B, typical shapes of intrapulmonary lymph nodes on CT.

Fig. 2.14  The right lower lobe artery. The diameter indicated by the arrows should be between 9 mm and 16 mm. upright patients and found that the artery/bronchus ratio was 0.85 (SD 0.15) for the upper zone and 1.34 (SD 0.25) for the lower zone. • Vessels in the first anterior interspace should not exceed 3 mm in diameter.65 The acinus, which is 5–6 mm in diameter, comprises respiratory bronchioles, alveolar ducts, and alveoli. Up to 24 acini are grouped together in secondary pulmonary lobules, each 1–3 cm in diameter, which in the lung periphery are separated by interlobular septa. When thickened by disease, these septa form so-called septal lines (Kerley B lines). The anatomy of the pulmonary lobule and the appearance of the normal pulmonary parenchyma on high-resolution CT (HRCT) is discussed in Chapter 4. A rich network of lymphatics drains the lung and pleura. The subpleural lymphatic vessels are found just beneath the pleura, at the junction of the interlobular septa and pleura, where they interconnect with one another as well as with the lymphatic vessels in the interlobular septa. The lymph then flows to the hilum by way of lymphatic channels that run peribronchially and in the deep septa. The lymphatic network is radiographically invisible, but in certain conditions, such as when the lung is edematous or when the lymphatic channels are occluded by tumor, the thickened septa containing the dilated lymphatics may become visible. There are a few intrapulmonary lymph nodes, which are small and are not identifiable on plain chest radiographs. CT shows them as small, peripherally located, often coffeebean-shaped nodules (Figs 2.15–2.18).66,67 In one series of 19 cases shown by CT, the intrapulmonary lymph nodes were either abutting the pleura or within 8 mm of the pleura, were round or oval in shape with homogeneous density and had well-defined borders, with the exception

Fig. 2.16  An intrapulmonary lymph node (arrow) identified at CT (proved following surgical resection, undertaken because the finding was thought to be a possible small lung cancer).

of one node which showed an irregular border resembling a small carcinoma. None of the nodes was larger than 12 mm. All were in the lower lobes or middle lobe/lingula.68 The subpleural, lower lobe predominance of intrapulmonary lymph nodes, and the fact that one or two have an irregular outline indistinguishable from lung cancer on CT, has also been reported by others.69,70 Pathologically, intrapulmonary lymph nodes are believed to result from the presence of inorganic dust within the lungs and lymphatic obstruction.71

51

Chapter 2 • The Normal Chest

A

B

Fig. 2.17  A, B, CT shows intrapulmonary lymph nodes (arrows) in two different patients, both located in the middle lobe. In A, septal lines can be seen contacting the lymph node, a typical feature.

A

B

Fig. 2.18  CT shows A, intrapulmonary lymph node (arrow) at baseline CT and B, at follow-up 4 years later. In the interval, minimal growth was observed and the nodule was resected because of suspicion for lung cancer – its nature was confirmed on histopathologic examination.

52

Airways and Lungs

Anterolateral / Posterolateral

Paravertebral

Lung

7

1 3

6

Posterior

4 Rib

2 5

Rib

Fig. 2.19  Diagrammatic anatomy of the lung–chest wall interface. The component layers vary in different segments. Anatomically identifiable layers (as illustrated) are not necessarily separately demonstrated on images and consist of (1) parietal and visceral pleura, which is too thin to image; (2) subpleural fat, which may be absent or if present is of variable thickness; (3) endothoracic fascia; (4) innermost intercostal muscle (3 and 4 appear as one structure on images); (5) intercostal fat and intercostal vessels; (6) internal and external intercostal muscles; and (7) subcostal muscle (anteriorly the transverse thoracic muscle).

The pleura The pleural space is lined by a smooth membrane consisting of a single layer of flat, in part cuboidal, mesothelial cells, lubricated by a small amount of fluid. Inferiorly the parietal pleura is tucked into the costophrenic sulcus. The disposition of the sulcus is important in upper abdominal interventional procedures. On the surface of the body the inferior edge of the sulcus crosses the xiphoid and eighth costochondral junction to reach the midaxillary line at the level of the tenth rib.72,73 It then passes horizontally across the eleventh and twelfth ribs to reach the first lumbar vertebral body. The cephalad part of the sulcus is occupied to a variable extent by lung, whereas caudally the sulcus is empty and the diaphragm and chest wall are separated only by the two layers of parietal pleura. The distance between the lowest part of the sulcus and the lung edge depends on the phase of respiration and the segment of sulcus being considered. The right midaxillary intercostal approach is often used for percutaneous introduction of needles into the upper abdomen, and because the pleural reflection reaches the tenth rib in this region, it is common for the pleura to be punctured, for example, during percutaneous transhepatic biliary or subphrenic abscess drainage when bile or pus may flow into the pleural space. The parietal mesothelial cells lie on loose, fat-containing, areolar connective tissue bounded externally by the endothoracic fascia. Five layers can be defined in the visceral pleura:74,75 (1) a mesothelial layer; (2) a thin layer of connective tissue; (3) a strong layer of connective tissue – the chief layer; (4) a vascular layer; and (5) the limiting lung membrane, connected by collagen and elastic fibers to the chief layer.74 The normal pleura cannot be imaged as such by CT, even by HRCT, because it cannot be separated from immediately adjacent structures (Fig. 2.19). The CT appearances of the normal interface between chest wall and pulmonary parenchyma have been reported in detail by Im and co-workers.76 In normal subjects, there is a linear opacity of soft tissue density, 1–2 mm thick, overlying an intercostal space, connecting the inner aspects of the ribs (Figs 2.20 and 2.21). This opacity, the intercostal stripe, is produced by two layers of pleura, extrapleural fat, the endothoracic fascia, and the innermost intercostal muscle. It is marginated centrally by air in the lung and peripherally by fat lying between the innermost and internal intercostal muscles. The intercostal stripe disappears on the inner aspect of ribs, since at this point it generally consists only of pleura, extra-

Fig. 2.20  The lung–chest wall interface on computed tomography at 10 mm collimation. Joining the inner rib margins is a soft tissue layer made up of pleura, endothoracic fascia, and innermost intercostal muscle (yellow arrow). It lies on intercostal fat, outside which are internal and external intercostal muscles. No soft tissue is seen inside the ribs (red arrow) except where the thinner rib margin is sectioned (blue arrow). The paravertebral interface is marginated by a thin or invisible line (white arrow), adjacent to which it is ‘thickened’ by a posterior intercostal vein draining into the hemiazygos vein.

pleural fat, and endothoracic fascia, which are too thin to resolve. In some circumstances, however, it can be seen: • Posteriorly, where the ribs are parallel to the scan plane and the CT section is through the lower tapering edge, the intercostal stripe is then seen on the inner aspect of the rib (Fig. 2.20). • When there is significant fat between the parietal pleura and endothoracic fascia; this characteristically occurs laterally at the

53

Chapter 2 • The Normal Chest

Fig. 2.21  The lung–chest wall interface in the paravertebral region on HRCT. The normal interface is marginated by a layer that is undetectable (yellow arrow) or very thin (red arrow). The soft tissue density on the left (blue arrow) is a posterior intercostal vein. That on the right (white arrow) is probably also venous but at this low level in the chest could be caused by subcostal muscle. level of the fourth to eighth ribs, and in obese individuals may be conspicuous on the plain chest radiograph. • Low in the parasternal and paravertebral region, poorly developed muscle slips (anteriorly the sternocostal muscle and posteriorly the subcostal muscle) lie on the inside of the ribs, producing linear, soft tissue opacities 1–2 mm thick (Fig. 2.19). The sternocostal muscle is commonly identified, but the subcostal muscle is seen less often (Fig. 2.21). These muscles are distinguished from pleural thickening by being smooth, uniform, and bilateral. • Paravertebrally, intercostal muscles are absent and the lung– soft tissue interface is formed by a very thin line produced by two layers of pleura and the endothoracic fascia (Figs 2.19 and 2.20). Linear soft tissue opacities 2–3  mm thick lying immediately underneath this interface are produced by intercostal veins, which can be positively identified when they join the azygos or hemiazygos vein.

Fig. 2.22  Major fissures on lateral chest radiograph. The inferior part of both fissures can be seen. The right major fissure (red arrows) descends to abut the higher right dome of the diaphragm (small red arrow). The left major fissure (yellow arrows) descends to abut the lower left dome of the diaphragm that can be recognized by the nearby gas bubble in the stomach (asterisk).

Fissures The lobes of the lungs are separated by fissures,77 which in the majority of people are incomplete. In other words, lung parenchyma, together with its bronchovascular bundles and draining veins, passes from one lobe to another through holes in the fissures.26,78,79 The frequency of incomplete fissures in different series ranges from 12.5% to 73% for the major fissures80 and from 60% to 90% for the minor fissures.81–83 These defects are important because they allow collateral air drift between lobes, permit disease to ‘cross’ fissures, and also limit the accumulation of pleural fluid in the interlobar portions of the pleural cavity.84–86 The major fissures on each side are similar. The left major (oblique) fissure divides the left lung into an upper and lower lobe. The right lung has an additional fissure, the minor (horizontal) fissure, which separates the middle from the right upper lobe. The major fissures run obliquely forward and downward, passing through the hilum, commencing at approximately the level of the fifth thoracic vertebra to contact the diaphragm up to 3 cm behind the anterior chest wall. Portions of one or both major fissures are frequently seen on the lateral chest radiograph (Figs 2.22 and 2.23).

54

Fig. 2.23  Frontal chest radiograph shows fat extending into the right major fissure as a curvilinear structure (yellow arrows). Note ample extrapleural fat (red arrows).

Airways and Lungs It is, however, unusual to be able to trace both fissures in their entirety on chest radiographs. In Proto and Speckman’s study87 of lateral chest radiographs, part of a right fissure was seen in 22% of the images, part of a left fissure was seen in 14%, and part of a major fissure of indeterminate side was seen in 62%; in only 2% of radiographs was a complete major fissure identified. When the major fissure is incompletely seen, it is almost always the lower portion that is detected. Each major fissure follows a gently curving plane somewhat similar to that of a propeller blade, with the upper portion facing forward and laterally and the lower portion facing forward and medially. Below the hila the lateral portions of the major fissures lie further forward than do the medial portions, whereas above the hila this relationship reverses (Fig. 2.24). These undulations cannot be traced on the chest radiograph. Therefore, on a lateral view the radiologist cannot be certain what portion of the fissure is being profiled, and it is easy to misinterpret a fissure as displaced when it is in fact in normal position. The inferior few centimeters of either or both major fissures are often wide as a result of fat or pleural thickening between the leaves of the pleura. This thickening may lead to loss of silhouette where the fissure contacts the diaphragm. The major fissure is not usually seen on a frontal radiograph, but it may be detected under three circumstances. First, the upper edge may become visible where it contacts the posterior chest wall when extrapleural fat enters the lips of the fissure. This generates the ‘superolateral major fissure’, a curved line or stripe that starts medially above the hilum and curves downward and laterally.88 Second,

A

the upper aspect of the major fissure can be tangential to the X-ray beam, particularly on lordotic projections,89 generating a hairline opacity that runs obliquely across the mid-zone (Fig. 2.25). Medially, this fissure line often crosses the hilum to end against the spine, allowing it to be distinguished from the minor fissure, which never crosses hilar vessels. Third, reorientation of the lateral aspect of the lower part of the oblique fissure probably accounts for the vertical fissure,90–92 seen particularly on the right, low down close to the chest wall. It is most often described in babies with lower lobe volume loss and cardiomegaly.90 The minor fissure fans out forward and laterally in a horizontal direction from the right hilum. On a standard upright frontal chest radiograph the minor fissure contacts the lateral chest wall at or near the axillary portion of the right sixth rib. The fissure curves gently, usually downward in the anterior and lateral portions. Because of the undulations of the major fissure the posterior portion of the minor fissure may be projected posterior to the right major fissure on a normal lateral view. On frontal chest radiographs some or all of the minor fissure is seen in about 50–60% of patients.93 The whole fissure is seen in only 7% of individuals. When just a portion is seen, it is much more commonly the lateral than the medial portion. Felson93 pointed out that on a frontal chest radiograph the fissure ends medially at the interlobar pulmonary artery within about 1 cm of the point at which the superior venous trunk crosses the lower lobe artery (Fig. 2.26). This observation can be helpful in finding and identifying the fissure. On a lateral view, the minor fissure is seen in about half of chest radiographs: in part in 44% and in total in 6%.94

B

Inferior

Superior

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D

Fig. 2.24  Pleural fissures (HRCT). A, Section through the upper zones. The curving major fissures are clearly seen as lines. B, The minor fissure is seen as a zone of avascularity radiating out from the right hilum. C, Section through the lower zones showing the major fissures. Note the reverse curvature compared with the section through the upper zones. D, The common configuration of major fissures oriented as for CT. The arrows indicate the direction of the X-ray beam for lateral chest radiography.

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Chapter 2 • The Normal Chest

Fig. 2.26  The minor fissure. The fissure stops medially at the lateral margin of the interlobar pulmonary artery at a point approximately 1 cm beyond the Y-point of the hilum where the artery and vein cross. This is a useful identifying feature of the minor fissure.

Fig. 2.25  The major fissure on a frontal radiograph. The reoriented major fissure (yellow arrows) is visible on a frontal radiograph as an oblique line. It can be distinguished from the minor fissure (red arrow) because it passes more medially, overlying the right hilum and ending at the spine.

On 5–10  mm CT sections the position of the major fissures can usually be predicted by noting the relatively avascular zone that forms the outer cortex of the lobe.79,95,96 The region of the major fissures is seen as a band of avascularity, or a zone with much smaller vessels, traversing the lung. The major fissures may be seen as lines but, because they run obliquely through the sections, the fissure itself may be invisible or may be seen as a poorly defined band of density.79,97 With thin-section CT the left major fissure is seen as a line throughout its course in almost all subjects (see Fig. 2.24), but the line may not be visible in upper and middle portions of the right major fissure in up to a quarter of patients, presumably because the right major fissure is more obliquely oriented to the scanning plane.79 The minor fissure is in the plane of section of the CT scanner, and therefore when in normal position it is not seen as a line in axial sections. Its position can usually be inferred from the large, triangular, or oval deficiency of vessels on one or more sections just above the level of the bronchus intermedius.96,98,99 With HRCT, a variety of normal patterns are encountered, depending on the precise shape of the minor fissure.78 Because the fissure may assume the shape of an upward-arching dome, some portions may run sufficiently obliquely through the section to be seen as a line, an illdefined band shadow or a rounded density (Fig. 2.27).78,99

Accessory fissures Accessory fissures are clefts of varying depth in the outer surface of the lung that delineate accessory lobes. In one CT study of 50 patients, 22% had some form of accessory fissure;100 and in another

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study of 186 patients, 32% had an accessory fissure.101 Four accessory fissures are either common or easily recognized: • The best known accessory fissure, seen in up to 1% of the population, is the ‘azygos lobe fissure’ (Fig. 2.28), so-called because it contains the azygos vein within its lower margin. The fissure is almost invariably on the right side, although left-sided ‘azygos’ fissures have been described, in which case the vein at the base of the fissure is the superior intercostal vein.102 The fissure results from failure of normal migration of the azygos vein from the chest wall through the upper lobe to its usual position in the tracheobronchial angle, so that the invaginated visceral and parietal pleurae persist to form a fissure in the lung. The altered course of the azygos vein together with the fissure is readily seen at CT.103 Since there is no corresponding alteration in the segmental architecture of the lung, the term ‘lobe’ is a misnomer: the portion of the lung is supplied by branches of the apical segment bronchus with or without a contribution from the posterior segmental airway.104 The ‘azygos lobe’ is not unduly susceptible to disease. A potential diagnostic pitfall is that the ‘azygos lobe’ may occupy less volume than the equivalent normal lung and may therefore appear relatively opaque,105 even when no disease is present (Fig. 2.29). The right brachiocephalic vein may on rare occasion course through the anterior portion of the azygos fissure.106 • The ‘inferior accessory fissure’ usually incompletely separates the medial basal segment from the rest of the lower lobe. Because this segment lies anteromedially in the lower lobe, the accessory fissure has components that are oriented both sagittally and coronally (Fig. 2.30) and are tangential to frontal and lateral X-ray beams, respectively; even so the fissure is rarely seen on lateral radiographs. The frequency of occurrence is difficult to ascertain because the fissure varies greatly in depth and prominence from one examination to the next.100 The reported prevalence also depends on the method of detection. The fissure is present in 30–50% of anatomic specimens,90 in 16–21% of CT scans,100,101 and in 5–10% of chest radiographs.90,100,107 On the frontal radiograph, the fissure is a hairline that arises from the medial aspect of the hemidiaphragm and ascends obliquely

Airways and Lungs

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Fig. 2.27  HRCT of the minor fissure. A, Sometimes the minor fissure is bounded by a curvilinear band of density because the section is close to the dome of the fissure. B, The minor fissure may be seen as a faint homogeneous density when the section is through the apex of the dome of the fissure.

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Fig. 2.28  A typical example of the azygos fissure. A, The yellow arrow points to the fissure. The red arrow points to the azygos vein in the lower margin of the fissure. Note that the azygos vein is not in its usual position in the tracheobronchial angle. B, CT in a different patient shows fissure of azygos lobe (arrows); and C, the azygos vein in its complete intrapulmonary course (arrows).

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Fig. 2.29  Opaque lung medial to the azygos fissure. This appearance can be a normal finding. The opacity does not represent disease.

A

toward the hilum (Fig. 2.31). Sometimes there is a small triangular peak at its diaphragmatic end, and this, with a very short fissure line, may be all that is seen. At the other extreme the fissure may be long, reaching all the way to the hilum.93 Although the left lower lobe lacks a separate medial basal segment, the anteromedial basal bronchus divides early into two components analogous to the medial and anterior segmental bronchi on the right,100 and an inferior accessory fissure is about as common on the left as the right. However, it is not detected with equal frequency on radiographic examination; in one series of 500 radiographs 80% of inferior accessory fissures were right sided, 12% were left sided, and 7% were bilateral.107 On the lateral radiograph the inferior accessory fissure is occasionally seen as a vertical line, often associated with a diaphragmatic peak in the region of the esophagus.100 The inferior pulmonary ligament is close to the medial portion of the inferior accessory fissure, and some diaphragmatic peaks on the lateral radiograph in this region are really due to the inferior pulmonary ligament and its septum. On CT the fissure appears on sections near the diaphragm as an arc, concave to the mediastinum, extending from the major fissure back to the mediastinum near the esophagus.100,101 Should the inferior accessory fissure marginate a pneumonia in the medial basal segment, the triangular opacity has a sharp outer border,108 which may mimic a collapsed lower lobe. Other lesions such as pleural effusion, mediastinal mass, hernia, or fat pad may be simulated.100 • The ‘superior accessory fissure’ separates the superior (apical) segment of a lower lobe from the basal segments (Fig. 2.32) and superficially resembles a minor fissure on a frontal radiograph. It was identified on 6% of lateral radiographs in one series,94 a figure that seems high when judged by general experience and CT series.101 The minor fissure lies above the middle lobe bronchus, and the superior accessory fissure lies below the superior segmental bronchus. Because both of these airways arise at

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Fig. 2.30  CT sections in two different individuals show A, incomplete (arrows) and B, complete (arrows) accessory fissure delineating the cardiac lobe.

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Airways and Lungs

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Fig. 2.31  A, CT section shows both a lower lobe accessory fissure (red arrow) and middle lobe accessory fissure (yellow arrow) separating the medial from the lateral segment. B, This latter accessory fissure can also be seen on the coronal reconstruction (arrows).

line or a boundary to atelectasis or pleural fluid, similar to the major fissures.109 • The ‘left minor fissure’ is present in 8–18% of people but is only rarely detected on posteroanterior (PA) and lateral radiographs, with a reported frequency of 1.6%.110 It separates the lingula from the rest of the left upper lobe and is analogous to the minor fissure. It is usually arched and located more cephalad than the minor fissure, and slopes medially and downward (Fig. 2.33). Other rare accessory fissures include intersegmental fissures between the medial and lateral segments of the right middle lobe (Fig. 2.31), the superior and inferior segments of the lingula, the segments of the upper lobes (Fig. 2.34), and the anterobasal and laterobasal segments of both right and left lower lobes.101

Incomplete fissures Not all pleural fissures are completely separated, and it is estimated that up to 73% of all fissures are in fact incomplete, i.e. that the pleural layers are not complete, such that the lung parenchyma of two neighboring lobes are in direct contact.111,112 These incomplete fissures, which are best seen on CT examinations (Fig. 2.35),111–114 are of clinical relevance in three circumstances:

Fig. 2.32  Sagittal reconstruction shows superior accessory fissure (arrows) separating the upper segment of the lower lobe from the remaining segments of the lower lobe.

approximately the same level, the superior accessory fissure is projected below the minor fissure on frontal radiographs. On the lateral view it differs from the minor fissure in that it extends backward across the vertebral bodies.94 The original descriptions of the superior accessory fissure suggested it was horizontal in orientation, but a recent evaluation of CT images suggests that it is often oriented obliquely,109 travelling upward as it sweeps laterally and posteriorly from the hilum. On CT, like the minor fissure, it may appear as an avascular area, which should be distinguished from downward angulation of the upper end of the major fissure, a distinction that depends on identification of the superior segmental bronchus.100 It may also be seen as a

• Unexpected distribution of effusion on chest radiographs: pleural fluid cannot freely distribute in the intrafissural space. • Unexpected ventilation of a given lobe, despite a central airways obstruction: there is no anatomic barrier and collateral ventilation, therefore, allows unhindered exchange of gas between anatomically different lobes (also relevant in endobronchial valve placement for the treatment of severe emphysema). • Unexpected spread of disease: absence of parts of a given fissure allows unhindered spread of disease, most commonly tumor or infection, from one lobe to another (Fig. 2.36).

(Inferior) pulmonary ligaments The (inferior) pulmonary ligaments consist of a double sheet of pleura that hangs down from each hilum like a curtain and joins the lungs to the mediastinum and to the medial part of the hemidiaphragms.115 The two layers of pleura contact each other below the inferior pulmonary vein and end in a free border that usually lies over the inner third of the hemidiaphragm but is sometimes displaced toward the hilum. The right inferior pulmonary ligament is short and wide based and is related on its mediastinal aspect to the azygos vein. On the left the ligament is longer and attaches to the

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Fig. 2.33  A, Transverse CT section shows accessory left minor fissure (arrows) separating the lingula from the left upper lobe. B, The oblique course of this accessory fissure (arrows) is better seen on the sagittal reconstruction.

variations in its degree of development have been considered important for the following reasons: • The ligament determines the shape of a collapsed lower lobe. • The ligament determines the ultimate shape of the collapsed lung in a pneumothorax.122 • Pleural effusion collecting posterior to the ligament tends to produce a triangular opacity, not unlike a lower lobe collapse.122 • The juxtaphrenic peak sign described with volume loss of an upper lobe may be due to diaphragmatic traction by way of the ligament and septum. • The ligament provides a pathway from lung to mediastinum and allows pathologic processes to travel in either direction.

MEDIASTINUM Fig. 2.34  CT section shows accessory fissure separating the anterior and posterior segment of the right upper lobe (arrows). Note normal position of the left major fissure.

mediastinum close to the esophagus and anterior to the aorta (Fig. 2.37).115 The ligament overlies a septum within the lung that separates posterior and medial basal segments.116 The bare area of the ligament contains connective tissue, small systemic vessels, lymphatics, and lymph nodes.117 The ligament is not visible on chest radiographs. On CT it is visible in about 50–75% of patients (Fig. 2.37).116,118,119 It is best detected just above the diaphragm as a thin curvilinear line passing outward and slightly backward from the mediastinum at the level of the esophagus. There is strong evidence that this line represents an intrapulmonary septum associated with the ligament rather than the ligament itself.116,120,121 Often a small, triangular elevation is present at the mediastinal base of the ligament. The ligament and

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The mediastinum is divided by anatomists into superior, anterior, middle, and posterior divisions. The exact anatomic boundaries between these divisions are unimportant to the radiologist because these boundaries neither provide a clear-cut guide to disease nor form barriers to the spread of disease. Moreover, almost every writer on the subject seems to have a different definition.81,117,123,124 The mediastinal structures and spaces as seen on CT and MRI are described before the appearances on plain film because the complex interfaces between the mediastinum and the lungs are best understood by careful correlation with cross-sectional images.

Normal mediastinum The normal mediastinal structures always identified at CT (Fig. 2.12) and MRI are the heart and blood vessels, which make up the bulk of the mediastinum; the major airways; and the esophagus. These structures are surrounded by a variable amount of connective

Mediastinum

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Fig. 2.35  A, CT and B, coronal reconstruction show incomplete right major fissure. Yellow arrows point at visible and red arrows at invisible parts of the fissure.

tissue, largely fat, within which lie lymph nodes, the thymus, the thoracic duct, and the phrenic and laryngeal nerves.

Mediastinal blood vessels On transverse CT images the vertically oriented ascending and descending portions of the aorta appear round, whereas the arch is seen as a tapering oval that becomes narrower as it gives rise to the arteries to the neck, head, and arms. The average diameter of the ascending aorta is 3.5  cm, and that of the descending aorta is 2.5 cm.125 Sections above the aortic arch show the three major aortic branches arranged in a curve lying anterior and to the left of the trachea. Their order from right to left is the brachiocephalic (innominate), left common carotid, and left subclavian arteries. The brachiocephalic artery is appreciably larger than the other two vessels. It varies slightly in position: in about half the population it is directly anterior to the trachea, and in the remainder, although still anterior to the trachea, it is either slightly to the right or left of the midline.126 The left common carotid artery lies to the left of the trachea; the left subclavian artery also lies either to the left of the trachea or posterior to it. It is the most lateral vessel of the three and often contacts the left lung. In 0.5% of the population, the right subclavian artery arises as a separate fourth major branch of the aorta, known as an aberrant right subclavian artery. Instead of arising from the brachiocephalic artery, it runs behind the esophagus from left to right, at or just above the level of the aortic arch, to lie against the right side of the vertebral bodies before entering the root of the neck. In individuals with an aberrant right subclavian artery the brachiocephalic artery (now the right common carotid artery) is smaller than usual and is similar in diameter to the left common carotid artery. As the descending aorta travels through the chest, it gradually moves from a position to the left of the vertebral bodies to an almost midline position before exiting from the chest through the aortic hiatus in the diaphragm. The diameter should remain nearly constant, but dilatation and tortuosity may develop with increasing age.

The mediastinal venous anatomy127 is illustrated in Fig. 2.38. The superior vena cava (SVC) has an oval or round configuration on transaxial section. Its diameter is one-third to two-thirds the diameter of the ascending aorta.125 It can, however, be considerably smaller and may appear flattened. A left SVC is present in 0.3–0.5% of the healthy population, but in 4.4–12.9% of those with congenital heart disease (Fig. 2.39).128,129 This anomaly results from failure of obliteration of the left common cardinal vein during fetal development. A right SVC and an interconnecting brachiocephalic vein are also present in most cases. A left SVC arises from the junction of the left jugular and subclavian veins and travels vertically through the left mediastinum, passing anterior to the left main bronchus before joining the coronary sinus on the back of the heart. From this point the blood flows into the right atrium through the coronary sinus, which is significantly larger than normal because of the increased blood flow. At unenhanced CT, a left SVC may be confused with lymphadenopathy if the full course of the vessel is not appreciated on contiguous sections. The left brachiocephalic vein forms a curved band anterior to the arteries arising from the arch of the aorta. Since it takes an oblique, downward course to join the SVC, its image on axial sections is usually oval rather than tubular. On rare occasions the left brachiocephalic vein descends vertically through the mediastinum before crossing the midline to join the right brachiocephalic vein,130 and like the left SVC (which it resembles), it may mimic lymphadenopathy. The right brachiocephalic vein, which travels vertically, lies anterolateral to the trachea in line with the three major arteries; it is often oval in configuration, larger than the arteries, and is the farthest right of the vessels. The azygos vein travels anterior to the spine, either behind or to the right of the esophagus, until at some variable point it arches forward to join the posterior wall of the SVC. Usually it remains within the mediastinum and occupies the right tracheobronchial angle. In the l% of the population who have an azygos lobe, the azygos vein traverses the lung before entering the SVC, in which case the SVC may appear distorted on both plain film and CT.103

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Chapter 2 • The Normal Chest

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Fig. 2.36  Implications of incomplete fissure. A, B, Transverse CT shows right upper lobe carcinoma with surrounding lymphangitic infiltration apparently delimited by the major fissure. C, Coronal reconstruction shows disease contained by the fissure (yellow arrow) and spread of disease through the incomplete fissure (red arrow).

B

Fig. 2.37  Transverse CT sections through the lower lobes show left and right pulmonary ligaments (arrows) extending from the A, lower aspects of the hila and B, caudally through the lungs.

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Mediastinum

Right brachiocephalic vein

Left brachiocephalic vein

Right internal thoracic vein

Left superior intercostal vein

Right superior intercostal vein Right pericardiophrenic vein

Azygos vein

Left internal thoracic vein

Left pericardiophrenic vein Accessory hemiazygos vein

Hemiazygos vein

Right brachiocephalic vein

Internal thoracic vein

Left brachiocephalic vein

Pericardiophrenic vein Left superior intercostal vein

Azygos vein

Superior vena cava

Accessory hemiazygos vein

Hemiazygos vein

Fig. 2.38  Diagrammatic illustration of mediastinal venous anatomy. (Redrawn with permission from Godwin JD, Chen JT. Thoracic venous anatomy. AJR Am J Roentgenol 1986;147:674–684. Reprinted with permission from the American Journal of Roentgenology.) The hemiazygos and accessory hemiazygos veins also lie against the vertebral bodies but in a more posterior plane, usually just behind the descending aorta. The accessory hemiazygos vein may cross the midline in the midthoracic level to join the azygos vein, or it may drain into the left superior intercostal vein, which arches around the aorta more or less at the junction of the arch and the descending portion to join the left brachiocephalic vein. The azygos and hemiazygos veins are routinely identifiable on CT, but they are generally not big enough to confuse with lymphadenopathy or other masses.131 The left superior intercostal vein is much smaller than the azygos vein and is only occasionally identified on chest radiographs or on CT, although in 1–9.5% of normal patients it is seen on plain chest radiography as a small nipple on the lateral margin of the aortic arch (see Fig. 2.47 below).132–134

Occasionally the inferior vena cava (IVC) does not develop in the usual fashion and the azygos vein forms the venous conduit draining IVC blood back to the heart, an arrangement known as azygos continuation of the IVC. The hepatic veins in these cases drain into the right atrium, not into the IVC. The azygos vein is therefore enlarged and is only slightly smaller than the IVC. Its anatomy is otherwise unaltered. Azygos continuation of the IVC may resemble a mediastinal mass or lymphadenopathy. The main pulmonary artery runs obliquely backward and upward to the left of the ascending aorta. Its average diameter in a study of 100 normal subjects was 2.72 cm (SD 0.3); in another series the diameter averaged 2.8  cm.125,135 It divides into right and left branches. The right branch travels more or less horizontally through the mediastinum, between the ascending aorta and SVC anteriorly

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Fig. 2.39  A, Transverse and B, coronal CT images showing persistent left superior vena cava with its typical course through the left lateral part of the mediastinum (arrows). and the major bronchi posteriorly. The left pulmonary artery arches higher than the right pulmonary artery and passes over the left main bronchus to descend posterior to it. This configuration leads to two important observations: the left pulmonary artery is often seen on a higher CT section than the right pulmonary artery; and the lung abuts the posterior wall of the right airway but is partly or totally excluded from contact with the left airway by the descending limb of the left pulmonary artery. The right pulmonary artery is approximately two-thirds the diameter of the main pulmonary artery.

Esophagus The esophagus is visible on all CT and MRI axial sections from the root of the neck down to the esophageal hiatus through the diaphragm. In approximately 80% of normal people the esophagus contains air, sometimes just a small amount. If there is sufficient mediastinal fat, the entire circumference of the esophagus can be identified. If air is present in the lumen, the uniform thickness of the wall can be appreciated. Without air, the collapsed esophagus appears either circular or oval and is usually approximately l cm in its narrowest diameter. On MRI the signal intensity on T1-weighted images is similar to that of muscle, but on T2-weighted images the esophagus often shows a much higher signal intensity than muscle.

Thymus Microscopic examination of the thymus shows many lobules, each divided into a medulla, consisting predominantly of epithelial cells, and a cortex containing the major cell of the thymus, the T lymphocyte. Epithelioid cells form a general framework. Hassall corpuscles are a characteristic feature of the medulla of the thymus; they consist of mature keratinized epithelial cells that layer on each other in concentric fashion. Myoid cells, similar to striated skeletal muscle, are found adjacent to Hassall corpuscles; they are much more prevalent in children than in adults. The thymus is anterior to the aorta and the right ventricular outflow tract or pulmonary artery. At CT it is usually found inferior to the left brachiocephalic vein and superior to the level of the horizontal portion of the right pulmonary artery; it is often best appreciated on a section through the aortic arch.136 Before puberty,137 the thymus occupies most of the mediastinum in front of the great vessels (Fig. 2.40). The gland remains fairly constant in weight, enlarging slightly until puberty, after which the thymic follicles

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atrophy and fatty replacement occurs until eventually little or no residual thymic tissue can be seen. In children the gland varies so greatly in size that measurement is of little value in deciding normality. Shape is a more useful criterion: the thymus is soft and fills in the spaces between the great vessels and the anterior chest wall as if molded by these structures. The lateral margins may be concave, straight or bulging outward, but approximate symmetry is the rule. In children under 5 years the gland is usually quadrilateral in shape with a convex lateral margin.138 A sharp angular border equivalent to the sail sign on plain films is occasionally visible at CT.129,137 In young children the thymus may extend all the way into the posterior mediastinum139,140 and may occasionally be confused with a posterior mediastinal mass.141–144 The thymus consists of two lobes, each enclosed in its own fibrous sheath.145 Up to 30% of the population have a fat cleft visible by CT at the junction of the two lobes. The left lobe is usually larger146 and slightly higher than the right.147 But these asymmetries are moderate, and the two lobes cannot always be clearly defined.136 A focal swelling, or a large lobe on one side with little or no thymic tissue visible on the other, suggests a mass. At CT the thymus is bilobed, triangular or shaped like an arrowhead. In one series of normal children, the mean thickness of the right lobe was 9 mm and that of the left lobe was 11 mm.148 The maximum width and thickness of each lobe decrease with advancing age. Between 20 and 50 years, the average thickness measured by CT decreases from 8–9 mm to 5–6 mm, the maximum thickness of one lobe being up to l.5 cm.140,149 These diameters are greater at MRI, presumably because MRI demonstrates the thymic tissue even when it is partially replaced by fat.146 At MRI, sagittal images demonstrate that the gland is 5–7 cm in craniocaudad dimension.146 It is impractical to measure the craniocaudad dimension at CT, but the gland may be visible over a similar distance.140,149 In younger patients the CT density of the thymus is homogeneous and close to, or slightly higher, than muscle. The gland often enhances appreciably with intravenous contrast material.137 After puberty the density gradually decreases owing to fatty replacement.150 In individuals older than 40 years, the thymus may have an attenuation value identical to that of fat.149 In some individuals the whole gland shows fat density149,151 and is therefore indistinguishable from mediastinal fat. In others, residual thymic parenchyma is visible as a streaky or nodular density (Fig. 2.40).136,151 As a response to chemotherapy, however, the thymus of adults can regain its preadolescent size and shape, a phenomenon termed ‘thymic rebound’. On T1-weighted MR images the intensity of the normal thymic tissue is similar to or slightly higher than that of muscle.138,152 As

Mediastinum

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Fig. 2.40  Ranges of CT appearances of the thymus in four different adult patients. A, Normal appearance of the thymus with near total fatty replacement of the thymic tissue. B, Subtotal fatty replacement of the thymic tissue (a small strip of thymus remains) in an obese patient. Note mediastinal lipomatosis and the presence of an azygos lobe. C, Increase of thymic tissue (arrows) in a patient on chemotherapy (‘thymic rebound’). D, Enlarged thymus in a patient with myasthenia gravis (arrows).

fatty replacement progresses, the thymus shows higher signal intensity to eventually blend in with the surrounding fat. On T2-weighted images the signal intensity is similar to or sometimes higher than fat138,152,153 and does not change with age. Proton density images show considerably less signal than the surrounding fat. Ultrasonography has been used to evaluate the thymus in children.154–156 Longitudinal ultrasound scans can be obtained by scanning intercostally, to the right and left of the sternum, angling the probe medially to visualize the substernal thymus. Axial images can be obtained by scanning in the suprasternal notch.154 On longitudinal scans the thymus appears triangular or teardrop in shape, but may rarely be round in shape. On transverse scans the gland is trapezoid in shape with slight lateral convexity and molds to the shape of the adjacent great vessels. In general the gland is symmetric about the midline.154,155 Adam and Ignotus154 gave the following measurements for children aged 2–8 years: mean anteroposterior (AP) and longitudinal measurements were 1.4  cm and 2.5  cm, respectively, for the right lobe, and 1.4 cm and 2.9 cm, respectively, for the left lobe. The internal echogenicity of the thymus in both infants and children is similar to that of the liver.154–156 The normal thymus may take up various radionuclides, such as fluoro-deoxyglucose (FDG) and iodine-131, and should not be confused with disease.157–159

Mediastinal spaces The nomenclature of the connective tissue spaces within the mediastinum is not standard, and there are no exact definitions for the boundaries between them. Nevertheless, radiologists need to understand the terms in common use. Four named spaces surround the central airways: the pretracheal space, the aortopulmonary window, the subcarinal space, and the right paratracheal space. All four contain lymph nodes that drain the lung and are therefore likely to be involved by bronchial carcinoma. In addition to these central spaces there are the junction areas, so-called because in these areas the two lungs approximate each other. One lies anterior to the aorta and pulmonary artery and is variously known as the anterior junction160 or the prevascular space;126 the other lies posterior to the trachea and esophagus, and is known as the posterior junction.161 Finally, there are the paraspinal lines on either side of the spine, and the junctional area between mediastinum and retroperitoneum known as the retrocrural space.

Pretracheal space The pretracheal space162 has no boundary with the lung and is therefore not imaged on plain chest radiographs. It is well known

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C

D

Fig. 2.41  The superior pericardial recess. A, CT showing a normal superior pericardial recess posterior to the ascending aorta (arrow). B, MRI showing a similar appearance (arrow). C, HRCT showing a normal superior pericardial recess (yellow arrow) tucking into the aortopulmonary window, and mimicking a node. The red arrow points to an enlarged mediastinal lymph node. Note that this node is not immediately next to the aorta. D, A patient with a large pericardial effusion showing marked distension of the anterior superior pericardial recess on CT. to surgeons because it is the space explored by transcervical mediastinoscopy. The space is triangular in axial cross-section; the three boundaries are the trachea or carina posteriorly, either the SVC or the right innominate vein anteriorly to the right, and the ascending aorta with its enveloping superior pericardial sinus anteriorly to the left.163 The superior pericardial recess is a small pocket of pericardium investing the aorta. When distended the pericardial configuration is easy to recognize (Fig. 2.41). In normal individuals, however, a small amount of pericardial fluid in the retroaortic extension of the superior pericardial recess (Fig. 2.41) may mimic lymphadenopathy on CT. At spin-echo MRI, the signal characteristics of fluid permit differentiation from lymphadenopathy or other masses, but on gradient-recalled-echo MRI the high signal intensity of fluid may resemble the signal from flowing blood and the superior pericardial recess may then mimic aortic dissection.164 The pretracheal space is continuous with the right paratracheal space, the aortopulmonary window, and the subcarinal space. Con-

66

sequently, lymph nodes or other masses arising in any of these spaces may grow large enough to encroach on the pretracheal space and vice versa.

Aortopulmonary window The aortopulmonary window is situated under the aortic arch above the left pulmonary artery. It is bounded medially by the trachea and esophagus and laterally by the lung.165 Its fatty density is not always appreciated at CT because so often the sections include either the aortic arch or the left pulmonary artery, and volume averaging results in higher than fat density. The ligamentum arteriosum and the recurrent laryngeal nerve traverse this space. They are rarely identified with conviction, but in any event they are not likely to be confused with lymphadenopathy or other masses. In older patients, calcification of the ligamentum is common and causes recognizable curvilinear calcification in

Mediastinum approximately half of patients undergoing chest CT.166 However, it is often confused with atheromatous calcification of the adjacent aortic wall. It is easier to distinguish from atheromatous aortic calcification in younger patients, in whom calcification of the ligamentum was seen in 13% of 53 patients in one series,167 but none had evidence of a patent ductus arteriosus. The left pulmonic recess of the pericardium envelops the main pulmonary artery and even normal amounts of pericardial fluid can mimic lymphadenopathy if the anatomic position and shape of this pericardial extension is not recognized (Fig. 2.41).168

Subcarinal space The subcarinal space, lying beneath the tracheal carina, is bounded on either side by the major bronchi. The azygoesophageal recess of the right lung lies behind the subcarinal space, and distortion of the azygoesophageal recess is a sensitive method of detecting masses, usually lymphadenopathy, in this space. The posterior boundary is partly formed by the esophagus.

Right paratracheal space and posterior tracheal space These two adjacent spaces (they should more properly be called strips) are best considered together. Normally the right lung is separated from the trachea only by a thin layer of fat (the only exception being at the tracheobronchial angle, where the azygos vein lies between the lung and the airway). The degree to which the lung envelopes the posterior wall of the trachea is variable. In up to half the population a substantial portion of the posterior tracheal wall is outlined by lung as it interposes between the spine and the trachea to contact the esophagus.

Anterior junction (prevascular space) The anterior junction160 lies anterior to the pulmonary artery, the ascending aorta, and the three major branches of the aortic arch. It lies between the two lungs and is bounded anteriorly by the chest wall. If the two lungs approximate each other closely enough, the intervening mediastinum may consist of little more than four layers of pleura and is then sometimes known as the anterior junction line (see Fig. 2.49 below). Coursing through the prevascular space superiorly is the left brachiocephalic vein. The internal mammary vascular bundles are to be found laterally and are visible at CT only if intravenous contrast material is administered. Embedded within the prevascular space are lymph nodes, the thymus, and the phrenic nerve.

Posterior junction and paraspinal areas The term ‘posterior junction’ describes the mediastinal region posterior to the trachea and the heart, where the two lungs lie close to each other (see Figs 2.50 and 2.51 below).161 The right lung always invaginates behind the right hilar structures and heart to contact the pleura overlying the azygos vein and esophagus, forming the so-called azygoesophageal recess. Displacement of the lung from the azygoesophageal recess is an important sign of a subcarinal mediastinal mass, particularly lymphadenopathy. Above the level of the azygos arch, the lung contacts the esophagus alone. On the left the lung interface is with the aortic arch and descending aorta rather than with the esophagus, but in some individuals the lung below the aortic arch invaginates anterior to the descending aorta to almost reach the midline. The paraspinal areas are contiguous with the posterior junction. Normally there is little or no discernible connective tissue between the lateral margins of the spine and the lungs but fat may make these lines more evident (Figs 2.42 and 2.43). The only structures contained in these areas are intercostal vessels and small lymph nodes.

Fig. 2.42  Chest radiograph shows lateral displacement of the right paraspinal line by extensive spondylophytes (arrows).

Retrocrural space The aorta exits the chest by passing through the aortic hiatus, which is bounded by the diaphragmatic crura and the spine (Fig. 2.44). The diaphragmatic crura are ligaments that blend with the anterior longitudinal ligament of the spine. Apart from the aorta, the structures that pass through the aortic hiatus are the azygos and hemiazygos veins, intercostal arteries, and splanchnic nerves. All these structures are too small to be mistaken for lymphadenopathy.169

Mediastinal and hilar lymph nodes Lymph nodes are widely distributed through the mediastinum and hila. There have been several classifications over the years. The following description uses terms agreed by the American Joint Committee on Cancer and the Union Internationale Contre le Cancer (AJCC-UICC) designed primarily for the staging of carcinoma of the bronchus (see Box 2.1 and Fig. 2.45).170–172 The nomenclature is similar to that previously used by the American Thoracic Society (ATS),173 except that all nodes around the main bronchi lying inside the mediastinal pleura are classified as paratracheal and all hilar nodes lie outside the mediastinal pleura. Furthermore, the nodes in the midline should be classified as N2 rather than N3. The AJCC-UICC classification is based on cross-sectional imaging in that it is directly referable to axial cross-sectional anatomy. The plane tangential to the upper margin of the aortic arch is an important dividing plane with nodes above this level being designated as: ‘highest mediastinal nodes’ (station 1 if they are above the upper rim of the left brachiocephalic vein); ‘right, left, and posterior upper paratracheal’ (stations 2R, 2L, and 3P, respectively); and ‘prevascular’ if they lie anterior to the arteries to the head and neck (station 3A).

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Chapter 2 • The Normal Chest

A

B

Fig. 2.43  A, Chest radiograph shows focal widening of the paraspinal line (arrows) caused by traumatic vertebral compression, which is confirmed on B, CT.

Box 2.1  AJCC-UICC classification of regional lymph nodes170

Fig. 2.44  The retrocrural spaces (RCS) (arrows) behind the diaphragmatic crura. The nodes below the plane tangential to the upper margin of the aortic arch include the following: right and left lower paratracheal nodes (stations 4R and 4L); subaortic (aortopulmonary window) nodes (station 5); paraaortic nodes which lie anterior and lateral to the ascending aorta, the aortic arch, or the proximal brachiocephalic artery (station 6); and subcarinal nodes, which lie beneath the main bronchi within the mediastinal pleura (station 7). Low down in the mediastinum are the paraesophageal (station 8) and pulmonary ligament nodes (station 9). Nodes are also present in the retrocrural areas and cardiophrenic angles. The nodes outside the mediastinal pleura are hilar (station 10), interlobar (station 11), lobar, segmental, and subsegmental (stations 12–14).

Normal lymph node size The CT series documenting normal mediastinal lymph node size are in general agreement.162,170,174–176 In these studies 95% of normal

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1. Highest mediastinal nodes lie above a horizontal line at the upper rim of the brachiocephalic (left innominate) vein 2. Upper paratracheal nodes lie above a horizontal line drawn tangential to the upper margin of the aortic arch and below the inferior boundary of No. 1 nodes 3. Prevascular and retrotracheal nodes may be designated 3A and 3P; midline nodes are considered to be ipsilateral 4. Lower paratracheal nodes lie to the right or left of the midline of the trachea between a horizontal line drawn tangential to the upper margin of the aortic arch and a line extending across the right or left main bronchus at the upper margin of the ipsilateral upper lobe bronchus. They are contained within the mediastinal pleural envelope. NB: The left lower paratracheal nodes lie medial to the ligamentum arteriosum 5. Subaortic (aortopulmonary window) nodes lie lateral to the ligamentum arteriosum or the aorta or left pulmonary artery and proximal to the first branch of the left pulmonary artery and lie within the mediastinal pleural envelope 6. Paraaortic nodes (ascending aorta or phrenic) lie anterior and lateral to the ascending aorta and the aortic arch or the innominate artery, beneath a line tangential to the upper margin of the aortic arch 7. Subcarinal nodes lie caudal to the carina of the trachea, but not associated with the lower lobe bronchi or arteries within the lung 8. Paraesophageal nodes (below carina) lie adjacent to the wall of the esophagus and to the right or left of the midline, excluding subcarinal nodes 9. Pulmonary ligament nodes lie within the pulmonary ligament, including those against the posterior wall and lower part of the inferior pulmonary vein 10. Hilar nodes lie distal to the mediastinal pleura reflection and the nodes adjacent to the bronchus intermedius on the right 11. Interlobar nodes lie between the lobar bronchi 12. Lobar nodes lie adjacent to the distal lobar bronchi 13. Segmental nodes lie adjacent to the segmental bronchi 14. Subsegmental nodes lie around the subsegmental bronchi NB. Station 1–9 nodes lie within the mediastinal pleural envelope whereas station 10–14 nodes lie outside the mediastinal pleura within the visceral pleura.

Mediastinum

Brachiocephalic (innominate) artery

Ligamentum arteriosum

3

2R

Left pulmonary artery

Ao 4R Azygos vein

6

4L 10R

11R

Phrenic nerve

PA

5 Ao

7 11L

PA 8

12, 13,14R

Inferior 10L pulmonary ligament 9

Superior mediastinal nodes Highest mediastinal Upper paratracheal Pre-vascular and retrotracheal

12, 13,14L

Aortic nodes Subaortic (AP window) Paraaortic (ascending aorta or phrenic)

Lower paratracheal (including azygos nodes) N2 = single digit, ipsilateral. N3 = single digit, contralateral or supraclavicular

Inferior mediastinal nodes Subcarinal

N1 Nodes Hilar

Paraesophageal (below carina)

Interlobar

Pulmonary ligament

Segmental

Lobar Subsegmental

Fig. 2.45  The AJCC-UICC1997 lymph node classification. mediastinal lymph nodes were less than 10  mm in short-axis diameter, and the remainder, with very few exceptions, were less than 15  mm in short-axis diameter. There is considerable variation in the number and size of lymph nodes seen in different locations within the mediastinum. Nodes in the region of the brachiocephalic veins are generally smaller, with over 90% measuring 5 mm or less, whereas nodes in the aortopulmonary window, the pretracheal and lower paratracheal spaces, and the subcarinal compartment are often 6–10  mm in short-axis diameter. Importantly, nodes in the paracardiac areas are rarely visible in healthy subjects: their maximum size in a series of 50 people was 3.5 mm.177 Nodes in the retrocrural area do not normally exceed 6  mm in diameter.169

Normal mediastinal contours on plain chest radiographs, frontal view For descriptive convenience the frontal and lateral projections are treated separately, although in practice the information from these two views should be integrated. For further details of the normal appearances in the lateral projection, the reader is referred to the excellent accounts by Proto and Speckman.87,94

Left mediastinal border Above the aortic arch the mediastinal shadow to the left of the trachea is of low density and is due to the left carotid and left subclavian arteries and the jugular veins. The usual appearance in the frontal projection is a gently curving border that fades out where the artery enters the neck (Fig. 2.46). The border is formed by the

Fig. 2.46  The shadow of the left subclavian artery (arrow) may simulate a pleural or parenchymal density.

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Chapter 2 • The Normal Chest left subclavian artery or more usually by the adjacent fat;178 occasionally, the interface is with the left carotid artery.178 A separate interface may be discernible for the left carotid artery. The outer margin of the left tracheal wall is very rarely outlined179 because the lung is almost invariably separated from the trachea by the aorta and great vessels.180 Below the aortic arch the left mediastinal border is formed by the aortopulmonary pleural stripe,165,181 the main pulmonary artery, and the heart. A small ‘nipple’ may occasionally be seen projecting laterally from the aortic knob. This projection is caused by the left superior intercostal vein arching forward around the aorta just beyond the origin of the left subclavian artery before entering the left brachiocephalic vein (Figs 2.47 and 2.48).182 This vein should not be misinterpreted as lymphadenopathy projecting from the aortopulmonary window. Fat can sometimes be identified in the aortopulmonary window beneath the aortic arch. The left border of the descending aorta can be traced through the shadow of the main pulmonary artery and heart as a continuous border from the aortic arch down to the aortic hiatus in the diaphragm in the great majority of normal patients. In a small proportion, 9% in a series from Japan, a portion of the interface between lung and descending aorta is indistinct due to contact with or proximity to the aortic margin branches of the left hilar vessels.183 In patients with pectus excavatum a small portion of the left wall of the middle descending aorta may appear indistinct because it is in contact with the left atrium and left inferior pulmonary vein.184

Right mediastinal border The right mediastinal border is normally formed by the right brachiocephalic (innominate) vein, the SVC, and the right atrium. The right paratracheal stripe can be seen through the right brachiocephalic vein and SVC because the lung contacts the right tracheal wall from the clavicles down to the arch of the azygos vein. This stripe,185 which should be of uniform thickness and no greater than 4  mm in width, is visible in approximately two-thirds of healthy subjects. It consists of the wall of the trachea and adjacent mediastinal fat, but there should be no focal bulges caused by individual

paratracheal lymph nodes. The azygos vein is outlined by air in the lung at the lower end of this stripe. The diameter of the azygos vein in the tracheobronchial angle is variable; it may be considered normal when 10  mm or less. The nodes immediately beneath the azygos vein, which are sometimes known as azygos nodes, are not recognizable on normal chest radiographs. The right paratracheal stripe has diagnostic value because it excludes space-occupying processes in the area where the stripe is visible and appears normal.180

Anterior junction The two lungs approximate each other above the level of the heart and below the manubrium; the term ‘anterior junction’ has therefore been applied to this area of the mediastinum.160 When the two lungs are separated only by pleura, the anterior junction forms a visible line, known as the anterior junction line (Fig. 2.49), which is usually straight and diverges to fade out superiorly as it reaches the clavicles. It descends for a variable distance, usually deviating to the left. The anterior junction line sometimes follows a vertical course or, very rarely, deviates to the right. It cannot extend below the point where the two lungs separate to envelop the right ventricle. Since the line is only occasionally seen, failure to identify it is of no consequence. More often the two lungs are separated by fat and thymus, with the result that the borders of the anterior junction are invisible on plain film or that only one of the borders can be identified. Bulging of one or both borders indicates the presence of a mass. In young children the thymus can be a prominent structure and the sail shape is characteristic. Proto et  al.160 used the terms ‘superior’ and ‘inferior’ recesses to describe the lung interfaces above and below the anterior junction region. The interfaces of the superior recesses are concave laterally. They are formed by mediastinal fat anterior to the arteries that supply the head and neck (the left and right brachiocephalic veins course through this fat but do not form visible borders on the frontal view). The inferior recesses are due to divergence of the lungs around fat in the lower mediastinum anterior to the heart.160

Fig. 2.47  A, The left superior intercostal vein (arrow) seen as a so-called ‘aortic nipple’. B, CT in another patient shows left superior intercostal vein lying lateral and just above the aortic arch (arrows).

A

70

B

Mediastinum

A

C

Posterior junction and azygoesophageal recess In some patients the lungs almost touch each other behind the esophagus to form the posterior junction line (Figs 2.50 and 2.51), a structure that can be thought of as an esophageal mesentery (Fig. 2.52).,81 This line, unlike the anterior junction line, diverges to envelop the aortic and azygos arches. Above the aortic arch the posterior junction line extends to the lung apices, where it diverges and disappears at the root of the neck, well above the level of the clavicles. The differences in the superior extent of the anterior and posterior junction lines are related to the sloping boundary between the thorax and the neck. Once again the width of the line depends on the amount of mediastinal fat. Whether both sides of the line are seen on plain chest radiograph depends on the tangent formed with the adjacent lung. Bulging of the borders of any portion of the posterior junction line or its superior recesses suggests a mass or other space-occupying process.180 The only normal convexities are those attributable to the azygos vein or aortic arch. Whether or not there is a visible posterior junction line above the aortic arch, the interface between the lung and the right wall of the esophagus can often be seen as a very shallow S extending from the lung apex down to the azygos arch. If there is air in the esophagus, which there frequently is, the right wall of the esophagus is seen as

B

Fig. 2.48  A, Atypical caudal course of left superior intercostal vein can cause apparent infilling of the aortopulmonary window on chest radiography (arrow). B, Transverse and (C) coronal CT images clearly demonstrate this vessel (arrow).

a stripe, usually 3–5  mm thick.186 This interface is known as the pleuroesophageal line or stripe (Fig. 2.52). Below the aortic arch the right lower lobe makes contact with the right wall of the esophagus and the azygos vein as it ascends next to the esophagus. This portion of lung is known as the ‘azygoesophageal recess’, and the interface is known as the azygoesophageal line (Fig. 2.53). The shape of the azygos arch varies considerably in different subjects, and therefore the shape of the upper portion of the azygoesophageal line varies accordingly. In its upper few centimeters, however, the azygoesophageal line in adults is always straight or concave toward the lung, and a convex shape suggests a subcarinal mass. Before 3 years of age the azygoesophageal line is usually convex and various configurations, including a high proportion showing a convex or straight border, are seen as the child becomes older.187,188 The azygoesophageal line can be traced down into the posterior costophrenic angle in subjects with normal anatomy. The left wall of the esophagus (Fig. 2.54) is rarely visible; the near vertical border seen through the heart represents the left wall of the descending aorta. This border can be traced, with virtually no loss of continuity, upward to the aortic arch and downward to the diaphragm. In a few subjects a small segment of aortic outline may be invisible because of contact between the aorta and the descending division of the left pulmonary artery behind the left main bronchus.

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Chapter 2 • The Normal Chest

B

A

Fig. 2.49  A, Chest radiograph and B, CT showing anterior junction line (arrows). Note normal course of intravenous catheter.

A

B

Fig. 2.50  A, Chest radiograph and B, CT showing posterior junction line (arrows).

72

Mediastinum Occasionally, the lung contacts the left wall of the esophagus, and then the esophagus is outlined from both the right and the left. Because air is frequently present in the esophagus, identifying separately the thickness of the right and left walls may even be possible. The usual site for ‘trapped air’ within the esophagus is just beneath the aortic arch (Fig. 2.55).189

vertebral space is usually thicker than the right. The paravertebral stripes are usually less than 1 cm wide, although they can be wider in obese persons. Aortic unfolding contributes to the thickness of the left paraspinal line; as the aorta moves posteriorly, it strips the pleura away from its otherwise close contact with the profiled portions of the spine.

Paraspinal lines The term ‘paraspinal line’ refers to a stripe of soft tissue density parallel to the left and right margins of the thoracic spine. Although lymph nodes and intercostal veins share this space with mediastinal fat and pleura, these structures cannot normally be recognized individually. With little fat the interface may closely follow the undulations of the lateral spinal ligaments, but with larger quantities of fat these undulations are smoothed out (see Fig. 2.42). The left para-

Fig. 2.51  CT section in a patient with severe emphysema enhances the identification of the anterior (yellow arrows) and posterior (red arrows) junction lines due to increased lung volumes.

A

Fig. 2.53  The azygoesophageal line (arrows).

B

Fig. 2.52  A, The pleuroesophageal line (arrowheads). B, CT shows the origin of the line (arrow) in the same patient.

73

Chapter 2 • The Normal Chest

Fig. 2.55  Air in the esophagus may be confused with free air in the mediastinum. In elderly people, the esophagus follows the ectatic descending aorta and air is trapped in the knuckle of the esophagus below the arch (arrow). (From Proto AV. Air in the oesophagus: a frequent radiologic finding. AJR Am J Roentgenol 1977;129:433. Reprinted with permission from the American Journal of Roentgenology.)

Fig. 2.54  The right and left walls of the esophagus. The yellow arrows point to the left wall. The red arrows point to the right wall (azygoesophageal line). The uppermost red arrow points to air in the lumen of the esophagus trapped beneath the aortic arch.

Lateral view Mediastinum above the aortic arch A variable portion of the aortic arch and head and neck vessels is visible in the lateral view, depending on the degree of aortic unfolding. The brachiocephalic artery is the only artery recognized with frequency. It arises anterior to the tracheal air column. Unless involved by atheromatous calcification, the origin is usually invisible, but after a variable distance its posterior wall can be seen as a gentle S-shaped interface crossing the tracheal air column. The left and right brachiocephalic veins are also visible in the lateral view. The left brachiocephalic vein often forms an extrapleural bulge behind the manubrium (Fig. 2.56).190 The posterior border of the right brachiocephalic vein and SVC can occasionally be identified curving downward in much the same position and direction as the brachiocephalic artery, but they are sometimes traceable below the upper margin of the aortic arch.

Trachea and retrotracheal area191 The air column in the trachea can be seen throughout its length as it descends obliquely downward and posteriorly. The course of the trachea in the lateral view of adult subjects is straight, or bowed

74

Fig. 2.56  The anterior extrapleural line (arrows) represents deviation of the pleura produced by the innominate artery and vein and the costal cartilage of the first ribs. It should not be mistaken for a lesion of the sternum or a mediastinal mass. forward in patients with aortic unfolding, with no visible indentation by adjacent vessels. The carina is not visible on the lateral view. The anterior wall of the trachea is visible in only a minority of patients, but its posterior wall is usually visible because lung often passes behind the trachea, allowing the radiologist to see the ‘posterior tracheal stripe or band’ (Fig. 2.57).4,179 This stripe is seen in 50–90% of healthy adults.179,192 It is uniform in width and measures up to 3 mm (rarely, 4 mm). There is, however, a problem in apply-

Diaphragm and Chest Wall

Fig. 2.58  A normal collapsed esophagus appearing as a band shadow (arrows) posterior to the trachea. Fig. 2.57  The posterior tracheal band (yellow arrow). Note that the posterior walls of the trachea, right main bronchus (red arrow), and bronchus intermedius (blue arrows) are seen as a continuous thin band.

ing this measurement. Because air is frequently present in the esophagus, the anterior wall of the esophagus may contribute to the thickness of the stripe in healthy subjects.192 Alternatively, the lung may be separated from the trachea by the full width of a collapsed esophagus, leading to a band of density l cm or more in thickness (Fig. 2.58). Thus caution is needed in diagnosing abnormalities on the basis of an increase in thickness of the posterior tracheal stripe. A CT study has shown that the visibility of the posterior tracheal stripe is dependent on the degree to which the lung passes behind the trachea.193 Sometimes the airway is close to the spine and what little is present is occupied by the esophagus and connective tissue.180 Clearly the quantity of mediastinal fat is an important factor in determining how much lung invaginates behind the trachea.

Retrosternal line A bandlike opacity simulating pleural or extrapleural disease is often seen in healthy individuals along the lower half or lowest third of the anterior chest wall on the lateral view (Fig. 2.59).194 This density is due to the differing anterior extent of the left and right lungs. The left lung does not contact the most anterior portion of the left thoracic cavity at these levels because the heart and its epicardial fat occupies the space.

Inferior vena cava In most healthy subjects the posterior wall of the IVC is visible just before it enters the right atrium. Even patients with azygos continu-

ation of the IVC may show a similar vessel formed by the continuation of the hepatic veins as they drain into the right atrium. In approximately 5% of healthy people the posterior wall of the IVC is not visible on the lateral chest radiograph.

DIAPHRAGM AND CHEST WALL The diaphragm (Figs 2.1, 2.2, 2.61, and 2.62) consists of a large, dome-shaped central tendon with a sheet of striated muscle radiating from the central tendon to attach to ribs 7–12 and to the xiphisternum.195–198 The two crura arise from the upper three lumbar vertebrae and arch upward and forward to form the margins of the aortic and esophageal hiati. The median arcuate ligament connecting the two crura forms the anterior margin of the aortic hiatus, and the crura themselves form the lateral boundary of the aortic hiatus. Accompanying the aorta through this opening are the azygos and hemiazygos veins and the thoracic duct. Anterior to the aortic hiatus lies the esophageal hiatus, through which run the esophagus, the vagus nerve, and the esophageal arteries. The most anterior of the three diaphragmatic hiati is the hiatus for the IVC, which is situated within the central tendon immediately beneath the right atrium. The diaphragm has a smooth dome shape in most individuals, but a scalloped outline is also common. The position of the diaphragm in healthy subjects on upright chest radiographs taken at full inspiration was investigated by Lennon and Simon.199 They used the anterior ribs to describe the position of each hemidiaphragm because the dome is closer to the anterior chest wall and both the domes and the anterior ribs are closer to the film in the PA projection. The normal right hemidiaphragm is found at about the level of the anterior sixth rib, being slightly higher in women and in individuals over 40 years of age. The range covers approximately one interspace above or below this level. In most people the right hemidiaphragm is 1.5–2.5 cm higher

75

Chapter 2 • The Normal Chest

A

B

Fig. 2.59  A, The retrosternal line (arrow). B, CT in the same patient shows that the anterior margin of the left lung lies more posterior than the anterior margin of the right lung, in part because of the heart and in part because of epicardial fat.

Fig. 2.60  The phrenic nerve (or, according to some authors, the phrenic vessels) (arrows) coursing over the surface of the right hemidiaphragm.

than the left, but the two hemidiaphragms are at the same level in about 9% of the population. In a few (3% in the series by Felson93) the left hemidiaphragm is higher than the right, but by less than 1  cm. The normal excursion of the domes of the diaphragm as measured by plain chest radiography is usually between 1.5 cm and

76

2.5 cm, although greater degrees of movement are sometimes seen. Ultrasonography, which allows more accurate real-time measurement of movement, shows that the normal range is considerable: between 2  cm and 8.6  cm, with the mean excursion of the right hemidiaphragm on deep inspiration 53  mm (SD 16.4) and that of the left side 46 mm (SD 12.4).200 Incomplete muscularization, known as eventration, is also common. An eventration is composed of a thin membranous sheet replacing what should be muscle. Usually it is partial, involving half to a third of the hemidiaphragm, frequently the anteromedial portion of the right hemidiaphragm. The lack of muscle manifests itself radiographically as elevation of the affected portion of the diaphragm, and the usual pattern is a smooth hump on the contour of the diaphragm. Total eventration of a hemidiaphragm, which is much more common on the left than on the right, results in elevation of the whole hemidiaphragm; on fluoroscopy, hemidiaphragm movement is poor, absent, or paradoxical. In severe cases, eventration cannot be distinguished from acquired paralysis of the phrenic nerve. A linear density arising from the lateral wall of the IVC is often seen coursing over the superior surface of the right hemidiaphragm. This line represents an envelope of fat with investing pleura surrounding either the phrenic nerve, according to Berkmen and coworkers,201 or the inferior phrenic artery and vein, according to Ujita and associates (see Fig. 2.60).121 The chest wall structures that commonly cause diagnostic problems are the nipples. If dense and symmetric, they are easily recognized (Fig. 2.63). If asymmetric and visible in just one projection, the nipples can be mistaken as lung nodules (Fig. 2.64). The nipples are best identified by their circular appearance with a sharp and a nonsharp half.

Diaphragm and Chest Wall

A

B

Fig. 2.61  Chest radiograph shows right diaphragmatic hump (arrows).

Fig. 2.62  Chest radiograph in a patient after abdominal surgery and free abdominal air shows the diaphragm as a fine opaque band (yellow arrows). Note surgical material after ‘gastric banding’ (red arrow).

77

Chapter 2 • The Normal Chest

A

B

Fig. 2.63  Chest radiograph shows dense bilateral nipples (arrows) in both A, frontal and B, lateral projections.

A

B

Fig. 2.64  A, Unilaterally visible left nipple on chest radiograph (arrow) mimics intrapulmonary nodule. B, CT confirms normal anatomy (arrow).

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References

REFERENCES 1. Holbert JM, Strollo DC. Imaging of the normal trachea. J Thorac Imaging 1995;10:171–179. 2. Dennie CJ, Coblentz CL. The trachea: normal anatomic features, imaging and causes of displacement. Can Assoc Radiol J 1993;44:81–89. 3. Bhalla M, Noble ER, Shepard JA, et al. Normal position of trachea and anterior junction line on CT. J Comput Assist Tomogr 1993;17:714–718. 4. Gamsu G, Webb WR. Computed tomography of the trachea: normal and abnormal. AJR Am J Roentgenol 1982;139: 321–326. 5. Lloyd DC, Taylor PM. Calcification of the intrathoracic trachea demonstrated by computed tomography. Br J Radiol 1990;63: 31–32. 6. Bravo JM, Stark P, Jacobson F. Tracheobronchial cartilage calcifications in an inpatient population. J Thorac Imaging 1995;10:220–222. 7. Davis SD, Maldjian C, Perone RW, et al. CT of the airways. Clin Imaging 1990;14: 280–300. 8. Gamsu G, Webb WR. Computed tomography of the trachea and mainstem bronchi. Semin Roentgenol 1983;18:51–60. 9. Breatnach E, Abbott GC, Fraser RG. Dimensions of the normal human trachea. AJR Am J Roentgenol 1984;142:903–906. 10. Vock P, Spiegel T, Fram EK, et al. CT assessment of the adult intrathoracic cross section of the trachea. J Comput Assist Tomogr 1984;8:1076–1082. 11. Griscom NT, Wohl ME. Dimensions of the growing trachea related to age and gender. AJR Am J Roentgenol 1986;146:233–237. 12. Dimopoulos PA, Yarmenitis SD, Nikiforidis G, et al. Anatomical shape of the airways in two different European populations. A radio-anatomical study of the airways. Acta Radiol 1995;36:448–452. 13. Stern EJ, Graham CM, Webb WR, et al. Normal trachea during forced expiration: dynamic CT measurements. Radiology 1993;187:27–31. 14. Boiselle PM. Multislice helical CT of the central airways. Radiol Clin North Am 2003;41:561–574. 15. Boiselle PM. Imaging of the large airways. Clin Chest Med 2008;29:181–193, vii. 16. Boiselle PM, Dippolito G, Copeland J, et al. Multiplanar and 3D imaging of the central airways: comparison of image quality and radiation dose of single-detector row CT and multi-detector row CT at differing tube currents in dogs. Radiology 2003;228: 107–111. 17. Boiselle PM, Lee KS, Ernst A. Multidetector CT of the central airways. J Thorac Imaging 2005;20:186–195. 18. Boiselle PM, Reynolds KF, Ernst A. Multiplanar and three-dimensional imaging of the central airways with multidetector CT. AJR Am J Roentgenol 2002;179:301–308. 19. Murray JG, Brown AL, Anagnostou EA, et al. Widening of the tracheal bifurcation on chest radiographs: value as a sign of left atrial enlargement. AJR Am J Roentgenol 1995;164:1089–1092. 20. Haskin PH, Goodman LR. Normal tracheal bifurcation angle: a reassessment. AJR Am J Roentgenol 1982;139:879–882.

21. Remy-Jardin M, Remy J. Comparison of vertical and oblique CT in evaluation of bronchial tree. J Comput Assist Tomogr 1988;12:956–962. 22. Naidich DP, Terry PB, Stitik FP, et al. Computed tomography of the bronchi: 1. Normal anatomy. J Comput Assist Tomogr 1980;4:746–753. 23. Osborne D, Vock P, Godwin JD, et al. CT identification of bronchopulmonary segments: 50 normal subjects. AJR Am J Roentgenol 1984;142:47–52. 24. Webb WR, Glazer G, Gamsu G. Computed tomography of the normal pulmonary hilum. J Comput Assist Tomogr 1981;5: 476–484. 25. Lee KS, Im JG, Bae WK, et al. CT anatomy of the lingular segmental bronchi. J Comput Assist Tomogr 1991;15:86–91. 26. Otsuji H, Uchida H, Maeda M, et al. Incomplete interlobar fissures: bronchovascular analysis with CT. Radiology 1993;187:541–546. 27. Lee KS, Bae WK, Lee BH, et al. Bronchovascular anatomy of the upper lobes: evaluation with thin-section CT. Radiology 1991;181:765–772. 28. Otsuji H, Hatakeyama M, Kitamura I, et al. Right upper lobe versus right middle lobe: differentiation with thin-section, highresolution CT. Radiology 1989;172: 653–656. 29. Jardin M, Remy J. Segmental bronchovascular anatomy of the lower lobes: CT analysis. AJR Am J Roentgenol 1986;147:457–468. 30. Naidich DP, Zinn WL, Ettenger NA, et al. Basilar segmental bronchi: thin-section CT evaluation. Radiology 1988;169:11–16. 31. Atwell SW. Major anomalies of the tracheobronchial tree: with a list of the minor anomalies. Dis Chest 1967;52: 611–615. 32. Boyden EA. Developmental anomalies of the lungs. Am J Surg 1955;89:79–89. 33. Beigelman C, Howarth NR, ChartrandLefebvre C, et al. Congenital anomalies of tracheobronchial branching patterns: spiral CT aspects in adults. Eur Radiol 1998;8: 79–85. 34. Wu JW, White CS, Meyer CA, et al. Variant bronchial anatomy: CT appearance and classification. AJR Am J Roentgenol 1999; 172:741–744. 35. Ghaye B, Szapiro D, Fanchamps JM, et al. Congenital bronchial abnormalities revisited. RadioGraphics 2001;21: 105–119. 36. Freeman SJ, Harvey JE, Goddard PR. Demonstration of supernumerary tracheal bronchus by computed tomographic scanning and magnetic resonance imaging. Thorax 1995;50:426–427. 37. Doolittle AM, Mair EA. Tracheal bronchus: classification, endoscopic analysis, and airway management. Otolaryngol Head Neck Surg 2002;126:240–243. 38. Lee KH, Yoon CS, Choe KO, et al. Use of imaging for assessing anatomical relationships of tracheobronchial anomalies associated with left pulmonary artery sling. Pediatr Radiol 2001;31:269–278. 39. Carpenter LM, Merten DF. Radiographic manifestations of congenital anomalies affecting the airway. Radiol Clin North Am 1991;29:219–240.

40. Morrison SC. Demonstration of a tracheal bronchus by computed tomography. Clin Radiol 1988;39:208–209. 41. McLaughlin FJ, Strieder DJ, Harris GB, et al. Tracheal bronchus: association with respiratory morbidity in childhood. J Pediatr 1985;106:751–755. 42. Hosker HS, Clague HW, Morritt GN. Ectopic right upper lobe bronchus as a cause of breathlessness. Thorax 1987;42: 473–474. 43. Ritsema GH. Ectopic right bronchus: indication for bronchography. AJR Am J Roentgenol 1983;140:671–674. 44. Setty SP, Michaels AJ. Tracheal bronchus: case presentation, literature review, and discussion. J Trauma 2000;49:943–945. 45. Siegel MJ, Shackelford GD, Francis RS, et al. Tracheal bronchus. Radiology 1979; 130:353–355. 46. Mannes GP, van der Jagt EJ, Wouters B, et al. Dextrocardia? Chest 1989;96: 391–392. 47. Mangiulea VG, Stinghe RV. The accessory cardiac bronchus. Bronchologic aspect and review of the literature. Dis Chest 1968;54: 433–436. 48. McGuinness G, Naidich DP, Garay SM, et al. Accessory cardiac bronchus: CT features and clinical significance. Radiology 1993;189:563–566. 49. Endo S, Saitoh N, Murayama F, et al. Symptomatic accessory cardiac bronchus. Ann Thorac Surg 2000;69:262–264. 50. Jackson GD, Littleton JT. Simultaneous occurrence of anomalous cardiac and tracheal bronchi: a case study. J Thorac Imaging 1988;3:59–60. 51. Bentala M, Grijm K, van der Zee JH, et al. Cardiac bronchus: a rare cause of hemoptysis. Eur J Cardiothorac Surg 2002; 22:643–645. 52. Landay MJ, Chaw C, Bordlee RP. Bilateral left lungs: unusual variation of hilar anatomy. AJR Am J Roentgenol 1982;138: 1162–1164. 53. Landing BH, Lawrence TY, Payne VC Jr, et al. Bronchial anatomy in syndromes with abnormal visceral situs, abnormal spleen and congenital heart disease. Am J Cardiol 1971;28:456–462. 54. Starshak RJ, Sty JR, Woods G, et al. Bridging bronchus: a rare airway anomaly. Radiology 1981;140:95–96. 55. Genereux GP. Conventional tomographic hilar anatomy emphasizing the pulmonary veins. AJR Am J Roentgenol 1983;141: 1241–1257. 56. Naidich DP, Khouri NF, Scott WW Jr, et al. Computed tomography of the pulmonary hila: 1. Normal anatomy. J Comput Assist Tomogr 1981;5:459–467. 57. Vix VA, Klatte EC. The lateral chest radiograph in the diagnosis of hilar and mediastinal masses. Radiology 1970;96: 307–316. 58. Remy-Jardin M, Duyck P, Remy J, et al. Hilar lymph nodes: identification with spiral CT and histologic correlation. Radiology 1995;196:387–394. 59. Shimoyama K, Murata K, Takahashi M, et al. Pulmonary hilar lymph node metastases from lung cancer: evaluation based on morphology at thin-section, incremental, dynamic CT. Radiology 1997;203:187–195.

79

Chapter 2 • The Normal Chest 60. Kim JS, Müller NL, Park CS, et al. Bronchoarterial ratio on thin section CT: comparison between high altitude and sea level. J Comput Assist Tomogr 1997;21: 306–311. 61. Webb WR, Gamsu G. Computed tomography of the left retrobronchial stripe. J Comput Assist Tomogr 1983;7: 65–69. 62. Park CK, Webb WR, Klein JS. Inferior hilar window. Radiology 1991;178:163–168. 63. Ashida C, Zerhouni EA, Fishman EK. CT demonstration of prominent right hilar soft tissue collections. J Comput Assist Tomogr 1987;11:57–59. 64. Woodring JH. Pulmonary artery-bronchus ratios in patients with normal lungs, pulmonary vascular plethora, and congestive heart failure. Radiology 1991; 179:115–122. 65. Jefferson K, Rees S. Clinical cardiac radiology. London: Butterworths, 1973. 66. Bankoff MS, McEniff NJ, Bhadelia RA, et al. Prevalence of pathologically proven intrapulmonary lymph nodes and their appearance on CT. AJR Am J Roentgenol 1996;167:629–630. 67. Perez N, Lhoste-Trouilloud A, Boyer L, et al. Computed tomographic appearance of three intrapulmonary lymph nodes. Eur J Radiol 1998;28:147–149. 68. Oshiro Y, Kusumoto M, Moriyama N, et al. Intrapulmonary lymph nodes: thin-section CT features of 19 nodules. J Comput Assist Tomogr 2002;26:553–557. 69. Fujimoto N, Segewa Y, Takigawa N, et al. Two cases of intrapulmonary lymph node presenting as a peripheral nodular shadow: diagnostic differentiation from lung cancer. Lung Cancer 1998;20:203–209. 70. Yokomise H, Mizuno H, Ike O, et al. Importance of intrapulmonary lymph nodes in the differential diagnosis of small pulmonary nodular shadows. Chest 1998; 113:703–706. 71. Kradin RL, Mark EJ. Benign lymphoid disorders of the lung, with a theory regarding their development. Hum Pathol 1983;14:857–867. 72. Neff CC, Mueller PR, Ferrucci JT Jr, et al. Serious complications following transgression of the pleural space in drainage procedures. Radiology 1984;152: 335–341. 73. Nichols DM, Cooperberg PL, Golding RH, et al. The safe intercostal approach? Pleural complications in abdominal interventional radiology. AJR Am J Roentgenol 1984;142: 1013–1018. 74. Light RW. Pleural diseases. Philadelphia: Lippincott Williams and Wilkins, 1995. 75. Wang NS. Anatomy and physiology of the pleural space. Clin Chest Med 1985;6: 3–16. 76. Im JG, Webb WR, Rosen A, et al. Costal pleura: appearances at high-resolution CT. Radiology 1989;171:125–131. 77. Hayashi K, Aziz A, Ashizawa K, et al. Radiographic and CT appearances of the major fissures. RadioGraphics 2001;21: 861–874. 78. Berkmen YM, Auh YH, Davis SD, et al. Anatomy of the minor fissure: evaluation with thin-section CT. Radiology 1989;170: 647–651. 79. Glazer HS, Anderson DJ, DiCroce JJ, et al. Anatomy of the major fissure: evaluation

80

80.

81. 82. 83. 84. 85.

86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96.

97.

98. 99.

100. 101.

102. 103.

with standard and thin-section CT. Radiology 1991;180:839–844. Raasch BN, Carsky EW, Lane EJ, et al. Radiographic anatomy of the interlobar fissures: a study of 100 specimens. AJR Am J Roentgenol 1982;138:1043–1049. Heitzman ER. The mediastinum: radiologic correlations with anatomy and pathology. Berlin: Springer-Verlag, 1988. Kent EM, Blades B. Surgical anatomy of pulmonary lobes. J Thorac Surg 1942;12: 18–30. Medlar EM. Variations in interlobar fissures. AJR Am J Roentgenol 1947;57: 723–725. Dandy WE Jr. Incomplete pulmonary interlobar fissure sign. Radiology 1978;128: 21–25. Hogg JC, Macklem PT, Thurlbeck WM. The resistance of collateral channels in excised human lungs. J Clin Invest 1969;48: 421–431. Scanlon TS, Benumof JL. Demonstration of interlobar collateral ventilation. J Appl Physiol 1979;46:658–661. Proto AV, Speckman JM. The left lateral radiograph of the chest. Med Radiogr Photogr 1980;56:38–64. Proto AV, Ball JB Jr. The superolateral major fissures. AJR Am J Roentgenol 1983;140:431–437. Fisher MS. Significance of a visible major fissure on the frontal chest radiograph. AJR Am J Roentgenol 1981;137:577–580. Davis LA. The vertical fissure line. AJR Am J Roentgenol 1960;84:451–453. Friedman E. Further observations on the vertical fissure line. Am J Roentgenol Radium Ther Nucl Med 1966;97:171–173. Webber MM, O’Loughlin BJ. Variations of the pleural vertical fissure line. Radiology 1964;82:461–462. Felson B. Chest roentgenology. Philadelphia: WB Saunders, 1973. Proto AV, Speckman JM. The left lateral radiograph of the chest. Part 1. Med Radiogr Photogr 1979;55:29–74. Marks BW, Kuhns LR. Identification of the pleural fissures with computed tomography. Radiology 1982;143:139–141. Proto AV, Ball JB Jr. Computed tomography of the major and minor fissures. AJR Am J Roentgenol 1983;140: 439–448. Sakai O, Takahashi K, Nakashima N, et al. CT visualization of the major pulmonary fissures: value of 25 degrees cranially tilted axial scans. AJR Am J Roentgenol 1993;161: 523–526. Goodman LR, Golkow RS, Steiner RM, et al. The right mid-lung window. Radiology 1982;143:135–138. Frija J, Yana C, Laval-Jeantet M. Anatomy of the minor fissure: evaluation with thin-section CT. Radiology 1989;173: 571–572. Godwin JD, Tarver RD. Accessory fissures of the lung. AJR Am J Roentgenol 1985; 144:39–47. Ariyurek OM, Gulsun M, Demirkazik FB. Accessory fissures of the lung: evaluation by high-resolution computed tomography. Eur Radiol 2001;11:2449–2453. Takasugi JE, Godwin JD. Left azygos lobe. Radiology 1989;171:133–134. Speckman JM, Gamsu G, Webb WR. Alterations in CT mediastinal anatomy

104.

105.

106.

107. 108. 109.

110. 111. 112.

113. 114.

115.

116. 117. 118.

119. 120.

121.

122.

produced by an azygos lobe. AJR Am J Roentgenol 1981;137:47–50. Boyden EA. The distribution of bronchi in gross anomalies of the right upper lobe, particularly lobes subdivided by the azygos vein and those containing pre-parietal bronchi. Radiology 1942;58: 797–807. Caceres J, Mata JM, Alegret X, et al. Increased density of the azygos lobe on frontal chest radiographs simulating disease: CT findings in seven patients. AJR Am J Roentgenol 1993;160:245–248. Mata JM, Caceres J, Llauger J, et al. CT demonstration of intrapulmonary right brachiocephalic vein associated with an azygos lobe. J Comput Assist Tomogr 1990;14:305–306. Rigler LG. The inferior accessory lobe of the lung. AJR Am J Roentgenol 1933;29: 384–392. Trapnell DH. The differential diagnosis of linear shadows in chest radiographs. Radiol Clin North Am 1973;11:77–92. Davis SD, Yu LS, Hentel KD. Obliquely oriented superior accessory fissure of the lower lobe of the lung: CT evaluation of the normal appearance and effect on the distribution of parenchymal and pleural opacities. Radiology 2000;216:97–106. Austin JH. The left minor fissure. Radiology 1986;161:433–436. Satoh K, Sato A, Kobayashi T, et al. Septal structure of incomplete interlobar fissures of the lung. Acad Radiol 1996;3:475–478. Tarver RD. How common are incomplete pulmonary fissures, and what is their clinical significance? AJR Am J Roentgenol 1995;164:761. Mori K. Vascular anatomy at the medial ends of incomplete major fissures. J Thorac Imaging 2003;18:190–194. Aziz A, Ashizawa K, Nagaoki K, et al. High resolution CT anatomy of the pulmonary fissures. J Thorac Imaging 2004;19:186–191. Rabinowitz JG, Cohen BA, Mendleson DS. Symposium on Nonpulmonary Aspects in Chest Radiology. The pulmonary ligament. Radiol Clin North Am 1984;22:659–672. Godwin JD, Vock P, Osborne DR. CT of the pulmonary ligament. AJR Am J Roentgenol 1983;141:231–236. Fraser RS, Müller NL, Colman N, et al. Diagnosis of diseases of the chest. Philadelphia: WB Saunders, 1999. Cooper C, Moss AA, Buy JN, et al. CT appearance of the normal inferior pulmonary ligament. AJR Am J Roentgenol 1983;141:237–240. Rost RC Jr, Proto AV. Inferior pulmonary ligament: computed tomographic appearance. Radiology 1983;148:479–483. Berkmen YM, Drossman SR, Marboe CC. Intersegmental (intersublobar) septum of the lower lobe in relation to the pulmonary ligament: anatomic, histologic, and CT correlations. Radiology 1992;185: 389–393. Ujita M, Ojiri H, Ariizumi M, et al. Appearance of the inferior phrenic artery and vein on CT scans of the chest: a CT and cadaveric study. AJR Am J Roentgenol 1993;160:745–747. Rabinowitz JG, Wolf BS. Roentgen significance of the pulmonary ligament. Radiology 1966;87:1013–1020.

References 123. Zylak CJ, Pallie W, Jackson R. Correlative anatomy and computed tomography: a module on the mediastinum. RadioGraphics 1982;2:255–292. 124. Felson B. The mediastinum. Semin Roentgenol 1969;4:41–58. 125. Guthaner DF, Wexler L, Harell G. CT demonstration of cardiac structures. AJR Am J Roentgenol 1979;133:75–81. 126. Gamsu G, Moss AA, Gamsu G, et al. Computed tomography of the mediastinum. Philadelphia: WB Saunders, 1983. 127. Godwin JD, Chen JT. Thoracic venous anatomy. AJR Am J Roentgenol 1986;147: 674–684. 128. Buirski G, Jordan SC, Joffe HS, et al. Superior vena caval abnormalities: their occurrence rate, associated cardiac abnormalities and angiographic classification in a paediatric population with congenital heart disease. Clin Radiol 1986;37:131–138. 129. Cha EM, Khoury GH. Persistent left superior vena cava. Radiologic and clinical significance. Radiology 1972;103:375–381. 130. Fujimoto K, Abe T, Kumabe T, et al. Anomalous left brachiocephalic (innominate) vein: MR demonstration. AJR Am J Roentgenol 1992;159:479–480. 131. Takasugi JE, Godwin JD. CT appearance of the retroaortic anastomoses of the azygos system. AJR Am J Roentgenol 1990;154: 41–44. 132. Ball JB Jr, Proto AV. The variable appearance of the left superior intercostal vein. Radiology 1982;144:445–452. 133. Friedman AC, Chambers E, Sprayregen S. The normal and abnormal left superior intercostal vein. AJR Am J Roentgenol 1978;131:599–602. 134. McDonald CJ, Castellino RA, Blank N. The aortic ‘nipple’. The left superior intercostal vein. Radiology 1970;96:533–536. 135. Edwards PD, Bull RK, Coulden R. CT measurement of main pulmonary artery diameter. Br J Radiol 1998;71:1018–1020. 136. Moore AV, Korobkin M, Olanow W, et al. Age-related changes in the thymus gland: CT-pathologic correlation. AJR Am J Roentgenol 1983;141:241–246. 137. Heiberg E, Wolverson MK, Sundaram M, et al. Normal thymus: CT characteristics in subjects under age 20. AJR Am J Roentgenol 1982;138:491–494. 138. Siegel MJ, Glazer HS, Wiener JI, et al. Normal and abnormal thymus in childhood: MR imaging. Radiology 1989; 172:367–371. 139. Cohen MD, Weber TR, Sequeira FW, et al. The diagnostic dilemma of the posterior mediastinal thymus: CT manifestations. Radiology 1983;146:691–692. 140. Francis IR, Glazer GM, Bookstein FL, et al. The thymus: reexamination of age-related changes in size and shape. AJR Am J Roentgenol 1985;145:249–254. 141. Bach AM, Hilfer CL, Holgersen LO. Left-sided posterior mediastinal thymus– MRI findings. Pediatr Radiol 1991;21: 440–441. 142. Meaney JF, Roberts DE, Carty H. Case of the month: pseudo-tumour of the postero-superior mediastinum. Br J Radiol 1993;66:741–742. 143. Rollins NK, Currarino G. MR imaging of posterior mediastinal thymus. J Comput Assist Tomogr 1988;12:518–520.

144. Shackelford GD, McAlister WH. The aberrantly positioned thymus: a cause of mediastinal or neck masses in children. Am J Roentgenol Radium Ther Nucl Med 1974;120:291–296. 145. Rosai J, Levine GD. Normal thymus. Washington DC: Armed Forces Institute of Pathology, 1976. 146. de Geer G, Webb WR, Gamsu G. Normal thymus: assessment with MR and CT. Radiology 1986;158:313–317. 147. Sagel SS, Aronberg DJ, Lee JKT, et al. Thoracic anatomy and mediastinum. New York: Raven Press, 1982. 148. St Amour TE, Siegel MJ, Glazer HS, et al. CT appearances of the normal and abnormal thymus in childhood. J Comput Assist Tomogr 1987;11:645–650. 149. Baron RL, Lee JK, Sagel SS, et al. Computed tomography of the normal thymus. Radiology 1982;142:121–125. 150. Siegelman SS, Scott WW, Baker RR, et al. CT of the thymus. New York: Churchill Livingstone, 1984. 151. Dixon AK, Hilton CJ, Williams GT. Computed tomography and histological correlation of the thymic remnant. Clin Radiol 1981;32:255–257. 152. Boothroyd AE, Hall-Craggs MA, DicksMireaux C, et al. The magnetic resonance appearances of the normal thymus in children. Clin Radiol 1992;45:378–381. 153. Molina PL, Siegel MJ, Glazer HS. Thymic masses on MR imaging. AJR Am J Roentgenol 1990;155:495–500. 154. Adam EJ, Ignotus PI. Sonography of the thymus in healthy children: frequency of visualization, size, and appearance. AJR Am J Roentgenol 1993;161:153–155. 155. Han BK, Babcock DS, Oestreich AE. Normal thymus in infancy: sonographic characteristics. Radiology 1989;170:471–474. 156. Hasselbalch H, Nielsen MB, Jeppesen D, et al. Sonographic measurement of the thymus in infants. Eur Radiol 1996;6: 700–703. 157. Patel PM, Alibazoglu H, Ali A, et al. Normal thymic uptake of FDG on PET imaging. Clin Nucl Med 1996;21:772–775. 158. Veronikis IE, Simkin P, Braverman LE. Thymic uptake of iodine-131 in the anterior mediastinum. J Nucl Med 1996;37:991–992. 159. Weinblatt ME, Zanzi I, Belakhlef A, et al. False-positive FDG-PET imaging of the thymus of a child with Hodgkin’s disease. J Nucl Med 1997;38:888–890. 160. Proto AV, Simmons JD, Zylak CJ. The anterior junction anatomy. Crit Rev Diagn Imaging 1983;19:111–173. 161. Proto AV, Simmons JD, Zylak CJ. The posterior junction anatomy. Crit Rev Diagn Imaging 1983;20:121–173. 162. Schnyder PA, Gamsu G. CT of the pretracheal retrocaval space. AJR Am J Roentgenol 1981;136:303–308. 163. Aronberg DJ, Peterson RR, Glazer HS, et al. The superior sinus of the pericardium: CT appearance. Radiology 1984;153:489–492. 164. Black CM, Hedges LK, Javitt MC. The superior pericardial sinus: normal appearance on gradient-echo MR images. AJR Am J Roentgenol 1993;160:749–751. 165. McComb BL. Reflecting upon the left superior mediastinum. J Thorac Imaging 2001;16:56–64. 166. Wimpfheimer O, Haramati LB, Haramati N. Calcification of the ligamentum

167.

168.

169.

170. 171.

172. 173.

174.

175.

176. 177.

178. 179.

180.

181.

182. 183.

184.

185.

arteriosum in adults: CT features. J Comput Assist Tomogr 1996;20:34–37. Bisceglia M, Donaldson JS. Calcification of the ligamentum arteriosum in children: a normal finding on CT. AJR Am J Roentgenol 1991;156:351–352. Protopapas Z, Westcott JL. Left pulmonic recess of the pericardium: findings at CT and MR imaging. Radiology 1995;196: 85–88. Callen PW, Korobkin M, Isherwood I. Computed tomographic evaluation of the retrocrural prevertebral space. AJR Am J Roentgenol 1977;129:907–910. Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718–1723. Cymbalista M, Waysberg A, Zacharias C, et al. CT demonstration of the 1996 AJCC-UICC regional lymph node classification for lung cancer staging. RadioGraphics 1999;19:899–900 poster. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:1710–1717. Glazer GM, Gross BH, Quint LE, et al. Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping. AJR Am J Roentgenol 1985;144:261–265. Genereux GP, Howie JL. Normal mediastinal lymph node size and number: CT and anatomic study. AJR Am J Roentgenol 1984;142:1095–1100. Ingram CE, Belli AM, Lewars MD, et al. Normal lymph node size in the mediastinum: a retrospective study in two patient groups. Clin Radiol 1989;40: 35–39. Murray JG, O’Driscoll M, Curtin JJ. Mediastinal lymph node size in an Asian population. Br J Radiol 1995;68:348–350. Sussman SK, Halvorsen RA Jr, Silverman PM, et al. Paracardiac adenopathy: CT evaluation. AJR Am J Roentgenol 1987;149: 29–34. Proto AV, Corcoran HL, Ball JB Jr. The left paratracheal reflection. Radiology 1989;171: 625–628. Bachman AL, Teixidor HS. The posterior tracheal band: a reflector of local superior mediastinal abnormality. Br J Radiol 1975; 48:352–359. Gibbs JM, Chandrasekhar CA, Ferguson EC, et al. Lines and stripes: where did they go? From conventional radiography to CT. RadioGraphics 2007;27:33–48. Keats TE. The aortic-pulmonary mediastinal stripe. Am J Roentgenol Radium Ther Nucl Med 1972;116: 107–109. Lane EJ, Heitzman ER, Dinn WM. The radiology of the superior intercostal veins. Radiology 1976;120:263–267. Takahashi K, Shinozaki T, Hyodo H, et al. Focal obliteration of the descending aortic interface on normal frontal chest radiographs: correlation with CT findings. Radiology 1994;191:685–690. Takahashi K, Sugimoto H, Ohsawa T. Obliteration of the descending aortic interface in pectus excavatum: correlation with clockwise rotation of the heart. Radiology 1992;182:825–828. Savoca CJ, Austin JH, Goldberg HI. The right paratracheal stripe. Radiology 1977; 122:295–301.

81

Chapter 2 • The Normal Chest 186. Cimmino CV. The esophageal-pleural stripe: an update. Radiology 1981;140: 609–613. 187. Fitzgerald SW, Donaldson JS. Azygoesophageal recess: normal CT appearance in children. AJR Am J Roentgenol 1992;158:1101–1104. 188. Miller FH, Fitzgerald SW, Donaldson JS. CT of the azygoesophageal recess in infants and children. RadioGraphics 1993;13: 623–634. 189. Proto AV, Lane EJ. Air in the esophagus: a frequent radiographic finding. AJR Am J Roentgenol 1977;129:433–440. 190. Whalen JP, Oliphant M, Evans JA. Anterior extrapleural line: superior extension. Radiology 1975;115:525–531. 191. Raider L, Landry BA, Brogdon BG. The retrotracheal triangle. RadioGraphics 1990; 10:1055–1079.

82

192. Palayew MJ. The tracheo-esophageal stripe and the posterior tracheal band. Radiology 1979;132:11–13. 193. Kormano M, Yrjana J. The posterior tracheal band: correlation between computed tomography and chest radiography. Radiology 1980;136:689–694. 194. Whalen JP, Meyers MA, Oliphant M, et al. The retrosternal line. A new sign of an anterior mediastinal mass. Am J Roentgenol Radium Ther Nucl Med 1973;117:861–872. 195. Gale ME. Anterior diaphragm: variations in the CT appearance. Radiology 1986;161:635–639. 196. Heitzman ER. Kerley Pergamon lecture: The diaphragm. Radiologic correlations with anatomy and pathology. Clin Radiol 1990;42:15–19. 197. Kleinman PK, Raptopoulos V. The anterior diaphragmatic attachments: an anatomic

198.

199.

200.

201.

and radiologic study with clinical correlates. Radiology 1985;155:289–293. Panicek DM, Benson CB, Gottlieb RH, et al. The diaphragm: anatomic, pathologic, and radiologic considerations. RadioGraphics 1988;8:385–425. Lennon EA, Simon G. The height of the diaphragm in the chest radiograph of normal adults. Br J Radiol 1965;38: 937–943. Houston JG, Morris AD, Howie CA, et al. Technical report: quantitative assessment of diaphragmatic movement – a reproducible method using ultrasound. Clin Radiol 1992;46:405–407. Berkmen YM, Davis SD, Kazam E, et al. Right phrenic nerve: anatomy, CT appearance, and differentiation from the pulmonary ligament. Radiology 1989;173:43–46.

CHAPTER

3

Basic patterns in lung disease

SILHOUETTE SIGN AIR BRONCHOGRAM PULMONARY OPACITY AIRSPACE OPACITIES Differential diagnosis of airspace filling ATELECTASIS/COLLAPSE Mechanisms of atelectasis Imaging lobar atelectasis Bronchial dilatation and air bronchograms within atelectatic lobes Right upper lobe atelectasis Left upper lobe atelectasis Right middle lobe atelectasis Lower lobe atelectasis Whole lung atelectasis Combined right upper and middle lobe atelectasis Combined right lower and middle lobe atelectasis Distinguishing lower lobe collapse from pleural fluid Lobar atelectasis due to bronchiectasis Round atelectasis SOLITARY PULMONARY NODULE/MASS Calcification

One of the crucial decisions when viewing chest radiographs is determining the location of a potential lesion, in particular whether the lesion is primarily in the lung, the hilum, the mediastinum, the pleura, the chest wall, or the diaphragm. Indeed the distinction is so important that most textbooks, including this one, are organized according to anatomic divisions. In this chapter and the following one on high-resolution computed tomography (HRCT), the discussion is centered on the signs of diseases of the lungs on chest radiography and on CT. Two interrelated chest radiographic signs – the silhouette sign and the air bronchogram – are considered first because they have widespread diagnostic applicability.

SILHOUETTE SIGN Felson and Felson1 popularized the term ‘silhouette sign’. They wrote, ‘An intrathoracic lesion touching a border of the heart, aorta, or diaphragm will obliterate that border on the roentgenogram. An intrathoracic lesion not anatomically contiguous with a border of one of the structures will not obliterate that border’. The lesion responsible for obliterating a silhouette (Figs 3.1 and 3.2) does not have to be large, nor does the opacity have to originate within the lung; pleural fluid, extrapleural fat, chest wall deformity, and mediastinal masses may all cause a loss of silhouette.2,3 Felson and Felson believed the sign depended solely on direct contact. It may, however, be due to absorption of X-rays by what-

Fat density within a nodule Ground-glass opacity Contrast enhancement Rate of growth Size and shape Air bronchograms and bubblelike lucencies Cavities and air crescent sign The CT halo sign Adjacent bone destruction Management considerations MULTIPLE PULMONARY NODULES Management considerations CYSTS LINEAR AND BANDLIKE OPACITIES Focal parenchymal and pleuroparenchymal scars Mucoid impaction Septal lines Bronchial wall (peribronchial) thickening NODULAR AND RETICULONODULAR OPACITIES AND HONEYCOMBING INCREASED TRANSRADIANCY OF THE LUNG

ever lies in the path of the beam; the reason the border is lost only in cases of direct contact is that precise anatomic conformity of shape occurs only when intimate contact is present. The silhouette sign can be used in two ways: • To localize a radiographic density (Figs 3.3 and 3.4) because, in practice, the lesion lies immediately adjacent to the structure in question. Thus opacities in the right middle lobe or lingula may obliterate the right and left borders of the heart, respectively (Figs 3.1 and 3.5), whereas opacities in the lower lobes may partially obliterate the outline of the descending aorta and diaphragm but leave the cardiac outline clearly visible (Fig. 3.6). Similarly, the aortic knob will be rendered invisible if there is no air in the adjacent left upper lobe. A good example of detecting lesions of low radiopacity is collapse of the right middle lobe (Fig. 3.5). • to detect lesions of low radiopacity when the loss of silhouette is more obvious than the opacity itself (Fig. 3.2). Felson and Felson1 warned that mistakes will be made unless the following points are borne in mind: • The technical quality of the radiograph must be such that the diseased area is adequately penetrated. Underpenetration may result in loss of visibility of a normal border. • The outline of a portion of the cardiovascular structure in question must be clearly visible beyond the opacity formed by the spine. In many healthy individuals the right border of the heart and ascending aorta do not project into the right hemithorax. In these patients the silhouette sign cannot be applied on the right.

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Chapter 3 • Basic Patterns in Lung Disease

A

B

Fig. 3.1  The silhouette sign. The left heart border is invisible because of consolidation in the adjacent left upper lobe. A, Posteroanterior view. B, Lateral view.

A

B

Fig. 3.2  The silhouette sign. A, A small patch of pneumonia in the anterior segment of the left lower lobe has resulted in lack of visibility of the outer half of the left hemidiaphragm. (The lateral view in this patient is shown in Fig. 3.14.) B, Normal diaphragm outline after the pneumonia has resolved.

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Air Bronchogram

A

B

Fig. 3.3  A, Preservation of the silhouette of the aortic knob and descending aorta in the posteroanterior view is good evidence that the pulmonary mass does not lie in the superior segment of the lower lobe. B, The lateral view shows that the mass, in fact, lies well anteriorly. (It proved to be a squamous cell carcinoma.)

• In patients with pectus excavatum the right border of the heart is frequently obliterated because the depressed thoracic wall replaces aerated lung alongside the cardiac silhouette (Fig. 3.7). Felson and Felson1 also pointed out that there are patients in whom no disease and no satisfactory explanation for the loss of the right heart border is found. These cases are, however, few and do not reduce the overall value of the sign.

AIR BRONCHOGRAM Normal intrapulmonary airways are invisible on chest radiographs unless end on to the X-ray beam, but air within bronchi, or bronchioles, passing through airless parenchyma may be visible as branching linear lucencies. The resulting image is called an air bronchogram (Fig. 3.8). An air bronchogram within an opacity reliably indicates that the opacity is intrapulmonary and not pleural or mediastinal in location.3 The sign is particularly well seen on CT (Fig. 3.9). The most common causes of an air bronchogram (see Box 3.1) are consolidations of various origins and pulmonary edema. Similarly, widespread air bronchograms are seen in hyaline membrane disease. Air bronchograms are also seen in atelectatic lobes on chest radiographs when the airway is patent, notably when atelectasis is caused by pleural effusion, pneumothorax, or bronchiectasis. There are four less predictable causes of air bronchograms: Fig. 3.4  The loss of silhouette of the left cardiac border in the frontal view localizes the pulmonary consolidation to the lingula. It proved to be postobstructive pneumonia beyond a carcinoma in the lingular bronchus.

• Bronchioloalveolar cell carcinoma (Fig. 3.10) and lymphoma grow around airways without compressing them. Therefore, in these diseases, air bronchograms may be visible even on chest radiographs. Air bronchograms in other lung malignancies, such as small adenocarcinomas, may only be defectable on CT.4–8 • Interstitial fibrosis, notably advanced usual interstitial pneumonia and radiation fibrosis, may be so intense that in addition to

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Chapter 3 • Basic Patterns in Lung Disease

A

B

Fig. 3.5  Right middle lobe atelectasis and consolidation obliterating the right heart border. A, Posteroanterior view. B, Lateral view.

A

B

Fig. 3.6  Left lower lobe atelectasis and consolidation obliterating the outline of the adjacent descending aorta and medial left hemidiaphragm. A, Posteroanterior view. B, Lateral view.

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Air Bronchogram

A

B

Fig. 3.7  Pectus excavatum causing obliteration of the right border of the heart. A, Posteroanterior view. B, Lateral view.

Fig. 3.9  Air bronchograms (arrows) within consolidated lung shown by CT in a patient with bilateral infective pneumonia. Fig. 3.8  An air bronchogram. The branching linear lucencies within the consolidation in the right lower lobe are particularly well demonstrated in this example of staphylococcal pneumonia.

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A

B

Fig. 3.10  An air bronchogram in bronchioloalveolar carcinoma. A, Chest radiograph. B, CT of a different patient with bronchioloalveolar carcinoma. Box 3.1  Examples of causes of air bronchograms on chest radiography • • • • • • • •

Normal expiratory radiograph Infective consolidation Pulmonary edema Acute respiratory distress syndrome (in adults) or hyaline membrane disease (in neonates) Compression atelectasis (e.g. pleural effusion) Scarring, e.g. radiation fibrosis, bronchiectatic lobe Severe interstitial disease, e.g. sarcoidosis Certain neoplasms (notably bronchioloalveolar cell carcinoma, lymphoma)

causing dilatation of the bronchi, which remain patent, the lung parenchyma is almost airless, producing an air bronchogram (Fig. 3.11).9,10 Air bronchograms may also be seen in areas of dense involvement of the lung by sarcoidosis (Fig. 3.12). • Air bronchograms can occasionally be seen in postobstructive pneumonia, particularly on CT, even though replacement of air by secretions beyond the obstruction might have been expected. • Air bronchograms can be normal on chest radiography at low lung volumes and in the segmental bronchi behind the heart in children.

PULMONARY OPACITY Pulmonary opacity is defined as an ‘area that preferentially attenuates the x-ray beam and therefore appears more opaque than the surrounding area’.3 A pulmonary opacity is readily detected in the frontal radiograph by comparing one lung with the other. In the

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Fig. 3.11  An air bronchogram (arrows) in radiation fibrosis of the right upper lobe following treatment of carcinoma of the breast.

lateral view such right-to-left comparisons are not possible and therefore alternative signs are needed. In the normal lateral view, each thoracic vertebral body appears more translucent than the one above it, as the eye travels down the spine, until the diaphragm is reached. Pulmonary opacities projected over the spine alter this graduation (Fig. 3.13). Moreover, in a healthy individual, there is no abrupt change in density across the heart in the lateral view (Fig. 3.14). Less reliably, the high retrosternal area is usually more trans-

Airspace Opacities lucent than all other areas on the lateral chest radiograph, except the region immediately behind the heart. As parenchymal opacities can be subtle, a systematic approach should be adopted when analyzing a chest radiograph. The apices, the hila, the retrocardiac regions, the lung below the domes of the diaphragm, and the area just inside the chest wall should be examined with particular care, because experience shows that opacities in these areas are easily overlooked. The characteristics of a parenchymal opacity depend on the absorptive capacity and geometry of the object. In order of increasing absorptive capacity, the major components of the chest are air, fat, fluid and soft tissues, and bone. For practical purposes, fluid and soft tissues, apart from fat, are isodense on chest radiographs. The following geometric features are worth noting (Fig. 3.15):11 • Interfaces tangential to the X-ray beam are sharp and distinct, whereas oblique interfaces are not seen because they fade off and cannot be identified (Fig. 3.15A).

• Hollow cylinders and hollow spheres are most absorptive at their edges because at the edge the beam has a longer path within the object and is therefore more attenuated. Also, the outside and inside marginal interfaces are sharp and distinct (Fig. 3.15B). • A thin sheet perpendicular to an X-ray beam usually causes no detectable opacity (Fig. 3.15C), whereas a thin sheet oriented in the direction of the beam can cause an opacity (Fig. 3.15D). There are innumerable patterns of pulmonary opacities, with no clear-cut divisions between them. Nevertheless, categorizing these patterns is worthwhile; the more certain the observer is of the description of an individual opacity, the shorter the differential diagnostic list will be. The diagnostic considerations for a particular pattern may be further reduced by reviewing serial images. The following classification of pulmonary opacities is used in this chapter: • • • • • •

Airspace opacities Atelectasis (collapse) Nodules and masses Linear and bandlike opacities Cysts and bullae Nodular and reticulonodular opacities, and honeycombing.

More than one pattern may be present on the same imaging study. Calcifications and cavitations should be looked for; their presence will limit the number of diagnostic possibilities.

AIRSPACE OPACITIES

Fig. 3.12  An air bronchogram in ‘airspace’ sarcoidosis of the lung shown by CT.

A

This term designates the ‘filling of airspaces with the products of disease’.3 Airspace opacities can be heterogeneous in appearance, and do not necessarily obscure vascular or bronchial margins. On the other hand, the term ‘consolidation’, widely used by pathologists, refers to the products of disease ‘that replace alveolar air, rendering the lung solid’.3 Consolidation causes a relatively homogeneous increase in lung attenuation that obscures the margins of vessels and airways.

B

Fig. 3.13  Alteration in opacity of the thoracic vertebrae on lateral projection as a sign of lower lobe density. In this case, increasing opacity of the vertebral bodies as the eye travels down the spine is one of the most obvious signs indicating the presence of right lower lobe atelectasis. A, Posteroanterior view. B, Lateral view.

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Chapter 3 • Basic Patterns in Lung Disease

Fig. 3.14  Abrupt change in density overlying the cardiac silhouette. A lateral view in a patient with pneumonia in the anterior segment of the left lower lobe. (The posteroanterior view of this patient is shown in Fig. 3.2.)

Beam

Object

Image

A

The features of airspace opacities on chest radiographs are one or more opacities with ill-defined margins, except where the shadow abuts the pleura. When multiple, the shadows may coalesce. An air bronchogram may be visible. On chest radiography, the normal vascular markings within the opacity are indistinct or invisible. The lack of clarity of the edge of the opacities results, in part, from the piecemeal spread of the process through the alveoli, the poorly defined margin being analogous to the edge of a threedimensional jigsaw puzzle. Once the process abuts a fissure, the edge appears sharp. The ease with which it is possible to appreciate this edge on chest radiographs depends on how tangential a fissure is to the X-ray beam. Many sublobar processes are vaguely conical, and sometimes resemble the shape of a segment. Precise conformity to a segment almost never occurs because, with the rare exception of accessory fissures, there are no anatomic barriers to prevent the spread of pathologic processes across segmental boundaries. Airspace opacities are often peripheral in location, crossing segmental boundaries with impunity. Spherical consolidations are comparatively less common. Ill-defined nodular opacities between 0.5 cm and 1 cm are sometimes seen within or adjacent to the larger opacities of airspace opacities, particularly with pulmonary edema and lung infections, notably varicella or tuberculosis (Fig. 3.16; see also Fig. 3.19). These opacities have been called ‘acinar shadows’, since they are believed to be opaque acini contrasted against aerated lung.12 They may coalesce as disease progresses. The converse of the acinar opacity is the air alveologram (Fig. 3.17), a pattern of small rounded lucencies seen when aerated acini are surrounded by opaque lung. Cavitation may occur within airspace opacities and consolidations. A cavity is defined as a ‘gas-filled space, seen as a lucency or lowattenuation area’.3 The cavity is usually the result of the expulsion or drainage of a necrotic part of the lesion via the bronchial tree. Although air–fluid levels may be seen in cavitations, the term is not synonymous with abscess3 (Fig. 3.18). The term ‘ground glass’ has a slightly different meaning depending on whether it is being applied to chest radiographs or to CT images, notably HRCT. When applied to chest radiographs it refers to an ‘area of hazy increased lung opacity, usually extensive, within

B

C

D

Fig. 3.15  The density characteristics of pulmonary opacities. See text for explanation. (With permission from Wilson AG. The interpretation of shadows on the adult chest radiograph. Br J Hosp Med 1987;37:526–534.)

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Fig. 3.16  Acinar opacities in pulmonary tuberculosis (arrow). The acinar opacities have become confluent in the lateral portion of the right upper lobe. (The appearance of acinar shadows on CT is shown in Fig. 3.19.)

Airspace Opacities which margins of pulmonary vessels may be indistinct’.3 Groundglass opacity on HRCT refers to an increase in attenuation of the lung parenchyma without obscuration of the underlying bronchovascular structures. The pathogenesis of ground-glass opacities is complex and partial filling of the airspaces is only one of several mechanisms; this pattern is discussed more fully in Chapter 4.

Given its excellent contrast discrimination, CT, and particularly HRCT, may provide additional information about airspace opacities (Fig. 3.19). CT allows airspace opacities to be seen when chest radiographs still have a normal appearance.13 It can also demonstrate the size, shape, and precise position of any cavities (Fig. 3.20).14 Other morphological features of airspace opacities that are particularly well demonstrated by CT are air bronchograms (see Figs 3.9 and 3.10), the satellite lesions of infectious inflammation, including a tree-in-bud pattern, and the conformity of radiation fibrosis to the radiation port (Fig. 3.21). The term ‘CT angiogram sign’15 refers to the presence of visible contrast-enhanced blood vessels coursing through areas of consolidation (Fig. 3.22).16 The sign was originally described as reasonably specific for bronchioloalveolar cell carcinoma,16 but with the more rapid rate of contrast medium injection that has become common in the past decade it is apparent that the CT angiogram sign is seen in a variety of other causes of consolidation, notably pneumonia, obstructive pneumonitis, pulmonary edema, and lymphoma.16–20 The CT angiogram sign, however, is useful in the differential diagnosis of atelectatic lung resembling pleural effusion: its presence definitively indicates pulmonary pathology, since the sign cannot occur within a pleural abnormality.21

Differential diagnosis of airspace opacities

Fig. 3.17  An air alveologram in bronchogenic spread of tuberculosis.

A

Solitary airspace opacities (Fig. 3.23) are usually the result of pneumonia, atelectasis, infarction (Fig. 3.24), or hemorrhage (Fig. 3.25). Neoplasms, particularly bronchioloalveolar cell carcinoma (see Figs 3.10, 3.26 and 3.89) and lymphoma (Fig. 3.27), may also appear illdefined enough to be called focal consolidations. The full list of causes for solitary airspace opacities is given in Table 3.1. Airspace filling is often multifocal and tends to coalesce as it progresses (Fig. 3.28). The list of causes is given in Boxes 3.2 and 3.3. The following considerations may be helpful when analyzing airspace opacities: • Clinical correlation is essential and is often decisive. A few examples confirm this point: (a) in patients with noncardiogenic pulmonary edema, the chest radiograph may not become

B

Fig. 3.18  Cavitation. A, In this example of staphylococcal pneumonia there are multiple transradiant areas within consolidation but no air–fluid levels. B, Another patient, illustrating an air–fluid level in a cavity within an area of pneumonia.

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Fig. 3.19  Acinar opacities, some of which have coalesced. CT of bronchogenic spread of tuberculous pneumonia. Fig. 3.21  Radiation fibrosis. CT showing conformity of the radiation fibrosis to the radiation portal. Note the obvious air bronchograms in the fibrotic lung.

A

C

92

B

Fig. 3.20  CT showing: A, complex eccentrically placed cavitation (arrow) within infective pneumonia; B and C, cavitating disease in Wegener granulomatosis (red arrows). Note coexisting solid nodule in C (yellow arrow).

Airspace Opacities

Fig. 3.22  CT angiogram sign. Branching contrast-enhanced pulmonary vessels are seen coursing through low-density pulmonary consolidation. In this instance, the diagnosis was lymphoma. (With permission from Vincent JM, Ng YY, Norton AJ, et al. CT ‘angiogram sign’ in primary pulmonary lymphoma. J Comput Assist Tomogr 1992;16:829–831.)

A

B

Fig. 3.23  A solitary airspace opacity, in this case resulting from bacterial pneumonia. Note that the pneumonia occupies the gravitationally dependent portions of lobes, rather than being distributed according to segmental anatomy. A, Posteroanterior view. B, Lateral view.

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Chapter 3 • Basic Patterns in Lung Disease

A

B

Fig. 3.24  Small focus of pulmonary consolidation caused by pulmonary infarction. A, Coronal reconstruction shows peripheral pulmonary infarct (arrow). B, CT angiogram shows embolus (arrow).

Fig. 3.25  A solitary airspace opacity caused by pulmonary hemorrhage (contusion) following a motor vehicle accident. (A pneumomediastinum is also present.)

Fig. 3.26  Consolidation of the right lung caused by bronchioloalveolar carcinoma.

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Airspace Opacities

A

B

Fig. 3.27  A solitary airspace opacity with obvious air bronchograms in a mucosa-associated lymphoid tumor of the lung parenchyma. A, Chest radiograph. B, CT of the same patient.

Box 3.2  Causes of multifocal airspace opacities on chest radiographs

Box 3.3  Widespread airspace opacities on chest radiographs: likelihood of bat’s wing pattern

Exudates and transudates

Common pattern for disease

• • • • • •

• Pulmonary edema, both circulatory and noncirculatory (acute respiratory distress syndrome) • Pneumonia, notably pneumonia caused by aspiration or Pneumocystis jirovecii • Inhalation of noxious gases or liquids • Alveolar proteinosis • Pulmonary hemorrhage – Spontaneous – Goodpasture syndrome – Bleeding tendency

• • • • •

Pneumonia Organizing pneumonia Pulmonary emboli causing infarction (bland or septic) Eosinophilic pneumonia Connective tissue disease and vasculitis Pulmonary edema, both circulatory and noncirculatory (acute respiratory distress syndrome) Inhalation of noxious gases or liquids Hydrocarbon ingestion Drug reactions Allergic reactions Alveolar proteinosis

Hemorrhage • • • •

Pulmonary contusion and hematoma Hemorrhage due to pulmonary embolus Aspiration of blood Idiopathic hemorrhage, Goodpasture syndrome, bleeding tendency

Neoplasm • • • •

Bronchioloalveolar cell carcinoma Lymphangitis carcinomatosa Metastases Lymphoma

Miscellaneous • • • •

Sarcoidosis Silicosis, coal worker’s pneumoconiosis Alveolar microlithiasis Diffuse pulmonary calcification

Occasional or rare pattern for disease • • • • • • • • • • •

Aspiration of blood Bronchioloalveolar cell carcinoma Lymphangitis carcinomatosa Alveolar microlithiasis Diffuse pulmonary calcification Lymphoma Pulmonary emboli causing hemorrhage or infarction (bland or septic) Connective tissue disease/vasculitis Drug reactions Allergic reactions Amyloidosis

Extremely rare pattern for disease • • • •

Eosinophilic pneumonia Metastases Sarcoidosis Silicosis, coal worker’s pneumoconiosis

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Chapter 3 • Basic Patterns in Lung Disease Table 3.1  Differential diagnosis of solitary airspace opacities on chest radiographs Diagnosis

Comments

Pneumonia

Pneumonia is the most common cause of solitary airspace filling. The opacity may be almost any shape from segmental/lobar to round or irregular. Cavitation and accompanying pleural effusion are both distinct features. In adults an associated hilar mass suggests a centrally located neoplasm causing postobstructive pneumonia, whereas in children an associated hilar mass suggests primary tuberculosis

Organizing pneumonia

Can be responsible for a variety of radiographic patterns, including a focal or segmentalshaped area of consolidation

Atelectasis

The diagnosis of atelectasis is based on its characteristic shape. The appearances and causes are discussed in the section ‘Atelectasis/Collapse’ later in this chapter. Discoid atelectasis results in a characteristic bandlike shape coursing through the lung, often in a horizontal orientation. Large areas of atelectasis that do not conform to either of these patterns may be indistinguishable from the other causes of airspace shadowing listed in this table

Infarction or hemorrhage associated with pulmonary embolism

Infarcts are usually segmental in size, rarely larger. Their shape is similar to a truncated cone with the base on the pleura. The apex of the cone, which may be rounded, points towards the hilum. The rounded medial margin, known as Hampton hump (see Chapter 7), is a well known but infrequent sign suggestive, but not diagnostic, of the condition. Septic infarcts cavitate frequently, whereas bland infarcts rarely cavitate

Pulmonary contusion

Contusions appear within hours of injury and clear within a few days. They are usually maximal in the general area of injury, although contrecoup damage may be seen at a distance. Pneumatocele formation is a distinct feature. Pulmonary contusion may surround a pulmonary hematoma. Hematomas resemble masses, may liquefy and cavitate, and take much longer to clear than contusions

Connective tissue disease, vasculitis

These conditions are infrequent causes of solitary airspace shadowing. They need to be considered in patients with appropriate clinical features. The opacity is usually sublobar in size and nonspecific in shape. Cavitation may be seen. Most solitary shadows in patients with connective tissue disease or vasculitis represent pneumonia, organizing pneumonia or infarction

Drug reactions and allergic reactions

Airspace opacities in these conditions are rarely solitary. They may be almost any shape except lobar

Hemorrhage

Solitary airspace opacities caused by hemorrhage are usually due to pulmonary emboli or to pulmonary trauma. When caused by systemic disease, pulmonary hemorrhage is usually multifocal. When single, the opacity can be any shape, even including lobar

Neoplasm

Postobstructive pneumonia is a common cause of solitary airspace opacities. Some neoplasms, particularly bronchioloalveolar cell carcinoma and lymphoma, can closely resemble focal pneumonia and may even contain air bronchograms. The absence of clinical features of pneumonia and the lack of change of the shadow over many weeks point to one of these neoplasms. The longer the opacity persists, particularly if it grows slowly, the more likely it is to be a neoplasm

Radiation pneumonitis/fibrosis

Airspace opacities caused by radiation therapy conforms, usually but not invariably, to the approximate shape of the radiation port, a feature that is particularly evident on CT. The shape and the fact that radiation therapy was given usually permit a specific diagnosis to be made

Eosinophilic pneumonia

Airspace opacities in this condition are almost invariably multifocal; they are very rarely solitary. The opacities are likely to be noticeably peripheral in location

abnormal until several hours after the onset of symptoms, whereas with cardiogenic pulmonary edema the pulmonary opacities are almost always evident early on; (b) widespread pneumonia is almost invariably accompanied by cough and fever; (c) aspiration should be suspected as the cause of airspace opacities in patients who have known predisposing factors such as alcoholism, a recent seizure, or a period of unconsciousness; (d) widespread pulmonary opacities in immunocompromised patients usually indicate infection, often from opportunistic organisms; and (e) substantial hemoptysis associated with widespread pulmonary consolidations often indicate pulmonary hemorrhage.

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• Opacities of over half a lobe with no loss of volume are virtually diagnostic of pneumonia (Fig. 3.29). The common causes in patients living in the community are pneumococcal or Mycoplasma pneumonia and pneumonia distal to a bronchial neoplasm. Neoplastic obstruction of a lobar bronchus usually causes some degree of atelectasis, but consolidation without loss of volume due to an obstructing neoplasm is not uncommon. Bronchioloalveolar cell carcinoma and lymphoma may on occasion appear identical to lobar pneumonia. The lobar consolidation in these cases is due to neoplastic tissue spreading through the alveolar spaces without necessarily occluding the central bronchi.

Airspace Opacities

•

Fig. 3.28  Multiple coalescent airspace opacities resulting from bacterial pneumonia. • Lobar consolidation with expansion of the lobe suggests bacterial pneumonia (particularly due to Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus) or obstructive pneumonia caused by a centrally positioned carcinoma of the bronchus, the so-called ‘drowned lung’. • Spherical consolidation is likely to be due to pneumonia (Fig. 3.30). The organisms most likely to cause round, spherical, or nodular pneumonia are S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Legionella pneumophila or Legionella micdadei, Mycobacterium tuberculosis, and a variety of fungi. Clearly the major differential diagnosis is that of pulmonary neoplasm. Groundglass opacities surrounding rounded consolidation on CT are

A

•

• •

highly suggestive of hemorrhage; the causes of this so-called ‘CT halo sign’ (see Fig. 3.91) are discussed on p. 131. Lucencies within consolidated lung may be due to: (a) intervening normal lung, either because those particular portions of lung, often secondary pulmonary lobules, were never involved or because they have cleared prior to the remainder of the pneumonia; (b) preexisting centrilobular emphysema; (c) necrosis of tissue with cavitation; or (d) pneumatoceles.22 The development of air–fluid levels within an area of consolidation that is known or presumed to be pneumonia strongly suggests necrotizing pneumonia. Bacteria are the likely pathogens, notably S. aureus, Gram-negative bacteria (notably K. pneumoniae, Proteus and P. aeruginosa), anaerobic bacteria, and tuberculosis. Those few cases of segmental or lobar consolidation with cavitation not caused by infection may be the consequence of a vasculitis or, rarely, lymphoma. A meniscus of air within an area of segmental or lobar consolidation almost always represents resolving invasive fungal infection. The presence of rib or vertebral body destruction in the vicinity of a pulmonary opacity or consolidation, whatever the shape of the alteration, is virtually diagnostic of invasion by primary carcinoma of the lung. With the rare exception of actinomycosis23 and the occasional case of pulmonary tuberculosis24 or fungal disease, neither pulmonary infections nor other non-neoplastic pulmonary processes invade the adjacent bones. Multiple airspace opacities that are clearly lobar or segmental in shape constitute another potentially useful diagnostic subgroup (Fig. 3.31; Box 3.4). It is useful to separate those cases of multifocal airspace opacities that show the so-called bat wing or butterfly pattern, because the presence of this pattern makes certain diagnoses more or less likely. The fanciful descriptors for this pattern are an attempt to describe bilateral perihilar opacities. The opacities consist of coalescent densities with ill-defined borders, some-

B

Fig. 3.29  Lobar consolidation resulting from bacterial pneumonia. In this case, the superior segment of the right lower lobe is spared. A, Posteroanterior view. B, Lateral view.

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Chapter 3 • Basic Patterns in Lung Disease

A

B

Fig. 3.30  Round (spherical) pneumonia in a patient with bacterial pneumonia. A, Radiograph on admission to hospital. B, One day later, the pneumonia has spread through the adjacent lung.

Box 3.4  Differential diagnosis of multiple airspace opacities on chest radiographs when their shape is clearly lobar or segmental • • • •

Pneumonia Infarction or hemorrhage caused by pulmonary emboli Pulmonary edema* Neoplasm (bronchioloalveolar cell carcinoma, lymphangitis carcinomatosa,* malignant lymphoma)

*Segmental or lobar shapes are a rare manifestation of the entity.

Fig. 3.31  Multiple airspace opacities with a lobar–segmental distribution in a case of bacterial pneumonia. times with acinar components at their periphery. The outer portion of each lobe is less involved than the perihilar area and is often normal (Fig. 3.32). Bat wing opacities may be symmetric, but are often more severe on one side than the other. Air bronchograms may be visible. By far the most common cause is pulmonary edema (Fig. 3.32), particularly if air bronchograms or acinar opacities are present. Cases of bat wing opacities not caused by pulmonary edema are likely to be due to pneumonia,

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inhalation of noxious gases or liquids (including aspiration of gastric contents), multifocal pulmonary hemorrhage (Fig. 3.33), vasculitis, or neoplasm, particularly lymphangitis carcinomatosa. Multifocal pneumonia can be due to a vast array of organisms, but the bat wing pattern in the immunocompetent patient should suggest particularly aspiration pneumonia, Gram-negative bacterial pneumonia, and nonbacterial pneumonias such as mycoplasmal, viral, and rickettsial pneumonia. Pneumonia in the immunocompromised host often results in the bat wing pattern, most notably in infections with opportunistic organisms such as P. jirovecii and various fungi. The coexistence of thickened interlobular septa (Kerley A and B lines) visible on chest radiographs, for practical purposes, limits the diagnostic possibilities to pulmonary edema and lymphangitis carcinomatosa. Bat wing opacities that remain unchanged over several weeks and are associated with nonspecific chronic symptoms suggest alveolar proteinosis (Fig. 3.34) or a neoplasm, notably lymphangitis carcinomatosa (Fig. 3.35), bronchioloalveolar cell carcinoma, or malignant lymphoma. Sarcoidosis and Wegener granulomatosis are rare possibilities for such opacities. • Nonsegmental airspace opacities that are widespread, yet clearly peripheral in location (sometimes called ‘the photographic negative of pulmonary edema’), strongly suggest chronic eosinophilic pneumonia when the upper zone is pre-

Airspace Opacities

Fig. 3.32  Bat wing pattern caused by pulmonary edema. This example is typical in that it is bilateral, but asymmetric. The opacification is maximal in the central (perihilar) portions of the lung, and the outer portions of the lungs are relatively clear.

Fig. 3.34  Bat wing opacity due to alveolar proteinosis.

Fig. 3.33  Bat wing opacity due to idiopathic pulmonary hemorrhage.

dominant (Fig. 3.36).25 The peripheral distribution may be more readily apparent on CT than on the chest radiograph.26 When there is no upper zone predominance the differential diagnosis widens to include drug reactions and organizing pneumonia (Fig. 3.37). • Many of the causes of multiple airspace opacities appear rapidly, but pulmonary edema and hemorrhage are the only ones that clear within hours. • Airspace opacities that resolve only to reappear either in the same area or in some other part of either lung suggest: pulmo-

Fig. 3.35  Bat wing opacity due to lymphangitis carcinomatosa.

nary edema; eosinophilic pneumonia, either acute or chronic; or asthma, particularly when associated with bronchopulmonary aspergillosis. • Subtle punctate calcification may cause focal or multifocal areas of pulmonary opacity, closely resembling consolidation on chest radiographs (Fig. 3.38). This phenomenon occurs in patients with hypercalcemia caused by conditions such as

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Fig. 3.36  Chronic eosinophilic pneumonia. Two examples showing nonsegmental peripheral distribution of airspace opacities. A, As is more usual, the airspace opacity is bilateral. B, An example with unilateral airspace opacity.

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Fig. 3.37  Cryptogenic organizing pneumonia showing patchy, peripherally predominant, airspace opacities. A, Chest radiograph. B, CT of a similar case.

hyperparathyroidism, particularly secondary hyperparathyroidism resulting from renal failure, and in children who have had cardiac surgery or liver transplants.27–31 The calcifications may be so minute that it is not possible to appreciate on chest radiographs that the cloudlike opacities are in fact due to a myriad of calcifications. The appearance may then be confused with the other causes of multiple airspace opacities. CT allows the observation of widespread parenchymal calcification to be made with greater confidence. • Acute respiratory distress syndrome (ARDS) is the most likely diagnosis for uniform opacity of the whole of both lungs without pleural effusion in the immunocompetent patient (Fig.

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3.39). Air bronchograms are a noteworthy feature in these patients. • Sarcoidosis occasionally causes patchy opacities in the lungs that tend to be spherical, contain air bronchograms, and are associated with obvious hilar and mediastinal lymph node enlargement. Sometimes these opacities dominate the picture and, when irregular in shape, are indistinguishable on imaging from multifocal pneumonia (Fig. 3.40). • Progressive massive fibrosis may, rarely, resemble airspace opacities (Fig. 3.41). The changes are, however, characteristic in shape and position, do not contain air bronchograms, and often cause volume loss of the lungs.

Atelectasis/Collapse

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Fig. 3.38  Pulmonary calcification caused by hyperparathyroidism. Fine calcifications are deposited in the lung in a patchy fashion and produce coalescent cloudlike shadows. The patient died despite parathyroidectomy. A, Posteroanterior radiograph. B, An autopsy radiograph of the same patient shows the pulmonary calcifications to advantage.

Fig. 3.39  Widespread, uniform airspace opacities in acute respiratory distress syndrome.

ATELECTASIS/COLLAPSE The terms ‘atelectasis’ and ‘collapse’ are often used synonymously, although the term ‘collapse’ is sometimes restricted to mean total atelectasis.3

Mechanisms of atelectasis There are several mechanisms for atelectasis, the most frequent being bronchial obstruction.32,33 Bronchial obstruction in adults is usually the result of a bronchial neoplasm or mucus plug. On occasion, it is due to an inhaled foreign body, inflammatory or posttraumatic bronchostenosis, a broncholith, or extrinsic compression

by, for example, enlarged lymph nodes, aortic aneurysm, or left atrial enlargement. Because bronchial tumors are uncommon in children, the probable causes of childhood obstructive atelectasis differ substantially from those in adults. In young children the airways are smaller and more vulnerable to obstruction by inflammatory exudate and mucus in pneumonia or mucus plug obstruction in conditions such as asthma or cystic fibrosis. The other likely cause of lobar atelectasis in children is an inhaled foreign body. Rare causes include inflammatory or posttraumatic bronchostenosis, compression of the bronchial tree by anomalous vessels and, very rarely, neoplastic obstruction. Any process which occupies space within the thorax either compresses the lung (compressive atelectasis) or allows it to retract (passive atelectasis). With large pleural effusions the lobes surrounded by fluid may show substantial atelectasis. Large intrathoracic masses frequently press on the lung and may therefore acquire an illdefined margin because of adjacent atelectatic lung. Similarly, emphysematous bullae are often surrounded by atelectatic lung. The best example of passive atelectasis, due to normal elastic recoil, is pneumothorax, which allows retraction of the lung. Following infection a lobe may lose volume because of destruction, often accompanied by bronchiectasis, and fibrosis. The most common cause in the upper lobes and superior segment of the lower lobes is previous granulomatous infection. If the disease affects the dependent portions of the lung, the patient may have the clinical features of bronchiectasis. The middle lobe syndrome is a particular example of this phenomenon. The following features, all of which are best seen at CT, may be inferred from chest radiographs: no endobronchial mass; dilated, thick-walled bronchi within the atelectatic lobe; and associated extensive pleural thickening.34–37 The loss of volume can be very severe and may be greater than is generally observed in lobar collapse caused by endobronchial obstruction. Widespread pulmonary fibrosis causes generalized loss of lung volume. Reticulonodular opacities are then the dominant radiographic feature. Discoid atelectasis (also known as ‘platelike’ or ‘linear’ atelectasis) is a form of adhesive atelectasis.3 First described by Fleischner,38 and formerly known as Fleischner lines, the atelectasis is disk or plate

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Fig. 3.40  A, Sarcoidosis showing multiple, rounded, ill-defined areas of pulmonary opacities closely resembling pneumonia. B, A similar case with bilateral hilar and mediastinal adenopathy.

Fig. 3.41  Progressive massive fibrosis (PMF) in a coal miner. The conglomerate PMF lesion in the left upper lobe is ill-defined enough to resemble airspace opacities, but the typical location and the presence of widespread small nodules in the lungs are characteristic of mineral dust pneumoconiosis. shaped (Fig. 3.42). Sometimes the disk is so large that it crosses the whole lobe. Discoid atelectasis may be single or multiple. It usually abuts the pleura and is perpendicular to the pleural surface39 with no predisposition to point toward the hilum. The orientation may be in any plane from horizontal to vertical. The thickness ranges from a few millimeters to a centimeter or more, and the lesions are therefore usually seen as line or bandlike opacities. Westcott and Cole39 reviewed the mechanisms that lead to discoid atelectasis. In summary, discoid atelectasis is due to hypoventilation, which leads to alveolar collapse. Alveoli lying at the lung bases and those lying posteriorly are most likely to collapse, not only because they have the lowest volume but also because the physiologic mechanisms responsible for keeping the small airways and

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Fig. 3.42  Discoid atelectasis showing a typical bandlike opacity. alveoli open are at their most vulnerable in these sites. In addition, discoid atelectasis may be seen in the lingula in patients with substantial collapse of the left lower lobe, possibly because of kinking of bronchi in the hyperexpanded lingula.40,41 Discoid atelectasis is common, particularly in hospitalized patients. Since it reflects hypoventilation, it is seen in a large variety of conditions.42 Of itself, it is usually of little clinical importance, although the causative condition may be important. Occasionally, discoid atelectasis is of such magnitude and so widespread that it

Atelectasis/Collapse causes hypoxemia. Radiographs may substantially underestimate the extent of the condition. Following general anesthesia, for example, widespread atelectasis can be clinically significant, even in cases that show few signs on chest radiographs.

Imaging lobar atelectasis Chest radiography is usually sufficient to diagnose the presence of lobar atelectasis. CT can be useful when conventional film findings are ambiguous;42 for example, when pleural fluid and pulmonary disease processes are both present. The fundamental signs of lobar atelectasis on both radiographs32,43–45 and CT44–46 are the opacity of a given lobe and evidence of loss of volume. They can be divided into: direct signs, such as displacement of fissures, pulmonary blood vessels, and major bronchi; and shift of other structures to compensate for the loss of volume (Fig. 3.43). The compensatory shifts are in principle similar for each lobe, and they are therefore discussed before describing the appearance of atelectasis of individual lobes. Compensatory overexpansion of the adjacent lobe may result in recognizable spreading of the vessels so there are fewer vessels per unit volume. This sign should not be relied upon if it is an isolated finding, since previous lung damage, from infection for example, can lead to a similar appearance. The amount of mediastinal shift accompanying lobar atelectasis is variable. In general, it is greatest with lower lobe atelectasis or chronic fibrotic loss of volume of an upper lobe, relatively mild with acute upper lobe atelectasis, and virtually nonexistent with atelectasis of the middle lobe. Its recognition depends on noting displacement of the trachea and mediastinum. Normally, on a correctly centered frontal view, the trachea lies midway, or slightly to the right of the midpoint, between the medial ends of the clavicles. Minor obliquity of the chest radiograph does not make much difference because the trachea is only just behind the plane of the medial ends of the clavicles. The normal position of the mediastinum varies so greatly that displacement of the mediastinal contour is an insensitive sign of loss of volume. Normally one-fifth to onehalf of the cardiac shadow lies to the right of the midline. More than one-half or less than one-fifth suggests mediastinal shift.

A

Hemidiaphragm elevation is another manifestation of compensatory shift. Loss of volume of either lower lobe or of the left upper lobe may lead to obvious elevation of the ipsilateral hemidiaphragm. It is usually unrecognizable in right middle lobe collapse and may be subtle in right upper lobe atelectasis. The sign is, however, of limited value because the position of the normal diaphragm is highly variable, particularly in a hospital population. Diaphragm position depends on many factors, including the amount of gas in the stomach, and can vary from day to day. Therefore great care must be taken before relying on elevation of a hemi­ diaphragm to support the diagnosis of lobar atelectasis. Inward movement of the chest wall causes narrowing of the spaces between the affected ribs. This sign, which is seen only with a severely collapsed lobe, can be difficult to evaluate on chest radiographs. It is easier to recognize on transverse CT sections where the cross-sectional area of each hemithorax can be readily compared. Clearly, confusion with preexisting chest wall deformity, particularly when caused by scoliosis, may cloud the issue. Obliteration or narrowing of the bronchial air column at the site of any obstruction is often visible, even on radiographs. Opaque foreign bodies or calcified broncholiths may be directly visible. Even though CT demonstrates the size and site of the responsible obstructing lesion in virtually all patients with a lobar collapse47–50 (Figs 3.44 and 3.45), bronchoscopy is indicated to diagnose the nature of the obstruction and where possible, as with foreign body inhalation, mucus plug obstruction and broncholith, to treat the cause. When the peripheral lung collapses and the central portion is prevented from collapsing by the presence of a mass, the relevant fissures are concave peripherally but convex centrally; the shape of the fissure then resembles an S or a reverse S – hence the name Golden S sign, after Golden’s description of cases of lobar collapse caused by carcinoma of the lung.51 This sign is recognizable both on chest radiography and at CT (Fig. 3.46).42,52,53 On occasion, the fact that there is lobar atelectasis may be overlooked and the patient misdiagnosed as having a mediastinal or hilar mass (see Fig. 3.49). Similarly, massively dilated bronchi due to tuberculosis may deform the central portion of the atelectatic lobe leading to a misdiagnosis of a pulmonary, hilar, or mediastinal mass.53,54

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Fig. 3.43  Displacement of a calcified granuloma secondary to right lower lobe atelectasis: A, at a time when mild right lower lobe collapse is present; B, when complete atelectasis of the right lower lobe is present.

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Right upper lobe atelectasis

Bronchial dilatation and air bronchograms within atelectatic lobes Mucus-filled, dilated bronchi are frequently present beyond an obstructing lesion responsible for lobar atelectasis. They cannot be recognized on radiographs, although they are readily identified on CT as low-density branching structures (Figs 3.45B and 3.47).42,55,56 The low density is due to trapped secretions. Finding a so-called mucoid or fluid bronchogram should prompt a search for a central obstructing lesion. Air bronchograms within atelectatic lobes are very rarely identified on chest radiographs, but may be seen on CT even when the loss of volume is due to central bronchial obstruction, possibly because of collateral air drift or necrosis of the obstructing tumor.33,50 In one series,57 the magnetic resonance (MR) signal intensity on proton density and T2-weighted images was high in atelectasis due to central obstruction but was low in nonobstructive atelectasis. The authors postulated that the high T2 signal was related to trapped secretions, which were present only when the atelectasis was due to obstruction.

Fig. 3.44  Carcinoma of bronchus obstructing the left upper lobe bronchus and causing left upper lobe atelectasis. Bronchial occlusion by tumor (arrow) is well shown by CT.

A

In right upper lobe atelectasis (Figs 3.46 and 3.48), the major and minor fissures move upward toward each other rather like a halfclosed book, the spine of which is represented by the hilum. At the same time these fissures rotate towards the mediastinum, with the result that the right upper lobe packs against the mediastinum and lung apex. The more the loss of volume, the greater is the concavity of the minor fissure. Eventually, with extreme collapse, the minor fissure parallels the mediastinum and thoracic apex and resembles pleural thickening or mediastinal widening. The lobe is attached to the hilum by a conical wedge of collapsed lung, and therefore the curving inferior margin of the lobe always connects to the hilum. The intrinsic bulk of the central vessels and bronchi means there is a limit to the loss of volume possible at the hilum; hence a slight outward bulge is discernible at the hilum in examples of extreme collapse even when no hilar mass is present. Because the atelectatic right upper lobe has extensive contact with the mediastinum, the normal superior vena caval border is ‘silhouetted’ out on the frontal chest radiograph, as is the ascending aorta on the lateral view. The middle and lower lobes expand to occupy the vacated space, leading to outward and upward displacement of the right lower lobe artery. This displacement is most readily seen on frontal radiographs. The corresponding upward angulation of the right main stem and lower lobe bronchi is more difficult to recognize. Over­ expansion of the opposite upper lobe is usually minor; for practical purposes it is visible only at CT. On the lateral view, the upward displacement of the major and minor fissures is usually well seen. With severe loss of volume the wedge of collapsed lung radiating out from the hilum may be no more than an indistinct density on lateral views, since neither of the fissures are tangential to the X-ray beam. The elevation of the right pulmonary artery and the anterior displacement of the right bronchial tree can be identified on the lateral projection,58 but only with great difficulty. Occasionally, collapse of the right upper lobe around a large obstructing bronchial tumor mimics a mediastinal mass (Fig. 3.49). An error in interpretation can be avoided by carefully analyzing the film for compensatory shift of other intrathoracic structures. On rare occasions, the normal chest wall contact is maintained even in severe collapse.59 This appearance (Fig. 3.50) is most frequently reported in neonates and young children,60 but is also seen in adults. It has been termed peripheral atelectasis33,60,61 because the atelectatic lobe lies against the lateral chest wall and the over­

B

Fig. 3.45  Left upper lobe collapse due to bronchial carcinoma. A, Severe collapse. Note that the carcinoma has caused ‘rat tail’ narrowing of the left upper bronchus. B, Moderately severe collapse with substantial consolidation. Fluid-filled bronchi are seen within the obstructed lobe.

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Fig. 3.47  Fluid bronchogram at CT. Fluid-filled bronchi beyond a carcinoma in the atelectatic lower left lobe are clearly visible.

A

At CT,34,45,46,48,68 an atelectatic right upper lobe appears as a triangular soft tissue density lying against the mediastinum and the anterior chest wall. The border formed by the major and minor fissure is sharp (Fig. 3.51). In the absence of large intrapulmonary masses, each fissural boundary should be uniformly concave or convex, not a combination of the two. A severely collapsed right upper lobe assumes a bandlike configuration plastered against the mediastinum, an appearance that can be confused with mediastinal disease. Sometimes the hyperexpanded superior segment of the lower lobe insinuates itself between the mediastinum and the medial border of the atelectatic lobe. Elevation of the right upper lobe bronchus may cause the bronchus intermedius to move laterally, and the right middle lobe bronchus may be displaced anteriorly and reoriented in a more horizontal position.

Left upper lobe atelectasis

B

Fig. 3.46  Golden S sign. A, Chest radiograph showing right upper lobe atelectasis with the Golden S sign. The outward bulge (arrow) of a displaced minor fissure indicates the underlying mass, which proved to be bronchial carcinoma. B, CT in a patient with a large carcinoma obstructing the right lower lobe bronchus causing lobar collapse. The arrow points to the bulge of the major fissure which cannot move more medially because of the underlying tumor.

expanded lower lobe lies centrally.62 The appearance may mimic loculated pleural effusion.61 A juxtaphrenic peak may be visible.63 This term refers to a small triangular shadow based on the apex of the dome of the hemidiaphragm with loss of silhouette of the adjacent hemidiaphragm (Fig. 3.48), usually caused by traction on an inferior accessory fissure,64–66 or, on occasions, due to traction on the intrapulmonary septum associated with the inferior pulmonary ligament.65 The sign may also be seen after lobar resection.67

Because there is no minor fissure on the left, the appearance of atelectasis of the left upper lobe is significantly different from atelectasis of the right upper lobe (Fig. 3.52). The lobe moves predominantly forward, pulling the expanded left lower lobe behind it. Except at the edges, the lobe retains much of its original contact with the anterior chest wall and mediastinum. Since the lobe thins as the fissure is pulled forward, the usual appearance on a frontal radiograph is a hazy density extending out from the left hilum, often reaching the lung apex, and fading laterally and inferiorly. The loss of the left cardiac and mediastinal silhouette is a striking feature on the frontal view. With mild loss of volume – provided the lobe is opaque – the entire cardiac and upper mediastinal border, together with the diaphragm outline adjacent to the cardiac apex, becomes invisible. With increasing loss of volume the upper margin of the aortic knob once again becomes visible because the superior segment of the lower lobe takes the place of the posterior segment of the upper lobe – a sign that has been called the ‘luftsichel’ sign.69–71 With further loss of volume the upper border of the pulmonary opacity becomes hazy and its medial border becomes sharp because the apex is now occupied by the greatly overexpanded superior segment of lower lobe (Fig. 3.53). The superior mediastinal and left hemidiaphragm contours then reappear, but with very few exceptions the left border of the

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Fig. 3.48  Right upper lobe atelectasis – a typical example. Also note the juxtaphrenic peak (arrow). A, Posteroanterior view. B, Lateral view.

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Fig. 3.49  Right upper lobe atelectasis around a large, centrally obstructing bronchial carcinoma (Golden S sign) resembling a mediastinal mass. The best clue to the correct interpretation is elevation of the right lower lobe artery. A, Posteroanterior view. B, Lateral view.

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Atelectasis/Collapse

Fig. 3.51  CT of right upper lobe atelectasis, due to a centrally located lung cancer, showing a characteristic wedge-shaped density radiating from the right hilum with a broad base against the anterior chest wall.

Fig. 3.50  “Peripheral atelectasis” of right upper lobe (arrows) in an infant following cardiac surgery. The lobe has collapsed against the chest wall.

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Fig. 3.52  Left upper lobe atelectasis due to bronchial carcinoma. A, Posteroanterior view. B, Lateral view.

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Fig. 3.53  Left upper lobe atelectasis. A, Posteroanterior view. In this example, the greatly expanded superior segment of the left lower lobe occupies the apex, and consequently the upper surface of the aortic arch is visible. B, Lateral view. The posterior boundary of the collapsed left upper lobe is formed by the displaced major fissure. The anterior boundary is against the anterior chest wall. The ascending aorta is particularly well seen, and should not be mistaken for the anterior boundary of the collapsed lobe.

A

B

Fig. 3.54  Left upper lobe atelectasis showing reorientation of the left mainstem bronchus and left lower lobe bronchus. Note the near horizontal alignment of the mainstem bronchus and the near vertical alignment of the lower lobe bronchus. A, Posteroanterior view. B, Lateral view. heart remains indistinct even in the most severe cases of left upper lobe atelectasis. The overexpansion of the left lower lobe results in elevation of the left hilum and outward angulation of the left lower lobe artery. The left bronchial tree assumes an S-shaped configuration, the left main bronchus running a near horizontal

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course and the lower lobe bronchus being more vertical than usual (Fig. 3.54). On the lateral view the lateral portion of the major fissure is usually seen as a clearly defined concave margin running approximately parallel to the anterior chest wall. The wedge of tissue radi-

Atelectasis/Collapse ating from the hilum is indistinct on the lateral view unless there is a hilar mass to alter the tangents. The lingula segment, being thinner to start with, often is no more than a sliver. The entire fissure may be so far forward that a collapsed upper lobe can be overlooked or misinterpreted as an anterior mediastinal density. Sometimes the fissure rotates, so that no part of it is tangential to the X-ray beam and, in these cases, the edge of the shadow is ill-defined in the lateral view also. A striking feature of left upper lobe atelectasis is herniation of the opposite lung into the left hemithorax in front of the aorta (see Figs

3.44 and 3.45), which leads to increased visibility of the ascending aorta on the lateral chest radiograph (see Fig. 3.53), an appearance that should not be misinterpreted as the anterior edge of the collapsed lobe. In rare instances the edge of the herniated lung can project over the aortic knob on a frontal view. The more usual cause of aerated lung lying medial to the opacity of an atelectatic left upper lobe is overexpansion of the left lower lobe invaginating between the atelectatic lung and the mediastinum (see Fig. 3.53). A juxtaphrenic peak on the hemidiaphragm (Fig. 3.55) and the phenomenon of ‘peripheral’ atelectasis may be seen on the left just as they may with atelectasis of the right upper lobe. On CT (Figs 3.44, 3.45, and 3.56)34,45,46,48,68 atelectatic left and right upper lobes appear similar, but with left upper lobe atelectasis the airless lingular segments are identified on sections below the carina as a narrow triangular density based on the heart and anterior chest wall extending almost to the diaphragm. The herniation of the right lung anterior to the aorta is particularly well seen on CT.

Right middle lobe atelectasis

Fig. 3.55  Left upper lobe atelectasis showing a juxtaphrenic peak (yellow arrow) and a Golden S sign (red arrows). The atelectasis was caused by a centrally obstructing bronchial carcinoma.

A

The opacity of an atelectatic middle lobe on the frontal chest radiograph may, in severe cases, be so minimal that middle lobe atelectasis is easy to overlook, because its depth in the plane of the beam may be no more than a few millimeters (Fig. 3.57), but loss of silhouette of the right border of the heart is almost always a key feature. The bronchial and vascular realignments in right middle lobe atelectasis are so slight that there is no recognizable alteration in the appearance of the right hilum. The atelectatic lobe is, however, easily and reliably recognized on the lateral chest radiograph. The major and minor fissures approximate one another and, if the atelectasis is pronounced, the lobe resembles a curved, elongated wedge. The wedge tapers in two directions: medial to lateral, and anterior to posterior. The collapsed lobe may be so thin that it may be misinterpreted as a thickened fissure. Alternatively, there may occasionally be difficulty in distinguishing between atelectasis of the middle lobe and loculated fluid in the major fissure. With atelectasis the inferior margin of the opacity is concave, whereas with loculated fluid the fissure bulges downward. Also the fissures should not be separately visible in their normal positions, an important point in the differential diagnosis from pleural fluid, pleural thickening, or tumors lying within the fissures. On CT (Figs 3.58 and 3.59),34,45,46,48,68 right middle lobe atelectasis appears as a triangular opacity bounded posteriorly by the major

B

Fig. 3.56  CT showing left upper lobe atelectasis. Note the forward displacement of the major fissure and mediastinal shift to the left. A, A section above the level of the left mainstem bronchus showing the atelectatic anterior, posterior, and apical segments. B, A section through the collapsed lingular segments.

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Fig. 3.57  Right middle lobe atelectasis. A, The lobe is so severely atelectatic that the opacity is difficult to see in the frontal view. There is, however, loss of the right heart border due to the silhouette sign. B, The lateral view shows the atelectatic lobe to advantage. In this case, the atelectasis was chronic and the result of the ‘middle lobe syndrome’.

A

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Fig. 3.58  CT of right middle lobe atelectasis in the same patient as in Figure 3.57. Note the patent middle lobe bronchus and air bronchogram. Two adjacent sections are shown: A, a section at the level of the right middle lobe bronchus; B, a lower section.

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Atelectasis/Collapse

Fig. 3.59  CT of right middle lobe atelectasis showing dilated air-filled bronchi within the atelectatic lobe. This combination is typical of the ‘right middle lobe syndrome’. fissure, medially by the mediastinum at the level of the right atrium, and anteriorly by the minor fissure. The posterior boundary should be well defined. Unless the minor fissure is pulled well down, the anterior margin may be poorly defined on the CT images. The right middle lobe bronchus enters the posteromedial corner of the opacity, an important point in the differential diagnosis from loculated pleural fluid. Because the atelectatic middle lobe is effectively a sheet of tissue running obliquely through the chest, transverse CT sections are not aligned with the lobe and only small portions of the atelectatic lobe are seen on any one section. The term ‘middle lobe syndrome’ refers to chronic nonobstructive middle lobe collapse (see Figs 3.57 to 3.59).33 The condition was originally thought to be due to tuberculous lymphadenopathy pressing on the middle lobe or lingular bronchus, but it is now believed that the entity is due to chronic inflammatory disease, which clears very slowly because of poor collateral drift.72 Pathologically, the atelectatic lung may show bronchiectasis, chronic bronchitis with lymphoid hyperplasia, organizing pneumonia, and abscess formation.73 In one series of 129 patients with chronic disease in the right middle lobe or lingula, most of whom were middle-aged women, 58 had no evidence of central obstruction, either by endobronchial or by extrabronchial masses.74

Lower lobe atelectasis The appearance of atelectasis of the lower lobes is sufficiently similar on the two sides that it is convenient to consider right and left lower atelectasis together. The loss of volume may affect the whole lobe, but the superior segment is frequently spared. With atelectasis of either lower lobe (Figs 3.60 and 3.61), the major fissure rotates backward and medially, and the upper half of the fissure swings downward. Thus atelectatic lower lobes lie posteromedially in the lower thoracic cavity. The resulting triangular opacity is based on the diaphragm and mediastinum, with the fissure running obliquely through the thorax. On frontal projection the opacity of an atelectatic lower lobe is easier to recognize on the right than on the left because on the left it is often hidden by the heart, notably if the film is underpenetrated. With severe loss of volume the lobe becomes notably thin and appears as a sliver lying against the mediastinum (see Fig. 3.61). Sometimes, presumably when the inferior pulmonary ligament does not attach to the diaphragm, the lobe is plastered against the mediastinum but has little if any contact with the diaphragm. In these cases the atelectatic lobe assumes a rounded configuration and may resemble a mediastinal mass (Fig. 3.61). Care should be taken not to confuse a large

but normal left cardiophrenic fat pad with left lower lobe collapse (Fig. 3.62). If the superior segment remains aerated, the upper half of the major fissure will often be identified on the frontal radiograph (Fig. 3.63). In these cases the major fissure may be confused with the minor fissure, a misinterpretation that can be avoided by remembering that the minor fissure does not cross medial to the hilum. Lower lobe atelectasis is sometimes more obvious on the lateral than on the frontal radiograph. Unless the atelectasis is very severe, the density of the posterior thorax, notably the spine, is increased and the outline of the posterior half of the right or left hemidiaphragm shadow is lost. Normally, on the lateral view, each vertebra appears blacker than the one above as the eye travels down through the thorax to the diaphragm. In lower lobe atelectasis the lower vertebrae appear whiter than those higher up (see Figs 3.60 and 3.61). With very severe collapse, the outline of the ipsilateral hemidiaphragm may once again become visible, because compensatory expansion of the upper and middle lobe brings them into contact with the previously effaced diaphragm (Fig. 3.61). The opacity of the collapsed lobe may be difficult to recognize unless the observer is careful to observe the density of the vertebrae. The major vessels supplying the lobes are displaced but, more importantly from a diagnostic point of view, they are invisible because they are coursing through an opaque lobe. Therefore, with complete lower lobe collapse, the lower lobe artery and its segmental divisions are displaced but invisible. Careful analysis of the hilum may, however, be needed to recognize this difference because displaced middle or upper lobe vessels may resemble the lower lobe arteries. A similar analysis of the bronchi may be more revealing: in most cases air within the bronchus can be identified coursing into the triangular density of the collapsed lobe. Bronchial displacement can also be recognized on lateral chest films, but the signs are subtle and demand confident knowledge of the normal.58 Normally the central bronchi run in the same direction as the trachea and travel obliquely backward as they descend, so that the right and left major airways are virtually superimposed on one another in a true lateral projection. The only difference is the higher origin of the right upper lobe bronchus and the differences inherent in the right lung having a middle lobe. Lower lobe atelectasis leads to backward displacement of the relevant airways. This displacement is useful in differentiating opacities caused primarily by pleural fluid from that caused by lower lobe collapse. With collapse the bronchi are pulled back, whereas with pleural fluid the bronchi may be pushed forward.75 The appearance of the upper mediastinal contours may occasionally be helpful in drawing attention to, or confirming, the possibility of lower lobe atelectasis. Kattan76 emphasized three signs: • The upper triangle sign77 – this refers to a low-density, clearly marginated triangular opacity on frontal chest radiographs that resembles right-sided mediastinal widening. It is seen in right lower lobe atelectasis and is caused by rightward displacement of the anterior junctional tissues of the mediastinum (Fig. 3.64). The appearance superficially resembles right upper lobe atelectasis but should not be confused with it, because the fissural, vascular, and bronchial realignments all point to overexpansion of the right upper lobe rather than to atelectasis. • The flat waist sign78 refers to flattening of the contours of the aortic knob and adjacent main pulmonary artery (see Fig. 3.61). It is seen in severe collapse of the left lower lobe and is due to leftward displacement and rotation of the heart. The appearance therefore resembles a shallow right anterior oblique view of the normal mediastinum. • The outline of the top of the aortic knob may be obliterated in severe left lower lobe collapse.76 On CT34,45,46,48,68 an atelectatic lower lobe produces a triangular opacity of soft tissue density in the posterior chest against the spine

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C

Fig. 3.60  Right lower lobe atelectasis due to bronchial carcinoma. A, Posteroanterior radiograph. B, Lateral radiograph. C, CT in a different patient.

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D

Fig. 3.61  Left lower lobe atelectasis. A, B, Atelectasis due to lung cancer. In this example, the displacement of the left hilar vessels is particularly well demonstrated. The left lower lobe artery is invisible because it is within the atelectatic lobe. Note also the splaying of the blood vessels in the overexpanded left upper lobe and the flat waist sign. C, Very severe atelectasis in which the lobe is no more than a sliver against the mediastinum. The altered configuration of the left hilum is perhaps the most obvious sign. (Arrows point to the displaced major fissure in A and C) D, Atelectasis in a patient with an underdeveloped pulmonary ligament with resultant lack of tethering of the lower lobe to the diaphragm. The collapsed lobe mimics a mediastinal mass. The disposition of the left main bronchus, lack of visibility of the left lower lobe artery, and air bronchograms within the opacity indicate the correct diagnosis.

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B

Fig. 3.62  A, A large cardiophrenic fat pad, which mimics left lower lobe atelectasis on the posteroanterior chest radiograph. B, CT showing the fat pad and the absence of left lower lobe atelectasis.

Fig. 3.63  Right lower and right middle lobe atelectasis with partial aeration of the superior segment of the right lower lobe. Arrows point to the displaced major fissures.

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Atelectasis/Collapse

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B

Fig. 3.64  Right lower lobe atelectasis caused by bronchiectasis showing the ‘upper triangle sign’ (yellow arrow). The displaced major fissure (red arrows) and the right lower lobe artery entering the atelectatic lobe are well demonstrated. A, Posteroanterior radiograph. B, Bronchogram showing the arrangement of the bronchi. (Figs 3.60 and 3.65). The major fissure rotates to lie obliquely across the thoracic cavity. The lobe is fixed at the hilum, and the medial basal segment cannot move further back than the attachment of the inferior pulmonary ligament to the mediastinum. In cases where the inferior pulmonary ligament is incomplete, collapse of the basal segments may simulate a mass on CT just as it may on chest radiography.79

Whole lung atelectasis Whole lung atelectasis on either side leads to complete opacification of the hemithorax. The signs of compensatory shift are usually obvious. Mediastinal shift is invariably present, and herniation of the opposite lung is usually a striking feature (Fig. 3.66).

Combined right upper and middle lobe atelectasis As there is no single bronchus to the right upper and middle lobes that does not also supply the right lower lobe, collapse of these two lobes with normal aeration of the lower lobe is unusual. This phenomenon is seen particularly with neoplastic disease, when, for instance, tumor obstructs one bronchus and extends through lung parenchyma or peribronchially to obstruct the other bronchus. The appearances80,81 are virtually identical to those seen with left upper lobe atelectasis on both chest radiography (Fig. 3.67) and CT. Occasionally atelectasis of the right upper lobe alone precisely mimics combined collapse of the right upper and middle lobes.82

Combined right lower and middle lobe atelectasis The combination of right lower and middle lobe atelectasis is seen with obstruction of the bronchus intermedius. The appearances are similar to atelectasis of the right lower lobe alone in both postero­ anterior and lateral chest radiographs except that the abnormal

Fig. 3.65  Contrast-enhanced CT of left lower lobe atelectasis. density extends all the way to the lateral costophrenic angle (Fig. 3.68).43,80 The upper border of the opacity, formed by a combination of the major and minor fissures, can be convex or concave. In either case, the appearances can be confused with a subpulmonary pleural effusion. Similarly, on the lateral view the opacity extends from the front to the back of the thorax.43 Diagnosing combined middle and lower lobe atelectasis is easier at CT.44,45 Because the bronchi can be individually identified it is possible to identify the middle lobe specifically and so diagnose or exclude the presence of combined middle and lower lobe atelectasis.

Distinguishing lower lobe collapse from pleural fluid Lower lobe atelectasis can be difficult, and sometimes impossible, to distinguish from pleural effusion on posteroanterior and lateral

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B

Fig. 3.66  Atelectasis of the left lung. The left lung is opaque, and there is striking shift of the mediastinum. A, Posteroanterior view. B, Lateral view.

A

B

Fig. 3.67  Combined right upper and middle lobe atelectasis. Note the similarity to left upper lobe atelectasis. Arrows point to the greatly displaced major fissure. A, Posteroanterior view. B, Lateral view. (Courtesy of Dr. Michael Pearson, London, UK.)

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Atelectasis/Collapse

A

B

Fig. 3.68  Combined right middle and lower lobe atelectasis. Note the similarity to right lower lobe atelectasis alone, except that the abnormal density extends all the way to the costophrenic angle in the frontal view and from front to back in the lateral view. A, Posteroanterior view. B, Lateral view. radiographs. This diagnostic dilemma is most frequent in post­ operative or acutely ill patients and is compounded by the fact that these patients are frequently examined with portable equipment in frontal projection only. The diagnosis of lobar atelectasis depends on recognizing shift of structures, particularly the fissures, the hilar blood vessels, and the major bronchi. If the position of the fissures can be confidently established, the diagnosis is easy. If not, attention should be turned to the hila, particularly the position of the lower lobe arteries and bronchi. Two questions should be addressed: do these structures enter the opacity in question; and are they displaced in a direction that suggests collapse? For example, in a patient with basal opacity, if the lower lobe artery is obscured and the lower lobe bronchus runs vertically through the opacity, lower lobe atelectasis should be diagnosed. If, on the other hand, the lower lobe artery is clearly seen lateral to the opacity and the bronchus is not surrounded by the density, the opacity is not the result of lower lobe atelectasis. Distinguishing between pleural effusion and lobar atelectasis is easy on CT (Fig. 3.69). On CT, the density of the atelectatic lobe is usually appreciably greater than that of the pleural effusion, particularly if intravenous contrast enhancement is used.34,48 Also, blood vessels and bronchi can be traced in the compressed lung.

Lobar atelectasis due to bronchiectasis Lobar atelectasis may be the result of bronchiectasis (Fig. 3.70). The loss of volume is due to a combination of multiple occlusions of bronchi beyond subsegmental bronchial divisions. The essential feature is lobar atelectasis, the lobe in question often being of strikingly low volume and containing dilated thick-walled bronchi.34

Round atelectasis Round atelectasis, also known as rounded atelectasis, folded lung, Blesovsky syndrome, or atelectatic pseudotumor, is a form of

Fig. 3.69  CT of combined pleural effusion and left lower lobe atelectasis. The atelectatic lobe with its air bronchogram is clearly distinguishable from the adjacent left pleural effusion. (The patient, who had small cell carcinoma of the lung, also had extensive mediastinal adenopathy, pericardial effusion, and right pleural effusion.) chronic atelectasis that resembles a mass, which on chest radiographs can be confused with bronchial carcinoma.83–85 The process is commonly encountered in individuals with asbestos-related pleural disease,86–88 but it has been reported in association with other benign pleural conditions,89,90 including tuberculosis, other infections, therapeutic pneumothorax, uremic pleuritis,91 pulmonary infarction, Dressler syndrome,92 as well as with idiopathic pleural exudates. It is also occasionally seen in association with malignant mesothelioma.93

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Chapter 3 • Basic Patterns in Lung Disease The mechanism leading to the formation of round atelectasis is uncertain but pleural thickening, usually benign fibrosis, is the common element.90,94 One suggestion is that a pleural exudate is the initial event and the resulting effusion causes passive atelectasis of the adjacent lung and pleural invagination.95 The pleural surface of the atelectatic lung may then develop fibrinous adhesions to the adjacent parietal pleura and across any adjacent fissure. As the pleural effusion clears, the atelectatic lung is trapped and folds in on itself. An alternative explanation is that a sheet of pleural fibrosis alone is responsible: as the pleural fibrosis matures, it retracts, causing infolding and atelectasis of the underlying lung.86,96,97 Probably both mechanisms operate in different patients.86 The imaging features on radiographs and CT are listed in Box 3.5.88,92,94,98–102 A constant sign is the peripheral location of the opacity in contact with thickened pleura. Round atelectasis is usually oval or wedge-shaped in configuration and angled with respect to the pleural surface (Fig. 3.71). The top, bottom, and lateral edges of the

Box 3.5  Imaging features of round atelectasis

Fig. 3.70  Right lower lobe atelectasis caused by bronchiectasis. Air in the dilated bronchi (yellow arrows) is an important clue to the cause of the atelectatic lobe. The red arrow points to the displaced major fissure.

A

• • • • • • • • • •

Rounded, oval, or wedge-shaped mass Smooth margin except at site of entry of bronchi and vessels Convergence of bronchovascular markings Curvilinear vessels and bronchi entering mass Subpleural in location Pleural thickening adjacent to mass Indistinct margins Air bronchograms within mass Loss of volume of affected lobe Pleural thickening/plaques elsewhere

B

Fig. 3.71  Round atelectasis (arrows) showing the typical features of an oval mass aligned obliquely against pleural thickening along the posterior chest wall. A, Posteroanterior radiograph. B, Lateral radiograph.

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Solitary Pulmonary Nodule/Mass mass are usually smooth, but the edge pointing to the hilum is often irregular or ill-defined and blends with the bronchi and blood vessels that lead into the atelectatic mass. A feature of great diagnostic value, and one that is almost universally present,92,101 is the distortion and displacement of the blood vessels and bronchi leading to, and immediately adjacent to, the area of round atelectasis. The vessels and bronchi appear pulled toward the lesion, are more numerous than normal for that portion of lung, and show a characteristic curvilinear configuration (Fig. 3.72), sometimes referred to as a ‘comet tail sign’. Air bronchograms are seen within the opacity on CT in the majority of cases; the thinner the CT section, the more frequently air bronchograms are identified. Calcifications may be seen within the area of rounded atelectasis, and the volume of the affected lobe is reduced. Round atelectasis, like lung cancer and many other pathologic conditions, enhances after intravenous injection of contrast agent; contrast enhancement is therefore of little diagnostic value.103 Although usually static, round atelectasis may grow104 or shrink,95 or even on occasion resolve spontaneously.86,91 CT (see Fig. 3.72) shows all the features to advantage and may display more extensive pleural disease than can be appreciated on radiographs. The CT findings may be definitive, so further investigation to exclude carcinoma, the major differential diagnosis, as the cause of the mass is often unnecessary. Ultrasonography can show a pleurally based mass with thickening of the adjacent pleura and extrapleural fat. A highly echogenic line extending from the pleural surface into the mass, believed to correspond to scarred invaginated pleura, is a frequent feature.105 Magnetic resonance imaging (MRI) can show the curving vessels to advantage, particularly on sagittal sections, and low intensity lines can be seen at MRI within the folded lung, thought to be due to thickened invaginated pleura.94,106,107 Round atelectasis shows signal that is higher than muscle and lower than fat on T1-weighted sequences and similar to or lower than fat on T2-weighted sequences; homogeneous enhancement occurs after intravenous contrast administration.107 Round atelectasis, unlike most lung carcinomas of similar size, is metabolically active on 18F-2-fluoro-2deoxy-d-glucose (FDG) positron emission tomography (PET) scanning on rare occasions only.108

A

SOLITARY PULMONARY NODULE/MASS The term ‘pulmonary mass’ refers to an essentially spherical opacity with a well-defined edge. The word ‘nodule’ has been recommended to describe a lesion of up to 3 cm in diameter and ‘mass’ for a lesion greater than 3 cm in diameter.3 The first step in the workup of a solitary pulmonary nodule (SPN) is to ensure the nodule is in fact solitary and truly arises in the lung parenchyma and is not merely, for example, callus around a rib fracture, a prominent costochondral junction (Fig. 3.73), an exostosis arising from a rib, a pleural nodule or plaque, or a skin nodule or other extrathoracic opacity projected over the lung on a chest radiograph. The possible differential diagnoses of an SPN seen on chest radiography or CT are numerous (see Box 3.6 and Fig. 3.74), but over 95% fall into one of three groups: • Malignant neoplasm, either primary or metastatic • Infectious granulomas, either tuberculous or fungal • Benign tumors, e.g. hamartoma. The subsequent steps are highly dependent on the size of the nodule, the age of the patient and certain clinical features, e.g. fever, or a known primary tumor with a propensity to metastasize to the lungs. A solitary nodule larger than 10  mm in diameter is sufficiently likely to be a primary lung cancer that a definitive diagnosis is required without undue delay, whereas a 6 mm nodule discovered incidentally on CT is up to 30 times more likely to be benign than malignant. Since, for practical purposes, the only lung cancers that can be recognized on chest radiographs as a discrete SPN are 10  mm or greater in diameter, the diagnostic workup for SPNs recognized on plain radiography is different from nodules less than 10 mm found only on CT.109,110 Patients with a SPN are generally divided into two groups: those in whom malignant neoplasm is either unlikely or impossible; and those in whom malignancy remains a serious consideration. If there is no known extrathoracic primary tumor, the problem usually centers on deciding whether or not the patient has a primary malignant neoplasm of the lung, notably bronchial carcinoma. In one

B

Fig. 3.72  Round atelectasis. A and B, CT shows a mass like lesion with a broad base on the pleura and crowding of vessels supplying the lesion, as well as comet-tail sign (arrows).

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A

B

D

C

Fig. 3.73  A pseudonodule (arrows in A) caused by a hypertrophied first costochondral junction projecting into the lung. A, Chest radiograph showing how closely a carcinoma of the lung can be simulated. B, CT (in another patient) showing the costochondral junction. C, D, CT sections show how the downward-projecting costochondral junction simulates a solitary pulmonary nodule.

large multicenter series of chest radiographs,111 only three of 877 resected SPNs were metastases, and in another study of 705 patients without a known primary tumor,112 only one nodule was a metastasis. If a patient has a known extrathoracic malignant neoplasm and a solitary pulmonary nodule, then the likelihood of a metastasis depends on the patient’s age and the site of origin of the extrathoracic neoplasm. In their analysis of 149 patients, Quint et al.113 found that patients with carcinomas of the head and neck, bladder, breast, cervix, bile ducts, esophagus, ovary, prostate, or stomach, in whom a solitary pulmonary nodule was discovered, were more likely to have primary lung carcinoma than metastasis. Patients with carcinomas of the salivary glands, adrenals, colon, kidney, thyroid, thymus or uterus had fairly even odds, and patients with melanoma,

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sarcoma, or testicular cancer were more likely to have a solitary metastasis than primary lung carcinoma. Morphologic features such as size, shape, and cavitation, which can be diagnostically helpful, are discussed later, but it must be emphasized that no imaging features are entirely specific for lung carcinoma (or other primary malignant tumors). There are, however, four imaging observations that exclude the diagnosis with reasonable certainty: the detection of a benign pattern of calcification; a rate of growth that is either too slow or too fast for the nodule to be primary lung cancer; a specific shape indicating a benign process; and unequivocal evidence on previous examinations that the nodule is the end stage of a previous benign process, such as infarction or granulomatous infection.109,110

Solitary Pulmonary Nodule/Mass Box 3.6  Differential diagnosis of a solitary pulmonary nodule or mass identified on chest radiographs

Neoplastic

Congenital

• • • • • •

• • • •

Lung cancer* Metastasis* Pulmonary lymphoma* Pulmonary carcinoid* Hamartoma Connective tissue and neural tumors, e.g. lipoma, fibroma, chondroma, neurofibroma, blastoma,* sarcoma

Inflammatory • Infective – Granuloma,* e.g. tuberculosis, histoplasmosis, cryptococcosis, blastomycosis, coccidioidomycosis, nocardiosis – Round pneumonia, acute or chronic* – Lung abscess* – Septic emboli* – Hydatid cyst* – Dirofilariasis • Noninfective – Rheumatoid arthritis* – Wegener granulomatosis* – Lymphomatoid granulomatosis* – Sarcoidosis* – Lipoid pneumonia – Behçet disease*

Arteriovenous malformation Sequestration* Lung cyst* Bronchial atresia with mucoid impaction

Miscellaneous • • • • • • • • • •

Organizing pneumonia Pulmonary infarct* Round atelectasis Intrapulmonary lymph node Progressive massive fibrosis* Mucoid impaction* Hematoma* Amyloidosis* Pulmonary artery aneurysm or venous varix First costochondral junction

Mimics of SPN • • • • •

External object (e.g. nipple, skin nodule) Bone island in rib Healing rib fracture Pleural plaque Loculated pleural fluid

*May cavitate.

Calcification Various types of calcification may be identified within an SPN: concentric, laminated, punctate, cloudlike and uniform or homogeneous. Concentric (laminated) calcification is suggestive of tuberculous or fungal granulomas (Fig. 3.75). Popcorn calcifications, which are randomly distributed, often overlapping, small rings of calcification, seen only when there is cartilage in the nodule, are a feature specific to hamartoma and cartilage tumors (Fig. 3.76). Punctate calcification occurs in a variety of benign and malignant lesions: granuloma, hamartoma, amyloid deposit, carcinoid, and metastases, particularly osteosarcoma. Punctate calcification is rare in bronchial carcinoma unless the tumor engulfs a preexisting calcified granuloma (Fig. 3.77), in which case the calcification is rarely randomly distributed or at the center of the nodule. The presence of one or more punctate calcifications arranged in an eccentric group and widespread cloudlike calcification of a nodule substantially reduces the probability of bronchial carcinoma, particularly if the calcification is present in sufficient quantities to be visible on plain chest radiographs, although, as discussed below, it does not exclude the diagnosis entirely. Uniform calcification of an SPN (Fig. 3.78) is virtually diagnostic of a calcified granuloma and excludes the diagnosis of bronchial carcinoma.114 Calcification is better seen on chest radiographs taken with low kilovoltage than high kilovoltage. Attempts to analyze nodules using single- or dual-energy kilovoltage techniques with chest radiography and CT have proven promising in the experimental setting but their clinical routine needs to be proved.115,116 CT, because of its superb density discrimination, is far superior to chest radiography for the detection of calcification in an SPN114 (Fig. 3.79). However, care must be taken not to misdiagnose artifactual high density as calcification at the edge of smaller nodules on high-spatial-frequency reconstruction algorithms.117 Siegelman and co-workers118 were the first to use CT to categorize nodules as benign by determining their CT density. They found that SPNs with a representative CT number of above 164 Hounsfield Units (HU) were benign. Proto and Thomas,119 using a different scanner, confirmed this observation, but recommended 200 HU for

the cut-off point above which the diagnosis of a benign lesion could be made. If the high density is either uniformly distributed or clearly lies centrally within the nodule, the nodule is unlikely to be a bronchial carcinoma, but as with radiographic and conventional tomographic evaluation, CT may show calcification within a lung cancer if the tumor engulfs a preexisting calcified granulomatous lesion.119,120 There are also well-documented reports of amorphous calcification in lung cancer (Fig. 3.80).121–127 It has been shown121,124 that 6–7% of lung cancers show calcification of some type or another within the tumor mass at CT. To avoid misdiagnosing a benign lesion in those cases of carcinoma that show calcification, the radiologist should consider a high-density lesion benign only if the edge of the nodule is smooth.120,121 Also, evaluation of a nodule by CT scanning rarely yields a confident diagnosis of benign disease if the nodule is larger than 3 cm. CT densitometry is therefore not recommended for lesions greater than 3  cm in diameter or for nodules with irregular or spiculated borders,121 nor is it recommended in patients with nodules that are known to be increasing in size at a rate compatible with bronchial carcinoma. Such nodules should not be automatically regarded as benign just because they show calcification.114 Accurate detection of diffuse calcification of a nodule at CT densitometry depends on obtaining a section through the equator of the nodule and ensuring the measurements are not artifactually reduced because air in the adjacent lung is included in the section. This is not possible with very small nodules. It has been suggested, however, that it is possible to detect diffuse calcification in 3–7 mm nodules lying within thick sections even when the measured CT density is well below 200  HU. Yankelevitz and Henschke128 showed in a phantom study that 3–7 mm individual nodules that are visible on conventional mediastinal window and level settings are probably diffusely calcified and therefore benign. Even with good technique and awareness of pitfalls, however, some malignant nodules will be misdiagnosed as benign based on CT densitometry: in the series of Swensen and associates127 at least 10 of the 85 nodules diagnosed as benign by nodule densitometry proved to be malignant. Zerhouni and associates121,129 designed a reference phantom that simulated the shape, dimensions, and density of the thorax at multiple levels, in order to replicate the conditions under which an SPN

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Chapter 3 • Basic Patterns in Lung Disease

A

B

D

C

Fig. 3.74  Examples of various causes of solitary pulmonary nodules on chest radiographs: A, lung cancer; B, hamartoma; C, bronchial carcinoid; D, pulmonary infarct.

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Solitary Pulmonary Nodule/Mass

A

B

C

D

Fig. 3.75  Concentric calcification in fungal and tuberculous granulomas. A, A histoplasmoma on chest radiograph showing laminated concentric calcification. B, A histoplasmoma on CT showing homogeneous concentric calcification. C, A histoplasmoma on CT showing laminated concentric calcification. D, A tuberculoma on CT showing laminated concentric calcification.

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Chapter 3 • Basic Patterns in Lung Disease

A

B

Fig. 3.76  Popcorn calcifications in pulmonary hamartoma: A, on chest radiograph; B, on CT.

Fig. 3.77  Focal calcification in a granuloma engulfed by a bronchial adenocarcinoma. Note another similar granuloma in the lung behind the tumor and widespread calcification in hilar lymph nodes.

Fig. 3.78  Uniform calcification in a tuberculoma shown by CT.

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Solitary Pulmonary Nodule/Mass

A

C

B

Fig. 3.79  A simple visual method of CT densitometry. A, By viewing the nodule at a window width (WW) of 1 HU and a window level (WL) of 200 HU, it is possible to see that over one-third of the area of the nodule on this section is heavily and uniformly calcified, and lung cancer for practical purposes is ruled out. B, The same lesion showing a nodule that could be a bronchial carcinoma if viewed only on a standard lung window (WW1000, WL700). C, The mediastinal window (WW350, WL35) also shows that on visual grounds the nodule is of calcific density.

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Chapter 3 • Basic Patterns in Lung Disease

A

B

C

D

Fig. 3.80  Calcification in a cavitating adenocarcinoma in the left lower lobe (red arrows): A, solid part of the carcinoma; B, cavitating part of the carcinoma. C, Calcifications in the wall of the adenocarcinoma (arrow). D, View of the tumor on coronal reconstruction (arrow). was measured, and provide a standard for density regardless of equipment- or patient-related variations. The patient’s nodule was considered to be above the critical density level if more than 10% of the voxels in the patient nodule were higher in density than in the phantom nodule. The phantom technique has not, however, remained in general use. Overall, CT densitometry has lost importance given the advent of multidetector CT and resulting thinner sections, the widespread use of PET, and computed methods used to analyze nodule growth and surface.109

Fat density within a nodule Unequivocal demonstration of fat within a solitary pulmonary nodule is virtually pathognomonic of a hamartoma (Fig. 3.81).

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Lipoid pneumonia and metastatic liposarcoma are comparatively rare alternatives.130 On CT, care must be taken not to include adjacent aerated lung in the section, because the density reading may then be a mixture of air and cancer and lie within the fat range.

Ground-glass opacity A number of different pathologic processes can give rise to a solitary small round area of pure ground-glass opacity (Fig. 3.82): a small area of focal pulmonary fibrosis;131 a patch of pneumonia; atypical adenomatous hyperplasia;132 bronchioloalveolar cell carcinoma; and invasive adenocarcinoma. The probability of invasive adenocarcinoma for a lesion composed entirely of ground-glass

Solitary Pulmonary Nodule/Mass opacity under 1 cm in diameter is relatively low.133 A small nodule of ground-glass opacity with a central area composed of standard soft tissue density is, however, likely to be a lung cancer, sometimes bronchioloalveolar cell carcinoma but often invasive adenocarcinoma.134 The increasing detection of ground-glass nodules with decreasing section thickness has made these lesions a substantial

Fig. 3.81  Fat within a hamartoma (arrow).

A

diagnostic problem, and new classifications of these nodules have been elaborated.135 The clinical implications of these nodules are discussed in Chapter 13.

Contrast enhancement SPNs caused by malignant neoplasm show a greater degree of contrast enhancement with iodinated contrast media than benign nodules. The basis of this enhancement is likely to be the phenomenon of angiogenesis.136 Littleton and co-workers137 first demonstrated contrast enhancement using very high-quality conventional tomography together with film densitometry. Swensen et  al. in a prospective127 and, subsequently, in a multicenter study138,139 of contrast-enhanced CT showed that enhancement of an SPN can be a good predictor of lung cancer and failure to enhance above a certain level can be a good predictor of a benign lesion. But careful attention to technique and interpretation is required. The prospective study139 demonstrated that all but one of 44 primary lung carcinomas showed at least a 20 HU increase in density during dynamic contrast enhancement, whereas 15 of 56 benign lesions failed to enhance to this degree (sensitivity 98%, specificity 73%, positive predictive value (PPV) 77%, negative predictive value (NPV) 98%). A multicenter study was designed to test the hypothesis that SPNs which enhance less than 15 HU on all the images obtained at 1, 2, 3, and 4 minutes are benign. In fact, only four out of 171 malignant SPNs showed less than 15 HU enhancement on all these images (i.e. sensitivity 98%); 100% sensitivity for diagnosing malignancy was achieved only if the threshold was reduced to 1× 109/L

2 weeks to 6 months

Hypereosinophilic syndrome

Idiopathic

Marked (>1.5× 109/L)

≥6 months

Churg–Strauss syndrome

Usually idiopathic vasculitis

Usual

Weeks to months

Eosinophilic bronchitis

Unknown

Not present

>8 weeks

Usual in acute ABPA

Days to weeks

Chronic EP

Eosinophilic pneumonia of known cause Allergic Immune response to bronchopulmonary Aspergillus aspergillosis (ABPA) Bronchocentric May be related to granulomatosis Aspergillus Drug reactions Nonsteroidal antiinflammatory drugs; antibiotics241 Tropical eosinophilia Lymphatic filarial parasites; Wuchereria bancrofti and Brugia malayi Parasitic infection Many parasites (Dirofilaria, Ascaris, Strongyloides, Toxocara)

Usual

Common Usually

Days to weeks

3000–80 000/mm3

Variable

Usual

Variable

in a firefighter who had spent 13 days working at the World Trade Center site immediately after September 11, 2001.252 AEP may also be related to drugs including minocycline, heroin, and progesterone.253 The average age at presentation is about 30 years and there is no sex predilection.254 Principal symptoms are those of cough, dyspnea, fever, and chest pain coming on over a period of a few days. On examination patients are tachypneic and hypoxic. A history of asthma or atopy may or may not be present.255,256 Respiratory failure, with requirement for mechanical ventilation, develops in most patients.250 There is bilateral chest radiographic opacity and the usual presumptive diagnosis is of a fulminant chest infection or acute respiratory distress syndrome (ARDS). Blood eosinophil levels are elevated in about 35% of cases at presentation, but become abnormal at some point in the course of disease in 70%.250 The key to diagnosis, however, is provided by bronchoalveolar lavage showing a greatly raised eosinophil percentage which may be in the order of 30–80%.250,254 The other important diagnostic clue lies with chest imaging, as detailed below. Acute eosinophilic pneumonia responds satisfactorily to steroids and patients become symptom-free with essentially normal respiratory function. The condition does not relapse.254 AEP is one of the few forms of acute interstitial pneumonia in which the diagnosis may be strongly suspected based on chest radiographic and CT features (Box 11.7). As stated above, radiographic findings (Fig. 11.34)246,254,256–259 are usually a mixture of airspace and interstitial opacity, including septal lines.254,260 These

Migratory opacities; mucoid impaction; central bronchiectasis Mass lesions, alveolar opacities Ground-glass/reticular

Reticulonodular basal opacities; migratory opacities; chest radiograph may be normal Migratory opacities; chest radiograph may be normal

Box 11.7  Imaging features of acute eosinophilic pneumonia • • • • •

Pleural effusions Septal thickening Peribronchovascular thickening Ground-glass abnormality Consolidation

changes are bilateral but range from being diffuse to localized. Either consolidation or septal thickening may be found in isolation.254 About 70% of patients have pleural effusions (bilateral more commonly than unilateral) at presentation,261,262 and during the course of the illness essentially all patients develop bilateral effusions.259 In a series of 22 patients studied by Philit et al.,250 pleural effusions were visible on the initial chest radiograph in only two patients, but were seen on CT in 10 of the 14 patients who underwent CT. This suggests that the pleural effusions were not visualized in some patients on chest radiograph, either because of the associated parenchymal abnormality or because erect frontal and lateral radiographs were not obtained in these ill patients. CT may be very helpful in suggesting the diagnosis, with typical findings of septal lines, pleural effusions, and areas of consolidative and ground-glass opacity (Fig. 11.34).257,259 Areas of ground-glass abnormality and/or consolidation are found in almost all

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Chapter 11 • Idiopathic Diffuse Lung Diseases

A

B

C

D

Fig. 11.34  Acute eosinophilic pneumonia. A, B, Chest radiograph with detail view shows bilateral effusions, with septal thickening (arrows), and basal consolidation. C, D, CT confirms septal thickening, patchy ground-glass abnormality, and basal consolidation.

patients.261–263 Thickened interlobular septa are seen in about 75%, with thickening of bronchovascular structures in about the same number, and pleural effusions in 70–80%. Pleural effusions may be small or large. About 30% of cases have an upper lung predominance of abnormality.262 The distribution of consolidation and ground-glass abnormality is peripheral in more than 50% of cases, but may be central or random.263 In patients with acute respiratory failure, the demonstration by chest radiograph or CT of prominent interlobular septal thickening, thickening of bronchovascular bundles, or pleural effusions should prompt the recommendation of BAL to identify the presence of eosinophilia, and make the diagnosis of AEP. If eosinophilia is demonstrated, lung biopsy is probably not indicated.264 This is an important diagnosis to make, because survival with appropriate management is close to 100%,250 much better than in most other forms of acute respiratory failure.

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Simple eosinophilic pneumonia (Löffler syndrome) The characteristic features of simple pulmonary eosinophilia or Löffler syndrome are (1) blood eosinophilia, (2) absent or mild symptoms and signs (cough, fever, dyspnea), (3) one or more nonsegmental pulmonary consolidations that are transitory and/or migratory, and (4) spontaneous clearing of consolidations. Originally, opacities were described as disappearing within 6–12 days,265 but this interval is now generally extended to a month.242 Presentation has been noted to vary seasonally.266 The prognosis is excellent.266 Löffler syndrome may be idiopathic (cryptogenic), or it may result from a variety of inciting agents, particularly allergic bronchopulmonary mycosis, drugs, parasites, and miscellaneous agents such as nickel carbonyl.267 It seems likely that some, if not all, of

Eosinophilic Lung Disease Löffler’s original cases were related to ascariasis.266 In developed countries, the commonest cause of Löffler syndrome is probably allergic bronchopulmonary aspergillosis (see Fig. 11.46 below).241 Careful evaluation will lead to an identification of a cause in most cases of Löffler syndrome, and, indeed, there is some doubt as to whether this syndrome is ever truly idiopathic.241 Pathologically, there is an eosinophilic pneumonia with edema and an eosinophilic infiltrate in both alveoli and interstitium. Radio­graphically the findings are one or more fairly homogeneous, nonsegmental consolidations that can be small or so large as to occupy much of a lobe. They are transitory and may be migratory, disappearing from one area and appearing in another. They have a tendency to be peripherally located. Pleural effusions, mediastinal adenopathy, and cavitation are not described. Recently, it has been asserted that pulmonary eosinophilia accounts for a substantial proportion of transient ground-glass, part-solid, or solid nodules incidentally identified when chest CT is used in screening programs for lung cancer.268 In a review of 40 such cases, about 50% had solitary opacities, and 50% had multiple lesions.269 The opacities were usually either solid nodules with ground-glass halos or poorly defined solid nodules. Nodules were relatively large, with a mean diameter of 1.6 cm. They were usually distributed in the lower zones and peripherally in the lung, and usually resolved completely on follow-up. It is possible that some of these cases of transient eosinophilic pneumonia may have been due to subclinical parasitic infection.

Chronic eosinophilic pneumonia CEP is a cryptogenic form of eosinophilic lung disease with consistent and characteristic clinicopathologic features. Pathologically, there is an eosinophil-rich exudate in alveoli and interstitium.270,271 Angiitis is mild, fibrosis sparse, and necrosis very rare.270 Many patients present in middle life but prevalence remains high from the third to seventh decade,272 range 7–77 years; women outnumber men by 2 : 1;271 50% of patients are atopic, 40% asthmatic, and 5–10% have allergic rhinitis and nasal polyps.272 Asthma can antedate the condition by many years273 or can develop with the onset of CEP. The symptoms are usually highly characteristic, range from mild to severe, and have often been present for several months. Typical

A

symptoms are cough with mucoid sputum; high fever, particularly in the evenings, often accompanied by drenching night sweats; dyspnea; wheeze; malaise; and marked weight loss (8–12 kg). Occasionally there is chest pain and hemoptysis. Blood eosinophilia is common, but not universal, occurring in nearly 90% of patients,272 ranging from mild to marked.271 There is sputum eosinophilia in less than 50% of patients.272 Total white blood cell count and the erythrocyte sedimentation rate (ESR) are raised. Serum IgE is normal or only minimally elevated,271 allowing distinction from those conditions such as allergic bronchopulmonary aspergillosis and tropical and parasitic pulmonary eosinophilias in which serum IgE levels are markedly elevated. However, there have been a number of reports of markedly raised IgE levels.274 BAL demonstrates high eosinophil percentages – in the order of 25% or more. The principal pathologic findings are filling of alveoli with eosinophils and macrophages, sometimes with necrosis and the formation of eosinophilic abscesses. Foci of organizing pneumonia may be seen. Changes are not confined to alveolar spaces and there is typically an interstitial pneumonia as well, but fibrosis is not usually seen.241 Some patients with chronic eosinophilic pneumonia have an imaging pattern that is virtually pathognomonic (Box 11.8). At its most classic, the pattern, seen in two-thirds of patients,272 consists of peripheral, nonsegmental, homogeneous consolidations sometimes with an air bronchogram, the so-called ‘photographic negative of pulmonary edema’ (Fig. 11.35).275 These opacities lie against the chest wall and may surround the lung or just occupy one or two zones, particularly the apices (Fig. 11.36). In one series the zonal distribution was 46% upper, 40% mid, and 14% lower.276 About 50% of patients have bilateral consolidation which may cloak the upper and outer aspects of the lung in a very characteristic fashion Box 11.8  Imaging features of chronic eosinophilic pneumonia • • • •

Consolidation Ground-glass abnormality Peripheral predominance Upper lung predominance

B

Fig. 11.35  Chronic eosinophilic pneumonia. Radiographs are of a 65-year-old woman with a 1-month fever, night sweats, cough, and weight loss. The patient did not have asthma but had blood eosinophilia (1.6 × 109/L). A, Posteroanterior radiograph shows bilateral, confluent, peripheral opacity in middle and upper zones. B, Radiograph 2 weeks after A shows complete resolution following steroid therapy.

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Fig. 11.36  Chronic eosinophilic pneumonia. Chest radiograph is of a 52-year-old man who when first examined had a 2-month fever, weight loss, and cough. He had blood eosinophilia (2 × 109/L) and had had nasal polypectomies in the past. Radiographic findings of bilateral apical consolidation coupled with history were considered very suggestive of tuberculosis, and the patient was inappropriately treated for 1 month despite lack of firm evidence.

(Fig. 11.35).242,277 However, this characteristic peripheral distribution is seen in only a minority of cases (Fig. 11.37).244,272 The consolidation may even be predominantly perihilar in distribution.276 A common pattern is mixed peripheral and central consolidation (Fig. 11.37).276 Opacities may appear in one lung to be followed by others on the opposite side, or they may disappear spontaneously. If they resolve they usually recur in the same place.276,277 Unilateral diffuse consolidation may occur.278 Isolated lesions in the upper zone may closely mimic those of tuberculosis. Other features that are infrequently seen include pleural effusions (2%), cavitation (5%),272 and occasional mediastinal lymphadenopathy, best appreciated on CT.279–281 CT is often unnecessary to confirm the diagnosis of CEP, if typical imaging findings are associated with blood eosinophilia. In general, CT studies confirm the chest radiographic findings, showing strikingly peripheral, multifocal consolidation or ground-glass abnormality (Fig. 11.38A), though there may also be areas of nonperipheral consolidation.280,282 In one study, ground-glass opacity was as common a finding as consolidation.282 However, it was infrequently the only finding (in 12% of patients) and was usually close to the margins of consolidated areas.282 The bilateral subpleural distribution is universal in patients who are scanned within 1 month of the onset of symptoms.282 Patients with CEP who are imaged more than 1 month after onset of symptoms have a different pattern on CT. The consolidation tends to be more patchy (Fig. 11.38B,C), and though the opacities remain peripheral, the subpleural zone is often relatively clear. A characteristic feature in these more chronic cases is the presence of a dense bandlike structure parallel and about 1–2 cm deep to the chest wall (Fig. 11.38B), which may traverse the fissures.279,282 In chronic cases of CEP, dense fibrosis and lung distortion may rarely be seen. The disease occasionally remits spontaneously;277 however, treatment is usually required, and CEP is remarkably sensitive to steroid therapy (Fig. 11.35). Rapid clearing is usually seen within a few days, with complete clearing by 1 month.270 In fact some authors

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Fig. 11.37  Chronic eosinophilic pneumonia (CEP). Radiograph shows multifocal peripheral and central consolidation. This is a recognized pattern but less common than the one shown in Fig. 11.35. Both costophrenic angles are blunted in this patient. Pleural effusions are very unusual in CEP.

recommend a therapeutic trial of steroids in previously well patients with classical clinical and imaging features.272 Radiographic resolution is usually complete. The characteristic bandlike opacities parallel to the chest wall may be seen during the resolving phase (Fig. 11.39).272,277,282 Clinical relapse occurs in about 30–60%,283 and in a review of 62 patients 21% relapsed during reduction of steroid dose and 58% after discontinuation.272 The majority of patients need long-term low-dose steroids284 and a proportion develop late-onset asthma.277 In some instances, patients who initially have all the features of CEP go on to develop the Churg–Strauss syndrome285 or a diffuse vasculitis.277,286 The imaging features of CEP overlap with those of cryptogenic organizing pneumonia, but may be distinguished by recognition of blood eosinophilia. CEP must also be distinguished from Churg– Strauss syndrome, which should be suspected if there is evidence of cardiac or other systemic involvement.244

Allergic bronchopulmonary mycosis Allergic bronchopulmonary mycosis is almost certainly the most common cause of eosinophilic lung disease in developed countries. Allergic bronchopulmonary aspergillosis (ABPA) accounted for 78% of the patients with a diagnosis of pulmonary eosinophilia in a series of 143 in the UK who were admitted to a tertiary referral center.287 First described in 1952,288 the disease is characterized by asthma, radiographic pulmonary opacities, blood eosinophilia, and evidence of allergy to antigens of Aspergillus species. Its importance lies in the fact that recurrent acute episodes cause progressive bronchial damage that can be controlled by steroid administration.289 Though it may be due to a wide variety of organisms, Aspergillus species are by far the most common causative agent, resulting in ABPA. In more than 90% of patients, the species involved is Aspergillus fumigatus, but occasionally other species are implicated, including Aspergillus flavus, Aspergillus niger, Aspergillus nidulans,290 Aspergillus terreus,291 Aspergillus oryzae,292 and Aspergillus ochraceus.293 In addition there are isolated case reports of an ABPA-like syndrome caused by fungi other than Aspergillus spp., including

Eosinophilic Lung Disease

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A

C

Fig. 11.38  Chronic eosinophilic pneumonia. A, Initial CT shows focal subpleural consolidation with other areas of subpleural ground-glass abnormality. B, C, CT images obtained during a recurrence shows more patchy, more central consolidation. A bandlike area is seen in the left upper lobe, parallel to the chest wall, on B.

Candida albicans, Curvularia (see Fig. 11.41 below) and at least seven other genera.294,295 These conditions may be more difficult to diagnose because Aspergillus precipitins may be absent. In ABPA, a hypersensitivity reaction develops to Aspergillus spp. that grow as a mycelial plug in proximal airways, usually the second or third order bronchi.296 Tissue invasion is either absent290 or very limited.297 The factors that favor the initial airway colonization by Aspergillus are unclear,290 but in part are probably related to the almost universal presence of asthma and atopy in affected patients. Other important factors are the size of the spores (2.5– 3.0 mm), which favors inhalation and airway deposition, and their thermotolerance, which allows hyphal growth at body temperatures.294,298 Certainly, once the fungus gets a foothold, local damage will promote further colonization. The immunology and pathogenesis of ABPA is complex. CD4+Th-2 lymphocyte activation is thought to be important in releasing mediators that increase eosinophil production, and stimulate B cells to produce IgE and IgG production.299 Because antigen production is localized to the mycelial plug in the proximal airway, tissue damage tends to be greatest in this region, giving rise to granulomatous airway inflammation that results in the characteristic proximal bronchiectasis. In addition, however, there appears to be a separate pathologic process centered on the lung parenchyma, giving an eosinophilic pneumonia which does not produce permanent damage.294 Typically, ABPA occurs in patients with atopy and longstanding asthma. A few patients, particularly older ones, develop asthma concurrently with their first attack of ABPA.287 Although unusual,

the disease is well-recognized in nonasthmatic patients.287,300 Overall there is a slight female preponderance.287,301,302 It may occur at any age,302–304 but typically presents between 20 and 40 years of age. The entity is familial in about 5% of cases.305 There is an association with several HLA alleles.306 The length of the interval between the onset of asthma and ABPA is inversely related to the age of onset of asthma. McCarthy and co-workers307 found that with asthma beginning before 10 years of age, there was an average gap of 24 years, but with late-onset asthma (30 years of age or more), the mean gap was only 3.5 years. Late-onset asthma was associated with more frequent attacks of ABPA and greater lung damage.307 ABPA also occurs in patients with cystic fibrosis in whom there is an approximately 10% prevalence.266 In about 10% of patients, allergic bronchopulmonary mycosis may be associated with allergic fungal sinusitis.308 This condition is characterized by accumulation of mucin in the sinuses, associated with polyposis in the sinuses and nose. It is associated with a wider range of organisms than allergic bronchopulmonary mycosis, including Curvularia and Bipolaris spp.309–312 On imaging, it is characterized by mucosal thickening and hyperattenuating sinus contents, often associated with bony erosions.313,314 ABPA runs a relapsing and remitting course and an acute attack may be indistinguishable from an uncomplicated exacerbation of asthma.294 Patterson et al.315 described five clinical stages of ABPA: acute, remission, exacerbation, steroid-dependent asthma, and fibrosis. These must not be regarded as phases of disease, as patients need not pass from one stage to the next in orderly progression. Characteristic symptoms in the acute stage are wheeze,

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Chapter 11 • Idiopathic Diffuse Lung Diseases diagnosis of ABPA can be made with reasonable certainty. The major criteria for ABPA are: 1. 2. 3. 4. 5. 6. 7.

Asthma Blood eosinophilia Immediate skin reactivity to Aspergillus antigen Precipitin antibodies to Aspergillus antigen Raised serum IgE (nonspecific/specific) History of radiographic pulmonary opacities Central bronchiectasis.

The minor criteria for ABPA are: 1. A. fumigatus in sputum 2. History of expectorating brown plugs 3. Late skin reactivity to Aspergillus antigen.

Fig. 11.39  Chronic eosinophilic pneumonia. Local view of left middle and upper zone. Partial resolution of classic peripheral consolidation has resulted in band opacity parallel to chest wall. dyspnea, and a cough that is often productive and associated with minor hemoptysis. Systemic symptoms such as fever, malaise, and weight loss are common. About 50% of patients have pleuritic pain, and about the same percentage give a history of coughing up sputum plugs.287 These contain fungal mycelia and are important pointers to the diagnosis.287 Plugs are about l–2  cm long, firm, friable, and pelletlike.287 An abnormal chest radiograph, blood eosinophilia, and an immediate skin ‘wheal and flare’ reaction to Aspergillus antigens are characteristic of the acute phase. Eosinophilia is usually mild to moderate, with 74% of patients having counts between l × 109/L and 3 × 109/L.287 The eosinophil level may be depressed by steroid treatment. Serum precipitins against Aspergillus antigens are detected in about 90% of patients in the acute phase, particularly if the serum is concentrated.287,294,301,316 It must be remembered, however, that this test is nonspecific in that 12–25% of patients with extrinsic asthma will have a positive precipitin test.317 Both nonspecific and Aspergillus antigen-specific IgE are greatly raised, perhaps 20 times normal.316 Smaller elevations may be found in simple asthma. As with the finding of positive precipitins, elevation of IgE per se is not diagnostic of ABPA. Nevertheless the IgE level is probably the single most useful laboratory test in ABPA since levels correlate with disease activity and a normal level virtually excludes the diagnosis.266,316 Criteria for the diagnosis of ABPA have changed over time as knowledge about the disease has become more sophisticated; yet even now there are no universally accepted diagnostic criteria. Rosenberg and co-workers316 have set out the following major and minor criteria and suggest that if the first six of the major criteria are satisfied, the

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ABPA can be present without bronchiectasis,266,318,319 and ABPA without bronchiectasis appears to carry a better prognosis, with fewer exacerbations.320,321 In one study, 11 of 31 patients with serologically diagnosed ABPA did not have bronchiectasis;321 these patients had less severe disease than those with bronchiectasis, and did not subsequently develop bronchiectasis on follow-up over 2 years.322 The prevalence of bronchiectasis may decrease with increasing use of serology to screen for ABPA: in a more recent study of 155 patients with ABPA, 37 (24%) had a normal findings on CT.323 In a prospective study of 255 patients with asthma, Eaton et al.324 found that 47 patients had positive skin prick tests for A. fumigatus, of whom 35 underwent CT. Central bronchiectasis was found on CT in 12 of these patients, eight of whom met all of the criteria for ABPA. These investigators found that performing CT in patients with skin prick positivity who had histories of sputum plugs, eczema, or steroid dependency would identify all cases of ABPA with bronchiectasis. These authors proposed the following minimal criteria for ABPA: asthma, skin prick test positivity, and central bronchiectasis. A great variety of imaging changes are found in ABPA, and may be related to the phase of the disease.301,302,304,307,325–327 The imaging findings are best considered as acute and transient or chronic and permanent (Table 11.2).307 The transient changes are listed in Table 11.2. Consolidation ranges from patchy subsegmental or smaller opacities (Fig. 11.40) to complete lobar or multisegmental opacity (Fig. 11.41). Areas of consolidation show little if any zonal predilection and are often multiple. The segmental configuration contrasts with the nonsegmental consolidation seen in other eosinophilic states. The pathologic basis of the consolidation is unclear: it might be related to airway obstruction or eosinophilia. Although consolidation is usually transient, it can last for 6 weeks or more. Phelan and Kerr302 described some patients with apparently permanent consolidation, perhaps due to endobronchial obstruction. When consolidation clears, it often leaves residual bronchiectasis (Fig. 11.41). Consolidation may recur

Table 11.2 Radiographic findings in allergic bronchopulmonary aspergillosis (% = prevalence of finding) Major

Minor

Acute (transient) Consolidation (80%) Airway wall thickening Mucoid impaction (bronchocele) (30%) Small nodules Atelectasis (20%) Pleural effusions Chronic (permanent) Bronchiectasis Pleural thickening Mid/upper zone volume loss and Mycetoma scarring Small nodules Linear scars

Eosinophilic Lung Disease

A

B

C

in 25–50% of cases, often in the same area. Radiographic consolidation may be asymptomatic in 20–30% of patients,289,304 and ABPA is one of those conditions in which gross radiographic changes may be accompanied by little in the way of symptoms.307 The most common transient change is mucoid impaction (bronchocele). In this condition, an airway becomes obstructed and distended by retained secretions, but the subtended lung remains aerated by collateral air drift, allowing direct visualization of the impacted airway. Mucoid impaction is characterized by a sharply demarcated, bandlike opacity, sometimes branching (Fig. 11.42), which points to the hilum, usually about 2–3  cm long and some 5–8  mm wide. Rounded opacities are produced by linear bronchoceles seen end-on. Impacted airways are usually proximal. They

Fig. 11.40  Consolidation in allergic bronchopulmonary aspergillosis. A–C, Three radiographs taken at approximately yearly intervals show recurring, multifocal areas of consolidation. Some of the opacities contain air bronchograms. There is associated airway wall thickening, best seen in B.

are often inseparable from the hilum and may simulate lymphadenopathy327 or a mass. Another variant is produced by distal bronchiectatic airways which, when impacted, give a band shadow with a club-shaped end – the ‘gloved finger shadow’. Bronchoceles show a strong upper zone predilection (Figs 11.42 and 11.43).304 They disappear once their contents have been coughed up, leaving dilated bronchi, manifested as ring or parallel line opacities (Fig. 11.43). Like consolidation in ABPA plugging may recur at the same site. Occasionally they persist for many months. On CT, the bronchoceles are seen as bandlike abnormalities in the expected position of the bronchi (Fig. 11.42). Their attenuation may be similar to that of water or soft tissue, or they may be hyperattenuating (Figs 11.41 and 11.42).328 The hyperattenuation is presumed to be due to

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B

A

C

Fig. 11.41  Multisegmental consolidation in allergic bronchopulmonary mycosis. A, Chest radiograph shows dense lingular consolidation. B, CT shows consolidation, with central hyperattenuating material representing mucoid impaction. C, CT following bronchoscopy and removal of mucus plug shows varicose bronchiectasis and tree-in-bud pattern. Examination of the plug showed that the responsible fungal species was Curvularia rather than Aspergillus.

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Eosinophilic Lung Disease

A

C

B

D

Fig. 11.42  Mucoid impaction in allergic bronchopulmonary aspergillosis. A, B, Frontal and lateral chest radiograph shows diffuse airway wall thickening, and bandlike opacities (arrows) in the right upper lobe. C, CT confirms a branching opacity in the posterior right upper lobe. D, Mediastinal window shows that the attenuation of the opacity is greater than that of soft tissue.

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A

B

Fig. 11.43  Bronchoceles in allergic bronchopulmonary aspergillosis. A, Local view of the right upper and middle lung shows multiple rounded bronchoceles. B, When these clear, they leave a collection of delicate curvilinear and ring opacities, which represent the walls of bronchiectatic airways. Such opacities close to the hilum in the middle and upper zones are a characteristic interval finding in allergic aspergillosis. calcium329 or metallic ions within chronically inspissated mucus, and is found in 20–30% of cases.330,323 Relapse of ABPA occurred in 23% of one series of 155 patients, and was more common in those with more severe bronchiectasis or with hyperattenuating mucus.323 Another major transient manifestation of ABPA is atelectasis (Fig. 11.44), which ranges in frequency from 3%304 to 46%.296 It may be subsegmental, segmental, lobar, or even affect a whole lung.302,326,331 Like consolidation and mucoid impaction, collapse has a tendency to recur in the same area. On CT, mucus plugs may be seen within the areas of atelectasis if they are hyperattenuating or of water attenuation. There have been a few reports of pleural effusion.304,332 Permanent changes (Table 11.2) are of importance because, first, they indicate irreversible lung damage and, second, they may be the only clue that an asthmatic patient has ABPA when a patient is in remission. Bronchiectasis is responsible for most of the permanent radiographic changes. The characteristic finding (Box 11.9) is proximal bronchiectasis, usually affecting first and second order subsegmental bronchi (Figs 11.45 and 11.46). Beyond the proximal bronchiectasis, more distal airways remain normal and patent, though a tree-in-bud pattern of abnormality is common on CT. Proximal bronchiectasis has been considered highly specific for ABPA316 and in a selected patient population of asthmatic patients, with skin tests positive for A. fumigatus, this is probably so.333 However, central bronchiectasis may also be found in other conditions such as cartilage deficiency syndromes, primary ciliary dyskinesia, and idiopathic bronchiectasis.334 Several papers have compared the CT features of ABPA with those of uncomplicated asthma.335–337 The prevalence of bronchial dilatation in patients with severe or chronic asthma ranges from 17% to 30%, compared with 90% or more in ABPA.335,336 However, the bronchial dilatation in asthma is usually mild, cylindric, and distal, in contrast to the more severe proximal varicose or cystic bronchiectasis of ABPA.335 Other distinguishing features on CT include a higher prevalence of centrilobular nodules and mucoid impaction in ABPA.335,336 The presence of bronchiectasis in three or more lobes is suggestive of ABPA.336

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Box 11.9  Characteristic CT features of bronchiectasis in ABPA • • • • •

Involve segmental and subsegmental bronchi Varicose or cystic Thin-walled Associated mucoid impaction (which may be hyperattenuating) Associated centrilobular nodularity

Parenchymal scarring representing the fibrotic stage of ABPA commonly follows bronchiectasis, and is manifest by linear abnormality and lobar shrinkage (Figs 11.46 and 11.47). Mirroring the distribution of bronchiectasis, these features have a strong upper zone predilection, with 78% being so distributed in one series.307 Such lobar shrinkage is accompanied by a variety of ring and linear opacities. Lower lobe shrinkage, though described, is very unusual.302 Although there is often chronic lobar shrinkage, the overall lung volume is frequently increased, reflecting airflow limitation, emphysema, and bulla formation. Between 30% and 40% of patients in one series showed overinflation.302 Pleural thickening is not a major feature, having a prevalence of 18% in the same series, though pleural thickening was seen on CT in 14 of 17 cases of ABPA in one series.333 Mycetomas may form in the bronchiectatic cavities. In one series of 111 patients with ABPA, eight had mycetomas, predominantly mid-zonal.307 Since mid-zone mycetomas are unusual in other conditions, it has been suggested that a mycetoma found in this position should raise the possibility of underlying ABPA.307 It is of interest that an ABPA-type syndrome has been recorded as developing as a result of a mycetoma lodged in a tuberculous cavity.338

ABPA in cystic fibrosis The reported prevalence of ABPA in patients with cystic fibrosis has varied from 1% to 50%, depending on diagnostic criteria and

Eosinophilic Lung Disease

A

C

on the aggressiveness of screening.339,340 The prevalence of ABPA in cystic fibrosis patients in the USA appears to be about 2%,339 compared with 7.8% in Europe.340,341 Box 11.10 shows the criteria for diagnosis of ABPA in this condition, based on a consensus statement.340 The diagnosis of ABPA in cystic fibrosis is difficult, and may often be delayed, because many of the diagnostic criteria overlap with common manifestations of the disease.340 From an imaging viewpoint, the problem with diagnosis of ABPA in cystic fibrosis is that bronchiectasis and pulmonary opacities are common in uncomplicated cystic fibrosis. The published criteria for diagnosis of ABPA in cystic fibrosis (Box 11.10) suggest that such abnormalities may support the diagnosis of ABPA if they are new and have not responded to standard treatment. The type and distribution of the bronchiectasis may assist in the diagnosis, since central bronchiectasis is relatively uncommon in cystic fibro-

B

Fig. 11.44  Atelectasis in allergic bronchopulmonary aspergillosis. A, B, Frontal and lateral chest radiographs show lingular consolidation associated with minor volume loss. C, Subsequent radiograph shows complete collapse of upper lobe.

Box 11.10  Criteria for diagnosis of ABPA in cystic fibrosis340

Classic case 1. Acute or subacute clinical deterioration not attributable to another etiology 2. Serum total IgE concentration of >1000 IU/mL 3. Skin test positivity to Aspergillus 4. Precipitating antibodies or IgG antibody to A. fumigatus 5. New or recent abnormalities on chest radiography (infiltrates or mucus plugging) or chest CT (bronchiectasis) that have not cleared with antibiotics and standard physiotherapy

Minimal diagnostic criteria • Criteria 1, 2, 3, and either 4 or 5

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A

B

Fig. 11.45  Bronchiectasis in allergic bronchopulmonary aspergillosis. A, Chest radiograph shows extensive airway wall thickening, seen both en face (yellow arrows) and in profile as a tubular shadow (red arrows). B, CT shows varicose thick-walled bronchiectasis involving subsegmental bronchi.

Fig. 11.46  Allergic bronchopulmonary aspergillosis – airways disease with scarring. CT through the upper zones shows dilated thick-walled bronchi and a 1.5 cm rounded opacity (arrow) caused by a bronchocele. Linear opacities seen anteriorly are caused by scarring.

Fig. 11.47  Bilateral middle and upper zone fibrosis following multiple acute attacks of allergic bronchopulmonary aspergillosis. Chest radiograph shows marked bilateral upper lobe volume loss, with linear, ring, and conglomerate opacities in the upper lungs, reflecting underlying bronchiectasis, scarring, and bulla formation.

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Eosinophilic Lung Disease sis, though common in ABPA. In a study of patients with bronchiectasis, central bronchiectasis without peripheral bronchiectasis was seen in 11 (37%) of 30 patients with ABPA and in only one (7%) of patients with mild cystic fibrosis.334 Although varicose or cystic bronchiectasis is quite common in cystic fibrosis, it appears to be more common in ABPA.340 High-attenuation mucus plugs have been reported in ABPA,330 but not in cystic fibrosis, so these might be suggestive of ABPA in the correct clinical context.

Drug-induced eosinophilic lung disease A large number of drugs has been recorded as producing pulmonary opacities as part of a hypersensitivity response together with blood eosinophilia (see p 509). Patients generally develop symptoms within days or a few weeks of starting the drug and some develop an associated rash and pyrexia, which provide helpful clues as to the nature of the imaging opacity. A variety of chest radiographic patterns are produced: • Airspace opacity (Fig. 11.48), which may be localized or diffuse. In some instances the pattern is that of Löffler syndrome. Illnesses vary from a mild, simple eosinophilic pneumonia to a fulminant acute eosinophilic pneumonia.266 Drugs that are particularly associated with a consolidative pattern include penicillin, sulfonamides, para-aminosalicylic acid, chlorpropamide, nitrofurantoin, methotrexate, carbamazepine, mephenesin, imipramine, trimipramine, and hydrochlorothiazide. • Hilar lymphadenopathy. This is recorded with the antiepileptic drugs phenytoin and trimethadione.342 • Pleural effusions. These are occasionally seen with nitrofurantoin (see p 1025). • Reticulonodular opacity. An interstitial pulmonary fibrosis type of pattern is produced in particular by nitrofurantoin and methotrexate. With nitrofurantoin the chronic interstitial pattern is associated with a blood eosinophilia in about 40% of patients.343 Other drugs that produce an interstitial pattern include gold342 and clofibrate.344 • Other patterns. Patterns other than those described and which are not easy to classify are recorded with a number of drugs such as penicillamine.345

Fig. 11.48  Drug-related eosinophilic lung disease. Multifocal nonsegmental consolidations in a 66-year-old man who developed a nonproductive cough and dyspnea after starting nonsteroidal anti-inflammatory drug (naproxen). There was blood eosinophilia (6.4 × 109/L). Opacities cleared after naproxen was discontinued and systemic steroids were begun. (Courtesy of Dr. J D Stevenson, Poole, Dorset, UK.)

A distinctive syndrome was described in association with ltryptophan ingestion (l-tryptophan eosinophilia myalgia syndrome). Principal features include peripheral eosinophilia, myopathy, peripheral neuropathy, eosinophilic fasciitis, and respiratory disorder. This latter is characterized on imaging by bilateral, often basally predominant, opacity with mixed alveolar and interstitial features, and pleural effusions.346,347 Pathologically there is chronic interstitial pneumonitis, tissue eosinophilia, and vasculitis.346

Tropical pulmonary eosinophilia This is a specific systemic disease caused by hypersensitivity to microfilariae – the early larval forms of various filarial nematodes, the most important being Brugia malayi and Wuchereria bancrofti.348,349 Transmission is by mosquito. Tropical pulmonary eosinophilia (TPE) is found in all parts of the world where filariasis is endemic, particularly the Indian subcontinent, South East Asia, the South Pacific, North Africa, and South America. It occurs chiefly in the indigenous residents (particularly in the Indian subcontinent),350,351 and is very uncommon in visitors unless they have resided in the area for many months.352 In nonendemic areas the disease is seen in immigrants and, because of persistence of the parasite in the host, may present as long as 3 years after returning from an endemic area.353 Occurrence is extremely rare in Caucasians.354 The disease is more common in males, in some series by as much as 4 : l,355 but this is not a universal finding.354 The usual age at presentation is between 5 and 40 years,355 though the range can be larger; in one series of 350 it varied from l.5 to 74 years.351 The principal features of the illness are a systemic disturbance marked by fatigue, weight loss, and low-grade fever together with chronic cough, which is particularly troublesome at night. Even without treatment, symptoms tend to remit after several weeks or months only to recur later.352 Patients who have not had treatment or who have responded inadequately may go on to develop progressive dyspnea secondary to interstitial fibrosis.349 There is a gross eosinophilia of more than 3 × 109/L, characteristically between 5 × 109/L and 60 × 109/L, IgE levels are greatly elevated, usually more than 1000  units/mL, and there is a high titer of antifilarial antibody. BAL shows a high percentage of eosinophils, in the order of 50%. Imaging findings in the chest351,354,356,357 may be caused by active alveolitis and/or interstitial scarring. The chest radiograph has a normal appearance in 2–13% of cases. The most common abnormalities, seen in 30–60% of patients, are fine linear opacities distributed diffusely and symmetrically, accompanied by hilar haziness, and an accentuation or blurring of vessels. Some authors354 describe a basal preponderance, and others stress a diffuse ground-glass type of pattern.351 Small nodules are a slightly less common finding, seen in about 30–50% of patients. The nodules range in size from l mm to 5 mm and may occur alone or with the linear opacities described above.354 Though generally bilateral and symmetric, nodules may be asymmetric or even unilateral. Other patterns are much less common and consist of areas of consolidation that are generally small and single. In a study of 10 patients with tropical pulmonary eosinophilia,358 CT showed reticulonodular abnormality, bronchiectasis, and air-trapping, but the extent of CT abnormalities did not correlate with physiologic impairment. Tropical pulmonary eosinophilia characteristically responds rapidly to diethylcarbamazine therapy and this is an important diagnostic criterion. However, 5% of patients, even early on in the natural history of the disease, fail to respond adequately and this figure rises to 20–40% in patients who have had longstanding symptoms.349 A 5-year follow-up of a large series of patients showed a 20% relapse rate349 and a significant number of patients develop chronic, progressive dyspnea on the basis of interstitial fibrosis.

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Chapter 11 • Idiopathic Diffuse Lung Diseases

Fig. 11.49  Eosinophilic lung disease following worm infestation. This 52-year-old woman had buttock rash caused by cutaneous larva migrans (Ancylostoma braziliense) acquired on vacation in West Indies. She had blood eosinophilia and dry cough. Chest radiograph shows two areas of consolidation: one in the left mid-zone and the other peripherally in the left upper zone. Both cleared in 2 weeks.

Eosinophilic lung disease from other worm infestations The larval stages of a number of worms other than filarial nematodes pass through the lung and may, in the process, induce an allergic response. This most commonly takes the form of simple eosinophilic pneumonia/Löffler syndrome with transient, migratory, nonsegmental areas of consolidation associated with a blood eosinophilia (Fig. 11.49).359 Nearly all the worms that cause this response are nematodes: Ascaris lumbricoides,360 Ascaris suum,361 Strongyloides stercoralis,359 Toxocara canis (visceral larva migrans),362 Toxocara cati,359 Ancylostoma braziliense (‘creeping eruption’),363 Ancylostoma duodenale, Necator americanus,364 and Trichuris trichiura.242 Exceptions are Taenia saginata and Echinococcus alveolaris,242 both cestodes, and Schistosoma spp., which are trematodes.365 It is possible that, in at least some of these infestations, the pulmonary reaction is not related to local larvae but rather is a remote response to a soluble antigen.363 Thus in 26 patients with eosinophilic lung disease due to Ankylostoma braziliense (Fig. 11.49), it was not possible to demonstrate larvae in the sputum.366 Some idea of the possible frequency of eosinophilic lung disease caused by nematode infestations may be gained from the last authors, who found lung parenchymal abnormality in 34% of 76 patients with cutaneous larva migrans (hookworm infestation). In the USA, the commonest parasites to consider are Strongyloides, Ascaris, Toxocara, and Ancylostoma.266 The last three agents usually give rise to simple eosinophilic pneumonia/Löffler-type changes on the chest radiograph. With Strongyloides the lung pathology is more complicated and in the autoinfection stage there is a pulmonary foreign body reaction with inflammatory pneumonitis, bronchopneumonia, and hemorrhage. The chest radiograph (Fig. 11.50) reflects this and shows mixed opacity – miliary nodules, reticular opacities, and airspace opacities, ranging from multifocal and patchy to lobar.367 About 90% of patients will have a blood eosinophilia. Should the hyperinfection syndrome supervene, the chest radiograph manifests widespread consolidation, at which stage peripheral eosinophilia may be absent.367 It is important to know that, for a variety of reasons, acute eosinophilic lung disease induced by Strongyloides, Ascaris, Toxacara,

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Fig. 11.50  Pulmonary eosinophilia due to Strongyloides. Chest radiograph shows bilateral patches of consolidation. and Ancylostoma is usually not accompanied by ova in the stool.241,266 Ascariasis and Strongyloides may be diagnosed by finding larvae in the sputum, BAL, or gastric aspirates, but ova may not be found in the stool until females are mature, which in ascariasis may be delayed up to 3 months after initial pulmonary manifestations.241 Toxocara and Ancylostoma do not replicate in the gut, so ova are not usually found in the stool. Both conditions may be suspected on the basis of a skin rash; toxocariasis may be confirmed by serology.241

Bronchocentric granulomatosis This uncommon form of pulmonary granulomatosis, first described by Liebow in 1973,368 differs from other lung granulomatoses, such as Wegener granulomatosis, in that it is localized to the lung, and centered around airways (bronchocentric) rather than vessels (angio­centric). Pathologically, small airways and bronchioles are filled and replaced by cellular debris and necrotic granulomas surrounded by palisaded epithelioid cells. At least 30% of cases are related to asthma, and in these individuals is probably part of the spectrum of ABPA.369,370 In asthmatic people, the major part of the cellular infiltrate is made up of eosinophils, whereas in nonasthmatic people the plasma cell is dominant.371 Large airways may show bronchocele formation, and distal lung is often consolidated by an eosinophilic or obstructive pneumonitis. Vasculitic changes appear to be minor and incidental. Only four series of patients with bronchocentric granulomatosis have been recorded,371–374 representing a total of 60 cases. However, there have been many additional case reports. Patients commonly present in their forties, but there is a wide age range (9–76 years) and a tendency for asthmatic patients to present at a younger age (mean age 22 years) than nonasthmatic patients (mean age 50 years).371 The incidence in both sexes is equal. Symptoms may be absent or minor and, when present, consist of fever, cough, chest pain, wheeze, and hemoptysis. About 50% of patients have had a blood eosinophilia, a finding that appears to be limited to asthmatic people.371,373 On imaging,371–373,375 two major patterns are seen: consolidation and masslike lesions. Consolidation may be lobar or sublobar and may be accompanied by volume loss (Fig. 11.51). They are thought to represent either eosinophilic or obstructive pneumonitis.371 They tend to be more common in the upper zones,371,375 and are unilateral in about 75% of patients. Sublobar consolidation was the common-

Eosinophilic Lung Disease impaction was seen in two patients. The imaging findings were felt to be due to granuloma formation with or without proximal airway obstruction. Prognosis is good. Lesions may clear spontaneously or with steroids and generally do not recur following surgical removal. If this should happen, recurrences can usually be controlled with steroid treatment.

Hypereosinophilic syndrome

Fig. 11.51  Bronchocentric granulomatosis. This 52-year-old woman presented with weight loss and cough. Chest radiograph shows right upper zone consolidation with some volume loss and scattered linear and nodular opacities in the left upper zone. Cavitation subsequently developed in the right upper lobe.

Fig. 11.52  Bronchocentric granulomatosis. CT at carinal level shows an irregular, lobulated, and spiculated 3 cm mass lesion in the right upper lobe. Marginal irregularity and spiculation, suggestive of malignancy, are not uncommon in bronchocentric granulomatosis.

est finding (16 out of 22) in one large series.371 Masslike lesions (Fig. 11.52) are commonly solitary, but can be multiple. They are considered to represent a mass of necrotic tissue with surrounding granulomatous or organizing pneumonia. They vary in size from 2 cm to 15 cm,376 and are often not particularly well defined. They may be centered on an airway. Occasionally they cavitate.371,376,377 Less common imaging patterns include mucoid impaction368,371,377,378 and reticulonodular opacities.377 On some occasions the reticulonodular abnormality has evolved from antecedent consolidation. Adenopathy and pleural disease are not features.377 In a study of five patients with bronchocentric granulomatosis,374 CT showed spiculated mass lesions in three cases and consolidation in two. Extensive mucoid

Hypereosinophilic syndrome is an uncommon heterogeneous group of disorders in which the eosinophilia may be neoplastic (such as an eosinophilic leukemia) or reactive, and in the latter instance some appear to be truly idiopathic in that a cause is not established even at death.379 It is characterized by: (1) prolonged and marked eosinophilia (a blood count of more than 1.5 × 109/L for more than 6 months); (2) no recognizable cause for the eosinophilia such as parasitic infestation or allergy; and (3) signs or symptoms of organ dysfunction (Box 11.11).380 The sustained hypereosinophilia causes tissue damage, particularly cardiac, and this is a key element to the syndrome. The illness varies in severity from mild to fatal, involving in particular the cardiovascular and nervous systems. The cardiac abnormality consists primarily of endocardial thickening and fibrosis related to widespread tissue infiltration with mature eosinophils,381 leading to endocardial fibrosis, res­ trictive cardiomyopathy, and thrombosis. Several subtypes of hypereosinophilic syndrome have been described, including myeloproliferative, lymphocytic, and familial variants.382 A significant recent advance in understanding of this condition has been the recognition of FIP1L1-platelet-derived growth factor receptor-a fusion protein in up to 50% of individuals with this syndrome, and the recognition that these individuals may respond to treatment with the protein kinase inhibitor imatinib.245,382 Other forms of this condition may respond to treatment with mepolizumab.383 Almost all patients have been men, typically young or middleaged adults who present with progressive cardiopulmonary symptoms, skin rash, or myalgia, together with systemic symptoms such as weight loss, weakness, fatigue, and fever. The peripheral blood shows a marked eosinophilia, often in the order of 30–70% of the total white blood cell count (10–50 × 109/L), some of the eosinophils being degranulated and vacuolated. Some patients have a mild increase in IgE. The organ systems most commonly affected are the nervous and cardiovascular systems and the skin. Cardiovascular involvement is usually the dominant feature and is a major cause of morbidity, with signs of restrictive cardiomyopathy and pump failure, mitral and tricuspid regurgitation, and endocardial thrombosis. The last leads to systemic emboli in about 5% of patients384 or pulmonary emboli if the thrombus is right sided.381 Clinical pulmonary involvement has been recorded in about 40% of patients.380,381 In most, these are findings related to heart failure,385 and include pulmonary edema (Fig. 11.53) and pleural effusions.380 Because the cardiomyopathy is restrictive in type, any accompanying cardiomegaly is often mild.384 Pulmonary emboli were recorded in 9% of 57 patients reviewed from the literature.380 Other less common pulmonary manifestations include transient consolidations, which are presumably eosinophilic pneumonias and diffuse interstitial fibrosis.380,384 HRCT findings in five patients in whom chest radiographs were normal (3/5) or showed nonspecific focal opacities (2/5) consisted of scattered nodules (about 2–10 mm) with

Box 11.11  Clinical manifestations of hypereosinophilic syndrome • Cardiac – Endocardial thickening – Restrictive cardiomyopathy • Skin rash – Pulmonary parenchymal opacity

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Fig. 11.53  A 55-year-old man with hypereosinophilic syndrome. A, Chest radiograph shows cardiomegaly and bilateral effusions, thought to be due to heart failure. B, CT shows patchy ground-glass abnormality, which may be due to lung edema or eosinophilic infiltration.

ground-glass halos (5/5) and focal areas of ground-glass attenuation (3/5) (Fig. 11.53). There was no pathologic correlation, but the authors considered that the lesions probably represented areas of eosinophilic infiltration.386 In three patients studied by Johkoh et al.,262 the common imaging features were ground-glass attenuation and nodules, with septal thickening and thickening of bronchovascular bundles. The challenge in these cases is to distinguish findings due to heart failure from those due to pulmonary involvement. Before the use of steroids, cytotoxic drugs, and monoclonal antibodies, the prognosis of hypereosinophilic syndrome was poor, with a 25% 2-year survival rate,380 but this figure has now improved considerably, and the 3-year mortality has reduced to 4%.383,387

Other conditions associated with eosinophilia (Box 11.12) There is often a mild to moderate eosinophilia in patients with asthma.388 The radiology of asthma is discussed elsewhere (p 752). In addition, asthma is often a prominent symptom in a number of specific eosinophilic lung states such as ABPA and the Churg– Strauss syndrome. Other pulmonary conditions associated with blood eosinophilia, and often with tissue eosinophilia, are listed in Box 11.12. The degree of eosinophilia in these conditions is generally relatively slight (less than 1 × 109/L). Box 11.12 emphasizes the importance of considering infection and neoplasm (Fig. 11.54) in patients presenting with eosinophilia and pulmonary parenchymal abnormalities.

Hyperimmunoglobulin E syndrome This rare primary immunodeficiency syndrome was first described in 1966389 and is characterized by recurrent bacterial infections of the lungs, sinuses, and skin dating from birth or early childhood, and a more than 10-fold elevation of serum IgE.390 The immunologic derangement is complex and only partly understood.391 The number of suppressor T cells is reduced, and this appears to result in increased production of IgE antibodies to staphylococcal antigens. A neutrophil chemotactic defect may also be present.392 Recurrent bronchitis and pneumonia is a major feature, often due to Staphylococcus aureus though other bacteria and fungi may also be responsible. There is commonly an eczematous dermatitis, mucocutaneous candidiasis, recurrent furunculosis, and cutaneous cold abscesses. The lack of the usual systemic and local inflammatory findings with the abscesses is a striking feature, particularly because most are due

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Box 11.12  Other pulmonary conditions which may be associated with eosinophilia Asthma Hyperimmunoglobulin E syndrome Langerhans cell histiocytosis Infections – Bacterial (Brucella, Mycobacterium) – Chlamydia – Viral (adenovirus) – Protozoal (Pneumocystis, Triomonas) – Fungal (Coccidioides, Histoplasma) • Neoplasms – Bronchogenic carcinoma, bronchial carcinoid – Metastases – Irradiated neoplasms – Lymphoma (Hodgkin and non-Hodgkin, lymphomatoid granulomatosis) • ‘Immunologic’ conditions – Wegener granulomatosis – Rheumatoid disease – Hypersensitivity pneumonitis – Sarcoidosis – Idiopathic pulmonary fibrosis – Cryptogenic organizing pneumonia • Miscellaneous – Hemodialysis • • • •

to Staphylococcus aureus. Pneumonia and cystic lung disease is the most common cause of death, and Aspergillus and/or Pseudomonas infection is usually found at autopsy.393 Mild or mild to moderate eosinophilia occurs in 77–100% of patients.390,391 Occasionally, however, eosinophilia is marked.394 Imaging findings in the chest391,392,395 consist of recurrent infective consolidation (beginning before the age of 3 years) and cyst formation. All the patients in the series of Merten and co-workers,391 in which the average age was 18 years, had lung cysts. Some cysts disappeared after a few years while others were recurrent or persistent. About a third of cysts were multiple and could be very large, occupying much of a hemithorax, while their walls were usually smooth but of varying thickness. The cysts probably represent the residue of lung abscesses or pneumatoceles.393 Other pulmonary findings include empyema, fungal superinfection of

Pulmonary Alveolar Proteinosis Box 11.13  Types of PAP Idiopathic

Secondary • Dust/chemical exposure – Silica – Aluminum – Titanium • Infection-related – Pneumocystis • Hematologic/immunocompromise – Lymphoma – Myeloid leukemia – Severe combined immune deficiency – Lung transplant • Medications • Congenital – Surfactant apoprotein deficiency • Familial

Fig. 11.54  Metastases associated with blood eosinophilia. Frontal chest radiograph of an 82-year-old woman who presented with a subacute history of malaise, weight loss, and cough. There was a peripheral blood eosinophilia of 8.6 × 109/L. The radiograph shows numerous well-defined and poorly defined nodules. The liver was enlarged and contained multiple focal lesions revealing adenocarcinoma on biopsy.

pneumatocele,396 bronchopleural fistula,392,397 bronchiectasis,391,396 and pneumothorax.392,396,398 Eighty percent in Merten’s series had chronic sinusitis.391

PULMONARY ALVEOLAR PROTEINOSIS Pulmonary alveolar proteinosis (PAP) is a rare disorder first described in 1958399 and characterized pathologically by alveolar filling with a lipid-rich, proteinaceous material (positive to periodic acid–Schiff stain), while the lung interstitium remains relatively normal. Its incidence is 0.2–0.5 new cases per 1 000 000 persons each year, and its prevalence is 2–6 cases per 1 000 000 persons.400,401 PAP may be divided into idiopathic and secondary forms (Box 11.13).401 Idiopathic PAP accounts for about 90% of all cases. Secondary forms are seen in association with: • Dust and chemical exposure.402,403 Inhalation of silica as in acute silicosis404 – especially caused by sandblasting,405,406 aluminum dust,407 and particulate titanium.408 • Infections. The association is complicated and some infections (see below) are undoubtedly secondary to primary PAP whereas other infections are themselves probably the primary process that precipitates the proteinosis. An example of the latter is pneumocystis infection, both HIV and non-HIV related.409 • Hematologic malignancy or immunocompromise. An association with hematologic malignancies (lymphoma, myeloid leukemia, myelodysplastic syndrome) is described, particularly in children.410–413 In another review 30% of children with PAP had thymic alymphoplasia.414 PAP is also described with severe combined immune deficiency (SCID) in both mice415 and

humans.416 Three cases of PAP developing in lung allograft recipients performed for conditions other than PAP have been recorded.417 • Medications, including leflunomide,418 imatinib,419 and sirolimus.420 • Congenital or familial PAP. This may be related to surfactant deficiency,421 abnormality of the GM-CSFR alpha gene,422,423 or mutation of the ABCA3 gene.424 The intraalveolar lipoproteinaceous material in PAP consists primarily of surfactant and associated apoproteins.421 Both congenital and primary PAP are associated with deficiency or impaired function of granulocyte–macrophage colony-stimulating factor (GMCSF), which regulates surfactant homeostasis and immune defense.401 Patients with idiopathic PAP all have high levels of autoantibodies against GM-CSF, which neutralize the role of GM-CSF in the differentiation of alveolar macrophages, thus critically impairing the process of surfactant clearance in the lung.401 These antibodies also appear to neutralize the antimicrobial activity of GM-CSF by inducing lung neutrophil dysfunction.425,426 Knockout mice with deficiencies of the GM-CSF, or the β-GM-CSF receptor all develop PAP.427 PAP is most common in adults, particularly between 30 and 60 years of age, although cases are seen in children (including neonates) and up to the age of 72 years.400,427 Sixty to eighty percent of patients are male.400,402,426,427 About 50–70% are cigarette smokers, and the male predominance may be due to the higher frequency of cigarette smoking in males.400,427 In children, PAP is usually associated with surfactant deficiency or immunocompromise, and the disease is progressive and often fatal, whereas adults generally have no underlying disorder. In about one-fifth of cases the onset is acute, with fever, weight loss, and dyspnea, either with or without a superadded opportunistic infection.402 Most of the other cases have an insidious onset with progressive dyspnea and cough. Median duration of symptoms prior to presentation is 7 months.427 Cough is usually dry but is sometimes productive of white sticky sputum. Other features include pleuritic chest pain, hemoptysis,426 and pneumothorax.402 The clinical signs consist of crackles and occasionally clubbing. PAP is one of the conditions in which symptoms and clinical signs may be mild in the face of striking imaging signs (‘clinicoimaging discrepancy’).401,428 In up to 30% of cases the disease is discovered by chest radiography in asymptomatic or minimally symptomatic individuals.400 Seventy percent of patients have a mild to moderate elevation of serum lactate dehydrogenase (LDH). The serum levels of surfactant apoproteins A and D (SP-A, SP-D) are markedly elevated, though nonspecific.429 Antibodies to GM-CSF may be diagnostically

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Fig. 11.55  Pulmonary alveolar proteinosis in a 54-year-old man with mild dyspnea on exertion. A, Chest radiograph shows bibasilar ground-glass abnormality with reticular abnormality. Note the characteristic thin rim of spared lung above the diaphragm (arrows). B, CT shows typical crazy-paving pattern, with septal thickening and intralobular lines superimposed on ground-glass abnormality, without architectural distortion. useful. Respiratory function tests show a restrictive defect with hypoxemia and impaired diffusion.426 Diagnosis is established by BAL showing the characteristic eosinophilic, granular, PAS positive lipoproteinaceous material in the washings.429 A recent report suggests that elevated levels of the apoprotein SP-D in the washings may be specific for PAP.430 In problematic patients it may occasionally be necessary to obtain a transbronchial lung biopsy for histologic study.429 On the chest radiograph, the main findings are consolidation ground-glass abnormality, due to alveolar filling.399 The classic imaging finding is bilateral, symmetric consolidation, or, more commonly, ground-glass abnormality, particularly in a perihilar or hilar and basal distribution (Fig. 11.55).399,402,431 This opacity often has a fine granularity and air bronchograms are unusual. At other times the pattern consists of rather coarse (5 mm), ill-defined acinar nodules, perhaps in part confluent.432 In some cases, septal thickening or reticular abnormality may be seen (Fig. 11.56).399,402,433,434 Although usually symmetric, the consolidation can be asymmetric,433 unilateral,399,426 or lobar.399,410 Sometimes the consolidation is basally predominant,410 peripheral rather than central,428 and multifocal rather than diffuse.426 Lung apices and costophrenic sulci are usually spared, and a thin zone of clear lung immediately above the diaphragm is characteristic, perhaps because diaphragmatic movement helps squeeze proteinaceous material out of the adjacent airspaces. Simultaneous evolution and regression, producing a shifting pattern similar to that found in Löffler syndrome, has been described.435 On HRCT, PAP is characterized by the following features:401,436–441 • Geographic ground-glass abnormality • Lines perpendicular to the pleura and forming polygonal structures, representing thickened interlobular septa • A finer network of intralobular lines • Absence of architectural distortion or traction bronchiectasis. The superimposition of the reticular pattern formed by thickened interlobular septa and intralobular lines on a background of groundglass abnormality produces the characteristic ‘crazy-paving’ pattern

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(Figs 11.55 and 11.56). Imaging changes tend to be diffuse,437,440 but may predominate in any lung region or zone.401,440 Involved areas are bordered by normal lung and have a sharp, geographic margin reflecting lobular boundaries.401 In an AFIP series, 25% of cases were characterized by ground-glass abnormality without crazy-paving pattern.401 Other airspace opacities that may be found include acinar nodules, limited air bronchograms, and areas of consolidation where the density of the opacity obscures underlying vessels. If consolidation is present, the possibility of superimposed infective consolidation should be considered. The ground-glass abnormality is due to accumulation of protein within the alveoli, and the interlobular and interlobular lines are due to expansion of interlobular septa by edema and markedly dilated lymphatics.401 Unusual cases of PAP may be associated with histologic lung fibrosis, indicated by traction bronchiectasis and fissural or architectural distortion.401 Following therapeutic whole-lung lavage the ground-glass opacity decreases440 (Fig. 11.56) and the reticulation may become more prominent.437 The crazy-paving pattern has been described in a wide variety of lung diseases,441,442 including exogenous lipoid pneumonia,443 bronchioloalveolar cell carcinoma,444 drug toxicity, sarcoidosis, nonspecific interstitial pneumonia, organizing pneumonia, pulmonary hemorrhage, Pneumocystis jirovecii pneumonia, and ARDS. The crazy-paving pattern of PAP may distinguished from these other entities in the following ways: clinical presentation is indolent; extent of imaging abnormality is out of proportion to clinical symptoms and physiologic impairment; architectural distortion and traction bronchiectasis are typically absent; distribution is geographic; and thickened interlobular septa are more prominent than in the other conditions mentioned above. Where PAP is the leading imaging diagnosis, it is appropriate to recommend BAL to confirm the diagnosis and exclude other entities such as infection, hemorrhage, bronchioloalveolar cell carcinoma, and lipoid pneumonia. Because of the functional macrophage and neutrophil impairment, complicating infections by pathogenic bacteria431 or opportunistic bacterial, fungal, and viral410 agents are common. In one review,445 15% of 160 patients had such infections, and they were a

Pulmonary Alveolar Microlithiasis

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major cause of death402 before therapeutic lavage was introduced.426 Agents most commonly recorded are Nocardia,402,410,433 Mycobacterium tuberculosis and nontuberculous mycobacteria,446,447 and Cryptococcus.446 It seems likely that nocardial infections have become less frequent following the adoption of therapeutic lavage.429 Radiographic pointers to such an opportunistic infection include the development of focal consolidation, cavitation, and pleural effusion.402 CT may identify focal pneumonia not apparent on chest radiographs.436 PAP improves spontaneously in about 10% of patients.402,426,427 Most of the remaining patients will require treatment, and the standard treatment up to recently has been with unilateral or bilateral saline whole-lung lavage.448 Lavage has virtually eliminated mortality449 and results in complete remission in 75% of patients.426 Chest radiograph or chest CT may be used to decide which side should be treated and to detect any complications.450 Recurrence of PAP has been documented in a patient who had a double lung transplant for progressive disease.451 Recently, small-scale clinical trials of GM-CSF have resulted in clinical improvement in 35–70% of cases, but the value of this treatment remains unclear.427,452

PULMONARY ALVEOLAR MICROLITHIASIS Pulmonary alveolar microlithiasis was first described in 1918.453 It is a rare disorder, with 225 cases recorded in the world literature.454 A recent advance has been the identification of a mutation in the SLC34A2 gene, which encodes a phosphate transporter gene, in all

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Fig. 11.56  Pulmonary alveolar proteinosis (PAP). A, CT of the mid/ lower zones shows extensive bilateral opacity with a geographic distribution. There is both consolidation and ground-glass opacity. A fine reticular pattern with interlobular septal thickening is superimposed on the ground-glass abnormality, producing the ‘crazy-paving’ pattern. B, CT 2 months later at the same level as A following bilateral saline bronchoalveolar lavage. Consolidative and ground-glass opacity have essentially cleared. There is residual reticular opacity but it is much improved. C, CT 2 years later shows recurrence. The geographic nature of the opacity in PAP is well shown.

of 13 patients in two studies.455,456 This gene may also be associated with testicular microlithiasis.455 Alveolar microlithiasis is characterized pathologically by the accumulation of numerous, largely intraalveolar, calcified bodies (calcispherites or microliths). Microliths have a mean diameter of about 200 µm457 and contain calcium phosphate.369 Dystrophic ossification occasionally develops around microliths.457 There have been rare descriptions of extrapulmonary microliths in the testes or kidneys.458–460 Alveolar walls are commonly normal461 but later in the disease interstitial fibrosis may develop together with bullae and blebs.460,462 Although alveolar microlithiasis occurs worldwide, nearly a quarter of recorded patients are from Turkey.454 About 40% of cases are sporadic, while the remainder show a strong familial association,462 consistent with an autosomal recessive transmission.463,464 Other congenital disorders are occasionally associated such as Waardenburg anophthalmia syndrome464 and diaphyseal aclasia.465 There is no gender difference in incidence.461 The disease is commonly first detected in the third and fourth decades,461 but the range is large, with the disorder recorded in premature neonates466 and in an 80-year-old woman.460 Like PAP, gross radiographic changes are often present in the face of minor clinical symptoms. In an analysis of published papers comprising 576 subjects, 50% were asymptomatic at the time of diagnosis.467 The interval between radiographic diagnosis and onset of symptoms may be from 5 to 40 years.463 Later in the course of the disease cough may appear, and in a small proportion of patients hemoptysis, clubbing, hypertrophic osteoarthropathy,454 pneumo­ thorax, dyspnea, and cor pulmonale develop.461,462 Respiratory func-

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Fig. 11.57  Pulmonary alveolar microlithiasis. Chest radiograph shows extensive coarse reticular abnormality, with polygonal structures formed by thickened interlobular septa. The minor fissure is thickened. A black pleural line is visible in the right lower chest. tion tests have been abnormal in about a third of reported cases and most commonly show a restrictive defect or a decreased carbon monoxide diffusing capacity.461 Identification of microliths in expectorated sputum or BAL can be diagnostic,468,469 and wholelung lavage has been used to relieve symptoms of dyspnea.468 The chest radiograph is characteristic,462 with innumerable, widespread, pinpoint nodules of calcific density. Nodules are less than 1 mm in diameter, but they may summate in areas to give a groundglass, reticular, or more coarsely nodular (up to 5 mm) pattern (Fig. 11.57).470 The radiographic opacity, which tends to be greatest at the bases, sometimes shows subpleural462,470–472 or peribronchovascular accentuation.470 In advanced disease the radiographic opacity is so great that anatomic landmarks become completely obscured. Thus the heart may ‘vanish’470 or even appear as a transradiant area on a penetrated radiograph. The parietal pleural region may appear as a thin dark band (Fig. 11.57),462 which is shown by CT to be due to subpleural cysts or paraseptal emphysema.473–476 Pleural fissures can appear dense, thickened (Fig. 11.57), and beaded,477 and septal lines are occasionally seen.470,478 Bullae and blebs develop with late fibrosis,460–462 and these are particularly well seen on CT.457,479 Such blebs and bullae probably predispose patients to pneumothorax and pneumomediastinum, which are recognized complications.460,479 On CT, the predominant distribution of abnormality is usually posterobasal (Fig. 11.58).457,464,471,473–476,479–482 Because of volume averaging of the tiny microliths, their calcific density may not be apparent, resulting in a micronodular or ground-glass pattern, even on thin-section CT. With larger nodules, the calcification may be visible. The occasional 5  mm nodule presumably represents dystrophic ossification seen histopathologically. Ground-glass abnormality is the most common pattern, seen in nine out of 10 patients in a Brazilian study.476 Calcification may be uniform, producing dense consolidation (seen in 50%) (see Fig. 3.118B), or may be linear or nodular. Linear calcification may be subpleural, with nodular fissural thickening, or along interlobular septa or bronchovascular bundles (Fig. 11.58).464,471,473,474,479,482 Crazy-paving pattern may be

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Fig. 11.58  Pulmonary alveolar microlithiasis. A basal CT shows predominantly posterior micronodular opacity. Nodules are not visibly calcified because of the wide window setting. Selective accumulation of calcific deposits accentuates various structures including: superficial and deep interlobular septa (yellow arrows), some of which are nodular and irregular; major fissures (red arrow) and subpleural parenchyma peripherally (blue arrow). A Harrington rod is present.

seen.483 All CT studies showed airspaces (blebs or bullae) either apically,473,474,479,480 or throughout the lung, or subpleurally.471,473,480 The cysts represent dilated alveolar ducts.484 A striking subpleural peel of paraseptal emphysema may be seen.473,475 There is a single case report of MR findings in alveolar microlithiasis.480 This surprisingly shows the calcific regions as high signal on T1-weighted images (and low on T2-weighted images) – an appearance also described in metastatic pulmonary calcification485 and ascribed to a surface effect of diamagnetic calcific particles in shortening T1 relaxation. Very few patients with microlithiasis are recorded in whom a preceding normal chest radiograph has been documented.486,487 The micronodular opacities in microlithiasis usually appear to be of calcific density from the beginning. A few patients, however, have been described with nodulation that was initially of soft tissue density and that later became definitely calcific.486 Scintigraphic uptake of technetium-99m diphosphonate by the microliths may be seen,488,489 but absence of uptake does not exclude the diagnosis.490 FDG-PET can show increased metabolic activity, with a standard uptake value of 7.3 in one case.491 The prognosis is variable. Many patients remain asymptomatic with stable chest radiographs for many years.488 Others, sometimes after many years of stability, go on to experience pulmonary fibrosis or cor pulmonale and ultimately die of the disease.457,460,492

Other causes of pulmonary calcification The imaging differential diagnosis of pulmonary alveolar microlithiasis includes several other conditions which cause diffuse pulmonary calcification (Box 11.14).469 Metastatic calcification occurs when calcium salts deposit in previously normal tissue, whereas dystrophic calcification occurs in previously damaged tissue. Metastatic pulmonary calcification is commonly found at autopsy in hemodialysis patients, but is not commonly seen on premortem imaging.469 Several factors predispose to pulmonary calcification in patients with renal failure.469,493 Acidosis contributes

Pulmonary Alveolar Microlithiasis to leaching of calcium from the bone. Hyperparathyroidism may cause pulmonary calcification in both the presence and absence of uremia. Intermittent alkalosis favors the precipitation of calcium salts, and also increases the activity of alkaline phosphatase, which catalyzes the release of phosphates. Finally, a diminished glomerular filtration rate causes hyperphosphatemia, elevating the calcium phosphate product, favoring crystallization. Use of vitamin D may contribute, as hypervitaminosis D has been associated with metastatic and vascular calcification. However, patients with markedly elevated calcium phosphate product may escape pulmonary calcification, and pulmonary calcification may occur in early azotemia without appreciable elevation of calcium phosphate product. For unclear reasons, metastatic pulmonary calcification may be seen in 5% of orthotopic liver transplant recipients.469 Metastatic calcification is not usually associated with clinical symptoms or physiologic impairment, but occasionally may contribute to renal failure.469 Its main importance is that it may lead to radiographic misdiagnosis of pneumonia, interstitial lung disease, or lung edema. On chest radiographs, metastatic pulmonary calcification is usually upper lung predominant, in contrast to the lower lung predominance of pulmonary alveolar microlithiasis, and is commonly associated with widespread vascular calcification (Fig. 11.59).494 The deposited material is usually amorphous whitlockite, which contains magnesium, rather than crystalline hydroxyapatite, which is Box 11.14  Differential diagnosis of diffuse pulmonary calcification • Metastatic pulmonary calcification • Renal failure • Previous infection – Varicella – Histoplasmosis • Pulmonary ossification in lung fibrosis • Dendriform pulmonary ossification • Alveolar microlithiasis • Amyloidosis • Sarcoidosis • Pneumoconiosis

A

seen in bone and vascular calcification.493 On CT,494–497 the calcification may be too fine to cause calcific attenuation values, and may appear as centrilobular ground-glass abnormality, quite similar to that seen in hypersensitivity pneumonitis.498,499 Other CT findings may include diffuse ground-glass attenuation, and patchy consolidation.500 The nodules may show ring calcification.495 The presence of vascular calcifications in the soft tissues and mediastinum may provide an important clue to this diagnosis. Metastatic calcification may occur in coexisting pneumonia.501 Metastatic calcification may or may not improve following aggressive treatment, and may occasionally resolve spontaneously.500 Calcifications due to previous infection are usually less profuse and more punctate than in pulmonary alveolar microlithiasis. Calcification in lesions of sarcoidosis,502 pneumoconiosis, or amyloidosis are usually associated with other typical features of these disorders.

Diffuse pulmonary ossification Diffuse pulmonary ossification is an uncommon condition characterized by metaplastic bone formation in the lung parenchyma.503 Pathologically, the ossification may be nodular or dendriform. Nodular ossification commonly occurs in individuals with untreated chronic mitral valve disease or other causes of chronic left heart failure. The dendriform pattern is sometimes associated with pulmonary inflammation, and is most common in men aged between 40 and 60.503 It may be familial.504 It may be seen in isolation, or may be associated with pulmonary fibrosis or bronchiectasis. We have seen several cases associated with chronic aspiration, and believe that it represents an uncommon pattern of lung injury response. Dendriform pulmonary ossification in patients with lung fibrosis505 is usually quite localized, and associated with typical features of pulmonary fibrosis (see Fig. 10.6, p 567). In a systematic study, punctate calcifications indicating ossification were found in five of 75 patients with usual interstitial pneumonia, and in none of 44 patients with nonspecific interstitial pneumonia.506 Pulmonary calcification or ossification also occurs in patients with amyloidosis.469,503 On CT, nodular pulmonary ossification is associated with densely calcified 1–5 mm nodules that can coalesce or be trabeculated and may be difficult to distinguish from healed granulomatous infec-

B

Fig. 11.59  Metastatic pulmonary calcification in chronic renal failure. A, Chest radiograph shows upper lung predominant confluent dense nodules. B, CT shows poorly defined, confluent centrilobular nodules, some of which are calcified. Marked coronary artery calcification is visible.

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Chapter 11 • Idiopathic Diffuse Lung Diseases Box 11.15  Neurofibromatosis I – diagnostic criteria • Positive if two or more of the following are presented in an adult: – Café au lait macules: six or more over 15 mm maximum diameter – Neurofibromas: more than two, or one plexiform neurofibroma – Freckling in axillary or inguinal regions – Optic glioma – Lisch nodules (iris hamartomas): two or more – Distinctive osseous lesions (e.g. splenoid dysplasia) – First-degree relative affected Based on Neurofibromatosis Conference Statement.513

Table 11.3 Thoracic lesions of neurofibromatosis Location Fig. 11.60  Dendriform pulmonary ossification. CT through the lower lungs shows a characteristic combination of hyperattenuating linear opacities (arrows) and punctate nodules, with some associated reticular abnormality. tion.503,507 This condition should be suspected in individuals with underlying mitral valve disease or left heart failure who have calcified pulmonary nodules. The dendriform pattern of ossification manifests as 1–4 mm fine nodular and linear branching opacities in which calcification may or may not be visible (Fig. 11.60).469 Associated findings of lung fibrosis or bronchiectasis may be seen.

NEUROCUTANEOUS SYNDROMES Five conditions are included in the neurocutaneous syndromes: neurofibromatosis, tuberous sclerosis, ataxia telangiectasia, Sturge– Weber syndrome, and von Hippel–Lindau syndrome. In these conditions aberrant development of neuroectodermal tissue causes neurologic abnormalities associated with skin and eye lesions. In some cases there are additional mesodermal and endodermal abnormalities.508 Neurofibromatosis and tuberous sclerosis are considered in this section. Pulmonary lymphangioleiomyomatosis (LAM) is also discussed here because, although it is not a neurocutaneous disorder, it has many features in common with pulmonary tuberous sclerosis.

Neurofibromatosis type I Neurofibromatosis type I (von Recklinghausen disease) is an autosomal dominant neurocutaneous syndrome with a prevalence rate of about 1 per 3000 births,509 one-half being mutations. The abnormal gene (nf 1) has been identified on chromosome 17.510 No sex or racial predominance has been found. The principal features are café au lait spots, peripheral nerve tumors (neurofibromas and schwannomas) that particularly affect the skin (fibroma molluscum), and Lisch nodules (pigmented hamartomas of the iris). However, there are a multitude of other possible findings and virtually any organ can be affected.511 There is marked phenotypic variability of neurofibromatosis I. A set of diagnostic criteria has been proposed510 (Box 11.15). Neurofibromatosis has a variety of manifestations in the chest (Table 11.3). In a review of chest radiographs of 156 patients, extrapulmonary nodules or masses were seen in 22 (14%), skeletal abnormalities in 16 (10%), pulmonary nodules or masses in eight (5%), emphysema in six (4%), pleural abnormalities in five (3%), and bilateral interstitial abnormality in three (2%).512

682

Chest wall

Lesion Skin Nerves Spine Ribs

Mediastinum

Lungs

Middle Posterior

Cutaneous tumors (fibroma molluscum) Intercostal nerve tumors Kyphoscoliosis, vertebral body modeling abnormality Modeling and architecture abnormality, notching Neural tumor Lateral meningocele, neural tumor, pheochromocytoma Interstitial fibrosis, cysts, airway tumors

Chest wall involvement Cutaneous tumors, especially if they are polypoid, appear as nodules on the chest radiograph (Fig. 11.61). If they are peripheral and unequivocally cutaneous in position, they establish the diagnosis of neurofibromatosis. If, however, they are projected over the lungs, they may resemble intrapulmonary nodules. It should not be assumed that because some nodules are unequivocally cutaneous they all are;514 to do so runs the risk of missing a primary or secondary pulmonary neoplasm. The latter consideration is particularly important, since in about 5% of patients with generalized neuro­ fibromatosis, neurofibrosarcomas develop,515 often metastasizing to the lungs.516 A neural tumor arising from intercostal nerves away from the spine, if large enough, will give rise to the signs of an extrapleural soft tissue mass (Fig. 11.61),517 possibly with pressure remodeling (notching) of adjacent upper or lower rib borders (see Fig. 15.16, p 1012). The resulting well-marginated defect is usually relatively wide and shallow compared with the notches seen in coarctation of the aorta. A primary defect in bone formation may also give rise to rib notching,518 as well as the characteristic ‘twisted ribbon’ deformity.519,520 Another described pattern of rib abnormality is altered architecture with cyst formation.521 Bony thoracic abnormality, particularly kyphoscoliosis, is common and, although a prevalence of about 10% is usually quoted for kyphoscoliosis,520 some series have recorded it in up to 60% of patients.519 Kyphosis occurs only in the presence of scoliosis.522 Although the appearance of the scoliosis may be nonspecific, some patterns are characteristic, in particular low thoracic, short-segment, angular scolioses involving five vertebrae or fewer in the primary curve.520,522,523 Vertebral lesions include the following modeling and developmental abnormalities: vertebral body scalloping (posterior, lateral, or anterior);524 hypoplastic or pressure remodeled pedicles, particularly mesial flattening; intervertebral foramen enlargement; and transverse process hypoplasia. The most common and best known

Neurocutaneous Syndromes

Fig. 11.62  Neurofibromatosis. Mid-zone CT shows extensive cyst formation from 2 mm to 25 mm diameter. Scattered amongst the cysts are numerous linear opacities indicating inter- and intralobular septal thickening. In the right mid-zone, air-spaces are beginning to coalesce giving the appearance of panacinar emphysema. Other airspaces appear to contain preserved centrilobular vessels. There is a skin nodule (arrow). (Courtesy of Dr. H Massouh, Surrey, UK.)

Fig. 11.61  Neurofibromatosis. Frontal chest radiograph shows a large left pleural-based mass, bilateral upper lobe volume loss and a spontaneous right pneumothorax. There has been previous right thoracotomy for resection of a neural tumor. Multiple cutaneous nodules (arrows) provide a pivotal clue to the diagnosis. of these abnormalities is posterior vertebral scalloping, which is typically sharply marginated and smooth and extends over several segments.519,523 It is usually associated with, and probably causally related to, dural ectasia, although it will occasionally result from pressure by a tumor or simply be caused by developmental hypoplasia.

Mediastinal masses Posterior mediastinal masses are usually caused by neural tumor (neurofibroma or neurilemmoma and their malignant counterparts) or a lateral thoracic meningocele. Lateral thoracic meningoceles are produced by protrusion of dura and arachnoid through an exit foramen, and the majority occur at the apex of a scoliosis on its convex aspect, particularly between T3 and T7.511 Right-sided lesions predominate,525 and about 10% are multiple.526 They are often, but not invariably, associated with vertebral scalloping, increased interpedicular distance, pedicle thinning, expansion of intervertebral foramina, and rib erosion.526 Sometimes, the associated ribs and vertebrae are fused and hypoplastic.525 Affected patients are commonly middle aged (30–60 years) and more often than not asymptomatic.526 Some consider that lateral thoracic meningoceles are the most common posterior mediastinal mass in neurofibromatosis,511,525 but this is not borne out in all series.519 The imaging features of lateral thoracic meningocele are discussed in Chapter 14 (p 890). Neural tumors are usually benign and cause well-demarcated, rounded paraspinal masses (discussed in detail in the section on posterior mediastinal masses). Neural tumors can become malignant with a transformation rate that is probably of the order of 5%.508 The third type of associated posterior mediastinal mass is the pheochromocytoma, with a 1% prevalence in neurofibromatosis.511 It should be considered a possible explanation for hypertension in neurofibromatosis.

Two types of middle mediastinal masses are recognized in neuro­ fibromatosis: one localized and the other diffuse. Discrete masses are the result of solitary neurofibromas, neurilemmomas, or their malignant counterparts affecting the vagus or phrenic nerves. They are more commonly left sided and usually asymptomatic, but they may cause hoarseness if the recurrent laryngeal nerve is affected.527 In a review of 29 such tumors arising from the vagus, a third were associated with neurofibromatosis I and only one lesion was sarcomatous.527 Diffuse masses often involve adjacent mediastinal compartments, extending down from the thoracic inlet to the hilar level, and may be bilateral. They are the result of plexiform neurofibromas, normal nerve elements bizarrely arranged in a network of fusiform swellings that often infiltrate and incorporate adjacent fat and muscle.508 On CT they appear as low-attenuation masses, often in all compartments of the upper mediastinum, surrounding vessels in an infiltrative fashion.528 The attenuation of these lesions may be close to that of water, mimicking paraspinal cysts.529 Although usually slow growing and asymptomatic, they can cause tracheal and bronchial compression.530

Lung involvement Although parenchymal fibrosis or bullous abnormality was previously reported to occur in 10–20% of individuals with neuro­ fibromatosis,531,532 recent reports of this entity have been sparse. Reported findings have included linear and reticular abnormality,533,534 honeycombing,532 and upper lung bullae or cysts (Fig. 11.62).531,532,534,535 A review of the chest radiographs of 156 patients with neurofibromatosis identified bullae or cysts in six patients, all of whom were current or former smokers.512 Interstitial changes were found in three individuals, all of whom had alternative explanations for lung fibrosis. Thus, lung fibrosis or cystic disease in this condition is not as common as previously reported. Pulmonary hypertension may occur, and may be associated with a mosaic attenuation pattern on CT.536 Rarely a neurofibroma or neurilemmoma produces a parenchymal mass that appears as a peripheral well-demarcated, lobulated nodule.537 Just as rarely these lesions may arise endobronchially and cause obstructive bronchiectasis.532 A patient is also described in whom there were multiple 2 mm intramural schwannomas involving the airways of a single lung subsegment.538 Metastatic neuro­ fibrosarcoma may also account for parenchymal nodules.512

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Lymphangioleiomyomatosis and tuberous sclerosis complex The tuberous sclerosis complex (TSC) and the pulmonary condition LAM are closely linked genetically. In both conditions, linkage mapping has identified two separate gene loci on chromosomes 9 (TSC1) and 16 (TSC2), which encode for the proteins hamartin and tuberin respectively.539,540 These genes control cell growth, survival, and motility through the Akt/mammalian target of rapamycin (mTOR) signaling pathway. In patients with the full TSC syndrome, the mutations are present in all somatic cells, and neoplasms and dysplasias occur when ‘second hit’ mutations occur in affected organs. In individuals with spontaneous LAM, mutations are confined to the lung, kidneys, and lymph nodes.539 TSC has a prevalence of 6–10 per 100 000 population541 (about half that of neurofibromatosis) and is autosomal dominant with an equal sex incidence. About 60% of cases are sporadic, arising by mutation.541,542 Penetrance is high but expression variable giving rise to various phenotypes and difficulty in defining the condition for diagnostic purposes. The classic clinical features make up a triad (Vogt) of mental retardation, epilepsy, and dermal angiofibromas (adenoma sebaceum). However, only about one-third of patients with tuberous sclerosis have all features of this classic triad.543 Additional major manifestations include other skin lesions (ungual fibromas, shagreen patches, fibrous forehead plaques, achromic patches), cerebral and paraventricular hamartomas, renal angiomyolipomas, retinal phakomas, bone lesions including calvarial sclerosis, and rhabdomyomas of the heart. Currently the diagnosis is established clinically and considered to be definite, presumptive (probable), or suspect depending on the mix of signs present in an individual.544,545 The following findings are definitive features, even when present in isolation: cortical tuber, subependymal nodules, giant cell astrocytoma, retinal hamartomas, facial angiofibromas, ungual fibroma, fibrous forehead plaque, and multiple angiomyolipomas.544 In TSC, CT scanning has proved particularly useful in the detection of the highly prevalent intracranial calcifications546 and renal angiomyolipomas and cysts,547 whereas MR is highly successful at identifying soft tissue central nervous system (CNS) lesions.548 Although previous reports have indicated that clinical pulmonary involvement is unusual in TSC, occurring in 1–2.3% of cases,549–551 more recent series using CT have indicated that 25–35% of women with TSC have pulmonary cysts.552,553 As indicated above, considerable clinical, imaging, and pathologic similarities exist between pulmonary involvement in tuberous sclerosis and that found in LAM (Table 11.4). On pathologic study the lungs in TSC/LAM show perivascular smooth muscle proliferation and small adenomatoid nodules,554 some of which have been identified as type II pneumocyte hyperplasia.555–557 Although micronodular type II pneumocyte hyperplasia is characteristic of tuberous sclerosis, it is not specific and is also occasionally seen in LAM and occasionally in patients without either condition.558 The adenomatoid proliferations are a few millimeters in diameter and are scattered throughout the lung.550 Proliferating smooth muscle spreads into the walls of airspaces, bronchioles, lymphatics, arterioles, and venules and causes obstruction of these structures. The clinical and imaging manifestations of pulmonary involvement in TSC are produced by obstruction of the airways by LAM tissue, producing cysts. Venular obstruction by LAM may cause hemoptysis. Some workers consider that smooth muscle proliferation tends to spare lymphatics554,559 but this is not a universal view.560 Chylothorax may occur, but appears to be less common than in sporadic LAM.542 The clinical features of patients with pulmonary involvement by tuberous sclerosis549 differ from those of tuberous sclerosis in general. Almost all patients with TSC who develop LAM are women, with only three case reports of this entity developing in

684

Table 11.4  Comparison of spontaneous lymphangioleiomyomatosis (S-LAM) and LAM occurring in tuberous sclerosis (TSC/LAM)542 Feature

S-LAM

TSC/LAM

Familial Female sex Age Adenoma sebaceum Epilepsy Intelligence (IQ) Dyspnea Pneumothorax Lymph node involvement Chylous pleural effusions, ascites Hemoptysis Cysts on CT Nodules on CT Renal angiomyolipoma Hepatic angiomyolipoma

No All Reproductive No No Normal Yes Yes Common Yes Yes Yes Uncommon Common Uncommon

Some Almost all Any age 85% 20% Low (46%) Yes Yes Unusual Uncommon Yes Yes Common Very common Common

males.539,561 Other manifestations of TSC such as pneumocyte hyperplasia558 or intrapleural cysts562 may develop in males. Patients with pulmonary tuberous sclerosis are older than the general population with tuberous sclerosis (the mean age of presentation with respiratory symptoms is about 34 years), and with a lower prevalence of mental retardation (46%) and epilepsy (20%). However, most patients have adenoma sebaceum,563 and 60% have renal angiomyo­ lipomas. Once respiratory symptoms develop, they tend to dominate the clinical picture, with progressive dyspnea, recurrent pneumothoraces (in 50%) and, less seriously, cough and hemoptysis. The radiographic findings in the chest consist of an interstitial process with symmetric nodular, reticular, or reticulonodular opacities. The nodules are small, about 1–2 mm,550,564 and are often overshadowed by a more dominant, linear element.550 The changes may be diffuse or basally predominant.564 With progression of the disease the linear and reticular element becomes more marked and honeycomb and cystic changes develop.550,564,565 The cysts tend to be less than 1  cm in diameter. Large cysts are uncommon.565 Unlike most other interstitial processes the lung volume tends to be increased because of small airway obstruction, focal emphysema, air-trapping,566 and cyst formation. Respiratory function tests support this observation, and show airflow obstruction, increased static compliance, and increased total lung volume, together with impaired carbon monoxide diffusion.550,551 CT findings are similar to those in LAM (see below) (Fig. 11.63).551,567,568 The main difference is that nodules are more commonly seen in tuberous sclerosis (Fig. 11.64).542,557,569 In a study by Moss et al.,553 nodules were found in 25 of 59 females and two of 10 males with TSC. Nodules were seen with or without the presence of LAM cysts. These nodules probably represent areas of adenomatoid pneumocyte hyperplasia558 (see above). On dynamic expiratory HRCT, the cysts of pulmonary tuberous sclerosis demonstrate air-trapping.566 In a review of 256 patients with sporadic LAM and 67 with LAM in TSC, three or more nodules measuring more than 2  mm were found in eight (12%) of those with LAM/TSC compared with only three (1%) of those with sporadic LAM. The extent of lung abnormality was less than that in sporadic LAM. Hepatic and renal angio­ myolipomas were much more common in tuberous sclerosis, seen in 33% and 93% of cases respectively, compared with 2% and 32% in sporadic LAM. Atypical findings may include unilateral or upper lung predominant cysts.570

Lymphangioleiomyomatosis

A

B

Fig. 11.63  A, CT of the upper zones in a 29-year-old woman with tuberous sclerosis. There are numerous well-defined 2–12 mm cysts scattered evenly throughout the lung. The intervening parenchyma is normal. Posteriorly on the left there is a large bulla. B, CT of the juxtadiaphragmatic region in the same patient shows that the cysts extend into the costophrenic angles.

Fig. 11.64  Tuberous sclerosis with nodule. Coronal CT reconstruction shows scattered small cysts and a 5 mm nodule in the right upper lobe (arrow), thought to represent micronodular pneumocyte hyperplasia. Bone changes are described and may be visible on the chest radiograph, notably an expanded dense rib resembling fibrous dysplasia or Paget disease.508 Sclerotic lesions within the spine are also described.571 Mortality varies; in one series, 85% of patients with pulmonary tuberous sclerosis died within 5 years from either cor pulmonale (59%) or pneumothorax (41%).549 The prognosis in other series in which hormone treatment has been used has been better with a 78% survival in the Mayo Clinic series followed for an average of 17 years.551 There was no difference in prognosis between TSC patients with and without pulmonary involvement.

LYMPHANGIOLEIOMYOMATOSIS LAM (also called lymphangiomyomatosis) is a rare disorder seen in females of childbearing age, characterized by smooth muscle proliferation occurring both in the lungs (related to lymphatics, airways, vessels, and alveolar septa) and also in the mediastinum and retroperitoneum (related to lymphatics). It causes recurrent

pneumothoraces, chylous effusions, hemoptysis, and cystic lung disease with eventual respiratory failure. Although not a neurocutaneous disorder, LAM shares many pulmonary features with pulmonary tuberous sclerosis. It differs from the latter in that it is not heredofamilial and lacks the neuroectodermal features of TSC, such as adenoma sebaceum, epilepsy, and mental retardation. Furthermore, some findings, such as lymph node enlargement and chylothorax, that are unusual in pulmonary tuberous sclerosis are common in LAM. The features of LAM and pulmonary tuberous sclerosis are compared in Table 11.4. When the lungs are involved in TSC the pathology is that of pulmonary LAM. LAM is commonly associated with mutations in the TSC1 gene, but not in the TSC2 gene.572 Genetic and protein alterations characteristic of TSC are commonly found in the lung tissue of patients with LAM, and also in angiomyolipomas.572,573 Although some writers have suggested that LAM should be considered to be a presumptive feature of TSC,544,545 the vast majority of women with LAM do not have any manifestations of intracranial TSC, even in the 50% of patients who have associated renal angiomyolipomas.574–576 Also, there is no recorded case of a woman with PLAM and renal angiomyolipomas having had a child with TSC. In the lungs LAM is characterized pathologically by a benign, disorderly proliferation of smooth muscle in the interstitium in relation to vessels, airways, lymphatics, alveolar septa, and pleura.369,577 Scattered air-filled cysts lined by flattened epithelial and ciliated bronchiolar elements578 are distributed throughout the lungs and have smooth muscle bundles which may form nodules (myoblastic foci) in their walls.554 Other small nodules are produced by micronodular type II pneumocyte hyperplasia, but these are much more common in tuberous sclerosis.558 Cysts are thought to arise from air-trapping produced by muscle proliferation in small airways.369 Some workers, however, consider there is an element of collagen/elastin destruction as well,579 possibly metalloproteinase induced.580 Scattered hemosiderin deposits with or without an associated foreign body granulomatous reaction may also be seen,554 the hemosiderin being derived from small hemorrhages secondary to muscular obstruction of venules. The muscle cells in LAM stain with HMB-45 (a monoclonal antibody derived from melanoma hybridomas) and in the context of examining lung smooth muscle this finding is highly sensitive and specific for LAM.581 The pathologic changes in the lung described above are similar to those in pulmonary tuberous sclerosis but in LAM muscle proliferation is also found in relation to the lymphatic ducts and nodes in the mediastinum and retroperitoneum,559,582–585 findings that are very unusual in pulmonary tuberous sclerosis. Chylothorax and chyloperitoneum produced by such lymphangiomyomas is thus a common feature of LAM,586 but unusual in pulmonary tuberous

685

Chapter 11 • Idiopathic Diffuse Lung Diseases sclerosis. In one series of patients with LAM, 69% had mediastinal and 53% retroperitoneal node involvement pathologically.582 Lymphangiomyomas of the mediastinum and retroperitoneum, associated with chylothorax and chylous ascites, may be found in the absence of lung involvement by LAM.582 Some of these latter patients have been reported to develop lung disease many years later.582 Renal angiomyolipomas, which are a characteristic finding in TSC, are also found in LAM, with a recorded prevalence of about 50% when screening abdominal CT is performed.574,575 The prevalence of angiomyolipoma in TSC may be up to 93%.587 The abnormal smooth muscle in angiomyolipomas stains with the HMB-45 antibody as does the smooth muscle in lung lesions.588 The etiology of LAM is unclear. A number of observations suggest that it may be related to female hormone secretion: LAM occurs only in females, usually those of childbearing age; its onset and exacerbations sometimes coincide with pregnancy and parturition; the abnormal smooth muscle commonly has estrogen/progesterone receptors; and LAM may be exacerbated by exogenous estrogens.589,590 Despite this evidence of the importance of hormones in LAM, hormone manipulations of various sorts have proved at best to be of only modest benefit. Virtually all patients with LAM are female and most are of childbearing age with a mean age at presentation of about 30–40 years.591,592 There is one case report of LAM occurring in a male.593 The oldest recorded patient at presentation was 76 years of age.590 The most common initial manifestations are dyspnea, cough, pneumothorax, chest pain, hemoptysis, and chylothorax. Respiratory function tests, in those who are symptomatic, usually show airflow obstruction, increased total lung capacity, increased compliance, and impaired diffusion.275 Pneumothorax occurs as a presenting manifestation of LAM in up to 40–50% of patients (see Fig. 11.66 below),594–596 while 60–80% develop pneumothorax at some time during the course of their disease.595,597,598 In patients presenting with pneumothorax, the chest

A

radiograph often shows no other evidence to suggest LAM as the underlying cause,599 though computed tomography will usually show cysts. Pneumothorax is more likely in those with cyst size larger than 5  mm.600 Pneumothorax is recurrent in about 70% of cases, and may even recur after chemical or surgical pleurodesis.539,597 LAM is a recognized cause of a bilateral pneumothorax597,598 and should be a primary consideration in a female of reproductive age presenting with bilateral pneumothorax without other radiographic abnormalities.599 Chylous pleural effusions are another recognized presenting feature of LAM, and were the initial event in 7% of patients in three series.554,594,597 Chylous effusions occur during the course of the disease in 10–23% of cases.597,598,601 Effusions may be unilateral or bilateral and are typically large and recurrent.582,583 Hemoptysis occurs in 20% of cases598 and is occasionally the initial feature.554,595 Chylous ascites may occur at some stage in the illness but is uncommon (7% of one series)554 and is usually accompanied by a pleural effusion.582 Some unusual manifestations include chylopericardium, chyluria, and chyloptysis.582,598 In a group of seven patients, delayed pulmonary parenchymal changes developed up to 5 years after the recognition of lymph node involvement or chylous effusion.582 The earliest radiographic signs of LAM consist of symmetric diffuse fine nodular, reticular, or reticulonodular opacities.554 With time the reticular pattern, which may be very delicate and sharp,554 predominates and tends to become coarser and more irregular (see Fig. 11.66 below). Cysts may become visible.275 Lung volumes are increased in about 50% of cases.567,594,595,602 The combination of a reticular interstitial pattern and increasing lung volume is characteristic of LAM (Fig. 11.65), contrasting with the progressive loss in volume that accompanies most other interstitial lung disorders.275 In advanced disease the proximal pulmonary arteries enlarge, with the development of cor pulmonale.554

B

Fig. 11.65  A 54-year-old woman with LAM. A, Chest radiograph shows marked hyperinflation with a diffuse coarse reticular pattern. There is a small left effusion. B, CT shows profuse round cysts, each with a well-defined thin wall. The cysts are so numerous that they appear clustered.

686

Birt–Hogg–Dubé Syndrome

Fig. 11.66  Lymphangioleiomyomatosis. CT of the upper zones in a 25-year-old nonsmoking woman who presented with a pneumothorax. A small pneumothorax is still present in the right oblique fissure. The lung parenchyma is normal apart from a moderate number of well-defined cysts ranging in size from 2 mm to 8 mm. The CT features of LAM may be diagnostic in the correct clinical context. Cysts are the pathognomonic feature (Figs 11.65 and 11.66).567,603–608 The cysts are usually multiple, thin-walled, and distributed in a uniform fashion in lung that is otherwise essentially normal (Fig. 11.66). Cysts are clearly demarcated by a thin even wall (1–2  mm thick) (Fig. 11.66) and are usually rounded, although larger ones are occasionally polygonal or bizarrely shaped, sometimes suggesting coalescence.567,602 Vessels are typically seen at the margins of the cysts, rather than at their centers, as is characteristically seen with emphysema. The size of cysts ranges from 2 to 50 mm, with most in the 5–15 mm range. Cyst size increases as the disease becomes more widespread.605 In general, cysts show no preferential distribution of any type, although two studies record relative sparing of the extreme apices.604,606 Cystic involvement of the juxtaphrenic lung and costophrenic sulci can be helpful in distinguishing LAM from pulmonary Langerhans cell histiocytosis (PLCH), this area is usually relatively spared in PLCH (see Chapter 8, Page 454). The number of cysts varies widely, depending on the clinical presentation; cysts are usually extensive in those who present with symptoms of pulmonary impairment, but often quite sparse in those who present with complications such as pneumothorax, pleural effusion, etc. Cyst size usually decreases on expiration.609,610 A density mask technique may be used to quantify disease extent, and correlates quite closely with physiologic evaluation (Fig. 11.67).611,612 Patients with a history of pleurodesis have greater impairment of physiology (forced expiratory volume in 1 second, DLCO, and total lung capacity) than those without.612 There has been one report of LAM occurring with a normal HRCT but a positive biopsy.605 In addition to cysts, other CT abnormalities are occasionally seen in LAM. Small centrilobular nodules have been described,613 perhaps representing nodules of hyperplastic muscle or pneumocyte hyperplasia. Occasionally septal thickening may be seen, presumed to be due to lymphatic obstruction.606,608 Small focal areas of ground-glass opacity were found in 59% of patients in one series, and ascribed to hemosiderosis or muscle cell proliferation.594,613 Localized consolidation may occur,605 presumed to be due to pulmonary hemorrhage. Fissural irregularity may be seen, perhaps related to adjacent cysts.602 Chylous pleural effusions (see Chapter 15, p 1027) are found in 10– 20% of cases.597,598,601 They may be unilateral or bilateral586 and are typically large and recurrent.582 Pleural effusion and pneumothorax may coexist.586 Lymphadenopathy is seen on CT in 13–50% of cases607,614 but is usually not visible on the chest radiograph.

CT has enhanced awareness of the intraabdominal manifestations of LAM. In addition to renal angiomyolipomas (found in 30–50% of patients) (Fig. 11.68), other manifestations include hepatic angiomyolipomas (2%), lymphangiomyomas (Fig. 11.69) (29%), enlarged retroperitoneal lymph nodes, chylous ascites (10%), and dilation of the thoracic duct or cisterna chyli (4%).542,574 Lymphangio­ myomas in the pelvis or elsewhere may present with painful swelling as the first manifestation of LAM.598,615 On CT, they usually are shown to contain material of water density, and they may exhibit diurnal variation in size.616 Other features may include retroperitoneal hemorrhage589 and lymphedema of legs.589 Mortality of LAM is about 10–20% at 10 years after onset of symptoms, but varies widely.539,617,618 There is no established specific treatment for LAM. Progesterone is widely used, but data to support its use are weak. There are ongoing clinical trials of sirolimus, which has resulted in decreased size of angiomyolipomas.539 Lung transplantation is a therapeutic option, with 5-year survival after transplantation of about 65%.619 Several cases of recurrence of LAM in the transplanted lung (Fig. 11.70) have been reported.620–622 The diagnosis of LAM can be made with confidence when characteristic cysts are seen on CT in association with hepatic or renal angiomyolipomas or chylothorax. If these extrapulmonary findings are not present, biopsy is usually recommended to exclude other potential causes of cystic lung disease such as lymphoid interstitial pneumonia, light-chain deposition disease, and Birt–Hogg–Dubé syndrome.539

BIRT–HOGG–DUBÉ SYNDROME Birt–Hogg–Dubé syndrome, first described in 1977,623 is an autosomal dominant genetic disease characterized by dermal fibrofolliculomas (follicular hamartomas), clear cell renal cell carcinomas, renal oncocytomas, spontaneous pneumothorax, and lung cysts.624 Thyroid neoplasms,623 colonic polyps,625 and renal cysts have also been described. The responsible gene, BHD, which encodes for the protein folliculin, has been identified, and may represent a tumorsuppressor gene. The condition appears to be equally common in men and women.626 Patients typically present in middle age (median age 54 years)627 but may be identified at an earlier stage if they are screened as part of a family survey, or if they present with spontaneous pneumothorax, since the median age of occurrence of pneumothorax is 34 years. Dermal fibrofolliculomas, found in 90% of cases, are characterized by asymptomatic papules over the face, neck, and/or upper trunk.627 Other cutaneous lesions including angiofibroma, trichodiscoma, and perifollicular fibroma may also occur. Renal tumors of varying histologies occur in 20–35% of individuals; the prognosis of these tumors is relatively good, and death from metastatic renal cancer is quite uncommon.627 Twenty-four percent of individuals with this syndrome have a history of unilateral or bilateral spontaneous pneumothorax, usually occurring before clinical presentation with the full-blown syndrome.626 Occurrence of pneumothorax is related to the presence of cysts, to total cyst volume, and to the volume of the largest cyst.626 Pneumothorax recurs in about 75% of cases. Lung cysts are found on CT in 85–90% of patients with the syndrome (Fig. 11.71).627 Pathologically, the lung cysts of this condition are characterized by intraparenchymal or subpleural collections of air surrounded by normal lung or by a thin fibrous wall.628 The cysts range in size from 3 mm to 8 cm, and may be sparse or innumerable. Although usually diffuse, they tend to involve the lower lungs more than the upper lungs, and large oval subpleural cysts, often para­ cardiac, are notable in several published cases.626,629–632 The condition should be suspected by the radiologist when spontaneous pneumothorax occurs in a nonsmoking patient, when basal predominant subpleural cysts or bullae are identified, and when associated renal masses are identified.

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LUNG DISEASE ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE Ulcerative colitis and Crohn disease are associated with a wide variety of pulmonary complications (Box 11.16). Although these complications were thought to be relatively uncommon, the association may be stronger than previously thought. In a study of 36 patients with inflammatory bowel disease, physiologic abnormality was found in 21 (58%), and CT showed abnormality in 52%.653 The commonest findings were expiratory air-trapping, and upper lobe reticular abnormality. CT abnormality was more common in Crohn disease than in ulcerative colitis. A retrospective review of 2192 patients diagnosed with airways disease at an outpatient respiratory clinic identified 37 cases of inflammatory bowel disease, rep-

688

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Fig. 11.67  Quantitative CT of lymphangioleiomyomatosis. A, Coronal CT reconstruction in a woman with moderately severe LAM shows diffuse cysts of varying sizes. B, Density mask technique outlines all pixels with CT attenuation less than −950 HU. The areas of low attenuation are color coded by lobe. C, Threedimensional reconstruction provides a psychedelic representation of cyst size.

resenting a fourfold increase in prevalence over expected.654 The increased prevalence was found in patients with diagnoses of chronic bronchitis, bronchiectasis, COPD, and chronic cough, but not in those with asthma, and there was no significant difference between ulcerative colitis and Crohn disease. Pulmonary complications may precede the diagnosis of inflammatory bowel disease, or may occur years after the initial diagnosis, and even after complete colectomy for ulcerative colitis. Indeed there is some suggestion that pulmonary complications may be more common after surgical treatment, perhaps because antiinflammatory treatment is withdrawn.655 Both Crohn disease and ulcerative colitis can be associated with an intense tracheobronchitis, sometimes associated with subglottic, tracheal, or bronchial stenosis.633,634 Bronchiectasis may also occur (Fig. 11.72). Small airway involvement can have a pattern of pan-

Lung Disease Associated with Inflammatory Bowel Disease

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B

Fig. 11.68  Lymphangioleiomyomatosis with angiomyolipoma. A, CT shows multiple round or elliptical cysts of varying sizes. The largest cysts are grouped along the major fissure. B, Abdominal CT shows large left renal angiomyolipoma (arrows).

Fig. 11.69  Mediastinal lymphangioma in a 44-year-old woman with lymphangioleiomyomatosis. Axial CT shows enlarged lymph nodes of water attenuation, anterior and posterolateral to the trachea.

Fig. 11.70  Lymphangioleiomyomatosis with recurrence in the transplanted lung. A 49-year-old woman with LAM who had a right lung transplant 2 years previously. CT shows a hyperexpanded, grossly cystic end-stage lung on the left. The transplanted lung on the right shows numerous small (1–5 mm) cysts, proven by biopsy to be caused by LAM.

Box 11.16  Respiratory disease associated with inflammatory bowel disease • • • •

Tracheobronchitis633–635 Tracheal or bronchial stenosis633–636 Bronchiectasis633–635 Bronchiolitis – Panbronchiolitis pattern637 – Constrictive bronchiolitis pattern638 – Granulomatous bronchiolitis639

• • • • • •

Organizing pneumonia640–642 Lung fibrosis643,644 Pulmonary hemorrhage645 Granulomatous lung disease (Crohn disease only)639,646–648 Amyloidosis649 Drug-induced disease – Sulfsalazine650–652

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Fig. 11.71  Birt–Hogg–Dubé syndrome. A, Axial CT shows scattered cysts in the upper lobes. B, Axial CT through the lower lungs shows oval cysts, some with septa, and located in a paracardiac and peribronchovascular location. There is a right basal pneumothorax.

ERDHEIM–CHESTER DISEASE

Fig. 11.72  Large and small airways disease in ulcerative colitis. CT in a patient with longstanding ulcerative colitis shows marked bronchial wall thickening, right middle and lower lobe bronchiectasis, and focal tree-in-bud pattern in the right lower lobe.

bronchiolitis637 or, in Crohn disease, of granulomatous bronchiolitis.639 In a series of seven patients with inflammatory airway disease related to ulcerative colitis,633 all had bronchial wall thickening, six had bronchiectasis, and three had airway stenosis. Four patients had evidence of small airways disease with a pattern similar to that of panbronchiolitis. Parenchymal abnormalities associated with inflammatory bowel disease include organizing pneumonia,639–642 pulmonary hemorrhage,645 and granulomatous infiltration in Crohn disease.639,656 In patients presenting with an organizing pneumonia pattern, and in those with eosinophilic pneumonia, it is important to be aware of the treatment history, as sulfasalazine is a common cause of these abnormalities.650–652 More recently, the common use of infliximab, an antitumor necrosis factor agent, in treatment of inflammatory bowel disease has been associated with development of interstitial pneumonitis characterized by diffuse ground-glass abnormality.657 Infliximab and similar agents may also be associated with tuberculosis and nontuberculous mycobacterial infection.

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Erdheim–Chester disease is a very rare non-Langerhans cell histiocytosis characterized by symmetric lower limb osteosclerosis caused by histiocytic infiltration. At the time of diagnosis about 50% of patients have extraskeletal involvement that mainly affects the skin, retroperitoneum, retroorbital region, heart, hypothalamus/posterior pituitary, and lungs. Age at presentation is about 50 years with a wide range (7–84 years) and there is no sex predilection.658 The commonest presenting symptom is bone pain and skeletal radiology shows a characteristic symmetric long bone (particular legs) metaphyseal/diaphyseal sclerosis, which is very active on radionuclide bone scan.659 Osteolytic lesions in flat bones are described. Lungs are involved in about 15–30% of patients658,660 with about 30 cases in the world literature up to 2003.661–663 Pulmonary involvement causes progressive shortness of breath and some patients develop end-stage lung and die of respiratory involvement. Histologically there is an interstitial lung infiltrate of foamy histiocytes with additional lymphocytes, giant cells, and fibrosis. These changes are distributed along lymphatics and affect visceral pleura, interlobular septa, and bronchovascular bundles.661 The histiocytes are distinguished from Langerhans cells by the absence of CD1a staining, and by the absence of Birbeck granules on electron microscopy.664 Also, the CT features of this condition are quite distinct from those of Langerhans histiocytosis. Chest radiographic appearances661 consist of diffuse interstitial opacities, usually described as reticular. These changes commonly show a mid- to upper zone predominance and may be accompanied by cysts or honeycomb opacity. Septal lines and thickened fissures and pleura are also described. On CT the major finding is widespread smooth thickening of interlobar fissures and interlobular septa (Fig. 11.73).663 The coarse peribronchovascular and septal thickening may mimic pulmonary lymphangitic carcinoma,665 particularly when associated with mediastinal or pleural infiltration. These findings are usually associated with multifocal ground-glass attenuation, and centrilobular nodules.663 Focal consolidation may be seen.666 Intervening lung may be normal667 or replaced by cystic/ emphysematous areas.660,668 Pleural effusions are seen in about half the patients.663 Review of the soft tissues showed pericardial thickening or areas of soft tissue infiltration in six of nine patients in the series by Wittenberg et al.663 Periaortic or perirenal infiltration is particularly characteristic, and may be associated with vascular

Storage Diseases

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narrowing.669 Rarely, Erdheim–Chester disease may involve the lung without any evidence of skeletal involvement.663

STORAGE DISEASES Pulmonary involvement may occur in several storage diseases, including Gaucher disease, Niemann–Pick disease, Fabry disease, and Hermansky–Pudlak syndrome (Table 11.5).664 Gaucher disease is characterized by hepatosplenomegaly and bone marrow infiltration. Although physiologic abnormalities are quite common in this condition, symptomatic pulmonary involvement is rare; in a study of 411 patients, symptomatic lung disease was found in only four adults and four children.670 It is characterized pathologically by masses of Gaucher cells (alveolar macrophages stuffed with glucocerebroside) in the alveoli and interstitium, producing an appearance reminiscent of desquamative interstitial pneumonia.664 On the chest radiograph, it is characterized by reticular abnormality, or less commonly a miliary pattern. Reported abnormalities on CT have included a reticular pattern, a mosaic pattern, ground-glass abnormality, and septal thickening.671–673 Other intrathoracic manifestations have included pulmonary hypertension,664,670 recurrent pneumonia,670 upper zone honeycombing,674 and extramedullary hematopoiesis.675 Niemann–Pick disease is associated with accumulation of sphingomyelin in the reticuloendothelial system and central nervous

B

Fig. 11.73  Erdheim–Chester disease. A–C, CT images show a characteristic combination of findings: thickening of interlobular septa and interlobar fissures, mediastinal infiltration by soft tissue attenuation material, pleural thickening, and perirenal infiltration.

system.664 Foamy ‘sea-blue’ macrophages accumulate in the alveoli, resulting in a miliary or reticulonodular pattern on chest radiograph. Ground-glass abnormality is the salient CT finding in most patients, though occasionally septal thickening may predominate.676–680 Subpleural cysts,681 consolidation,679 or profuse centrilobular nodules682 may also be seen (Fig. 11.74). In a series of 53 adults and children with this condition, the primary CT findings were ground-glass abnormality, interlobular septal thickening, and intralobular lines, more extensive in the lower lungs. The extent of abnormality on CT correlated weakly with physiologic impairment.683 The extent of abnormality may decrease following whole lung lavage.679 In Fabry disease, glycosphingolipids accumulate in the heart, kidney, skin, and brain.664 Pulmonary involvement appears to be rare,684,685 though pulmonary hemorrhage may occur, related to endothelial dysfunction.664 Lysosomal storage of sphingolipid products may occur in the lungs, particularly around bronchioles and vascular walls. Patients typically present with dyspnea or chronic cough.685,686 Physiologic airway obstruction is common,687 and was found in 36% of 25 unselected cases.685 Mixed obstructive and restrictive lung disease may occur, characterized by mosaic attenuation688 or patchy ground-glass abnormality.689 The abnormalities may respond to enzyme replacement. Hermansky–Pudlak syndrome is an autosomal recessive syndrome characterized by partial oculocutaneous albinism, platelet dysfunction, and accumulation of ceroid in various tissues including the lung.664 The syndrome occurs quite extensively in individu-

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Chapter 11 • Idiopathic Diffuse Lung Diseases Table 11.5  Pulmonary involvement in storage diseases Disease

Storage metabolite

Site of storage in lungs

Other sites of involvement

Gaucher disease

Glucocerebroside

Alveolar walls and alveolar interstitium

Liver, spleen, bone marrow

Fabry disease

Glycosphingolipid

Not defined

Kidney, heart, skin, brain

Niemann–Pick disease

Sphingomyelin

Interstitium

Liver, spleen, nodes, brain

Hermansky–Pudlak syndrome

Ceroid

Alveolar macrophages

Albinism, platelet dysfunction

Imaging findings Reticular abnormality, ground-glass abnormality, pulmonary hypertension Pulmonary hemorrhage, obstructive and infiltrative lung disease Miliary or reticulonodular pattern Lung fibrosis

extensive abnormality, and seven had extensive abnormality on CT. The CT findings varied with the severity of the abnormality. In patients with minimal disease, septal thickening was the most common finding, followed by ground-glass abnormality and reticular abnormality was the most prominent finding, and subpleural honeycombing was seen in about half of the patients (Fig. 11.75). The abnormality showed subpleural predominance, but was generally diffusely distributed in the craniocaudal plane, with some cases showing predominance in mid- or lower lung zones. Five cases showed peribronchovascular thickening. This condition should be considered in the imaging differential diagnosis of nonspecific interstitial pneumonia and usual interstitial pneumonia.

AMYLOIDOSIS Amyloidosis is a disorder in which amyloid, a substance consisting largely of autologous protein fibrils, is deposited extracellularly in a variety of organs and tissues. Amyloid has a pathognomonic staining reaction because of its unique structure, binding with Congo red and giving a green birefringence in polarized light. In the past the classification of amyloidosis has depended on the identification of various clinicopathologic entities with major subdivisions into primary/secondary amyloidosis and local/systemic disease. However, current categorization is based on the type of fibrillar protein in the amyloid deposit.693–695 Important proteins are identified in the following list, with the suffix ‘A’ being used to indicate amyloid followed by an abbreviation for the protein itself:

Fig. 11.74  Niemann–Pick disease. HRCT shows widespread ground-glass opacity and reticular pattern with posterior consolidation and subpleural cysts. als in northwest Puerto Rico. The syndrome is associated with slowly progressive lung fibrosis occurring in individuals aged between 20 and 40 years. A syndrome of inflammatory bowel disease may also be present.690 Pulmonary involvement in this syndrome is most commonly associated with a mutation on the HPS1 gene,691 but seven HPS genes have been identified.692 On the chest radiograph, a reticular abnormality is usually seen (Fig. 11.75).691 In a study of 67 patients with this condition,691 31 had normal high resolution CT, 22 had minimal abnormalities, seven had moderately

692

• AL (amyloid light chain). AL is made up from the variable fragment of immunoglobulin light chains, γ chains more commonly than κ. The light chains are manufactured by plasma cells and AL amyloidosis is now considered to be a plasma cell dyscrasia with a monoclonal gammopathy. AL amyloidosis is also seen in association with multiple myeloma and macro­ globulinemia. This condition was formerly called primary amyloidosis. • AA (amyloid A). This is an α-globulin derived from serum amyloid A (SAA) which is an acute phase reactant produced particularly in infectious and inflammatory conditions.696 AA amyloidosis used to be called reactive systemic amyloidosis or secondary amyloidosis. AA amyloidosis is also seen in familial Mediterranean fever. • ATTR (amyloid transthyretin). Transthyretin is the same as prealbumin, a normal plasma protein that can act as a carrier for thyroxine. Genetically determined mutations substitute amino acids and alter its structure, giving rise to more than 20 heredofamilial forms of amyloidosis. Rarely other proteins may be involved in other familial forms of amyloidosis. • Aβ2M (amyloid β2-microglobulin). This normal component of plasma is not cleared and metabolized in patients on chronic

Amyloidosis

A

B

Fig. 11.75  Hermansky–Pudlak syndrome. A, Chest radiograph in a 29-year-old man with partial albinism shows basal-predominant parenchymal opacity. B, CT shows basal reticular abnormality compatible with lung fibrosis.

Table 11.6  Major clinical forms of amyloidosis and amyloid deposition with type of respiratory involvement* Category

Protein/clinicopathogenic entity

Chest involvement

Systemic amyloidosis

AL – AL amyloidosis (immunocyte dyscrasia amyloidosis) Amyloidosis with monoclonal gammopathy (formerly primary systemic amyloidosis) Multiple myeloma Waldenstrom macroglobulinemia Others AA – AA amyloidosis (formerly secondary amyloidosis or reactive amyloidosis) ATTR – Heredofamilial amyloidosis (minority not ATTR) Neuropathic Nephropathic Cardiomyopathic ATTR – Senile systemic amyloidosis (formerly senile cardiac amyloidosis) Ab2M – Hemodialysis associated AL – Lung

Diffuse parenchymal (usually subclinical) ± lymph nodes Lymph nodes per se Pleural effusion

Localized amyloidosis

Senile (heart, joints) Cerebral amyloid angiopathy Endocrine (thyroid, pancreas, atrium) Skin, bladder, larynx, eye

Diffuse parenchymal (subclinical) Diffuse parenchymal (rarely)

Diffuse parenchymal – Tracheobronchial Parenchymal Nodular Diffuse ± Lymph nodes – – Metastatic medullary carcinoma of thyroid –

*Modified from Pepys.698

hemodialysis, leading to a form of amyloidosis unique to this clinical situation. • Polypeptide hormones. A number of these can generate amyloid including atrial natriuretic factor (isolated atrial amyloid) and procalcitonin (medullary carcinoma of the thyroid). At least 25 types of amyloid protein have been described to date.697 Some of these predispose to hereditary amyloidosis, which does not usually involve the chest. A classification of the major clinical forms of amyloidosis and amyloid deposition together with the type of chest involvement is given in Table 11.6.

Amyloid is laid down in a number of conditions and as part of the aging process. Organ dysfunction occurs if enough amyloid material accumulates. Broadly speaking the deposition may be generalized (systemic amyloidosis) or it may be localized to a single organ. Local deposition within an organ may itself be diffuse or focal. However, cases with overlap features are not uncommon. Difficulties most commonly occur with so-called localized disease which, although not systemic, is in many instances clearly not limited to a single organ. This occurs for example in the chest when lung or airway disease can be accompanied by mediastinal and cervical adenopathy.699–701

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Systemic amyloidosis Respiratory involvement is an unimportant part of systemic amyloidosis, and clinical and imaging findings in the chest are usually incidental or secondary to a complication such as heart failure. Should direct involvement by amyloid deposition occur, it takes the form of interstitial parenchymal disease, lymphadenopathy, or pleural disease.

AL amyloidosis AL amyloidosis may be associated with monoclonal gammopathy (formerly primary amyloidosis), with multiple myeloma, and/or with B cell lymphoma. In AL amyloidosis, infiltration with amyloid material affects mesenchymal tissues and, to a lesser extent, kidney, liver, and spleen. There is a 2 : 1 male predominance with a mean age at presentation of about 60 years.702,703 The clinical features of AL amyloidosis may be nonspecific, such as weight loss and weakness, or may be part of one or more classic disorders, including nephrotic syndrome, carpal tunnel syndrome, restrictive cardiomyopathy, peripheral neuropathy, orthostatic hypotension, and occasionally macroglossia, purpura, papular skin rash, and arthropathy.704 Some 80% of patients will have protein­ uria. Electrophoresis of serum shows a protein spike in 40% and, on immunoelectrophoresis, there is a monoclonal protein in 68%. When urine and blood test results are combined, 89% of patients will have a monoclonal protein.704 The diagnosis can be made by abdominal fat aspiration which is positive in approximately 80% of patients.705 Bone marrow aspiration is positive in about 50% of patients and allows assessment of plasma cells for the possible presence of myeloma. If both abdominal fat and bone marrow aspiration is negative, rectal biopsy (80% positive) is recommended, followed if necessary by biopsy of a suspect organ. The median survival in a series of 153 patients with AL amyloidosis was 12 months, with fewer than 20% alive at 5 years.703 Heart failure was associated with a particularly bad prognosis. Patients with cardiac involvement survive 4–6 months, while those without cardiac involvement at the time of diagnosis have a median survival of 30 months.706 Myeloma is also associated with a poor prognosis.704 Involvement of the lungs on pathologic examination is common in AL amyloidosis, with a prevalence ranging between 70% and 92%,707–711 but it is rarely of clinical importance. For example in a major clinical review of 229 patients with AL amyloid, there is no mention of the lung being clinically affected,704 while in a later report of 153 patients with AL amyloidosis just two patients had diffuse interstitial pulmonary involvement.703 Reports of significant lung involvement occur mostly in individual case reports or in small selected series.707,712–716 In one such series, five of 12 patients with ‘primary amyloidosis’ developed radiographic and pathologic evidence of diffuse alveolar septal amyloidosis and, in one patient, it contributed to death709 as it did in another small series.716 A further point of importance is that cardiac amyloidosis commonly accompanies lung involvement,710 and the clinical and imaging signs of pulmonary amyloid infiltration can be obscured by heart failure.716,717 Persistent imaging changes despite adequate treatment of heart failure should raise the possibility of amyloid infiltration of the lungs.718 The prevalence of lung involvement in AL amyloidosis is the same in patients with isolated gammopathy or myelomatosis.710 Isolated massive mediastinal deposition of amyloid, presumably in nodes, has been described in myeloma-related AL amyloidosis.719

AA amyloidosis AA amyloidosis (reactive systemic amyloidosis/secondary amyloidosis) is usually secondary to chronic infectious or inflammatory processes (see above).720,721 Rare cryptogenic cases are described.721,722 In Western societies the most common cause is undoubtedly rheu-

694

matoid arthritis711,721,723 in which the prevalence of amyloidosis is usually quoted as 10%, although this figure seems rather high.724 In a review of 64 patients with AA amyloidosis from the Mayo Clinic, 48% were secondary to rheumatoid arthritis.721 Other causes are: chronic rheumatic diseases – Sjögren syndrome, ankylosing spondylitis, psoriatic arthritis, juvenile chronic arthritis, Behçet syndrome; chronic infections – tuberculosis, leprosy, osteomyelitis, bronchiectasis, chronically infected decubitus ulcers; chronic inflammations – inflammatory bowel disease, familial Mediterranean fever; and neoplasm – Castleman disease,725 Hodgkin or non-Hodgkin lymphoma, renal cell carcinoma.702,720,721 When AA amyloidosis is caused by rheumatic disorders, the underlying disease is usually severe and longstanding with a median duration of disease of 19 years in one series.723 The organs most commonly affected by amyloid deposition are the kidneys, liver, spleen, and adrenals. AA amyloidosis usually presents with renal disease (proteinuria, nephrotic syndrome, renal insufficiency, hypertension) or hepato­ splenomegaly. Gastrointestinal involvement is not uncommon, occurring in about 20% of patients, and is manifest as malabsorption, nausea, and vomiting. A small number of patients (5%) present with goiter. The prevalence of lung involvement pathologically varies considerably in different series. Two studies give a prevalence rate of 1–5%,707,710 whereas in others the prevalence approaches 100%.709,724 These discrepancies are probably unimportant as the involvement is usually diffuse within the lung and not severe enough to cause functional or imaging changes. There have been a few reports of significant clinical lung involvement.709,722,726 The distribution of amyloid deposition (alveolar septal vs perivascular) differs from patient to patient and affects the type of pathophysiologic disturbance. Predominant perivascular deposits can give pulmonary arterial hypertension.727

Imaging findings The chest radiograph is normal in the majority of patients with generalized amyloidosis and lung involvement.728 When abnormalities are seen, the commonest finding is that of an interstitial process reflecting the predominantly septal and perivascular nature of amyloid deposition.710 The radiographic appearances in the AA and AL forms are probably similar, but descriptions in AA amyloidosis are rare.722 Diffuse parenchymal amyloidosis is also seen in senile systemic and familial amyloidosis, and as a lung limited process (see below). The interstitial infiltration is manifest as a diffuse micro­ nodular, reticulonodular, or linear pattern with accentuation of bronchovascular structures.716,729 Such changes are usually diffuse and symmetric, but they can be segmental.711 In time the nodules may become conglomerate or calcify.707 CT descriptions are few.722,730–732 The main findings are nodules and linear opacities (Fig. 11.76). In general nodules are in the 2–4 mm range but larger nodules, a centimeter or more in diameter, are described.732 Nodules range in number from 10 to innumerable with a diffuse or predominantly subpleural distribution. Some nodules are calcified. Linear opacities are mainly basal and peripheral and are produced by thickened interlobular septa or irregular interstitial lines (Fig. 11.76). These linear opacities may also calcify (Fig. 11.76B). Other less common abnormalities include ground-glass opacity, honeycombing, and traction bronchiolectasis.732 Since septal thickening and groundglass abnormality can be produced by hydrostatic lung edema733 this can be a source of confusion in patients with cardiac amyloidosis. Pleural effusions in amyloidosis are commonly caused by heart failure secondary to myocardial infiltration,707,709 or by nephrotic syndrome. However, amyloid involvement of the pleura is seen pathologically734,735 and undoubtedly on occasion causes pleural effusion.732,736–740 In a study of 636 patients with AL amyloidosis, 35 (6%) had persistent effusions requiring three or more thoracenteses;735 these patients had a very poor prognosis, with median survival of 1.8 months in untreated patients. Hilar and mediastinal nodal enlargement (Fig. 11.77) is not described in AA amyloidosis, and is uncommon in localized

Amyloidosis

A

B

Fig. 11.76  AL alveolar septal amyloidosis in a 53-year-old man. The patient was thought to have heart failure, but diffuse interstitial lung opacity persisted in the face of normal cardiac function. Further investigation including transbronchial lung biopsy revealed AL amyloidosis secondary to myeloma. A, CT shows widespread interstitial opacity consisting of subpleural and parenchymal nodules, enlarged centrilobular structures, irregular thickening of interlobular septa, and peribronchovascular thickening. B, CT imaged on mediastinal settings shows calcific densities within septa. This combination of findings is suggestive of amyloidosis: differential diagnosis might include dendriform pulmonary ossification.

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Fig. 11.77  AL amyloidosis – mediastinal nodal and pleural involvement. The patient was a 61-year-old man who presented with neck swelling, cough, and weight loss. Initial mediastinal and cervical adenopathy was followed by the development of a large right pleural effusion. There was an IgG gammopathy with biopsy evidence of pleural and nodal amyloidosis but no evidence of disease elsewhere. A, Chest radiograph shows massive, mainly right-sided, mediastinal adenopathy. B, CT at the level of the aortic arch (arrow) demonstrates massive adenopathy and a right pleural effusion. C, CT at mid-left atrial level shows massive lymphadenopathy containing flecks of calcification (arrows) in the azygoesophageal recess. There is also a right pleural effusion.

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Fig. 11.78  Airway amyloidosis in a 57-year-old man. A, CT at the level of the inferior pulmonary vein shows mural irregularity and thickening of segmental bronchi caused by amyloid deposits which are also heavily calcified. B, CT of the lower zones shows bronchiectasis at the left base secondary to more proximal airway obstruction.

amyloidosis, but is quite common in AL amyloidosis, either as the sole imaging finding in the chest711,736,741–743 or with interstitial disease.707,732,744 In one series of 12 patients with diffuse lung involvement (83% with AL amyloidosis) CT showed that thoracic lymphadenopathy, either alone or with interstitial disease, was the commonest finding (in 75% of cases).732 Both mediastinal and hilar nodes may be involved, often massively, giving a pattern that may resemble sarcoidosis.736 Nodal calcification is common (Fig. 11.77C).736,745 The pattern of calcification is usually described as coarse or nonspecific; it may occasionally be of the eggshell type.741 Nodal enlargement has also been described in AL amyloidosis associated with multiple myeloma746 and Waldenström macroglobulinemia.709,741 Amyloidosis associated with lymphoproliferative disease may be associated with cystic lung disease.747,748 In these individuals, it is unclear whether the cysts are due to the amyloid or to the associated lymphoproliferative disease. In particular, several cases of amyloidosis have been described in patients with Sjögren syndrome who developed benign or malignant lymphoproliferative disease.749–751 This complication should be suspected when the CT scan of a patient with Sjögren syndrome demonstrates a combination of cysts and regular or irregular nodules, more marked in the lower lungs. However, it is unlikely that one can distinguish between lymphoproliferative disease and amyloidosis as a cause of these nodules.

Localized amyloidosis Localized amyloidosis may affect either the lung parenchyma or the airways (Table 11.7). These structures are usually involved independently;716 but very occasionally both are affected together.752 The frequency of airway involvement is about the same as that of parenchymal involvement.753 A few cases are also recorded in which there is isolated amyloidosis of mediastinal nodes.

Tracheobronchial amyloidosis Amyloid may occur in the airways as focal or diffuse submucosal deposits of AL amyloid;754–756 both are considered together here. The mean age of patients in a large review was 53 years, with a range of 16–76 years.757 Twice as many men as women experience the disease.737 Affected patients are often symptomatic728 for several

696

Table 11.7  Localized forms of lower respiratory tract amyloidosis with relative percentage prevalence Classification

Prevalence (%)

Tracheobronchial

45

Parenchymal

8 44 4

Form Multifocal submucosal plaques or diffuse narrowing Tumorlike masses Nodular: solitary/multiple Diffuse alveolar septal

years before they finally present,758 an indication that the disease progresses relatively slowly. The major symptoms are cough, dyspnea, hemoptysis, stridor, and hoarseness.737,758 A number of patients are believed initially to have asthma,759,760 and recurrent pulmonary infections are common.737 Airway amyloid is more commonly diffuse than focal.753,761 When diffuse, it can involve the trachea and main stem, lobar, and proximal segmental bronchi, together or in part. This involvement can be demonstrated by bronchoscopy, by spiral CT, preferably with three-dimensional or multiplanar imaging,762 or by MRI.732 Such examinations show multiple concentric or eccentric strictures and mural nodules (Figs 11.78 and 11.79). Amyloid tissue is commonly partly calcified, and usually spares the posterior membrane763 (Fig. 11.79). Local as opposed to diffuse lesions give rise to endoluminal masses (amyloidomas) that may be indistinguishable from neoplasms on imaging.753,764 In the trachea, amyloidomas are usually subglottic and may be calcified or ossified.765 Localized airway amyloid shows intermediate signal intensity on T1-weighted images and low signal on T2-weighted images.765 In patients with diffuse or focal airway lesions, the chest radiograph may be normal759 or may show one of a number of obstructive features, most commonly collapse, which may be seen in more than 50% of patients.737 Other manifestations include recurrent pneumonia, obstructive hyperinflation, and bronchiectasis (Fig. 11.79).766 A few patients have had hilar or mediastinal masses on plain chest radiography or on CT, usually representing nodal enlargement.767,768 Such nodes may be calcified.701

Amyloidosis

A B

C

If treatment is required, the amyloid deposits may be removed, by intermittent bronchoscopic resection,769 or laser photoresection.760 Other treatment options include stenting and radiation therapy.770,771 Prognosis is not good, and there is a tendency for lesions to recur 6–12 months after treatment.737 In one review of 39 patients, 21 were well at 4–6 years, but 18 had died, 12 from respiratory causes.737

Parenchymal nodular amyloidosis This form of organ-limited amyloidosis produces one or more parenchymal nodules. It is a rare condition, with only 55 reports in a 1983 literature review.753 Reviews of previous cases have appeared at regular intervals.734,737,772,773 Pathologically773 amyloid nodules are discrete and often subpleural, puckering the adjacent pleura to which they may be adherent. They are firm, well-demarcated but not encapsulated, and, when sectioned, waxy. Microscopically, lung tissue is replaced by eosinophilic amyloid containing nests of plasma cells and lymphocytes surrounded peripherally by a low-grade inflammatory infiltrate with giant cells. Calcification, cartilage formation, and ossification within the tumor are common. Bronchioles, alveolar septa, and blood vessels in the region of the tumor often contain amyloid as well. Amyloid is of the AL type774 and usually polyclonal though monoclonal cases are reported.775

Fig. 11.79  Tracheobronchial stenosis due to amyloid in a 70-yearold woman. A, CT through distal trachea shows irregular narrowing and mural thickening, sparing the posterior tracheal membrane. B, CT through distal bronchus intermedius shows similar findings, with complete obstruction of right middle lobe bronchus resulting in right middle lobe collapse. C, CT with mediastinal window settings shows calcification in the thickened bronchial wall.

The mean age at presentation in several series was 68 years,734,772,773 the youngest patient being 38 years old;776 sex incidence has been equal. Unless the disease is extensive, the patients are usually asymptomatic, with only occasional reports of cough and hemoptysis.753 The nodules may be single or multiple (Fig. 11.80). In some series both patterns have been equally prevalent,737 whereas in others multiple nodules have been predominant.772 When tumors are multiple, the numbers vary from two to innumerable, with twothirds being bilateral and one-third unilateral.772 There is no lobar predilection737,773 but on CT they tend to be peripheral or subpleural.732 Characteristically, nodules are sharp and round,728 both radiographically and on CT, but they may also be oval, lobulated,718,732 irregular,736,777 or ill-defined and spiculated resembling a cancer.718,732,778 Marginal irregularity is presumed to be due to amyloid infiltration of septa, blood vessels, and airways adjacent to the amyloidoma.779 Generally, in any one patient, the nodules vary in size and shape. Some authors stress that a radiograph with multiple nodules of different shapes should raise the possibility of amyloidosis. Nodules are commonly 0.5–5  cm in diameter, but range from micronodular718,780 to massive – up to 15 cm in diameter. Calcification is quite common in both small728,773 and large nodules; in the latter it is variously described as irregular, cloudy, flocculent, or stippled. It may occur centrally or throughout the nodule.718,728,772 Calcification is detected in approximately 30–50% of cases,737,752 depending on the method of assessment. Although calcification

697

Chapter 11 • Idiopathic Diffuse Lung Diseases

A

C

may be seen on the plain radiograph,728 computed tomography is more sensitive.781 Calcification is clearly a very helpful finding that may suggest the nature of such lesions.718 Although cavitation was described in 11% of cases in one review series,737 this is probably an overestimate.744 It would seem generally to be a rare complication.728,782 Occasionally, the nodules are locally confluent and mimic consolidation. The nodules tend to behave in a rather indolent fashion, growing slowly and sometimes remaining stable over several years.752 In rare cases they grow more rapidly, behaving like a neoplasm.772,777 On MRI, nodules are isointense with muscle on T1-weighted images and hypointense on T2-weighted images.777 In a few cases, additional mediastinal lymphadenopathy has been described.711,734,753,783 Nodules of amyloid are occasionally seen on a background of lymphoid interstitial pneumonia in patients with Sjögren syndrome (see p. 602) (Fig 11.81). The diagnosis is usually established by thoracotomy or percutaneous needle biopsy.784 In patients with one or a few nodules only, the prognosis is excellent, and recurrence after removal of a nodule, though recorded, is extremely rare.785 Very occasionally, the disease is so widespread that it contributes to780 or causes death.734 Because amyloid nodules may show increased metabolic

698

B

Fig. 11.80  Parenchymal nodular amyloidosis. A, B, Chest radiographs obtained 4 years apart show a slowly growing oval nodule in the right lower lung. C, CT through the right lower lobe shows a noncalcified solitary pulmonary nodule, resected because of concern for malignancy, but proven to be due to amyloidosis.

activity on scanning with FDG-PET, scanning cannot be reliably used to discriminate between amyloid, lymphoma, and lung cancer.778,786,787

Parenchymal alveolar septal disease Although alveolar septal deposition of amyloid is typical of systemic amyloidosis, it is occasionally found in disease that appears to be limited to the lung.737,761,788,789 Unlike patients with the systemic disorder most patients have had symptoms and deaths are recorded.788 Pathologically, amyloid deposition in the interstitium may be diffuse or micronodular.761 The imaging pattern is of an interstitial process with fine linear or reticulonodular opacities that can become confluent. Micronodular calcification and cyst formation are described.789 On CT, reticular abnormality, septal thickening, and small well-defined 2–4  mm nodules are seen, mainly in the subpleural region (Fig. 11.76).732,790 The diffuse micronodular pattern may sometimes be accompanied by larger nodules, and they may be considered as one end of the spectrum of parenchymal nodular amyloidosis.711,718,780,791 These patients are often sympto-

References matic. Alveolar septal, micronodular, and nodular parenchymal amyloidosis may thus be regarded as a continuum.

PULMONARY LIGHT CHAIN DEPOSITION DISEASE

Fig. 11.81  Benign pulmonary lymphocytic infiltration and amyloidosis. Lower zone CT in a 44-year-old woman who had dyspnea and lower zone reticulonodular opacity on the chest radiograph. Investigation revealed airflow obstruction and reduced diffusion capacity. Antinuclear antibodies and rheumatoid factor were present in the serum. The CT shows multiple thin-walled cysts ranging in size from 2 mm to 50 mm together with a number of irregular nodules (arrows). Histologically there was a lymphocytic infiltrate and widespread amyloid deposition including cyst wall involvement.

Light chain deposition disease is an entity characterized by nonamyloid light chain deposition in multiple organs, with almost universal involvement of the kidney. Histologically, the abnormality does not have the fibrillary appearance or Congo red staining characteristic of amyloidosis. Pulmonary involvement in systemic light chain deposition disease is relatively uncommon792 and usually characterized by asymptomatic nodules. However, there are several reports of light chain deposition restricted to the lung, usually manifesting as single or multiple pulmonary nodules,793 though diffuse pulmonary involvement has also been described.794 More recently, pulmonary cysts have been reported in pulmonary light chain deposition disease, either alone or in association with lung nodules.795–797 In three reported cases, the cysts were numerous, and diffusely distributed in the lung, resulting in respiratory failure.796

REFERENCES 1. Thomas PD, Hunninghake GW. Current concepts of the pathogenesis of sarcoidosis. Am Rev Respir Dis 1987;135:747–760. 2. Moller DR. Etiology of sarcoidosis. Clin Chest Med 1997;18:695–706. 3. Kon OM, du Bois RM. Mycobacteria and sarcoidosis. Thorax 1997;52(Suppl 3): S47–51. 4. Barnard J, Rose C, Newman L, et al. Job and industry classifications associated with sarcoidosis in a case-control etiologic study of sarcoidosis (ACCESS). J Occup Environ Med 2005;47:226–234. 5. Newman LS, Rose CS, Bresnitz EA, et al. A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med 2004; 170:1324–1330. 6. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007;357: 2153–2165. 7. Rossman MD, Thompson B, Frederick M, et al. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet 2003;73:720–735. 8. Sharma OP, Neville E, Walker AN, et al. Familial sarcoidosis: a possible genetic influence. Ann N Y Acad Sci 1976;278: 386–400. 9. Rybicki BA, Iannuzzi MC, Frederick MM, et al. Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS). Am J Respir Crit Care Med 2001;164:2085–2091. 10. Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med 1997;336:1224– 1234. 11. Freiman DG. The pathology of sarcoidosis. Semin Roentgenol 1985;20:327–339.

12. Müller NL, Kullnig P, Miller RR. The CT findings of pulmonary sarcoidosis: analysis of 25 patients. Am J Roentgenol 1989; 152:1179–1182. 13. Muns G, West WW, Gurney J, et al. Non-sarcoid granulomatous disease with involvement of the lungs. Sarcoidosis 1995;12:99–110. 14. Leslie KO, Colby TV, Swensen SJ. Anatomic distribution and histopathologic patterns of interstitial lung disease. In: Schwarz M, King T (eds). Interstitial lung disease, 4th ed. Toronto: Brian C Decker, 2003:31–54. 15. Mayock RL, Bertrand P, Morrison CE, et al. Manifestations of sarcoidosis. Analysis of 145 patients, with a review of nine series selected from the literature. Am J Med 1963;35:67–89. 16. Levinsky L, Cummiskey J, Romer FK, et al. Sarcoidosis in Europe: a cooperative study. Ann N Y Acad Sci 1976;278: 335–346. 17. Milman N, Selroos O. Pulmonary sarcoidosis in the Nordic countries 1950–1982. Epidemiology and clinical picture. Sarcoidosis 1990;7:50–57. 18. Poukkula A, Huhti E, Lilja M, et al. Incidence and clinical picture of sarcoidosis in a circumscribed geographical area. Br J Dis Chest 1986;80:138–147. 19. Pietinalho A, Hiraga Y, Hosoda Y, et al. The frequency of sarcoidosis in Finland and Hokkaido, Japan. A comparative epidemiological study. Sarcoidosis 1995; 12:61–67. 20. Rybicki BA, Major M, Popovich J Jr, et al. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol 1997;145:

234–241. 21. Littner MR, Schachter EN, Putman CE, et al. The clinical assessment of roentgenographically atypical pulmonary sarcoidosis. Am J Med 1977;62:361–368. 22. Scadding J. Further observations on sarcoidosis associated with M tuberculosis infection. In: Proceedings of 5th International Conference on Sarcoidosis, 1969–1971. Prague, 1969:89–92. 23. Gomez V, Smith PR, Burack J, et al. Sarcoidosis after antiretroviral therapy in a patient with acquired immunodeficiency syndrome. Clin Infect Dis 2000;31: 1278–1280. 24. Mirmirani P, Maurer TA, Herndier B, et al. Sarcoidosis in a patient with AIDS: a manifestation of immune restoration syndrome. J Am Acad Dermatol 1999;41:285–286. 25. Lenner R, Bregman Z, Teirstein AS, et al. Recurrent pulmonary sarcoidosis in HIV-infected patients receiving highly active antiretroviral therapy. Chest 2001;119:978–981. 26. Goldberg HJ, Fiedler D, Webb A, et al. Sarcoidosis after treatment with interferonalpha: a case series and review of the literature. Respir Med 2006;100:2063–2068. 27. Pelletier F, Manzoni P, Jacoulet P, et al. Pulmonary and cutaneous sarcoidosis associated with interferon therapy for melanoma. Cutis 2007;80:441–445. 28. Shigemitsu H. Is sarcoidosis frequent in patients with cancer? Curr Opin Pulm Med 2008;14:478–480. 29. Paparel P, Devonec M, Perrin P, et al. Association between sarcoidosis and testicular carcinoma: a diagnostic pitfall.

699

Chapter 11 • Idiopathic Diffuse Lung Diseases

30.

31.

32.

33.

34.

35. 36. 37. 38. 39. 40.

41. 42.

43.

44.

45.

46.

47.

700

Sarcoidosis Vasc Diffuse Lung Dis 2007;24: 95–101. Abdel-Galiil K, Anand R, Sharma S, et al. Incidence of sarcoidosis in head and neck cancer. Br J Oral Maxillofac Surg 2008;46: 59–60. Risbano MG, Groshong SD, Schwarz MI. Lung nodules in a woman with a history of breast cancer. Diagnosis: a sarcoid-like reaction in metastatic breast cancer. Chest 2007;132:1697–1701. Piscioli I, Donato S, Morelli L, et al. Renal cell carcinoma with sarcomatoid features and peritumoral sarcoid-like granulomatous reaction: report of a case and review of the literature. Int J Surg Pathol 2008;16:345–348. Kirks DR, McCormick VD, Greenspan RH. Pulmonary sarcoidosis. Roentgenologic analysis of 150 patients. Am J Roentgenol Radium Ther Nucl Med 1973;117:777–786. Hillerdal G, Nou E, Osterman K, et al. Sarcoidosis: epidemiology and prognosis. A 15-year European study. Am Rev Respir Dis 1984;130:29–32. Hetherington S. Sarcoidosis in young children. Am J Dis Child 1982;136:13–15. Costabel U, Ohshimo S, Guzman J. Diagnosis of sarcoidosis. Curr Opin Pulm Med 2008;14:455–461. James DG, Neville E, Siltzbach LE. A worldwide review of sarcoidosis. Ann N Y Acad Sci 1976;278:321–334. Sharma OP. Sarcoidosis: clinical, laboratory, and immunologic aspects. Semin Roentgenol 1985;20:340–355. Edmondstone WM, Wilson AG. Sarcoidosis in caucasians, blacks and asians in London. Br J Dis Chest 1985;79:27–36. Honeybourne D. Ethnic differences in the clinical features of sarcoidosis in SouthEast London. Br J Dis Chest 1980;74: 63–69. Lofgren S. Primary pulmonary sarcoidosis. Acta Med Scand 1953;145:421–431. Sharma SK, Mohan A, Guleria JS. Clinical characteristics, pulmonary function abnormalities and outcome of prednisolone treatment in 106 patients with sarcoidosis. J Assoc Physicians India 2001;49:697– 704. Renston JP, Goldman ES, Hsu RM, et al. Peripheral blood eosinophilia in association with sarcoidosis. Mayo Clin Proc 2000;75: 586–590. Adams JS, Sharma OP, Gacad MA, et al. Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis. J Clin Invest 1983;72: 1856–1860. Sandler LM, Winearls CG, Fraher LJ, et al. Studies of the hypercalcaemia of sarcoidosis: effect of steroids and exogenous vitamin D3 on the circulating concentrations of 1,25-dihydroxy vitamin D3. Q J Med 1984;53:165–180. Meyrier A, Valeyre D, Bouillon R, et al. Resorptive versus absorptive hypercalciuria in sarcoidosis: correlations with 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3 and parameters of disease activity. Q J Med 1985;54: 269–281. Shorr AF, Torrington KG, Parker JM. Serum angiotensin converting enzyme does not correlate with radiographic stage at initial diagnosis of sarcoidosis. Respir Med

1997;91:399–401. 48. Lieberman J, Nosal A, Schlessner A, et al. Serum angiotensin-converting enzyme for diagnosis and therapeutic evaluation of sarcoidosis. Am Rev Respir Dis 1979;120: 329–335. 49. Lieberman J. Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med 1975;59:365–372. 50. Costabel U, Teschler H. Biochemical changes in sarcoidosis. Clin Chest Med 1997;18:827–842. 51. Studdy P, Bird R, James DG. Serum angiotensin-converting enzyme (SACE) in sarcoidosis and other granulomatous disorders. Lancet 1978;2:1331–1334. 52. Nagai S, Izumi T. Bronchoalveolar lavage. Still useful in diagnosing sarcoidosis? Clin Chest Med 1997;18:787–797. 53. Lynch JP 3rd, Kazerooni EA, Gay SE. Pulmonary sarcoidosis. Clin Chest Med 1997;18:755–785. 54. Levinson RS, Metzger LF, Stanley NN, et al. Airway function in sarcoidosis. Am J Med 1977;62:51–59. 55. Winterbauer RH, Hutchinson JF. Use of pulmonary function tests in the management of sarcoidosis. Chest 1980;78: 640–647. 56. Fazzi P, Sbragia P, Solfanelli S, et al. Functional significance of the decreased attenuation sign on expiratory CT in pulmonary sarcoidosis: report of four cases. Chest 2001;119:1270–1274. 57. Magkanas E, Voloudaki A, Bouros D, et al. Pulmonary sarcoidosis. Correlation of expiratory high-resolution CT findings with inspiratory patterns and pulmonary function tests. Acta Radiol 2001;42:494–501. 58. Davies CW, Tasker AD, Padley SP, et al. Air trapping in sarcoidosis on computed tomography: correlation with lung function. Clin Radiol 2000;55:217–221. 59. Hansell DM, Milne DG, Wilsher ML, et al. Pulmonary sarcoidosis: morphologic associations of airflow obstruction at thin-section CT. Radiology 1998;209: 697–704. 60. McLoud TC, Epler GR, Gaensler EA, et al. A radiographic classification for sarcoidosis: physiologic correlation. Invest Radiol 1982;17:129–138. 61. Miller A, Chuang M, Teirstein AS, et al. Pulmonary function in stage I and II pulmonary sarcoidosis. Ann N Y Acad Sci 1976;278:292–300. 62. Statement on sarcoidosis. Am J Respir Crit Care Med 1999;160:736–755. 63. Teirstein AS, Chuang M, Miller A, et al. Flexible-bronchoscope biopsy of lung and bronchial wall in intrathoracic sarcoidosis. Ann N Y Acad Sci 1976;278:522–527. 64. Gilman MJ, Wang KP. Transbronchial lung biopsy in sarcoidosis. An approach to determine the optimal number of biopsies. Am Rev Respir Dis 1980;122:721–724. 65. Koerner SK, Sakowitz AJ, Appelman RI, et al. Transbronchial lung biopsy for the diagnosis of sarcoidosis. N Engl J Med 1975;293:268–270. 66. Mitchell DM, Mitchell DN, Collins JV, et al. Transbronchial lung biopsy through fibreoptic bronchoscope in diagnosis of sarcoidosis. BMJ 1980;280:679–681. 67. Roethe RA, Fuller PB, Byrd RB, et al. Transbronchoscopic lung biopsy in sarcoidosis. Optimal number and sites for

diagnosis. Chest 1980;77:400–402. 68. Rosen Y, Amorosa JK, Moon S, et al. Occurrence of lung granulomas in patients with stage I sarcoidosis. AJR Am J Roentgenol 1977;129:1083–1085. 69. Hunsaker AR, Munden RF, Pugatch RD, et al. Sarcoidlike reaction in patients with malignancy. Radiology 1996;200:255–261. 70. Fossa SD, Abeler V, Marton PF, et al. Sarcoid reaction of hilar and paratracheal lymph nodes in patients treated for testicular cancer. Cancer 1985;56:2212–2216. 71. Munro CS, Mitchell DN. The Kveim response: still useful, still a puzzle. Thorax 1987;42:321–331. 72. Consensus conference: activity of sarcoidosis. Third WASOG meeting, Los Angeles, USA, September 8–11, 1993. Eur Respir J 1994;7:624–627. 73. Sharma OP. Pulmonary sarcoidosis and corticosteroids. Am Rev Respir Dis 1993; 147:1598–1600. 74. Selroos O. Glucocorticosteroids and pulmonary sarcoidosis. Thorax 1996;51: 229–230. 75. Barbers RG. Role of transplantation (lung, liver, and heart) in sarcoidosis. Clin Chest Med 1997;18:865–874. 76. Martinez FJ, Orens JB, Deeb M, et al. Recurrence of sarcoidosis following bilateral allogeneic lung transplantation. Chest 1994;106:1597–1599. 77. Kazerooni EA, Cascade PN. Recurrent miliary sarcoidosis after lung transplantation. Radiology 1995;194: 913. 78. Collins J, Hartman MJ, Warner TF, et al. Frequency and CT findings of recurrent disease after lung transplantation. Radiology 2001;219:503–509. 79. Johns C, MacGregor M, Zachary J, et al. Chronic sarcoidosis: outcome, unusual features and complications. In: Williams W, Davies B (eds). Eighth International Conference on sarcoidosis and other granulomatous diseases. Cardiff, Wales: Alpha Omega Publishing Ltd, 1980: 368–377. 80. Huang C, Heurich A, Rosen Y, et al. Pulmonary sarcoidosis: a radiographic, functional and pathological correlation. In: Williams W, Davies B (eds). Eighth International Conference on sarcoidosis and other granulomatous diseases. Cardiff, Wales: Alpha Omega Publishing Ltd, 1980:368–377. 81. Perry A, Vuitch F. Causes of death in patients with sarcoidosis. A morphologic study of 38 autopsies with clinicopathologic correlations. Arch Pathol Lab Med 1995;119:167–172. 82. Smedema JP, Snoep G, van Kroonenburgh MP, et al. Cardiac involvement in patients with pulmonary sarcoidosis assessed at two university medical centers in the Netherlands. Chest 2005;128:30–35. 83. Siltzbach LE, James DG, Neville E, et al. Course and prognosis of sarcoidosis around the world. Am J Med 1974;57: 847–852. 84. Scadding JG, Mitchell DN. Sarcoidosis. London: Chapman and Hall, 1985. 85. DeRemee RA. The roentgenographic staging of sarcoidosis. Historic and contemporary perspectives. Chest 1983;83:128–133. 86. Brauner M, Grenier P, Mompoint D, et al.

References

87.

88.

89.

90.

91. 92. 93.

94.

95.

96.

97.

98.

99. 100.

101. 102.

103. 104.

105.

Pulmonary sarcoidosis: evaluation with high resolution CT. Radiology 1989;172: 467–471. Müller N, Mawson J, Mathieson J, et al. Sarcoidosis: correlation of extent of disease at CT with clinical, functional, and radiographic findings. Radiology 1989;171: 613–618. Lynch D, Webb W, Gamsu G, et al. Computed tomography in sarcoidosis. J Comput Assist Tomogr 1989;13:405– 410. Bein ME, Putman CE, McLoud TC, et al. A reevaluation of intrathoracic lymphadenopathy in sarcoidosis. AJR Am J Roentgenol 1978;131:409–415. Rabinowitz JG, Ulreich S, Soriano C. The usual unusual manifestations of sarcoidosis and the ‘hilar haze’: a new diagnostic aid. Am J Roentgenol Radium Ther Nucl Med 1974;120:821–831. Smellie H, Hoyle C. The hilar lymph-nodes in sarcoidosis with special reference to prognosis. Lancet 1957;2:66–70. Romer FK. Presentation of sarcoidosis and outcome of pulmonary changes. Dan Med Bull 1982;29:27–32. Ellis K, Renthal G. Pulmonary sarcoidosis. Roentgenographic observations on course of disease. AJR Am J Roentgenol 1962;88: 1070–1083. Conant EF, Glickstein MF, Mahar P, et al. Pulmonary sarcoidosis in the older patient: conventional radiographic features. Radiology 1988;169:315–319. Spann RW, Rosenow EC 3rd, DeRemee RA, et al. Unilateral hilar or paratracheal adenopathy in sarcoidosis: a study of 38 cases. Thorax 1971;26:296–299. Hamper UM, Fishman EK, Khouri NF, et al. Typical and atypical CT manifestations of pulmonary sarcoidosis. J Comput Assist Tomogr 1986;10:928–936. Solomon A, Kreel L, McNicol M, et al. Computed tomography in pulmonary sarcoidosis. J Comput Assist Tomogr 1979;3:754–758. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 11–1984. Long-standing sarcoidosis with the recent onset of the superior-vena-cava syndrome. N Engl J Med 1984;310:708–716. McLoud TC, Putman CE, Pascual R. Eggshell calcification with systemic sarcoidosis. Chest 1974;66:515–517. Tsou E, Romano MC, Kerwin DM, et al. Sarcoidosis of anterior mediastinal nodes, pancreas, and uterine cervix: three unusual sites in the same patient. Am Rev Respir Dis 1980;122:333–338. Berkmen YM. Radiologic aspects of intrathoracic sarcoidosis. Semin Roentgenol 1985;20:356–375. Talbot F, Katz S, Matthews M. Bronchopulmonary sarcoidosis. Some unusual manifestations and the serious complications thereof. Am J Med 1959;26: 340–355. Karasick SR. Atypical thoracic lymphadenopathy in sarcoidosis. AJR Am J Roentgenol 1979;133:928–929. Kutty CP, Varkey B. Sarcoidosis presenting with posterior mediastinal lymphadenopathy. Postgrad Med 1982;71: 64–66. Israel HL, Sperber M, Steiner RM. Course

106. 107. 108. 109.

110. 111. 112. 113. 114.

115.

116.

117.

118.

119. 120.

121.

122. 123. 124. 125.

126. 127.

of chronic hilar sarcoidosis in relation to markers of granulomatous activity. Invest Radiol 1983;18:1–5. Olliff JF, Eeles R, Williams MP. Mimics of metastases from testicular tumours. Clin Radiol 1990;41:395–399. Parr MJ, Williams MV. Sarcoidosis mimicking metastatic testicular tumour. Br J Radiol 1988;61:516–518. Steiger V, Fanburg BL. Recurrence of thoracic lymphadenopathy in sarcoidosis. N Engl J Med 1986;314:1512. Brincker H, Wilbek E. The incidence of malignant tumours in patients with respiratory sarcoidosis. Br J Cancer 1974;29: 247–251. Macfarlane JT. Recurrent erythema nodosum and pulmonary sarcoidosis. Postgrad Med J 1981;57:525. Symmons DP, Woods KL. Recurrent sarcoidosis. Thorax 1980;35:879. Kent D. Recurrent unilateral hilar adenopathy in sarcoidosis. Am Rev Respir Dis 1965;91:272–276. Rockoff SD, Rohatgi PK. Unusual manifestations of thoracic sarcoidosis. AJR Am J Roentgenol 1985;144:513–528. Israel HL, Lenchner G, Steiner RM. Late development of mediastinal calcification in sarcoidosis. Am Rev Respir Dis 1981;124: 302–305. Berkmen YM, Javors BR. Anterior mediastinal lymphadenopathy in sarcoidosis. AJR Am J Roentgenol 1976;127: 983–987. Gawne-Cain ML, Hansell DM. The pattern and distribution of calcified mediastinal lymph nodes in sarcoidosis and tuberculosis: a CT study. Clin Radiol 1996;51:263–267. Gross BH, Schneider HJ, Proto AV. Eggshell calcification of lymph nodes: an update. AJR Am J Roentgenol 1980;135: 1265–1268. Murdoch J, Müller N. Pulmonary sarcoidosis: changes on followup examination. AJR Am J Roentgenol 1992;159:473–477. Smellie H, Hoyle C. The natural history of pulmonary sarcoidosis. Q J Med 1960; 29:539–559. Israel HL, Karlin P, Menduke H, et al. Factors affecting outcome of sarcoidosis. Influence of race, extrathoracic involvement, and initial radiologic lung lesions. Ann N Y Acad Sci 1986;465: 609–618. Putman CE, Hoeck B. Reassessing the standard chest radiograph for intraparenchymal activity. Ann N Y Acad Sci 1986;465:595–608. Israel H, Sones M. Sarcoidosis. Clinical observation on one hundred sixty cases. Arch Intern Med 1958;102:766–776. Mesbahi SJ, Davies P. Unilateral pulmonary changes in the chest X-ray in sarcoidosis. Clin Radiol 1981;32:283–287. Demicco WA, Fanburg BL. Sarcoidosis presenting as a lobar or unilateral lung infiltrate. Clin Radiol 1982;33:663–669. Hafermann DR, Solomon DA, Byrd RB. Sarcoidosis initially occurring as apical infiltrate and pleural reaction. Chest 1978;73:413–414. Scadding J. Calcification in sarcoidosis. Tubercle 1961;42:121–135. Kuhlman JE, Fishman EK, Hamper UM,

128.

129.

130.

131.

132.

133.

134.

135.

136.

137.

138.

139.

140.

141.

142.

143.

et al. The computed tomographic spectrum of thoracic sarcoidosis. RadioGraphics 1989;9:449–466. Nishimura K, Itoh H, Kitaichi M, et al. Pulmonary sarcoidosis: correlation of CT and histopathologic findings. Radiology 1993;189:105–109. Remy-Jardin M, Beuscart R, Sault MC, et al. Subpleural micronodules in diffuse infiltrative lung diseases: evaluation with thin-section CT scans. Radiology 1990;177:133–139. Gruden JF, Webb WR, Warnock M. Centrilobular opacities in the lung on high-resolution CT: diagnostic considerations and pathologic correlation. AJR Am J Roentgenol 1994;162:569–574. Grenier P, Valeyre D, Cluzel P, et al. Chronic diffuse interstitial lung disease: diagnostic value of chest radiography and high-resolution CT. Radiology 1991;179:123–132. Akira M, Kozuka T, Inoue Y, et al. Long-term follow-up CT scan evaluation in patients with pulmonary sarcoidosis. Chest 2005;127:185–191. Munk P, Müller N, Miller R, et al. Pulmonary lymphangitic carcinomatosis: CT and pathologic findings. Radiology 1988;166:705–709. Murata K, Khan A, Herman PG. Pulmonary parenchymal disease: evaluation with high-resolution CT. Radiology 1989;170:629–635. Johkoh T, Ikezoe J, Tomiyama N, et al. CT findings in lymphangitic carcinomatosis of the lung: correlation with histologic findings and pulmonary function tests. AJR Am J Roentgenol 1992;158:1217–1222. Stein M, Mayo J, Müller N, et al. Pulmonary lymphangitic spread of carcinoma: appearance on CT scans. Radiology 1987;162:371–375. Collins J, Müller NL, Leung AN, et al. Epstein-Barr-virus-associated lymphoproliferative disease of the lung: CT and histologic findings. Radiology 1998;208:749–759. McGuinness G, Scholes JV, Jagirdar JS, et al. Unusual lymphoproliferative disorders in nine adults with HIV or AIDS: CT and pathologic findings. Radiology 1995;197:59–65. Honda O, Johkoh T, Ichikado K, et al. Comparison of high resolution CT findings of sarcoidosis, lymphoma, and lymphangitic carcinoma: is there any difference of involved interstitium? J Comput Assist Tomogr 1999;23:374–379. Bergin C, Roggli V, Coblentz C, et al. The secondary pulmonary lobule: normal and abnormal CT appearances. AJR Am J Roentgenol 1988;151:21–25. Padley SP, Padhani AR, Nicholson A, et al. Pulmonary sarcoidosis mimicking cryptogenic fibrosing alveolitis on CT. Clin Radiol 1996;51:807–810. Remy-Jardin M, Giraud F, Remy J, et al. Pulmonary sarcoidosis: role of CT in the evaluation of disease activity and functional impairment and in prognosis assessment. Radiology 1994;191:675–680. Leung AN, Brauner MW, Caillat-Vigneron N, et al. Sarcoidosis activity: correlation of HRCT findings with those of 67Ga scanning, bronchoalveolar lavage, and serum angiotensin-converting enzyme

701

Chapter 11 • Idiopathic Diffuse Lung Diseases

144.

145.

146.

147.

148.

149.

150.

151.

152.

153. 154. 155.

156. 157.

158.

159.

160.

161.

162. 163.

702

assay. J Comput Assist Tomogr 1998;22: 229–234. Brauner M, Lenoir S, Grenier P, et al. Pulmonary sarcoidosis: CT assessment of lesion reversibility. Radiology 1992;182: 349–354. Müller NL, Miller RR. Ground-glass attenuation, nodules, alveolitis, and sarcoid granulomas. Radiology 1993;189: 31–32. Traill ZC, Maskell GF, Gleeson FV. High-resolution CT findings of pulmonary sarcoidosis. AJR Am J Roentgenol 1997;168: 1557–1560. Nishimura K, Itoh H, Kitaichi M, et al. CT and pathological correlation of pulmonary sarcoidosis. SemUltrasound CT MR 1995; 16:361–370. Freundlich IM, Libshitz HI, Glassman LM, et al. Sarcoidosis. Typical and atypical thoracic manifestations and complications. Clin Radiol 1970;21:376–383. Reed JC, Madewell JE. The air bronchogram in interstitial disease of the lungs. A radiological-pathological correlation. Radiology 1975;116:1–9. Sahn SA, Schwarz MI, Lakshminarayan S. Sarcoidosis: the significance of an acinar pattern on chest roentgenogram. Chest 1974;65:684–687. Shigematsu N, Emori K, Matsuba K, et al. Clinicopathologic characteristics of pulmonary acinar sarcoidosis. Chest 1978;73:186–188. Battesti JP, Saumon G, Valeyre D, et al. Pulmonary sarcoidosis with an alveolar radiographic pattern. Thorax 1982;37: 448–452. Sharma OP. Sarcoidosis: unusual pulmonary manifestations. Postgrad Med 1977;61:67–73. Kirks DR, Greenspan RH. Sarcoid. Radiol Clin North Am 1973;11:279–294. Johkoh T, Ikezoe J, Takeuchi N, et al. CT findings in ‘pseudoalveolar’ sarcoidosis. J Comput Assist Tomogr 1992;16:904– 907. Glazer HS, Levitt RG, Shackelford GD. Peripheral pulmonary infiltrates in sarcoidosis. Chest 1984;86:741–744. Judson MA, Ghent S, Close TP. Sarcoidosis manifested as peripheral pulmonary infiltrates. AJR Am J Roentgenol 1993;160:1359–1360. Baumann MH, Strange C, Sahn SA. Do chest radiographic findings reflect the clinical course of patients with sarcoidosis during corticosteroid withdrawal? AJR Am J Roentgenol 1990;154:481–485. Sharma OP, Hewlett R, Gordonson J. Nodular sarcoidosis: an unusual radiographic appearance. Chest 1973;64: 189–192. Nakatsu M, Hatabu H, Morikawa K, et al. Large coalescent parenchymal nodules in pulmonary sarcoidosis: ‘sarcoid galaxy’ sign. AJR Am J Roentgenol 2002;178: 1389–1393. Bergin CJ, Bell DY, Coblentz CL, et al. Sarcoidosis: correlation of pulmonary parenchymal pattern at CT with results of pulmonary function tests. Radiology 1989;171:619–624. Battesti JP, Georges R, Basset F, et al. Chronic cor pulmonale in pulmonary sarcoidosis. Thorax 1978;33:76–84. McCort J, Pare P. Pulmonary fibrosis and

164. 165. 166.

167. 168.

169. 170. 171.

172.

173. 174.

175.

176. 177.

178.

179.

180. 181.

182.

183.

cor pulmonale in sarcoidosis. Radiology 1954;62:496–504. Hennebicque AS, Nunes H, Brillet PY, et al. CT findings in severe thoracic sarcoidosis. Eur Radiol 2005;15:23–30. Primack SL, Hartman TE, Hansell DM, et al. End-stage lung disease: CT findings in 61 patients. Radiology 1993;189:681–686. Hours S, Nunes H, Kambouchner M, et al. Pulmonary cavitary sarcoidosis: clinicoradiologic characteristics and natural history of a rare form of sarcoidosis. Medicine (Baltimore) 2008;87:142–151. Brandstetter RD, Messina MS, Sprince NL, et al. Tracheal stenosis due to sarcoidosis. Chest 1981;80:656. Lefrak S, Di Benedetto R. Systematic sarcoidosis with severe involvement of the upper respiratory tract. Am Rev Respir Dis 1970;102:801–807. Henry DA, Cho SR. Tracheal stenosis in sarcoidosis. South Med J 1983;76: 1323–1324. Kirschner BS, Holinger PH. Laryngeal obstruction in children sarcoidosis. J Pediatr 1976;88:263–265. Weisman RA, Canalis RF, Powell WJ. Laryngeal sarcoidosis with airway obstruction. Ann Otol Rhinol Laryngol 1980;89:58–61. Mendelson DS, Norton K, Cohen BA, et al. Bronchial compression: an unusual manifestation of sarcoidosis. J Comput Assist Tomogr 1983;7:892–894. Hadfield JW, Page RL, Flower CD, et al. Localised airway narrowing in sarcoidosis. Thorax 1982;37:443–447. Olsson T, Bjornstad-Pettersen H, Stjernberg NL. Bronchostenosis due to sarcoidosis: a cause of atelectasis and airway obstruction simulating pulmonary neoplasm and chronic obstructive pulmonary disease. Chest 1979;75:663–666. Udwadia ZF, Pilling JR, Jenkins PF, et al. Bronchoscopic and bronchographic findings in 12 patients with sarcoidosis and severe or progressive airways obstruction. Thorax 1990;45:272–275. Dorman RL Jr, Whitman GJ, Chew FS. Thoracic sarcoidosis. AJR Am J Roentgenol 1995;164:1368. Corsello BF, Lohaus GH, Funahashi A. Endobronchial mass lesion due to sarcoidosis: complete resolution with corticosteroids. Thorax 1983;38:157–158. Munt PW. Middle lobe atelectasis in sarcoidosis. Report of a case with prompt resolution concomitant with corticosteroid administration. Am Rev Respir Dis 1973;108:357–360. Fouty BW, Pomeranz M, Thigpen TP, et al. Dilatation of bronchial stenoses due to sarcoidosis using a flexible fiberoptic bronchoscope. Chest 1994;106:677–680. Iles PB. Multiple bronchial stenoses: treatment by mechanical dilatation. Thorax 1981;36:784–786. Curtin JJ, Innes NJ, Harrison BD. Thin-section spiral volumetric CT for the assessment of lobar and segmental bronchial stenoses. Clin Radiol 1998;53: 110–115. Lenique F, Brauner MW, Grenier P, et al. CT assessment of bronchi in sarcoidosis: endoscopic and pathologic correlations. Radiology 1995;194:419–423. Shorr AF, Torrington KG, Hnatiuk OW.

184. 185.

186.

187.

188. 189. 190.

191.

192. 193.

194.

195. 196.

197. 198.

199.

200.

201.

202.

203.

Endobronchial involvement and airway hyperreactivity in patients with sarcoidosis. Chest 2001;120:881–886. Carrington CB. Structure and function in sarcoidosis. Ann N Y Acad Sci 1976;278: 265–283. Gleeson FV, Traill ZC, Hansell DM. Evidence on expiratory CT scans of small-airway obstruction in sarcoidosis. AJR Am J Roentgenol 1996;166:1052–1054. Bartz RR, Stern EJ. Airways obstruction in patients with sarcoidosis: expiratory CT scan findings. J Thorac Imaging 2000;15: 285–289. Miller A, Teirstein AS, Jackler I, et al. Airway function in chronic pulmonary sarcoidosis with fibrosis. Am Rev Respir Dis 1974;109:179–189. Sharma OP. Airway obstruction in sarcoidosis. Chest 1978;73:6–7. Mixides G, Guy E. Sarcoidosis confined to the airway masquerading as asthma. Can Respir J 2003;10:114–116. Terasaki H, Fujimoto K, Müller NL, et al. Pulmonary sarcoidosis: comparison of findings of inspiratory and expiratory high-resolution CT and pulmonary function tests between smokers and nonsmokers. AJR Am J Roentgenol 2005; 185:333–338. Handa T, Nagai S, Fushimi Y, et al. Clinical and radiographic indices associated with airflow limitation in patients with sarcoidosis. Chest 2006;130:1851–1856. Schermuly W, Behrend H. Angiography of pulmonary sarcoidosis. Radiologe 1968;8:116–123. Faunce HF, Ramsay GC, Sy W. Protracted yet variable major pulmonary artery compression in sarcoidosis. Radiology 1976;119:313–314. Goffman TE, Bloom RL, Dvorak VC. Topics in radiology/case of the month. Acute dyspnea in a young woman taking birth control pills. JAMA 1984;251:1465–1466. Hietala SO, Stinnett RG, Faunce HF 3rd, et al. Pulmonary artery narrowing in sarcoidosis. JAMA 1977;237:572–573. Khan MM, Gill DS, McConkey B. Myopathy and external pulmonary artery compression caused by sarcoidosis. Thorax 1981;36:703–704. Westcott JL, DeGraff AC Jr. Sarcoidosis, hilar adenopathy, and pulmonary artery narrowing. Radiology 1973;108:585–586. Preston IR, Klinger JR, Landzberg MJ, et al. Vasoresponsiveness of sarcoidosisassociated pulmonary hypertension. Chest 2001;120:866–872. Nunes H, Humbert M, Capron F, et al. Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax 2006;61:68–74. Rodman DM, Lindenfeld J. Successful treatment of sarcoidosis-associated pulmonary hypertension with corticosteroids. Chest 1990;97:500–502. Padia SA, Budev M, Farver CF, et al. Intravascular sarcoidosis presenting as pulmonary vein occlusion: CT and pathologic findings. J Thorac Imaging 2007;22:268–270. Hoffstein V, Ranganathan N, Mullen JB. Sarcoidosis simulating pulmonary veno-occlusive disease. Am Rev Respir Dis 1986;134:809–811. Narayan D, Brown L, Thayer JO. Surgical

References

204.

205.

206.

207. 208. 209.

210.

211. 212.

213. 214. 215. 216.

217.

218.

219. 220. 221.

222. 223. 224.

225.

management of superior vena caval syndrome in sarcoidosis. Ann Thorac Surg 1998;66:946–948. Simpson JC, Callaway MP, Taylor PM, et al. Recurrent venous obstruction caused by sarcoidosis. Respir Med 1998;92: 785–786. Javaheri S, Hales CA. Sarcoidosis: a cause of innominate vein obstruction and massive pleural effusion. Lung 1980;157: 81–85. Radke JR, Kaplan H, Conway WA. The significance of superior vena cava syndrome developing in a patient with sarcoidosis. Radiology 1980;134:311–312. Da Costa JL, Chiang SC. Pleural sarcoidosis. Singapore Med J 1975;16: 224–226. Gardiner IT, Uff JS. Acute pleurisy in sarcoidosis. Thorax 1978;33:124–127. Beekman JF, Zimmet SM, Chun BK, et al. Spectrum of pleural involvement in sarcoidosis. Arch Intern Med 1976;136:323–330. Johnson NM, Martin ND, McNicol MW. Sarcoidosis presenting with pleurisy and bilateral pleural effusions. Postgrad Med J 1980;56:266–267. Nicholls AJ, Friend JA, Legge JS. Sarcoid pleural effusion: three cases and review of the literature. Thorax 1980;35:277–281. Durand DV, Dellinger A, Guerin C, et al. Pleural sarcoidosis: one case presenting with an eosinophilic effusion. Thorax 1984;39:468–469. Chusid EL, Siltzbach LE. Sarcoidosis of the pleura. Ann Intern Med 1974;81:190–194. Wilen SB, Rabinowitz JG, Ulreich S, et al. Pleural involvement in sarcoidosis. Am J Med 1974;57:200–209. Kanada DJ, Scott D, Sharma OP. Unusual presentations of pleural sarcoidosis. Br J Dis Chest 1980;74:203–205. Watts R Jr, Thompson JR, Jasuja ML. Sarcoidosis presenting with massive pleural effusion. IMJ Ill Med J 1983;163: 57–58. Szwarcberg JB, Glajchen N, Teirstein AS. Pleural involvement in chronic sarcoidosis detected by thoracic CT scanning. Sarcoidosis Vasc Diffuse Lung Dis 2005;22: 58–62. Knox AJ, Wardman AG, Page RL. Tuberculous pleural effusion occurring during corticosteroid treatment of sarcoidosis. Thorax 1986;41:651. Jarman PR, Whyte MK, Sabroe I, et al. Sarcoidosis presenting with chylothorax. Thorax 1995;50:1324–1325. Soskel NT, Sharma OP. Pleural involvement in sarcoidosis. Curr Opin Pulm Med 2000;6:455–468. Omori H, Asahi H, Irinoda T, et al. Pneumothorax as a presenting manifestation of early sarcoidosis. Jpn J Thorac Cardiovasc Surg 2004;52:33–35. Akelsson IG, Eklund A, Skold CM, et al. Bilateral spontaneous pneumothorax and sarcoidosis. Sarcoidosis 1990;7:136–138. Gorske KJ, Fleming RJ. Mycetoma formation in cavitary pulmonary sarcoidosis. Radiology 1970;95:279–285. Wollschlager C, Khan F. Aspergillomas complicating sarcoidosis. A prospective study in 100 patients. Chest 1984;86: 585–588. Israel HL, Lenchner GS, Atkinson GW.

226.

227.

228.

229. 230.

231.

232.

233.

234.

235.

236. 237.

238.

239.

240.

241.

242. 243.

Sarcoidosis and aspergilloma. The role of surgery. Chest 1982;82:430–432. Libshitz HI, Atkinson GW, Israel HL. Pleural thickening as a manifestation of aspergillus superinfection. Am J Roentgenol Radium Ther Nucl Med 1974;120:883–886. Roberts CM, Citron KM, Strickland B. Intrathoracic aspergilloma: role of CT in diagnosis and treatment. Radiology 1987; 165:123–128. Kaplan J, Johns CJ. Mycetomas in pulmonary sarcoidosis: non-surgical management. Johns Hopkins Med J 1979; 145:157–161. Breuer R, Baigelman W, Pugatch RD. Occult mycetoma. J Comput Assist Tomogr 1982;6:166–168. Mana J, Teirstein AS, Mendelson DS, et al. Excessive thoracic computed tomographic scanning in sarcoidosis. Thorax 1995;50: 1264–1266. Sulavik SB, Spencer RP, Weed DA, et al. Recognition of distinctive patterns of gallium-67 distribution in sarcoidosis. J Nucl Med 1990;31:1909–1914. Mana J. Nuclear imaging. 67Gallium, 201thallium, 18F-labeled fluoro-2-deoxy-Dglucose positron emission tomography. Clin Chest Med 1997;18:799–811. Braun JJ, Kessler R, Constantinesco A, et al. 18F-FDG PET/CT in sarcoidosis management: review and report of 20 cases. Eur J Nucl Med Mol Imaging 2008;35:1537–1543. Nishiyama Y, Yamamoto Y, Fukunaga K, et al. Comparative evaluation of 18F-FDG PET and 67Ga scintigraphy in patients with sarcoidosis. J Nucl Med 2006;47: 1571–1576. Brudin LH, Valind SO, Rhodes CG, et al. Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography. Eur J Nucl Med 1994;21:297–305. Lewis PJ, Salama A. Uptake of fluorine-18fluorodeoxyglucose in sarcoidosis. J Nucl Med 1994;35:1647–1649. Teirstein AS, Machac J, Almeida O, et al. Results of 188 whole-body fluorodeoxyglucose positron emission tomography scans in 137 patients with sarcoidosis. Chest 2007;132:1949–1953. Prabhakar HB, Rabinowitz CB, Gibbons FK, et al. Imaging features of sarcoidosis on MDCT, FDG PET, and PET/CT. AJR Am J Roentgenol 2008;190:S1–6. Ohira H, Tsujino I, Ishimaru S, et al. Myocardial imaging with 18F-fluoro-2deoxyglucose positron emission tomography and magnetic resonance imaging in sarcoidosis. Eur J Nucl Med Mol Imaging 2008;35:933–941. Tadamura E, Yamamuro M, Kubo S, et al. Effectiveness of delayed enhanced MRI for identification of cardiac sarcoidosis: comparison with radionuclide imaging. AJR Am J Roentgenol 2005;185:110– 115. Cordier JF. Eosinophilic pneumonias. In: Schwarz M, King T (eds). Interstitial lung disease, 4th ed. Toronto: Brian C Decker, 2003:657–700. Crofton J, Livingstone J, Oswald N, et al. Pulmonary eosinophilia. Thorax 1952;7: 1–35. Citro LA, Gordon ME, Miller WT.

244.

245. 246.

247.

248.

249.

250.

251.

252.

253. 254.

255. 256.

257.

258.

259.

260.

261.

262.

Eosinophilic lung disease (or how to slice P.I.E.). Am J Roentgenol Radium Ther Nucl Med 1973;117:787–797. Jeong YJ, Kim KI, Seo IJ, et al. Eosinophilic lung diseases: a clinical, radiologic, and pathologic overview. RadioGraphics 2007;27:617–637, discussion 637–639. Frankel SK, Groshong SD, Lynch DA. Invited commentary. RadioGraphics 2007;27:637–639. Allen JN, Pacht ER, Gadek JE, et al. Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure. N Engl J Med 1989;321:569–574. Badesch DB, King TE Jr, Schwarz MI. Acute eosinophilic pneumonia: a hypersensitivity phenomenon? Am Rev Respir Dis 1989;139:249–252. Tazelaar H, Linz L, Colby T, et al. Acute eosinophilic pneumonia: histopathologic findings in nine patients. Am J Respir Crit Care Med 1997;155:296–302. Uchiyama H, Suda T, Nakamura Y, et al. Alterations in smoking habits are associated with acute eosinophilic pneumonia. Chest 2008;133:1174–1180. Philit F, Etienne-Mastroianni B, Parrot A, et al. Idiopathic acute eosinophilic pneumonia: a study of 22 patients. Am J Respir Crit Care Med 2002;166:1235–1239. Shorr AF, Scoville SL, Cersovsky SB, et al. Acute eosinophilic pneumonia among US military personnel deployed in or near Iraq. JAMA 2004;292:2997–3005. Rom WN, Weiden M, Garcia R, et al. Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust. Am J Respir Crit Care Med 2002;166:797–800. Allen JMD. Acute eosinophilic pneumonia. Semin Respir Crit Care Med 2006:142–147. Pope-Harman AL, Davis WB, Allen ED, et al. Acute eosinophilic pneumonia. A summary of 15 cases and review of the literature. Medicine (Baltimore) 1996;75: 334–342. Hayakawa H, Sato A, Toyoshima M, et al. A clinical study of idiopathic eosinophilic pneumonia. Chest 1994;105:1462–1466. Ogawa H, Fujimura M, Matsuda T, et al. Transient wheeze. Eosinophilic bronchobronchiolitis in acute eosinophilic pneumonia. Chest 1993;104:493–496. Cheon JE, Lee KS, Jung GS, et al. Acute eosinophilic pneumonia: radiographic and CT findings in six patients. AJR Am J Roentgenol 1996;167:1195–1199. Buchheit J, Eid N, Rodgers G Jr, et al. Acute eosinophilic pneumonia with respiratory failure: a new syndrome? Am Rev Respir Dis 1992;145:716–718. King MA, Pope-Harman AL, Allen JN, et al. Acute eosinophilic pneumonia: radiologic and clinical features. Radiology 1997;203:715–719. Okubo Y, Hossain M, Kai R, et al. Adhesion molecules on eosinophils in acute eosinophilic pneumonia. Am J Respir Crit Care Med 1995;151:1259–1262. Tomiyama N, Müller NL, Johkoh T, et al. Acute parenchymal lung disease in immunocompetent patients: diagnostic accuracy of high-resolution CT. AJR Am J Roentgenol 2000;174:1745–1750. Johkoh T, Müller NL, Akira M, et al. Eosinophilic lung diseases: diagnostic accuracy of thin-section CT in 111 patients.

703

Chapter 11 • Idiopathic Diffuse Lung Diseases Radiology 2000;216:773–780. 263. Daimon T, Johkoh T, Sumikawa H, et al. Acute eosinophilic pneumonia: thin-section CT findings in 29 patients. Eur J Radiol 2008;65:462–467. 264. du Bois R. Rare lung diseases: orphans no more? 2002;166:1157–1158. 265. Löffler W. Zur differential-diagnose der lungen infiltreierunger: III uber fluchtige succedan – infiltrate (mit eosinophilia). Beitr Klin Tuberk 1932;79:368–392. 266. Allen JN, Davis WB. Eosinophilic lung diseases. Am J Respir Crit Care Med 1994;150:1423–1438. 267. Sunderman F, Sunderman F Jr. Loffler’s syndrome associated with nickel sensitivity. Arch Intern Med 1961;107: 405–408. 268. Oh JY, Kwon SY, Yoon HI, et al. Clinical significance of a solitary ground-glass opacity (GGO) lesion of the lung detected by chest CT. Lung Cancer 2007;55:67–73. 269. Kim HY, Naidich DP, Lim KY, et al. Transient pulmonary eosinophilia incidentally found on low-dose computed tomography: findings in 40 individuals. J Comput Assist Tomogr 2008;32:101–107. 270. Carrington CB, Addington WW, Goff AM, et al. Chronic eosinophilic pneumonia. N Engl J Med 1969;280:787–798. 271. Turner-Warwick M, Assem ES, Lockwood M. Cryptogenic pulmonary eosinophilia. Clin Allergy 1976;6:135–145. 272. Jederlinic PJ, Sicilian L, Gaensler EA. Chronic eosinophilic pneumonia. A report of 19 cases and a review of the literature. Medicine (Baltimore) 1988;67:154–162. 273. Liebow AA, Carrington CB. The eosinophilic pneumonias. Medicine (Baltimore) 1969;48:251–285. 274. Gonzalez EB, Hayes D, Weedn VW. Chronic eosinophilic pneumonia (Carrington’s) with increased serum IgE levels. A distinct subset? Arch Intern Med 1988;148:2622–2624. 275. Carrington CB, Cugell DW, Gaensler EA, et al. Lymphangioleiomyomatosis. Physiologic-pathologic-radiologic correlations. Am Rev Respir Dis 1977;116: 977–995. 276. McCarthy DS, Pepys J. Cryptogenic pulmonary eosinophilias. Clin Allergy 1973;3:339–351. 277. Gaensler EA, Carrington CB. Peripheral opacities in chronic eosinophilic pneumonia: the photographic negative of pulmonary edema. AJR Am J Roentgenol 1977;128:1–13. 278. Luks AM, Altemeier WA. Typical symptoms and atypical radiographic findings in a case of chronic eosinophilic pneumonia. Respir Care 2006;51:764–767. 279. Onitsuka H, Onitsuka S, Yokomizo Y, et al. Computed tomography of chronic eosinophilic pneumonia. J Comput Assist Tomogr 1983;7:1092–1094. 280. Mayo JR, Müller NL, Road J, et al. Chronic eosinophilic pneumonia: CT findings in six cases. AJR Am J Roentgenol 1989;153: 727–730. 281. Zaki I, Wears R, Parnell A, et al. Case report: mediastinal lymphadenopathy in eosinophilic pneumonia. Clin Radiol 1993;48:61–62. 282. Ebara H, Ikezoe J, Johkoh T, et al. Chronic eosinophilic pneumonia: evolution of chest radiograms and CT features. J Comput

704

Assist Tomogr 1994;18:737–744. 283. Marchand E, Reynaud-Gaubert M, Lauque D, et al. Idiopathic chronic eosinophilic pneumonia. A clinical and follow-up study of 62 cases. The Groupe d’Etudes et de Recherche sur les Maladies ‘Orphelines’ Pulmonaires (GERM’O’P). Medicine (Baltimore) 1998;77:299–312. 284. Naughton M, Fahy J, FitzGerald MX. Chronic eosinophilic pneumonia. A long-term follow-up of 12 patients. Chest 1993;103:162–165. 285. Hueto-Perez-de-Heredia JJ, Dominguezdel-Valle FJ, Garcia E, et al. Chronic eosinophilic pneumonia as a presenting feature of Churg-Strauss syndrome. Eur Respir J 1994;7:1006–1008. 286. Cogen FC, Mayock RL, Zweiman B. Chronic eosinophilic pneumonia followed by polyarteritis nodosa complicating the course of bronchial asthma. Report of a case. J Allergy Clin Immunol 1977; 60:377–382. 287. McCarthy DS, Pepys J. Allergic bronchopulmonary aspergillosis. Clinical immunology. 2. Skin, nasal and bronchial tests. Clin Allergy 1971;1:415–432. 288. Hinson K, Moon A, Plummer N. Bronchopulmonary aspergillosis: a review and a report of eight new cases. Thorax 1952;7:317–333. 289. Safirstein BH, D’Souza MF, Simon G, et al. Five-year follow-up of allergic bronchopulmonary aspergillosis. Am Rev Respir Dis 1973;108:450–459. 290. Glimp RA, Bayer AS. Fungal pneumonias. Part 3. Allergic bronchopulmonary aspergillosis. Chest 1981;80:85–94. 291. Laham MN, Carpenter JL. Aspergillus terreus, a pathogen capable of causing infective endocarditis, pulmonary mycetoma, and allergic bronchopulmonary aspergillosis. Am Rev Respir Dis 1982;125: 769–772. 292. Akiyama K, Takizawa H, Suzuki M, et al. Allergic bronchopulmonary aspergillosis due to Aspergillus oryzae. Chest 1987;91: 285–286. 293. Novey HS, Wells ID. Allergic bronchopulmonary aspergillosis caused by Aspergillus ochraceus. Am J Clin Pathol 1978;70:840–843. 294. Elliott MW, Newman Taylor AJ. Allergic bronchopulmonary aspergillosis. Clin Exp Allergy 1997;27(Suppl 1):55–59. 295. Thompson PJ. Allergic bronchopulmonary fungal disease. Postgrad Med J 1988; 64(Suppl 4):96–102. 296. Gefter W, Epstein D, Miller W. Allergic bronchopulmonary aspergillosis: less common patterns. Radiology 1981;140: 307–312. 297. Greene R. The pulmonary aspergilloses: three distinct entities or a spectrum of disease. Radiology 1981;140:527–530. 298. Bateman ED. A new look at the natural history of Aspergillus hypersensitivity in asthmatics. Respir Med 1994;88:325–327. 299. Tillie-Leblond I, Tonnel AB. Allergic bronchopulmonary aspergillosis. Allergy 2005;60:1004–1013. 300. Glancy JJ, Elder JL, McAleer R. Allergic bronchopulmonary fungal disease without clinical asthma. Thorax 1981;36:345–349. 301. Henderson AH. Allergic aspergillosis: review of 32 cases. Thorax 1968;23:501–512. 302. Phelan M, Kerr I. Allergic

303.

304.

305.

306.

307.

308.

309. 310.

311. 312.

313. 314.

315.

316.

317.

318.

319.

320.

bronchopulmonary aspergillosis: the radiologic appearance during long-term follow-up. Clin Radiol 1984;35:385–392. Imbeau SA, Cohen M, Reed CE. Allergic bronchopulmonary aspergillosis in infants. Am J Dis Child 1977;131:1127– 1130. Malo JL, Pepys J, Simon G. Studies in chronic allergic bronchopulmonary aspergillosis. 2. Radiological findings. Thorax 1977;32:262–268. Shah A, Kala J, Sahay S, et al. Frequency of familial occurrence in 164 patients with allergic bronchopulmonary aspergillosis. Ann Allergy Asthma Immunol 2008;101: 363–369. Virnig C, Bush RK. Allergic bronchopulmonary aspergillosis: a US perspective. Curr Opin Pulm Med 2007;13: 67–71. McCarthy DS, Simon G, Hargreave FE. The radiological appearances in allergic broncho-pulmonary aspergillosis. Clin Radiol 1970;21:366–375. Panchal N, Bhagat R, Pant C, et al. Allergic bronchopulmonary aspergillosis: the spectrum of computed tomography appearances. Respir Med 1997;91:213–219. Huchton DM. Allergic fungal sinusitis: an otorhinolaryngologic perspective. Allergy Asthma Proc 2003;24:307–311. Willard CC, Eusterman VD, Massengil PL. Allergic fungal sinusitis: report of 3 cases and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003; 96:550–560. Venarske DL, deShazo RD. Sinobronchial allergic mycosis: the SAM syndrome. Chest 2002;121:1670–1676. Schubert MS, Goetz DW. Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis. J Allergy Clin Immunol 1998;102:387–394. deShazo RD, Swain RE. Diagnostic criteria for allergic fungal sinusitis. J Allergy Clin Immunol 1995;96:24–35. Manning S, Merkel M, Kriesel K, et al. Computed tomography and magnetic resonance imaging diagnosis of allergic fungal sinusitis. Laryngoscope 1997;107: 170–176. Patterson R, Greenberger PA, Radin RC, et al. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med 1982;96: 286–291. Rosenberg M, Patterson R, Mintzer R, et al. Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med 1977;86: 405–414. Hoehne JH, Reed CE, Dickie HA. Allergic bronchopulmonary aspergillosis is not rare. With a note on preparation of antigen for immunologic tests. Chest 1973;63:177–181. Currie DC, Goldman JM, Cole PJ, et al. Comparison of narrow section computed tomography and plain chest radiography in chronic allergic bronchopulmonary aspergillosis. Clin Radiol 1987;38:593–596. Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol 1988;81:646–650. Greenberger PA, Miller TP, Roberts M, et al. Allergic bronchopulmonary aspergillosis in patients with and without

References

321.

322.

323.

324.

325. 326.

327.

328.

329.

330.

331.

332.

333.

334.

335.

336.

337.

evidence of bronchiectasis. Ann Allergy Asthma Immunol 1993;70:333–338. Kumar R, Chopra D. Evaluation of allergic bronchopulmonary aspergillosis in patients with and without central bronchiectasis. J Asthma 2002;39:473–477. Kumar R. Mild, moderate, and severe forms of allergic bronchopulmonary aspergillosis: a clinical and serologic evaluation. Chest 2003;124:890–892. Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients. Chest 2007;132: 1183–1190. Eaton T, Garrett J, Milne D, et al. Allergic bronchopulmonary aspergillosis in the asthma clinic. A prospective evaluation of CT in the diagnostic algorithm. Chest 2000;118:66–72. Zimmerman RA, Miller WT. Pulmonary aspergillosis. Am J Roentgenol Radium Ther Nucl Med 1970;109:505–517. Lipinski JK, Weisbrod GL, Sanders DE. Unusual manifestations of pulmonary aspergillosis. J Can Assoc Radiol 1978;29: 216–220. Mintzer RA, Rogers LF, Kruglik GD, et al. The spectrum of radiologic findings in allergic bronchopulmonary aspergillosis. Radiology 1978;127:301–307. Goyal R, White CS, Templeton PA, et al. High attenuation mucous plugs in allergic bronchopulmonary aspergillosis: CT appearance. J Comput Assist Tomogr 1992;16:649–650. Modem RR, Florence RR, Goulart RA, et al. Pulmonary Aspergillus-associated calcium oxalate crystals. Diagn Cytopathol 2006;34: 692–693. Logan PM, Müller NL. High-attenuation mucous plugging in allergic bronchopulmonary aspergillosis. Can Assoc Radiol J 1996;47:374–377. Berkin KE, Vernon DR, Kerr JW. Lung collapse caused by allergic bronchopulmonary aspergillosis in non-asthmatic patients. BMJ (Clin Res Ed) 1982;285:552–553. Murphy D, Lane DJ. Pleural effusion in allergic bronchopulmonary aspergillosis: two case reports. Br J Dis Chest 1981;75: 91–95. Angus RM, Davies ML, Cowan MD, et al. Computed tomographic scanning of the lung in patients with allergic bronchopulmonary aspergillosis and in asthmatic patients with a positive skin test to Aspergillus fumigatus. Thorax 1994;49: 586–589. Reiff DB, Wells AU, Carr DH, et al. CT findings in bronchiectasis: limited value in distinguishing between idiopathic and specific types. AJR Am J Roentgenol 1995; 165:261–267. Mitchell TA, Hamilos DL, Lynch DA, et al. Distribution and severity of bronchiectasis in allergic bronchopulmonary aspergillosis (ABPA). J Asthma 2000;37:65–72. Ward S, Heyneman L, Lee MJ, et al. Accuracy of CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients. AJR Am J Roentgenol 1999;173:937–942. Neeld DA, Goodman LR, Gurney JW, et al.

338.

339.

340.

341.

342. 343.

344. 345. 346.

347.

348. 349. 350. 351. 352. 353.

354.

355. 356. 357.

Computerized tomography in the evaluation of allergic bronchopulmonary aspergillosis. Am Rev Respir Dis 1990;142: 1200–1205. Ein ME, Wallace RJ Jr, Williams TW Jr. Allergic bronchopulmonary aspergillosislike syndrome consequent to aspergilloma. Am Rev Respir Dis 1979;119:811–820. Geller DE, Kaplowitz H, Light MJ, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis: reported prevalence, regional distribution, and patient characteristics. Scientific advisory group, investigators, and coordinators of the epidemiologic study of cystic fibrosis. Chest 1999;116:639–646. Stevens DA, Moss RB, Kurup VP, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis – state of the art: cystic fibrosis foundation consensus conference. Clin Infect Dis 2003;37(Suppl 3):S225–264. Mastella G, Rainisio M, Harms HK, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis. A European epidemiological study. Epidemiologic registry of cystic fibrosis. Eur Respir J 2000;16:464–471. Morrison DA, Goldman AL. Radiographic patterns of drug-induced lung diseases. Radiology 1979;131:299–304. Cooper JA Jr, White DA, Matthay RA. Drug-induced pulmonary disease. Part 2: noncytotoxic drugs. Am Rev Respir Dis 1986;133:488–505. Hendrickson RM, Simpson F. Clofibrate and eosinophilic pneumonia. JAMA 1982;247:3082. Davies D, Jones JK. Pulmonary eosinophilia caused by penicillamine. Thorax 1980;35:957–958. Tazelaar HD, Myers JL, Drage CW, et al. Pulmonary disease associated with L-tryptophan-induced eosinophilic myalgia syndrome. Clinical and pathologic features. Chest 1990;97:1032–1036. Strumpf IJ, Drucker RD, Anders KH, et al. Acute eosinophilic pulmonary disease associated with the ingestion of L-tryptophan-containing products. Chest 1991;99:8–13. Ottesen EA, Nutman TB. Tropical pulmonary eosinophilia. Annu Rev Med 1992;43:417–424. Udwadia FE. Tropical eosinophilia: a review. Respir Med 1993;87:17–21. Donohugh D. Tropical eosinophilia. An etiologic inquiry. N Engl J Med 1963;269: 1357–1364. Herlinger H. Pulmonary changes in tropical eosinophilia. Br J Radiol 1963;36:889–901. Neva FA, Ottesen EA. Tropical (filarial) eosinophilia. N Engl J Med 1978;298: 1129–1131. Dalrymple W. Tropical eosinophilia. Report of two cases occurring more than a year after departure from India. N Engl J Med 1955;252:585–586. Khoo F, Danaraj T. The roentgenographic appearance of eosinophilic lung (tropical eosinophilia). AJR Am J Roentgenol 1960; 83:251–259. Spry CJ, Kumaraswami V. Tropical eosinophilia. Semin Hematol 1982;19: 107–115. Ball J. Tropical pulmonary eosinophilia. Trans Roy Soc Trop Med Hyg 1950;44: 237–258. Basu S. X-ray appearances in the lung

358.

359. 360. 361.

362.

363. 364. 365. 366.

367.

368. 369.

370.

371.

372. 373. 374.

375.

376.

377.

fields in tropical eosinophilia. Indian Med Gaz 1954;89:212–217. Sandhu M, Mukhopadhyay S, Sharma SK. Tropical pulmonary eosinophilia: a comparative evaluation of plain chest radiography and computed tomography. Australas Radiol 1996;40:32–37. Reeder MM, Palmer PE. Acute tropical pneumonias. Semin Roentgenol 1980;15: 35–49. Gelpi AP, Mustafa A. Ascaris pneumonia. Am J Med 1968;44:377–389. Phills JA, Harrold AJ, Whiteman GV, et al. Pulmonary infiltrates, asthma and eosinophilia due to Ascaris suum infestation in man. N Engl J Med 1972; 286:965–970. Roig J, Romeu J, Riera C, et al. Acute eosinophilic pneumonia due to toxocariasis with bronchoalveolar lavage findings. Chest 1992;102:294–296. Butland RJ, Coulson IH. Pulmonary eosinophilia associated with cutaneous larva migrans. Thorax 1985;40:76–77. Fraser R, Pare J, Pare P, et al. Diagnosis of diseases of the chest. Philadelphia: WB Saunders, 1989. De Leon EP, Pardo de Tavera M. Pulmonary schistosomiasis in the Philippines. Dis Chest 1968;53:154–161. Wright D, Gold E. Löffler’s syndrome associated with creeping eruption (cutaneous helminthiasis). Arch Intern Med 1946;78:303–312. Woodring JH, Halfhill H 2nd, Reed JC. Pulmonary strongyloidiasis: clinical and imaging features. AJR Am J Roentgenol 1994;162:537–542. Liebow A. Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 1973;108:1–18. Katzenstein AL. Katzenstein and Askin’s surgical pathology of non-neoplastic lung disease, 3rd ed. Philadelphia: WB Saunders, 1997. Hanson G, Flor N, Wells I, et al. Bronchocentric granulomatosis: a complication of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 1977;59:83–90. Katzenstein AL, Liebow AA, Friedman PJ. Bronchocentric granulomatosis, mucoid impaction, and hypersensitivity reactions to fungi. Am Rev Respir Dis 1975;111: 497–537. Saldana M. Bronchocentric granulomatosis: clinicopathologic observations in 17 patients. Lab Invest 1979;40:281–282. Koss MN, Robinson RG, Hochholzer L. Bronchocentric granulomatosis. Hum Pathol 1981;12:632–638. Ward S, Heyneman LE, Flint JD, et al. Bronchocentric granulomatosis: computed tomographic findings in five patients. Clin Radiol 2000;55:296–300. Robinson R, Wehunt W, Tsou E, et al. Bronchocentric granulomatosis: roentgenographic manifestations. Am Rev Respir Dis 1982;125:751–756. Berendsen HH, Hofstee N, Kapsenberg PD, et al. Bronchocentric granulomatosis associated with seropositive polyarthritis. Thorax 1985;40:396–397. Frazier AA, Rosado-de-Christenson ML, Galvin JR, et al. Pulmonary angiitis and granulomatosis: radiologic-pathologic correlation. RadioGraphics 1998;18:687–

705

Chapter 11 • Idiopathic Diffuse Lung Diseases 710. 378. Clee MD, Lamb D, Urbaniak SJ, et al. Progressive bronchocentric granulomatosis: case report. Thorax 1982;37:947–949. 379. Bain BJ. Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome. Br J Haematol 1996;95:2–9. 380. Chusid M, Dale D, West B, et al. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine 1975;54:1–27. 381. Fauci AS, Harley JB, Roberts WC, et al. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med 1982;97: 78–92. 382. Klion AD, Bochner BS, Gleich GJ, et al. Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol 2006;117:1292–1302. 383. Rothenberg ME, Klion AD, Roufosse FE, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 2008;358: 1215–1228. 384. Parrillo JE, Borer JS, Henry WL, et al. The cardiovascular manifestations of the hypereosinophilic syndrome. Prospective study of 26 patients, with review of the literature. Am J Med 1979;67:572– 582. 385. Epstein DM, Taormina V, Gefter WB, et al. The hypereosinophilic syndrome. Radiology 1981;140:59–62. 386. Kang EY, Shim JJ, Kim JS, et al. Pulmonary involvement of idiopathic hypereosinophilic syndrome: CT findings in five patients. J Comput Assist Tomogr 1997;21:612–615. 387. Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Intern Med 1978;89:167–172. 388. Luksza AR, Jones DK. Comparison of whole-blood eosinophil counts in extrinsic asthmatics with acute and chronic asthma. BMJ (Clin Res Ed) 1982;285:1229–1231. 389. Davis SD, Schaller J, Wedgwood RJ. Job’s syndrome. Recurrent, ‘cold,’ staphylococcal abscesses. Lancet 1966;1:1013–1015. 390. Donabedian H, Gallin JI. The hyperimmunoglobulin E recurrentinfection (Job’s) syndrome. A review of the NIH experience and the literature. Medicine (Baltimore) 1983;62:195–208. 391. Merten DF, Buckley RH, Pratt PC, et al. Hyperimmunoglobulinemia E syndrome: radiographic observations. Radiology 1979;132:71–78. 392. Jhaveri KS, Sahani DV, Shetty PG, et al. Hyperimmunoglobulinaemia E syndrome: pulmonary imaging features. Australas Radiol 2000;44:328–330. 393. Freeman AF, Kleiner DE, Nadiminti H, et al. Causes of death in hyper-IgE syndrome. J Allergy Clin Immunol 2007;119:1234–1240. 394. Buckley RH, Wray BB, Belmaker EZ. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics 1972;49:59–70. 395. Manson DE, Sikka S, Reid B, et al. Primary immunodeficiencies: a pictorial immunology primer for radiologists. Pediatr Radiol 2000;30:501–510. 396. Santambrogio L, Nosotti M, Pavoni G,

706

397.

398.

399. 400.

401.

402. 403. 404.

405.

406. 407.

408.

409.

410.

411.

412.

413.

et al. Pneumatocele complicated by fungal lung abscess in Job’s syndrome. Successful lobectomy with the aid of videothoracoscopy. Scand Cardiovasc J 1997;31:177–179. Kirchner SG, Sivit CJ, Wright PF. Hyperimmunoglobulinemia E syndrome: association with osteoporosis and recurrent fractures. Radiology 1985;156:362. Fitch SJ, Magill HL, Herrod HG, et al. Hyperimmunoglobulinemia E syndrome: pulmonary imaging considerations. Pediatr Radiol 1986;16:285–288. Rosen S, Castleman B, Liebow A. Pulmonary alveolar proteinosis. N Engl J Med 1958;258:1123–1142. Inoue Y, Trapnell BC, Tazawa R, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med 2008;177:752–762. Frazier AA, Franks TJ, Cooke EO, et al. From the archives of the AFIP: pulmonary alveolar proteinosis. RadioGraphics 2008;28:883–899, quiz 915. Davidson JM, Macleod WM. Pulmonary alveolar proteinosis. Br J Dis Chest 1969; 63:13–28. McEuen DD, Abraham JL. Particulate concentrations in pulmonary alveolar proteinosis. Environ Res 1978;17:334–339. Heppleston AG, Wright NA, Stewart JA. Experimental alveolar lipo-proteinosis following the inhalation of silica. J Pathol 1970;101:293–307. Buechner HA, Ansari A. Acute silicoproteinosis. A new pathologic variant of acute silicosis in sandblasters, characterized by histologic features resembling alveolar proteinosis. Dis Chest 1969;55:274–278. Suratt PM, Winn WC Jr, Brody AR, et al. Acute silicosis in tombstone sandblasters. Am Rev Respir Dis 1977;115:521–529. Miller RR, Churg AM, Hutcheon M, et al. Pulmonary alveolar proteinosis and aluminum dust exposure. Am Rev Respir Dis 1984;130:312–315. Keller CA, Frost A, Cagle PT, et al. Pulmonary alveolar proteinosis in a painter with elevated pulmonary concentrations of titanium. Chest 1995;108:277–280. Tran Van Nhieu J, Vojtek AM, Bernaudin JF, et al. Pulmonary alveolar proteinosis associated with Pneumocystis carinii. Ultrastructural identification in bronchoalveolar lavage in AIDS and immunocompromised non-AIDS patients. Chest 1990;98:801–805. Carnovale R, Zornoza J, Goldman AM, et al. Pulmonary alveolar proteinosis: its association with hematologic malignancy and lymphoma. Radiology 1977;122: 303–306. Pollack SM, Gutierrez G, Ascensao J. Pulmonary alveolar proteinosis with myeloproliferative syndrome with myelodysplasia: bronchoalveolar lavage reduces white blood cell count. Am J Hematol 2006;81:634–638. Inaba H, Jenkins JJ, McCarville MB, et al. Pulmonary alveolar proteinosis in pediatric leukemia. Pediatr Blood Cancer 2008;51: 66–70. Sergeeva A, Ono Y, Rios R, et al. High titer autoantibodies to GM-CSF in patients with AML, CML and MDS are associated with active disease. Leukemia 2008;22:

783–790. 414. Colon AR Jr, Lawrence RD, Mills SD, et al. Childhood pulmonary alveolar proteinosis (PAP). Report of a case and review of the literature. Am J Dis Child 1971;121: 481–485. 415. Jennings VM, Dillehay DL, Webb SK, et al. Pulmonary alveolar proteinosis in SCID mice. Am J Respir Cell Mol Biol 1995;13: 297–306. 416. Mahut B, Delacourt C, Scheinmann P, et al. Pulmonary alveolar proteinosis: experience with eight pediatric cases and a review. Pediatrics 1996;97:117–122. 417. Yousem SA. Alveolar lipoproteinosis in lung allograft recipients. Hum Pathol 1997; 28:1383–1386. 418. Wardwell NR Jr, Miller R, Ware LB. Pulmonary alveolar proteinosis associated with a disease-modifying antirheumatoid arthritis drug. Respirology 2006;11:663–665. 419. Wagner U, Staats P, Moll R, et al. Imatinibassociated pulmonary alveolar proteinosis. Am J Med 2003;115:674. 420. Pedroso SL, Martins LS, Sousa S, et al. Pulmonary alveolar proteinosis: a rare pulmonary toxicity of sirolimus. Transpl Int 2007;20:291–296. 421. Chetcuti PA, Ball RJ. Surfactant apoprotein B deficiency. Arch Dis Child Fetal Neonatal Ed 1995;73:F125–127. 422. Martinez-Moczygemba M, Doan ML, Elidemir O, et al. Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1. J Exp Med 2008;205:2711–2716. 423. Suzuki T, Sakagami T, Rubin BK, et al. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med 2008;205:2703–2710. 424. Doan ML, Guillerman RP, Dishop MK, et al. Clinical, radiological and pathological features of ABCA3 mutations in children. Thorax 2008;63:366–373. 425. Uchida K, Beck DC, Yamamoto T, et al. GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis. N Engl J Med 2007;356: 567–579. 426. Prakash UB, Barham SS, Carpenter HA, et al. Pulmonary alveolar phospholipoproteinosis: experience with 34 cases and a review. Mayo Clin Proc 1987;62:499–518. 427. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med 2002;166:215–235. 428. Anton HC, Gray B. Pulmonary alveolar proteinosis presenting with pneumothorax. Clin Radiol 1967;18:428–431. 429. Wang BM, Stern EJ, Schmidt RA, et al. Diagnosing pulmonary alveolar proteinosis. A review and an update. Chest 1997;111:460–466. 430. Honda Y, Kuroki Y, Matsuura E, et al. Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids. Am J Respir Crit Care Med 1995;152:1860–1866. 431. Ramirez R. Pulmonary alveolar proteinosis. A roentgenologic analysis. AJR Am J Roentgenol 1964;92:571–577. 432. McCook TA, Kirks DR, Merten DF, et al. Pulmonary alveolar proteinosis in children. AJR Am J Roentgenol 1981;137:1023–1027. 433. Rubin E, Weisbrod GL, Sanders DE.

References

434.

435. 436. 437.

438.

439.

440.

441.

442.

443.

444.

445.

446.

447.

448. 449.

450.

451.

Pulmonary alveolar proteinosis: relationship to silicosis and pulmonary infection. Radiology 1980;135:35–41. Miller PA, Ravin CE, Smith GJ, et al. Pulmonary alveolar proteinosis with interstitial involvement. AJR Am J Roentgenol 1981;137:1069–1071. Phillips W, Constance T. Pulmonary alveolar proteinosis. Med J Aust 1963;2: 357–359. Godwin J, Müller N, Takasugi J. Pulmonary alveolar proteinosis: CT findings. Radiology 1988;169:609–613. Lee KN, Levin DL, Webb WR, et al. Pulmonary alveolar proteinosis: highresolution CT, chest radiographic, and functional correlations. Chest 1997;111: 989–995. Murch CR, Carr DH. Computed tomography appearances of pulmonary alveolar proteinosis. Clin Radiol 1989;40: 240–243. Newell JD, Underwood GH, Russo DJ, et al. Computed tomographic appearance of pulmonary alveolar proteinosis in adults. CT 1984;8:21–29. Holbert JM, Costello P, Li W, et al. CT features of pulmonary alveolar proteinosis. AJR Am J Roentgenol 2001;176:1287– 1294. Rossi SE, Erasmus JJ, Volpacchio M, et al. ‘Crazy-paving’ pattern at thin-section CT of the lungs: radiologic-pathologic overview. RadioGraphics 2003;23: 1509–1519. Murayama S, Murakami J, Yabuuchi H, et al. ‘Crazy paving appearance’ on high resolution CT in various diseases. J Comput Assist Tomogr 1999;23:749–752. Franquet T, Gimenez A, Bordes R, et al. The crazy-paving pattern in exogenous lipoid pneumonia: CT-pathologic correlation. AJR Am J Roentgenol 1998;170: 315–317. Tan RT, Kuzo RS. High-resolution CT findings of mucinous bronchioloalveolar cell carcinoma: a case of pseudopulmonary alveolar proteinosis. AJR Am J Roentgenol 1997;168:99–100. Bedrossian CW, Luna MA, Conklin RH, et al. Alveolar proteinosis as a consequence of immunosuppression. A hypothesis based on clinical and pathologic observations. Hum Pathol 1980;11:527–535. Witty LA, Tapson VF, Piantadosi CA. Isolation of mycobacteria in patients with pulmonary alveolar proteinosis. Medicine (Baltimore) 1994;73:103–109. Goldschmidt N, Nusair S, Gural A, et al. Disseminated Mycobacterium kansasii infection with pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia. Am J Hematol 2003;74:221–223. Ramirez J. Bronchopulmonary lavage. New techniques and observations. Dis Chest 1966;50:581–588. Rogers RM, Levin DC, Gray BA, et al. Physiologic effects of bronchopulmonary lavage in alveolar proteinosis. Am Rev Respir Dis 1978;118:255–264. Gale ME, Karlinsky JB, Robins AG. Bronchopulmonary lavage in pulmonary alveolar proteinosis: chest radiograph observations. AJR Am J Roentgenol 1986;146:981–985. Parker LA, Novotny DB. Recurrent

452.

453. 454. 455.

456.

457.

458.

459.

460. 461.

462.

463.

464. 465.

466. 467.

468.

469.

470.

alveolar proteinosis following double lung transplantation. Chest 1997;111:1457–1458. Venkateshiah SB, Yan TD, Bonfield TL, et al. An open-label trial of granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis. Chest 2006;130:227–237. Harbitz F. Extensive calcification of the lungs as a distinct disease. Arch Intern Med 1918;21:139–146. Ucan ES, Keyf AI, Aydilek R, et al. Pulmonary alveolar microlithiasis: review of Turkish reports. Thorax 1993;48:171–173. Corut A, Senyigit A, Ugur SA, et al. Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis. Am J Hum Genet 2006;79:650–656. Huqun, Izumi S, Miyazawa H, et al. Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis. Am J Respir Crit Care Med 2007;175:263–268. Chalmers AG, Wyatt J, Robinson PJ. Computed tomographic and pathological findings in pulmonary alveolar microlithiasis. Br J Radiol 1986;59:408–411. Pant K, Shah A, Mathur RK, et al. Pulmonary alveolar microlithiasis with pleural calcification and nephrolithiasis. Chest 1990;98:245–246. Coetzee T. Pulmonary alveolar microlithiasis with involvement of the sympathetic nervous system and gonads. Thorax 1970;25:637–642. Sears MR, Chang AR, Taylor AJ. Pulmonary alveolar microlithiasis. Thorax 1971;26:704–711. Prakash UB, Barham SS, Rosenow EC 3rd, et al. Pulmonary alveolar microlithiasis. A review including ultrastructural and pulmonary function studies. Mayo Clin Proc 1983;58:290–300. Sosman MC, Dodd GD, Jones WD, et al. The familial occurrence of pulmonary alveolar microlithiasis. Am J Roentgenol Radium Ther Nucl Med 1957;77:947–1012. Castellana G, Gentile M, Castellana R, et al. Pulmonary alveolar microlithiasis: clinical features, evolution of the phenotype, and review of the literature. Am J Med Genet 2002;111:220–224. Schmidt H, Lorcher U, Kitz R, et al. Pulmonary alveolar microlithiasis in children. Pediatr Radiol 1996;26:33–36. Ritchie DA, O’Connor SA, McGivern D. An unusual presentation of pulmonary alveolar microlithiasis and diaphyseal aclasia. Br J Radiol 1992;65:178–181. Caffrey P, Altman R. Pulmonary alveolar microlithiasis occurring in premature twins. J Pediatr 1965;66:758–763. Mariotta S, Ricci A, Papale M, et al. Pulmonary alveolar microlithiasis: report on 576 cases published in the literature. Sarcoidosis Vasc Diffuse Lung Dis 2004;21:173–181. Pracyk JB, Simonson SG, Young SL, et al. Composition of lung lavage in pulmonary alveolar microlithiasis. Respiration 1996;63:254–260. Chan ED, Morales DV, Welsh CH, et al. Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med 2002;165:1654–1669. Balikian JP, Fuleihan FJ, Nucho CN.

471.

472.

473.

474.

475.

476.

477.

478.

479.

480.

481.

482.

483.

484.

485.

486.

487. 488.

Pulmonary alveolar microlithiasis. Report of five cases with special reference to roentgen manifestations. AJR Am J Roentgenol 1968;103:509–518. Helbich TH, Wojnarovsky C, Wunderbaldinger P, et al. Pulmonary alveolar microlithiasis in children: radiographic and high-resolution CT findings. AJR Am J Roentgenol 1997;168: 63–65. Volle E, Kaufmann HJ. Pulmonary alveolar microlithiasis in pediatric patients: review of the world literature and two new observations. Pediatr Radiol 1987;17: 439–442. Deniz O, Ors F, Tozkoparan E, et al. High resolution computed tomographic features of pulmonary alveolar microlithiasis. Eur J Radiol 2005;55:452–460. Cluzel P, Grenier P, Bernadac P, et al. Pulmonary alveolar microlithiasis: CT findings. J Comput Assist Tomogr 1991; 15:938–942. Korn MA, Schurawitzki H, Klepetko W, et al. Pulmonary alveolar microlithiasis: findings on high-resolution CT. AJR Am J Roentgenol 1992;158:981–982. Marchiori E, Goncalves CM, Escuissato DL, et al. Pulmonary alveolar microlithiasis: high-resolution computed tomography findings in 10 patients. J Bras Pneumol 2007;33:552–557. Thurairajasingam S, Dharmasena BD, Kasthuriratna T. Pulmonary alveolar microlithiasis. Australas Radiol 1975;19: 175–180. Miro JM, Moreno A, Coca A, et al. Pulmonary alveolar microlithiasis with an unusual radiological pattern. Br J Dis Chest 1982;76:91–96. Winzelberg GG, Boller M, Sachs M, et al. CT evaluation of pulmonary alveolar microlithiasis. J Comput Assist Tomogr 1984;8:1029–1031. Hoshino H, Koba H, Inomata S, et al. Pulmonary alveolar microlithiasis: high-resolution CT and MR findings. J Comput Assist Tomogr 1998;22:245–248. Chang YC, Yang PC, Luh KT, et al. High-resolution computed tomography of pulmonary alveolar microlithiasis. J Formos Med Assoc 1999;98:440–443. Chai JL, Patz EF Jr. CT of the lung: patterns of calcification and other high-attenuation abnormalities. AJR Am J Roentgenol 1994;162:1063–1066. Gasparetto EL, Tazoniero P, Escuissato DL, et al. Pulmonary alveolar microlithiasis presenting with crazy-paving pattern on high resolution CT. Br J Radiol 2004;77:974–976. Sumikawa H, Johkoh T, Tomiyama N, et al. Pulmonary alveolar microlithiasis: CT and pathologic findings in 10 patients. Monaldi Arch Chest Dis 2005;63:59–64. Taguchi Y, Fuyuno G, Shioya S, et al. MR appearance of pulmonary metastatic calcification. J Comput Assist Tomogr 1996;20:38–41. Kino T, Kohara Y, Tsuji S. Pulmonary alveolar microlithiasis. A report of two young sisters. Am Rev Respir Dis 1972;105:105–110. Thind GS, Bhatia JL. Pulmonary alveolar microlithiasis. Br J Dis Chest 1978;72:151–154. Brown ML, Swee RG, Olson RJ, et al.

707

Chapter 11 • Idiopathic Diffuse Lung Diseases

489.

490.

491.

492.

493.

494.

495.

496.

497.

498.

499.

500.

501.

502.

503. 504.

505.

506.

708

Pulmonary uptake of 99mTc diphosphonate in alveolar microlithiasis. AJR Am J Roentgenol 1978;131:703–704. Shah TC, Talwar A, Shah RD, et al. Pulmonary alveolar microlithiasis: radiographic and scintigraphic correlation. Clin Nucl Med 2007;32:249–251. Sahin U, Yildiz M, Bircan HA, et al. Absence of pulmonary uptake of Tc-99m methylenediphosphonate in alveolar microlithiasis. Ann Nucl Med 2004;18: 695–698. Ito K, Kubota K, Yukihiro M, et al. FDG-PET/CT finding of high uptake in pulmonary alveolar microlithiasis. Ann Nucl Med 2007;21:415–418. Moran CA, Hochholzer L, Hasleton PS, et al. Pulmonary alveolar microlithiasis. A clinicopathologic and chemical analysis of seven cases. Arch Pathol Lab Med 1997; 121:607–611. Eggert CH, Albright RC. Metastatic pulmonary calcification in a dialysis patient: case report and a review. Hemodial Int 2006;10(Suppl 2):S51–55. Hartman TE, Müller NL, Primack SL, et al. Metastatic pulmonary calcification in patients with hypercalcemia: findings on chest radiographs and CT scans. AJR Am J Roentgenol 1994;162:799–802. Lingam RK, Teh J, Sharma A, et al. Case report. Metastatic pulmonary calcification in renal failure: a new HRCT pattern. Br J Radiol 2002;75:74–77. Ullmer E, Borer H, Sandoz P, et al. Diffuse pulmonary nodular infiltrates in a renal transplant recipient. Metastatic pulmonary calcification. Chest 2001;120:1394–1398. Johkoh T, Ikezoe J, Nagareda T, et al. Metastatic pulmonary calcification: early detection by high-resolution CT. J Comput Assist Tomogr 1993;17:471–473. Okada F, Ando Y, Yoshitake S, et al. Clinical/pathologic correlations in 553 patients with primary centrilobular findings on high-resolution CT scan of the thorax. Chest 2007;132:1939–1948. Chung MJ, Lee KS, Franquet T, et al. Metabolic lung disease: imaging and histopathologic findings. Eur J Radiol 2005;54:233–245. Marchiori E, Müller NL, Souza AS Jr, et al. Unusual manifestations of metastatic pulmonary calcification: high-resolution CT and pathological findings. J Thorac Imaging 2005;20:66–70. Kang EH, Kim ES, Kim CH, et al. Atypical radiological manifestation of pulmonary metastatic calcification. Korean J Radiol 2008;9:186–189. Weinstein DS. Pulmonary sarcoidosis: calcified micronodular pattern simulating pulmonary alveolar microlithiasis. J Thorac Imaging 1999;14:218–220. Kanne JP, Godwin JD, Takasugi JE, et al. Diffuse pulmonary ossification. J Thorac Imaging 2004;19:98–102. Azuma A, Miyamoto H, Enomoto T, et al. Familial clustering of dendriform pulmonary ossification. Sarcoidosis Vasc Diffuse Lung Dis 2003;20:152–154. Gevenois PA, Abehsera M, Knoop C, et al. Disseminated pulmonary ossification in end-stage pulmonary fibrosis: CT demonstration. AJR Am J Roentgenol 1994;162:1303–1304. Kim TS, Han J, Chung MP, et al.

507. 508. 509. 510.

511.

512.

513.

514.

515.

516.

517. 518.

519.

520. 521. 522. 523.

524. 525.

526.

Disseminated dendriform pulmonary ossification associated with usual interstitial pneumonia: incidence and thin-section CT-pathologic correlation. Eur Radiol 2005;15:1581–1585. Woolley K, Stark P. Pulmonary parenchymal manifestations of mitral valve disease. RadioGraphics 1999;19:965–972. Aughenbaugh GL. Thoracic manifestations of neurocutaneous diseases. Radiol Clin North Am 1984;22:741–756. Riccardi VM. Von Recklinghausen neurofibromatosis. N Engl J Med 1981;305:1617–1627. Mulvihill JJ, Parry DM, Sherman JL, et al. NIH conference. Neurofibromatosis 1 (Recklinghausen disease) and neurofibromatosis 2 (bilateral acoustic neurofibromatosis). An update. Ann Intern Med 1990;113:39–52. Klatte EC, Franken EA, Smith JA. The radiographic spectrum in neurofibromatosis. Semin Roentgenol 1976;11:17–33. Ryu JH, Parambil JG, McGrann PS, et al. Lack of evidence for an association between neurofibromatosis and pulmonary fibrosis. Chest 2005;128:2381–2386. Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol 1988;45:575–578. Schabel SI, Schmidt GE, Vujic I. Overlooked pulmonary malignancy in neurofibromatosis. J Can Assoc Radiol 1980;31:135–136. Patel YD, Morehouse HT. Neurofibrosarcomas in neurofibromatosis: role of CT scanning and angiography. Clin Radiol 1982;33:555–560. Kumar AJ, Kuhajda FP, Martinez CR, et al. Computed tomography of extracranial nerve sheath tumors with pathological correlation. J Comput Assist Tomogr 1983;7:857–865. Felson B. The extrapleural space. Semin Roentgenol 1977;12:327–333. Klaas VE. A diagnostic approach to asbestosis, utilizing clinical criteria, high resolution computed tomography, and gallium scanning. Am J Ind Med 1993; 23:801–809. Casselman ES, Miller WT, Shu Ren L, et al. Von Recklinghausen’s disease: incidence of roentgenographic findings with a clinical review of the literature. CRC Crit Rev Diagn Imaging 1977;9:387–419. Hunt J, Pugh D. Skeletal lesions in neurofibromatosis. Radiology 1961;76:1–20. Rosenberg DM. Inherited forms of interstitial lung disease. Clin Chest Med 1982;3:635–641. Holt JF. 1977 Edward B. D. Neuhauser lecture: neurofibromatosis in children. AJR Am J Roentgenol 1978;130:615–639. Meszaros WT, Guzzo F, Schorsch H. Neurofibromatosis. Am J Roentgenol Radium Ther Nucl Med 1966;98:557– 569. Salerno NR, Edeiken J. Vertebral scalloping in neurofibromatosis. Radiology 1970;97: 509–510. Gibbens DT, Argy N. Chest case of the day. Lateral thoracic meningocele in a patient with neurofibromatosis. AJR Am J Roentgenol 1991;156:1299–1300. Miles J, Pennybacker J, Sheldon P.

527. 528.

529.

530. 531.

532.

533.

534. 535. 536.

537. 538.

539. 540.

541. 542.

543.

544.

545.

Intrathoracic meningocele. Its development and association with neurofibromatosis. J Neurol Neurosurg Psychiatry 1969;32: 99–110. Dabir RR, Piccione W Jr, Kittle CF. Intrathoracic tumors of the vagus nerve. Ann Thorac Surg 1990;50:494–497. Bourgouin PM, Shepard JO, Moore EH, et al. Plexiform neurofibromatosis of the mediastinum: CT appearance. AJR Am J Roentgenol 1988;151:461–463. Fortman BJ, Kuszyk BS, Urban BA, et al. Neurofibromatosis type 1: a diagnostic mimicker at CT. RadioGraphics 2001;21: 601–612. Chalmers AH, Armstrong P. Plexiform mediastinal neurofibromas. A report of two cases. Br J Radiol 1977;50:215–217. Massaro D, Katz S. Fibrosing alveolitis: its occurrence, roentgenographic, and pathologic features in von Recklinghausen’s neurofibromatosis. Am Rev Respir Dis 1966;93:934–942. Webb WR, Goodman PC. Fibrosing alveolitis in patients with neurofibromatosis. Radiology 1977;122:289–293. Patchefsky AS, Atkinson WG, Hoch WS, et al. Interstitial pulmonary fibrosis and von Recklinghausen’s disease. An ultrastructural and immunofluorescent study. Chest 1973;64:459–464. White JE, Greaves M, Mohan M, et al. Breathlessness with bumps, lumps, and humps. Chest 1994;105:589–590. Bergin CJ, Müller NL. CT in the diagnosis of interstitial lung disease. AJR Am J Roentgenol 1985;145:505–510. Stewart DR, Cogan JD, Kramer MR, et al. Is pulmonary arterial hypertension in neurofibromatosis type 1 secondary to a plexogenic arteriopathy? Chest 2007;132:798–808. Madewell J, Feigin D. Benign tumors of the lung. Semin Roentgenol 1977;12:175–186. Unger PD, Geller GA, Anderson PJ. Pulmonary lesions in a patient with neurofibromatosis. Arch Pathol Lab Med 1984;108:654–657. McCormack FX. Lymphangioleiomyomatosis: a clinical update. Chest 2008;133:507–516. Wienecke R, Maize JC Jr, Reed JA, et al. Expression of the TSC2 product tuberin and its target Rap1 in normal human tissues. Am J Pathol 1997;150:43–50. Osborne JP, Fryer A, Webb D. Epidemiology of tuberous sclerosis. Ann N Y Acad Sci 1991;615:125–127. Avila NA, Dwyer AJ, Rabel A, et al. Sporadic lymphangioleiomyomatosis and tuberous sclerosis complex with lymphangioleiomyomatosis: comparison of CT features. Radiology 2007;242:277–285. Bell DG, King BF, Hattery RR, et al. Imaging characteristics of tuberous sclerosis. AJR Am J Roentgenol 1991;156:1081–1086. Gomez MR. Phenotypes of the tuberous sclerosis complex with a revision of diagnostic criteria. Ann N Y Acad Sci 1991; 615:1–7. Roach ES, Smith M, Huttenlocher P, et al. Diagnostic criteria: tuberous sclerosis complex. Report of the diagnostic criteria committee of the national tuberous sclerosis association. J Child Neurol

References 1992;7:221–224. 546. Fleury P, de Groot WP, Delleman JW, et al. Tuberous sclerosis: the incidence of sporadic cases versus familial cases. Brain Dev 1980;2:107–117. 547. Mitnick JS, Bosniak MA, Hilton S, et al. Cystic renal disease in tuberous sclerosis. Radiology 1983;147:85–87. 548. Braffman BH, Bilaniuk LT, Naidich TP, et al. MR imaging of tuberous sclerosis: pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review. Radiology 1992;183:227–238. 549. Dwyer JM, Hickie JB, Garvan J. Pulmonary tuberous sclerosis. Report of three patients and a review of the literature. Q J Med 1971;40:115–125. 550. Lie JT, Miller RD, Williams DE. Cystic disease of the lungs in tuberous sclerosis: clinicopathologic correlation, including body plethysmographic lung function tests. Mayo Clin Proc 1980;55:547–553. 551. Castro M, Shepherd CW, Gomez MR, et al. Pulmonary tuberous sclerosis. Chest 1995;107:189–195. 552. Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangioleiomyomatosis in women with tuberous sclerosis complex. Mayo Clin Proc 2000;75:591–594. 553. Moss J, Avila NA, Barnes PM, et al. Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex. Am J Respir Crit Care Med 2001;164: 669–671. 554. Corrin B, Liebow AA, Friedman PJ. Pulmonary lymphangiomyomatosis. A review. Am J Pathol 1975;79:348–382. 555. Maruyama H, Seyama K, Sobajima J, et al. Multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis with a TSC2 gene. Mod Pathol 2001;14:609–614. 556. Popper HH, Juettner-Smolle FM, Pongratz MG. Micronodular hyperplasia of type II pneumocytes: a new lung lesion associated with tuberous sclerosis. Histopathology 1991;18:347–354. 557. Lantuejoul S, Ferretti G, Negoescu A, et al. Multifocal alveolar hyperplasia associated with lymphangioleiomyomatosis in tuberous sclerosis. Histopathology 1997;30:570–575. 558. Muir TE, Leslie KO, Popper H, et al. Micronodular pneumocyte hyperplasia. Am J Surg Pathol 1998;22:465–472. 559. Stovin PG, Lum LC, Flower CD, et al. The lungs in lymphangiomyomatosis and in tuberous sclerosis. Thorax 1975;30:497–509. 560. Valensi QJ. Pulmonary lymphangiomyoma, a probable forme frust of tuberous sclerosis. A case report and survey of the literature. Am Rev Respir Dis 1973;108: 1411–1415. 561. Aubry MC, Myers JL, Ryu JH, et al. Pulmonary lymphangioleiomyomatosis in a man. Am J Respir Crit Care Med 2000;162:749–752. 562. Bowen J, Beasley SW. Rare pulmonary manifestations of tuberous sclerosis in children. Pediatr Pulmonol 1997;23: 114–116. 563. Harris JO, Waltuck BL, Swenson EW. The pathophysiology of the lungs in tuberous sclerosis. A case report and literature

564. 565. 566.

567.

568.

569.

570. 571. 572.

573.

574.

575.

576.

577.

578.

579.

580.

581.

review. Am Rev Respir Dis 1969;100: 379–387. Green GJ. The radiology of tuberose sclerosis. Clin Radiol 1968;19:135–147. Medley BE, McLeod RA, Houser OW. Tuberous sclerosis. Semin Roentgenol 1976;11:35–54. Stern EJ, Webb WR, Golden JA, et al. Cystic lung disease associated with eosinophilic granuloma and tuberous sclerosis: air trapping at dynamic ultrafast highresolution CT. Radiology 1992;182:325–329. Lenoir S, Grenier P, Brauner MW, et al. Pulmonary lymphangiomyomatosis and tuberous sclerosis: comparison of radiographic and thin-section CT findings. Radiology 1990;175:329–334. Polosa R, Magnano M, Crimi N, et al. Pulmonary tuberous sclerosis in a woman of child-bearing age with no mental retardation. Respir Med 1995;89:227– 231. Hanna RM, Dahniya MH, al-Marzouk N, et al. Extrarenal angiomyolipomas of the perinephric space in tuberose sclerosis. Australas Radiol 1997;41:339–341. Wenaden AE, Copley SJ. Unilateral lymphangioleiomyomatosis. J Thorac Imaging 2005;20:226–228. Pui MH, Kong HL, Choo HF. Bone changes in tuberous sclerosis mimicking metastases. Australas Radiol 1996;40:77–79. Pacheco-Rodriguez G, Kristof AS, Stevens LA, et al. Filley lecture. Genetics and gene expression in lymphangioleiomyomatosis. Chest 2002;121:S56–60. Johnson SR, Clelland CA, Ronan J, et al. The TSC-2 product tuberin is expressed in lymphangioleiomyomatosis and angiomyolipoma. Histopathology 2002;40:458–463. Avila NA, Kelly JA, Chu SC, et al. Lymphangioleiomyomatosis: abdominopelvic CT and US findings. Radiology 2000;216:147–153. Bernstein S, Newell J, Adamczyk D, et al. How common are renal angiomyolipomas in patients with pulmonary lymphangiomyomatosis? Am J Respir Crit Care Med 1995;152:2138–2143. Kerr L, Blute M, Ryu J, et al. Renal angiomyolipoma in association with pulmonary lymphangioleiomyomatosis: forme fruste of tuberous sclerosis? Urology 1993;41:440–444. Kristof AS, Moss J. Lymphangioleiomyomatosis. In: Schwarz M, King T (eds). Interstitial lung disease, 4th ed. Toronto: Brian C Decker, 2003: 851–864. Johnson S. Rare diseases. 1. Lymphangioleiomyomatosis: clinical features, management and basic mechanisms. Thorax 1999;54:254–264. Fukuda Y, Kawamoto M, Yamamoto A, et al. Role of elastic fiber degradation in emphysema-like lesions of pulmonary lymphangiomyomatosis. Hum Pathol 1990;21:1252–1261. Hayashi T, Fleming MV, Stetler-Stevenson WG, et al. Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM). Hum Pathol 1997;28:1071–1078. Bonetti F, Chiodera PL, Pea M, et al. Transbronchial biopsy in

582.

583.

584.

585.

586.

587. 588.

589. 590.

591. 592.

593.

594.

595.

596.

597. 598.

lymphangiomyomatosis of the lung. HMB45 for diagnosis. Am J Surg Pathol 1993;17:1092–1102. Silverstein EF, Ellis K, Wolff M, et al. Pulmonary lymphangiomyomatosis. Am J Roentgenol Radium Ther Nucl Med 1974;120:832–850. Kruglik GD, Reed JC, Daroca PJ. Radiologic-pathologic correlation from the Armed Forces Institute of Pathology. Lymphangiomyomatosis. Radiology 1976;120:583–588. Ernst JC, Sohaey R, Cary JM. Pelvic lymphangioleiomyomatosis. Atypical precursor to pulmonary disease. Chest 1994;106:1267–1269. Guinee DG Jr, Feuerstein I, Koss MN, et al. Pulmonary lymphangioleiomyomatosis. Diagnosis based on results of transbronchial biopsy and immunohistochemical studies and correlation with high-resolution computed tomography findings. Arch Pathol Lab Med 1994;118:846–849. Miller WT, Cornog JL Jr, Sullivan MA. Lymphangiomyomatosis. A clinicalroentgenologic-pathologic syndrome. Am J Roentgenol Radium Ther Nucl Med 1971;111:565–572. Casper KA, Donnelly LF, Chen B, et al. Tuberous sclerosis complex: renal imaging findings. Radiology 2002;225:451–456. Hoon V, Thung SN, Kaneko M, Unger PD. HMB-45 reactivity in renal angiomyolipoma and lymphangioleiomyomatosis. Arch Pathol Lab Med 1994;118:732–734. King TE Jr. Restrictive lung disease in pregnancy. Clin Chest Med 1992;13:607–622. Baldi S, Papotti M, Valente ML, et al. Pulmonary lymphangioleiomyomatosis in postmenopausal women: report of two cases and review of the literature. Eur Respir J 1994;7:1013–1016. Kitaichi M, Izumi T. Lymphangioleiomyomatosis. Curr Opin Pulm Med 1995;1:417–424. Ryu JH, Moss J, Beck GJ, et al. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med 2006;173:105–111. Schiavina M, Di Scioscio V, Contini P, et al. Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex. Am J Respir Crit Care Med 2007;176:96–98. Kitaichi M, Nishimura K, Itoh H, et al. Pulmonary lymphangioleiomyomatosis: a report of 46 patients including a clinicopathologic study of prognostic factors. Am J Respir Crit Care Med 1995;151:527–533. Taylor JR, Ryu J, Colby TV, et al. Lymphangioleiomyomatosis. Clinical course in 32 patients. N Engl J Med 1990;323:1254–1260. Urban T, Kuttenn F, Gompel A, et al. Pulmonary lymphangiomyomatosis. Follow-up and long-term outcome with antiestrogen therapy: a report of eight cases. Chest 1992;102:472–476. Johnson SR, Tattersfield AE. Clinical experience of lymphangioleiomyomatosis in the UK. Thorax 2000;55:1052–1057. Chu SC, Horiba K, Usuki J, et al. Comprehensive evaluation of 35 patients

709

Chapter 11 • Idiopathic Diffuse Lung Diseases

599.

600.

601. 602.

603.

604.

605.

606.

607. 608.

609.

610.

611.

612.

613.

614.

615.

710

with lymphangioleiomyomatosis. Chest 1999;115:1041–1052. Berkman N, Bloom A, Cohen P, et al. Bilateral spontaneous pneumothorax as the presenting feature in lymphangioleiomyomatosis. Respir Med 1995;89:381–383. Steagall WK, Glasgow CG, Hathaway OM, et al. Genetic and morphologic determinants of pneumothorax in lymphangioleiomyomatosis. Am J Physiol Lung Cell Mol Physiol 2007;293:L800–808. Ryu JH, Doerr CH, Fisher SD, et al. Chylothorax in lymphangioleiomyomatosis. Chest 2003;123:623–627. Abbott GF, Rosado-de-Christenson ML, Frazier AA, et al. From the archives of the AFIP: lymphangioleiomyomatosis: radiologic-pathologic correlation. RadioGraphics 2005;25:803–828. Bergin CJ, Coblentz CL, Chiles C, et al. Chronic lung diseases: specific diagnosis by using CT. AJR Am J Roentgenol 1989;152:1183–1188. Aberle DR, Hansell DM, Brown K, et al. Lymphangiomyomatosis: CT, chest radiographic, and functional correlations. Radiology 1990;176:381–387. Müller NL, Chiles C, Kullnig P. Pulmonary lymphangiomyomatosis: correlation of CT with radiographic and functional findings. Radiology 1990;175:335–339. Rappaport D, Weisbrod G, Herman S, et al. Pulmonary lymphangioleiomyomatosis: high-resolution CT findings in four cases. AJR Am J Roentgenol 1989;152:961–964. Sherrier RH, Chiles C, Roggli V. Pulmonary lymphangioleiomyomatosis: CT findings. AJR Am J Roentgenol 1989;153:937–940. Templeton PA, McLoud TC, Müller NL, et al. Pulmonary lymphangioleiomyomatosis: CT and pathologic findings. J Comput Assist Tomogr 1989;13:54–57. Lee KN, Yoon SK, Choi SJ, et al. Cystic lung disease: a comparison of cystic size, as seen on expiratory and inspiratory HRCT scans. Korean J Radiol 2000;1:84–90. Worthy SA, Brown MJ, Müller NL. Technical report: cystic air spaces in the lung: change in size on expiratory high-resolution CT in 23 patients. Clin Radiol 1998;53:515–519. Crausman R, Lynch D, Mortenson R, et al. Quantitative CT predicts the severity of physiologic dysfunction in patients with lymphangioleiomyomatosis. Chest 1996; 109:131–137. Avila NA, Kelly JA, Dwyer AJ, et al. Lymphangioleiomyomatosis: correlation of qualitative and quantitative thin-section CT with pulmonary function tests and assessment of dependence on pleurodesis. Radiology 2002;223:189–197. Pallisa E, Sanz P, Roman A, et al. Lymphangioleiomyomatosis: pulmonary and abdominal findings with pathologic correlation. RadioGraphics 2002;22: S185–198. Boehler A, Speich R, Russi EW, et al. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med 1996;335:1275–1280. Wong YY, Yeung TK, Chu WC. Atypical presentation of lymphangioleiomyomatosis as acute abdomen: CT diagnosis.

616.

617.

618.

619.

620.

621.

622.

623.

624.

625.

626.

627.

628. 629.

630. 631.

632.

AJR Am J Roentgenol 2003;181:284– 285. Avila NA, Bechtle J, Dwyer AJ, et al. Lymphangioleiomyomatosis: CT of diurnal variation of lymphangioleiomyomas. Radiology 2001;221:415–421. Johnson SR, Whale CI, Hubbard RB, et al. Survival and disease progression in UK patients with lymphangioleiomyomatosis. Thorax 2004;59:800–803. Schiavina M, Contini P, Fabiani A, et al. Efficacy of hormonal manipulation in lymphangioleiomyomatosis. A 20-yearexperience in 36 patients. Sarcoidosis Vasc Diffuse Lung Dis 2007;24:39–50. Kpodonu J, Massad MG, Chaer RA, et al. The US experience with lung transplantation for pulmonary lymphangioleiomyomatosis. J Heart Lung Transplant 2005;24:1247–1253. Karbowniczek M, Astrinidis A, Balsara BR, et al. Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism. Am J Respir Crit Care Med 2003;167:976–982. O’Brien JD, Lium JH, Parosa JF, et al. Lymphangiomyomatosis recurrence in the allograft after single-lung transplantation. Am J Respir Crit Care Med 1995;151:2033–2036. Bittmann I, Rolf B, Amann G, et al. Recurrence of lymphangioleiomyomatosis after single lung transplantation: new insights into pathogenesis. Hum Pathol 2003;34:95–98. Birt AR, Hogg GR, Dube WJ. Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol 1977;113:1674–1677. Chen J, Futami K, Petillo D, et al. Deficiency of FLCN in mouse kidney led to development of polycystic kidneys and renal neoplasia. PLoS ONE 2008;3:e3581. Khoo SK, Giraud S, Kahnoski K, et al. Clinical and genetic studies of Birt-HoggDube syndrome. J Med Genet 2002;39:906–912. Toro JR, Pautler SE, Stewart L, et al. Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dube syndrome. Am J Respir Crit Care Med 2007;175:1044–1053. Toro JR, Wei MH, Glenn GM, et al. BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: a new series of 50 families and a review of published reports. J Med Genet 2008;45:321–331. Butnor KJ, Guinee DG Jr. Pleuropulmonary pathology of Birt-Hogg-Dube syndrome. Am J Surg Pathol 2006;30:395–399. Gupta P, Eshaghi N, Kamba TT, et al. Radiological findings in Birt-Hogg-Dube syndrome: a rare differential for pulmonary cysts and renal tumors. Clin Imaging 2007;31:40–43. Ayo DS, Aughenbaugh GL, Yi ES, et al. Cystic lung disease in Birt-Hogg-Dube syndrome. Chest 2007;132:679–684. Pittet O, Christodoulou M, Staneczek O, et al. Diagnosis of Birt-Hogg-Dube syndrome in a patient with spontaneous pneumothorax. Ann Thorac Surg 2006;82: 1123–1125. Souza CA, Finley R, Müller NL. Birt-HoggDube syndrome: a rare cause of pulmonary cysts. AJR Am J Roentgenol 2005;185:

1237–1239. 633. Garg K, Lynch DA, Newell JD. Inflammatory airways disease in ulcerative colitis: CT and high-resolution CT features. J Thorac Imaging 1993;8:159–163. 634. Camus P, Piard F, Ashcroft T, et al. The lung in inflammatory bowel disease. Medicine (Baltimore) 1993;72:151– 183. 635. Prince JS, Duhamel DR, Levin DL, et al. Nonneoplastic lesions of the tracheobronchial wall: radiologic findings with bronchoscopic correlation. RadioGraphics 2002;22:S215–230. 636. Kuzniar T, Sleiman C, Brugiere O, et al. Severe tracheobronchial stenosis in a patient with Crohn’s disease. Eur Respir J 2000;15:209–212. 637. Desai SJ, Gephardt GN, Stoller JK. Diffuse panbronchiolitis preceding ulcerative colitis. Chest 1989;95:1342–1344. 638. Wilcox P, Miller R, Miller G, et al. Airway involvement in ulcerative colitis. Chest 1987;92:18–22. 639. Casey MB, Tazelaar HD, Myers JL, et al. Noninfectious lung pathology in patients with Crohn’s disease. Am J Surg Pathol 2003;27:213–219. 640. Haralambou G, Teirstein AS, Gil J, et al. Bronchiolitis obliterans in a patient with ulcerative colitis receiving mesalamine. Mt Sinai J Med 2001;68:384–388. 641. Mahajan L, Kay M, Wyllie R, et al. Ulcerative colitis presenting with bronchiolitis obliterans organizing pneumonia in a pediatric patient. Am J Gastroenterol 1997;92:2123–2124. 642. Swinburn CR, Jackson GJ, Cobden I, et al. Bronchiolitis obliterans organising pneumonia in a patient with ulcerative colitis. Thorax 1988;43:735–736. 643. Mahadeva R, Walsh G, Flower CD, et al. Clinical and radiological characteristics of lung disease in inflammatory bowel disease. Eur Respir J 2000;15:41–48. 644. Chikano S, Sawada K, Ohnishi K, et al. Interstitial pneumonia accompanying ulcerative colitis. Intern Med 2001;40: 883–886. 645. Bar-Dayan Y, Ben-Zikrie S, Fraser G, et al. Pulmonary alveolar hemorrhage in a patient with ulcerative colitis and primary sclerosing cholangitis. Isr Med Assoc J 2002;4:464–465. 646. Al-Binali AM, Scott B, Al-Garni A, et al. Granulomatous pulmonary disease in a child: an unusual presentation of Crohn’s disease. Pediatr Pulmonol 2003;36:76–80. 647. Lucero PF, Frey WC, Shaffer RT, et al. Granulomatous lung masses in an elderly patient with inactive Crohn’s disease. Inflamm Bowel Dis 2001;7:256–259. 648. Vandenplas O, Casel S, Delos M, et al. Granulomatous bronchiolitis associated with Crohn’s disease. Am J Respir Crit Care Med 1998;158:1676–1679. 649. Beer TW, Edwards CW. Pulmonary nodules due to reactive systemic amyloidosis (AA) in Crohn’s disease. Thorax 1993;48:1287–1288. 650. Boyd O, Gibbs AR, Smith AP. Fibrosing alveolitis due to sulphasalazine in a patient with rheumatoid arthritis. Br J Rheumatol 1990;29:222–224. 651. Leino R, Liippo K, Ekfors T. Sulphasalazine-induced reversible hypersensitivity pneumonitis and fatal

References

652. 653.

654.

655.

656.

657.

658.

659. 660.

661.

662.

663.

664.

665.

666.

667.

668.

fibrosing alveolitis: report of two cases. J Intern Med 1991;229:553–556. Parry SD, Barbatzas C, Peel ET, et al. Sulphasalazine and lung toxicity. Eur Respir J 2002;19:756–764. Songur N, Songur Y, Tuzun M, et al. Pulmonary function tests and highresolution CT in the detection of pulmonary involvement in inflammatory bowel disease. J Clin Gastroenterol 2003;37:292–298. Raj AA, Birring SS, Green R, et al. Prevalence of inflammatory bowel disease in patients with airways disease. Respir Med 2008;102:780–785. Kelly MG, Frizelle FA, Thornley PT, et al. Inflammatory bowel disease and the lung: is there a link between surgery and bronchiectasis? Int J Colorectal Dis 2006;21:754–757. Piotrowski WJ, Zielinski KW, Kozlowska A, et al. Atypical lung changes in a 19-year-old woman with Crohn’s disease. Lung 2007;185:189–190. Weatherhead M, Masson S, Bourke SJ, et al. Interstitial pneumonitis after infliximab therapy for Crohn’s disease. Inflamm Bowel Dis 2006;12:427–428. Veyssier-Belot C, Cacoub P, CaparrosLefebvre D, et al. Erdheim-Chester disease. Clinical and radiologic characteristics of 59 cases. Medicine (Baltimore) 1996;75: 157–169. Martin W 3rd, Klein A, Buss D. Case report 213. Skeletal Radiol 1982;9:69– 71. Devouassoux G, Lantuejoul S, Chatelain P, et al. Erdheim-Chester disease: a primary macrophage cell disorder. Am J Respir Crit Care Med 1998;157:650–653. Egan AJ, Boardman LA, Tazelaar HD, et al. Erdheim-Chester disease: clinical, radiologic, and histopathologic findings in five patients with interstitial lung disease. Am J Surg Pathol 1999;23:17–26. Bourke SC, Nicholson AG, Gibson GJ. Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide and prednisolone. Thorax 2003;58:1004–1005. Wittenberg KH, Swensen SJ, Myers JL. Pulmonary involvement with ErdheimChester disease: radiographic and CT findings. AJR Am J Roentgenol 2000;174:1327–1331. Schwarz MI. Miscellaneous interstitial lung disease. In: Schwarz M, King T (eds). Interstitial lung disease, 4th ed. Toronto: Brian C Decker, 2003:877–916. Protopapadakis C, Antoniou KM, Nicholson AG, et al. Erdheim-Chester disease: pulmonary presentation in a case with advanced systemic involvement. Respiration 2008. [Epub ahead of print]. Ferretti GR, Jankowski A, Rodiere M, et al. CT-guided biopsy of nonresolving focal air space consolidation. J Thorac Imaging 2008;23:7–12. Kambouchner M, Colby TV, Domenge C, et al. Erdheim-Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone. Histopathology 1997;30: 353–358. Farre I, Copin MC, Boulanger E, et al. Erdheim-Chester disease. Clinicopathologic study of two cases. Annales de

Pathologie 1995;15:59–62. 669. Dion E, Graef C, Haroche J, et al. Imaging of thoracoabdominal involvement in Erdheim-Chester disease. AJR Am J Roentgenol 2004;183:1253–1260. 670. Goitein O, Elstein D, Abrahamov A, et al. Lung involvement and enzyme replacement therapy in Gaucher’s disease. Q J Med 2001;94:407–415. 671. Santamaria F, Parenti G, Guidi G, et al. Pulmonary manifestations of Gaucher disease: an increased risk for L444P homozygotes? Am J Respir Crit Care Med 1998;157:985–989. 672. Yassa NA, Wilcox AG. High-resolution CT pulmonary findings in adults with Gaucher’s disease. Clin Imaging 1998;22:339–342. 673. Aydin K, Karabulut N, Demirkazik F, et al. Pulmonary involvement in adult Gaucher’s disease: high resolution CT appearance. Br J Radiol 1997;70:93–95. 674. Copley SJ, Coren M, Nicholson AG, et al. Diagnostic accuracy of thin-section CT and chest radiography of pediatric interstitial lung disease. AJR Am J Roentgenol 2000;174:549–554. 675. Ch’en IY, Lynch D, Shroyer K, et al. Gaucher disease: an unusual cause of intrathoracic extramedullary hematopoiesis. Chest 1993;104:1923– 1924. 676. Nicholson AG, Florio R, Hansell DM, et al. Pulmonary involvement by Niemann-Pick disease. A report of six cases. Histopathology 2006;48:596–603. 677. Guillemot N, Troadec C, de Villemeur TB, et al. Lung disease in Niemann-Pick disease. Pediatr Pulmonol 2007;42:1207–1214. 678. Duchateau F, Dechambre S, Coche E. Imaging of pulmonary manifestations in subtype B of Niemann-Pick disease. Br J Radiol 2001;74:1059–1061. 679. Nicholson AG, Wells AU, Hooper J, et al. Successful treatment of endogenous lipoid pneumonia due to Niemann-Pick Type B disease with whole-lung lavage. Am J Respir Crit Care Med 2002;165:128–131. 680. Rodrigues R, Marchiori E, Müller NL. Niemann-Pick disease: high-resolution CT findings in two siblings. J Comput Assist Tomogr 2004;28:52–54. 681. Baldi BG, Santana AN, Takagaki TY, et al. Lung cyst: an unusual manifestation of Niemann-Pick disease. Respirology 2009; 14:134–136. 682. Falco F, Bembi B, Cavazza A, et al. Pulmonary involvement in an adult female affected by type B Niemann Pick disease. Sarcoidosis Vasc Diffuse Lung Dis 2005;22:229–233. 683. Mendelson DS, Wasserstein MP, Desnick RJ, et al. Type B Niemann-Pick disease: findings at chest radiography, thin-section CT, and pulmonary function testing. Radiology 2006;238:339–345. 684. Kariman K, Singletary WV Jr, Sieker HO. Pulmonary involvement in Fabry’s disease. Am J Med 1978;64:911–912. 685. Brown LK, Miller A, Bhuptani A, et al. Pulmonary involvement in Fabry disease. Am J Respir Crit Care Med 1997;155:1004–1010. 686. Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system

involvement. Genet Med 2006;8:539–548. 687. Rosenberg DM, Ferrans VJ, Fulmer JD, et al. Chronic airflow obstruction in Fabry’s disease. Am J Med 1980;68:898–905. 688. Kim W, Pyeritz RE, Bernhardt BA, et al. Pulmonary manifestations of Fabry disease and positive response to enzyme replacement therapy. Am J Med Genet A 2007;143:377–381. 689. Wang RY, Abe JT, Cohen AH, et al. Enzyme replacement therapy stabilizes obstructive pulmonary Fabry disease associated with respiratory globotriaosylceramide storage. J Inherit Metab Dis 2009 (in press). 690. Garay SM, Gardella JE, Fazzini EP, et al. Hermansky-Pudlak syndrome. Pulmonary manifestations of a ceroid storage disorder. Am J Med 1979;66:737–747. 691. Avila NA, Brantly M, Premkumar A, et al. Hermansky-Pudlak syndrome: radiography and CT of the chest compared with pulmonary function tests and genetic studies. AJR Am J Roentgenol 2002;179:887–892. 692. Pierson DM, Ionescu D, Qing G, et al. Pulmonary fibrosis in Hermansky-Pudlak syndrome. A case report and review. Respiration 2006;73:382–395. 693. Husby G. Nomenclature and classification of amyloid and amyloidoses. J Intern Med 1992;232:511–512. 694. Kyle R. Amyloidosis minisymposium. Introduction and overview. J Intern Med 1992;232:507–508. 695. Goldman AB, Bansal M. Amyloidosis and silicone synovitis: updated classification, updated pathophysiology, and synovial articular abnormalities. Radiol Clin North Am 1996;34:375–394. 696. Skinner M. Protein AA/SAA. J Intern Med 1992;232:513–514. 697. Rocken C, Sletten K. Amyloid in surgical pathology. Virchows Arch 2003;443:3–16. 698. Pepys M. Amyloidosis: some recent developments. Q J Med 1988;67:283–298. 699. Garcia Gallego F, Calleja Canelas JL. Letter: Hilar enlargement in amyloidosis. N Engl J Med 1974;291:531. 700. Desai RA, Mahajan VK, Benjamin S, et al. Pulmonary amyloidoma and hilar adenopathy. Rare manifestations of primary amyloidosis. Chest 1979;76: 170–173. 701. Crestani B, Monnier A, Kambouchner M, et al. Tracheobronchial amyloidosis with hilar lymphadenopathy associated with a serum monoclonal immunoglobulin. Eur Respir J 1993;6:1569–1571. 702. Glenner G. Amyloid deposits and amyloidosis. The ß fibrilloses. N Engl J Med 1980;302:1283–1292, 1333–1343. 703. Gertz MA, Kyle RA. Primary systemic amyloidosis: a diagnostic primer. Mayo Clin Proc 1989;64:1505–1519. 704. Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc 1983;58:665–683. 705. Kyle R. Primary systemic amyloidosis. J Intern Med 1992;232:523–524. 706. Gertz MA, Lacy MQ, Dispenzieri A. Amyloidosis: recognition, confirmation, prognosis, and therapy. Mayo Clin Proc 1999;74:490–494. 707. Wang C, Robbins L. Amyloid disease. Its roentgen manifestations. Radiology 1956;66:489–501. 708. Cohen HI, Merigan TC, Kosek JC, et al.

711

Chapter 11 • Idiopathic Diffuse Lung Diseases

709.

710.

711.

712. 713. 714.

715. 716.

717. 718. 719. 720. 721.

722. 723. 724.

725.

726.

727.

728.

729.

712

Sequoiosis. A granulomatous pneumonitis associated with redwood sawdust inhalation. Am J Med 1967;43:785–794. Celli BR, Rubinow A, Cohen AS, et al. Patterns of pulmonary involvement in systemic amyloidosis. Chest 1978;74:543–547. Smith RR, Hutchins GM, Moore GW, et al. Type and distribution of pulmonary parenchymal and vascular amyloid. Correlation with cardiac amyloid. Am J Med 1979;66:96–104. Browning MJ, Banks RA, Tribe CR, et al. Ten years’ experience of an amyloid clinic: a clinicopathological survey. Q J Med 1985;54:213–227. Brown J. Primary amyloidosis. Clin Radiol 1964;15:358–367. Crosbie WA, Lewis ML, Ramsay ID, et al. Pulmonary amyloidosis with impaired gas transfer. Thorax 1972;27:625–630. Road J, Jacques J, Sparling J. Diffuse alveolar septal amyloidosis presenting with recurrent hemoptysis and medial dissection of pulmonary arteries. Am Rev Respir Dis 1985;132:1368–1370. Kanada D, Sharma O. Long-term survival with diffuse interstitial pulmonary amyloidosis. Am J Med 1979;67:879–882. Cordier JF, Loire R, Brune J. Amyloidosis of the lower respiratory tract. Clinical and pathologic features in a series of 21 patients. Chest 1986;90:827–831. Poh S, Tjia T, Seah H. Primary diffuse alveolar septal amyloidosis. Thorax 1975;30:186–191. Himmelfarb E, Wells S, Rabinowitz JG. The radiologic spectrum of cardiopulmonary amyloidosis. Chest 1977;72:327–332. Jenkins MC, Potter M. Calcified pseudotumoural mediastinal amyloidosis. Thorax 1991;46:686–687. Kyle RA, Bayrd ED. Amyloidosis: review of 236 cases. Medicine (Baltimore) 1975;54:271–299. Gertz MA, Kyle RA. Secondary systemic amyloidosis: response and survival in 64 patients. Medicine (Baltimore) 1991;70: 246–256. Planes C, Kleinknecht D, Brauner M, et al. Diffuse interstitial lung disease due to AA amyloidosis. Thorax 1992;47:323–324. Gertz MA. Secondary amyloidosis (AA). J Intern Med 1992;232:517–518. Wright JR, Calkins E. Clinical-pathologic differentiation of common amyloid syndromes. Medicine (Baltimore) 1981;60: 429–448. Ordi J, Grau JM, Junque A, et al. Secondary (AA) amyloidosis associated with Castleman’s disease. Report of two cases and review of the literature. Am J Clin Pathol 1993;100:394–397. Monreal F. Pulmonary amyloidosis: ultrastructural study of early alveolar septal deposits. Hum Pathol 1984;15: 388–390. Shiue ST, McNally DP. Pulmonary hypertension from prominent vascular involvement in diffuse amyloidosis. Arch Intern Med 1988;148:687–689. Gross BH, Felson B, Birnberg FA. The respiratory tract in amyloidosis and the plasma cell dyscrasias. Semin Roentgenol 1986;21:113–127. Morgan RA, Ring NJ, Marshall AJ. Pulmonary alveolar-septal amyloidosis: an

730.

731.

732. 733.

734.

735.

736. 737.

738. 739. 740. 741. 742.

743.

744. 745. 746.

747.

748.

749.

750.

unusual radiographic presentation. Respir Med 1992;86:345–347. Graham CM, Stern EJ, Finkbeiner WE, et al. High-resolution CT appearance of diffuse alveolar septal amyloidosis. AJR Am J Roentgenol 1992;158:265–267. Geusens EA, Verschakelen JA, Bogaert JG. Primary pulmonary amyloidosis as a cause of interlobular septal thickening. AJR Am J Roentgenol 1997;168:1116–1117. Pickford HA, Swensen SJ, Utz JP. Thoracic cross-sectional imaging of amyloidosis. AJR Am J Roentgenol 1997;168:351–355. Storto ML, Kee ST, Golden JA, et al. Hydrostatic pulmonary edema: highresolution CT findings. AJR Am J Roentgenol 1995;165:817–820. Laden SA, Cohen ML, Harley RA. Nodular pulmonary amyloidosis with extrapulmonary involvement. Hum Pathol 1984;15:594–597. Berk JL, Keane J, Seldin DC, et al. Persistent pleural effusions in primary systemic amyloidosis: etiology and prognosis. Chest 2003;124:969–977. Wilson SR, Sanders DE, Delarue NC. Intrathoracic manifestations of amyloid disease. Radiology 1976;120:283–289. Rubinow A, Celli BR, Cohen AS, et al. Localized amyloidosis of the lower respiratory tract. Am Rev Respir Dis 1978;118:603–611. Kavuru MS, Adamo JP, Ahmad M, et al. Amyloidosis and pleural disease. Chest 1990;98:20–23. Romero Candeira S, Martin Serrano C, Hernandez Blasco L. Amyloidosis and pleural disease. Chest 1991;100:292–293. Bontemps F, Tillie-Leblond I, Coppin MC, et al. Pleural amyloidosis: thoracoscopic aspects. Eur Respir J 1995;8:1025–1027. Gross BH. Radiographic manifestations of lymph node involvement in amyloidosis. Radiology 1981;138:11–14. Borge MA, Parker LA, Mauro MA. Amyloidosis: CT appearance of calcified, enlarged periaortic lymph nodes. J Comput Assist Tomogr 1991;15:855–857. Hiller N, Fisher D, Shmesh O, et al. Primary amyloidosis presenting as an isolated mediastinal mass: diagnosis by fine needle biopsy. Thorax 1995;50:908–909. Weiss L. Isolated multiple nodular pulmonary amyloidosis. Am J Clin Pathol 1960;33:318–329. Shaw P, Grossman R, Fernandes BJ. Nodular mediastinal amyloidosis. Hum Pathol 1984;15:1183–1185. Melato M, Antonutto G, Falconieri G, et al. Massive amyloidosis of mediastinal lymph nodes in a patient with multiple myeloma. Thorax 1983;38:151–152. King CS, Holley AB, Sherner JH. Severe bullous lung disease due to marginal-zonelymphoma-associated amyloidosis. Respir Care 2008;53:1495–1498. Lantuejoul S, Moulai N, Quetant S, et al. Unusual cystic presentation of pulmonary nodular amyloidosis associated with MALT-type lymphoma. Eur Respir J 2007;30:589–592. Kobayashi H, Matsuoka R, Kitamura S, et al. Sjogren’s syndrome with multiple bullae and pulmonary nodular amyloidosis. Chest 1988;94:438–440. Desai SR, Nicholson AG, Stewart S, et al. Benign pulmonary lymphocytic infiltration

751.

752.

753. 754.

755.

756.

757. 758. 759.

760.

761.

762.

763.

764. 765. 766. 767.

768.

769.

and amyloidosis: computed tomographic and pathologic features in three cases. J Thorac Imaging 1997;12:215–220. Jeong YJ, Lee KS, Chung MP, et al. Amyloidosis and lymphoproliferative disease in Sjogren syndrome: thin-section computed tomography findings and histopathologic comparisons. J Comput Assist Tomogr 2004;28:776–781. Teixidor HS, Bachman AL. Multiple amyloid tumors of the lung. A case report. Am J Roentgenol Radium Ther Nucl Med 1971;111:525–529. Thompson P, Citron K. Amyloid and the lower respiratory tract. Thorax 1983;38:84–87. Calatayud J, Candelas G, Gomez A, et al. Nodular pulmonary amyloidosis in a patient with rheumatoid arthritis. Clin Rheumatol 2007;26:1797–1798. Minogue SC, Morrisson M, Ansermino M. Laryngo-tracheo-bronchial stenosis in a patient with primary pulmonary amyloidosis: a case report and brief review. Can J Anaesth 2004;51:842–845. Toyoda M, Ebihara Y, Kato H, et al. Tracheobronchial AL amyloidosis: histologic, immunohistochemical, ultrastructural, and immunoelectron microscopic observations. Hum Pathol 1993;24:970–976. Gottlieb LS, Gold WM. Primary tracheobronchial amyloidosis. Am Rev Respir Dis 1972;105:425–429. Prowse C. Amyloidosis of the lower respiratory tract. Thorax 1958;13:308–320. Naef AP, Savary M, Gruneck JM, et al. Amyloid pseudotumor treated by tracheal resection. Ann Thorac Surg 1977;23: 578–581. Breuer R, Simpson GT, Rubinow A, et al. Tracheobronchial amyloidosis: treatment by carbon dioxide laser photoresection. Thorax 1985;40:870–871. Hui AN, Koss MN, Hochholzer L, et al. Amyloidosis presenting in the lower respiratory tract. Clinicopathologic, radiologic, immunohistochemical, and histochemical studies on 48 cases. Arch Pathol Lab Med 1986;110:212–218. Remy J, Remy-Jardin M, Artaud D, et al. Multiplanar and three-dimensional reconstruction techniques in CT: impact on chest diseases. Eur Radiol 1998;8:335–351. O’Regan A, Fenlon HM, Beamis JF Jr, et al. Tracheobronchial amyloidosis. The Boston University experience from 1984–1999. Medicine (Baltimore) 2000;79:69–79. Cotton R, Jackson J. Localized amyloid ‘tumours’ of the lung simulating malignant neoplasms. Thorax 1964;19:97–103. Weissman B, Wong M, Smith DN. Image interpretation session: 1996. RadioGraphics 1997;17:244–245. Dood A, Manan J. Primary diffuse amyloidosis of the respiratory tract. Arch Pathol 1959;67:39–42. Dalton H, Featherstone T, Athanasou N. Organ limited amyloidosis with lymphadenopathy. Postgrad Med J 1992;68:47–50. Schmidt H, McDonald J, Clagett O. Amyloid tumours of the lower respiratory tract and mediastinum. Ann Otol Rhinol Laryngol 1953;62:880–893. Flemming AF, Fairfax AJ, Arnold AG, et al. Treatment of endobronchial amyloidosis by

References

770.

771.

772. 773.

774.

775.

776.

777.

778.

779. 780.

intermittent bronchoscopic resection. Br J Dis Chest 1980;74:183–188. Yang S, Chia SY, Chuah KL, et al. Tracheobronchial amyloidosis treated with rigid bronchoscopy and stenting. Surg Endosc 2003;17:658–659. Kalra S, Utz JP, Edell ES, et al. Externalbeam radiation therapy in the treatment of diffuse tracheobronchial amyloidosis. Mayo Clin Proc 2001;76:853–856. Firestone FN, Joison J. Amyloidosis. A cause of primary tumors of the lung. J Thorac Cardiovasc Surg 1966;51:292–299. Saab SB, Burke J, Hopeman A, et al. Primary pulmonary amyloidosis. Report of two cases. J Thorac Cardiovasc Surg 1974;67:301–307. Miura K, Shirasawa H. Lambda III subgroup immunoglobulin light chains are precursor proteins of nodular pulmonary amyloidosis. Am J Clin Pathol 1993;100: 561–566. Davis CJ, Butchart EG, Gibbs AR. Nodular pulmonary amyloidosis occurring in association with pulmonary lymphoma. Thorax 1991;46:217–218. Condon R, Pinkham R, Hames G. Primary isolated nodular pulmonary amyloidosis. Report of a case. J Thorac Cardiovasc Surg 1964;48:498–505. Matsumoto K, Ueno M, Matsuo Y, et al. Primary solitary amyloidoma of the lung: findings on CT and MRI. Eur Radiol 1997;7:586–588. Pusztaszeri M, Kamel EM, Artemisia S, et al. Nodular pseudotumoral pulmonary amyloidosis mimicking pulmonary carcinoma. Thorax 2005;60:440. Leu CY, Lynch DA, Chan ED. The case of the torpid thoracic tumor. Chest 1997;112:535–537. Fenoglio C, Pascal RR. Nodular

781.

782.

783. 784.

785. 786. 787. 788. 789.

790.

791.

amyloidosis of the lungs. An unusual case associated with chronic lung disease and carcinoma of the bladder. Arch Pathol 1970;90:577–582. Ayuso MC, Gilabert R, Bombi JA, et al. CT appearance of localized pulmonary amyloidosis. J Comput Assist Tomogr 1987;11:197–199. Sumimoto H, Yamada K, Nomura I, et al. Primary pulmonary amyloidosis mimicking primary lung cancer. J Comput Assist Tomogr 1993;17:826–827. Mata JM, Caceres J, Senac JP, et al. General case of the day. Nodular amyloidosis of the lung. RadioGraphics 1991;11:716–718. Bierny J. Multinodular primary amyloidosis of the lung; diagnosis by needle biopsy. AJR Am J Roentgenol 1978;131:1082–1083. Dyke PC, Demaray MJ, Delavan JW, et al. Pulmonary amyloidoma. Am J Clin Pathol 1974;61:301–305. Currie GP, Rossiter C, Dempsey OJ, et al. Pulmonary amyloid and PET scanning. Respir Med 2005;99:1463–1464. Grubstein A, Shitrit D, Sapir EE, et al. Pulmonary amyloidosis: detection with PET-CT. Clin Nucl Med 2005;30:420–421. Zundel WE, Prior AP. An amyloid lung. Thorax 1971;26:357–363. Ohdama S, Akagawa S, Matsubara O, et al. Primary diffuse alveolar septal amyloidosis with multiple cysts and calcification. Eur Respir J 1996;9:1569–1571. Kim HY, Im JG, Song KS, et al. Localized amyloidosis of the respiratory system: CT features. J Comput Assist Tomogr 1999;23:627–631. Gordonson JS, Sargent EN, Jacobson G, et al. Roentgenographic manifestations of pulmonary amyloidosis (classification and case illustrations). J Can Assoc Radiol

1972;23:269–272. 792. Kijner CH, Yousem SA. Systemic light chain deposition disease presenting as multiple pulmonary nodules. A case report and review of the literature. Am J Surg Pathol 1988;12:405–413. 793. Khoor A, Myers JL, Tazelaar HD, et al. Amyloid-like pulmonary nodules, including localized light-chain deposition: clinicopathologic analysis of three cases. Am J Clin Pathol 2004;121:200–204. 794. Bhargava P, Rushin JM, Rusnock EJ, et al. Pulmonary light chain deposition disease: report of five cases and review of the literature. Am J Surg Pathol 2007;31: 267–276. 795. Colombat M, Stern M, Groussard O, et al. Pulmonary cystic disorder related to light chain deposition disease. Am J Respir Crit Care Med 2006;173:777–780. 796. Colombat M, Caudroy S, Lagonotte E, et al. Pathomechanisms of cyst formation in pulmonary light chain deposition disease. Eur Respir J 2008;32:1399–1403. 797. Colombat M, Gounant V, Mal H, et al. Light chain deposition disease involving the airways: diagnosis by fibreoptic bronchoscopy. Eur Respir J 2007;29: 1057–1060. 798. Kaira K, Oriuchi N, Otani Y, et al. Diagnostic usefulness of fluorine-18alpha-methyltyrosine positron emission tomography in combination with 18F-fluorodeoxyglucose in sarcoidosis patients. Chest 2007;131:1019–1027.

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Diseases of the airways

TRACHEAL DISORDERS Tracheal narrowing Saber-sheath trachea Cryptogenic stenosis Tuberculosis Scleroma Tracheo(broncho)pathia osteo(chondro)-plastica Tracheal widening Tracheobronchomegaly (Mounier–Kuhn syndrome) Tracheomalacia Tracheal filling defects Ectopic thyroid Tracheal papilloma Paratracheal cysts Tracheoesophageal fistula BRONCHIECTASIS HRCT signs of bronchiectasis Accuracy of HRCT for the detection of bronchiectasis Disease-specific patterns of bronchiectasis Cystic fibrosis Ciliary dyskinesia syndrome (immobile cilia syndrome) BRONCHOLITHIASIS

TRACHEAL DISORDERS Tracheal lesions that are part of a generalized pulmonary or systemic disorder, together with congenital, traumatic, and neoplastic processes, are discussed in the relevant chapters. With a few exceptions, consideration is given here only to conditions in adults that are essentially confined to the trachea. Given that the trachea is rightly regarded as something of a blind spot on chest radiography,1 computed tomography (CT) has become the imaging examination of choice for the investigation of tracheal disorders2–5 (Fig. 12.1), with magnetic resonance imaging (MRI) occasionally providing additional information.6–8 Coronal reformations and threedimensional reconstructions of volumetric CT data usefully clarify tracheobronchial anatomy in some situations.9–16 The trachea may be affected by a wide variety of extrinsic or intrinsic processes. Extrinsic processes, particularly masses, displace and distort the trachea, while intrinsic ones cause narrowing, widening, or a mass effect. Tracheal diseases can be further conveniently divided into those that show focal4 and those that show diffuse5 involvement.

Tracheal narrowing Tracheal narrowing may affect a long or short segment, but since the distinction is somewhat subjective, both types are considered together. The causes of tracheal narrowing, some of which are exceedingly rare, are listed in Box 12.1.

SMALL AIRWAYS DISEASES Pathologic classification and clinical background Constrictive obliterative bronchiolitis Diffuse panbronchiolitis Miscellaneous conditions with small airways involvement Hypersensitivity pneumonitis Sarcoidosis Follicular bronchiolitis Respiratory bronchiolitis Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia Swyer–James or McLeod syndrome CHRONIC OBSTRUCTIVE PULMONARY DISEASE Asthma Chest radiography High-resolution computed tomography Chronic bronchitis Emphysema Chest radiography Computed tomography α1-Antitrypsin deficiency Imaging and lung volume reduction techniques Bullae

Saber-sheath trachea (Box 12.2) Saber-sheath deformity is limited to the intrathoracic part of the trachea, which is flattened from side to side so that the coronal diameter is two-thirds or less of the sagittal diameter at the same level.27 The condition occurs almost exclusively in men, usually in those more than 50 years of age; the youngest recorded patient was 37 years of age.73 Saber-sheath trachea is strongly associated with the presence of chronic obstructive pulmonary disease (COPD), and in one series COPD was present in 93% of patients with the deformity compared with 18% of control subjects.73 The pathogenesis of the lesion is obscure, but probably it is an acquired deformity related to the abnormal pattern and magnitude of intrathoracic pressure changes in COPD. In a study of 40 patients, 20 of whom had a saber-sheath trachea, there was a significant relationship between the ratio of the coronal:sagittal tracheal diameter on CT and functional residual capacity (r = 0.61, p < 0.001), supporting the view that saber-sheath trachea is a consequence of hyperinflation.74 A reduction in coronal diameter of the trachea, short of the forme complète of saber-sheath deformity, correlates significantly with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC).75 Saber-sheath trachea can be detected on chest radiography (Fig. 12.2) but is better demonstrated on CT. The narrowing usually affects the whole of the intrathoracic trachea, with an abrupt return to normal caliber at the thoracic inlet27 (Fig. 12.3). In Greene’s73 series of 60 patients with saber-sheath trachea and 60 control subjects, the mean coronal diameter of the deformed trachea was reduced to 61% and the sagittal diameter increased to 115%, giving

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Chapter 12 • Diseases of the Airways

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Fig. 12.1  Adenoid cystic tumor in distal trachea images reconstructed from volumetric CT data. A, Standard CT section at the level of the azygos vein showing the tumor arising from the thickened right anterolateral tracheal wall, protruding into the lumen. B, Volume rendered display showing luminal indentation by the tumor. C, Virtual bronchoscopic rendition showing the endoluminal component of the tumor.

Box 12.1  Causes of tracheal narrowing

Extrinsic • Mass lesions – Thyroid,17sometimes acute18,19 – Lymph nodes – Vessels20,21 – Mediastinal mass or hematoma22 • Invading tumors – Thyroid or esophageal carcinoma – Paraganglioma18 • Mediastinal fibrosis – Tuberculosis23,24 – Histoplasmosis25

Intrinsic

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• Cryptogenic26 – Saber-sheath trachea27 • Congenital28,29 – Tracheal stenosis30 – Complete tracheal rings31,32 – Down syndrome33

– Tracheal ‘diaphragm’34 • Infective – Laryngotracheobronchitis35,36 – Papillomatosis37 – Tuberculosis23,24,38 – Bacillary angiomatosis39 – Scleroma40,41 • Fungal42 – Histoplasmosis25 – Coccidioidomycosis43 – Mucormycosis44 – Candidiasis45 – Necrotizing tracheobronchial aspergillosis46,47 • Granulomatous – Necrotizing cytomegalovirus tracheitis48 – Wegener granulomatosis49,50 – Sarcoidosis51 – Crohn disease52

• Neoplastic53 – Benign or malignant neoplasm – Lymphoproliferative diseases54–56 – Sinus histiocytosis57 • Traumatic – Tracheostomy or endotracheal intubation58–60 – Right pneumonectomy syndrome61 – Radiotherapy62 – Blunt or penetrating trauma63 – Foreign body64 • Deposition or dysplastic – Tracheopathia osteoplastica65,66 – Mucopolysaccharidoses67 – Chrondrodysplasia punctata68 • Immunologic – Amyloidosis69 – Epidermolysis bullosa70 – Relapsing polychondritis71,72

Tracheal Disorders Box 12.2  Saber-sheath trachea • Saber-sheath deformity is a common finding in men >50 years and is strongly associated with COPD • The coronal narrowing of the trachea abruptly returns to normal at the thoracic inlet and carina • Saber-sheath deformity is usually of no clinical consequence, but can rarely be problematic for patients undergoing intubation

deformity, intervention in the form of balloon dilation with or without stenting may rarely be required.83–85

Cryptogenic stenosis (Box 12.3) Fibrotic tracheal stenoses of obscure, presumed inflammatory, origin have been described, but truly idiopathic cases are extremely rare.86 These may occur at any site but tend to be subglottic and are occasionally multiple.45,87,88 In a series of 15 cases of idiopathic laryngotracheal stenoses, patients were, in common with other reports, predominantly female (94%) and middle aged (30–60 years).26 Onethird of the stenoses were tracheal, and these were hourglass or eccentric in configuration with smooth or less commonly irregular lobulated internal margins (Fig. 12.5). Stenoses were 2–4  cm long and 3–5 mm wide. The histologic changes were nonspecific, consisting of scarring of the adventitia and lamina propria. Some patients with cryptogenic stenoses have positive titers of antineutrophil cytoplasmic antibodies.89 In these patients stenoses have been recurrent and the histologic features either granulomatous or nonspecific. It seems likely that such cases are part of the Wegener granulomatosis spectrum. Box 12.3  Cryptogenic stenosis • Very rare, usually middle-aged women affected • Eccentric or concentric fibrotic stricture of variable length • Some cases may be the consequence of an inflammatory vasculitis

Tuberculosis (Box 12.4)

Fig. 12.2  Saber-sheath trachea. Posteroanterior radiograph in which the coronal diameter of the trachea in the cervical region is 19 mm, decreasing to 9 mm in the intrathoracic portion. The transitional zone is at the level of the thoracic inlet, and narrowing affects the whole of the intrathoracic trachea. The patient had chronic bronchitis. a mean tracheal area of 75% compared with control subjects. Cartilage rings are commonly calcified or ossified (but not thickened) both pathologically and on imaging.27,76 Patients with both saber-sheath trachea and mediastinal lipomatosis are described, in whom the appearance on the plain radiograph therefore strongly resembles a mediastinal mass.77 The original studies described the trachea as displaying the usual changes in configuration in relation to respiration and considered the trachea to be normally compliant (Fig. 12.4).73 Others, however, have described an abnormal degree of narrowing on forced expiration76 and have noted that the cross-sectional area was reduced mainly by apposition of the lateral walls with slight invagination of the posterior membrane.78 Saber-sheath deformity, although usually of little functional consequence, may occasionally cause difficulties for patients undergoing general anesthesia, specifically in terms of intubation,79,80 ventilation,81 and the rare association with negative-pressure pulmonary edema.82 Preoperative awareness of the deformity is clearly desirable, but even when a chest radiograph is available, a sabersheath trachea will often be overlooked. In the few individuals in whom marked airflow obstruction can be ascribed to a saber-sheath

Tuberculosis of the trachea is now very rare. It may be associated with cavitary lung disease and grossly infected sputum.38,45 Pathologic study shows mucosal thickening and ulceration and subsequent healing by fibrosis with stricture formation.45 Occasionally the trachea is involved by direct spread from adjacent nodes24 and fistula formation subsequent to this is described.90 On CT the extent of irregular and circumferential tracheobronchial narrowing is clearly demonstrated23,91 (Fig. 12.6) and in some patients an accompanying mediastinitis (opacification of the mediastinal fat) is evident. CT shows differences between active disease in which the narrowed trachea (and frequently one or other main bronchus) has an irregularly thickened wall; by contrast in the fibrotic or healed phase the trachea is narrowed but has a smooth and sometimes normal thickness wall.91 Surgical resection or balloon dilation and stenting may be required to treat the resulting stenosis.24,92 Box 12.4  Tracheal tuberculosis • Tuberculosis confined to tracheal wall involvement is rare • Often accompanied by involvement of one or other mainstem bronchus • Pronounced tracheal wall thickening in active disease • Wall thickness may return to normal in healed phase (lumen narrowed)

Scleroma Scleroma is a chronic progressive granulomatous infection that affects primarily the nose but may also involve the nasopharynx, larynx, trachea, and bronchi. It is caused by Gram-negative coccobacilli. Scleroma is uncommon in the West, occurring mainly in Asia, north Africa, Central and South America, and eastern Europe. The disease passes through three phases: catarrhal, granulomatous and proliferative, and scarring.93 Occasionally there is a soft tissue

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Fig. 12.3  Saber-sheath trachea. A, At and above the level of the thoracic inlet the trachea is of normal shape and diameter. B, The intrathoracic trachea shows the typical saber-sheath configuration. C, Abrupt return to a normal shape just above the carina.

A

B

Fig. 12.4  Saber-sheath trachea. Ultrafast CT images at the beginning and end of a rapid expiratory maneuver. A, At maximum inspiration. B, At maximum expiration. The cross-sectional area (A) of the trachea is essentially the same in A and B, but its configuration has changed with development of coronal narrowing and sagittal widening on expiration. The trachea is not hypercompliant. mass or bone destruction suggesting a nasal carcinoma. Laryngeal involvement is usually manifest as glottic or subglottic narrowing and vocal cord thickening.94,95 About 5% of patients have tracheal involvement, which is nearly always accompanied by laryngeal disease and almost invariably paranasal sinus disease.45 Scleroma can be treated by antibiotics such as ciprofloxacin.41 All or, more commonly, part of the trachea is involved (bronchial involvement is rare), typically the proximal rather than the distal segment.40 Stenoses are usually concentric and may be nodular or smooth.96

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Tracheo(broncho)pathia osteo(chondro)plastica (Box 12.5) Tracheopathia osteoplastica was first described more than 100 years ago,97 yet it remains a curiosity of obscure etiology. Although rare, it is more common than airway amyloidosis, a condition that some have considered to be the precursor of tracheopathia osteoplastica.98 Pathologic characteristics include the development of cartilaginous and bony submucosal nodules45 in the trachea and proximal airways. The nodules are typically found in the lower two-thirds of

Tracheal Disorders

Fig. 12.5  Coronal CT showing an irregular hourglass-shape subglottic tracheal stenosis in a female patient (no cause identified). Box 12.5  Tracheopathia osteoplastica • Very rare slowly progressive disease, characterized by nodular thickening of tracheal cartilage • Usually involves lower trachea and may extend out as far as segmental bronchi • Calcification within nodular thickening conspicuous on CT

the trachea and in the main, lobar, and segmental bronchi.99 The disorder, however, sometimes starts more proximally and affects the first tracheal ring region.65 The osteochondral nodules develop adjacent to the airway cartilages and rarely,100 if ever,101 involve the posterior membranous part of the trachea. The nodules give rise to sessile and polypoidal elevations of the mucosa, which produce airway narrowing,65 and sometimes lobar collapse.102 The cause of the condition is obscure. One theory considers the nodules to be a form of ecchondrosis of the airway cartilage because of their distribution in the airways and because they have bony, cartilaginous, and fibrous connections to the cartilage rings themselves.65 A second theory is that the disorder is due to amyloidosis, a condition in which cartilage and bone formation is known to occur. Several workers have in fact found evidence of amyloid in pathologic specimens from patients with tracheopathia.98,103 Most patients are male, and the disease usually develops in middle age (sixth decade), although the age range is wide, from 11 to 78 years.45 The common early symptoms are dyspnea, hoarseness, cough that is often productive, hemoptysis, and recurrent pulmonary infections.99 The disease progresses very slowly. The chest radiograph may be normal99 or may demonstrate evidence of collapse or infective consolidation. Airway calcification has diagnostic value but may be invisible on chest radiography.45 Tracheal calcification is manifest as irregular or scalloped opacities lying inside the cartilage rings.65 If the tracheal air column is clearly seen, the irregular nodularity of the tracheal wall and the encroachment of these nodules on the lumen can be appreciated. CT descriptions of the condition are sparse but confirm the expected finding of strikingly nodular thickening of the tracheal wall, with calcification in some of the nodules102,104–107 (Fig. 12.7). The definitive diagnosis is made with bronchoscopy,66 during which the passage of the instrument may generate a grating sensation.

Tracheal widening Several studies have documented the normal tracheal dimensions in adults using various imaging techniques.73,108–111 The most useful study using plain chest radiographs is that of Breatnach et al.,108 who studied 808 subjects. Measurements were made 2  cm above the aortic arch and were subject to 8% magnification. Tracheal

Fig. 12.6  Diffuse thickening of the tracheal wall caused by tuberculosis. The interface between the trachea and the surrounding mediastinal fat is indistinct and there is some opacification of the adjacent fat, presumably due to inflammation and edema. diameter increased slightly with age, and taking the largest measurements (between 60 and 80 years of age) the coronal diameter in men (mean ± SD) was 19.7 ± 2.2 mm and in women it was 16.8 ± 2.0 mm. In light of these data, a coronal diameter on a chest radiograph of 26 mm in men and 23 mm in women may be considered abnormal. For coronal diameter on CT, this dimension is smaller, since it is not subject to magnification; values are 3–4 mm less. A limited number of disorders cause tracheal widening, in some the widening is generalized, and in others it is local, as with a tracheocele or following endotracheal tube cuff damage. It is worth pointing out that a few diseases that cause tracheal widening can also be responsible for narrowing the trachea (e.g. relapsing polychondritis). In some forms of diffuse disease, widening is mild and confined to one diameter. Thus in cystic fibrosis the sagittal diameter may be mildly increased (by about 3–5 mm) while the coronal dimension remains normal.112 However, in a small study that investigated the distensibility and CT dimensions of the trachea in five patients with cystic fibrosis compared with five healthy volunteers, no significant differences were found.113 In day-to-day clinical practice the most common cause of mild dilatation of the trachea is upper zone or diffuse lung fibrosis as seen in sarcoidosis or tuberculosis114 (Fig. 12.8). Causes of local and generalized tracheal widening are listed in Box 12.6. Box 12.6  Tracheal widening • • • • • • • • • • • •

Tracheobronchomegaly (Mounier–Kuhn syndrome)115 Heritable connective tissue disorders Ehlers–Danlos complex116,117 Cutis laxa118 Immune deficiency states and recurrent childhood infections Ataxia telangiectasia119 Immunoglobulin deficiency119 Cystic fibrosis112 Endotracheal cuff damage Relapsing polychondritis72 Tracheocele120 Upper lobe fibrosis114

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Fig. 12.7  Tracheopathia osteoplastica. A, There is irregular thickening of the right tracheal wall (arrows). B, CT shows nodular thickening and calcific densities in the tracheal wall. Box 12.7  Tracheobronchomegaly • Tracheobronchomegaly is rare and characterized by marked tracheal and bronchial dilatation, usually associated with focal saccular bronchiectasis • Presents at any age, usually before middle age, with symptoms of bronchiectasis, almost exclusively in males • May be associated with congenital anomalies • Prognosis highly variable

Fig. 12.8  Wide trachea (coronal diameter 27 mm; normal diameter on CT 1) to the trachea. A lunate trachea is easily deformed in a sagittal direction, giving rise to a particular form of tracheomalacia. A lunate trachea may be associated with COPD, which is probably the commonest cause of tracheomalacia,141 but in others it is cryptogenic. Importantly, in one series of 17 patients with bronchoscopically confirmed tracheomalacia, only one individual (6%) had a lunate-shaped trachea on inspiratory CT, compared with nine (53%) individuals who showed an exaggerated lunate or crescentic (‘frown’) shape on dynamic expiratory CT,165 highlighting the insensitivity of static inspiratory CT for the detection of tracheomalacia.

Tracheal Disorders

Fig. 12.15  Tracheomalacia in an elderly woman with a history of recurrent pneumonia and ‘asthma’. Inspiratory (Insp) and expiratory (Exp) CT images show marked expiratory collapse of the proximal main bronchi (arrows) and some air-trapping in the right lower lobe and left lung. A

B

Fig. 12.14  Patient with relapsing polychondritis and hypercompliant trachea. A, CT at near total lung capacity showing the caliber reduced by the thick-walled trachea. B, CT performed at near residual volume with marked decrease in sagittal diameter of the trachea (and air-trapping in the left lung, reflecting collapse of the left main stem bronchus). During forced expiration or coughing a normal trachea shows narrowing both coronally and sagittally, the latter caused by invagination of the membranous posterior wall. Reliable data on the degree of narrowing to be expected are not available, and most studies have been performed in ignorance of the transmural pressure gradient generated. Some authors consider that caliber changes of more than 50% indicate increased wall compliance.157,166 Changes in cross-sectional area, and sagittal and coronal diameters in patients with acquired tracheomalacia have been studied on static inspiratory and expiratory CT by Aquino et al.167 Patients with tracheomalacia showed considerably greater diminution in sagittal (not coronal) diameter and cross-sectional area (Fig. 12.14); more specifically, there was a greater than 89% chance of tracheomalacia if the tracheal cross-sectional change was more than 18% (upper trachea) or 28% (mid-trachea), particularly if the sagittal diameter decreased by more than 28%.167 With the advent of rapid acquisition CT it has become possible to image the trachea during quiet breathing168 and forced dynamic maneuvers.135,163,169 During forced inspiration and expiration the intrathoracic tracheal cross-sectional area varies by 35% ± 18% (SD)169 and, in view of these data, Stern and co-workers169 suggested that changes in area greater than 70% indicate tracheomalacia (Fig. 12.15), a figure recently endorsed by Boiselle et al.170 Dynamic studies with CT are particularly effective in identifying tracheomalacic segments.135,163,168,169,170 It is unsurprising that the degree of tracheal collapse considered abnormal varies widely depending on the

nature and vigor of the expiratory maneuver (breathholding at end expiration167 through to forced coughing163) and data on the normal range of tracheal wall excursion in a large population of healthy individuals are still needed. The exact incidence of individuals with clinically important tracheomalacia, of whatever cause, is not easy to divine. In a review of patients undergoing CT pulmonary angiography for suspected pulmonary embolism, careful scrutiny of the major airways revealed that 10% of these patients had possible tracheomalacia (trachea showing luminal narrowing of 50% or more; as noted above this criterion may result in overcall).166 An important message of this study is that abnormal narrowing or collapse of the major airways may be easily overlooked, particularly when the CT examination of the dyspneic patient is targeted at other possible causes, such as pulmonary embolism, and so does not include expiratory maneuvers to allow formal assessment of major airway collapsibility. In infants and children some cases occur secondary to external compression of the trachea (aberrant subclavian arteries, vascular rings, etc).171 Primary tracheomalacia, caused by defects or complete deficiency of the supporting cartilaginous structures, is rare146,172 and may be associated with more severe congenital malformations such as esophageal atresia.147,173,174 The cartilage is deficient and the membranous portion of the trachea is widened.175 The entire airway, or just short segments, may be affected. Affected infants may not manifest symptoms for several months after birth.176 Many cases of tracheomalacia, particularly milder forms, are managed conservatively because spontaneous resolution in the first few years of life is common.161 In such self-limiting cases the presumed defect is immaturity of cartilage.142 The diagnosis is made by observing marked expiratory collapse of the trachea in the anteroposterior dimension.176 Bronchoscopy is probably the mainstay for diagnosis of tracheomalacia,143 but bronchoscopy in neonates usually requires general anesthesia and is thus a last resort. Less invasive approaches to diagnosis include fluoroscopy, dynamic helical or electron-beam CT,9,135,176 and MRI.148,177

Tracheal filling defects In adults, tracheal filling defects are most commonly produced by neoplasms (see Chapter 13), but there are a number of other causes (Box 12.10).

Ectopic thyroid Ectopic thyroid is a rare cause of an intratracheal filling defect,180 with about 150 cases in the literature.181 Females outnumber males by about 3 : 1.182 The ectopic thyroid may be histologically normal, although it is usually goitrous. Occasionally it is malignant.183 Three-quarters of intratracheal thyroid nodules are associated with extratracheal goiter. Foci of ectopic thyroid may occur anywhere between the subglottis and main carina,181 but typically they are a few centimeters below the vocal cords, arising as smooth, sessile nodules from the posterolateral wall of the trachea.182 Ectopic

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Chapter 12 • Diseases of the Airways Box 12.10  Causes of tracheal filling defects

Neoplasm53,178 • Benign (epithelial and mesenchymal) • Malignant • Carcinoma (squamous, adenoid cystic [Fig. 12.1], adenocarcinoma) • Sarcoma • Plasmacytoma • Lymphoma • Malignant invasion from without

Infection or granulomatous • • • • • • •

Viral papilloma Membranous croup Fungal infection Tuberculosis Rhinoscleroma Wegener granulomatosis Bacillary angiomatosis

Trauma • Hematoma

Miscellaneous179 • • • • • •

Ectopic thyroid and thymus Amyloidosis Tracheopathia osteoplastica Foreign body Mucoid pseudotumor Cyst or mucocele

thymus has also been described as causing a submucosal intratracheal mass.184

Tracheal papilloma Squamous papillomas of the trachea are usually multiple and may be a manifestation of laryngeal papillomatosis with tracheobronchial dissemination (see p. 834).183,185 Recurrent respiratory papillomatosis seems to have a bimodal age distribution with the mean age of the juvenile form being 2 years old, and adult-onset approximately 40 years of age.37,186 Solitary squamous cell papillomas of the trachea are also recognized in adults and may undergo malignant transformation.183,187

Paratracheal cysts Small air-filled cysts (ranging in size from 1 cm to a few centimeters) arising from the mid- or upper trachea are usually an incidental radiographic or CT finding188 (Fig. 12.16). They usually occur on the right side, and on thin-section CT a communicating channel between the cyst and trachea may occasionally be identified. Although usually considered rare, a Korean study has characterized right paratracheal cysts in 65 individuals.189 In all but one patient the cysts arose from the right posterolateral aspect of the trachea. Most cysts were approximately 1 cm in diameter and the majority of patients had functional evidence of obstructive lung disease.189 Nevertheless, it is not entirely clear whether these cysts are congenital or acquired,188 and their relationship, in terms of pathogenesis, to tracheoceles120 is unclear. Surgical resection may be undertaken because of the potential for infection within the cyst.

Tracheoesophageal fistula In the pediatric age group tracheoesophageal fistula is, almost invariably, congenital.190 Occasionally such congenital fistulas present in adulthood.191 Malignant neoplasia, particularly esophageal, is the most common cause in adults. Infection and trauma are

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Fig. 12.16  Paratracheal cyst displacing the trachea anteriorly and the esophagus to the left. The cyst contains a fluid level (the patient complained of a gurgling sensation). There are a few adjacent separate locules of gas within the mediastinum, possibly arising from the paratracheal cyst. Box 12.11  Causes of tracheo-/bronchoesophageal fistulas • Congenital192 • Neoplasm193 – Carcinoma of esophagus or trachea – Lymphoma • Trauma – Closed chest194,195 – Penetrating – Postendoscopy or postoperative – Endotracheal intubation196 – Corrosive esophagitis197 – Esophageal foreign body198 – Postirradiation199 • Infection – Histoplasmosis200 – Actinomycosis201 – Tuberculosis202

the most frequent nonmalignant causes (Fig. 12.17). The etiology of bronchoesophageal fistula is similar to that of tracheoesophageal fistula and various causes are shown in Box 12.11.

BRONCHIECTASIS Bronchiectasis is a chronic condition characterized by irreversible dilatation of bronchi, caused by inflammation.203 The qualification ‘irreversible’ is included in the definition to exclude the transient airway dilatation that has been observed in pneumonia and atelectasis.204–206 Dilatation of the airway in these circumstances is probably partly related to inflammatory changes in bronchial walls, altering compliance, and to exaggerated lung stresses after collapse. On rare occasions some adult patients show some reversibility of what would otherwise be considered typical idiopathic bronchiectasis.207 By contrast, in children reversibility of what may be considered bronchiectatic airways by HRCT criteria is more frequent.208 On macroscopic study, bronchiectatic airways are dilated in a variety of patterns that were historically classified into two203 or three types.209 The three-grade Reid classification is applicable to gross pathologic, bronchographic, and CT appearances. However,

Bronchiectasis

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Fig. 12.17  Acquired tracheoesophageal fistula in a 2-year-old child who swallowed a model soldier. A, The hyperdense object has eroded through the esophageal wall and impinges on the trachea (slightly to the right of the midline). B, Following thoracotomy and removal of the foreign body there is a large tracheoesophageal fistula. There is an endotracheal tube in place (midline) and a nasogastric tube in the dilated esophagus to the left. The fistula subsequently healed.

the clinical utility of designating bronchiectasis as cylindrical, varicose, or cystic is not obvious, although it is generally agreed that cystic bronchiectasis represents the most advanced disease. The Reid classification, most elegantly shown by bronchography (Fig. 12.18), is as follows: • Cylindrical bronchiectasis. Bronchial dilatation is mild, and the bronchi retain their regular and relatively straight outline. • Varicose bronchiectasis. Bronchial dilatation is greater than in cylindrical bronchiectasis and is accompanied by local constrictions that give the airway an irregular outline. Obstruction and obliteration of small airways is more pronounced. • Cystic (saccular) bronchiectasis. This is the most severe form of bronchiectasis. The airway takes on a ballooned appearance and the number of bronchial divisions is greatly reduced. Histologic study of bronchiectatic airways shows the walls to be thickened and chronically inflamed with chronic granulation tissue and the bronchial arteries to be hypertrophied210,211 (and these bronchial arteries may be conspicuous at CT).212 Ciliated epithelium is largely replaced by squamous epithelium or areas of squamous metaplasia. The mucosa is sometimes ulcerated or thrown into transverse ridges by circular muscle hypertrophy. Airways are surrounded by fibrosis and there may be organizing pneumonia in the adjacent parenchyma.211 The pathogenesis of bronchiectasis is complex, as shown by the large number of recognized causes and associations.210,213–215 The most important and commonly implicated pathogenic factor is bronchial wall weakness, often brought about by infective inflammatory damage. It seems probable that such damage is self-perpetuating and this has led to the ‘vicious circle’ hypothesis, which proposes that colonizing microbes impair normal host clearance mechanisms, thereby modifying the environment within the airways so allowing microbial growth. The host immune response is ineffective in dealing with the microbial colonization and, paradoxically, the immune response further damages mucociliary clearance, thus setting up a vicious circle of host damage and further microbial growth.216 Recognized associations and causes210,214 are listed in Box 12.12. Gross bronchiectasis is characterized by persistent cough, with copious purulent sputum and recurrent pulmonary infections. Symptoms frequently date from childhood, when there may have been a precipitating pneumonic event. With widespread disease there may be dyspnea and, ultimately, cor pulmonale. Such severe

bronchiectasis is becoming unusual and is largely limited to patients with impaired defense mechanisms. A recognized presentation of mild bronchiectasis is recurrent hemoptysis,276 but mild bronchiectasis may be asymptomatic. The classic description of the radiographic changes in bronchiectasis is that of Gudbjerg.277 In this historic series 93% of radiographs were said to be abnormal. Although this might seem a high figure as judged by some clinical reports,278,279 later studies have reiterated that careful analysis of chest radiographs of patients with bronchiectasis will reveal abnormalities in the majority of cases.280,281 Some varieties of bronchiectasis such as occur in cystic fibrosis and the ciliary dyskinesia syndrome282 almost invariably show radiographic changes, which comprise: • Visible bronchial walls – these are visible either as single thin lines or as parallel line opacities (Fig. 12.19). • Ring and curvilinear opacities – these are generated by thickened airway walls seen end on. Ring opacities range in size from 5  mm to 20  mm and can have very thin (hairline) walls (Figs 12.20 and 12.21). They may contain air–fluid levels. • Plugged airways – these give rise to band shadows of variable size (Fig. 12.22), which may branch, giving V, Y, or even more complex-shaped opacities. • Vascular structures – these may appear increased in size and may be indistinct because of adjacent peribronchial inflammation and fibrosis. • Volume change – in generalized bronchiectasis, such as that associated with cystic fibrosis, there is often generalized overinflation282 (Fig. 12.20). Localized forms, however, are frequently accompanied by atelectasis (Fig. 12.22), which may be mild and detected only because of vascular crowding, fissural displacement, or obscuration of part of the diaphragm (Fig. 12.19). • Other signs – these include evidence of scarring, bulla formation, and pleural thickening. Areas of pulmonary consolidation may be due to infection, for example Pseudomonas aeruginosa, but can also be a manifestation of allergic bronchopulmonary aspergillosis, which may be superimposed on other bronchiectatic conditions (for example, cystic fibrosis).283

HRCT signs of bronchiectasis By pathologic definition, dilatation of the airways is a prerequisite for the diagnosis of bronchiectasis. Thus the major sign of HRCT

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B

C

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Fig. 12.18  Patterns of bronchiectasis. A, Cylindrical bronchiectasis. Left posterior oblique projection of a left bronchogram showing cylindrical bronchiectasis affecting the whole of the lower lobe except for the superior segment. Few side branches fill. The basal airways are crowded together, indicating volume loss of the lower lobe, a common feature in bronchiectasis. B, Varicose bronchiectasis. Left posterior oblique projection of a left bronchogram in a patient with ciliary dyskinesia. All the basal bronchi are affected by varicose bronchiectasis. C, Cystic bronchiectasis. Right lateral bronchogram showing cystic bronchiectasis affecting mainly the lower lobe and posterior segment of the upper lobe.

Bronchiectasis Box 12.12  Causes and associations of bronchiectasis

Congenital • Cartilage deficiency145,217–219 • Pulmonary sequestration220

Postinfection • Childhood pneumonia, measles, pertussis, Mycoplasma pneumonia,221,222 tuberculosis223 • Swyer–James (McLeod) syndrome224

Obstruction • • • • •

Neoplasm Lymph nodes (including ‘middle lobe syndrome’)225 Broncholith226 Foreign body227 Bronchostenosis, including sarcoidosis228

Inhalation and aspiration • • • • •

Ammonia229,230 Mustard gas231 Riley–Day syndrome232 Gastric aspiration233 Heroin overdose234

Impaired host defense and immunologic • • • • • • • • • • • • •

Primary ciliary dyskinesia Cystic fibrosis235,236 Primary impaired humoral or cellular immunity237–239 Infantile X-linked agammaglobulinemia (Bruton disease)240,241 Variable immunodeficiency222,242–244 Good syndrome245 Acute and chronic leukemia (with or without IgM deficiency) Ataxia telangiectasia (Louis–Bar syndrome)246 Human immunodeficiency virus (HIV) associated247–249 Lung transplant250,251 Ulcerative colitis252–254 Crohn disease255 Celiac disease256

Fig. 12.19  Bronchiectasis. Posteroanterior radiograph on which thickened bronchial walls are seen as line opacities through the heart. Some lines appear paired (arrows) and probably represent the opposite walls of a single airway. Separation of these lines is such that the airway must be dilated. Note crowding of the bronchi and obscuration of the medial part of the hemidiaphragm.

Allergy • Allergic bronchopulmonary aspergillosis257,258

Pulmonary fibrosis • End-stage lung fibrosis259 • Radiation260,261

Miscellaneous • • • • • • • • •

Idiopathic Purulent rhinosinusitis Tracheobronchomegaly (Mounier–Kuhn syndrome)115 α1-Antitrypsin deficiency262–265 Obstructive azoospermia (Young syndrome)266,267 Anhidrotic ectodermal dysplasia268 Rheumatoid disease, Sjögren syndrome269–272 Marfan syndrome273,274 Yellow nail syndrome275

bronchiectasis is dilatation of the bronchi (with or without bronchial wall thickening). The characteristics of bronchiectasis on CT, first described over 25 years ago,284 have withstood the test of time with subsequent minor refinements and additions.285–290 Absolute measurements for the diameter of all generations of the bronchi are not available for normal individuals, and relating the size of a bronchus to its immediately adjacent (homologous) pulmonary artery has been the most widely used criterion for the detection of abnormal dilatation.291 In normal individuals the overall diameter of a bronchus is approximately the same, at any given level, as that of its accompanying pulmonary artery. The ratio of the diameter of the bronchus (internal lumen) to the pulmonary artery diameter for subjects has been estimated to be 0.62 ± 0.13 (mean ± SD).292 Recognition of abnormal dilatation of a bronchus by comparison with its

Fig. 12.20  Gross cystic bronchiectasis. Posteroanterior chest radiograph showing overinflated lungs. There are multiple ring opacities, most obvious at the lung bases, ranging from 3 mm to 15 mm in diameter.

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Fig. 12.21  Ciliary dyskinesia syndrome – Kartagener syndrome. This 62-year-old woman gave a 40-year history consistent with bronchiectasis. The aortic arch, descending aorta, heart, and gastric air bubble are all on the right. There is diffuse complex pulmonary shadowing with many ring opacities. Broad-branching band shadows can just be seen through the heart and represent dilated fluid-filled airways.

A

Fig. 12.22  Lower lobe bronchiectasis. The marked volume loss of the left lower lobe is indicated by a depressed hilum, vertical left mainstem bronchus, mediastinal shift, and left-sided transradiancy. There are dilated plugged airways adjacent to both heart borders.

B

Fig. 12.23  Signet ring sign. Patients with A, cystic fibrosis and B, idiopathic bronchiectasis, showing several thick-walled bronchi which are dilated by comparison with the accompanying pulmonary artery.

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Bronchiectasis accompanying pulmonary artery can be readily made for airways running perpendicular to the CT section. When bronchial dilatation is marked, the cross-sectional appearance of the combined bronchus and artery resembles a pearl or signet ring293 (Fig. 12.23). In healthy individuals minor discrepancies in the bronchoarterial diameter ratio may occasionally be encountered.291,294 Furthermore, there are many factors that can cause transient or permanent changes in diameter of the relatively compliant pulmonary arteries, so invalidating this sign. For example, a left-to-right cardiac shunt will result in generalized increase in perfusion and thus caliber of the pulmonary arteries; conversely any cause of underventilation of a region of lung will result in hypoxic vasoconstriction. Thus bronchial dilatation in isolation cannot always be regarded as diagnostic of bronchiectasis and this is especially true in children.208 This caveat has been emphasized by Lynch et al.,294 who showed that 59% of normal individuals had at least one bronchus with a diameter greater than that of the homologous pulmonary artery; in these healthy subjects bronchial wall thickening was not a common association. One of the factors that appears to have contributed to the apparently high frequency of a decreased bronchoarterial ratio in normal individuals, in this particular study, was hypoxic vasoconstriction: the study group investigated were all examined in Colorado, at approximately 1600  m above sea level.294 Kim et al.292 subsequently performed a detailed study which compared the bronchoarterial ratio of normal individuals at sea level with that of normal individuals at high altitude (1600  m above sea level). The mean bronchoarterial ratio in individuals at altitude was 0.76 (SD 0.14) compared with 0.62 (SD 0.13) at sea level (p < 0.001).

A

B

When airways lie parallel to the plane of section, abnormal dilatation is recognized by a lack of normal tapering, producing a tramline or even flared appearance (Fig. 12.24). These airways are conspicuous in the lung periphery because of associated bronchial wall thickening. The cylindrical and varicose patterns of bronchiectasis, described by Reid,209 can be appreciated only for bronchi that lie within the plane of the CT section. Cylindrical bronchiectasis is by far the commonest morphologic pattern of bronchiectasis identified on CT.295 A bronchoarterial ratio of greater than 1 has been reported in 95% of patients with cylindrical bronchiectasis.290 Varicose bronchiectasis is characterized by a beaded appearance (Fig. 12.25) and cystic (or saccular) bronchiectasis is seen as thin-walled cystic spaces which may contain fluid levels. In cystic bronchiectasis, recognition that large cystic airspaces represent massively dilated bronchi may sometimes be difficult or impossible (Fig. 12.26). In this type of severe bronchiectasis the accompanying pulmonary artery is often obliterated. When varicose bronchiectatic airways are imaged in cross-section, they may appear as either cystic or cylindrical bronchiectatic airways because the characteristic corrugation of the bronchial walls cannot be identified in this orientation. Sections obtained at end-expiration have been advocated to differentiate cystic bronchiectasis from other cystic lung diseases;296 bronchiectatic airways usually decrease in size on expiratory scans in contrast with other cystic lesions. However, one study has reported that most cystic lesions in the lungs, whether bronchiectatic or another etiology, decrease in size,297 rendering this sign of doubtful discriminatory value.

Fig. 12.24  Cylindrical bronchiectasis. A, B, Examples from two patients. Airways parallel to the plane of section in the anterior segment of an upper lobe show changes of cylindrical bronchiectasis; bronchi are wider than normal and fail to taper as they proceed towards the lung periphery.

Fig. 12.25  Varicose bronchiectasis. Patient with allergic bronchopulmonary aspergillosis and cystic fibrosis. The bronchiectatic airways have a corrugated, or beaded, appearance.

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B

Fig. 12.26  Cystic bronchiectasis in the upper lobes in two patients. In such advanced disease, it is often impossible to distinguish between markedly dilated bronchi and cystic airspaces in destroyed lung. A, Etiology of the bronchiectasis was unknown in this patient. B, Patient had cystic fibrosis.

Fig. 12.27  Bronchial wall thickening of variable severity in a patient with idiopathic bronchiectasis. It is likely that at least part of the apparent wall thickening is due to retained secretions. There is a tree-in-bud pattern most conspicuous in the periphery of the left lower lobe.

Bronchial wall thickening is a usual, but inconstant, feature of bronchiectasis (Fig. 12.27). Problems with this variable feature have been widely debated and the definition of what constitutes ‘abnormal bronchial wall thickening’ remains unresolved.289 Minor to mild degrees of bronchial wall thickening are seen in healthy subjects, particularly elderly individuals,298 asthmatic people, individuals with acute lower respiratory tract infections,299 and asymptomatic smokers.294,300,301 There is no simple and robust criterion for the identification of abnormal bronchial wall thickening.302 Remy-Jardin et al.300 defined a bronchus as being thick walled when the bronchial wall was at least double the thickness of a normal bronchus. However, such a judgment is possible only when comparable ‘normal’ bronchi can be identified. An assessment can also be made by relating the bronchial wall thickness to the diameter of accompanying pulmonary artery,295,303 but in practice this does not overcome the difficulties of identifying subtle bronchial wall thickening.304 Diederich et al.305 defined abnormal bronchial wall thickening as being present if the internal diameter of the bronchus was less than 80% of the external diameter. While this sign was associated with

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Fig. 12.28  Patient with mild cylindrical bronchiectasis. The numerous peripheral nodular and branching opacities (tree-in-bud pattern) represent exudate in and around the small airways. good interobserver agreement it cannot be applied to conditions in which there is marked accompanying bronchial dilatation. Normal airways within 2  cm of the visceral pleural surface are not usually visible because their walls are below the spatial resolution of HRCT.306 However, perhaps as a consequence of improving CT technology, it has been pointed out that bronchi may be identified within 1 cm of the mediastinal pleura in normal subjects, but that airways seen within 1 cm of the costal pleura or paravertebral pleura should be regarded as abnormal.290 Large plugged bronchi are visible as lobulated or branching opacities – such airways are usually seen in the presence of nonfluid-filled but obviously bronchiectatic airways. A less frequent pattern is plugging and thickening of the smaller peripheral centrilobular airways, producing V- and Y-shaped opacities, the so-called ‘tree-in-bud’ appearance307–309 (Fig. 12.28); similarly, this pattern is almost invariably accompanied by abnormal, if not frankly bronchiectatic, larger airways.

Bronchiectasis

Fig. 12.29  Cylindrical bronchiectasis in the lower lobes. There is regional inhomogeneity of the attenuation of the lung parenchyma (mosaic pattern) reflecting coexisting small airways obliteration.

In many patients with bronchiectasis, areas of decreased attenuation of the lung parenchyma can be identified (Fig. 12.29); this mosaic attenuation pattern reflects accompanying obliteration of small airways disease.286,310 Sections taken at end-expiration enhance the feature of decreased attenuation, the extent of which correlates with functional indices of airways obstruction.310,311 This finding is most prevalent in lobes with severe bronchiectasis but may be seen in some lobes in which there are no CT features of bronchiectasis. Kang et al.286 identified a mosaic pattern in just over half of bronchiectatic lobes subsequently resected, and there was pathologic evidence of obliterative bronchiolitis in 85% of these resected lobes. Areas of decreased attenuation on CT representing constrictive obliterative bronchiolitis may sometimes be confused with the features of emphysema.312 Nevertheless, the rare association of bronchiectasis and true emphysema does sometimes occur. When a panacinar emphysema pattern (uniform decrease in attenuation of the lung parenchyma – see p. 763) is identified in the lower lobes, as part of α1-antitrypsin deficiency, it is often accompanied by bronchiectasis.313,314 Serial fluctuation in pulmonary function measures of airflow obstruction most closely correlate with alterations in the degree of mucus plugging on serial HRCTs.315 Subtle degrees of volume loss may be seen in lobes in relatively early bronchiectasis and this is most evident in the lower lobes where crowding of the mildly bronchiectatic airways and posterior displacement of the oblique fissure may be an early sign of bronchiectasis (Fig. 12.30). CT will readily show completely collapsed lobes containing bronchiectatic airways although the diagnosis of bronchiectasis in acutely collapsed or consolidated lobes is usually considered uncertain because of the reversibility of bronchial dilatation in these situations.204,205 An interesting and not readily explained accompaniment to bronchiectasis is thickening of the interlobular septa; this occurs in up to 60% of patients with idiopathic bronchiectasis and appears to be more prevalent in cases of more severe and extensive bronchiectasis316 (Fig. 12.31). Distortion and dilatation of segmental and subsegmental bronchi are predictable features in patients with retractile interstitial fibrosis,317 of whatever cause, and this has been termed (not particularly usefully) ‘traction bronchiectasis’. Many of the HRCT signs of bronchiectasis coexist, particularly in longstanding disease. The signs of bronchiectasis, discussed above, are summarized in Box 12.13 in the approximate sequence in which they occur. There are several situations in which the signs of bronchiectasis may be obscured by technical artifacts, or mimicked by other lung

Fig. 12.30  Mild cylindrical bronchiectasis in the left lower lobe. Note the crowding of the affected bronchi and loss of volume of the left lower lobe, as judged by the relative positions of the oblique fissures (arrows).

Box 12.13  HRCT features of bronchiectasis • Bronchial wall thickening – Nonspecific and variable • Lobar volume loss – May be minimal; most obvious in the lower lobes • Bronchial dilatation – Signet ring sign or nontapering bronchiectasis – The cardinal sign of bronchiectasis • Mosaic attenuation pattern – Reflecting coexistent constrictive bronchiolitis, may be an early feature • Tree-in-bud pattern – Representing exudate in and around small airways • Mucus plugging of large airways – A late sign • Interlobular septal thickening – An occasional feature linked to the severity of bronchiectasis

pathologies,287,288 and these are summarized in Chapter 4 (Box 4.9, p. 189).

Accuracy of HRCT for the detection of bronchiectasis In the absence of a reliable gold standard, the accuracy of HRCT in confirming or excluding bronchiectasis is difficult to ascertain. Evidence from early CT studies (using widely different technical parameters, particularly section collimation278,318–320) does not allow any definite conclusions to be drawn, particularly as bronchography (the then gold standard) cannot be regarded as a wholly reproducible technique.321,322 In one study in which thin-section CT findings were compared with pathologic features, from surgically resected bronchiectatic lobes, Kang et al.286 showed that CT identified bronchiectasis in 41 (87%) of 47 lobes with pathologically proven bronchiectasis. Because the patients selected for this study had relatively severe disease, the authors suggested that the detection rate of CT may be less in patients with mild bronchiectasis. However, the less than perfect performance of HRCT in this study might have reflected the fact that the deranged state of scarred lungs in end-stage bronchiectasis precludes the reliable identification of bronchiectatic airways. In the lobes considered to have bronchiectasis on CT, the most frequently identified sign was a lack of

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A

B

Fig. 12.31  Patient with longstanding multilobar bronchiectasis (idiopathic). There are A, several thickened interlobular septa, B, most conspicuous in the periphery of the left lung.

tapering of the bronchial lumens (37/41), followed by bronchial wall thickening (32/41), bronchial dilatation (28/41), identification of bronchi in the lung periphery (21/41), and mucus-filled dilated bronchi (3/41). The causes of the 9/47 (13%) false negatives were due to either masslike lesions or areas of dense opacification or scarring in which dilated bronchi were not identifiable. In a further study that compared the CT features of patients with surgically proven or CT-diagnosed bronchiectasis with normal subjects, lack of tapering of the bronchi was identified in 95% of patients with bronchiectasis compared with 10% of healthy subjects.290 The results of these studies reinforce the observation of Lynch et al.294 that lack of bronchial tapering should be regarded as the most reliable CT feature of bronchiectasis.

Disease-specific patterns of bronchiectasis In some patients, the cause for bronchiectasis may be deduced from ancillary CT features. For example, the diagnosis of Swyer–James (McLeod) syndrome (p. 750) can be readily made from the asymmetric involvement and additional features of decreased attenuation and reduced pulmonary vasculature of the ipsilateral lung.323,324 Similarly, the diagnosis of α1-antitrypsin deficiency may be suggested by the combination of widespread cylindrical or cystic bronchiectasis and panacinar emphysema in the lower lobes.313,314 However, an underlying cause for bronchiectasis is found in less than half of patients213,215 and CT features alone do not usually allow a confident distinction between idiopathic bronchiectasis and a known cause of bronchiectasis.295,325 Nevertheless, in some cases the pattern and lobar distribution of bronchiectasis may be sufficiently characteristic for a specific underlying cause to be diagnosed.326–328 For example, the bronchiectasis of allergic bronchopulmonary aspergillosis is typically upper zone and central in distribution, with more normal distal bronchi. These features may be helpful in distinguishing this condition from other causes or idiopathic bronchiectasis.329–332 Several other distinctive, if not diagnostic, patterns have been described in patients with a known cause of bronchiectasis. A lower

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and middle lobe distribution of cylindrical bronchiectasis with particularly marked bronchial wall thickening is typical in patients with hypogammaglobulinemia,222,333 and in patients with common variable immune deficiency there is often a background reticular pattern reflecting granulomatous fibrosis.243 The upper lobe predilection for the cylindrical bronchiectasis of cystic fibrosis is well known.235,334,335 In patients with bronchiectasis due to nontuberculous mycobacterial infection, there is usually an accompanying nodular pattern;336,337 indeed, there appear to be some differences in patterns of disease between the subspecies of nontuberculous mycobacteria.338 Apart from the localized bronchiectasis associated with post-tuberculous fibrocalcific damage, the range of possible manifestations of post-tuberculous bronchiectasis remains poorly documented. Idiopathic bronchiectasis has been reported to be predominantly basal in distribution.295,327 However, studies that have sought to determine whether observers can reliably distinguish between idiopathic bronchiectasis and bronchiectasis of known cause have not been conclusive and suggest that, although several CT features occur more frequently in certain groups of patients with an identifiable underlying cause, none of the CT features evaluated can be regarded as pathognomonic.295,325,328 Some conditions with more or less distinctive features on HRCT (including the distribution of disease, pattern of bronchiectasis, and ancillary features) are listed in Box 12.14.

Box 12.14  Causes of bronchiectasis with distinctive HRCT features • • • • • •

Allergic bronchopulmonary aspergillosis Swyer–James (McLeod) syndrome Tracheobronchomegaly (Mounier–Kuhn syndrome) α1-Antitrypsin deficiency Cystic fibrosis Mycobacterium avium–intracellulare complex

Bronchiectasis

Cystic fibrosis Cystic fibrosis, also known as cystic fibrosis of the pancreas, fibrocystic disease, and mucoviscidosis, is the most common autosomal recessive disorder in the Caucasian population, with a frequency of about 1 in 2500 livebirths.339,340 The disease is uncommon in African Americans and rare in Asians and Native Americans. Worldwide, 60 000 people are affected.341 Cystic fibrosis is caused by a mutation in a gene on chromosome 7 that codes for the cystic fibrosis transmembrane conductance regulator (CTFR).342,343 Although over 800 mutations have been identified,344 the most common mutation that causes cystic fibrosis is known as delta-F508.342 CFTR functions primarily as a chloride ion channel and the defective protein affects pancreatic function and the consistency of mucosal secretions. Although the defective gene has been identified, gene replacement therapy is still far from clinical realization.345 The primary manifestations of cystic fibrosis include abnormal sweat electrolytes, sinus and pulmonary disease, exocrine pancreatic insufficiency, and male infertility.346 However, most organ systems are affected, to a greater or lesser extent, because of the wide tissue distribution of CFTR, but the lungs bear the brunt of the disease. Despite major advances in treatment, pulmonary infection remains the major cause of morbidity and mortality. Staphylococcus aureus and Haemophilus influenzae are the most common infecting organisms in the first decade of life, but infections caused by Pseudomonas and Burkholderia species dominate thereafter. By adulthood, 80% of patients are colonized with P. aeru­ ginosa and 3.5% with Burkholderia cepacia, Stenotrophomonas mal­ tophilia, and Achromobacter xylosoxidans. Nontuberculous mycobacteria are emerging as important pathogens in patients with cystic fibrosis, particularly Mycobacterium abscessus, M. avium– intracellulare, Mycobacterium fortuitum and Mycobacterium kansasii.347,348 There are difficulties in interpreting the importance (colonization versus infection) of the presence of these organisms when they are isolated from the sputum of patients with cystic fibrosis,349 especially because of the similarity in HRCT appearances of cystic fibrosis with or without nontuberculous infection. Although the disease is present at birth, radiographic abnormalities may not become apparent for months or years, but thereafter are progressive (Fig. 12.32). The earliest findings are nonspecific and include diffuse bronchial wall thickening, focal atelectasis, and recurrent pneumonia. At this stage, the clinical features of the disease, not the chest radiographic findings, suggest the diagnosis. Progression of disease with worsening radiographic abnormalities is usually inexorable, despite treatment, but the rate of deterioration is highly variable. Patients with early manifestations of the disease tend to deteriorate the most rapidly.350 In the fully developed form of the disease the radiographic findings are remarkably uniform and include the following:351–355 • Bronchial wall thickening and bronchiectasis – which result from chronic inspissation of mucus and airway infection, are the hallmarks of the disease (Fig. 12.32D). These findings are seen on chest radiographs as peribronchial cuffing, tram-tracking and ring shadows. Associated mucoid impactions that manifest as ‘finger-in-glove’, ‘toothpaste’, or nodular opacities are also common. Bronchiectasis may be cylindrical or cystic depending upon the severity and chronicity of the disease. Cystic bronchiectasis may be an impressive feature of the disease (Fig. 12.33). The cysts can be up to 3 cm in diameter and usually have thin walls. The walls may be thickened by associated infection and the cysts may contain variable quantities of fluid. In advanced disease it may be impossible to distinguish between cystic lung destruction and grossly dilated airways, particularly in the upper lobes. • Atelectasis and focal consolidation – these are also common and may wax and wane in association with acute infection. Extensive cicatricial atelectasis in the upper lobes may result from chronic or recurrent infection (Fig. 12.34). Large areas of consolidation are uncommon but are seen in overwhelming, usually

P. aeruginosa, infection or, more frequently, allergic broncho­ pulmonary aspergillosis283,356 (Fig. 12.35). • Enlarged hila and diffuse perihilar opacities – enlargement of the hila is caused by lymphadenopathy, dilatation of the pulmonary arteries (reflecting pulmonary hypertension), and inflammatory changes adjacent to the hila (Fig. 12.36). Lymphadenopathy, presumably due to reactive hyperplasia, is a common finding in patients with cystic fibrosis.355 Diffuse perihilar opacities are due to peribronchial inflammation and central bronchiectasis (Fig. 12.36), and in some individuals may reflect coexisting allergic bronchopulmonary aspergillosis. • Progressive airway obstruction results in pulmonary hyper­ inflation – the thorax becomes barrel-shaped with an increased anteroposterior diameter (Fig. 12.32E). The diaphragms are usually low and flattened. Parenchymal findings seen on chest radiographs of patients with longstanding cystic fibrosis are usually more severe in the upper than lower lungs (Fig. 12.34). Nevertheless, in younger children this upper lobe predominance may be less noticeable.357 Chest radiographs over a number of years generally reflect the patient’s deteriorating status, but short-term clinical fluctuations are not necessarily accompanied by any readily detectable radiographic changes. Greene et al.358 studied 14 specific radiographic findings in a group of adults with and without acute exacerbations of cystic fibrosis. They were unable to find a statistically significant association between any of the findings and the presence or absence of acute symptoms. These authors concluded that the value of the chest radiograph in the setting of an acute cystic fibrosis exacerbation lay more in excluding a major complication such as pneumo­ thorax. In part, this must reflect the inherent difficulties in detecting small focal radiographic abnormalities against a background of diffuse bronchiectasis and lung destruction. Nevertheless, a number of scoring systems use findings on chest radiographs to grade the severity of cystic fibrosis.351,359 Common complications of cystic fibrosis include pneumothorax and hemoptysis. Pneumothorax is caused by rupture of emphysematous blebs or bullae.360 Hemoptysis usually originates from hypertrophied bronchial arteries and varies in severity from minor blood-streaked sputum to massive hemoptysis (greater than 240  mL/24  h).361 Affected patients tend to have very severe lung disease and a high incidence of infection by multidrug-resistant bacteria.361 Bronchial artery embolization (BAE) is an effective treatment for cystic fibrosis patients with pulmonary bleeding.361–363 Brinson et al.361 reviewed their experience with BAE in 18 patients treated over a 10-year period. They found that the overall efficacy of BAE for initial control of bleeding was 75% after one, 89% after two, and 93% after three treatments. Unfortunately, they also found that the rate of recurrent bleeding was high (46%); the mean time to recurrence was approximately 12 months. They also found a high incidence (75%) of bleeding from nonbronchial systemic collateral vessels in the patients who had undergone previous BAE, indicating the necessity of evaluating all potential systemic collateral vessels. Lung abscess and empyema are surprisingly uncommon complications of cystic fibrosis. The CT findings of cystic fibrosis on conventional364 and thinsection CT have been extensively documented.235,236,334,365–370 As might be expected, CT delineates the morphologic changes of cystic fibrosis with much greater accuracy and detail than chest radiographs. As with chest radiography, CT has only limited usefulness in the investigation of patients with acute exacerbations of cystic fibrosis. The only finding in the study of Shah et al.368 that had a correlation with acute exacerbation was the presence of air–fluid levels. Another study has confirmed that changes in mucus plugging on HRCT are the most labile abnormality in acute exacerbations.371 Brody et al.372 have shown that scores of severity of disease on CT over a period correlate with the number of exacerbations in that period, although no CT feature reliably predicted exacerbations. Numerous investigators have reported moderate to good correlation between functional impairment and CT findings using a variety

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B

C D

Fig. 12.32  Cystic fibrosis. Serial chest imaging over a 26-year period showing the progressive changes of cystic fibrosis. A, At 3 years of age, the patient presented with right middle lobe pneumonia. B, There is mild hyperinflation and bronchial wall thickening (arrows) by age 7 years. C, At age 15 years, the chest radiograph shows progressive hyperinflation, bronchiectasis, and enlargement of the hila. D, Frontal and

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Bronchiectasis

F

E

G

Fig. 12.32  Continued E, lateral chest radiographs at 29 years show typical findings of end-stage cystic fibrosis. Note marked hyperinflation and ‘barrel chest’ deformity, severe bronchiectasis, and tubular opacities consistent with mucus plugs. F, G, Standard CT images at 29 years show extensive bronchiectasis (arrows), which is more severe in the upper (F) than the lower (G) lobes, mucoid impaction (arrows) and mosaic attenuation due to small airways obstruction.

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Chapter 12 • Diseases of the Airways Box 12.15  CT pulmonary findings in cystic fibrosis • Bronchiectasis – Cylindrical or cystic, upper lobe predominant • Peribronchial thickening • Mucus plugging – Tree-in-bud pattern through to bronchoceles • Mosaic attenuation pattern • Consolidation and atelectasis – Consolidation may be noninfective (e.g. allergic bronchopulmonary aspergillosis [ABPA]) • Bullae • Pleural thickening – Usually limited pleural ‘tags’ in the upper zones posteriorly

Fig. 12.33  Cystic fibrosis in a 24-year-old woman. Frontal chest radiograph shows marked hyperinflation, and diffuse cystic bronchiectasis.

Fig. 12.34  Cystic fibrosis in a 27-year-old woman. Frontal chest radiograph shows extensive bronchiectasis with bilateral upper lobe volume loss and retraction of both hila.

of CT scoring methods.236,357,365,369,373–377 While these methods for quantifying disease severity may be useful from a research standpoint, potentially providing surrogate endpoints in clinical trials, the usefulness of routine monitoring of individuals with cystic fibrosis with CT in everyday clinical practice remains controversial.378–380 The CT findings of CF vary with duration and severity of disease.236,357,365,369,370,373,374,381,382 Bronchiectasis is the predominant abnormality. Cylindrical bronchiectasis is more common than cystic bronchiectasis, particularly in patients with mild lung disease.235,334 Over time the bronchiectasis progresses and HRCT

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may depict changes in the face of stable or minimal decline in lung function382,383 (Fig. 12.37). In advanced cases, both cylindrical and cystic forms of bronchiectasis tend to be more severe in the upper lungs (Fig. 12.38). Bronchial and peribronchial thickening is also a common finding on CT384 that reflects the chronic inflammatory changes in the bronchial wall. Mucus plugs, a very common finding, are seen to advantage with CT (Fig. 12.39). Abscesses may be difficult to distinguish from cystic bronchiectasis, particularly as both may contain air–fluid levels. Other CT findings include: focal areas of collapse or consolidation; tree-in-bud pattern; mosaic attenuation; bullae, hilar, and mediastinal adenopathy; and pleural thickening. Bullae may be difficult to distinguish from cystic bronchiectasis, particularly in fibrotic upper lobes (Fig. 12.40). A mosaic attenuation pattern likely reflects obstruction of small airways (Fig. 12.40). Pleural thickening is often apparent on chest radiographs and is demonstrated to advantage by CT.235 The extent of such thickening may have some bearing on difficulties at lung transplantation, although it has been convincingly shown that assessment with pretransplantation CT is, in fact, of little value.385 In some patients who develop a pneumothorax CT may usefully identify the optimal site for chest drain insertion because the visceral pleura is often tethered to the chest wall as a result of pleural adhesions386 (Fig. 12.41). The CT features of cystic fibrosis are summarized in Box 12.15. MRI has been used for investigation of patients with cystic fibrosis;387,388 it can demonstrate many of the salient features of cystic fibrosis, but lacks the spatial resolution of CT. Donnelly et al.344 used hyperpolarized 3He-enhanced MRI to image patients with cystic fibrosis. The technique is quite sensitive for small airway obstruction389 and can provide a means of evaluating progression of disease in patients with cystic fibrosis without use of ionizing radiation, a use which is likely to be limited to research applications.

Ciliary dyskinesia syndrome (immobile cilia syndrome) (Box 12.16) The ciliary dyskinesia syndrome (CDS) is an example of one of many specific causes of bronchiectasis, and with changing patterns of etiology it is becoming relatively more important. In a selected

Box 12.16  Ciliary dyskinesia syndrome • One of the commonest identifiable causes of bronchiectasis in the pediatric age range • Associated with infertility in males • Presentation with bronchiectasis may be delayed until adulthood • Accompanying sinusitis is invariable • HRCT pattern of bronchiectasis is cylindrical with a predilection for the right middle lobe and lingula

Bronchiectasis

B A

C

series of patients referred to a specialist hospital for investigation of chronic cough and sputum production, ciliary dyskinesia was, after postinfection bronchiectasis, the most frequent etiology,390 but was less prevalent in another series.215 In, ciliary dyskinesia, first identified in 1976,391 a variety of genetically determined defects in ciliary structure and function392 interfere with mucociliary clearance.393 Impaired mucus clearance is associated with recurrent upper and lower respiratory tract infections.394 CDS shares many features with cystic fibrosis but is less disabling and carries a better prognosis.282,395 Kartagener syndrome396 – situs inversus, paranasal sinusitis, and bronchiectasis – is a subtype of CDS, and about 50% of patients with CDS have Kartagener syndrome282,394,397 (see Fig. 12.21). About one-fifth of subjects with dextrocardia have Kartagener syndrome.398 CDS has autosomal recessive transmission with an equal sex incidence. In Europe and the USA CDS has a prevalence of about 1 : 20 000 individuals.399 Ciliary function is abnormal throughout the body, and sperm are immotile; thus males are infertile. Fertility in females is generally unaffected, although there are exceptions.397 Respiratory symptoms may be delayed in onset but

Fig. 12.35  Patient with cystic fibrosis and allergic bronchopulmonary aspergillosis (ABPA). A, Recent onset of dense right perihilar consolidation. B, Two months later there is multifocal consolidation with spontaneous resolution of the right perihilar consolidation. C, Seven months later, after the diagnosis of ABPA was made, and steroid treatment was started, there is complete resolution of the consolidation.

can generally be traced back to childhood, and CDS is increasingly recognized as a cause of neonatal respiratory distress.400,401 Symptoms are those of bronchitis, rhinitis, and sinusitis, which are universal, and otitis, which is less common. Bronchiectasis develops in childhood and adolescence and is associated with recurrent infections. Prognosis is generally good, and the diagnosis is compatible with a full lifespan.398 The diagnosis is regarded as established in the following circumstances: (1) complete Kartagener syndrome, (2) men with normal situs but a classic history and immotile sperm, (3) women and children with normal situs but typical history and an affected sibling, and (4) subjects with normal situs but with a classic history and ultrastructural defects of nasal or bronchial cilia on biopsy.394,402 Findings on the chest radiograph and CT are of bronchial wall thickening (almost invariably) and bronchiectasis with a predilection for involvement of the middle lobe and lingula403 (Fig. 12.42). In a few patients with CDS there is abnormal calcium deposition within the affected airways, such that this may be visible on imaging; lithoptysis (coughing up of broncholiths) is also a rare association.404

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Chapter 12 • Diseases of the Airways

Fig. 12.36  Cystic fibrosis in a 24-year-old man. Frontal chest radiograph shows extensive bronchiectasis, central perihilar opacities, and enlarged hila due to reactive lymphadenopathy or pulmonary artery hypertension or both.

A

B

Fig. 12.37  Progression of cystic fibrosis in an 8-year-old boy. A, Mild cylindrical bronchiectasis and bronchial wall thickening in the upper lobes, which, 5 years later, B, has progressed despite no significant deterioration in pulmonary function testing.

A

B

Fig. 12.38  Cystic fibrosis. A, Typical upper lobe predominant distribution of bronchiectasis in a 14-year-old patient, with B, relative sparing of the lower lobes.

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Bronchiectasis

Fig. 12.39  Coronal CT of a 19-year-old patient with cystic fibrosis showing panlobular bronchiectasis and large mucus plugs at both lung bases. Incidental pneumomediastinum.

Fig. 12.40  Cystic fibrosis coronal CT. Severe upper lobe disease. Distinction between bullous destruction and end-stage cystic bronchiectasis is not possible in this case. Note the mosaic attenuation pattern reflecting obliterated small airways.

Fig. 12.41  Cystic fibrosis. Complex fibrobullous destruction in both upper lobes. Left-sided pneumothorax – there are several pleural adhesions likely caused by previous infective exacerbations and consequent pleural reactions.

A

B

Fig. 12.42  Ciliary dyskinesia syndrome. A, Mild bronchial wall thickening in the upper lobes. B, Typically the cylindrical bronchiectasis is distributed mainly in the lingual and right middle lobe (the latter is collapsed in this case).

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Chapter 12 • Diseases of the Airways Young syndrome266,267 clinically resembles CDS. However, in Young syndrome ciliary function is normal and infertility is due to obstructive azoospermia. Obstruction occurs at the level of the epididymis, which is palpably enlarged. The pathogenesis of increased sinopulmonary infection in these patients is obscure.

BRONCHOLITHIASIS (Box 12.17) The term ‘broncholithiasis’ is generally interpreted more widely than meaning simply the condition resulting from endobronchial calcified material.405 Most authors include, in addition, the effects of airway distortion or inflammation caused by calcified peribronchial nodes406 or other rarer causes of focal calcific endoluminal lesions.407 Nearly all cases are due to infective nodes, particularly following histoplasmosis.408,409 Other causal infections include tuberculosis, actinomycosis, coccidioidomycosis, and cryptococcosis. A few cases have been reported with silicosis410 and in association with ciliary dyskinesia.404 Calcified material in an airway or luminal distortion caused by peribronchial disease results in airway obstruction. This in turn leads to collapse, obstructive pneumonitis, mucoid impaction, or bronchiectasis. Rarely fistulas can form from the airway to the esophagus,411 pleural space, or aorta408 and mediastinal abscess formation has been reported.412 Symptoms commonly include cough, hemoptysis, and recurrent episodes of fever and purulent sputum.226,408 The classic symptom of lithoptysis is uncommon, with a reported frequency of between 13% and 16%.226,408 In a review of the plain radiographic findings three major types of change were distinguished:405 (1) disappearance of a previously identified calcified nidus; (2) change in position of a calcified nidus; and (3) evidence of airway obstruction including segmental or lobar atelectasis, mucoid impaction, obstructive pneumonitis, and obstructive overinflation with air trapping. Predictably there may be signs of bronchiectasis. Calcified hilar or mediastinal nodes are a key feature of the radiograph, and it is important to inspect all calcifications, assess their position, and look for evidence of movement on serial radiographs. Movement can be difficult to detect and may just be a relatively subtle rotation.405 Broncholithiasis is more common on the right,408 and obstructive changes particularly affect the right middle lobe. The diagnosis may not be suspected on chest radiography. CT and fiberoptic bronchoscopy complement each other in this condition, neither on its own being necessarily diagnostic. Principal findings on CT226,407,413–415 are a calcified lymph node within an airway or immediately adjacent to a distorted airway, distal changes secondary to bronchial obstruction, and absence of an associated soft tissue mass (Fig. 12.43, see also Fig. 5.63, p 236). CT is not always correct in accurately localizing calcification because of partial volume effects, and in one series 40% of truly endobronchial lesions were interpreted on CT as extrabronchial.226 Reconstruction of volumetric CT data, including three-dimensional depictions,416 can be used to overcome this problem.407 The CT appearance of broncholithiasis can be mimicked by calcified endobronchial hamartomas or carcinoid tumors.417

Box 12.17  Broncholithiasis • There are many causes of a calcified endobronchial obstructing lesion, the commonest result from granulomatous infections • Consequences include postobstructive atelectasis, mucoid impaction, and bronchiectasis • Diagnosis on chest radiography may be difficult in the absence of heavy calcification of the broncholith • CT with reconstructions and/or bronchoscopy are needed to make the diagnosis of broncholithiasis

740

Fig. 12.43  Broncholithiasis in a 50-year-old man who had been treated for pulmonary tuberculosis 10 years earlier. CT shows several calcified lymph nodes in the subcarinal region and adjacent to segmental bronchi of the right middle and lower lobes (yellow arrows). There is also a small irregular calcified nodule in the superior segmental bronchus of the left lower lobe (red arrow) with distal consolidation. Bronchoscopy revealed a broncholith, which was removed. (With permission from Seo JB, Song KS, Lee JS, et al. Broncholithiasis: review of the causes with radiologic-pathologic correlation. RadioGraphics 2002;22:S199–213. Copyright Radiological Society of North America.)

SMALL AIRWAYS DISEASES Bronchiolitis includes a spectrum of inflammatory and fibrosing disorders that predominantly affect the small airways (terminal and respiratory bronchioles). Diseases affecting the small airways show great variability as regards cause, clinical features, and histopathologic changes. A number of attempts to classify these conditions have been made,418–423 and one of the more comprehensive schemes, described by Myers and Colby,420 is shown below: 1. Constrictive bronchiolitis (obliterative bronchiolitis, bronchiolitis obliterans) 2. Cryptogenic organizing pneumonia (bronchiolitis obliterans organizing pneumonia [BOOP], proliferative bronchiolitis) 3. Acute bronchiolitis (infectious bronchiolitis) 4. Small airways disease (adult bronchiolitis) 5. Respiratory bronchiolitis (smoker’s bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease) 6. Mineral dust airways disease (early pneumoconiosis) 7. Follicular bronchiolitis 8. Diffuse panbronchiolitis. Diseases affecting the small airways are difficult to detect by conventional radiographic and physiologic tests; widespread involvement occurs before symptoms or abnormalities on pulmonary function testing become apparent. An understanding of the distribution of disease in relation to the airways at a pathologic level allows some prediction of the likely CT appearances in this wide spectrum of conditions, and thus helps to refine differential diagnosis. The difficulty in detecting small airways dysfunction on pulmonary function testing can be readily appreciated by considering the fact that the summed cross-sectional area of the small airways luminal diameters is much greater than that of the central airways and so accounts for less than a quarter of total airflow resistance. Thus an extraordinary number of small airways need to be affected before there is a measurable physiologic effect on airflow limitation.

Small Airways Diseases The terminology used to classify diseases of the small airways is confusing but can, for imaging purposes, be greatly simplified. Manifestation of small airways disease on HRCT can be broadly categorized into direct and indirect signs: considerable thickening of the bronchiolar walls by inflammatory infiltrate and/or luminal and surrounding exudate render affected airways directly visible (tree-in-bud pattern). By contrast, cicatricial scarring of many bronchioles results in the indirect sign of patchy density differences of the lung parenchyma, the areas of decreased attenuation reflecting areas of underventilated, and consequently underperfused, lung (mosaic attenuation pattern); these two basic patterns of small airways disease are more fully discussed in Chapter 4.

Pathologic classification and clinical background Inflammation of the bronchioles (bronchiolitis) with or without subsequent scarring and obliteration is a very common lesion in the lungs.424 However, the extent of such lesions is rarely extensive enough to cause clinical symptoms. Texts in the pathology often emphasize the frequent involvement of the bronchioles in diverse diffuse lung diseases. The specific and classical term obliterative bronchiolitis (synonymous with bronchiolitis obliterans) has historically been the subject of confusion, primarily because of its use in the context of BOOP. The clinicopathologic entity of BOOP, now termed cryptogenic organizing pneumonitis,425,426 is now regarded as quite distinct from obliterative bronchiolitis (Fig. 12.44). There are several reports in the older literature describing cases of ‘bronchiolitis obliterans’ whose pathologic descriptions contain all the hallmarks of an organizing pneumonia (characterized by buds of loose granulation tissue occupying the airspaces and respiratory bronchioles, without any obliteration of the small airways).427–429 It is now generally accepted that there is no direct connection between obliterative bronchiolitis and BOOP,430 such that in the interests of clarity most authorities suggest that the bronchiolitis obliterans part of BOOP should be discarded. In those patients in whom no causative agent for the organizing pneumonia can be found, the term cryptogenic organizing pneumonia is more appropriate426 (see p. 575). The various conditions included within the term ‘small airways diseases’ are usually classified into pathologic subtypes or by less precise clinical criteria (usually by presumed cause or association). While pathologists categorize small airways diseases according to their histopathologic subtypes, the difficulty with this classical approach is that there are not always obvious clinical (or HRCT) correlates with these subtypes.431–434 A simple approach relies on the fundamental difference between the indirect HRCT signs of constrictive obliterative bronchiolitis and the direct visualization of exudative forms of bronchiolitis (typified by diffuse panbronchiolitis).435 These two patterns of small airways disease account for the majority encountered in clinical practice. Other miscellaneous forms of small airways disease with more or

A

less distinctive pathologic and imaging features, if not clinical presentations, are dealt with separately.

Constrictive obliterative bronchiolitis Constrictive obliterative bronchiolitis (hereafter referred to as constrictive bronchiolitis) is, as its name implies, a condition characterized by bronchiolar and peribronchiolar inflammation and fibrosis that ultimately leads to luminal obliteration.418,420,436 The early change is a cellular inflammation that is intraluminal, mural, and peribronchial, affecting membranous and respiratory bronchioles. Inflammatory cells are a mixture of neutrophils, lymphocytes, and plasma cells. The mature lesion is a peribronchiolar fibrosis, encroaching on the lumen with eventual occlusion of the airway.420 Other features include smooth muscle hyperplasia and bronchiolectasis with mucoid impaction.418 Given the close proximity of pulmonary arterioles, some inflammatory involvement is to be expected; however in later stages remodeling of these vessels, probably in response to chronic underventilation and hypoxia, becomes evident (an irreversible phenomenon, not to be confused with ‘reversible’ hypoxic vasoconstriction encountered in, for example, the bronchospasm of acute asthma). Clinical findings are extremely variable in severity and vary according to cause and severity, but symptoms typically consist of progressive dyspnea and nonproductive cough unaccompanied by significant wheezing. On auscultation of the chest, crackles and, apparently characteristic, inspiratory squeaks and squawks are heard. Pulmonary function tests show airflow obstruction, sometimes with restriction, with a normal gas transfer adjusted for alveolar volume (Kco).437,438 There is evidence of gas trapping with a low forced vital capacity and a high residual volume. Airflow limitation is volume-dependent and may be demonstrated by use of flow volume loops that allow calculation of maximum midexpiratory flow rates (MMEFRs). However, a reduced MMEFR is not specific for small airways disease.439 Constrictive bronchiolitis is a relatively uncommon disorder that in most cases is associated with a recognized cause and is rarely truly cryptogenic. Reported causes and associations are listed in Box 12.18. From the radiologist’s viewpoint it may be useful to consider the general situations in which the HRCT signs of constrictive bronchiolitis may be encountered, and their significance (see Box 12.19). Viral infections, particularly by respiratory syncytial virus and adenovirus,441,471 are a common cause of constrictive bronchiolitis in children. Nonviral agents are much less commonly implicated, although Mycoplasma pneumoniae is a particularly potent cause of constrictive bronchiolitis440,444,445 (Fig. 12.45). Caution is needed in interpreting reports that suggest bacterial infections, for example Nocardia asteroides and Legionella pneumophila, may be responsible for constrictive bronchiolitis:429,472 the pathology described in these particular reports is of an organizing pneumonia rather than constrictive bronchiolitis (highlighting the historical confusion sur-

B

Fig. 12.44  Schematic representation of the pathology of A, constrictive obliterative bronchiolitis and B, organizing pneumonia (formerly referred to as bronchiolitis obliterans organizing pneumonia [BOOP]); in the latter, the dominant process is plugging of the airspaces and small airways with loose granulation tissue rather than peribronchiolar fibrosis and luminal obliteration.

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Chapter 12 • Diseases of the Airways Box 12.18  Causes of and associations with constrictive bronchiolitis • Postinfection • Viral440 (adenovirus,441 respiratory syncytial virus, influenza,442,443 and parainfluenza444) • Mycoplasma445 • Postinhalation (toxic fumes and gases)446,447 • Nitrogen dioxide (silo-filler disease), sulfur dioxide, ammonia, chlorine, phosgene448 • Mustard gas449 • Hot gases450 • Connective tissue disorders439 • Rheumatoid arthritis451,452 • Sjögren syndrome453,454 • Others very rarely • Allograft recipients • Bone marrow transplant455,456 • Heart–lung or lung transplant457–460 • Drugs • Penicillamine461 • Ulcerative colitis462,463 • Cryptogenic437 (truly idiopathic cases very rare) • Other conditions • Bronchiectasis286,310 • Chronic bronchitis464 • Cystic fibrosis465 • Hypersensitivity pneumonitis466 • Diffuse idiopathic pulmonary neuroendocrine hyperplasia467,468 • Sauropus androgynus ingestion469 • Popcorn production workers470

rounding the terminology of ‘bronchiolitis obliterans’). Postinfectious constrictive bronchiolitis is largely confined to children; although repeated viral lower respiratory tract infections are a usual fact of adult life, clinically important constrictive bronchiolitis as a consequence is fortunately rare473 (Fig. 12.46). Swyer–James (or McLeod) syndrome is a particular form of constrictive bronchiolitis that occurs following an insult, usually a viral infection, to the developing lung and this is discussed on pages 750–752. Constrictive bronchiolitis is a predictable consequence of the inhalation of many toxic fumes and gases which reach the small airways.447 It has been most frequently described following nitrogen dioxide inhalation (silo-filler disease),474,475 and more recently in individuals exposed to mustard gas in war zones.449 Among the connective tissue diseases, constrictive bronchiolitis is most strongly associated with rheumatoid arthritis.439,451,476,477 Constrictive bronchiolitis associated with rheumatoid arthritis is occasionally rapidly progressive with refractory airflow obstruction unresponsive to any treatment.451 Nevertheless, minor degrees of

Box 12.19  Situations in which HRCT signs of constrictive bronchiolitis are identified • Trivial extent – e.g. subclinical post mild viral lower respiratory tract infection; asthma; healthy individuals • Expected – e.g. bronchiectasis; cigarette smoker • Component of chronic interstitial lung disease – e.g. sarcoidosis; hypersensitivity pneumonitis • Dominates clinical picture – e.g. post-transplantation; following severe viral pneumonia; rheumatoid arthritis; fume inhalation

Fig. 12.45  Sequel of Mycoplasma pneumonia in a 6-year-old child. CT obtained during breathholding at full inspiration. There are dramatic segmental differences in attenuation of the lung parenchyma, reflecting severe constrictive bronchiolitis. There is a marked reduction in the caliber of the pulmonary vasculature in the affected (decreased attenuation) parts of the lung. Numbers

Re so (we lve eks )

Recover

Viral respiratory infections

olve Res hs) nt (mo

Acute Broncho bronchiolitis

Chronic

Pro

gre

Mild

ssiv

e Severe

Irreversible airflow obstruction Respiratory failure

Obliterative bronchiolitis

Fig. 12.46  Natural history and potential outcomes of lower respiratory tract viral infections. (Modified with permission from Green M, Turton CW. Bronchiolitis and its manifestations. Eur J Respir Dis Suppl 1982;121:36–42.)

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Small Airways Diseases constrictive bronchiolitis are probably present and subclinical in many patients with rheumatoid arthritis.272,478,479 In historical reports about half of patients with rheumatoid arthritis and constrictive bronchiolitis had been taking penicillamine,437,451 and a cause and effect relationship was proposed.480,481 This was supported by a study of 602 patients with rheumatoid arthritis in which there was a 3% prevalence of constrictive bronchiolitis in patients receiving penicillamine but there were no cases of constrictive obliterative bronchiolitis in those not taking the drug.461 Furthermore, a close temporal relationship often exists between starting penicillamine medication and the onset of symptoms.439 It remains possible that penicillamine treatment is merely a ‘marker’ of those patients with more severe rheumatoid arthritis, who are thus more likely to develop complications of the disease, including constrictive bronchiolitis. Studies using indirect measures, such as pulmonary function testing and HRCT, suggest that small airways disease is probably more prevalent than earlier authors indicated.477,478 Patients with Sjögren syndrome may have a combination of interstitial disease (usually lymphoid interstitial pneumonia) and airways disease but, unlike rheumatoid arthritis, constrictive bronchiolitis is rarely the dominant presenting feature.453,482 Constrictive bronchiolitis is an important and frequent cause of morbidity and mortality in patients receiving heart and lung transplants.456,460,483–485 It has a prevalence of between 25% and 50% and usually manifests itself between 9 and 15 months (range 60 days to 5.6 years) after transplantation.485 It is probable that subclinical damage to small airways epithelium occurs earlier, within the first few weeks following transplantation. Subtle abnormalities on HRCT may predate the functional abnormalities of supervening small airways obliteration.486 Nevertheless, the sensitivity of HRCT for the early detection of constrictive bronchiolitis in patients receiving transplants remains controversial,487–490 and the correlation between the functional severity of the so-called bronchiolitis obliterans syndrome and extent of CT abnormalities is not strong491 and some authors assert that the simple measure of monitoring FEV1 may be sufficient for detecting the development of clinically important constrictive bronchiolitis.492,493 Frequent and severe episodes of acute rejection, potentiated by cytomegalovirus and other infective agents, increase the risk of development of constrictive bronchiolitis. Modification of the immunosuppressive regimen may be successful in delaying the development of constrictive bron­ chiolitis, but relapses are common.485 Constrictive bronchiolitis is also a well-recognized complication of bone marrow trans­ plantation.456,494 The disorder develops usually within 18 months of transplantation and is also variably responsive to increased immunosuppression.495 Constrictive bronchiolitis is rarely truly cryptogenic.437,496,497 Most reported cases probably have an undisclosed precipitating cause or association, such as a connective tissue disease which subsequently declares itself.498 The radiographic features of constrictive bronchiolitis can be summarized as overinflation of the lungs, reduced pulmonary vasculature, with or without bronchial wall thickening499 (Fig. 12.47); these nonspecific abnormalities, seen in any form of chronic obstructive pulmonary disease, are prone to considerable observer variation. Furthermore, these signs are not present in all patients finally diagnosed as having constrictive bronchiolitis.294,500 In an early CT study of constrictive bronchiolitis, 15 patients who fulfilled the criteria of Turton et al.437 were examined with 10 mm section thickness and thin section CT (interspaced 3 mm sections).496 Chest radiographs were normal in 5/15 patients; the remaining 10 patients showed ‘limited vascular attenuation and hyperinflation’. In 13/15 a pattern of ‘patchy irregular areas of high and low attenuation in variable proportions, accentuated in expiration’ was recorded; this, and a report of two cases by Eber et al.,501 were the first studies to identify inhomogeneity of the density of the lung parenchyma as the indirect, but key, CT feature of constrictive bronchiolitis. Subsequent descriptions have confirmed and refined the HRCT features of constrictive bronchiolitis.438,502–507 The HRCT signs com-

Fig. 12.47  Chest radiograph of a patient with advanced constrictive bronchiolitis awaiting lung transplantation. The lungs are of large volume and there is flattening of the hemidiaphragms. There are subtle and nonspecific features of a reduction of the pulmonary vasculature in the upper zones and mild peribronchial thickening in the lower zones. Box 12.20  HRCT signs of constrictive bronchiolitis • Areas of decreased attenuation (black lung) • Reduction in caliber of the macroscopic pulmonary vessels within black lung • Patchy involvement (mosaic attenuation pattern) unless advanced and end stage • Abnormalities of the large airways – may be bronchiectasis or wall thickening • Air-trapping seen as enhancement of the mosaic pattern at expiratory CT

prise patchy areas of reduced parenchymal attenuation (the ‘mosaic attenuation pattern’), reduction in the caliber of the pulmonary vessels within areas of decreased lung density, bronchial abnormalities (Fig. 12.48), and a relative lack of change of cross-sectional area of affected parts of the lung on sections obtained at end-expiration323,508 (Fig. 12.49). The individual HRCT signs of constrictive bronchiolitis, listed in Box 12.20, are considered in more detail in Chapter 4. The sensitivity and specificity of the sign of decreased attenuation for the diagnosis of constrictive bronchiolitis depend largely upon the context in which it is encountered: for example, in patients who have received lung transplants, one study has reported a sensitivity of 40%, and specificity of 78%, for the mosaic pattern. This increased to 80% and 94%, respectively, for the expiratory CT sections.509 If the other HRCT features associated with constrictive bronchiolitis are also included (bronchial dilatation, bronchial wall thickening)510 specificity, and to a lesser extent the sensitivity, of HRCT is increased.509 Abnormalities of the macroscopic bronchi are a variable feature on HRCT, but are not unexpected given their anatomic

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Chapter 12 • Diseases of the Airways continuity with the small airways; it seems that bronchial dilatation and bronchial wall thickening are relatively late features of constrictive bronchiolitis, and are more frequent in immunologically driven disease, such as rheumatoid arthritis511(Fig. 12.50) or post lung transplantation.512 The regional inhomogeneity of the lung attenuation may be extremely subtle in constrictive bronchiolitis, and is sometimes invisible on inspiratory CTs; the attenuation differences may be enhanced on CTs obtained at end-expiration484,508,513–515 (Fig. 12.51) or by postprocessing of the image data.516–518 In some patients with extensive or end-stage constrictive bronchiolitis, the mosaic attenuation pattern may be absent. Furthermore, CT sections taken at end-expiration will appear remarkably similar to inspiratory sections: there will be no obvious change in

Fig. 12.48  Constrictive bronchiolitis in a patient with rheumatoid arthritis. There is a mosaic attenuation pattern and, within the areas of decreased attenuation, the pulmonary vasculature is of reduced caliber. Several of the subsegmental bronchi are thick walled and dilated.

A

cross-sectional area of the lungs (which normally decreases, at the level of the carina, by approximately 55%)519 (Fig. 12.52). However, the generalized paucity of vessels and bronchial abnormalities will be present, although these findings may be very similar to those seen in widespread and severe panacinar emphysema.313,520 The HRCT signs listed above are not, by themselves, specific for constrictive bronchiolitis and may be encountered in other chronic obstructive pulmonary diseases; for example, the mosaic attenuation pattern may be found in asthmatic patients, albeit usually less extensive than in patients with constrictive bronchiolitis.521 However, in the context of a known cause or association of constrictive bronchiolitis, an HRCT showing this constellation of features can be regarded as diagnostic. Nevertheless, there are circumstances in which the distinction between constrictive bronchiolitis and other forms of obstructive pulmonary disease, particularly in patients with severe disease, can be difficult.522 Areas of decreased attenuation of the lung parenchyma on HRCT in patients with constrictive bronchiolitis may sometimes be interpreted as ‘emphysema’; in constrictive bronchiolitis, the pulmonary vessels in affected lung are attenuated, but not distorted, as is the case in centrilobular emphysema. Furthermore, the extent of decreased attenuation caused by constrictive bronchiolitis does not correlate with gas diffusing capacity, the functional hallmark of emphysema.438 However, the differentiation between panacinar emphysema (typified by patients with α1-antitrypsin deficiency) and advanced obliterative bronchiolitis may be less straightforward on HRCT appearances alone. Both conditions tend to show large areas of uniform, relatively featureless, decreased attenuation (‘black’) lung, and both are characterized by bronchial wall thickening and dilatation (Fig. 12.53). A quite useful discriminator is the presence of a ‘spider’s web’ of preserved interlobular septa just above the diaphragmatic surface in patients with panacinar emphysema (see Fig. 4.14, p. 175). A recent study that tested the ability of observers to distinguish, on the basis of HRCT findings, between cases of constrictive bronchiolitis, asthma, centrilobular emphysema, panacinar emphysema and normal individuals showed that the first choice diagnosis was correct in 199/276 (72%) observations, and agreement on distinguishing between cases of constrictive bronchiolitis and panacinar emphysema was reasonable (kappa 0.63).522

B

Fig. 12.49  Constrictive bronchiolitis of unknown etiology. A, Patchy attenuation differences and mild bronchial abnormalities on CT obtained at near total lung capacity. B, End-expiratory CT accentuating the mosaic attenuation pattern and showing relative lack of change in the area of the decreased attenuation of the lung.

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Small Airways Diseases

Fig. 12.50  Patient with rheumatoid arthritis and clinical and pulmonary function tests consistent with severe constrictive bronchiolitis. The lung parenchyma is of uniformly decreased attenuation and the pulmonary vessels are of reduced caliber. In this case the bronchial abnormalities are particularly severe with widespread cylindrical bronchiectasis.

A

B

Fig. 12.51  Patient with rheumatoid arthritis and obstructive pulmonary function tests. A, Inspiratory CT showing no obvious mosaic attenuation pattern or emphysema. B, Expiratory CT revealing extensive patchy air-trapping, consistent with constrictive bronchiolitis.

A

B

Fig. 12.52  Severe postviral constrictive obliterative bronchiolitis on inspiratory and expiratory CT. A, On the inspiratory section the lung is generally of decreased attenuation (most striking in the right middle lobe, which is of increased volume). B, On the section taken at end-expiration at approximately the same anatomic level there is virtually no change in the appearance or cross-sectional area of the right lung. There is a moderate increase in the density of the parenchyma in the lingula indicating less severe involvement.

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Chapter 12 • Diseases of the Airways

A

B

Fig. 12.53  Two patients with severe obstructive lung disease. A, Advanced constrictive bronchiolitis. B, Panacinar emphysema (α1-antitrypsin deficiency). Both cases demonstrate nonspecific uniform decreased attenuation of the lung parenchyma and bronchial abnormalities.

Diffuse panbronchiolitis Diffuse panbronchiolitis is the exudative small airways disease par excellence and is characterized by a tree-in-bud pattern at HRCT.523 Diffuse (Japanese) panbronchiolitis is a sino-bronchial disease and was initially thought to be confined to Asian countries but sporadic cases have been reported in every continent;524 nevertheless there appear to be predisposing racial and genetic (human leukocyte antigen [HLA]-associated genes) factors.525 Symptoms include cough, sputum, chronic sinusitis and signs of progressive obstructive airways disease; given these invariable clinical features, it has been suggested that the inclusive term ‘sino-bronchial syndrome’ would be more appropriate,526 but the original pathologic term diffuse panbronchiolitis is relatively unambiguous and well established. Some patients respond to long-term treatment with a macrolide,527 although the exact mechanism of action of erythromycin is unknown (and is probably ascribable to its anti-inflammatory properties).528 The prognosis may be poor with a reported 10-year survival rate as low as 25%.529 Most of the definitive pathologic and imaging studies originate from Japan.307,530,531 The typical histopathologic features of diffuse panbronchiolitis are chronic inflammatory cell infiltration resulting in bronchiolectasis and striking hyperplasia of lymphoid follicles in the walls of the respiratory bronchioles; profuse foamy macrophages fill the bronchiolar lumens and the immediately adjacent alveoli, although the distal airspaces tend to be spared. This bronchiolocentric exudate is visible macroscopically as yellow nodules. As the disease progresses, an element of fibrotic bronchiolar constriction supervenes but, in the absence of longitudinal histopathologic studies, it is not clear the extent to which the basic ‘exudative’ pathology progresses to constrictive bronchiolar obliteration. On chest radiography the dominant pattern is of numerous small (5 cm T3 Tumor >7 cm or any of the following: Directly invades any of the following: chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, main bronchus 2 cm but 5 cm but ≤7 cm) • T2 tumors >7 cm are reclassified as T3 • T4 tumors with satellite nodules in the same lobe as the primary tumor are reclassified as T3 • Additional nodules in a different lobe of the same lung are reclassified as T4 rather than M1 • Malignant pleural or pericardial effusions or pleural nodules are now classified as metastasis (M1a) rather than T4

• • • • •

Regional nodes (N)

• • • •

• No changes

Metastasis (M)

T2a N1 M0 lesions are classified as IIA, rather than IIB T2b N0 M0 lesions are classified as IIA, rather than IB T3 (>7 cm) N0 M0 lesions are classified as IIB, rather than IB T3 (>7 cm) N1 M0 lesions are classified as IIIA, rather than IIB T3 N0 M0 (nodules in same lobe) lesions are classified as IIB, rather than IIIB T3 N1 M0 or T3 N2 M0 (nodules in same lobe) are classified as IIIA, rather than IIIB T4 M0 (ipsilateral lung nodules) lesions are classified as IIIA (if N0 or N1) and IIIB (if N2 or N3), rather than stage IV T4 M0 (direct extension) lesions are classified as IIIA (if N0 or N1), rather than IIIB Malignant pleural effusions (M1a) are classified as IV, rather than IIIB

• Subdivided into M1a (malignant pleural or pericardial effusion, pleural nodules, nodules in contralateral lung) and M1b (distant metastasis)

Table 13.5  Five-year survival figures (%) for nonsmall cell lung cancer based on stage Clinical staging Stage IA IB IIA IIB IIIA IIIB IV

99

USA 61 38 34 24 13 5 1

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Japan 71 44 41 37 23 20 22

Pathological staging USA (%)99

Japan (%)100

67 57 55 39 23 – –

79 60 57 45 24 16 5

astinal nodes (N3). Patients with stage IIIB tumors are not considered to be surgical candidates, unless preoperative neoadjuvant chemotherapy is given to ‘downstage’ the tumor.99,106 In patients with NSCLCs deemed unsuitable for surgery, due to either intrathoracic spread or metastatic disease, treatment options include various chemotherapy and radiotherapy regimens, which in suitable patients in some centers may be followed by surgical resection. Radical radiation therapy requires the tumor volume to be encompassed within a suitable radiation field, in a manner that critical organ and total body doses are not exceeded. The oncologist needs to know the total disease burden, and disease quantification is also important when measuring therapeutic response. In addition, imaging can help to guide biopsy and can confirm and characterize metastases. Small cell lung cancer is almost always treated medically,98,107 but may be treated, in highly selected cases of early disease, by surgery alone or combined surgery and chemotherapy.101,108,109

Imaging for staging nonsmall cell lung cancer Currently, the standard imaging techniques used to stage the intrathoracic spread of lung cancer are chest radiography and CT.31,110 In some centers bronchoscopy is undertaken prior to CT, but in other centers CT is done routinely before bronchoscopy, an approach that can be justified on the grounds that it is costeffective and, on occasion, will obviate the need for bronchoscopy

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by showing irresectable disease, or by showing benign disease only.111 CT is usually performed following intravenous contrast enhancement, but the evidence for the routine use of contrast is relatively weak. In a series of 96 patients with pathologically proven lung cancer, no change in management resulted from the availability of contrast-enhanced CT of the chest and liver compared with unenhanced CT of the chest down to the adrenal glands.112 Another study investigated whether more enlarged mediastinal nodes were evident on post- as opposed to noncontrast-enhanced examinations113 and found that only in station 2R were significantly more nodes appreciated following contrast. The detection of hilar lymph nodes using CT is, however, significantly better following contrast enhancement.114 It should be appreciated that even CT, which is significantly more sensitive than chest radiographs, disagrees with the TNM stage found at surgery in a significant proportion of patients.88,115 In 40% of cases in one typical series CT categorized the extent of tumor sufficiently poorly that the overall stage was overestimated or underestimated.116 The preoperative decision whether lobectomy or pneumonectomy will be required for centrally situated tumors, or whether conservative bronchoplastic surgery, i.e. sleeve lobectomy or pneumonectomy,117 will be feasible, depends on whether or not the tumor has crossed fissures, invaded central vessels, or spread centrally within the bronchial tree. Chest radiography and CT, particularly multiplanar CT using multidetector scanners, and virtual CT bronchoscopy provide important information, but have not, in general, proved sufficiently accurate in predicting whether or not a pneumonectomy will be required. Currently, therefore, the surgeon still mostly makes this decision based on bronchoscopic findings or on the findings at thoracotomy.115,118 Even with tumors amenable to surgical resection, a major decision in many patients is whether or not lung function will remain adequate once a pneumonectomy has been carried out. Pulmonary perfusion scans have a role here. The relative perfusion of each lung can be quantified from the number of radioactive counts in the combined anterior and posterior scans. The percentage contribution of each lung is then multiplied by the overall forced expiratory volume in 1 second (FEV1) to predict the FEV1 of the lung that would remain after surgery.119 Quantitative regional ventilation and perfusion can also be assessed using nuclear medicine techniques in order to predict postoperative loss of lung function.120 Recently, dynamic perfusion MRI has been shown able to predict postoperative lung function in patients after lung cancer resection.121

Lung Cancer

Staging the primary tumor

Mediastinal invasion

T1 and T2 tumors are confined to the lung and its investing pleura, or to bronchi more than 2  cm from the carina. T3 tumors have limited extrapulmonary extension, including invasion of the chest wall, mediastinal pleura, pericardium, diaphragm, and thoracic apex, but are mostly considered to be resectable. Tumors that extend to within 2 cm of the carina, but do not involve the carina are also classified as T3. T4 tumors invade the heart, great vessels, trachea, carina, esophagus, or vertebral body. Any tumor associated with a malignant pleural effusion is also designated T4. The distinction between T3 and T4 tumors is critical because it reflects the dividing line between conventional surgical and nonsurgical management. T4 tumors make the disease at least stage IIIB and are regarded as irresectable by the great majority of surgeons, either because they have invaded the vertebrae or critical mediastinal structures, such as the heart and great vessels, trachea and carina, and esophagus, or because they have disseminated to the pleura or within a lobe. A few surgeons try to resect tumors in the occasional highly selected patient with a T4 tumor, provided complete resection can be performed.122 Some of the patients will have had a preoperative course of neoadjuvant chemotherapy in order to ‘downstage’ the tumor.123,124 There are anecdotal reports of 5-year survivors who have undergone reconstruction of the superior vena cava, resection of vertebral bodies, or partial cardiac dissections.125,126 However, most surgeons believe that such radical surgery is not justified. (Invasion of the diaphragm is classified as T3, but deep invasion of the diaphragm was shown in one large surgical series to be associated with an outcome similar to T4 tumors.127) It is easy to assess the size and position of a primary tumor surrounded by aerated lung on chest radiographs and with CT. It may, however, be difficult to distinguish the tumor from distal collapsed or consolidated lung on CT and, therefore, overestimate or underestimate tumor size and extent of chest wall or mediastinal contact. At contrast-enhanced CT, collapsed lung enhances more than central tumor,128 and may show mucus-filled bronchi, an indicator of collapsed lung. T2-weighted MRI can be useful for separately identifying tumor from distal collapse/consolidation.129 The tumor usually shows much lower T2 signal than the distal changes, and mucus-filled dilated bronchi can be specifically identified as highintensity tubular structures. Despite its overall importance in cancer staging, PET scanning has not proved to be of use in determining the extent of the primary tumor.130

The chest radiograph is a poor indicator of mediastinal invasion, although involvement of the phrenic nerve is suggested by elevation of the ipsilateral hemidiaphragm, particularly if it is a new finding. Caution is needed before deciding that a high hemidiaphragm is caused by phrenic nerve invasion, because lobar collapse can lead to diaphragm elevation, and subpulmonary effusion may mimic it. Ultrasonography can provide information about diaphragmatic movement and, by inference, phrenic nerve involvement.131 Both CT and MRI (see Table 13.4) can show the presence of extensive tumor within the mediastinum. Clear-cut encasement of vital structures such as the esophagus, trachea, or major vessels, or deep penetration of tissue planes, is conclusive evidence of a T4 tumor (Figs 13.20 and 13.21). Mere contact with the mediastinum is not enough for the diagnosis of invasion (Figs 13.21CD, 13.22), and apparent interdigitation with mediastinal fat can be a misleading sign on both CT and MRI. Also, associated pneumonia or atelectasis may make it difficult to determine whether mediastinal contact is even present (Fig. 13.23). Multidetector CT has enabled better assessment of mediastinal invasion.88 Advantages include more reliable contrast opacification of vascular structures, reduced cardiac and respiratory motion artifact, and limitation of partial volume averaging. High-quality multiplanar reformations allow detailed assessment of important regions such as the tracheal carina, aortopulmonary window, and aortic arch. Visualization of the bronchial tree using planar and three-dimensional (3D) techniques is now an established technique.

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Box 13.5  Mediastinal invasion • The CT features of limited mediastinal contact or preserved mediastinal fat plane (2.5 (SUV is quantified as the ratio of the activity per estimated tumor volume compared with the activity administered to the patient, corrected for lean body mass).197 The studies published so far have consistently shown significantly greater accuracy with PET than with CT for the detection or exclusion of mediastinal nodal disease,198–212 and PET has been shown to reduce the rate of futile thoracotomy213 and to influence patient management decisions.212,214 False-positive results are seen less frequently than with CT; the usual cause is inflammation of the

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lymph nodes due to incidental inflammatory disease or to reactive hyperplasia associated with pneumonia or atelectasis beyond the primary tumor.215 In a metaanalysis of 514 patients who had undergone PET and 2226 patients who had undergone CT, the mean sensitivity of PET was 79% and the mean specificity was 91%, compared with a mean sensitivity for CT of 60% and a mean specificity of 77%.216 FDG-PET imaging using a coincidence mode gamma camera has a significantly lower sensitivity and specificity than a dedicated PET scanner.217,218 Correlating PET and CT images improves the accuracy of FDG-PET compared with viewing the PET images in isolation.207 For example, Vansteenkiste et al.,198 in a carefully conducted study, compared the accuracy of CT alone and FDG-PET plus CT for intrathoracic lymph node staging of 68 patients with potentially operable nonsmall cell lung cancer. The sensitivity of FDG-PET plus CT was 93% and the specificity was 95%. CT and PET image coregistration using computer techniques219 or collocation using combined CT and PET scanners, so called PET-CT machines, further increases the accuracy of PET scanning.220,221 Because of the excellent sensitivity of PET, it has been suggested that invasive mediastinal nodal staging can be substantially reduced when PET is negative (Fig. 13.38),222,223 particularly when both the PET and CT are

Lung Cancer normal.198,224 This recommendation is particularly strong for patients with presumed stage 1 disease.225 False-positive PET images, due to infection, active inflammation, hyperplasia, etc., are sufficiently frequent to justify invasive staging in selected cases when PET is positive. A decision analysis, using variables based on the literature, showed that a strategy whereby patients with enlarged nodes on chest CT or positive appearances on PET scanning undergo preoperative nodal biopsy whereas those in whom both the chest CT and the PET scan are normal go direct to thoracotomy can be cost-effective, compared with basing decisions on CT alone, without denying surgery to patients with resectable disease. The savings come from identifying inoperable patients prior to thoracotomy. A subsequent more detailed analysis from the same center confirmed the cost-effectiveness of adding PET to chest CT over a wide range of variables.226

Endoscopic ultrasound for staging nodal metastases In some centers, transesophageal ultrasound techniques are used to assess both the operability of the primary tumor and the presence of enlarged nodes.227–229 The technique is primarily of value in visualizing and sampling the right and left paratracheal (station 2R, 4L, and 4R) and subcarinal (station 7) nodes. The information regarding mediastinal lymph node metastases can be significantly more accurate than CT. Endosonographic features of neoplastic involvement of the nodes are rounded rather than oval shape, sharply demarcated border, and inhomogeneous hypoechoic texture, but the major value is to guide transesophageal fine-needle aspiration of visible nodes.

Spread to distant pulmonary sites NSCLC can metastasize to the lungs.230 The International Staging System classifies nodules of tumor in the same lobe as T4, whereas tumor nodules in another lobe on the ipsilateral side and all tumor nodules in the contralateral lung are classified as metastases, a

distinction that is borne out by evidence that the prognosis of metastases to these different locations corresponds to T4 and M1, respectively.231 The likelihood that pulmonary nodules detected by CT during staging for NSCLC are deposits of tumor is poorly quantified. Keogan et al.232 showed that 16% of their 551 patients with potentially operable lung cancer had small noncalcified pulmonary nodules. Adequate follow-up was possible in only 25 patients and 70% of the nodules in these 25 patients proved to be benign. Kim et al.233 found that 44% of 141 patients had small (10 mm diameter or less) nodules in lobes other than the lobe containing the primary carcinoma. Only six nodules in these 141 patients were malignant.

Pleural involvement Lung carcinoma may involve the pleura by direct spread, lymphatic permeation, or tumor emboli. Visceral pleural invasion carries deleterious prognostic implications compared with tumors that do not invade the pleura.234 This fact is recognized in the staging system by classifying all tumors that invade the visceral pleura as T2, even those below 3  cm in diameter. A study from Japan found that patients with tumors crossing a fissure to invade the adjacent lobe have the same survival as those with T3 tumors.235 Pleural effusions occur with lung carcinoma of all cell types, but appear to be most frequent with adenocarcinoma. They may be freely mobile or may be loculated. Pleural effusion in association with a primary lung cancer designates the tumor as T4 except in the few patients who have clinical evidence of another cause for the effusion (such as heart failure) and in whom multiple pleural fluid cytologic examinations do not show tumor cells, in which case the effusion can be disregarded as a staging element. The presence of pleural effusion sufficiently large to be recognized at the time of diagnosis on chest radiographs in patients with lung cancer carries a poor prognosis, however, whether or not malignant cells are identified.236 FDG-PET and PET-CT may be useful in evaluating patients with NSCLC and questionable pleural involvement (Fig. 13.39). The

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Fig. 13.39  Extensive pleural thickening caused by a bronchial adenocarcinoma in two different patients. In the first patient (A–C), the right lung cancer is highly metabolic (red arrows) and metabolic activity is also seen along the major and minor fissure (yellow arrows). In the second patient (D–F), no such pleural activity is seen despite thickening of the fissure (yellow arrows), with abnormal PET activity confined to the focal adenocarcinoma (red arrows).

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura examination has proved highly sensitive in small series,237 but the specificity has yet to be determined, because the number of benign effusions in reported series is small. The ultrasound demonstration of a pleural mass indicates neoplastic involvement, but other signs such as echoes or septations within the fluid or sheetlike pleural thickening are seen in both benign and malignant pleural effusions.238

Staging lung cancer: a summary The prime issue for the surgeon is whether the tumor can be completely removed at thoracotomy whereas the radiotherapist considering radical radiation therapy needs to know that the tumor volume will be encompassed within a suitable radiation field. Disease quantification and therapeutic response are important for radiotherapists and chemotherapists treating patients deemed unsuitable for surgery. Staging the intrathoracic extent of NSCLC is a multidisciplinary process employing imaging, bronchoscopy, and biopsy (see Box 13.7). Thoracoscopy can be performed on patients with suspected pleural involvement. Thoracoscopy may also play a part in preventing fruitless surgery in patients with no CT evidence of nodal enlargement by enabling inspection of pleural surfaces and access to lower mediastinal nodes.239 Chest radiography and CT, along with PET-CT, are currently the routine imaging procedures for assessing intrathoracic spread and determining resectability, with MRI and ultrasound reserved for specific indications. Based on the studies published so far, MRI has not demonstrated enough advantages to replace chest CT as a routine staging procedure, though it can, in highly selected patients, be useful as a problem-solving technique. The poor specificity of chest CT for determining nodal involvement must be appreciated. Nodal enlargement, although it may be due to metastatic carcinoma, may also be due to coincidental benign disease or to reactive hyperplasia directly connected to the presence of the tumor. Thus, in practice, CT and MRI examinations for staging nodal involvement are used largely to decide whether to perform mediastinoscopy or mediastinotomy and, equally importantly, to demonstrate which nodes should be biopsied. A convenient policy is to consider nodes with a short-axis diameter of greater than 10 mm to be abnormal. Nodes above this diameter should be subjected to some form of biopsy. Clearly there are occasions when the chances of a negative biopsy are so slim that a surgeon may decide that the presence of greatly enlarged nodes is sufficient reason not to proceed with surgical resection, but these cases should be the exception to the general rule that the imaging diagnosis of mediastinal nodal metastases should be corroborated by biopsy before a patient is denied potentially curative surgery. Routine mediastinoscopy provides access only to the paratracheal nodes, proximal tracheobronchial nodes, and superior subcarinal nodes. The other nodal sites require alternative approaches such as mediBox 13.7  Summary of imaging for staging NSCLC • CT sensitivity and specificity for mediastinal nodal disease is about 65%, therefore targeted biopsy of enlarged nodes is required • CT predicts resectable tumors, but is unreliable for identifying inoperable mediastinal invasion • MRI is comparable to CT as a routine test, but can be useful for solving specific problems • PET is an accurate technique for diagnosing nodal disease but has no proven value for determining the extent of the primary tumor • Ultrasonography has a limited role • Patients should not be denied surgery based on indeterminate imaging findings

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astinotomy or PET. These other sites include nodal stations with a high propensity to early metastases, such as the aortopulmonary and anterior mediastinal nodes. Some thoracic surgeons believe it appropriate to proceed to thoracotomy without prior mediastinoscopy or mediastinotomy in patients with normal-sized mediastinal nodes.186 Others advocate routine mediastinoscopy even in those patients whose CT scans do not show enlarged nodes.240 A randomized controlled trial of the use of CT in 685 patients with apparently operable lung cancer (with mediastinoscopy for those patients who showed enlarged nodes or thoracotomy without prior mediastinoscopy for those patients who showed no enlarged nodes) versus no CT (all patients having mediastinoscopy) showed that the strategy of using CT to determine which patients should have mediastinoscopy is likely to produce the same number or fewer unnecessary thoracotomies in comparison with doing mediastinoscopy on all patients, and is also likely to be as or less expensive.241 Another argument against routine preoperative mediastinoscopy of patients with normalsized nodes is that patients with microscopic metastases discovered only at the time of thoracotomy have an improved survival rate if the primary tumor and the affected mediastinal nodes are resected. PET has proved significantly more accurate than CT for diagnosing or excluding mediastinal nodal metastases, but has not obviated the need for histologic confirmation of nodal involvement when the PET is positive. Patients with no enlarged nodes on CT and no abnormal uptake of FDG on PET have such a low incidence of nodal involvement that mediastinoscopy is very unlikely indeed to be positive and can be omitted. For lung cancers that have invaded the mediastinum or chest wall, the important decision is whether the tumor is nevertheless resectable for possible cure, recognizing the poorer prognosis compared with tumors confined to the lung. CT may show definitively that the tumor is too extensive for resective surgery. Alternatively, CT may leave the issue in doubt, and MRI can then be used as a problem-solving technique, but the introduction of multiplanar CT has significantly reduced the number of occasions when MRI is needed. In practice the use of MRI is largely limited to evaluating superior sulcus tumors, to define brachial plexus and subclavian and axillary artery involvement, and for establishing vertebral body involvement.110 The most important single message is that patients with primary NSCLC should not be denied potentially curative surgery based on indeterminate imaging findings.

Imaging extrathoracic metastases from lung cancer A reasonable approach for patients with no clinical features to suggest extrathoracic metastases is to extend the staging chest CT to image the liver and adrenals at the time of the thoracic staging scan. In most centers no further routine imaging is undertaken, and there is good evidence to support this approach.110 In centers where FDG-PET imaging is readily available, it should be used. The wider availability of FDG-PET imaging currently changes the approach to diagnosing asymptomatic extrathoracic metastases, because it is a single test which can encompass all the organs in the body. The results so far suggest higher accuracy than CT, MRI, ultrasound or most other radionuclide procedures for all body sites, apart from the brain. In particular, PET has been shown to be highly sensitive.205,242 Whole-body PET alters management in a significant proportion of patients, the proportion ranging from 24% to 65%.213 A randomized prospective trial in 188 patients with suspected operable NSCLC showed that the addition of PET to the conventional workup prevented unnecessary thoracotomy in 20%.213 Nine studies comprising 837 patients examining the utility of FDG-PET were reviewed by Shon et al.204 FDG-PET detected 94% of all metastases, considerably higher than a combination of the other standard tests. PET was the only technique to correctly exclude metastatic disease

Lung Cancer in 53 patients in whom other imaging had suggested metastases. Put another way,243 FDG-PET has been shown to detect occult extrathoracic metastases in 11–14% of patients selected for curative resection by conventional methods,201 with two studies244,245 having no false-positive results. Higher detection rates are seen with more advanced tumors.246 FDG-PET is relatively poor at detecting cerebral metastases, due to the high metabolic activity of normal brain.204 PET is superior to technetium-99m radionuclide bone scintigraphy for the detection of bone metastases. It had a 92% sensitivity and 99% specificity compared with a 50% sensitivity and 92% specificity of bone scans in one series.201 Apart from issues of availability and cost, the level of accuracy of PET could potentially eliminate the need for radionuclide bone scans. The results from whole-body imaging using PET suggest it is much more sensitive than CT and is also more specific in the detection of hepatic and adrenal metastases.204 Moving patient platforms with integrated surface coils have made whole-body MRI possible within a single examination.247 Whole-body MRI allows an overall assessment for metastases in the entire body. In one recent study of 203 patients with lung cancer, MRI had an improved sensitivity and specificity for the detection of metastases as compared with PET-CT.248

Liver metastases The presence of clinical and laboratory features suggestive of liver disease has only a 25% positive predictive value for metastases.249 The advent of multidetector CT provides rapid scanning with several technical advantages, including the optimal use of intravenous contrast medium, the limitation of respiratory misregistration, and the reduction of partial volume averaging by using overlapping image reconstruction or retrospective thin sections. The use of narrow reconstruction intervals can result in an increased detection

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rate of small lesions. An accepted figure for the accuracy of CT in detecting metastatic disease, extrapolated from studies of colorectal tumors,250,251 is approximately 85%, and given the appropriate circumstances biopsy confirmation is not usually required. A major diagnostic problem is distinguishing between small metastases and incidental benign lesions, such as simple cysts/hemangiomas. Ultrasound is also a suitable method to search for liver metastases, although it is less sensitive than CT. Most deposits are hypoechoic, although hyperechoic and targetlike appearances occur. Recent technical advances mean that body MRI is now superior to CT for imaging liver metastases. Greater tissue contrast results in increased sensitivity for the detection of metastases. However, the cost and speed limitations of MRI mean that it is currently reserved to solve specific problems.252

Adrenal metastases The adrenal gland is a common site for metastasis.249,253 However, incidental nonfunctioning adrenocortical adenomas are relatively common in patients undergoing CT, with a frequency of approximately 1%. A small solitary adrenal nodule in a patient with NSCLC is more likely to be an incidental benign adenoma than a metastasis. A study of 546 patients with lung cancer found one or more adrenal masses in 4% of patients. On percutaneous biopsy only 29% of these proved to be malignant.254 The relative incidence of benign adenoma and metastasis reverses when an adrenal mass is more than 2  cm in size. Given that there is a substantial chance that an adrenal mass of less than 2 cm will be an incidental adenoma,253 the diagnosis must be confirmed with a high degree of certainty in order to prevent an otherwise operable patient being denied surgery. Both MRI255 and PET256 provide good, but not perfect, results in differentiating benign from malignant adrenal lesions (Fig. 13.40).

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Fig. 13.40  A–C, PET-CT of metastases from a primary lung adenocarcinoma to the adrenal glands, stomach wall and D–F, a dorsal spine vertebral body. Arrows point to areas of increased metabolic activity indicating metastatic disease. The large vertebral body metastasis was not readily evident on the CT images. (Courtesy of John Anthony Parker, Boston, MA, USA.)

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

Brain metastases MRI of the brain is more sensitive and may be more specific for metastases than CT.257,258 Cerebral metastases occur commonly in lung cancer, particularly from poorly differentiated tumors and adenocarcinoma.249,259 MRI with contrast enhancement is the imaging technique of choice.258 It has particular advantages in showing lesions in the posterior fossa and adjacent to the skull. Given its overall higher sensitivity, MRI is therefore currently preferred over CT when screening patients with lung cancer for brain metastases.260–262 The incidence of a truly ‘silent’ brain metastasis is difficult to determine, and may be of the order of 2–4%,263 though it depends on the thoroughness of clinical examination and method of detection. There is some logic in limiting cerebral imaging to those patients with the more aggressive histologic types of primary tumors.264

Bone metastases Bone metastases are a relatively frequent finding at clinical presentation in patients with lung cancer, although the frequencies vary widely between series.249,265 Bone scintigraphy is considerably more sensitive than radiography for their detection.266 However, radionuclide bone scans have a high false-positive rate because of the presence of coincidental benign skeletal disorders, notably old trauma and degenerative disease, and this limits their value. The prevalence of asymptomatic bone deposits detected by radionuclide bone scan is probably of the order of 3–10%. One study of potentially operable nonsmall cell cancers demonstrated bone metastases in 3.4% of patients on radionuclide bone scans. Ichinose et al.267 studied the bone scans of 196 patients with NSCLC. Metastatic bone disease was identified in just under 10% and subsequently proven on biopsy or follow-up. Of these true-positive scans for metastases, 94% of patients were symptomatic or had abnormal biochemistry.267 Another study similarly showed that all patients with proven skeletal metastases had at least one clinical or biochemical indicator of bone involvement,268 emphasizing that bone scintigraphy should in general be performed only in patients with symptoms suggesting bone metastases. MRI is both sensitive and specific for diagnosing skeletal metastases, and previous limitations have been overcome with the introduction of whole-body MRI.248 Finally, the assessment for potential bone metastases is an integral part of staging examinations performed with PET-CT (Fig. 13.40).

Bronchioloalveolar carcinoma The World Health Organization classifies bronchioloalveolar carcinoma, also known as alveolar cell carcinoma or bronchiolar carcinoma, as a subtype of adenocarcinoma.269 Some published series contain a mixture of pure bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar features, leading to confusion over imaging findings and survival characteristics.270 Bronchioloalveolar carcinomas are divided into: nonmucinous, mucinous, and mixed mucinous and nonmucinous (indeterminate cell type) subsets. Cigarette smoking does not appear to play a prominent etiologic role,271 but the prevalence of this tumor within preexisting lung scars is striking.272 Bronchioloalveolar carcinomas account for 2–5% of all lung cancers, but with smoking on the decline the relative incidence of bronchioloalveolar carcinoma in some series is rising.23 The tumor occurs equally in both genders, and the average age at onset is between 55 and 65 years. The characteristic pathologic feature is a peripheral neoplasm showing lepidic growth, the malignant cells using the surrounding alveolar walls as a scaffold. These tumors are believed to arise from type II pneumocytes and probably also from bronchiolar epithelium273 or a common stem cell. The cells produce mucus, sometimes in such large amounts that one of the

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presenting symptoms in the consolidative form of the disease is the expectoration of large quantities of mucoid sputum. The tumor presents in two clinically different forms: a discrete solitary pulmonary nodule (sometimes more than one nodule is present), and unifocal or multifocal areas of pulmonary consolidation; the form presenting with a solitary pulmonary nodule being the more common.271,274,275 The mucinous type is more likely to be seen as airspace consolidation and the nonmucinous type is more likely to be masslike in configuration and associated with secondary scarring and inflammation, but there is no exact correlation between the cell type and the imaging appearance.276,277 The scarring may lead to difficulties in determining whether the carcinoma is an invasive adenocarcinoma with a prominent bronchioloalveolar growth pattern or a bronchioloalveolar carcinoma associated with scarring.55 Pathologists may find it difficult to distinguish histologically between the nonmucinous form of bronchioloalveolar carcinoma and atypical adenomatous hyperplasia, a benign proliferation of bronchioloalveolar cells that is now believed to be a precursor lesion to adenocarcinoma. This difficulty translates to interobserver variability in the diagnosis of these two conditions. The prognosis for bronchioloalveolar carcinoma when it occurs as a solitary pulmonary nodule is better than that seen with other lung cancer cell types.278 It is more likely to be stage I and therefore surgically resectable. Also, the tumor is relatively slow growing,271 so that 5-year survivals are better, regardless of stage.279 Bronchioloalveolar carcinomas less than 2 cm in diameter, showing a purely lepidic growth pattern without invasion, had no lymph node metastases and 100% 5- and 10-year survival in one series.55 The prognosis for the larger, more ill-defined lesion, which radiographically resembles pneumonia, and for the disseminated form are both poor.275,280 Because bronchioloalveolar carcinomas arise from the alveoli and the immediately adjacent small airways, they tend to appear as peripheral pulmonary opacities. The most common appearance is a solitary lobulated or spiculated pulmonary nodule of soft tissue density indistinguishable from other types of carcinoma (Fig. 13.41).281–283 There is a propensity to a subpleural location and the development of a pleuropulmonary tail; the tail is due to desmoplastic reaction in the peripheral septa of the lung.283,284 The nodular form may show a definite air bronchogram, a phenomenon that is best seen with CT,282,285 particularly high-resolution (HR) CT.281,286 Bubblelike lucencies corresponding to patent small bronchi or air-containing cystic lucencies are a frequent finding.66,281,282,285,286 The bubbles, as in the nodular form, correspond pathologically to small patent bronchi or cystic spaces within the tumor.287 It is a particular feature of the goblet cell subtype of bronchioloalveolar carcinoma.288 The tumor may be composed entirely of ground-glass density or there may be a halo of ground-glass density, surrounding the central soft tissue density.52,281,285,289,290 Frank cavitation, however, is unusual, but an appearance resembling cavitation may be produced by paracicatricial emphysema, fibrosis with honeycombing, and localized bronchiectasis.291 The radiographic presentation that distinguishes bronchiolo­ alveolar carcinoma from the other types of lung cancer is when the lesion takes the form of single or multiple areas of consolidation or ill-defined opacities. Bronchorrhea is a recognized clinical manifestation in this form of the disease. A variety of radiographic, CT, and HRCT appearances are seen with this form of the disease:277,283,292 ill-defined consolidation, resembling pneumonia; pure groundglass (Fig. 13.42),285,289,290,293 ground-glass surrounding a core of soft tissue density, mixed ground-glass opacity and denser consolidation,270 homogeneous consolidation of one or more lobes (Fig. 13.43),280 multifocal patchy consolidation,294 or multiple ill-defined nodules spread widely through multiple lobes in one or both lungs, which may show a centrilobular distribution on HRCT292. More than one of these patterns is often present simultaneously (Fig. 13.44).292 Extensive, patchy, ground-glass opacities and septal thickening, resembling alveolar proteinosis, has also been described

Lung Cancer

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Fig. 13.41  Two examples of bronchioloalveolar carcinoma occurring as a solitary pulmonary nodule or mass. A, Chest radiograph in a 47-year-old asymptomatic man. B, In a different patient, an ill-defined tumor that resembles pneumonia. C, However, on CT the lesion is clearly a lobular mass with irregular edges.

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B

C

C

Fig. 13.42  PET-CT of bronchioloalveolar carcinoma appearing as a bilateral ill-defined perihilar ground-glasslike opacity (arrows). The opacity is well seen on A, CT, but shows only little metabolic activity on B, the PET image. C, The fusion image matches the most intense ground-glass opacity with the greatest PET activity.

(Fig. 13.44).295,296 Both atelectasis and expansile consolidation (Fig. 13.45) have been reported.297 Cavitation within consolidation is unusual but has been recorded, as have multiple thin-walled cystic lesions at CT within or coexistent with the consolidative form of bronchioloalveolar carcinoma.292,298 In one reported case the wall of a preexisting lung cavity

became thickened, presumably by tumor growing around the wall of the cavity.297 Air bronchograms may be an obvious feature (Fig. 13.44); they are particularly well seen on CT.286 The bronchi may show uniform narrowing and stretching.299 CT may show a ‘bubblelike pattern’ (sometimes referred to as ‘pseudocavitation’) (Fig. 13.44) in the

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

A

B

Fig. 13.43  Bronchioloalveolar carcinoma occurring as lobar consolidation of the middle lobe. The patient complained of coughing up copious amounts of mucoid sputum. A, Posteroanterior radiograph. B, Lateral radiograph.

A

C

816

B

Fig. 13.44  Bronchioloalveolar carcinoma presenting as A, widespread ill-defined patchy areas of consolidation, B, multifocal ground-glass opacities with intervening thickened interlobular septa, C, focal mixed ground-glass and consolidation with air bronchograms and a ‘bubblelike pattern’.

Lung Cancer cell carcinoma, but was unusual in consolidation from other causes.302 The sign is now regarded as nonspecific, since it is seen in many conditions, notably pneumonia and lymphoma.303,304 Pleural effusions are seen in up to one-third of patients, and hilar and mediastinal lymphadenopathy is seen in close to one-fifth. CT is advocated as a routine before surgery in all patients with the consolidative form of disease to make sure that the tumor is confined to one lobe, since CT frequently shows further pulmonary foci that are not appreciated on plain chest radiographs.305 MRI provides little extra information compared with CT. Ground-glass opacities, an important CT feature, are not visible on MRI, but very heavily T2-weighted sequences can show the presence of mucin as high signal.306 The nodular forms of the tumor show enhancement following gadolinium enhancement.306 Bronchioloalveolar carcinomas may grow slowly, with doubling times far greater than the 18 months usually quoted as the upper limit for bronchial carcinoma.284 Similarly, reflecting the slow growth and hence relatively low metabolic activity, FDG-PET shows less uptake in bronchioloalveolar carcinoma than other cell types and may be negative.295,307

Recurrence of treated lung cancer Fig. 13.45  Bronchioloalveolar carcinoma presenting as expansile consolidation of the right lower lobe. consolidative form as well as in the nodular form.66 Thickened septal lines caused by lymphatic permeation may also be visible, as may branching tubular densities of mucoid impaction.297 Mucus within the tumor may be visible as ground-glass opacity or consolidation at CT.286 Differentiating between the consolidative forms of bronchioloalveolar carcinoma and various non-neoplastic conditions such as pulmonary infection, organizing pneumonia, aspiration, or pulmonary edema depends on knowing the clinical findings and appreciating the lack of response to treatment. The presence of coexistent nodules along with the consolidation and a peripheral distribution proved to be a statistically significant predictor of bronchioloalveolar carcinoma rather than pneumonia.300 In another study, stretching and squeezing of air bronchograms traversing the consolidated areas, and bulging of fissures, were significantly more frequent in bronchioloalveolar carcinoma than in pneumonia.301 The appearances have also been compared with tuberculous pneumonia, and it was shown that while both entities had a similar combination of signs, the ground-glass opacity in bronchioloalveolar carcinoma tended to be remote from the consolidation, whereas in tuberculosis it was adjacent.292 Also, the pulmonary abnormalities showed a lower lobe predominance in bronchioloalveolar carcinoma, but an upper lung predominance in tuberculosis. There is increased interest in bronchioloalveolar carcinoma manifesting as ground-glass nodules.56,58,59 One study investigated the predictive potential for malignancy in these lesions and found that lesion size and morphological characteristics enhance radiologists’ performance in determining malignancy of pure ground-glass nodules.59 Another study compared the clinical and imaging characteristics of solitary and multiple ground-glass nodules.58 The authors found that clinical, pathological, and CT features of persistent multiple ground-glass opacity nodules differed from those of solitary ground-glass opacity nodules. Nevertheless, the authors concluded that the two nodule types can probably be followed up and managed in a similar manner because their prognoses are similar.58 An interesting sign is the CT angiogram sign. It refers to clearly visible vessels coursing through the tumor on contrast-enhanced images, presumably because of the contrast against the background of abundant low-density mucus within the neoplasm. This sign was described before the advent of faster injection rates for contrast agent consequent on spiral CT; it was present in a high proportion of patients with lobar consolidation caused by bronchioloalveolar

There are only one or two reports in the literature on imaging local recurrence of the primary tumor following treatment and no generally accepted imaging protocols for follow-up of patients who have been or are undergoing treatment for lung cancer. It needs to be borne in mind that recurrent tumor is rarely amenable to cure; a retrospective survey of the experience at the M D Anderson Hospital in the USA showed that only 3% of patients with recurrent tumor were even offered potentially curative treatment.308 Also, the survival benefit of any form of routine imaging follow-up has yet to be demonstrated.309 Routine CT or MRI is not recommended, because they are both insensitive and nonspecific for detecting posttreatment recurrence; the only recommended follow-up technique for asymptomatic patients is chest radiography310 and possibly radionuclide imaging, notably FDG-PET. The signs of local recurrence on chest radiography, CT and MRI are, in general, similar to those used to diagnose the original tumor. CT has been shown to be significantly more sensitive than chest radiography.311 The general principle is recognizing or being able to exclude an abnormal mass, particularly a growing mass, or enlarging mediastinal lymph nodes. This is relatively easy to do following segmental resection, or lobectomy, because these two surgical procedures do not, in general, lead to confusing degrees of scar formation. Following pneumonectomy or radiation therapy, however, posttreatment fibrosis can make it very difficult to distinguish benign scar tissue from recurrent tumor. The consolidation and fibrosis of radiation pneumonitis may be impossible to distinguish from neoplastic tissue. Libshitz et al.312 made the interesting observation that opacification of previously air-filled dilated bronchi in areas of postradiation fibrosis is a reliable sign of locally recurrent lung cancer. Radionuclide imaging, notably FDG-PET, would appear to be the most accurate technique for diagnosing recurrent tumor.313–317 Since all forms of radionuclide imaging depend on the altered function of neoplastic cells rather than disordered anatomy, the distorted scarred background is not an impediment to diagnosis (Fig. 13.46). Shon et al.204 in a review of the literature stated that FDG-PET has been shown to be highly sensitive in the detection of recurrent lung cancer with sensitivities ranging from 97% to 100%, but the falsepositive rate, while not as poor as with CT or MRI, could be as high as 40%. The advice is to wait at least 3 months, and preferably 6 months after completion of radiation therapy before performing FDG-PET imaging in order to avoid false-positive results due to radiation fibrosis and glycolysis in macrophages in successfully treated tumors.204,317 Sequential scans can reduce the false-positive observations because uptake in non-neoplastic tissue decreases with time.

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura Table 13.6  Definition of the terms survival, mortality, fatality, and all-cause mortality with respect to screening Survival Mortality

Fatality All-cause mortality

Fig. 13.46  FDG-PET scan showing considerable activity in a recurrent lung cancer following radiation therapy.

Atypical adenomatous hyperplasia Atypical adenomatous hyperplasia (AAH) is a relatively recently described pulmonary neoplasm. On a genetic basis, it is considered by some, on the basis of genetic similarities, as a preinvasive form of pulmonary adenocarcinoma.318 Other authors suggest that AAH and the associated cancer are genetically independent and that AAH foci could represent an early spread of cells from the main tumor, rather than a precursor lesion.319 The lesion is defined by the WHO269 as ‘a focal lesion, often 5 mm or less in diameter, in which the involved alveoli and respiratory bronchioles are lined by monotonous, slightly atypical, cuboidal to low columnar epithelial cells with dense nuclear chromatin, inconspicuous nucleoli and scant cytoplasm’. Atypical adenomatous hyperplasia was originally reported as an incidental discovery in autopsy patients without lung cancer, and in up to 10% of lobes removed from patients who had had surgery for bronchial carcinoma, notably adenocarcinomas.320–322 The precise nature of the lesion is debated. The debate centers on whether the condition is a highly differentiated adenocarcinoma and part of a continuous spectrum with nonmucinous bronchiolo­ alveolar carcinoma, or whether the lesion is a potentially malignant benign neoplasm, in other words a precursor to bronchioloalveolar carcinoma/adenocarcinoma.323–333 The lesions are mostly too small and of insufficient density to be seen on chest radiography, but they can be seen on CT as a round area of ground-glass density, usually less than 10  mm, but sometimes as large as 32  mm in diameter.323,334–336 There may be a solid portion of soft tissue density in the center of the ground-glass density in a substantial number of cases.332,336 Another important feature is the lack of change on follow-up CT examinations.336

Population screening for lung cancer The underlying concept of an early lung cancer detection program is that more cures are achieved when stage I tumors are found in asymptomatic individuals, since the surgical results and 5-year survival figures are much better, compared with patients who first present with symptoms and those who have more advanced tumors. Considerably more than half of all patients currently present with stage III disease or higher and it is well accepted that the overall average 5-year survival is somewhere between 13% and 15%,337,338 whereas 5-year survival rates for stage IA NSCLC are 67% or better.99,163 It is generally held that the measure of success of a lung cancer screening program should be reduced mortality from lung cancer rather than improved 5-year survival, which suffers from lead-time

818

Number diagnosed with cancer alive/total number diagnosed with cancer (%) Number of cancer deaths/total number screened or in control group (deaths per 1000 per year) Number of cancer deaths/number of cancers detected (%) Number of deaths/number of patients screened (deaths per 1000 per year)

bias (see below). It has however been suggested that other outcome measures are more appropriate, notably fatality rate and all-cause mortality (see Table 13.6 for definitions). The major problem with using fatality rates is inherent overdiagnosis bias: if lesions that grow too slowly to kill the patient during their natural life expectancy are included in the denominator, the proportionate number of deaths is reduced and the test appears more beneficial than if only truly life-threatening cancers are included. All-cause mortality is a good measure, but is only a true guide in meticulously randomized trials.

Biases in cancer screening programs The presumption that earlier diagnosis necessarily equates to a decrease in mortality from lung cancer is simplistic because there are so many variables to take into account.339–344 Screening programs which are compared simply with historical or nonrandom controls suffer from three fundamental biases: leadtime bias, length bias, and overdiagnosis bias. Such programs have the following characteristics: earlier stage at diagnosis, improved resectability rates and improved survival, but no change in the number of late stage tumors and, most importantly, no reduction in mortality from the tumor. The inherent biases can be minimized by comparing disease-specific deaths (deaths due to lung cancer) in a randomized controlled trial of a screened versus a nonscreened population with sufficiently long follow-up to compensate for leadtime bias. A fourth potential bias operates even in randomized trials, namely selection bias, where conclusions may be based on series of patients in whom the randomization procedures do not result in truly similar groups which may not be representative of the population at large. The term ‘lead-time bias’ refers to the extra life expectancy that occurs simply from diagnosing a tumor earlier, regardless of whether or not treatment is effective. In other words, moving the time of diagnosis of a lung cancer forward inevitably improves 5-year survivals, which are calculated from the time of diagnosis, regardless of the effect on mortality. The term ‘length bias’ refers to the tendency for tumors with an inherently better prognosis, e.g. slow growing bronchioloalveolar carcinoma, to be discovered by population screening, particularly on the first round (referred to in screening parlance as the ‘prevalence’ round). An indication that length bias can be a highly significant factor is the observation that the volume-doubling times of the lung cancers found in one of the two large Japanese CT screening programs345 was a mean of 15 months (range 1–40 months); by way of comparison the vast majority of lung cancers found by means other than CT screening double their volume with median times of between 4 and 7 months.346–351 The term ‘overdiagnosis bias’ refers to overdiagnosing a benign lesion as a malignant tumor, or diagnosing a very slow growing malignancy that would not kill the patient during his or her natural life expectancy.339 Overdiagnosis bias is an extreme form of length bias. Atypical adenomatous hyperplasia, believed to be either a

Lung Cancer benign process or a preinvasive carcinoma, is found in a small but significant proportion of patients in all CT screening programs.326,334 It resembles the nonmucinous form of bronchioloalveolar carcinoma histologically,276,330 and histopathologists vary considerably among themselves over whether they designate very small lung lesions as atypical adenomatous hyperplasia, or whether they classify the lesion in question as invasive carcinoma. Another possible pointer to overdiagnosis in CT screening is that in one of the Japanese screening studies the rate of detection of lung cancer was similar among smokers and nonsmokers,352 whereas mortality from lung cancer is heavily slanted to smokers. The arguments against overdiagnosis being a significant factor center on: first, the comparatively few lung cancers demonstrated at screening CT of high-risk populations (the highest reported prevalence in population screening is 2.7%353) and on preoperative CTs of patients undergoing lung volume reduction surgery for emphysema where the lung cancer detection rate is between 2% and 5%;354–357 and, second, the low incidence of previously unsuspected indolent cancers at routine autopsy of older individuals.358 The reply from those who believe that overdiagnosis is a significant factor is that small lung cancers are not looked for carefully enough at routine autopsy and evidence has been provided to support the claim that the true incidence is higher than reported.359 There are conflicting data regarding survival and fatality from the small tumors likely to be found by population screening with CT. Patz et al.,360 rather than ask ‘does population screening diagnose lung cancer earlier’, investigated whether there was any correlation between survival and precise size in 510 patients with tumors under 3 cm in diameter without nodal or distant metastases (T1N0M0 or stage IA tumors). Rather unexpectedly, they found no correlation; in other words, the patients with lung cancers less than 1 cm in diameter did not show better survival than patients whose tumors were 2–3 cm in diameter. Their point was that survival following surgical resection from lung cancer is complex and multifactorial, depending not only on tumor size and stage, but also on tumor biology, the ability of body defense systems to cope with micrometastases, and a variety of other host factors.361 Koike et al.,362 on the other hand, found that 5-year survival for patients with tumors less than 2 cm in diameter was significantly better than for patients with tumors between 2 cm and 3 cm in diameter, a difference that could be explained by lead-time bias alone, particularly as there was no significant difference in the rate of mediastinal nodal involvement between the two groups. Henschke et  al.363 approached the same basic question in yet another way by analyzing the 8-year fatality rate of unresected T1 lung cancers of varying size in the National Institutes of Health Surveillance, Epidemiology, and End Results (SEER) registry and found that almost all lung cancers, even those less than 15  mm in diameter, are fatal if not treated.

Population screening for lung cancer using chest radiography Two large randomized controlled trials of population screening using chest radiography have been undertaken, the NCI (National Cancer Institute) Mayo Lung Project364–366 and the Czechoslovakian study367 as well as a number of trials of less rigorous design.368–374 The results have been broadly similar. The multicenter survey conducted by the NCI between 1971 and 1983 has been extensively analyzed and is the only one that will be discussed in any detail. From a population of approximately 10 000 high-risk patients at each of three centers (men over 45 years of age who were chronic excessive cigarette smokers), 0.73% had lung cancer diagnosed at their initial screening.364,365,375–379 After excluding nearly 1000 individuals who were ruled ineligible because of serious medical problems, the Mayo Clinic portion of the study randomly assigned half of those who did not have cancer at the initial screening to surveillance by chest radiography and sputum cytology every 4 months, the remaining half, who served as control

subjects, were recommended to have annual chest radiographs and sputum cytology.365,380 The rate of cancer diagnosis in the screened group was 5.5 per 1000 per year, compared with 4.3 per 1000 per year in the control group. The resectability rate was higher in the study group (46%) than in the control group (32%) and the median survival was at least three times better, but after a median of 20 years the lung cancer deaths were virtually identical in the two groups: 4.4 per 1000 in the screened arm compared with 3.9 per 1000 in the control group.366 The apparent disparity between the greatly improved survival and the lack of improvement in mortality from lung cancer is believed to be due to overdiagnosis in the screened population.366,381 Another piece of evidence pointing to biases in the study is that 70% of the cancers that had been overlooked on previous chest radiographs were still stage I when finally diagnosed.28 Huhti and colleagues340 also noted that, when the diagnosis was previously missed, the survival rates were better. Two of the three centers investigated the benefit of using sputum cytology as an adjunct to chest radiography. Some 15–20% of patients with cancer showed malignant cells in the sputum when the plain chest radiograph was normal. Interestingly, these patients, who all had either centrally situated squamous cell carcinoma or mixed histologic features with squamous cell carcinoma as one element, had a more favorable prognosis than those who had positive radiographic findings.28,365 However, neither study showed that the addition of sputum cytology reduced mortality from lung cancer.376,382 The conclusion was that large-scale radiographic and cytologic screening for lung cancer did not result in a mortality benefit. Critics of this conclusion have argued that there might have been a benefit to a subset of patients and that the chest radiography component of the study only had the power to show a reduction in mortality of 50%, rather than a more realistic expectation,81,381,383,384 but a subsequent detailed reanalysis of the data has confirmed the initial conclusions of no significant reduction in the death rate: 95% confidence intervals allowed for at most only a tiny improvement in mortality.366 The initial hope that intensive screening would detect a large proportion of early cases of squamous cell carcinoma, the cell type with the best surgical result, was also not fulfilled.364

Population screening for lung cancer using low-dose CT Low-dose CT has been used in several centers as the primary technique for screening an at-risk population for lung cancer. The points to note from the CT screening programs are: • The diagnostic yield of lung cancer from CT is far superior to chest radiography.353,385–388 At least twice as many small lung cancers are visible on CT than on chest radiography. The lesions that are invisible on chest radiographs are either below the threshold for noncalcified nodule detection or, when above this threshold, have infiltrating and, therefore, relatively ill-defined margins.389 • A very high proportion of the cancers diagnosed are stage IA (Fig. 13.47), fulfilling one of the primary objectives of screening, namely to diagnose asymptomatic early stage disease. • The cancer diagnosis rate is highly dependent on risk factors inherent in the inclusion criteria, with a much higher incidence of lung cancer when the age of those screened is above 60, and when screening CT is limited to those with a strong smoking history. • The pick-up rate of clinically insignificant benign nodules is very high (Fig. 13.48). Between 90% and 97% of uncalcified nodules proved to be benign. • As expected, the pick-up rate of lung cancers drops considerably in the later rounds of screening. The proportion of lung cancers diagnosed in the later rounds of screening is between a half and a quarter of those diagnosed in the initial round.

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura patients from a region with a high prevalence of granulomatous infection, showed that 51% of 1520 screened patients revealed one or more benign noncalcified nodules.392 It should be borne in mind, however, that several technical factors may have played a role: multidetector CT scanners, narrower collimation, and cine viewing rather than film viewing were used; therefore, the sensitivity for the detection of small nodules would have been higher than in the ELCAP and Japanese studies. Careful assessment of nodules avoids thoracotomy for a substantial proportion of benign nodules, but benign nodules are being removed surgically even in the best surgical centers.391 The false-positive rate is also surprisingly high in the subsequent rounds of screening. The ELCAP study found 30 new nodules on 1184 rescreens, 22 (73%) of which proved to be benign.393 The Mayo Clinic program390 has reported the findings of two annual incidence screens showing a 12–13% frequency of benign nodules first recognized on the incidence screens. Therefore, the growth rate of new small nodules must be assessed and shown to be consistent with lung carcinoma prior to surgical removal.393

Fig. 13.47  True-positive finding at CT lung cancer screening – a lung adenocarcinoma. (Courtesy of Dr. Mary Roddie, Medicsight, London, UK.)

Appearance of lung cancers detected in screening programs Cancers detected by CT screening may be:51 • Homogeneously solid (i.e. wholly of soft tissue density) • Pure ground-glass density • Central solid nodule (i.e. soft tissue density) surrounded by glass shadowing, sometimes referred to as a part solid nodule • Heterogeneous low density and soft tissue density. The correlations of these CT patterns are: • The greater the proportion of ground-glass shadowing the more likely it is that the lesion will grow relatively slowly54 and will be a well-differentiated tumor, such as a bronchioloalveolar carcinoma or atypical adenomatous hyperplasia.394–396 It has been postulated that these CT patterns may correlate with prognosis, with solitary nodules of pure ground-glass opacities being associated with a better prognosis and pure solid nodules being associated with a poorer prognosis.35 • Nodules that grow quickly tend mostly to be either homogeneously or predominantly solid at CT.54,397 • The less the solid component the less visible the lesion is at chest radiography.398

Imaging algorithms to determine the nature of a small pulmonary nodule

Fig. 13.48  False-positive finding (arrow) at CT lung cancer screening – diagnosed as an incidental benign nodule on the basis that it did not grow under observation for 18 months. The high false-positive rate of screening CT is a major disadvantage.390 In the ELCAP study,353 233 of 1000 (23.3%) patients were found to have at least one noncalcified nodule. Therefore, follow-up protocols to assess interval growth were developed for nodules less than 10  mm in diameter, with biopsy limited to those nodules whose growth characteristics make lung cancer likely. In the ELCAP study nodules larger than 10 mm were biopsied. Remarkably, using this algorithm, only 28 of the 233 patients with noncalcified nodules required biopsy. Of these nodules, all but one proved to be malignant. False-positive rates appear to be even higher in areas, such as the American mid-West, in which there is a very high prevalence of histoplasmosis, but they are also high in Europe,391 where histoplasmosis is rare. The CT screening study from the Mayo Clinic, with

820

The basic principles underlying the diagnostic approach to individual nodules detected during a lung cancer CT screening program are similar to those described for a solitary pulmonary nodule first detected on chest radiography. There is, however, a very important difference, namely that follow-up alone is an accepted approach for nodules under 10  mm in diameter. (It is generally regarded as unwise to follow a nodule larger than 1 cm with imaging characteristics compatible with lung cancer because the delay inherent in follow-up would be detrimental to life-expectancy.) Follow-up alone is an accepted approach for nodules under 1 cm in diameter, largely because of the much higher probability of any particular nodule being an incidental benign lesion. There is, in reality, no practical alternative: such small lesions are not in general suitable for biopsy, PET, or contrast enhancement, and a large majority of patients would be severely disadvantaged by indiscriminate surgical resection. The harm done by the delay inherent in follow-up, which may allow tumors to metastasize in the interval, is still not accurately quantified,399 but there are indications that the outcome may be affected relatively little.400 It is hoped that the delay required to check that the growth rate is compatible with lung cancer, thereby avoiding unnecessary surgery, will outweigh

Lung Cancer the disadvantage of delaying treatment for what should still be a small tumor at the time of surgery. A variety of algorithms for following nodules, which differ in points of detail, have been recommended.29,84,391,392,401 An approach advocated by us is: • Follow-up at 12 months for individuals with one to six noncalcified nodules 10 cm maximum dimension Clinical stage Pathological stage (PS) at a given site denoted by a subscript (i.e. M = marrow, H = liver, L = lung, O = bone, P = pleural, D = skin)

*Modifications from Ann Arbor system.

Table 13.9  Murphy staging system for childhood non-Hodgkin lymphoma624 Stage Criteria for extent of disease I

II

III

IV

A single tumor (extranodal) or single anatomical area (nodal) with the exclusion of the mediastinum or abdomen A single tumor (extranodal) with regional nodal involvement Two or more nodal areas on the same side of the diaphragm Two single (extranodal) tumors with or without regional node involvement of the same side of the diaphragm A primary gastrointestinal tract tumor, usually in the ileocecal area, with or without involvement of associated mesenteric nodes only, grossly completely resected Two single tumors (extranodal) on opposite sides of the diaphragm Two or more nodal areas above and below the diaphragm All primary intrathoracic tumors (mediastinal, pleural, thymic) All extensive primary intraabdominal disease, unresected All paraspinal or epidural tumors, regardless of other tumor site(s) Any of the above with initial central nervous system (CNS) and/or bone marrow involvement

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Imaging features of intrathoracic lymphadenopathy in lymphoma The cardinal feature of malignant lymphoma on chest radiography and CT is mediastinal and hilar node enlargement, which may be accompanied by pulmonary, pleural, or chest wall involvement. The appearances of intrathoracic lymphadenopathy on imaging examination are similar in Hodgkin and non-Hodgkin lymphoma, but the frequency and distribution differ. Any intrathoracic nodal group may be enlarged and the possible combinations are legion, but the following remarks regarding chest radiography, CT, and MRI may be useful: • Filly et  al.625 reviewed the chest radiographs of patients with untreated malignant lymphomas. Of the 164 patients with Hodgkin lymphoma, 67% had visible intrathoracic disease, and all but one had mediastinal or hilar adenopathy, whereas 43% of the patients with non-Hodgkin lymphoma had visible intrathoracic abnormality, 87% of which showed mediastinal/ hilar lymphadenopathy. Similarly, Castellino et  al.,626 who studied the prevalence of intrathoracic abnormalities on chest CT and chest radiography in 181 patients with newly diagnosed non-Hodgkin lymphoma, found that 45% of the patients had visible disease within the thorax, 80% of whom showed mediastinal/hilar adenopathy. The anterior mediastinal and para­ tracheal nodes are the most frequently involved groups (Fig. 13.75). The tracheobronchial and subcarinal nodes are also enlarged in many cases. In most cases the lymphadenopathy is bilateral but asymmetric. Large B cell non-Hodgkin lymphoma and Hodgkin lymphoma both have a propensity to involve the anterior mediastinal and paratracheal nodes – almost all patients with the nodular sclerosing form of Hodgkin lymphoma have disease in the anterior mediastinum. • The incidence of visible hilar and mediastinal lymphadenopathy on chest radiographs in younger patients with malignant lymphomas is lower: under 10 years of age, approximately 33% of those with Hodgkin lymphoma and only 20–25% of those

•

• • •

• • •

• •

with non-Hodgkin lymphoma show mediastinal and hilar node enlargement.618,623,627 The great majority of cases of Hodgkin lymphoma show enlargement of two or more nodal groups, whereas only one nodal group is involved in about half the cases of non-Hodgkin lymphoma. Hilar node enlargement is rare without accompanying mediastinal node enlargement, particularly in Hodgkin lymphoma. The posterior mediastinum is infrequently involved. The enlarged nodes are often low in the mediastinum (Fig. 13.76), and contiguous retroperitoneal disease is likely. The paracardiac nodes are rarely involved but become important as sites of recurrence because they may not be included in the radiation field (Fig. 13.77). They may be visibly enlarged on chest radiographs, but frequently CT is needed for their demonstration (Fig. 13.78). Compression of the pulmonary arteries, superior vena cava, and major bronchi by enlarged nodes may be seen in both Hodgkin and non-Hodgkin lymphoma. CT demonstrates enlarged mediastinal nodes despite normal chest radiographs in about 10% of those with both Hodgkin and non-Hodgkin lymphoma. At CT, the enlarged lymph nodes in any of the malignant lymphomas may be discrete or matted together, and their edges may be well defined or ill defined (Fig. 13.79). The nodes show minor or moderate enhancement following intravenous contrast material in most instances, but enhancement by more than 50 HU is seen in a small proportion of cases. Low-density areas (Fig. 13.79) resulting from cystic degeneration may be seen in both Hodgkin628 and non-Hodgkin lymphoma.629,630 The cystic areas may persist following therapy, when the rest of the nodal mass shrinks away. Lymph node calcification before therapy is rare, even at CT,631,632 but is seen occasionally following therapy. Irregular, eggshell, and diffuse patterns of calcification may be seen. MRI shows much the same anatomic features as CT, but MRI allows the demonstration of vascular and cardiac invasion or

A

Fig. 13.75  A, B, Anterior mediastinal lymph node enlargement in Hodgkin disease.

838

B

Malignant Lymphoma Box 13.11  Imaging findings in posttreatment residual mediastinal masses of lymphoma • CT shows soft tissue density which may calcify • Cystic change may be demonstrated, which may be degenerative or due to epithelial cyst formation • Gallium-67 scanning is helpful in excluding active disease if there is no uptake in a mass that previously showed substantial activity • PET can be both false positive and false negative for active lymphoma, but a negative scan in a patient with enlarged mediastinal nodes is good evidence against active lymphoma • MRI findings are uniform low signal on T2- as well as T1-weighted images, but this combination does not rule out active disease

Posttreatment residual mediastinal masses

Fig. 13.76  Posterior mediastinal lymph node enlargement in Hodgkin disease. The left paraspinal line is displaced by enlarged nodes. Note sclerosis of body of T12 resulting from lymphomatous involvement of bone.

compression without the use of intravascular contrast agents (Fig. 13.80). The MRI signal intensity of lymphomatous masses is usually homogeneous. On T1-weighted images lymphomatous tissue is slightly hyperintense compared with muscle and well below fat, whereas on T2-weighted images it is of greater signal intensity than muscle and isointense with fat. These findings appear to be independent of the grade of the tumor. Negendank and co-workers633 found that active tumor with dense fibrous tissue had unexpectedly high signal on T2-weighted images, perhaps explaining the tendency for Hodgkin lymphoma to show higher signal on T2-weighted images than nonHodgkin lymphoma.

Thymic lymphoma Thymic enlargement is seen in a high proportion of patients with lymphoma,634 particularly mediastinal large B cell and Hodgkin lymphoma, in adults and T cell lymphoblastic lymphoma in children. Since the thymus is of lymphatic origin, there is little point in determining on imaging whether an anterior mediastinal mass is of thymic or nodal origin, but it is worth noting that massive thymic enlargement is a highly characteristic presentation of mediastinal large B cell lymphoma and T cell lymphoblastic lymphoma. The thymus in children may enlarge following successful treatment of lymphoma or leukemia due to the phenomenon known as rebound thymic hyperplasia.

Successfully treated lymphomatous nodes often return to normal size and extranodal masses resolve, but bulky mediastinal nodal disease in both Hodgkin and non-Hodgkin lymphoma, particularly nodular sclerosing Hodgkin lymphoma, is often slow to resolve and may leave residual masses of sterilized fibrous tissue (Fig. 13.81), particularly when the initial tumor mass consists chiefly of fibrous tissue to start with.635 Determining the nature of such residual masses by imaging is difficult (see Box 13.11). CT shows soft tissue density masses, sometimes partially calcified, but cannot distinguish between tumor and fibrous tissue on density grounds alone. FDG-PET can be helpful in assessing posttreatment residual masses; it can be both false positive and false negative when trying to determine active disease in residual masses, but a negative PET scan in nodes which remain large following treatment is a reasonably strong indicator of inactive disease.636,637 At MRI, posttreatment residual masses show lower signal on T2-weighted images than prior to treatment, reflecting a reduction in water content. More recent investigations have shown that MRI on its own is too unreliable to be decision making.637 Active tumor cannot be excluded on the basis of signal intensity alone, because small foci of active disease within a mass of predominantly mature fibrosis are not detectable. MRI is also unreliable at diagnosing posttreatment active disease. High signal on T2-weighted images is seen within active tumor, but can also be seen with necrosis and inflammation in inactive tumor.638 The interval development of higher T2 signal on sequential scans taken at least 6 months apart is a more reliable finding than the presence of high signal alone.639 Significant reduction in gadolinium enhancement of the lymphomatous tissue on follow-up scans occurs in patients with complete remission, unlike patients with relapse whose residual mass shows the same or greater degree of enhancement as the initial untreated mass.638 Posttreatment cystic degeneration of the thymus can be confused with active tumor.640,641 Cysts, which may be degenerative or epithelial in nature, can develop in the thymus after radiation therapy for anterior mediastinal disease; they should not be confused with recurrent lymphoma. Either CT or MRI can be used to confirm the presence of cysts in the thymus.634

Pulmonary involvement in association with extrapulmonary disease Lymphoma usually involves the lung in association with extrapulmonary lymphomatous disease (Box 13.12), notably lymph node involvement, rather than by originating primarily in the lung. Parenchymal involvement of the lung becomes more frequent as the disease takes hold. It is three times more frequent in Hodgkin than in non-Hodgkin lymphoma as a whole, but mediastinal large B cell lymphoma has a propensity to invade the lung.

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

A

B

Fig. 13.77  Paracardiac node enlargement in Hodgkin disease. A, Radiograph before radiation therapy. There is enlargement of the paratracheal nodes bilaterally and of the nodes along the left heart border. Nodes in the left cardiophrenic angle are not enlarged. B, C, Four years later, at time of recurrence, posteroanterior and lateral radiographs show massive enlargement of the left cardiophrenic angle nodes but no detectable enlargement of mediastinal nodes in the original radiation field.

C

Box 13.12  Pulmonary involvement in lymphoma can be divided into three broad categories

1.  In association with existing (or previously treated) nodal disease • Seen in some 10–15% of untreated cases • Three times more frequent in Hodgkin than in non-Hodgkin lymphoma • Patterns of pulmonary involvement are highly variable • Pulmonary involvement usually extends from hilum or mediastinum in previously untreated Hodgkin lymphoma • Pulmonary non-Hodgkin lymphoma may grow very rapidly

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2.  Primary Hodgkin lymphoma of the lung • Rare entity • Pattern is usually solitary or multiple pulmonary nodules and/ or consolidations

3.  Primary non-Hodgkin lymphoma of the lung • MALT lymphomas are by far the most common • Rarely, non-MALT B cell lymphomas, notably lymphomatoid granulomatosis and intravascular large B cell lymphoma • Rarely, peripheral T-cell lymphomas

Malignant Lymphoma seen, perhaps reflecting spread by way of the bronchopulmonary lymphatics. Widespread, reticulonodular opacities (Fig. 13.85) resembling diffuse interstitial lung disease (sometimes called a ‘lymphangitic pattern’) and widespread micronodules are also seen.643 They are, however, an uncommon pattern in Hodgkin lymphoma. Hodgkin lymphoma often appears to spread from nodal sites into the adjacent lung parenchyma.643,644 However, peripheral subpleural masses or masses without visible connection to enlarged nodes in the mediastinum and hila (Fig. 13.86) are seen occasionally in Hodgkin lymphoma.645 If an individual presents with Hodgkin lymphoma and a focal pulmonary opacity, but no evidence of hilar or mediastinal disease, it is likely that the pulmonary process represents something other than Hodgkin lymphoma.644 A caveat here is that the patient should not previously have received radiation therapy to the mediastinum; when mediastinal and hilar nodes have been previously irradiated, then recurrence confined to the lungs may be seen in both Hodgkin and non-Hodgkin lymphoma. Rapid growth of pulmonary lesions may be seen with non-Hodgkin lymphoma. The development of large opacities or widespread disease in under 4 weeks, even in as little as 7 days, may cause great diagnostic confusion with pneumonia.

Primary pulmonary Hodgkin lymphoma

A

Primary pulmonary Hodgkin lymphoma is rare. In their review of the literature, Lee et  al.646 found fewer than 100 cases of Hodgkin lymphoma restricted to the pulmonary parenchyma at presentation. On imaging,647 the commonest feature is upper lobe predominant single or multiple nodules, some of which may be enlarged intrapulmonary lymph nodes. Some masses may be endobronchial in location. Single or multiple focal areas of consolidation may be seen in isolation or combined with pulmonary nodules. Cavitation of the pulmonary lesions may be seen.

Primary pulmonary non-Hodgkin lymphoma

B

Fig. 13.78  Paracardiac node enlargement in non-Hodgkin lymphoma. A, Distortion of the right mediastinal border is difficult to distinguish from right atrial enlargement on the chest radiograph (lateral projection was unremarkable). B, CT demonstrates enlarged lymph nodes (arrows) to advantage. The pulmonary opacities on chest radiography and CT in both Hodgkin and non-Hodgkin are varied and resist easy classification. The most frequent pattern is one or more discrete pulmonary nodules resembling primary or metastatic carcinoma, but usually rather less well-defined.642 Such nodules may, on rare occasions, cavitate (Fig. 13.82). Another common pattern is round or segmental-shaped, focal or patchy consolidations (Figs 13.83 and 13.84) which resemble pneumonia. A pattern of peribronchial pulmonary nodules or interstitial infiltration extending from the hila out into the parenchyma is sometimes seen at CT.643 Similarly focal, streaky shadowing, which at CT can be seen to be peribronchial,642 may be

Most lymphomas arising primarily in the lung are marginal zone MALT lymphomas.648 The distinct clinicopathologic entity of a ‘lowgrade’ B cell lymphoma arising from MALT was first described in 1983 in a patient with primary gastrointestinal lymphoma.649 Since then further reports have been published of similar tumors, of both low and intermediate grade, which have arisen in many other mucosal sites including in the lungs, salivary glands, thyroid gland, thymus, skin, orbit, bladder, and genitourinary tract. This particular form of lymphoma was previously categorized as pseudolymphoma and believed to be an inflammatory disorder with a propensity to convert to lymphoma. The lymphoid tissue in lung parenchyma comprises lymphoid aggregates called bronchial MALT, sited predominantly in the peribronchial interstitium at the divisions of the respiratory bronchioles and to a lesser extent in the bronchial walls, interlobular septa, and subpleural interstitium. When marginal zone non-Hodgkin lymphomas of MALT origin develop in the lung, they may be solitary or multicentric and the cell of origin is a small B lymphocyte with either plasmacytoid, lymphocyte-like or monocytoid features that is believed to be derived from bronchial MALT. The tumors show dense infiltration of the lung parenchyma by the lymphoid infiltrate, with destruction of alveoli but comparative preservation of airways (correlating with air bronchograms) and pulmonary arteries. At their periphery, lymphomatous spread is typically along the distribution of pulmonary lymphatics. Immunohistochemistry and/or molecular studies may show evidence of clonality to confirm the diagnosis. Spread from marginal zone non-Hodgkin lymphomas of MALT origin tends to be to lymph nodes as well as extranodal sites. Prognosis is generally good. However, a minority of primary pulmonary cases are diffuse large B cell non-Hodgkin lymphomas, some of which may represent transformation of marginal zone non-Hodgkin lymphomas of MALT origin. These tumors

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

A

B

C

Fig. 13.80  Hodgkin lymphoma (stage II) showing large lymph node masses compressing the right brachiocephalic vein and superior vena cava. MRI (T1-weighted coronal scan) shows venous compression without the need for contrast medium. (Courtesy of Dr. William C Black, Washington, DC, USA.)

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Fig. 13.79  CT of enlarged lymph nodes in malignant lymphoma. A, Multifocal, greatly enlarged, moderately discrete nodes. B, Hodgkin lymphoma. The nodes are matted together and appear as a conglomerate mass. Fluid density areas caused by necrosis are present. C, High-grade non-Hodgkin lymphoma showing multiple rounded areas of low density in greatly enlarged nodes. Note the large right pleural effusion.

comprise sheets of blastic lymphoid cells, often with necrosis and brisk mitotic activity, and they behave in a more aggressive fashion. The clinical features of MALT lymphoma are varied. The patients range in age from 11 to 80, the mean age being in the sixth decade. A substantial portion are asymptomatic, the lesions being detected incidentally on chest radiography. Those with symptoms have nonproductive cough, dyspnea, or respiratory infection.650,651 Systemic symptoms such as fever and weight loss are less common. There may also be extrathoracic sites of extranodal lymphoma, particularly in the stomach, salivary glands, bone marrow, and skin.651,652 A significant proportion of patients who develop MALT lymphoma have a history of inflammatory or autoimmune disease,651,653 such as Sjögren syndrome, dysgammaglobulinemia,654 and various collagen vascular diseases. On imaging,653,655 MALT lymphomas usually show one or more rounded or segmental-shaped consolidations varying in size from small to the size of a lobe (Fig. 13.87). The opacities may be sufficiently well defined to be called nodules or masses. There is no lobar predilection and the consolidations may be placed centrally or peripherally in the lung parenchyma. A few of the lesions show cavitation, but calcification does not occur. Air bronchograms are common and cystlike lucencies may be seen within the pulmonary opacities. These two features are well shown by CT (Fig. 13.87),653 on which it may be apparent that the bronchi within the lymphomatous process are dilated, stretched, or narrowed, similar to the appearances seen with bronchioloalveolar carcinoma.656 CT may show in addition centrilobular micronodules and thickened interlobular septa.657 Areas of ground-glass opacity are common. Diffuse interstitial shadowing closely resembling interstitial fibrosis has also been reported.653 Pleural effusion is demonstrated in up to 20% of cases. Hilar and/or mediastinal node enlargement may also be present. Primary pulmonary non-Hodgkin lymphomas other than

Malignant Lymphoma

A

C

B

D

Fig. 13.81  Residual fibrotic mass following successful radiation treatment for Hodgkin lymphoma. A, B, Enlarged nodes in the aortopulmonary window and left paratracheal area. C, D, Residual mass of fibrous tissue in the aortopulmonary window. This residual mass remained unchanged over 3 years with no further treatment.

MALT lymphoma are very rare and include lymphomatoid granulomatosis, intravascular large B cell lymphoma, and unspecified peripheral T cell lymphoma. Lymphomatoid granulomatosis (also known as angiocentric immuno­proliferative lesion) is believed to be an Epstein–Barr virusassociated B cell lymphoproliferative disorder in which T cells predominate over B cells.658 The literature on the appearances at chest radiography and CT needs to be interpreted with caution since it is largely based on histologic diagnoses that would now be questioned, because modern immunohistochemical techniques were unavailable at the time.659,660 The most frequent appearance, occurring in up to 80% of patients, is multiple pulmonary nodules, which are usually bilateral but may be unilateral; occasionally, only a solitary pulmonary mass is seen (Fig. 13.88). The nodules, which closely resemble metastases, are usually round in shape and have illdefined margins, though a small proportion have a well-defined edge. They may be very large: nodules of up to 10 cm in diameter

have been reported. Multiple, ill-defined areas of consolidation resembling pneumonia are a less common radiographic manifestation. Coalescence of the nodules or consolidations is a feature that may help in the radiographic differential diagnosis from pulmonary metastases. The lesions show a predisposition for the mid- and lower lung zones, with a tendency to spare the apices. A bronchocentric distribution may be noted at CT. Invasion into the lumen of a main pulmonary artery has been reported.661 At least some of the nodules seen on chest radiography are a result of infarcts related to the angiodestructive nature of the disease. Cavitation was seen in approximately 10% of patients in one review of the literature, but, in individual series, the rate of cavitation is as high as 25%.659,662 The cavities are usually thick walled, but thin-walled cystlike cavities have been reported.661 Cavitation appears to be associated with a poor prognosis. Air bronchograms are seen in some cases (Fig. 13.88), the highest reported incidence of air bronchograms being 40%. Widely distributed reticulonodular shadowing has been

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

Fig. 13.83  Hodgkin lymphoma of lung. The pulmonary involvement has taken the form of multifocal parenchymal consolidation with air bronchograms. There are some moderately enlarged lymph nodes at the lower pole of the right hilum. Fig. 13.82  Hodgkin lymphoma showing multiple cavitating pulmonary nodules (and right paratracheal nodal enlargement).

A

B

Fig. 13.84  Non-Hodgkin lymphoma of lung in a middle aged man. The solitary peribronchial nodule (arrowed) in the A, right middle lobe has B, decreased in size 4 weeks after therapy. reported in a few cases.663 When examined at biopsy, these lesions proved to result from cellular infiltration without infarction.663 In a single case the reverse halo sign has been reported to occur in lymphomatoid granulomatosis.664 The reported cases of MRI of lymphomatoid granulomatosis of the lung reveals no features that permit distinction from other lymphomas.661 Visible hilar and mediastinal adenopathy is very unusual. Pleural effusion does not appear to be a major feature of the disease, though small pleural effusions are seen on plain chest radiograph in up to one-third of patients.

Endobronchial disease Endobronchial disease is rare, particularly in non-Hodgkin lymphoma,665 but so is bronchial occlusion by neighboring lymph node enlargement. Therefore, when atelectasis is encountered, the possibility of endobronchial lymphoma should be seriously consid-

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ered. Endobronchial lymphoma may be seen as an intramural nodule or irregular tumor mass on CT.666,667

Pleural and pericardial disease Pleural effusions, mostly unilateral, were seen in up to a quarter of patients with lymphoma on plain chest radiographs in several larger series,625,626,668,669 and in 50% of patients on CT.642 Pleural effusion is accompanied by mediastinal lymphadenopathy, sufficiently large to be visible on chest radiographs or CT, in some 80% of patients with Hodgkin lymphoma.626 Pleural and adjacent extra­ pleural lymphomatous nodules or masses are found in some 25– 40% of patients with pleural effusion in both Hodgkin and non-Hodgkin lymphoma.670 The effusions are usually exudates and may disappear with irradiation of the mediastinal lymph nodes. Chylothorax is occasionally encountered.644 Lymphomatous pleural masses, particularly primary pleural lymphoma, are rare; the more

Malignant Lymphoma

A

Fig. 13.85  Non-Hodgkin lymphoma showing widespread reticulonodular opacities in both lungs (and enlargement of hilar and right paratracheal nodes).

B

Fig. 13.87  MALT (mucosa-associated lymphoid tumor) lymphoma taking the form of focal pulmonary consolidation. A, Chest radiograph. B, CT showing an obvious air bronchogram. (Courtesy of Dr. Leonard King, London, UK.)

Fig. 13.86  Peripheral deposit of Hodgkin disease (arrow), which has no visible connection with the mediastinal adenopathy.

usual ‘pleural’ manifestation is lymphomatous pulmonary disease in the subpleural region just beneath the visceral pleura.645 A rare pleural-based lymphoma is pyothorax-associated diffuse large B cell lymphoma, in which lymphoma develops in the walls of an empyema.671–673 So-called ‘primary effusion lymphoma’ is a rare and aggressive neoplasm of large B cells, which usually presents initially as serous effusions in the pleural, pericardial, or peritoneal cavities without detectable masses and no lymphadenopathy or organomegaly. It is mostly associated with human immunodeficiency virus infection.674 Some patients have coexistent Kaposi sarcoma or multicentric Castleman disease.675 Pericardial effusions are presumptive evidence of pericardial involvement. For practical purposes, pericardial effusion requires

ultrasound, CT, or MRI for its recognition. In Castellino’s series of 203 patients with Hodgkin lymphoma who had CT on initial presentation,626 6% had pericardial effusion, and in all these patients there were coexistent large lymph nodes adjacent to the cardiac margins. A nodular mass within the pericardium was seen in just one case.

Chest wall invasion Chest wall invasion and rib destruction are seen on occasion (Fig. 13.89). Chest wall invasion is well demonstrated by CT and is even better shown by MRI. As with many neoplasms which invade muscle and fat, it can be difficult to differentiate between tumor and surrounding edema, which means the true extent of tumor may be difficult to determine and the distinction between recurrence of lymphoma and postradiation therapy changes may not be possible.

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

A

B

C

D

Fig. 13.88  Various appearances of lymphomatoid granulomatosis. A, Large irregular, lobular mass adjacent to the left hilum. B, Multiple lobular pulmonary masses resembling metastases on CT. C, Multiple, ill-defined pulmonary opacities that, D, on CT are seen to be masses with very irregular edges and air bronchograms.

Fig. 13.89  Massive chest wall invasion by non-Hodgkin lymphoma.

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Leukemia

Role of imaging in lymphoma Chest radiography can accurately demonstrate the extent of lymphomatous involvement in many patients, but chest CT is more informative and may show that suspected lymphomatous involvement is due to an alternative process. In general, chest CT is more useful in the initial staging of Hodgkin than non-Hodgkin lymphoma,676 because radiation therapy is often a vital component of treatment for Hodgkin lymphoma and inadequate radiation portals are a potential cause of treatment failure. Castellino et al.626 found that the incremental information obtained from chest CT prompted a change in treatment in almost 10% of their 203 new patients with Hodgkin lymphoma. As expected, the impact was greatest in the 65 patients being treated with radiation therapy alone. Chest CT is most useful in patients in whom the appearance of the mediastinum on chest radiograph is normal or equivocal. Non-Hodgkin lymphoma is so often disseminated at the time of initial diagnosis that demonstrating the extent of intrathoracic disease may not change management, because the treatment for disseminated disease is chemotherapy rather than radiation therapy. Although the findings on routine chest CT can increase the stage of disease in some patients with non-Hodgkin lymphoma, it had no effect on the initial treatment of newly diagnosed nonHodgkin lymphoma in one large series.676 The role of chest CT may be rather different in children with non-Hodgkin lymphoma. In the series by Ng et al.,623 chest radiography provided the necessary management information in almost all cases; in only one of the 34 children who had chest CT did the CT findings increase the stage. Cohen et al.,677 however, found that chest CT altered the stage in three of 11 children with non-Hodgkin lymphoma. So far, MRI has not proved to be of greater value than CT in the routine staging of thoracic lymphoma, but it may answer highly specific questions such as the extent of pericardial, cardiac, chest wall, or spinal involvement.644,678,679 It has been suggested that it might be possible to predict prognostic grade in certain circumstances: patients with high-grade non-Hodgkin lymphoma and a homogeneous signal pattern tend to have a better survival rate than those with an inhomogeneous pattern.680 FDG-PET can achieve the same or greater accuracy as CT for initial staging and is better than CT for finding extranodal lymphoma,680 but it does give some false-positive results.636 According to some authors,636 but not all,637 FDG-PET can be helpful in assessing posttreatment residual masses; a negative FDG-PET in nodes which remain large following treatment is a strong indicator of inactive disease. FDG-PET imaging can alter management in a substantial proportion of patients with lymphoma, either by excluding active disease or by diagnosing active disease in sites where CT fails to show an abnormality.636 FDG-PET can also predict response to treatment. A negative PET scan appears to be reasonably reliable for predicting remission, whereas a positive scan is much less accurate for predicting relapse.681

NON-NEOPLASTIC LYMPHOID LESIONS OF THE LUNGS Included under the general heading of pulmonary lymphoid lesions of the lungs are true lymphomatous and leukemic lesions of the lung as well as several entities that are non-neoplastic (see Box 13.13). The understanding of many of the entities is constantly evolving and has changed significantly over the past two decades. For example: • Conditions that were previously regarded as non-neoplastic, such as lymphomatoid granulomatosis and most cases of pseudo­lymphoma are now classified as lymphomas. • Lymphoid interstitial pneumonia (LIP) has changed status frequently, being classified initially as an interstitial pneumonia,

Box 13.13  Non-neoplastic pulmonary lymphoid lesions Travis and Galvin684 classify five conditions as non-neoplastic pulmonary lymphoid lesions: • Intrapulmonary lymph node • Follicular bronchiolitis • LIP • Nodular lymphoid hyperplasia • Castleman disease

before it was recognized that most of the cases were low grade B cell lymphomas which would now be called marginal zone non-Hodgkin lymphomas of MALT origin. With these lymphomas stripped out, LIP is now once again regarded as a nonneoplastic, inflammatory, interstitial pneumonia. Idiopathic LIP is included in the recent American Thoracic Society/European Respiratory Society classification of the idiopathic interstitial pneumonias, but cases are exceptionally rare. LIP is far more commonly associated with a variety of autoimmune disorders and with HIV infection and AIDS. • Follicular bronchiolitis is an entity consisting of hyperplasia of bronchial MALT in relation to the airways. • Hyaline vascular Castleman disease is regarded as a form of reactive hyperplasia, which predominantly affects lymph nodes, although cases are described within the lung. • The entity ‘nodular lymphoid hyperplasia’, which refers to the occurrence of one or more pulmonary nodules consisting of reactive lymphoid cells, is a rare condition, cases of which were previously included in series of cases labeled as pulmonary pseudolymphoma. Pseudolymphoma was initially described in the early 1960s, but during the 1980s and early 1990s immunohistochemical and molecular studies showed that most cases were neoplastic from the outset.682,683 Patients with nodular lymphoid hyperplasia have a wide age range and are usually asymptomatic at presentation. Systemic symptoms (fever) and a high erythrocyte sedimentation rate are observed in a few cases. Usually, recurrence has not been reported after surgical excision. Steroids and cytotoxic drugs can have some benefit in patients with multiple lesions. Other conditions with proliferation of lymphoid cells include plasma cell granuloma and posttransplant lymphoproliferative disorder.

LEUKEMIA Several abnormalities may be seen on chest imaging in leukemic patients: • Intrathoracic lymph node enlargement, leukemic infiltration of the lungs and pleura, and granulocytic sarcoma • Non-neoplastic complications of leukemia or its treatment, notably pulmonary infection, organizing pneumonia, pulmonary hemorrhage (Fig. 13.90), pulmonary edema, and drug reactions • Cardiac enlargement and pulmonary venous congestion in patients with severe anemia. Leukemic infiltration of the lungs (Fig. 13.91) is defined as extravascular leukemic cells in portions of the lung parenchyma not involved by infection, infarction, or hemorrhage. Leukostasis is a separate category that may or may not be accompanied by leukemic infiltration of the lung parenchyma. Apart from patients with leukostasis, leukemic infiltration of the lungs does not appear to be a cause of pulmonary symptoms. When respiratory impairment is present, the leukemic infiltrates are accompanied by pulmonary infection, edema, or hemorrhage, and these are the likely cause of the patient’s symptoms.

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

Fig. 13.90  Acute pulmonary opacities in a 39-year-old man with acute myeloid leukemia. The bilateral opacities were due to intrapulmonary hemorrhage.

to death. In all except two, the opacities were the result of a complication of the disease, not leukemic infiltration per se. Focal masses or consolidations are very rare, but are reported.687 In one case multifocal consolidation due to leukemic infiltration showed an air-crescent sign,688 a feature previously reported only in cases complicated by infection. All 10 patients in one CT series689 with biopsy-proven leukemic infiltration, without coexisting pathology, had thickening of interlobular septa and small pulmonary nodules. In some cases the septal thickening was smooth; in others it was nodular; and in yet others a mixture of the two. In all but one case there was also thickening of the bronchovascular bundles. The nodules varied in number from numerous to just a few; most were small in size, varying from barely perceptible to 10 mm in diameter. They were either randomly distributed or showed bronchocentric or centrilobular predominance. Ground-glass attenuation and focal consolidation, with or without air bronchograms, were also common. Similarly, another CT series of 11 patients, seven of whom underwent pathological correlation, evaluated the relative frequency of CT signs in leukemic infiltration compared with the findings in 22 leukemic patients with other pulmonary complications.690 The signs seen significantly more frequently with leukemic infiltration were peribronchial thickening and prominence of peripheral pulmonary arteries, which corresponded pathologically to thickening of the interstitium. The other statistically significant differences were multifocal areas of nonlobular, nonsegmental airspace consolidation, or ground-glass opacity. The incidence of leukemic infiltration of the nodes on autopsy examination is very high, 50% in the large series of Klatte et al.,685 but most involved nodes show little or no enlargement on plain chest radiography. The distribution of nodal enlargement closely resembles the lymphomas. T cell leukemias may show massive mediastinal adenopathy that responds rapidly to chemotherapy or radiation treatment. Huge mediastinal masses of T cell leukemia may disappear within a few days with appropriate treatment (Fig. 13.92). Pleural effusion is common in leukemia. Subpleural deposits of leukemic cells are often found at autopsy, but pulmonary infection, infarction, hemorrhage, and edema so frequently coexist with these leukemic deposits that it is not possible to state the cause of the effusion with any confidence. A focal mass of leukemic cells in patients with myeloid leukemia, so-called granulocytic sarcoma or chloroma, may be encountered on rare occasions.691 Granulocytic sarcoma mostly presents before, or at the time of, the initial diagnosis of leukemia, but in approximately one-fifth of reported cases it developed after a previous remission. Granulocytic sarcoma may arise as a focal mediastinal mass or more generalized mediastinal widening. The other presentations include pleural effusion, an airway, hilar, pulmonary, or pleural mass, or cardiac enlargement due to the tumor or to pericardial effusion. Pulmonary masses may cavitate.692

Leukostasis Fig. 13.91  Leukemic opacities in the lungs. Note also the bilateral hilar adenopathy caused by leukemic involvement of lymph nodes.

The incidence of leukemic infiltration of the lungs, mediastinal lymph nodes, and pleura varies with the course of the disease. Clearly, the highest incidence is shown in autopsy series,685–687 but only rarely is this infiltration visible on chest radiography. In one typical series,686 41% of the patients showed leukemic infiltrates of the lung histologically, but the leukemic infiltration was almost never visible on imaging. Ninety percent of patients in the study had pulmonary opacities on chest radiographs immediately prior

848

Leukostasis is a condition seen in patients with acute myeloid leukemia who have very high white blood cell counts, in the order of 100 000 to 300 000 cells/mm3, together with accumulations of leukemic cells in small blood vessels, especially of the lungs, heart, brain, and testes. Central nervous system symptoms are frequent, and the patients may be dyspneic due to obliteration of small pulmonary blood vessels by the leukemic cells.693 The chest radiograph may be normal or may show airspace opacities (Fig. 13.93). In a report on the radiographic findings in 10 patients who died with leukostasis, four had a normal appearing chest radiograph, four showed wide airspace disease attributed to superimposed pulmonary edema, and one showed a small area of pulmonary consolidation.694 The radiographic opacities in leukostasis appear to be due to pulmonary edema rather than directly due to the accumulation of leukemic cells in the lungs.693–695

Localized Fibrous Tumor of the Pleura

A

B

Fig. 13.92  T cell leukemia/lymphoma in a 4-year-old girl. A, Massive mediastinal adenopathy. B, Following very rapid response to chemotherapy 9 days later.

Fig. 13.93  Leukostasis in a 43-year-old man in blast crisis, showing hazy opacity in lungs resembling pulmonary edema. The abnormalities cleared with leukaphoresis therapy.

LOCALIZED FIBROUS TUMOR OF THE PLEURA This tumor has been given a variety of names, including pleural fibroma, fibrous mesothelioma, localized pleural mesothelioma, and benign mesothelioma. Benign mesothelioma appears to be a particularly inappropriate term since the tumors are not mesothe-

liomas, nor do they all behave in a benign fashion (see later Fig. 13.98). The current term, localized fibrous tumor of the pleura, has been recommended because the lesion is thought to arise from subpleural mesenchymal cells rather than from epithelial cells.696 It is probably best to regard them as a spectrum from benign to malignant. Because of the difficulty distinguishing benign from malignant lesions, surgical resection is advised for all fibrous tumors of the pleura. Local recurrence is the major clinical problem with malignant tumors. Most patients are between 45 and 65 years (range 5–87 years), with no significant sex difference.696–698 Unlike diffuse malignant mesothelioma, the localized tumor is not asbestos related,696–698 though a relationship with previous irradiation has been recorded.699 Histologically, the lesion consists of spindle-shaped cells separated by collagen.700 It exists in benign and malignant forms, 14–30% being malignant.696,701,702 Macroscopically, the tumor is seen as a mass in contact with the pleura, but a small number appear to be totally encased within the lung.703 Up to 87% arise from visceral pleura, the remainder from parietal pleura.698 An origin from within a fissure is fairly common.704 Pedunculation is present in about half the cases;698,705 the stalk can be up to 9 cm in length.706 The benign tumors usually behave in a very indolent fashion and some have been known to be present for 20 years before removal,707 but rapid growth even of the benign form is encountered occasionally.702 Synchronous multiple tumors have been reported but are very unusual.698 Some 40–50% of patients are asymptomatic, the tumor being detected incidentally at chest radiography.705 The commonest symptoms are chest pain and dyspnea.705 Although hypertrophic osteoarthropathy and finger clubbing were common in earlier series, its prevalence in series reported since 1972 has been much lower, 4–12%; the phenomenon appears to be more common in tumors over 7  cm in diameter. Other reported symptoms include cough, chills and fevers, weight loss, and debility. Symptomatic hypoglycemia is seen in up to 7% of patients.705,708,709 On chest radiography, the usual finding is a slow-growing, rounded or oval, often lobulated, homogeneous mass in contact

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura with a pleural surface, which may invaginate into or arise within a fissure (Fig. 13.94).696,699,705,710 The lesions vary in size from less than 1 cm to 30 cm in diameter, but are usually large, 7 cm or more at initial presentation. They are slightly more common in the lower half of the chest (Fig. 13.95).699 When very large, the origin from pleura may not be obvious, and on occasion the tumor may simu-

Fig. 13.94  Localized fibrous tumor of the pleura in a 61-year-old woman. At surgery this lesion was found to lie in the major fissure and was benign.

A

late a raised hemidiaphragm (Fig. 13.96) There is usually an obtuse angle at the margin with the chest wall, a finding present in 16 out of 17 cases in one chest film series,704 but lesions with acute angles, resembling an intrapulmonary mass, are not uncommon. Tumors on pedicles may change in shape and position on images taken on different occasions and in different postures.711 If the lesion is not pedunculated, inspiration/expiration imaging will show whether the mass is in the lung or is attached to the chest wall.699 Pressure effects on the adjacent ribs are very unusual but have been reported in both benign and malignant tumors.705 On CT (Figs 13.95–13.98),705,711–714 the lesions are usually well marginated and based on a pleural surface, some 95% showing at least one acute angle with the chest wall. In other words they grow outwards from a relatively narrow base or pedicle, and a stalk may be visible at CT. The smaller lesions show uniform soft tissue density whereas a substantial proportion of the larger tumors show low attenuation centrally due to necrosis. The soft tissue elements enhance to a much greater degree than muscle following intra­ venous contrast administration; inhomogeneous contrast enhancement is a frequent feature in benign tumors and is virtually always seen with malignant tumors.705 Calcification is uncommon, but recorded in benign lesions,713 it appears to be more common in the localized malignant lesions.697 Pleural effusions are occasionally present,708 and are sometimes large enough to obscure the under­ lying mass. There are multiple reports of the MRI features of solitary fibrous tumor of the pleura,708,712,713,715–719 the largest series being those of Rosado-de-Christianson et  al.705 and Tateishi et  al.720 The signal intensity on both T1- and T2-weighted images is usually hetero­ geneous. On T1-weighted images the signal intensity is usually predominantly lower than muscle but may be the same or higher; on T2-weighted images the signal intensity is usually low, or mixed high and low, though it may occasionally be high. In the majority of reported cases the signal intensity seems to reflect the high fibrous content of the tumor, namely low signal on both T1- and T2-weighted images, though a high-intensity rim or more central, small, high-intensity foci may be seen on the T2-weighted images. The tumors enhance following intravenous gadolinium administration, and signal void due to the blood vessels within the tumor may be seen. There are no MRI features that allow a distinction between benign and malignant fibrous tumors of the pleura.705

B

Fig. 13.95  Small localized fibrous tumor of the pleura (arrows) in a middle-aged woman seen on A, transverse and B, coronal CT images.

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Diffuse Malignant Mesothelioma

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Fig. 13.96  Extensive localized fibrous tumor of the pleura (arrows) in an elderly man (interpreted as a raised hemidiaphragm on a chest radiograph) seen on A, coronal and B, transverse CT image. The tumor is relatively homogeneous but contains a few amorphous calcifications; it occupies the entire left lower hemithorax.

DIFFUSE MALIGNANT MESOTHELIOMA Asbestos exposure is documented in about half the patients with diffuse malignant mesothelioma,721 but the incidence of an exposure history in various series ranges from under 25%722 to almost 90%.723 The contribution of asbestos in the usual urban environment is unknown. Of the various forms of asbestos, crocidolite appears to be the most carcinogenic form, followed by chrysolite and then by amosite, but because chrysolite is the most widely used form of asbestos, it is believed to account for most cases of diffuse mesothelioma.724 The interval between first exposure to asbestos and presentation with the tumor is in the order of 20–40 years.725 Inhalation of other substances, such as nonoccupational exposure to erionite, have been etiologically implicated726 and the possibility of an association with AIDS has been questioned.727 Prior thoracic irradiation has occasionally been noted721,722,728 and may, therefore, play an etiologic role in a few cases. Pathologically, diffuse malignant mesothelioma appears as plaques and nodules on the visceral or parietal pleura which may form a lobular sheet of tumor up to several centimeters thick encasing the lungs, maximal in the lower thorax, extending through the pleural cavity and growing into the interlobar fissures. Invasion into the adjacent chest wall, diaphragm, and mediastinal structures usually occurs relatively late, but may be seen early.723 Lymphatic and hematogenous metastases are usually late manifestations which, though present in 50% of patients at autopsy, are generally clinically silent. Histologically, malignant mesotheliomas are divided into epithelial, mesenchymal (fibrous or sarcomatous), or mixed tumors; their relative prevalence varies considerably from series to series and also varies according to the diligence with which the entire tumor is examined for mixed cell-types. In Legha and Muggia’s729 compilation of 382 cases from the literature, 54% were epithelial, 21% were fibrosarcomatous, and 25% were mixed, and the proportions were very similar in the Mayo Clinic series.730 The pure epithelial type has a better prognosis following surgical treatment.731 The epithelial type consists of cuboidal cells in various

arrangements, whereas the mesenchymal type shows sheets of parallel spindle-shaped cells similar to many soft tissue sarcomas. Immunohistochemical techniques and electron microscopy are often needed to distinguish between malignant mesothelioma and bronchial adenocarcinoma.732 Focal osteosarcoma formation, which may produce a heavily calcified mass, has been reported to arise within malignant pleural mesothelioma.733 Pleural fluid associated with malignant mesothelioma is an exudate, which is serosanguineous in half the cases. With large tumors, the glucose and pH levels are low. On cytologic examination, the fluid may contain malignant mesothelial cells together with varying numbers of lymphocytes and polymorphonuclear leukocytes,729 but the cytologic distinction between benign and malignant mesothelial cells is difficult and biopsy of the pleura is usually needed to establish the diagnosis. A TNM staging system (Tables 13.10 and 13.11) has been adopted by the AJCC (American Joint Committee on Cancer). It is a modification of the staging system proposed by the International Mesothelioma Interest Group.734–736 The Brigham System is the most recent malignant mesothelioma staging system.737,738 The Brigham System looks at different variables such as the involvement of the lymph nodes and the surgical ability to resect a malignant mesothelioma tumor. For this reason, it is not used very often to stage mesothelioma, as the cancer is rarely operable. The Brigham System divides malignant mesothelioma into four stages: • Stage 1 – malignant mesothelioma tumor is still resectable and the lymph nodes are not affected • Stage 2 – malignant mesothelioma tumor is still resectable, but the lymph nodes are now affected • Stage 3 – malignant mesothelioma tumor is not resectable and the malignant mesothelioma has penetrated the heart, chest wall, abdominal cavity, or diaphragm. Lymph nodes may or may not be affected • Stage 4 – malignant mesothelioma tumor is not resectable and has completely metastasized.

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Fig. 13.97  CT of localized benign fibrous tumor of the pleura. A, Well-defined lobular, homogeneous, soft tissue, enhancing pleural mass. (Courtesy of Dr. Pablo Ros, Gainesville, FL, USA.) B, Large mass showing variable density and focal area of dense calcification. C, Well-defined multiple foci of calcification (same case as D). D, Part of the mass (same case as C) has dense uniform contrast enhancement. The yellow arrows point to the anterior surface of the tumor; the red arrow points to the enhancing portion; and the blue arrow points to a curvilinear band of dense calcification.

Fig. 13.98  Malignant fibrous tumor of pleura. Note the pleural effusion and the local invasion of the chest wall (arrow).

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Diffuse Malignant Mesothelioma Table 13.10  IMIG staging system for diffuse malignant pleural mesothelioma Primary tumor (T) TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor involves ipsilateral parietal pleural, with or without focal involvement of visceral pleura T1a Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura. No involvement of the visceral pleura T1b Tumor involves ipsilateral parietal (mediastinal, diaphragmatic) pleura, with focal involvement of the visceral pleura T2 Tumor involves any of the ipsilateral pleural surfaces with at least one of the following: Confluent visceral pleural tumor (including fissure) Invasion of diaphragmatic muscle Invasion of lung parenchyma T3* Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following: Invasion of the endothoracic fascia Invasion into mediastinal fat Solitary focus of tumor invading the soft tissues of the chest wall Non-transmural involvement of the pericardium T4** Tumor involves any of the ipsilateral pleural surfaces, with at least one of the following: Diffuse or multifocal invasion of soft tissues of the chest wall Any involvement of rib Invasion through the diaphragm to the peritoneum Invasion of any mediastinal organ(s) Direct extension to the contralateral pleura Invasion into the spine Extension to the internal surface of the pericardium Pericardial effusion with positive cytology Invasion of the myocardium Invasion of the brachial plexus Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastases N1 Metastases in the ipsilateral bronchopulmonary and/or hilar lymph node(s) N2 Metastases in the subcarinal lymph node(s) and/or the ipsilateral internal mammary or mediastinal lymph node(s) N3 Metastases in the contralateral mediastinal, internal mammary, or hilar lymph node(s) and/or the ipsilateral or contralateral supraclavicular or scalene lymph node(s) Distant metastasis (M) MX Distant metastases cannot be assessed M0 No distant metastasis M1 Distant metastasis *T3 describes locally advanced but potentially resectable tumor. **T4 describes locally advanced, technically unresectable tumor.

Table 13.11 AJCC stage groupings for mesothelioma Stage Stage Stage Stage Stage

I IA IB II III

Stage IV

T1 T1a T1b T2 T1, T2 T1, T2 T3 T4 Any T Any T

N0 N0 N0 N0 N1 N2 N0, N1, N2 Any N N3 Any N

M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

The peak age at presentation is between 40 and 70 years, with males predominating. The usual symptoms are chest wall pain, shortness of breath, and cough, followed by dyspnea and weight loss. There may be intermittent low-grade fever. Clubbing of the fingers and hypertrophic pulmonary osteoarthropathy are seen, but are much less common than with localized fibrous tumors of the pleura.739 The imaging features721,730,740–750 are essentially similar on chest radiographs, CT, and MRI (Figs 13.99–13.103), but CT and MRI show the extent of the tumor with greater accuracy than chest radiography and show the accompanying pleural fluid with greater sensitivity. CT is useful for detecting recurrent disease following surgical treatment.751 CT and MRI appear to be of similar diagnostic accuracy for surgical staging. MRI is superior to conventional CT for revealing solitary foci of chest wall involvement and for showing diaphragmatic invasion, but this advantage does not affect surgical

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Fig. 13.99  Bilateral malignant mesothelioma of pleura demonstrated on PET-CT. The lesions extend along the pleura (A–C), at the left lung base (D–F), over the left diaphragm (G–I), and ventral to the spleen (J–L).

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Diffuse Malignant Mesothelioma Fig. 13.100  Malignant mesothelioma of the right pleural cavity that transgresses the chest wall (red arrow). Note growth along the pleural surface (yellow arrow) and pericardial involvement (blue arrow).

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Fig. 13.101  CT of malignant mesothelioma. A, Relatively thin rind of nodular pleural thickening and a large loculus of pleural fluid. B, Radiograph of the same patient for comparison. C, D, Two images from a single examination showing extensive nodular pleural thickening surrounding the lung and invading through the chest wall. Note the variable degrees of enhancement of various parts of the tumor.

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Fig. 13.102  Malignant mesothelioma showing a very large pleural effusion that partially hides lobular neoplastic thickening of the pleura.

Fig. 13.103  Malignant mesothelioma causing widespread, uniform, mild thickening of the pleura and multiple fluid loculations. Note resemblance to empyema. treatment. CT is, therefore, considered the standard diagnostic study for pretreatment assessment.752 Involvement of mediastinal lymph nodes, chest wall invasion, bone destruction and direct extension to the pericardium, other mediastinal structures, or the opposite lung and pleura, and invasion through the diaphragm into the upper abdomen are all usually well seen on CT or MRI,747,749 but CT fails to show chest wall involvement in a proportion of patients.749 Extension to the contralateral thoracic cavity may also be seen. Extension beyond the pleural cavity is seen in approximately 11– 18% of patients at initial presentation, increasing to 30% or more during the course of the disease. The multiplanar imaging capability of MRI can be advantageous for demonstrating chest wall, dia-

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phragm, and mediastinal invasion. Extrathoracic spread can be diagnosed by FDG-PET imaging.753 Early changes on CT examinations include small pleural effusions undetected on chest radiography, thin soft tissue density layers on the mediastinal fat and subtle pleural or fissural nodules. In more advanced stages, the imaging findings typically consist of extensive nodular or lobular thickening of the pleura, which may conglomerate to form a circumferential lobular sheet of soft tissue density encasing the lung. The tumor often runs into the fissures, accompanied by varying amounts of pleural fluid, and the adjacent lung may show evidence of invasion. The nodularity/ lobulation of the pleural thickening is an important diagnostic feature (Fig. 13.99 and 13.101). Sometimes the accompanying pleural effusion is very large, and obscures the pleural masses on chest radiography (Fig. 13.102). In such cases, the chest radiographic appearances may be indistinguishable from other causes of pleural effusion. One point of distinction from other pleural effusions is that the neoplastic encasement of the lung may fix the position of the medi­astinum, so that shift away from the side of the effusion is not seen as often in patients with malignant mesothelioma as it is with nonmalignant causes of large pleural effusion. Indeed, the pleural shadowing is often associated with ipsilateral volume loss and a fixed mediastinum,754 and the hemithorax is frequently contracted owing to encasement of the lung by pleural tumor.721 The tumor nodules may become evident only on chest radiographs if air enters the pleural space following thoracentesis. At contrastenhanced CT, the soft tissue density of tumor tissue can be readily distinguished from the adjacent pleural effusion (Figs 13.101 and 13.103), but the nodules are not infrequently so tiny that they are unrecognizable and the only CT feature is, therefore, a pleural effusion. Calcification of the tumor is extremely rare, though reported. Asbestos-related pleural plaques may be seen in either pleural cavity, and calcified plaques may be engulfed by tumor.743 The typical MRI signal intensity is slightly greater than muscle on T1-weighted images and moderately greater than muscle on T2-weighted images. The tumor enhances significantly with gadolinium. MRI can help distinguish benign disease and other neoplasms from malignant mesothelioma, especially if contrastenhanced T1-weighted sequences with fat saturation are used, by showing the distribution of thickened pleural tissue.750 FDG-PET has proved highly sensitive in several small series of malignant mesothelioma,753,755 indicating a possible use of PET for initial diagnosis; the numbers of benign pleural processes included in these studies is, however, far too small to assess the false-positive rate. Overall, however, recent results support the potential role of PET in the workup of malignant mesothelioma.756,757 The differential diagnosis includes pleural involvement by other malignant tumors, notably bronchial adenocarcinoma, breast carcinoma, malignant thymoma, and lymphoma, as well as benign conditions such as asbestos-related benign pleural effusion, tuberculous pleural thickening, past or present empyema (Fig. 13.103), and asbestos-related pleural plaques. Unless there are other features to indicate the primary tumor, the distinction between adenocarcinoma of the lung and malignant mesothelioma cannot be made radiographically from the appearance of the pleural involvement alone. Although pleural involvement by breast carcinoma can also appear identical, there is usually no diagnostic difficulty because the primary tumor will have been diagnosed previously or will be clinically obvious. Pleural deposits of lymphoma and thymoma usually appear as more discrete localized masses than malignant mesothelioma, and the primary thymoma or other foci of lymphoma are visible or have previously been documented. The distinction from benign pleural thickening due to conditions such as previous tuberculosis or old hemothorax is usually readily made by noting the smoothness of the pleural shadowing in these disorders. A helpful feature in distinguishing benign pleural thickening from malignant mesothelioma is that circumferential pleural thickening and thickening extending over the mediastinal pleura are not infrequent in malignant mesothelioma but are rare in benign pleural disease.

Other Tumors of the Pleura The differentiation of early malignant pleural mesothelioma from noncalcified or partially calcified asbestos-related plaques can, on occasion, be difficult: some pleural plaques associated with advanced asbestosis can be large and irregular and can resemble mesothelioma.754 The uptake of FDG with PET imaging has been shown to correlate with prognosis; the higher the uptake the shorter the survival.758

OTHER TUMORS OF THE PLEURA Pleural and extrapleural lipomas are fairly unusual tumors with liposarcomas being distinctly unusual.759 The exact origin of pleural lipomas is not always clear, but they can arise from subpleural adipose tissue and be present as a local pleural mass. The benign lipoma is totally asymptomatic, though if it protrudes through the

rib interspaces it may produce a focal swelling and be palpable. On chest radiography, lipomas are seen as well-marginated, oval or lens-shaped soft tissue masses based on the pleura (Fig. 13.104). On CT,585,696,760,761 the uniform fat density, containing no more than a few linear strands of soft tissue density, makes the diagnosis straightforward (Fig. 13.104). Punctate calcification is occasionally visible at CT.760 Since they are soft lesions, they may change shape with respiration.762 On MRI, lipomas show standard fat signal, namely high signal on T1-weighted images and intermediate signal on T2-weighted images. Heterogeneity of density with a mixture of fat and soft tissue attenuation is the CT feature of liposarcoma. The commonest sarcomas of the pleura are metastatic. Primary pleural liposarcoma763 and osteosarcoma764 are rare tumors. The fat density within liposarcoma and the extensive calcification in osteo­ sarcoma on CT are of considerable diagnostic value. Plasmacytoma765 and epithelioid hemangioendothelioma766 are two other very rarely encountered pleural tumors which can appear similar to mesothelioma at imaging.767

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Fig. 13.104  Pleural lipoma. A, B, Frontal and oblique radiographs showing typical shape of a pleural mass. C, CT showing a similar mass composed mostly of fat (arrow), in another patient.

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Fig. 13.105  Typical hematogenous metastases. A, In a patient with colon carcinoma. B, In a patient with rhabdomyosarcoma of the anterior abdominal wall.

METASTASES Pulmonary metastases The incidence of pulmonary metastases varies with the primary tumor and the stage of disease. In autopsy series, the most common sources include tumors of the breast, colon, kidney, uterus, prostate, head, and neck.768 Tumors such as choriocarcinoma, osteosarcoma, Ewing sarcoma, testicular tumors, melanoma, and thyroid carcinoma have a high incidence of pulmonary metastases, but, because they are not as prevalent in the population, lung deposits from these tumors are encountered less frequently.768 The hallmark of bloodborne metastases to the lungs on imaging studies is one or more oval or spherical, discrete pulmonary nodules, maximal in the outer portions of the lungs (Figs 13.105 and 13.106). They vary in size from microscopic to many centimeters in diameter, are usually multiple, and have well or moderately welldefined smooth or irregular outlines.769 They are usually of soft tissue density, but may show calcification or conversely be of ground-glass density, if mucin producing, as in gastric carcinoma metastases770 or even lower density.771 A variety of other patterns are encountered.772 On occasion, particularly when due to metastatic adenocarcinoma, or if the metastases have bled into the surrounding lung, they show irregular or ill-defined edges or the features of airspace opacities. Metastases from highly vascular primary tumors, such as choriocarcinoma and angiosarcoma, may have a surrounding halo of ground-glass opacity, due to hemorrhage into the adjacent parenchyma.769 Irregular, sometimes frankly nodular, thickening of the interstitial pulmonary septa is a frequent finding on specimen CT.773 This finding, labeled the ‘beaded septum sign’, is regarded as suggestive of metastatic carcinoma. It corresponds to neoplastic invasion of the interlobular septa, their capillaries, and lymphatic vessels, and when widespread would be labeled lymphangitis carcinoma. Using CT, it is possible to show pulmonary vessels leading directly to individual metastases. The sign was observed in 30–75%

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Fig. 13.106  CT showing peripheral distribution of hematogenous metastases, in this case from a germ cell tumor of the testis.

of metastases in one series, the frequency depending on whether the lesion was in the upper, mid- or lower zone. In a CT–pathologic correlation, however, the sign was found in less than 20%.774 This variation is probably related to CT section thickness, thinner sections more accurately correlating with the macroscopic pathologic findings. The specificity of the sign is uncertain. Cavitation (Fig. 13.107) is most frequent in metastases from tumors of the uterine cervix, colon, and head and neck; the presence of cavitation is unrelated to the size of the metastasis. In general, metastases from squamous cell cancers originating in the head and neck undergo cavitation when quite small and may have strikingly thin walls, though many other cell types, such as adenocarcinoma, also show thin walls775 (Fig. 13.108). When multiple, it is usual for cavitary lesions to coexist with solid nodules.776 Metastatic sarcoma

Metastases

Fig. 13.107  CT of cavitating metastasis from squamous cell carcinoma (arrows).

Fig. 13.108  Cavitating metastasis from adenocarcinoma of the colon showing a relatively thin wall.

can also be accompanied by cavitation, and pneumothorax is then a relatively frequent complication.769 Detectable calcification in pulmonary metastases is very unusual, except in deposits from sarcomas, notably osteosarcoma and chondrosarcoma, in which the calcification is part of the tumor matrix just as it is in the primary tumor (Figs 13.109 and 13.110). Even in tumors such as breast, ovarian, colon, and thyroid carcinomas,

Fig. 13.109  Calcified metastases in a case of osteosarcoma (the primary tumor is visible in the upper right humerus). where calcification can be seen in the primary tumor, calcification in pulmonary metastases has been recognized in only a few isolated cases.777,778 Calcification may, however, be seen in successfully treated metastases. Miliary nodulation, a pattern of innumerable tiny nodules resembling miliary tuberculosis, is occasionally encountered but is decidedly rare (Fig. 13.111). Miliary metastases are most likely to be due to thyroid or renal carcinoma, bone sarcoma, trophoblastic disease, or melanoma. Very occasionally, metastases present radiographically as myriads of tiny shadows which summate to resemble pulmonary consolidation and may then be confused with infection, edema, or drug reaction. This pattern has been seen particularly with melanoma. One case of metastatic renal cell carcinoma has been reported in which innumerable tiny metastases resembling consolidation were confined to one lobe.779 In general, pulmonary metastases that respond to treatment with chemotherapy disappear and are no longer visible radiographically as nodules. Some may cavitate first. Rarely, however, a residual nodule of sterilized fibrous tissue may remain, and in this case there can be a major dilemma deciding whether treatment should be continued. This phenomenon has been observed particularly with choriocarcinoma and with testicular cancer. Thin-walled air cysts, also known as pulmonary lacunae, may persist in sites of metastases that have been successfully treated. This phenomenon is most frequently encountered with germ cell tumors of the testes (both seminoma and nonseminomatous germ cell tumors), though other tumors such as bladder carcinomas may, very rarely, show the phenomenon. Pulmonary lacunae were encountered in 7% of a series of 59 patients with teratomatous tumors of the testis.780 These air cysts seem to be different from cavitating metastases in that they appear to be healed deposits and do not contain viable tumor. The diagnosis depends on noting uniformly very thin, virtually imperceptible, walls to the cyst and no evidence of a mural nodule. Metastases from nonseminomatous germ cell tumors may enlarge despite responding successfully to chemotherapy.781 In such cases, they are transforming to a mature form of teratoma. The serum tumor markers are not raised, an important point in differential diagnosis.

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Fig. 13.110  Calcification and ossification in metastases from osteosarcoma. A, Posteroanterior radiograph. B, CT in the same patient. C, Another patient showing heavily calcified metastases in the lungs, mediastinum, and pleura on CT. D, Radionuclide bone scan showing matched uptake in the numerous metastases. (C, D, Courtesy of Dr. Abram Patterson, Roanoke, VA, USA.)

Parenchymal metastases occur at least 10 times as often as intrathoracic nodal metastases, and nodal disease alone is quite unusual, except in seminoma of the testis (Fig. 13.112).

Detection of pulmonary metastases The standard initial test for the detection of pulmonary metastases is the chest radiograph. A high-kilovoltage technique shows more lesions than low-kilovoltage films. Digital radiographic techniques, which lend themselves to computer processing, computer-aided diagnosis,75,782 and temporal subtraction, may also improve sensitivity.

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Computed tomography CT is currently the most sensitive technique for the detection of pulmonary metastases. Viewing the numerous images obtained with multidetector CT is best done at a computer console using cine (stack) mode. Stack mode viewing improves radiologists’ ability to detect small pulmonary nodules, notably by improving the distinction between normal blood vessels and nodules under 5  mm in diameter. The better contrast resolution of CT allows very small nodules to be demonstrated. Individual nodules as small as 2–3 mm in diameter may be visible on CT, whereas the lower limit for uncalcified nodules on chest radiographs is somewhere between 7  mm and

Metastases variety of extrathoracic primary tumors the great majority of nodules detected by CT in the presence of a normal chest radiograph surprisingly proved to be benign.786 General indications for CT include:

Fig. 13.111  Miliary metastases from breast carcinoma.

Fig. 13.112  Concomitant pulmonary and mediastinal metastases in a 17-year-old boy with a seminoma.

9 mm. But even with the best CT technique, very small metastases are undetectable. The increased sensitivity of CT for detecting metastases carries with it a decrease in specificity, since many of the smaller nodules, even in children,783 are benign lesions, notably granulomas, particularly in those parts of the world where fungal granulomas, such as histoplasmomas, are common.784 In countries such as the UK, where fungal granulomas are virtually nonexistent, the specificity of CT rises, but even in the UK caution is needed because 6% of noncalcified nodules revealed by CT in a series of 200 patients with seminoma of the testis were nonmetastatic in nature, presumably tuberculous granulomas;785 in another survey of patients with a

• Patients with a normal chest radiograph in whom the presence of pulmonary metastases would significantly alter patient management. CT scans of the chest are often obtained to find neoplastic deposits not visible on chest radiographs in patients with tumors such as osteosarcoma, choriocarcinoma, and testicular germ cell tumors, all of which have a significant incidence of pulmonary metastases at presentation, but which may have no detectable metastatic spread to other sites. The incidence of pulmonary metastases from seminoma is low, but since the incidence of mediastinal nodal disease can be as high as 12.5%, chest CT is recommended for initial staging as well as follow-up for potential relapse. Locally advanced melanoma is cited as an example of a tumor with high propensity to metastasize to the lungs, but whether routine chest CT is justified in cases with a normal chest radiograph is far from clear. In one series of 42 patients with locally advanced melanoma and either a solitary pulmonary nodule or no abnormality on chest radiographs, CT scanning showed further nodules believed to be metastases in approximately one-third of patients.787 The authors did, however, point out that in only one of the 42 patients did the discovery of an additional nodule by CT alter the management of the patient. In another similar sized series there was a change in management in 26% of patients following the CT scan.788 The incidence of pulmonary metastases in patients with head and neck carcinoma, superficial melanoma, and carcinomas of the kidney, bladder, and female genital tract is relatively low. In patients with these tumors, CT should be reserved for those with advanced local disease and thoracic symptoms. Similarly, patients with carcinoma of the gastrointestinal tract, breast, or prostate are unlikely to have pulmonary metastases in the absence of metastases to such organs as the liver and bones, and CT should, therefore, be reserved for those patients in whom thoracic involvement is uncertain on chest radiographs and in whom the information would change management. • Patients who are being considered for surgical resection of known pulmonary metastases. CT is clearly indicated to demonstrate all pulmonary metastases when pulmonary surgical resection is being considered. Currently, such surgery is recommended when the primary tumor has been (or can be) definitively treated and all known metastatic disease can be safely encompassed by the projected pulmonary resection. Extensive surgical experience indicates that resection of pulmonary metastases can be a safe and potentially curative procedure. Resection appears most beneficial for tumors of the urinary tract, testicular and uterine neoplasms, colon and rectal carcinoma, tumors of the head and neck, and various sarcomas, notably osteogenic sarcoma. • Distinguishing solitary from multiple pulmonary nodules where the diagnostic dilemma is metastasis versus new primary lung cancer. A solitary pulmonary nodule may represent a primary bronchogenic carcinoma rather than a metastasis, even in a patient with a known extrathoracic primary tumor. Clearly, the relative probabilities depend on the likelihood of the specific primary tumor metastasizing to the lungs and factors such as the smoking habits of the patient, and the interval between the original diagnosis and the appearance of the nodule.

Magnetic resonance imaging MRI currently has a limited role for detecting pulmonary metastases. Even though Feuerstein et al.,789 using a 0.5 T magnet, showed that MRI could be at least as sensitive as CT in detecting metastases, the general view is that CT, particularly using volumetric scanning techniques, is the most cost-effective method. There are, however, a few potential specific advantages of MRI: the absence of ionizing

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura radiation with MRI is a clear-cut advantage over CT, particularly for young patients undergoing repeated follow-up scans, and, secondly, MR imaging can sometimes distinguish between small centrally located metastases and adjacent normal blood vessels, based on the signal of flowing blood in arteries and veins. Recent technical advances can indeed overcome early limitations in using MRI for the detection of lung metastases, but relatively long acquisition times are still a drawback of this technique.790

Radionuclide imaging Radionuclide and PET imaging can be useful for demonstrating intrathoracic metastases791–793 when the neoplasms concentrate the chosen radionuclide.

Endobronchial metastases Metastases to the walls of a large bronchus are unusual. Braman and Whitcomb794 found the incidence to be only 2% in a very large series of patients who had died from solid neoplasms. The most common primary sites appear to be kidney, breast, colon, and rectum,795,796 but endobronchial metastases have been reported from melanoma797,798 and primary neoplasms of the stomach, thyroid, cervix, prostate, and testis. The clinical and imaging features are indistinguishable from those produced by other central tumors, namely cough, wheezing, hemoptysis, atelectasis, and obstructive pneumonitis795,799 (Fig. 13.113). On chest radiographs the lesion itself is not visible and the evidence for an endobronchial metastasis will be obstructive atelectasis. The endobronchial metastasis itself may be visible at CT.800,801

Lymphangitis carcinomatosa Lymphangitis carcinomatosa is the name given to permeation of pulmonary lymphatics by neoplastic cells. The most common tumors that spread in this manner are carcinomas of the bronchus, breast, pancreas, stomach, colon, and prostate. The route by which

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tumor cells reach the intrapulmonary lymphatics is debated. Spencer,273 when reviewing the subject, concluded that some cases are caused by bloodborne emboli that lodge in smaller pulmonary arteries and subsequently spread through the vessel walls into the lymphatic vessels. Some tumors, notably upper abdominal cancers, appear to spread by way of lymph vessels to hilar nodes and thence in retrograde fashion into the pulmonary lymphatics. Primary carcinoma of the lung can invade the pulmonary lymphatics directly and may give rise to segmental or lobar lymphangitis carcinomatosa as well as involving one or both lungs diffusely. Histologically, there is interstitial thickening of the interlobular septa due to a combination of tumor cells, desmoplastic response, and dilated lymphatics. The lymphatic obstruction can lead to interstitial edema. The hilar lymph nodes may, or may not, show histologic evidence of tumor involvement. The chest radiographic findings are fine reticulonodular opacities and/or thickened septal lines (Figs 13.114 and 13.115). These signs occur because of a combination of dilated lymphatics and interstitial edema, together with opacities due to the tumor cells themselves and any desmoplastic response. Another useful sign of lymphangitis carcinomatosa is subpleural edema resulting from lymphatic obstruction by tumor cells, a feature that is most readily visible as thickening of the fissures. The process can be unilateral (Fig. 13.116), particularly in cases resulting from lung cancer, but the pulmonary opacities are more often bilateral and symmetrical. Pleural effusion is very common. CT is more sensitive than chest radiography for the detection of lymphangitic spread and may show changes in patients whose chest radiograph is normal. CT shows nonuniform, often nodular, thickening of the interlobular septa and irregular thickening of the bronchovascular bundles (Fig. 13.117).773,802 There are often patchy airspace opacities. Small, peripherally located, wedge-shaped densities are sometimes seen as well; they may represent volume averaging of thickened septa. Nodular shadows may be seen scattered through the parenchyma. The distribution of the changes varies greatly. The abnormalities may involve all zones of both lungs or they may be centrally or peripherally predominant; sometimes they are confined to a lobe or one lung.

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Fig. 13.113  A, B, Endobronchial metastases from carcinoma of the kidney causing left upper lobe collapse.

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Metastases

Fig. 13.114  Lymphangitis carcinomatosa from carcinoma of the prostate showing bilateral centrally predominant reticulonodular opacities.

Fig. 13.116  Unilateral lymphangitis carcinomatosa from bronchial carcinoma. Note reticulonodular opacities and subpleural thickening of minor fissure and of the lung in the right cardiophrenic angle. Septal lines are also present.

Fig. 13.115  Lymphangitis carcinomatosa from carcinoma of the breast showing randomly distributed reticulonodular opacities with areas of confluence.

No studies have formally reported the sensitivity of CT for the diagnosis of lymphangitis carcinomatosa, but it is clear from autopsy correlation that, in patients with discrete pulmonary metastases, lymphangitis carcinomatosa is often present in areas of the lung which appear normal at CT.769 Hilar lymph node enlargement is seen in only some of the patients, five of the 12 cases in one series, supporting the supposition that lymphangitis carcinomatosa is sometimes the result of hematogenous spread of tumor to the interstitium. The major differential diagnosis of lymphangitis carcinomatosa is pulmonary edema. The nodularity of the septal thickening at CT

Fig. 13.117  Lymphangitis carcinomatosa. CT shows variably thickened interlobular septa (arrows).

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Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

Fig. 13.118  Pleural metastases shown as tumor nodules by CT in a patient with metastatic melanoma. The tumor was widely metastatic, involving not only the pleura bilaterally but also mediastinal lymph nodes.

is helpful and an important differential diagnostic feature from pulmonary edema is that many of the acini subtended by thickened interlobular septa are normally aerated. On chest radiographs, at least in those cases without visible lung cancer or lymphadenopathy, the findings may be so similar to pulmonary edema that distinguishing between the two conditions can be impossible. Clearly, knowledge of the clinical or radiographic progression of disease is helpful and frequently decisive.

Malignant pleural effusion and pleural metastases Carcinomatous metastases to the pleura can originate from almost any organ, but the lung appears to be the most frequent primary site, followed by breast, pancreas, stomach, and ovary.803 Carcinoma of the lung and breast, together with lymphoma, accounts for approximately 75% of malignant pleural effusions.804 Leukemic deposits and sarcomatous metastases are rare causes of pleural effusion.805,806 The responsible neoplasm usually involves both the visceral and parietal pleura. A malignant tumor can lead to a pleural effusion in several different ways.803,807 Decreased lymphatic drainage due to blockage of the small lymphatic stomas that drain the pleura is the probable mechanism in many cases, and obstruction to lymphatic drainage through mediastinal nodes which have been infiltrated by tumor is also believed to play a major role. Another, probably less common, mechanism is increased permeability of the pleural surfaces because of the presence of metastases so that more protein enters the pleural cavity than can be removed. Malignant tumors can also produce pleural effusions by obstructing the thoracic duct, in which case the resulting pleural effusion will be chylous. Not all patients with pleural metastases have pleural effusions. Meyer808 found that only 60% of autopsy patients with pleural

Fig. 13.119  Pleural metastasis from breast carcinoma. The patient was treated for right breast carcinoma; pleural metastatic disease occurred on the left, causing diffuse nodular pleural and fissural thickening (arrows).

metastases had pleural effusions and that the presence of a pleural effusion was more closely related to neoplastic invasion of the mediastinal lymph nodes than to the extent of pleural involvement by nodular metastases. Clinically, the most frequent symptom of pleural effusion resulting from metastases is dyspnea on exertion. Chest pain is relatively uncommon, being seen in less than a quarter of patients.809 Pleural effusions resulting from malignant tumor contain high levels of protein and may show a low pH, a low glucose level, and a high lactate dehydrogenase level. Approximately 10% of patients with malignant pleural effusion have an elevated level of amylase in the pleural fluid, even though the primary tumor is usually not in the pancreas. Bleeding may occur into the effusion, and typically the fluid contains a large number of lymphocytes. Unlike tuberculous effusions, which are also lymphocyte predominant, malignant effusions often contain mesothelial cells. The presence of definite malignant cells on cytologic examination or pleural biopsy removes all doubt about the diagnosis. The percentage of cases in which cytologic study of the pleural fluid establishes the diagnosis ranges from 40% to 80%. The rate varies with the cell type, the yield being low with squamous tumors.807 Usually the finding on chest radiograph, CT, and ultrasound is free or loculated pleural effusion without any specific features to the effusion itself. There may be recognizable tumor nodules in the pleura on CT (Fig. 13.118). Widespread pleural thickening, resembling mesothelioma, may be seen particularly with metastases from breast carcinoma (Fig. 13.119) and thymoma.

REFERENCES 1. Jemal A, Siegel R, Ward E, et al. Cancer statistics. CA Cancer J Clin 2008;58:71–96. 2. Travis WD, Brambilla C, Muller-Hermelink HK, et al. World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press, 2004. 3. Hiroshima K, Iyoda A, Shibuya K, et al. Prognostic significance of neuroendocrine

864

differentiation in adenocarcinoma of the lung. Ann Thorac Surg 2002;73:1732–1735. 4. Iyoda A, Hiroshima K, Baba M, et al. Pulmonary large cell carcinomas with neuroendocrine features are high-grade neuroendocrine tumors. Ann Thorac Surg 2002;73:1049–1054. 5. Takei H, Asamura H, Maeshima A, et al. Large cell neuroendocrine carcinoma of

the lung: a clinicopathologic study of eighty-seven cases. J Thorac Cardiovasc Surg 2002;124:285–292. 6. Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest 2003;123:S21–S49. 7. Doll R, Peto R, Boreham J, et al. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 2004;328:1519.

References 8. Wilkinson P, Hansell DM, Janssens J, et al. Is lung cancer associated with asbestos exposure when there are no small opacities on the chest radiograph? Lancet 1995; 345:1074–1078. 9. Hubbard R, Venn A, Lewis S, et al. Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. Am J Respir Crit Care Med 2000;161:5–8. 10. Brambilla C. From surgical to molecular scalpel: ERJ lung cancer series for 2009. Eur Respir J 2009;33:9–10. 11. Bepler G. Lung cancer epidemiology and genetics. J Thorac Imaging 1999;14:228–234. 12. Smith RA, Glynn TJ. Epidemiology of lung cancer. Radiol Clin North Am 2000;38: 453–470. 13. Lee HJ, Im JG, Ahn JM, et al. Lung cancer in patients with idiopathic pulmonary fibrosis: CT findings. J Comput Assist Tomogr 1996;20:979–982. 14. Choi YH, Leung AN, Miro S, et al. Primary bronchogenic carcinoma after heart or lung transplantation: radiologic and clinical findings. J Thorac Imaging 2000;15:36–40. 15. Collins J, Kazerooni EA, Lacomis J, et al. Bronchogenic carcinoma after lung transplantation: frequency, clinical characteristics, and imaging findings. Radiology 2002;224:131–138. 16. Haque AK. Pathology of carcinoma of lung: an update on current concepts. J Thorac Imaging 1991;7:9–20. 17. Barsky SH, Huang SJ, Bhuta S. The extracellular matrix of pulmonary scar carcinomas is suggestive of a desmoplastic origin. Am J Pathol 1986;124:412–419. 18. Didkowska J, Manczuk M, McNeill A, et al. Lung cancer mortality at ages 35–54 in the European Union: ecological study of evolving tobacco epidemics. BMJ 2005;331: 189–191. 19. Beckles MA, Spiro SG, Colice GL, et al. Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes. Chest 2003;123:S97–S104. 20. Jett JR, Cortese DA, Fontana RS. Lung cancer: current concepts and prospects. CA Cancer J Clin 1983;33:74–86. 21. Filderman AE, Shaw C, Matthay RA. Lung cancer. Part I. Etiology, pathology, natural history, manifestations, and diagnostic techniques. Invest Radiol 1986;21:80–90. 22. Hiraki A, Ueoka H, Takata I, et al. Hypercalcemia-leukocytosis syndrome associated with lung cancer. Lung Cancer 2004;43:301–307. 23. Auerbach O, Garfinkel L. The changing pattern of lung carcinoma. Cancer 1991;68: 1973–1977. 24. Byrd RB, Carr DT, Miller WE, et al. Radiographic abnormalities in carcinoma of the lung as related to histological cell type. Thorax 1969;24:573–575. 25. Lehar TJ, Carr DT, Miller WE, et al. Roentgenographic appearance of bronchogenic adenocarcinoma. Am Rev Respir Dis 1967;96:245–248. 26. Theros EG. 1976 Caldwell Lecture: varying manifestation of peripheral pulmonary neoplasms: a radiologic-pathologic correlative study. AJR Am J Roentgenol 1977;128:893–914. 27. Kundel HL. Predictive value and threshold detectability of lung tumors. Radiology 1981;139:25–29.

28. Muhm JR, Miller WE, Fontana RS, et al. Lung cancer detected during a screening program using four-month chest radiographs. Radiology 1983;148:609–615. 29. MacMahon H, Austin JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395–400. 30. Takashima S, Sone S, Li F, et al. Small solitary pulmonary nodules (< or =1 cm) detected at population-based CT screening for lung cancer: reliable high-resolution CT features of benign lesions. AJR Am J Roentgenol 2003;180:955–964. 31. Klein JS, Braff S. Imaging evaluation of the solitary pulmonary nodule. Clin Chest Med 2008;29:15–38, v. 32. Libby DM, Smith JP, Altorki NK, et al. Managing the small pulmonary nodule discovered by CT. Chest 2004;125:1522– 1529. 33. Heitzman ER, Markarian B, Raasch BN, et al. Pathways of tumor spread through the lung: radiologic correlations with anatomy and pathology. Radiology 1982; 144:3–14. 34. Kuriyama K, Tateishi R, Doi O, et al. CT-pathologic correlation in small peripheral lung cancers. AJR Am J Roentgenol 1987;149:1139–1143. 35. Aoki T, Tomoda Y, Watanabe H, et al. Peripheral lung adenocarcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival. Radiology 2001;220:803–809. 36. Mori K, Saitou Y, Tominaga K, et al. Small nodular lesions in the lung periphery: new approach to diagnosis with CT. Radiology 1990;177:843–849. 37. Woodring JH, Bernardy MO, Loh FK. Mucoid impaction of the bronchi. Australas Radiol 1985;29:234–239. 38. Marriott AE, Weisbrod G. Bronchogenic carcinoma associated with pulmonary infarction. Radiology 1982;145:593–597. 39. Rossi SE, Goodman PC, Franquet T. Nonthrombotic pulmonary emboli. AJR Am J Roentgenol 2000;174:1499–1508. 40. Erasmus JJ, McAdams HP, Connolly JE. Solitary pulmonary nodules. Part II. Evaluation of the indeterminate nodule. RadioGraphics 2000;20:59–66. 41. Good CA. The solitary pulmonary nodule: a problem of management. Radiol Clin North Am 1963;1:429–438. 42. Zerhouni EA, Stitik FP, Siegelman SS, et al. CT of the pulmonary nodule: a cooperative study. Radiology 1986;160: 319–327. 43. Penkrot RJ, Gordon R. Chest xerotomography: evaluation of calcification within lung nodules. Invest Radiol 1980; 15:517–519. 44. Grewal RG, Austin JH. CT demonstration of calcification in carcinoma of the lung. J Comput Assist Tomogr 1994;18:867–871. 45. Woodring JH, Fried AM, Chuang VP. Solitary cavities of the lung: diagnostic implications of cavity wall thickness. AJR Am J Roentgenol 1980;135:1269–1271. 46. Ryu JH, Swensen SJ. Cystic and cavitary lung diseases: focal and diffuse. Mayo Clin Proc 2003;78:744–752. 47. Chaudhuri MR. Primary pulmonary cavitating carcinomas. Thorax 1973;28: 354–366.

48. Felson B, Wiot JF. Some less familiar roentgen manifestations of carcinoma of the lung. Semin Roentgenol 1977;12: 187–206. 49. Byrd RB, Miller WE, Carr DT, et al. The roentgenographic appearance of small cell carcinoma of the bronchus. Mayo Clin Proc 1968;43:337–341. 50. Gaeta M, Blandino A, Scribano E, et al. Mucinous cystadenocarcinoma of the lung: CT-pathologic correlation in three cases. J Comput Assist Tomogr 1999;23: 641–643. 51. Henschke CI, Yankelevitz DF, Mirtcheva R, et al. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am J Roentgenol 2002;178:1053–1057. 52. Kuriyama K, Seto M, Kasugai T, et al. Ground-glass opacity on thin-section CT: value in differentiating subtypes of adenocarcinoma of the lung. AJR Am J Roentgenol 1999;173:465–469. 53. Yabuuchi H, Murayama S, Sakai S, et al. Resected peripheral small cell carcinoma of the lung: computed tomographic-histologic correlation. J Thorac Imaging 1999;14: 105–108. 54. Aoki T, Nakata H, Watanabe H, et al. Evolution of peripheral lung adenocarcinomas: CT findings correlated with histology and tumor doubling time. AJR Am J Roentgenol 2000;174:763–768. 55. Noguchi M, Morikawa A, Kawasaki M, et al. Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer 1995;75:2844–2852. 56. Chun EJ, Lee HJ, Kang WJ, et al. Differentiation between malignancy and inflammation in pulmonary ground-glass nodules: the feasibility of integrated (18) F-FDG PET/CT. Lung Cancer 2009;65: 180–186. 57. Funama Y, Awai K, Liu D, et al. Detection of nodules showing ground-glass opacity in the lungs at low-dose multidetector computed tomography: phantom and clinical study. J Comput Assist Tomogr 2009;33:49–53. 58. Kim TJ, Goo JM, Lee KW, et al. Clinical, pathological and thin-section CT features of persistent multiple ground-glass opacity nodules: comparison with solitary ground-glass opacity nodule. Lung Cancer 2009;64:171–178. 59. Lee HJ, Goo JM, Lee CH, et al. Predictive CT findings of malignancy in ground-glass nodules on thin-section chest CT: the effects on radiologist performance. Eur Radiol 2009;19:552–560. 60. Lee KW, Im JG, Kim TJ, et al. A new method of measuring the amount of soft tissue in pulmonary ground-glass opacity nodules: a phantom study. Korean J Radiol 2008;9:219–225. 61. Ohtsuka T, Watanabe K, Kaji M, et al. A clinicopathological study of resected pulmonary nodules with focal pure ground-glass opacity. Eur J Cardiothorac Surg 2006;30:160–163. 62. Park JH, Lee KS, Kim JH, et al. Malignant pure pulmonary ground-glass opacity nodules: prognostic implications. Korean J Radiol 2009;10:12–20. 63. Yoon HE, Fukuhara K, Michiura T, et al. Pulmonary nodules 10mm or less in diameter with ground-glass opacity

865

Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

64.

65.

66.

67.

68.

69.

70.

71.

72.

73.

74.

75.

76. 77. 78.

79.

80.

866

component detected by high-resolution computed tomography have a high possibility of malignancy. Jpn J Thorac Cardiovasc Surg 2005;53:22–28. Yoshida J, Nagai K, Yokose T, et al. Limited resection trial for pulmonary ground-glass opacity nodules: fifty-case experience. J Thorac Cardiovasc Surg 2005;129:991–996. Kuriyama K, Tateishi R, Doi O, et al. Prevalence of air bronchograms in small peripheral carcinomas of the lung on thin-section CT: comparison with benign tumors. AJR Am J Roentgenol 1991;156: 921–924. Zwirewich CV, Vedal S, Miller RR, et al. Solitary pulmonary nodule: high-resolution CT and radiologic-pathologic correlation. Radiology 1991;179:469–476. Choi JA, Kim JH, Hong KT, et al. CT bronchus sign in malignant solitary pulmonary lesions: value in the prediction of cell type. Eur Radiol 2000;10:1304–1309. Nambu A, Miyata K, Ozawa K, et al. Air-containing space in lung adenocarcinoma: high-resolution computed tomography findings. J Comput Assist Tomogr 2002;26:1026–1031. Tateishi U, Nishihara H, Watanabe S, et al. Tumor angiogenesis and dynamic CT in lung adenocarcinoma: radiologicpathologic correlation. J Comput Assist Tomogr 2001;25:23–27. Swensen SJ, Brown LR, Colby TV, et al. Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material. Radiology 1995;194:393–398. Swensen SJ, Brown LR, Colby TV, et al. Lung nodule enhancement at CT: prospective findings. Radiology 1996;201: 447–455. Hittmair K, Eckersberger F, Klepetko W, et al. Evaluation of solitary pulmonary nodules with dynamic contrast-enhanced MR imaging: a promising technique. Magn Reson Imaging 1995;13:923–933. Miles KA, Griffiths MR, Fuentes MA. Standardized perfusion value: universal CT contrast enhancement scale that correlates with FDG PET in lung nodules. Radiology 2001;220:548–553. Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am J Roentgenol 1997;168: 325–328. MacMahon H, Engelmann R, Behlen FM, et al. Computer-aided diagnosis of pulmonary nodules: results of a large-scale observer test. Radiology 1999;213:723–726. McAdams HP, Samei E, Dobbins J 3rd, et al. Recent advances in chest radiography. Radiology 2006;241:663–683. Lillington GA. Management of the solitary pulmonary nodule. Hosp Pract (Off Ed) 1993;28:41–48. Lillington GA, Caskey CI. Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med 1993;14:111–119. Gorlova O, Peng B, Yankelevitz D, et al. Estimating the growth rates of primary lung tumours from samples with missing measurements. Stat Med 2005;24:1117– 1134. Kostis WJ, Reeves AP, Yankelevitz DF, et al. Three-dimensional segmentation and growth-rate estimation of small pulmonary

81. 82.

83.

84.

85.

86.

87.

88.

89.

90. 91.

92.

93.

94.

95. 96.

97.

nodules in helical CT images. IEEE Trans Med Imaging 2003;22:1259–1274. Henschke CI, Yankelevitz DF. CT screening for lung cancer. Radiol Clin North Am 2000;38:487–495. Revel MP, Bissery A, Bienvenu M, et al. Are two-dimensional CT measurements of small noncalcified pulmonary nodules reliable? Radiology 2004;231:453–458. Revel MP, Lefort C, Bissery A, et al. Pulmonary nodules: preliminary experience with three-dimensional evaluation. Radiology 2004;231:459–466. Yankelevitz DF, Reeves AP, Kostis WJ, et al. Small pulmonary nodules: volumetrically determined growth rates based on CT evaluation. Radiology 2000;217:251–256. Padhani AR, Ollivier L. The RECIST (Response Evaluation Criteria in Solid Tumors) criteria: implications for diagnostic radiologists. Br J Radiol 2001;74: 983–986. Burke M, Fraser R. Obstructive pneumonitis: a pathologic and pathogenetic reappraisal. Radiology 1988; 166:699–704. Shin MS, Ho KJ. CT fluid bronchogram: observation in postobstructive pulmonary consolidation. Clin Imaging 1992;16: 109–113. Higashino T, Ohno Y, Takenaka D, et al. Thin-section multiplanar reformats from multidetector-row CT data: utility for assessment of regional tumor extent in non-small cell lung cancer. Eur J Radiol 2005;56:48–55. Erasmus JJ, Sabloff BS. CT, positron emission tomography, and MRI in staging lung cancer. Clin Chest Med 2008;29: 39–57, v. Laurent F, Montaudon M, Corneloup O. CT and MRI of lung cancer. Respiration 2006;73:133–142. Bourgouin PM, McLoud TC, Fitzgibbon JF, et al. Differentiation of bronchogenic carcinoma from postobstructive pneumonitis by magnetic resonance imaging: histopathologic correlation. J Thorac Imaging 1991;6:22–27. Woodring JH. Determining the cause of pulmonary atelectasis: a comparison of plain radiography and CT. AJR Am J Roentgenol 1988;150:757–763. Byrd RB, Miller WE, Carr DT, et al. The roentgenographic appearance of squamous cell carcinoma of the bronchus. Mayo Clin Proc 1968;43:327–332. Byrd RB, Miller WE, Carr DT, et al. The roentgenographic appearance of large cell carcinoma of the bronchus. Mayo Clin Proc 1968;43:333–336. Sobin LH, Wittekind CH. TNM classification of malignant tumors. New York: Wiley-Liss, 1997:91. Goldstraw P, Crowley J, Chansky K, et al. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007;2:706–714. Groome PA, Bolejack V, Crowley JJ, et al. The IASLC lung cancer staging project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the

98. 99. 100.

101. 102. 103. 104.

105. 106.

107.

108.

109.

110.

111.

112.

113.

114.

115.

forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2007;2:694–705. Simon GR, Wagner H. Small cell lung cancer. Chest 2003;123:S259–S271. Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997;111:1710–1717. Naruke T, Tsuchiya R, Kondo H, et al. Prognosis and survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience. Ann Thorac Surg 2001;71: 1759–1764. Park BJ, Louie O, Altorki N. Staging and the surgical management of lung cancer. Radiol Clin North Am 2000;38:545–561, ix. Smythe WR. Treatment of stage I non-small cell lung carcinoma. Chest 2003;123:S181–S187. Scott WJ, Howington J, Movsas B. Treatment of stage II non-small cell lung cancer. Chest 2003;123:S188–S201. End A, Hollaus P, Pentsch A, et al. Bronchoplastic procedures in malignant and nonmalignant disease: multivariable analysis of 144 cases. J Thorac Cardiovasc Surg 2000;120:119–127. Robinson LA, Wagner H Jr, Ruckdeschel JC. Treatment of stage IIIA non-small cell lung cancer. Chest 2003;123:S202–S220. Jett JR, Scott WJ, Rivera MP, et al. Guidelines on treatment of stage IIIB non-small cell lung cancer. Chest 2003; 123:S221–S225. Spiro SG, Porter JC. Lung cancer: where are we today? Current advances in staging and nonsurgical treatment. Am J Respir Crit Care Med 2002;166:1166–1196. Inoue M, Miyoshi S, Yasumitsu T, et al. Surgical results for small cell lung cancer based on the new TNM staging system. Thoracic Surgery Study Group of Osaka University, Osaka, Japan. Ann Thorac Surg 2000;70:1615–1619. Giordano KF, Jatoi A, Adjei AA, et al. Ramifications of severe organ dysfunction in newly diagnosed patients with small cell lung cancer: contemporary experience from a single institution. Lung Cancer 2005; 49:209–215. Silvestri GA, Tanoue LT, Margolis ML, et al. The noninvasive staging of non-small cell lung cancer: the guidelines. Chest 2003;123:S147–S156. Laroche C, Fairbairn I, Moss H, et al. Role of computed tomographic scanning of the thorax prior to bronchoscopy in the investigation of suspected lung cancer. Thorax 2000;55:359–363. Patz EF Jr, Erasmus JJ, McAdams HP, et al. Lung cancer staging and management: comparison of contrast-enhanced and nonenhanced helical CT of the thorax. Radiology 1999;212:56–60. Cascade PN, Gross BH, Kazerooni EA, et al. Variability in the detection of enlarged mediastinal lymph nodes in staging lung cancer: a comparison of contrast-enhanced and unenhanced CT. AJR Am J Roentgenol 1998;170:927–931. Remy-Jardin M, Duyck P, Remy J, et al. Hilar lymph nodes: identification with spiral CT and histologic correlation. Radiology 1995;196:387–394. Lahde S, Paivansalo M, Rainio P. CT for predicting the resectability of lung cancer.

References

116.

117.

118.

119.

120.

121.

122. 123.

124.

125.

126.

127.

128.

129. 130.

131.

132.

A prospective study. Acta Radiol 1991; 32:449–454. Lewis JW Jr, Pearlberg JL, Beute GH, et al. Can computed tomography of the chest stage lung cancer? Yes and no. Ann Thorac Surg 1990;49:591–595. Fadel E, Yildizeli B, Chapelier AR, et al. Sleeve lobectomy for bronchogenic cancers: factors affecting survival. Ann Thorac Surg 2002;74:851–858. Quint LE, Glazer GM, Orringer MB. Central lung masses: prediction with CT of need for pneumonectomy versus lobectomy. Radiology 1987;165:735–738. Chen CY, Kao CH, Hsu NY, et al. Prediction of probability of pneumonectomy for lung cancer using Tc-99m MAA perfusion lung imaging. Clin Nucl Med 1994;19:1094–1097. Ryo UY. Prediction of postoperative loss of lung function in patients with malignant lung mass. Quantitative regional ventilation-perfusion scanning. Radiol Clin North Am 1990;28:657–663. Ohno Y, Hatabu H, Higashino T, et al. Dynamic perfusion MRI versus perfusion scintigraphy: prediction of postoperative lung function in patients with lung cancer. AJR Am J Roentgenol 2004;182:73–78. Detterbeck FC, Jones DR, Kernstine KH, et al. Lung cancer. Special treatment issues. Chest 2003;123:S244–S258. Klepetko W, Wisser W, Birsan T, et al. T4 lung tumors with infiltration of the thoracic aorta: is an operation reasonable? Ann Thorac Surg 1999;67:340–344. Spaggiari L, Regnard JF, Magdeleinat P, et al. Extended resections for bronchogenic carcinoma invading the superior vena cava system. Ann Thorac Surg 2000;69:233–236. Dartevelle P, Chapelier A, Navajas M, et al. Replacement of the superior vena cava with polytetrafluoroethylene grafts combined with resection of mediastinalpulmonary malignant tumors. Report of thirteen cases. J Thorac Cardiovasc Surg 1987;94:361–366. Grunenwald D, Mazel C, Girard P, et al. Radical en bloc resection for lung cancer invading the spine. J Thorac Cardiovasc Surg 2002;123:271–279. Yokoi K, Tsuchiya R, Mori T, et al. Results of surgical treatment of lung cancer involving the diaphragm. J Thorac Cardiovasc Surg 2000;120:799–805. Onitsuka H, Tsukuda M, Araki A, et al. Differentiation of central lung tumor from postobstructive lobar collapse by rapid sequence computed tomography. J Thorac Imaging 1991;6:28–31. Haramati LB, White CS. MR imaging of lung cancer. Magn Reson Imaging Clin North Am 2000;8:43–57, viii. Sachs S, Bilfinger TV. The impact of positron emission tomography on clinical decision making in a university-based multidisciplinary lung cancer practice. Chest 2005;128:698–703. Houston JG, Fleet M, McMillan N, et al. Ultrasonic assessment of hemidiaphragmatic movement: an indirect method of evaluating mediastinal invasion in non-small cell lung cancer. Br J Radiol 1995;68:695–699. Murata K, Takahashi M, Mori M, et al. Chest wall and mediastinal invasion by lung cancer: evaluation with multisection

133.

134.

135. 136.

137.

138.

139.

140.

141.

142.

143. 144.

145.

146.

147.

148.

expiratory dynamic CT. Radiology 1994; 191:251–255. Ohtsuka T, Minami M, Nakajima J, et al. Cine computed tomography for evaluation of tumors invasive to the thoracic aorta: seven clinical experiences. J Thorac Cardiovasc Surg 1996;112:190–192. Yokoi K, Mori K, Miyazawa N, et al. Tumor invasion of the chest wall and mediastinum in lung cancer: evaluation with pneumothorax CT. Radiology 1991; 181:147–152. Molnar TF, Juhasz E, Benko I, et al. Predictive value of MRI in lung cancer. Acta Chir Hung 1999;38:95–99. Yi CA, Jeon TY, Lee KS, et al. 3-T MRI: usefulness for evaluating primary lung cancer and small nodules in lobes not containing primary tumors. AJR Am J Roentgenol 2007;189:386–392. Takahashi K, Furuse M, Hanaoka H, et al. Pulmonary vein and left atrial invasion by lung cancer: assessment by breath-hold gadolinium-enhanced three-dimensional MR angiography. J Comput Assist Tomogr 2000;24:557–561. Ohno Y, Adachi S, Motoyama A, et al. Multiphase ECG-triggered 3D contrastenhanced MR angiography: utility for evaluation of hilar and mediastinal invasion of bronchogenic carcinoma. J Magn Reson Imaging 2001;13:215–224. Cangemi V, Volpino P, D’Andrea N, et al. Results of surgical treatment of stage IIIA non-small cell lung cancer. Eur J Cardiothorac Surg 1995;9:352–359. Burkhart H, Allen M, Nichols F, et al. Results of en bloc resection for bronchogenic carcinoma with chest wall invasion. J Thorac Cardiovasc Surg 2002; 123:670–675. Guyatt GH, Lefcoe M, Walter S, et al. Interobserver variation in the computed tomographic evaluation of mediastinal lymph node size in patients with potentially resectable lung cancer. Canadian Lung Oncology Group. Chest 1995;107:116–119. Akata S, Kajiwara N, Park J, et al. Evaluation of chest wall invasion by lung cancer using respiratory dynamic MRI. J Med Imaging Radiat Oncol 2008;52:36–39. Dilege S, Toker A, Tanju S, et al. Chest wall invasion in lung cancer patients. Acta Chir Belg 2003;103:396–400. Matsuoka H, Nishio W, Okada M, et al. Resection of chest wall invasion in patients with non-small cell lung cancer. Eur J Cardiothorac Surg 2004;26:1200–1204. Roviaro G, Varoli F, Grignani F, et al. Non-small cell lung cancer with chest wall invasion: evolution of surgical treatment and prognosis in the last 3 decades. Chest 2003;123:1341–1347. Shiotani S, Sugimura K, Sugihara M, et al. Diagnosis of chest wall invasion by lung cancer: useful criteria for exclusion of the possibility of chest wall invasion with MR imaging. Radiat Med 2000;18:283–290. Watanabe A, Shimokata K, Saka H, et al. Chest CT combined with artificial pneumothorax: value in determining origin and extent of tumor. AJR Am J Roentgenol 1991;156:707–710. Kuriyama K, Tateishi R, Kumatani T, et al. Pleural invasion by peripheral bronchogenic carcinoma: assessment with

149.

150.

151.

152.

153.

154. 155.

156. 157.

158.

159. 160. 161.

162.

163.

164.

165.

three-dimensional helical CT. Radiology 1994;191:365–369. Padovani B, Mouroux J, Seksik L, et al. Chest wall invasion by bronchogenic carcinoma: evaluation with MR imaging. Radiology 1993;187:33–38. Sakai S, Murayama S, Murakami J, et al. Bronchogenic carcinoma invasion of the chest wall: evaluation with dynamic cine MRI during breathing. J Comput Assist Tomogr 1997;21:595–600. Akata S, Ohkubo Y, Park J, et al. Multiplanar reconstruction MR image of primary adenoid cystic carcinoma of the central airway: MPR of central airway adenoid cystic carcinoma. Clin Imaging 2001;25:332–336. Pancoast HK. Superior sulcus tumor: tumor characterized bypain, Horner’s syndrome, destruction of bone and atroopy of hand muscles. JAMA 1932;99: 1391–1396. Freundlich IM, Chasen MH, Varma DG. Magnetic resonance imaging of pulmonary apical tumors. J Thorac Imaging 1996;11: 210–222. Johnson DH, Hainsworth JD, Greco FA. Pancoast’s syndrome and small cell lung cancer. Chest 1982;82:602–606. O’Connell RS, McLoud TC, Wilkins EW. Superior sulcus tumor: radiographic diagnosis and workup. AJR Am J Roentgenol 1983;140:25–30. McLoud TC, Isler RJ, Novelline RA, et al. The apical cap. AJR Am J Roentgenol 1981;137:299–306. Bruzzi JF, Komaki R, Walsh GL, et al. Imaging of non-small cell lung cancer of the superior sulcus. Part 2. Initial staging and assessment of resectability and therapeutic response. RadioGraphics 2008; 28:561–572. Bruzzi JF, Komaki R, Walsh GL, et al. Imaging of non-small cell lung cancer of the superior sulcus. Part 1. Anatomy, clinical manifestations, and management. RadioGraphics 2008;28:551–560, quiz 620. Gefter WB. Magnetic resonance imaging in the evaluation of lung cancer. Semin Roentgenol 1990;25:73–84. Beale R, Slater R, Hennington M, et al. Pancoast tumor: use of MRI for tumor staging. South Med J 1992;85:1260–1263. Knisely BL, Broderick LS, Kuhlman JE. MR imaging of the pleura and chest wall. Magn Reson Imaging Clin North Am 2000; 8:125–141. Myrdal G, Lambe M, Gustafsson G, et al. Survival in primary lung cancer potentially cured by operation: influence of tumor stage and clinical characteristics. Ann Thorac Surg 2003;75:356–363. Naruke T, Tsuchiya R, Kondo H, et al. Prognosis and survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience. Ann Thorac Surg 2001;71: 1759–1764. Nakanishi R, Osaki T, Nakanishi K, et al. Treatment strategy for patients with surgically discovered N2 stage IIIA non-small cell lung cancer. Ann Thorac Surg 1997;64:342–348. Vansteenkiste JF, De Leyn PR, Deneffe GJ, et al. Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Leuven Lung Cancer

867

Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

166.

167.

168. 169.

170.

171.

172. 173.

174.

175.

176.

177.

178.

179.

180.

181.

868

Group. Ann Thorac Surg 1997;63:1441– 1450. Okada M, Tsubota N, Yoshimura M, et al. Prognosis of completely resected pn2 non-small cell lung carcinomas: what is the significant node that affects survival? J Thorac Cardiovasc Surg 1999;118:270–275. Suzuki K, Nagai K, Yoshida J, et al. Clinical predictors of N2 disease in the setting of a negative computed tomographic scan in patients with lung cancer. J Thorac Cardiovasc Surg 1999;117:593–598. Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718–1723. Cymbalista M, Waysberg A, Zacharias C, et al. CT demonstration of the 1996 AJCC-UICC regional lymph node classification for lung cancer staging. RadioGraphics 1999;19:899–900. Ko JP, Drucker EA, Shepard JA, et al. CT depiction of regional nodal stations for lung cancer staging. AJR Am J Roentgenol 2000;174:775–782. Watanabe S, Ladas G, Goldstraw P. Inter-observer variability in systematic nodal dissection: comparison of European and Japanese nodal designation. Ann Thorac Surg 2002;73:245–248. Friedman PJ. Lung cancer: update on staging classifications. AJR Am J Roentgenol 1988;150:261–264. Asamura H, Suzuki K, Kondo H, et al. Where is the boundary between N1 and N2 stations in lung cancer? Ann Thorac Surg 2000;70:1839–1845. Libshitz HI, McKenna RJ Jr, Mountain CF. Patterns of mediastinal metastases in bronchogenic carcinoma. Chest 1986;90: 229–232. Tateishi M, Fukuyama Y, Hamatake M, et al. Skip mediastinal lymph node metastasis in non-small cell lung cancer. J Surg Oncol 1994;57:139–142. Shimoyama K, Murata K, Takahashi M, et al. Pulmonary hilar lymph node metastases from lung cancer: evaluation based on morphology at thin-section, incremental, dynamic CT. Radiology 1997; 203:187–195. Takamochi K, Nagai K, Yoshida J, et al. The role of computed tomographic scanning in diagnosing mediastinal node involvement in non-small cell lung cancer. J Thorac Cardiovasc Surg 2000;119:1135– 1140. McLoud TC, Bourgouin PM, Greenberg RW, et al. Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. Radiology 1992; 182:319–323. Daly BD Jr, Faling LJ, Bite G, et al. Mediastinal lymph node evaluation by computed tomography in lung cancer. An analysis of 345 patients grouped by TNM staging, tumor size, and tumor location. J Thorac Cardiovasc Surg 1987;94: 664–672. Arita T, Kuramitsu T, Kawamura M, et al. Bronchogenic carcinoma: incidence of metastases to normal sized lymph nodes. Thorax 1995;50:1267–1269. Aronchick JM. CT of mediastinal lymph nodes in patients with non-small cell lung carcinoma. Radiol Clin North Am 1990; 28:573–581.

182. Gross BH, Glazer GM, Orringer MB, et al. Bronchogenic carcinoma metastatic to normal-sized lymph nodes: frequency and significance. Radiology 1988;166:71–74. 183. Asamura H, Nakayama H, Kondo H, et al. Lymph node involvement, recurrence, and prognosis in resected small, peripheral, non-small-cell lung carcinomas: are these carcinomas candidates for video-assisted lobectomy? J Thorac Cardiovasc Surg 1996;111:1125–1134. 184. Graham A, Chan K, Pastorino U, et al. Systematic nodal dissection in the intrathoracic staging of patients with non-small cell lung cancer. J Thorac Cardiovasc Surg 1999;117:246–251. 185. Webb WR, Gatsonis C, Zerhouni EA, et al. CT and MR imaging in staging non-small cell bronchogenic carcinoma: report of the Radiologic Diagnostic Oncology Group. Radiology 1991;178:705–713. 186. Daly BD, Mueller JD, Faling LJ, et al. N2 lung cancer: outcome in patients with false-negative computed tomographic scans of the chest. J Thorac Cardiovasc Surg 1993;105:904–910. 187. Arita T, Matsumoto T, Kuramitsu T, et al. Is it possible to differentiate malignant mediastinal nodes from benign nodes by size? Reevaluation by CT, transesophageal echocardiography, and nodal specimen. Chest 1996;110:1004–1008. 188. Dales RE, Stark RM, Raman S. Computed tomography to stage lung cancer. Approaching a controversy using meta-analysis. Am Rev Respir Dis 1990; 141:1096–1101. 189. Primack SL, Lee KS, Logan PM, et al. Bronchogenic carcinoma: utility of CT in the evaluation of patients with suspected lesions. Radiology 1994;193:795–800. 190. Ikezoe J, Kadowaki K, Morimoto S, et al. Mediastinal lymph node metastases from nonsmall cell bronchogenic carcinoma: reevaluation with CT. J Comput Assist Tomogr 1990;14:340–344. 191. Buy JN, Ghossain MA, Poirson F, et al. Computed tomography of mediastinal lymph nodes in nonsmall cell lung cancer. A new approach based on the lymphatic pathway of tumor spread. J Comput Assist Tomogr 1988;12:545–552. 192. Prenzel KL, Monig SP, Sinning JM, et al. Lymph node size and metastatic infiltration in non-small cell lung cancer. Chest 2003; 123:463–467. 193. Gdeedo A, Van Schil P, Corthouts B, et al. Prospective evaluation of computed tomography and mediastinoscopy in mediastinal lymph node staging. Eur Respir J 1997;10:1547–1551. 194. Oghabian MA, Guiti M, Haddad P, et al. Detection sensitivity of MRI using ultra-small super paramagnetic iron oxide nano-particles (USPIO) in biological tissues. Conf Proc IEEE Eng Med Biol Soc 2006;1:5625–5626. 195. Duhaylongsod FG, Lowe VJ, Patz EF Jr, et al. Lung tumor growth correlates with glucose metabolism measured by fluoride-18 fluorodeoxyglucose positron emission tomography. Ann Thorac Surg 1995;60:1348–1352. 196. Higashi K, Ueda Y, Yagishita M, et al. FDG PET measurement of the proliferative potential of non-small cell lung cancer. J Nucl Med 2000;41:85–92.

197. Goldsmith SJ, Kostakoglu L. Nuclear medicine imaging of lung cancer. Radiol Clin North Am 2000;38:511–524. 198. Vansteenkiste JF, Stroobants SG, De Leyn PR, et al. Lymph node staging in nonsmall-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients. J Clin Oncol 1998;16:2142–2149. 199. Vansteenkiste JF, Stroobants SG, De Leyn PR, et al. Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer: a prospective analysis of 50 cases. Leuven Lung Cancer Group. Chest 1997; 112:1480–1486. 200. Saunders CA, Dussek JE, O’Doherty MJ, et al. Evaluation of fluorine-18fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer. Ann Thorac Surg 1999;67:790–797. 201. Marom EM, McAdams HP, Erasmus JJ, et al. Staging non-small cell lung cancer with whole-body PET. Radiology 1999;212: 803–809. 202. Bury T, Dowlati A, Paulus P, et al. Whole-body 18FDG positron emission tomography in the staging of non-small cell lung cancer. Eur Respir J 1997;10:2529– 2534. 203. Kim S, Park CH, Han M, et al. The clinical usefulness of F-18 FDG coincidence PET without attenuation correction and without whole-body scanning mode in pulmonary lesions comparison with CT, MRI, and clinical findings. Clin Nucl Med 1999; 24:945–949. 204. Shon IH, O’Doherty MJ, Maisey MN. Positron emission tomography in lung cancer. Semin Nucl Med 2002;32:240–271. 205. Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-smallcell lung cancer with positron-emission tomography. N Engl J Med 2000;343: 254–261. 206. Toloza EM, Harpole L, McCrory DC. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Chest 2003;123:S137–S146. 207. Albes JM, Dohmen BM, Schott U, et al. Value of positron emission tomography for lung cancer staging. Eur J Surg Oncol 2002; 28:55–62. 208. De Wever W, Stroobants S, Coolen J, et al. Integrated PET/CT in the staging of nonsmall cell lung cancer: technical aspects and clinical integration. Eur Respir J 2009; 33:201–212. 209. Kagna O, Solomonov A, Keidar Z, et al. The value of FDG-PET/CT in assessing single pulmonary nodules in patients at high risk of lung cancer. Eur J Nucl Med Mol Imaging 2009;36:997–1004. 210. Shin KM, Lee KS, Shim YM, et al. FDG PET/CT and mediastinal nodal metastasis detection in stage T1 non-small cell lung cancer: prognostic implications. Korean J Radiol 2008;9:481–489. 211. Shinya T, Rai K, Okumura Y, et al. Dual-time-point F-18 FDG PET/CT for evaluation of intrathoracic lymph nodes in patients with non-small cell lung cancer. Clin Nucl Med 2009;34:216–221. 212. Subedi N, Scarsbrook A, Darby M, et al. The clinical impact of integrated FDG PET-CT on management decisions in

References

213.

214.

215.

216.

217.

218.

219.

220.

221.

222.

223.

224. 225.

226.

patients with lung cancer. Lung Cancer 2008;64:301–307. van Tinteren H, Hoekstra OS, Smit EF, et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial. Lancet 2002;359:1388– 1393. Seltzer MA, Yap CS, Silverman DH, et al. The impact of PET on the management of lung cancer: the referring physician’s perspective. J Nucl Med 2002;43:752–756. Roberts PF, Follette DM, von Haag D, et al. Factors associated with false-positive staging of lung cancer by positron emission tomography. Ann Thorac Surg 2000;70: 1154–1159. Dwamena BA, Sonnad SS, Angobaldo JO, et al. Metastases from non-small cell lung cancer: mediastinal staging in the 1990s: meta-analytic comparison of PET and CT. Radiology 1999;213:530–536. Tatsumi M, Yutani K, Watanabe Y, et al. Feasibility of fluorodeoxyglucose dual-head gamma camera coincidence imaging in the evaluation of lung cancer: comparison with FDG PET. J Nucl Med 1999;40:566–573. Shreve PD, Steventon RS, Deters EC, et al. Oncologic diagnosis with 2-[fluorine18]fluoro-2-deoxy-D-glucose imaging: dual-head coincidence gamma camera versus positron emission tomographic scanner. Radiology 1998;207:431–437. Aquino SL, Asmuth JC, Alpert NM, et al. Improved radiologic staging of lung cancer with 2-[18F]-fluoro-2-deoxy-D-glucosepositron emission tomography and computed tomography registration. J Comput Assist Tomogr 2003;27:479–484. D’Amico TA, Wong TZ, Harpole DH, et al. Impact of computed tomography-positron emission tomography fusion in staging patients with thoracic malignancies. Ann Thorac Surg 2002;74:160–163. Vansteenkiste JF, Stroobants SG, Dupont PJ, et al. FDG-PET scan in potentially operable non-small cell lung cancer: do anatometabolic PET-CT fusion images improve the localisation of regional lymph node metastases? The Leuven Lung Cancer Group. Eur J Nucl Med 1998;25:1495–1501. Kernstine KH, McLaughlin KA, Menda Y, et al. Can FDG-PET reduce the need for mediastinoscopy in potentially resectable nonsmall cell lung cancer? Ann Thorac Surg 2002;73:394–401. Graeter TP, Hellwig D, Hoffmann K, et al. Mediastinal lymph node staging in suspected lung cancer: comparison of positron emission tomography with F-18-fluorodeoxyglucose and mediastinoscopy. Ann Thorac Surg 2003; 75:231–235. Erasmus JJ, McAdams HP, Patz EF Jr. Non-small cell lung cancer: FDG-PET imaging. J Thorac Imaging 1999;14:247–256. Farrell MA, McAdams HP, Herndon JE, et al. Non-small cell lung cancer: FDG PET for nodal staging in patients with stage I disease. Radiology 2000;215:886–890. Scott WJ, Shepherd J, Gambhir SS. Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: a decision analysis. Ann Thorac Surg 1998;66: 1876–1883.

227. Wallace MB, Silvestri GA, Sahai AV, et al. Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung. Ann Thorac Surg 2001;72:1861–1867. 228. Fritscher-Ravens A, Bohuslavizki KH, Brandt L, et al. Mediastinal lymph node involvement in potentially resectable lung cancer: comparison of CT, positron emission tomography, and endoscopic ultrasonography with and without fine-needle aspiration. Chest 2003;123: 442–451. 229. Silvestri GA, Hoffman B, Reed CE. One from column A: choosing between CT, positron emission tomography, endoscopic ultrasound with fine-needle aspiration, transbronchial needle aspiration, thoracoscopy, mediastinoscopy, and mediastinotomy for staging lung cancer. Chest 2003;123:333–335. 230. Marom EM, Patz EF Jr, Swensen SJ. Radiologic findings of bronchogenic carcinoma with pulmonary metastases at presentation. Clin Radiol 1999;54:665– 668. 231. Okumura T, Asamura H, Suzuki K, et al. Intrapulmonary metastasis of non-small cell lung cancer: a prognostic assessment. J Thorac Cardiovasc Surg 2001;122:24–28. 232. Keogan MT, Tung KT, Kaplan DK, et al. The significance of pulmonary nodules detected on CT staging for lung cancer. Clin Radiol 1993;48:94–96. 233. Kim YH, Lee KS, Primack SL, et al. Small pulmonary nodules on CT accompanying surgically resectable lung cancer: likelihood of malignancy. J Thorac Imaging 2002;17: 40–46. 234. Manac’h D, Riquet M, Medioni J, et al. Visceral pleura invasion by non-small cell lung cancer: an underrated bad prognostic factor. Ann Thorac Surg 2001;71:1088–1093. 235. Okada M, Tsubota N, Yoshimura M, et al. How should interlobar pleural invasion be classified? Prognosis of resected T3 non-small cell lung cancer. Ann Thorac Surg 1999;68:2049–2052. 236. Sahn SA. Pleural effusion in lung cancer. Clin Chest Med 1993;14:189–200. 237. Erasmus JJ, McAdams HP, Rossi SE, et al. FDG PET of pleural effusions in patients with non-small cell lung cancer. AJR Am J Roentgenol 2000;175:245–249. 238. Gorg C, Restrepo I, Schwerk WB. Sonography of malignant pleural effusion. Eur Radiol 1997;7:1195–1198. 239. Roberts JR, Blum MG, Arildsen R, et al. Prospective comparison of radiologic, thoracoscopic, and pathologic staging in patients with early non-small cell lung cancer. Ann Thorac Surg 1999;68: 1154–1158. 240. Hammoud Z, Anderson R, Meyers B, et al. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg 1999;118:894–899. 241. Canadian Lung Oncology G. Investigation for mediastinal disease in patients with apparently operable lung cancer. Ann Thorac Surg 1995;60:1382–1389. 242. Vesselle H, Pugsley J, Vallieres E, et al. The impact of fluorodeoxyglucose F 18 positron-emission tomography on the surgical staging of non-small cell lung cancer. J Thorac Cardiovasc Surg 2002;124: 511–519.

243. Pope RJ, Hansell DM. Extra-thoracic staging of lung cancer. Eur J Radiol 2003;45:31–38. 244. Weder W, Schmid RA, Bruchhaus H, et al. Detection of extrathoracic metastases by positron emission tomography in lung cancer. Ann Thorac Surg 1998;66:886–892. 245. Valk PE, Pounds TR, Hopkins DM, et al. Staging non-small cell lung cancer by whole-body positron emission tomographic imaging. Ann Thorac Surg 1995;60:1573–1 581. 246. MacManus MP, Hicks RJ, Matthews JP, et al. High rate of detection of unsuspected distant metastases by PET in apparent stage III non-small-cell lung cancer: implications for radical radiation therapy. Int J Radiat Oncol Biol Phys 2001;50: 287–293. 247. Barkhausen J, Quick HH, Lauenstein T, et al. Whole-body MR imaging in 30 seconds with real-time true FISP and a continuously rolling table platform: feasibility study. Radiology 2001; 220:252–256. 248. Ohno Y, Koyama H, Onishi Y, et al. Non-small cell lung cancer: whole-body MR examination for M-stage assessment – utility for whole-body diffusion-weighted imaging compared with integrated FDG PET/CT. Radiology 2008;248:643–654. 249. Salvatierra A, Baamonde C, Llamas JM, et al. Extrathoracic staging of bronchogenic carcinoma. Chest 1990;97:1052– 1058. 250. Charnley RM, Morris DL, Dennison AR, et al. Detection of colorectal liver metastases using intraoperative ultrasonography. Br J Surg 1991;78:45–48. 251. Leen E, Angerson WJ, Wotherspoon H, et al. Detection of colorectal liver metastases: comparison of laparotomy, CT, US, and Doppler perfusion index and evaluation of postoperative follow-up results. Radiology 1995;195:113–116. 252. Namasivayam S, Martin DR, Saini S. Imaging of liver metastases: MRI. Cancer Imaging 2007;7:2–9. 253. Oliver TW Jr, Bernardino ME, Miller JI, et al. Isolated adrenal masses in nonsmallcell bronchogenic carcinoma. Radiology 1984;153:217–218. 254. Gillams A, Roberts CM, Shaw P, et al. The value of CT scanning and percutaneous fine needle aspiration of adrenal masses in biopsy-proven lung cancer. Clin Radiol 1992;46:18–22. 255. Reinig JW. Differentiation of hepatic lesions with MR imaging: the last word? Radiology 1991;179:601–602. 256. Maurea S, Mainolfi C, Bazzicalupo L, et al. Imaging of adrenal tumors using FDG PET: comparison of benign and malignant lesions. AJR Am J Roentgenol 1999;173: 25–29. 257. Sze G, Shin J, Krol G, et al. Intraparenchymal brain metastases: MR imaging versus contrast-enhanced CT. Radiology 1988;168:187–194. 258. Yokoi K, Kamiya N, Matsuguma H, et al. Detection of brain metastasis in potentially operable non-small cell lung cancer: a comparison of CT and MRI. Chest 1999; 115:714–719. 259. Newman SJ, Hansen HH. Proceedings: Frequency, diagnosis, and treatment of brain metastases in 247 consecutive

869

Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

260. 261.

262.

263.

264. 265.

266.

267.

268.

269.

270.

271. 272. 273. 274.

275. 276.

870

patients with bronchogenic carcinoma. Cancer 1974;33:492–496. Gore EM. Brain metastases in very young patients with lung cancer are still brain metastases. Onkologie 2008;31:297–298. Na, II, Lee TH, Choe du H, et al. A diagnostic model to detect silent brain metastases in patients with non-small cell lung cancer. Eur J Cancer 2008;44: 2411–2417. Seute T, Leffers P, ten Velde GP, et al. Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI). Cancer 2008;112:1827–1834. Hillers TK, Sauve MD, Guyatt GH. Analysis of published studies on the detection of extrathoracic metastases in patients presumed to have operable non-small cell lung cancer. Thorax 1994;49: 14–19. Muers MF. Preoperative screening for metastases in lung cancer. Thorax 1994;49: 1–2. Napoli LD, Hansen HH, Muggia FM, et al. The incidence of osseous involvement in lung cancer, with special reference to the development of osteoblastic changes. Radiology 1973;108:17–21. Donato AT, Ammerman EG, Sullesta O. Bone scanning in the evaluation of patients with lung cancer. Ann Thorac Surg 1979;27: 300–304. Ichinose Y, Hara N, Ohta M, et al. Preoperative examination to detect distant metastasis is not advocated for asymptomatic patients with stages 1 and 2 non-small cell lung cancer. Preoperative examination for lung cancer. Chest 1989;96:1104–1109. Michel F, Soler M, Imhof E, et al. Initial staging of non-small cell lung cancer: value of routine radioisotope bone scanning. Thorax 1991;46:469–473. Travis WD, Colby TV, Corrin B, et al. World Health Organization Pathology Panel: World Health Organization. Histological typing of lung and pleural tumors: international histological classification of tumors. New York: Springer Verlag, 1999. Mirtcheva RM, Vazquez M, Yankelevitz DF, et al. Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar features presenting as ground-glass opacities on CT. Clin Imaging 2002;26:95–100. Greco RJ, Steiner RM, Goldman S, et al. Bronchoalveolar cell carcinoma of the lung. Ann Thorac Surg 1986;41:652–656. Epstein DM. Bronchioloalveolar carcinoma. Semin Roentgenol 1990;25:105– 111. Spencer H. Pathology of the lung, 4th edn. Philadelphia: WB Saunders, 1985. Harpole DH, Bigelow C, Young WG Jr, et al. Alveolar cell carcinoma of the lung: a retrospective analysis of 205 patients. Ann Thorac Surg 1988;46:502–507. Hsu CP, Chen CY, Hsu NY. Bronchioloalveolar carcinoma. J Thorac Cardiovasc Surg 1995;110:374–381. Vazquez MF, Yankelevitz DF. The radiologic appearance of solitary pulmonary nodules and their cytologichistologic correlation. Semin Ultrasound CT MR 2000;21:149–162.

277. Shah RM, Balsara G, Webster M, et al. Bronchioloalveolar cell carcinoma: impact of histology on dominant CT pattern. J Thorac Imaging 2000;15:180–186. 278. Okubo K, Mark E, Flieder D, et al. Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival. J Thorac Cardiovasc Surg 1999; 118:702–709. 279. Daly RC, Trastek VF, Pairolero PC, et al. Bronchoalveolar carcinoma: factors affecting survival. Ann Thorac Surg 1991; 51:368–376. 280. Epstein DM, Gefter WB, Miller WT. Lobar bronchioloalveolar cell carcinoma. AJR Am J Roentgenol 1982;139:463–468. 281. Gaeta M, Barone M, Caruso R, et al. CT-pathologic correlation in nodular bronchioloalveolar carcinoma. J Comput Assist Tomogr 1994;18:229–232. 282. Kuhlman JE, Fishman EK, Kuhajda FP, et al. Solitary bronchioloalveolar carcinoma: CT criteria. Radiology 1988; 167:379–382. 283. Bonomo L, Storto ML, Ciccotosto C, et al. Bronchioloalveolar carcinoma of the lung. Eur Radiol 1998;8:996–1001. 284. Hill CA. Bronchioloalveolar carcinoma: a review. Radiology 1984;150:15–20. 285. Lee KS, Kim Y, Han J, et al. Bronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings. RadioGraphics 1997;17:1345–1357. 286. Adler B, Padley S, Miller RR, et al. High-resolution CT of bronchioloalveolar carcinoma. AJR Am J Roentgenol 1992; 159:275–277. 287. Gaeta M, Caruso R, Blandino A, et al. Radiolucencies and cavitation in bronchioloalveolar carcinoma: CT-pathologic correlation. Eur Radiol 1999;9:55–59. 288. Mihara N, Ichikado K, Johkoh T, et al. The subtypes of localized bronchioloalveolar carcinoma: CT-pathologic correlation in 18 cases. AJR Am J Roentgenol 1999;173: 75–79. 289. Jang HJ, Lee KS, Kwon OJ, et al. Bronchioloalveolar carcinoma: focal area of ground-glass attenuation at thin-section CT as an early sign. Radiology 1996;199: 485–488. 290. Gaeta M, Caruso R, Barone M, et al. Ground-glass attenuation in nodular bronchioloalveolar carcinoma: CT patterns and prognostic value. J Comput Assist Tomogr 1998;22:215–219. 291. Weisbrod GL, Chamberlain D, Herman SJ. Cystic change (pseudocavitation) associated with bronchioloalveolar carcinoma: a report of four patients. J Thorac Imaging 1995;10:106–111. 292. Akira M, Atagi S, Kawahara M, et al. High-resolution CT findings of diffuse bronchioloalveolar carcinoma in 38 patients. AJR Am J Roentgenol 1999; 173:1623–1629. 293. Kobayashi T, Satoh K, Sasaki M, et al. Bronchioloalveolar carcinoma with widespread ground-glass shadow on CT in two cases. J Comput Assist Tomogr 1997; 21:133–135. 294. Schulze ES, Mattia AR, Chew FS. Bronchioloalveolar carcinoma. AJR Am J Roentgenol 1994;162:1294. 295. Kim BT, Kim Y, Lee KS, et al. Localized form of bronchioloalveolar carcinoma: FDG

296.

297.

298.

299. 300.

301.

302.

303.

304.

305.

306.

307.

308.

309. 310. 311.

312.

313.

PET findings. AJR Am J Roentgenol 1998;170:935–939. Tan RT, Kuzo RS. High-resolution CT findings of mucinous bronchioloalveolar carcinoma: a case of pseudopulmonary alveolar proteinosis. AJR Am J Roentgenol 1997;168:99–100. Huang D, Weisbrod GL, Chamberlain DW. Unusual radiologic presentations of bronchioloalveolar carcinoma. Can Assoc Radiol J 1986;37:94–99. Weisbrod GL, Towers MJ, Chamberlain DW, et al. Thin-walled cystic lesions in bronchioalveolar carcinoma. Radiology 1992;185:401–405. Im JG, Choi BI, Park JH, et al. CT findings of lobar bronchioloalveolar carcinoma. J Comput Assist Tomogr 1986;10:320–322. Aquino SL, Chiles C, Halford P. Distinction of consolidative bronchioloalveolar carcinoma from pneumonia: do CT criteria work? AJR Am J Roentgenol 1998;171: 359–363. Jung JI, Kim H, Park SH, et al. CT differentiation of pneumonic-type bronchioalveolar cell carcinoma and infectious pneumonia. Br J Radiol 2001;74: 490–494. Im JG, Han MC, Yu EJ, et al. Lobar bronchioloalveolar carcinoma: ‘angiogram sign’ on CT scans. Radiology 1990;176: 749–753. Vincent JM, Ng YY, Norton AJ, et al. CT ‘angiogram sign’ in primary pulmonary lymphoma. J Comput Assist Tomogr 1992; 16:829–831. Shah RM, Friedman AC. CT angiogram sign: incidence and significance in lobar consolidations evaluated by contrastenhanced CT. AJR Am J Roentgenol 1998; 170:719–721. Metzger RA, Mulhern CB Jr, Arger PH, et al. CT differentiation of solitary from diffuse bronchioloalveolar carcinoma. J Comput Assist Tomogr 1981;5:830–833. Gaeta M, Blandino A, Scribano E, et al. Magnetic resonance imaging of bronchioloalveolar carcinoma. J Thorac Imaging 2000;15:41–47. Higashi K, Ueda Y, Seki H, et al. Fluorine18-FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 1998;39:1016–1020. Walsh GL, O’Connor M, Willis KM, et al. Is follow-up of lung cancer patients after resection medically indicated and cost-effective? Ann Thorac Surg 1995;60: 1563–1570. Younes RN, Gross JL, Deheinzelin D. Follow-up in lung cancer: how often and for what purpose? Chest 1999;115:1494–1499. Downey RJ. Follow-up of patients with completely resected lung cancer. Chest 1999;115:1487–1488. Gorich J, Beyer-Enke SA, Flentje M, et al. Evaluation of recurrent bronchogenic carcinoma by computed tomography. Clin Imaging 1990;14:131–137. Libshitz HI, Sheppard DG. Filling in of radiation therapy-induced bronchiectatic change: a reliable sign of locally recurrent lung cancer. Radiology 1999;210:25–27. Patz EF Jr, Lowe VJ, Hoffman JM, et al. Persistent or recurrent bronchogenic carcinoma: detection with PET and 2-[F-18]-2-deoxy-D-glucose. Radiology 1994;191:379–382.

References 314. Frank A, Lefkowitz D, Jaeger S, et al. Decision logic for retreatment of asymptomatic lung cancer recurrence based on positron emission tomography findings. Int J Radiat Oncol Biol Phys 1995;32:1495–1512. 315. Hicks RJ, Kalff V, MacManus MP, et al. The utility of (18)F-FDG PET for suspected recurrent non-small cell lung cancer after potentially curative therapy: impact on management and prognostic stratification. J Nucl Med 2001;42:1605–1613. 316. Inoue T, Kim EE, Komaki R, et al. Detecting recurrent or residual lung cancer with FDG-PET. J Nucl Med 1995;36: 788–793. 317. Marom EM, Erasmus JJ, Patz EF. Lung cancer and positron emission tomography with fluorodeoxyglucose. Lung Cancer 2000;28:187–202. 318. Sartori G, Cavazza A, Bertolini F, et al. A subset of lung adenocarcinomas and atypical adenomatous hyperplasiaassociated foci are genotypically related: an EGFR, HER2, and K-ras mutational analysis. Am J Clin Pathol 2008;129: 202–210. 319. Morandi L, Asioli S, Cavazza A, et al. Genetic relationship among atypical adenomatous hyperplasia, bronchioloalveolar carcinoma and adenocarcinoma of the lung. Lung Cancer 2007;56:35–42. 320. Miller RR. Bronchioloalveolar cell adenomas. Am J Surg Pathol 1990;14: 904–912. 321. Yokose T, Ito Y, Ochiai A. High prevalence of atypical adenomatous hyperplasia of the lung in autopsy specimens from elderly patients with malignant neoplasms. Lung Cancer 2000;29:125–130. 322. Yokose T, Doi M, Tanno K, et al. Atypical adenomatous hyperplasia of the lung in autopsy cases. Lung Cancer 2001;33: 155–161. 323. Kushihashi T, Munechika H, Ri K, et al. Bronchioloalveolar adenoma of the lung: CT-pathologic correlation. Radiology 1994;193:789–793. 324. Chapman AD, Kerr KM. The association between atypical adenomatous hyperplasia and primary lung cancer. Br J Cancer 2000;83:632–636. 325. Kitamura H, Kameda Y, Ito T, et al. Atypical adenomatous hyperplasia of the lung. Implications for the pathogenesis of peripheral lung adenocarcinoma. Am J Clin Pathol 1999;111:610–622. 326. Vazquez MF, Flieder DB. Small peripheral glandular lesions detected by screening CT for lung cancer. A diagnostic dilemma for the pathologist. Radiol Clin North Am 2000;38:579–589. 327. Colby TV, Wistuba II, Gazdar A. Precursors to pulmonary neoplasia. Adv Anat Pathol 1998;5:205–215. 328. Mori M, Rao SK, Popper HH, et al. Atypical adenomatous hyperplasia of the lung: a probable forerunner in the development of adenocarcinoma of the lung. Mod Pathol 2001;14:72–84. 329. Nakahara R, Yokose T, Nagai K, et al. Atypical adenomatous hyperplasia of the lung: a clinicopathological study of 118 cases including cases with multiple atypical adenomatous hyperplasia. Thorax 2001;56:302–305.

330. Ritter JH. Pulmonary atypical adenomatous hyperplasia. A histologic lesion in search of usable criteria and clinical significance. Am J Clin Pathol 1999;111:587–589. 331. Slebos RJ, Baas IO, Clement MJ, et al. p53 alterations in atypical alveolar hyperplasia of the human lung. Hum Pathol 1998;29: 801–808. 332. Takashima S, Maruyama Y, Hasegawa M, et al. CT findings and progression of small peripheral lung neoplasms having a replacement growth pattern. AJR Am J Roentgenol 2003;180:817–826. 333. Greenberg AK, Yee H, Rom WN. Preneoplastic lesions of the lung. Respir Res 2002;3:20. 334. Kawakami S, Sone S, Takashima S, et al. Atypical adenomatous hyperplasia of the lung: correlation between high-resolution CT findings and histopathologic features. Eur Radiol 2001;11:811–814. 335. Logan PM, Miller RR, Evans K, et al. Bronchogenic carcinoma and coexistent bronchioloalveolar cell adenomas. Assessment of radiologic detection and follow-up in 28 patients. Chest 1996;109: 713–717. 336. Park CM, Goo JM, Lee HJ, et al. CT findings of atypical adenomatous hyperplasia in the lung. Korean J Radiol 2006;7:80–86. 337. Jemal A, Thomas A, Murray T, et al. Cancer statistics, 2002. CA Cancer J Clin 2002;52:23–47. 338. Fry WA, Phillips JL, Menck HR. Ten-year survey of lung cancer treatment and survival in hospitals in the United States: a national cancer data base report. Cancer 1999;86:1867–1876. 339. Black WC, Welch HG. Screening for disease. AJR Am J Roentgenol 1997;168: 3–11. 340. Huhti E, Saloheimo M, Sutinen S. The value of roentgenologic screening in lung cancer. Am Rev Respir Dis 1983;128: 395–398. 341. Strauss GM. Measuring effectiveness of lung cancer screening: from consensus to controversy and back. Chest 1997;112: S216–S228. 342. Patz EF Jr, Goodman PC, Bepler G. Screening for lung cancer. N Engl J Med 2000;343:1627–1633. 343. Ellis JR, Gleeson FV. Lung cancer screening. Br J Radiol 2001;74:478–485. 344. Ellis SM, Husband JE, Armstrong P, et al. Computed tomography screening for lung cancer: back to basics. Clin Radiol 2001;56: 691–699. 345. Hasegawa M, Sone S, Takashima S, et al. Growth rate of small lung cancers detected on mass CT screening. Br J Radiol 2000;73: 1252–1259. 346. Hayabuchi N, Russell WJ, Murakami J. Slow-growing lung cancer in a fixed population sample. Radiologic assessments. Cancer 1983;52:1098–1104. 347. Nathan MH, Collins VP. Differentiation of benign and malignant pulmonary nodules by growth rate. Radiology 1962;79:221–232. 348. Steele JD, Buell P. Asymptomatic solitary pulmonary nodules. Host survival, tumor size, and growth rate. J Thorac Cardiovasc Surg 1973;65:140–151. 349. Straus MJ. The growth characteristics of lung cancer and its application to treatment design. Semin Oncol 1974;1:167–174.

350. Usuda K, Saito Y, Sagawa M, et al. Tumor doubling time and prognostic assessment of patients with primary lung cancer. Cancer 1994;74:2239–2244. 351. Winer-Muram HT, Jennings SG, Tarver RD, et al. Volumetric growth rate of stage I lung cancer prior to treatment: serial CT scanning. Radiology 2002;223:798–805. 352. Sone S, Li F, Yang ZG, et al. Results of three-year mass screening programme for lung cancer using mobile low-dose spiral computed tomography scanner. Br J Cancer 2001;84:25–32. 353. Henschke CI, McCauley DI, Yankelevitz DF, et al. Early lung cancer action project: overall design and findings from baseline screening. Lancet 1999;354:99–105. 354. Rozenshtein A, White CS, Austin JH, et al. Incidental lung carcinoma detected at CT in patients selected for lung volume reduction surgery to treat severe pulmonary emphysema. Radiology 1998; 207:487–490. 355. Pigula FA, Keenan RJ, Ferson PF, et al. Unsuspected lung cancer found in work-up for lung reduction operation. Ann Thorac Surg 1996;61:174–176. 356. McKenna RJ Jr, Fischel RJ, Brenner M, et al. Combined operations for lung volume reduction surgery and lung cancer. Chest 1996;110:885–888. 357. Hazelrigg SR, Boley TM, Weber D, et al. Incidence of lung nodules found in patients undergoing lung volume reduction. Ann Thorac Surg 1997;64: 303–306. 358. McFarlane MJ, Feinstein AR, Wells CK. Clinical features of lung cancers discovered as a postmortem ‘surprise’. Chest 1986; 90:520–523. 359. Dammas S, Patz EF Jr, Goodman PC. Identification of small lung nodules at autopsy: implications for lung cancer screening and overdiagnosis bias. Lung Cancer 2001;33:11–16. 360. Patz EF Jr, Rossi S, Harpole DH Jr, et al. Correlation of tumor size and survival in patients with stage IA non-small cell lung cancer. Chest 2000;117:1568–1571. 361. Black WC. Unexpected observations on tumor size and survival in stage IA non-small cell lung cancer. Chest 2000; 117:1532–1534. 362. Koike T, Terashima M, Takizawa T, et al. Clinical analysis of small-sized peripheral lung cancer. J Thorac Cardiovasc Surg 1998;115:1015–1020. 363. Henschke CI, Wisnivesky JP, Yankelevitz DF, et al. Small stage I cancers of the lung: genuineness and curability. Lung Cancer 2003;39:327–330. 364. Fontana RS, Sanderson DR, Taylor WF, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis 1984;130: 561–565. 365. Fontana RS, Sanderson DR, Woolner LB, et al. Lung cancer screening: the Mayo program. J Occup Med 1986;28:746–750. 366. Marcus PM, Bergstralh EJ, Fagerstrom RM, et al. Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. J Natl Cancer Inst 2000;92: 1308–1316. 367. Kubik AK, Parkin DM, Zatloukal P. Czech study on lung cancer screening: post-trial

871

Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

368. 369.

370. 371.

372. 373.

374.

375. 376.

377.

378.

379.

380.

381. 382.

383. 384. 385.

386.

387.

872

follow-up of lung cancer deaths up to year 15 since enrollment. Cancer 2000;89: 2363–2368. Nash FA, Morgan JM, Tomkins JG. South London lung cancer study. Br Med J 1968; 2:715–721. Kaneko M, Eguchi K, Ohmatsu H, et al. Peripheral lung cancer: screening and detection with low-dose spiral CT versus radiography. Radiology 1996;201:798–802. Hutchinson E. Caution over use of lung-cancer screening as standard practice. Lancet 2000;356:742. Flehinger BJ, Kimmel M, Melamed MR. The effect of surgical treatment on survival from early lung cancer. Implications for screening. Chest 1992;101:1013–1018. Brett GZ. The value of lung cancer detection by six-monthly chest radiographs. Thorax 1968;23:414–420. Wilde J. A 10 year follow-up of semiannual screening for early detection of lung cancer in the Erfurt County, GDR. Eur Respir J 1989;2:656–662. Lilienfield A, Archer PG, Burnett CH, et al. An evaluation of radiologic and cytologic screening for the early detection of lung cancer: a cooperative pilot study of the American Cancer Society and the Veterans Administration. Cancer Res 1966;26: 2083–2121. Sanderson DR. Lung cancer screening. The Mayo study. Chest 1986;89(suppl):S324. Tockman MS. Survival and mortality from lung cancer in a screened population. The Johns Hopkins study. Chest 1986; 89(suppl):S324–S325. Flehinger BJ, Melamed MR, Zaman MB, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Memorial Sloan-Kettering study. Am Rev Respir Dis 1984;130:555–560. Frost JK, Ball WC Jr, Levin ML, et al. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Respir Dis 1984;130:549–554. Heelan RT, Flehinger BJ, Melamed MR, et al. Non-small-cell lung cancer: results of the New York screening program. Radiology 1984;151:289–293. Fontana RS, Sanderson DR, Woolner LB, et al. Screening for lung cancer. A critique of the Mayo lung project. Cancer 1991;67: 1155–1164. Eddy DM. Screening for lung cancer. Ann Intern Med 1989;111:232–237. Melamed MR, Flehinger BJ, Zaman MB, et al. Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York. Chest 1984;86:44–53. Miettinen OS. Screening for lung cancer. Radiol Clin North Am 2000;38:479–486. Rubin SA. Lung cancer: past, present, and future. J Thorac Imaging 1991;7:1–8. Kaneko M, Kusumoto M, Kobayashi T, et al. Computed tomography screening for lung carcinoma in Japan. Cancer 2000;89: 2485–2488. Sone S, Takashima S, Li F, et al. Mass screening for lung cancer with mobile spiral computed tomography scanner. Lancet 1998;351:1242–1245. Sone S, Li F, Yang ZG, et al. Characteristics of small lung cancers invisible on conventional chest radiography and

388.

389.

390.

391.

392.

393.

394.

395.

396.

397.

398.

399. 400.

401.

402.

403.

detected by population based screening using spiral CT. Br J Radiol 2000;73: 137–145. Altorki N, Kent M, Pasmantier M. Detection of early-stage lung cancer: computed tomographic scan or chest radiograph? J Thorac Cardiovasc Surg 2001;121:1053–1057. Yang ZG, Sone S, Li F, et al. Visibility of small peripheral lung cancers on chest radiographs: influence of densitometric parameters, CT values and tumour type. Br J Radiol 2001;74:32–41. Swensen SJ, Jett JR, Hartman TE, et al. Lung cancer screening with CT: Mayo Clinic experience. Radiology 2003;226: 756–761. Diederich S, Wormanns D, Semik M, et al. Screening for early lung cancer with low-dose spiral CT: prevalence in 817 asymptomatic smokers. Radiology 2002; 222:773–781. Swensen SJ, Jett JR, Sloan JA, et al. Screening for lung cancer with low-dose spiral computed tomography. Am J Respir Crit Care Med 2002;165:508–513. Henschke CI, Naidich DP, Yankelevitz DF, et al. Early lung cancer action project: initial findings on repeat screenings. Cancer 2001;92:153–159. Yang ZG, Sone S, Takashima S, et al. Small peripheral carcinomas of the lung: thin-section CT and pathologic correlation. Eur Radiol 1999;9:1819–1825. Kodama K, Higashiyama M, Yokouchi H, et al. Natural history of pure ground-glass opacity after long-term follow-up of more than 2 years. Ann Thorac Surg 2002;73: 386–392. Suzuki K, Asamura H, Kusumoto M, et al. ‘Early’ peripheral lung cancer: prognostic significance of ground glass opacity on thin-section computed tomographic scan. Ann Thorac Surg 2002;74:1635–1639. Wang JC, Sone S, Feng L, et al. Rapidly growing small peripheral lung cancers detected by screening CT: correlation between radiological appearance and pathological features. Br J Radiol 2000; 73:930–937. Yang ZG, Sone S, Takashima S, et al. High-resolution CT analysis of small peripheral lung adenocarcinomas revealed on screening helical CT. AJR Am J Roentgenol 2001;176:1399–1407. Ginsberg RJ. The solitary pulmonary nodule: can we afford to watch and wait? J Thorac Cardiovasc Surg 2003;125:25–26. Quarterman RL, McMillan A, Ratcliffe MB, et al. Effect of preoperative delay on prognosis for patients with early stage non-small cell lung cancer. J Thorac Cardiovasc Surg 2003;125:108–113. Aberle DR, Gamsu G, Henschke CI, et al. A consensus statement of the Society of Thoracic Radiology: screening for lung cancer with helical computed tomography. J Thorac Imaging 2001;16:65–68. Zhao B, Yankelevitz D, Reeves A, et al. Two-dimensional multi-criterion segmentation of pulmonary nodules on helical CT images. Med Phys 1999;26: 889–895. Yankelevitz DF, Gupta R, Zhao B, et al. Small pulmonary nodules: evaluation with repeat CT: preliminary experience. Radiology 1999;212:561–566.

404. Wormanns D, Fiebich M, Saidi M, et al. Automatic detection of pulmonary nodules at spiral CT: clinical application of a computer-aided diagnosis system. Eur Radiol 2002;12:1052–1057. 405. Armato SG III, Giger ML, Moran CJ, et al. Computerized detection of pulmonary nodules on CT scans. RadioGraphics 1999;19:1303–1311. 406. Tillich M, Kammerhuber F, Reittner P, et al. Detection of pulmonary nodules with helical CT: comparison of cine and film-based viewing. AJR Am J Roentgenol 1997;169:1611–1614. 407. Armato SG III, Giger ML, MacMahon H. Automated detection of lung nodules in CT scans: preliminary results. Med Phys 2001;28:1552–1561. 408. Ko JP, Betke M, Chest CT: automated nodule detection and assessment of change over time – preliminary experience. Radiology 2001;218:267–273. 409. Reeves AP, Kostis WJ. Computer-aided diagnosis for lung cancer. Radiol Clin North Am 2000;38:497–509. 410. Armato SG III, Li F, Giger ML, et al. Lung cancer: performance of automated lung nodule detection applied to cancers missed in a CT screening program. Radiology 2002;225:685–692. 411. Brown MS, Goldin JG, Suh RD, et al. Lung micronodules: automated method for detection at thin-section CT: initial experience. Radiology 2003;226:256–262. 412. Ko JP, Naidich DP. Lung nodule detection and characterization with multislice CT. Radiol Clin North Am 2003;41:575–597, vi. 413. Oguchi K, Sone S, Kiyono K, et al. Optimal tube current for lung cancer screening with low-dose spiral CT. Acta Radiol 2000;41: 352–356. 414. Rusinek H, Naidich DP, McGuinness G, et al. Pulmonary nodule detection: low-dose versus conventional CT. Radiology 1998;209:243–249. 415. Itoh S, Ikeda M, Arahata S, et al. Lung cancer screening: minimum tube current required for helical CT. Radiology 2000; 215:175–183. 416. Itoh S, Koyama S, Ikeda M, et al. Further reduction of radiation dose in helical CT for lung cancer screening using small tube current and a newly designed filter. J Thorac Imaging 2001;16:81–88. 417. Patz EF Jr, Black WC, Goodman PC. CT screening for lung cancer: not ready for routine practice. Radiology 2001;221: 587–591. 418. Miettinen OS, Henschke CI. CT screening for lung cancer: coping with nihilistic recommendations. Radiology 2001;221: 592–596. 419. Smith IE. Screening for lung cancer: time to think positive. Lancet 1999;354:86–87. 420. Heffner JE, Silvestri G. CT screening for lung cancer: is smaller better? Am J Respir Crit Care Med 2002;165:433–434. 421. Jett JR. Spiral computed tomography screening for lung cancer is ready for prime time. Am J Respir Crit Care Med 2001;163:812–815. 422. Patz EF Jr, Goodman PC. Low-dose spiral computed tomography screening for lung cancer: not ready for prime time. Am J Respir Crit Care Med 2001;163: 813–814.

References 423. Bach PB, Niewoehner DE, Black WC. Screening for lung cancer: the guidelines. Chest 2003;123:S83–S88. 424. Chirikos TN, Hazelton T, Tockman M, et al. Screening for lung cancer with CT: a preliminary cost-effectiveness analysis. Chest 2002;121:1507–1514. 425. Marshall D, Simpson KN, Earle CC, et al. Potential cost-effectiveness of one-time screening for lung cancer (LC) in a high risk cohort. Lung Cancer 2001;32:227–236. 426. Marshall D, Simpson KN, Earle CC, et al. Economic decision analysis model of screening for lung cancer. Eur J Cancer 2001;37:1759–1767. 427. Wisnivesky JP, Braz-Parente D, Smith JP, et al. Cost-effectiveness evaluation of low-dose computed tomography screening for non-small cell lung cancer. Radiology 2000;217(suppl):244. 428. Wisnivesky JP, Mushlin AI, Sicherman N, et al. The cost-effectiveness of low-dose CT screening for lung cancer: preliminary results of baseline screening. Chest 2003; 124:614–621. 429. Gohagan J, Marcus P, Fagerstrom R, et al. Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph: the lung screening study of the National Cancer Institute. Chest 2004;126:114–121. 430. van Iersel CA, de Koning HJ, Draisma G, et al. Risk-based selection from the general population in a screening trial: selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON). Int J Cancer 2007;120:868–874. 431. Infante M, Lutman FR, Cavuto S, et al. Lung cancer screening with spiral CT: baseline results of the randomized DANTE trial. Lung Cancer 2008;59:355–363. 432. Heelan RT, Demas BE, Caravelli JF, et al. Superior sulcus tumors: CT and MR imaging. Radiology 1989;170:637–641. 433. Austin JH, Romney BM, Goldsmith LS. Missed bronchogenic carcinoma: radiographic findings in 27 patients with a potentially resectable lesion evident in retrospect. Radiology 1992;182:115–122. 434. Hayabuchi N, Russell WJ, Murakami J. Problems in radiographic detection and diagnosis of lung cancer. Acta Radiol 1989; 30:163–167. 435. Shah PK, Austin JH, White CS, et al. Missed non-small cell lung cancer: radiographic findings of potentially resectable lesions evident only in retrospect. Radiology 2003;226:235–241. 436. Quekel LG, Kessels AG, Goei R, et al. Miss rate of lung cancer on the chest radiograph in clinical practice. Chest 1999; 115:720–724. 437. Tsubamoto M, Kuriyama K, Kido S, et al. Detection of lung cancer on chest radiographs: analysis on the basis of size and extent of ground-glass opacity at thin-section CT. Radiology 2002;224: 139–144. 438. Davis SD. Through the ‘retrospectoscope’: a glimpse of missed lung cancer at CT. Radiology 1996;199:23–24. 439. Gurney JW. Missed lung cancer at CT: imaging findings in nine patients. Radiology 1996;199:117–122. 440. White CS, Romney BM, Mason AC, et al. Primary carcinoma of the lung overlooked

441.

442. 443. 444. 445. 446.

447.

448. 449.

450.

451. 452. 453. 454.

455.

456.

457.

458.

459.

460.

at CT: analysis of findings in 14 patients. Radiology 1996;199:109–115. Li F, Sone S, Abe H, et al. Lung cancers missed at low-dose helical CT screening in a general population: comparison of clinical, histopathologic, and imaging findings. Radiology 2002;225:673–683. Potchen EJ, Bisesi MA. When is it malpractice to miss lung cancer on chest radiographs? Radiology 1990;175:29–32. Woodring JH. Pitfalls in the radiologic diagnosis of lung cancer. AJR Am J Roentgenol 1990;154:1165–1175. Oestmann JW, Greene R, Bourgouin PM, et al. Chest ‘gestalt’ and detectability of lung lesions. Eur J Radiol 1993;16:154–157. Vincent JM, Armstrong P. Detection and diagnosis of the primary tumor in lung cancer. Curr Opin Radiol 1991;3:341–350. Krupinski EA, Nodine CF, Kundel HL. A perceptually based method for enhancing pulmonary nodule recognition. Invest Radiol 1993;28:289–294. Kundel HL, Nodine CF, Krupinski EA. Computer-displayed eye position as a visual aid to pulmonary nodule interpretation. Invest Radiol 1990;25: 890–896. Swensson RG, Theodore GH. Search and nonsearch protocols for radiographic consultation. Radiology 1990;177:851–856. White CS, Salis AI, Meyer CA. Missed lung cancer on chest radiography and computed tomography: imaging and medicolegal issues. J Thorac Imaging 1999;14:63–68. Flieder DB, Vazquez MF. Lung tumors with neuroendocrine morphology. A perspective for the new millennium. Radiol Clin North Am 2000;38:563–577, ix. Wang LT, Wilkins EW Jr, Bode HH. Bronchial carcinoid tumors in pediatric patients. Chest 1993;103:1426–1428. Davila DG, Dunn WF, Tazelaar HD, et al. Bronchial carcinoid tumors. Mayo Clin Proc 1993;68:795–803. Garcia-Yuste M, Matilla JM, GonzalezAragoneses F. Neuroendocrine tumors of the lung. Curr Opin Oncol 2008;20:148–154. Schreurs AJ, Westermann CJ, van den Bosch JM, et al. A twenty-five-year follow-up of ninety-three resected typical carcinoid tumors of the lung. J Thorac Cardiovasc Surg 1992;104:1470–1475. Harpole DH Jr, Feldman JM, Buchanan S, et al. Bronchial carcinoid tumors: a retrospective analysis of 126 patients. Ann Thorac Surg 1992;54:50–54. Ducrocq X, Thomas P, Massard G, et al. Operative risk and prognostic factors of typical bronchial carcinoid tumors. Ann Thorac Surg 1998;65:1410–1414. Martini N, Zaman MB, Bains MS, et al. Treatment and prognosis in bronchial carcinoids involving regional lymph nodes. J Thorac Cardiovasc Surg 1994;107:1–6. Marty-Ane CH, Costes V, Pujol JL, et al. Carcinoid tumors of the lung: do atypical features require aggressive management? Ann Thorac Surg 1995;59:78–83. Hallgrimsson JG, Jonsson T, Johannsson JH. Bronchopulmonary carcinoids in Iceland 1955–1984. A retrospective clinical and histopathologic study. Scand J Thorac Cardiovasc Surg 1989;23:275–278. Travis WD, Linnoila RI, Tsokos MG, et al. Neuroendocrine tumors of the lung with proposed criteria for large-cell

461. 462.

463.

464.

465.

466.

467.

468. 469.

470. 471. 472. 473.

474.

475.

476.

477.

478.

neuroendocrine carcinoma. An ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 1991;15:529–553. McCaughan BC, Martini N, Bains MS. Bronchial carcinoids. Review of 124 cases. J Thorac Cardiovasc Surg 1985;89:8–17. Schraufnagel D, Peloquin A, Pare JA, et al. Differentiating bronchioloalveolar carcinoma from adenocarcinoma. Am Rev Respir Dis 1982;125:74–79. Gould PM, Bonner JA, Sawyer TE, et al. Bronchial carcinoid tumors: importance of prognostic factors that influence patterns of recurrence and overall survival. Radiology 1998;208:181–185. Horton KM, Fishman EK. Cushing syndrome due to a pulmonary carcinoid tumor: multimodality imaging and diagnosis. J Comput Assist Tomogr 1998; 22:804–806. Shrager JB, Wright CD, Wain JC, et al. Bronchopulmonary carcinoid tumors associated with Cushing’s syndrome: a more aggressive variant of typical carcinoid. J Thorac Cardiovasc Surg 1997; 114:367–375. Doppman JL, Pass HI, Nieman L, et al. Failure of bronchial lavage to detect elevated levels of adrenocorticotropin (ACTH) in patients with ACTH-producing bronchial carcinoids. J Clin Endocrinol Metab 1989;69:1302–1304. Nessi R, Basso RP, Basso RS, et al. Bronchial carcinoid tumors: radiologic observations in 49 cases. J Thorac Imaging 1991;6:47–53. McGuinnis EJ, Lull RJ. Bronchial adenoma causing unilateral absence of pulmonary perfusion. Radiology 1976;120:367–368. Choplin RH, Kawamoto EH, Dyer RB, et al. Atypical carcinoid of the lung: radiographic features. AJR Am J Roentgenol 1986;146:665–668. Bateson EM, Whimster WF, Woo-Ming M. Ossified bronchial adenoma. Br J Radiol 1970;43:570–573. Altman RL, Miller WE, Carr DT, et al. Radiographic appearance of bronchial carcinoid. Thorax 1973;28:433–434. Good CA. Asymptomatic bronchial adenoma. Mayo Clin Proc 1953;28: 577–586. Rosado de Christenson ML, Abbott GF, Kirejczyk WM, et al. Thoracic carcinoids: radiologic-pathologic correlation. RadioGraphics 1999;19:707–736. Jeung MY, Gasser B, Gangi A, et al. Bronchial carcinoid tumors of the thorax: spectrum of radiologic findings. RadioGraphics 2002;22:351–365. Ferretti GR, Thony F, Bosson JL, et al. Benign abnormalities and carcinoid tumors of the central airways: diagnostic impact of CT bronchography. AJR Am J Roentgenol 2000;174:1307–1313. Magid D, Siegelman SS, Eggleston JC, et al. Pulmonary carcinoid tumors: CT assessment. J Comput Assist Tomogr 1989;13:244–247. Zwiebel BR, Austin JH, Grimes MM. Bronchial carcinoid tumors: assessment with CT of location and intratumoral calcification in 31 patients. Radiology 1991;179:483–486. Shin MS, Berland LL, Myers JL, et al. CT demonstration of an ossifying bronchial

873

Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

479.

480.

481.

482.

483.

484.

485.

486.

487.

488.

489.

490.

491.

492. 493. 494. 495.

874

carcinoid simulating broncholithiasis. AJR Am J Roentgenol 1989;153:51–52. Aronchick JM, Wexler JA, Christen B, et al. Computed tomography of bronchial carcinoid. J Comput Assist Tomogr 1986; 10:71–74. Davis SD, Zirn JR, Govoni AF, et al. Peripheral carcinoid tumor of the lung: CT diagnosis. AJR Am J Roentgenol 1990;155: 1185–1187. Marcilly MC, Howarth NR, Berthezene Y. Bronchial carcinoid tumor: demonstration by dynamic inversion recovery turbo-flash MR imaging. Eur Radiol 1998;8:1400–1402. Doppman JL, Pass HI, Nieman LK, et al. Detection of ACTH-producing bronchial carcinoid tumors: MR imaging vs CT. AJR Am J Roentgenol 1991;156:39–43. de Herder WW, Krenning EP, Malchoff CD, et al. Somatostatin receptor scintigraphy: its value in tumor localization in patients with Cushing’s syndrome caused by ectopic corticotropin or corticotropinreleasing hormone secretion. Am J Med 1994;96:305–312. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993;20:716–731. Westlin JE, Janson ET, Arnberg H, et al. Somatostatin receptor scintigraphy of carcinoid tumours using the [111In-DTPAD-Phe1]-octreotide. Acta Oncol 1993;32: 783–786. Doppman JL. Somatostatin receptor scintigraphy and the ectopic ACTH syndrome: the solution or just another test? Am J Med 1994;96:303–304. Nishizawa S, Higa T, Kuroda Y, et al. Increased accumulation of N-isopropyl-(I-123)p-iodoamphetamine in bronchial carcinoid tumor. J Nucl Med 1990;31:240–242. Erasmus JJ, McAdams HP, Patz EF Jr, et al. Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol 1998;170:1369–1373. Eriksson B, Bergstrom M, Sundin A, et al. The role of PET in localization of neuroendocrine and adrenocortical tumors. Ann N Y Acad Sci 2002;970:159–169. Wester HJ, Schottelius M, Scheidhauer K, et al. PET imaging of somatostatin receptors: design, synthesis and preclinical evaluation of a novel 18F-labelled, carbohydrated analogue of octreotide. Eur J Nucl Med Mol Imaging 2003;30: 117–122. Bateson EM. Relationship between intrapulmonary and endobronchial cartilage containing tumours, so called hamartomata. Thorax 1965;29 447–461. Gjevre JA, Myers JL, Prakash UB. Pulmonary hamartomas. Mayo Clin Proc 1996;71:14–20. Miura K, Hori T, Yoshizawa K, et al. Cystic pulmonary hamartoma. Ann Thorac Surg 1990;49:828–829. Mushtaq M, Ward SP, Hutchison JT, et al. Multiple cystic pulmonary hamartomas. Thorax 1992;47:1076–1077. Bennett LL, Lesar MS, Tellis CJ. Multiple calcified chondrohamartomas of the lung: CT appearance. J Comput Assist Tomogr 1985;9:180–182.

496. Poulsen JT, Jacobsen M, Francis D. Probable malignant transformation of a pulmonary hamartoma. Thorax 1979;34: 557–558. 497. Karasik A, Modan M, Jacob CO, et al. Increased risk of lung cancer in patients with chondromatous hamartoma. J Thorac Cardiovasc Surg 1980;80:217–220. 498. Ribet M, Jaillard-Thery S, Nuttens MC. Pulmonary hamartoma and malignancy. J Thorac Cardiovasc Surg 1994;107:611– 614. 499. Hedlund GL, Bisset GS III, Bove KE. Malignant neoplasms arising in cystic hamartomas of the lung in childhood. Radiology 1989;173:77–79. 500. Mark EJ. Mesenchymal cystic hamartoma of the lung. N Engl J Med 1986;315:1255– 1259. 501. Poirier TJ, Van Ordstrand HS. Pulmonary chondromatous hamartomas. Report of seventeen cases and review of the literature. Chest 1971;59:50–55. 502. Carney JA. The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma: a five-year review. Medicine (Baltimore) 1983;62:159–169. 503. Evans RA, Salisbury JR, Gimson A, et al. Indolent gastric epithelioid leiomyosarcoma in Carney’s Triad. Clin Radiol 1990;42:437–439. 504. Mazas-Artasona L, Romeo M, Felices R, et al. Gastro-oesophageal leiomyoblastomas and multiple pulmonary chondromas: an incomplete variant of Carney’s triad. Br J Radiol 1988;61:1181–1184. 505. Gabrail NY, Zara BY. Pulmonary hamartoma syndrome. Chest 1990; 97:962–965. 506. Schmutz GR, Fisch-Ponsot C, Sylvestre J. Carney syndrome: radiologic features. Can Assoc Radiol J 1994;45:148–150. 507. Darke CS, Day P, Grainger RG, et al. The bronchial circulation in a case of giant hamartoma of the lung. Br J Radiol 1972;45:147–150. 508. Doppman JL, Wilson G. Cystic pulmonary hamartoma. Br J Radiol 1965;38:629–631. 509. Siegelman SS, Khouri NF, Scott WW Jr, et al. Pulmonary hamartoma: CT findings. Radiology 1986;160:313–317. 510. Potente G, Macori F, Caimi M, et al. Noncalcified pulmonary hamartomas: computed tomography enhancement patterns with histologic correlation. J Thorac Imaging 1999;14:101–104. 511. Sakai F, Sone S, Kiyono K, et al. MR of pulmonary hamartoma: pathologic correlation. J Thorac Imaging 1994;9:51–55. 512. Ahn JM, Im JG, Seo JW, et al. Endobronchial hamartoma: CT findings in three patients. AJR Am J Roentgenol 1994; 163:49–50. 513. Stey CA, Vogt P, Russi EW. Endobronchial lipomatous hamartoma: a rare cause of bronchial occlusion. Chest 1998;113:254– 255. 514. McCarthy MJ, Rosado-de-Christenson ML. Tumors of the trachea. J Thorac Imaging 1995;10:180–198. 515. Regnard JF, Fourquier P, Levasseur P. Results and prognostic factors in resections of primary tracheal tumors: a multicenter retrospective study. The French Society of Cardiovascular Surgery. J Thorac Cardiovasc Surg 1996;111:808–813.

516. Allen HA, Angell F, Hankins J, et al. Leiomyoma of the trachea. AJR Am J Roentgenol 1983;141:683–684. 517. Davis WK, Roberts L Jr, Foster WL Jr, et al. Computed tomographic diagnosis of an endobronchial hamartoma. Invest Radiol 1988;23:941–944. 518. Swain ME, Coblentz CL. Tracheal chondroma: CT appearance. J Comput Assist Tomogr 1988;12:1085–1086. 519. Raymond GS, Murray SK, Logan PM. Granular cell tumour of the trachea: case report. Can Assoc Radiol J 1997;48:48–50. 520. Naidich DP. CT/MR correlation in the evaluation of tracheobronchial neoplasia. Radiol Clin North Am 1990;28:555–571. 521. Dennie CJ, Coblentz CL. The trachea: pathologic conditions and trauma. Can Assoc Radiol J 1993;44:157–167. 522. Koskinen SK, Niemi PT, Ekfors TO, et al. Glomus tumor of the trachea. Eur Radiol 1998;8:364–366. 523. Kim TS, Lee KS, Han J, et al. Mucoepidermoid carcinoma of the tracheobronchial tree: radiographic and CT findings in 12 patients. Radiology 1999; 212:643–648. 524. Kairalla RA, Carvalho CR, Parada AA, et al. Solitary plasmacytoma of the trachea treated by loop resection and laser therapy. Thorax 1988;43:1011–1012. 525. Logan PM, Miller RR, Müller NL. Solitary tracheal plasmacytoma: computed tomography and pathological findings. Can Assoc Radiol J 1995;46:125–126. 526. Chen JS, Chang YL, Shu HS, et al. Surgical treatment of a primary tracheal angiosarcoma. J Thorac Cardiovasc Surg 2003;125:191–193. 527. Allen MS. Malignant tracheal tumors. Mayo Clin Proc 1993;68:680–684. 528. Maziak DE, Todd TR, Keshavjee SH, et al. Adenoid cystic carcinoma of the airway: thirty-two-year experience. J Thorac Cardiovasc Surg 1996;112:1522–1531. 529. Kim TS, Lee KS, Han J, et al. Sialadenoid tumors of the respiratory tract: radiologicpathologic correlation. AJR Am J Roentgenol 2001;177:1145–1150. 530. Kwong JS, Müller NL, Miller RR. Diseases of the trachea and main-stem bronchi: correlation of CT with pathologic findings. RadioGraphics 1992;12:645–657. 531. Spizarny DL, Shepard JA, McLoud TC, et al. CT of adenoid cystic carcinoma of the trachea. AJR Am J Roentgenol 1986;146: 1129–1132. 532. Fitoz S, Atasoy C, Kizilkaya E, et al. Radiologic findings in primary pulmonary leiomyosarcoma. J Thorac Imaging 2000; 15:151–152. 533. Delany SG, Doyle TC, Bunton RW, et al. Pulmonary artery sarcoma mimicking pulmonary embolism. Chest 1993;103: 1631–1633. 534. Guccion JG, Rosen SH. Bronchopulmonary leiomyosarcoma and fibrosarcoma. A study of 32 cases and review of the literature. Cancer 1972;30:836–847. 535. McDonnell T, Kyriakos M, Roper C, et al. Malignant fibrous histiocytoma of the lung. Cancer 1988;61:137–145. 536. Reifsnyder AC, Smith HJ, Mullhollan TJ, et al. Malignant fibrous histiocytoma of the lung in a patient with a history of asbestos exposure. AJR Am J Roentgenol 1990; 154:65–66.

References 537. Yousem SA, Hochholzer L. Malignant fibrous histiocytoma of the lung. Cancer 1987;60:2532–2541. 538. Pui MH, Yu SP, Chen JD. Primary intrathoracic malignant fibrous histiocytoma and angiosarcoma. Australas Radiol 1999;43:3–6. 539. Petersen M. Radionuclide detection of primary pulmonary osteogenic sarcoma: a case report and review of the literature. J Nucl Med 1990;31:1110–1114. 540. Stark P, Smith DC, Watkins GE, et al. Primary intrathoracic extraosseous osteogenic sarcoma: report of three cases. Radiology 1990;174:725–726. 541. Doval DC, Kannan V, Acharya R, et al. Bronchial embryonal rhabdomyosarcoma: a case report. Acta Oncol 1994;33:832–833. 542. Shariff S, Thomas JA, Shetty N, et al. Primary pulmonary rhabdomyosarcoma in a child, with a review of literature. J Surg Oncol 1988;38:261–264. 543. Gimenez A, Franquet T, Prats R, et al. Unusual primary lung tumors: a radiologic-pathologic overview. RadioGraphics 2002;22:601–619. 544. Sheppard MN, Hansell DM, Du Bois RM, et al. Primary epithelioid angiosarcoma of the lung presenting as pulmonary hemorrhage. Hum Pathol 1997;28:383–385. 545. Simpson WL Jr, Mendelson DS. Pulmonary artery and aortic sarcomas: cross-sectional imaging. J Thorac Imaging 2000;15: 290–294. 546. Kacl GM, Bruder E, Pfammatter T, et al. Primary angiosarcoma of the pulmonary arteries: dynamic contrast-enhanced MRI. J Comput Assist Tomogr 1998;22:687–691. 547. Cox JE, Chiles C, Aquino SL, et al. Pulmonary artery sarcomas: a review of clinical and radiologic features. J Comput Assist Tomogr 1997;21:750–755. 548. Ablett MJ, Elliott ST, Mitchell L. Case report: pulmonary leiomyosarcoma presenting as a pseudoaneurysm. Clin Radiol 1998;53:851–852. 549. Wu YC, Wang LS, Chen W, et al. Primary pulmonary malignant hemangiopericytoma associated with coagulopathy. Ann Thorac Surg 1997;64:841–843. 550. Halle M, Blum U, Dinkel E, et al. CT and MR features of primary pulmonary hemangiopericytomas. J Comput Assist Tomogr 1993;17:51–55. 551. Katz DS, Scalzetti EM, Groskin SA, et al. Pleuropulmonary blastoma simulating an empyema in a young child. J Thorac Imaging 1995;10:112–116. 552. Kim KI, Flint JD, Müller NL. Pulmonary carcinosarcoma: radiologic and pathologic findings in three patients. AJR Am J Roentgenol 1997;169:691–694. 553. Koss MN, Hochholzer L, O’Leary T. Pulmonary blastomas. Cancer 1991;67: 2368–2381. 554. Solomon A, Rubinstein ZJ, Rogoff M, et al. Pulmonary blastoma. Pediatr Radiol 1982;12:148–149. 555. Weisbrod GL, Chamberlain DW, Tao LC. Pulmonary blastoma, report of three cases and a review of the literature. Can Assoc Radiol J 1988;39:130–136. 556. Han SS, Wills JS, Allen OS. Pulmonary blastoma: case report and literature review. Am J Roentgenol 1976;127:1048–1049. 557. Manivel JC, Priest JR, Watterson J, et al. Pleuropulmonary blastoma. The so-called

558. 559.

560.

561. 562. 563. 564.

565. 566.

567.

568.

569.

570.

571. 572. 573.

574.

575.

576.

pulmonary blastoma of childhood. Cancer 1988;62:1516–1526. Senac MO Jr, Wood BP, Isaacs H, et al. Pulmonary blastoma: a rare childhood malignancy. Radiology 1991;179:743–746. Kovanlikaya A, Pirnar T, Olgun N. Pulmonary blastoma: a rare case of childhood malignancy. Pediatr Radiol 1992;22:155. Priest JR, McDermott MB, Bhatia S, et al. Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer 1997;80:147–161. Kiziltepe TT, Patrick E, Alvarado C, et al. Pleuropulmonary blastoma and ovarian teratoma. Pediatr Radiol 1999;29:901–903. Arslanian A, Pischedda F, Filosso PL, et al. Primary choriocarcinoma of the lung. J Thorac Cardiovasc Surg 2003;125:193–196. Dines DE, Lillie JC, Henderson LL, et al. Solitary plasmacytoma of the trachea. Am Rev Respir Dis 1965;92:949–951. Egashira K, Hirakata K, Nakata H, et al. CT and MRI manifestations of primary pulmonary plasmacytoma. Clin Imaging 1995;19:17–19. Joseph G, Pandit M, Korfhage L. Primary pulmonary plasmacytoma. Cancer 1993;71:721–724. Quint LE, Glazer GM, Orringer MB, et al. Mediastinal lymph node detection and sizing at CT and autopsy. AJR Am J Roentgenol 1986;147:469–472. Shin MS, Carcelen MF, Ho KJ. Diverse roentgenographic manifestations of the rare pulmonary involvement in myeloma. Chest 1992;102:946–948. Askin FB, Rosai J, Sibley RK, et al. Malignant small cell tumor of the thoracopulmonary region in childhood: a distinctive clinicopathologic entity of uncertain histogenesis. Cancer 1979;43: 2438–2451. Cabezali R, Lozano R, Bustamante E, et al. Askin’s tumor of the chest wall: a case report in an adult. J Thorac Cardiovasc Surg 1994;107:960–962. Howman-Giles R, Uren RF, Kellie SJ. Gallium and thallium scintigraphy in pediatric peripheral primitive neuroectodermal tumor (Askin tumor) of the chest wall. J Nucl Med 1995;36:814–816. Takanami I, Imamura T. The treatment of Askin tumor: results of two cases. J Thorac Cardiovasc Surg 2002;123:391–392. Saifuddin A, Robertson RJ, Smith SE. The radiology of Askin tumours. Clin Radiol 1991;43:19–23. Sabate JM, Franquet T, Parellada JA, et al. Malignant neuroectodermal tumour of the chest wall (Askin tumour): CT and MR findings in eight patients. Clin Radiol 1994;49:634–638. Erasmus JJ, McAdams HP, Carraway MS. A 63-year-old woman with weight loss and multiple lung nodules. Chest 1997;111:236–238. Mukundan G, Urban BA, Askin FB, et al. Pulmonary epithelioid hemangioendothelioma: atypical radiologic findings of a rare tumor with pathologic correlation. J Comput Assist Tomogr 2000;24:719–720. Luburich P, Ayuso MC, Picado C, et al. CT of pulmonary epithelioid hemangioendothelioma. J Comput Assist Tomogr 1994;18:562–565.

577. Ledson MJ, Convery R, Carty A, et al. Epithelioid haemangioendothelioma. Thorax 1999;54:560–561. 578. England DM, Hochholzer L. Truly benign ‘bronchial adenoma’. Report of 10 cases of mucous gland adenoma with immunohistochemical and ultrastructural findings. Am J Surg Pathol 1995;19: 887–899. 579. Aisner SC, Chakravarthy AK, Joslyn JN, et al. Bilateral granular cell tumors of the posterior mediastinum. Ann Thorac Surg 1988;46:688–689. 580. Coleman BG, Arger PH, Stephenson LW. CT features of endobronchial granular cell myoblastoma. J Comput Assist Tomogr 1984;8:998–1000. 581. Deavers M, Guinee D, Koss MN, et al. Granular cell tumors of the lung. Clinicopathologic study of 20 cases. Am J Surg Pathol 1995;19:627–635. 582. Child SD, Staples CA, Chan N, et al. Lingular opacity with an endobronchial mass. Can Assoc Radiol J 1991;42:435– 437. 583. Mata JM, Caceres J, Ferrer J, et al. Endobronchial lipoma: CT diagnosis. J Comput Assist Tomogr 1991;15:750– 751. 584. Storey TF, Narla LD. Pleural lipoma in a child: CT evaluation. Pediatr Radiol 1991;21:141–142. 585. Trigaux JP, van Beers B, Weynants P. Hour-glass lipoma. Br J Radiol 1990; 63:497–498. 586. Budde RB Jr, Yankura JA. Leiomyomatosis with a solitary pleural metastasis. Clin Imaging 1989;13:228–230. 587. Abramson S, Gilkeson RC, Goldstein JD, et al. Benign metastasizing leiomyoma: clinical, imaging, and pathologic correlation. AJR Am J Roentgenol 2001; 176:1409–1413. 588. Lipton JH, Fong TC, Burgess KR. Miliary pattern as presentation of leiomyomatosis of the lung. Chest 1987;91:781–782. 589. Hertzanu Y, Heimer D, Hirsch M. Computed tomography of pulmonary endometriosis. Comput Radiol 1987; 11:81–84. 590. Morgan DE, Sanders C, McElvein RB, et al. Intrapulmonary teratoma: a case report and review of the literature. J Thorac Imaging 1992;7:70–77. 591. Nicholson AG, Magkou C, Snead D, et al. Unusual sclerosing haemangiomas and sclerosing haemangioma-like lesions, and the value of TTF-1 in making the diagnosis. Histopathology 2002;41:404–413. 592. Sakamoto K, Okita M, Kumagiri H, et al. Sclerosing hemangioma isolated to the mediastinum. Ann Thorac Surg 2003; 75:1021–1023. 593. Nam JE, Ryu YH, Cho SH, et al. Airtrapping zone surrounding sclerosing hemangioma of the lung. J Comput Assist Tomogr 2002;26:358–361. 594. Cheung YC, Ng SH, Chang JW, et al. Histopathological and CT features of pulmonary sclerosing haemangiomas. Clin Radiol 2003;58:630–635. 595. Im JG, Kim WH, Han MC, et al. Sclerosing hemangiomas of the lung and interlobar fissures: CT findings. J Comput Assist Tomogr 1994;18:34–38. 596. Katzenstein AL, Gmelich JT, Carrington CB. Sclerosing hemangioma of the lung: a

875

Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura

597.

598.

599. 600.

601.

602. 603. 604.

605.

606.

607.

608. 609.

610. 611.

612.

613.

614.

615.

876

clinicopathologic study of 51 cases. Am J Surg Pathol 1980;4:343–356. Fujiyoshi F, Ichinari N, Fukukura Y, et al. Sclerosing hemangioma of the lung: MR findings and correlation with pathological features. J Comput Assist Tomogr 1998;22:1006–1008. Kramer SS, Wehunt WD, Stocker JT, et al. Pulmonary manifestations of juvenile laryngotracheal papillomatosis. AJR Am J Roentgenol 1985;144:687–694. Clements R, Gravelle IH. Laryngeal papillomatosis. Clin Radiol 1986;37: 547–550. Lui D, Kumar A, Aggarwal S, et al. CT findings of malignant change in recurrent respiratory papillomatosis. J Comput Assist Tomogr 1995;19:804–807. Gruden JF, Webb WR, Sides DM. Adultonset disseminated tracheobronchial papillomatosis: CT features. J Comput Assist Tomogr 1994;18:640–642. Ravin CE, Bergin D, Bisset GS III, et al. Image interpretation session: 2000. RadioGraphics 2001;21:267–287. Naka Y, Nakao K, Hamaji Y, et al. Solitary squamous cell papilloma of the trachea. Ann Thorac Surg 1993;55:189–193. Hong SS, Lee JS, Lee KH, et al. Intravascular papillary endothelial hyperplasia of the lung. J Comput Assist Tomogr 2002;26:362–364. Matsubara O, Tan-Liu NS, Kenney RM, et al. Inflammatory pseudotumors of the lung: progression from organizing pneumonia to fibrous histiocytoma or to plasma cell granuloma in 32 cases. Hum Pathol 1988;19:807–814. Bragg DG, Chor PJ, Murray KA, et al. Lymphoproliferative disorders of the lung: histopathology, clinical manifestations, and imaging features. AJR Am J Roentgenol 1994;163:273–281. Copin MC, Gosselin BH, Ribet ME. Plasma cell granuloma of the lung: difficulties in diagnosis and prognosis. Ann Thorac Surg 1996;61:1477–1482. Cerfolio RJ, Allen MS, Nascimento AG, et al. Inflammatory pseudotumors of the lung. Ann Thorac Surg 1999;67:933–936. Agrons GA, Rosado-de-Christenson ML, Kirejczyk WM, et al. Pulmonary inflammatory pseudotumor: radiologic features. Radiology 1998;206:511–518. Narla LD, Newman B, Spottswood SS, et al. Inflammatory pseudotumor. RadioGraphics 2003;23:719–729. Kundu S, Weiser WJ, Chiu B. Inflammatory pseudotumour of the lung presenting as multiple pulmonary nodules: case report. Can Assoc Radiol J 1997;48:44–47. Shapiro MP, Gale ME, Carter BL. Variable CT appearance of plasma cell granuloma of the lung. J Comput Assist Tomogr 1987;11: 49–51. Verbeke JI, Verberne AA, Den Hollander JC, et al. Inflammatory myofibroblastic tumour of the lung manifesting as progressive atelectasis. Pediatr Radiol 1999;29:816–819. Erasmus JJ, McAdams HP, Patz EF Jr, et al. Calcifying fibrous pseudotumor of pleura: radiologic features in three cases. J Comput Assist Tomogr 1996;20:763–765. Morton LM, Turner JJ, Cerhan JR, et al. Proposed classification of lymphoid neoplasms for epidemiologic research from

616.

617.

618. 619.

620.

621. 622. 623.

624. 625.

626.

627.

628.

629. 630.

631.

632.

633.

the pathology working group of the international lymphoma epidemiology consortium (interLymph). Blood 2007; 110:695–708. Carbone PP, Kaplan HS, Musshoff K, et al. Report of the Committee on Hodgkin’s Disease Staging Classification. Cancer Res 1971;31:1860–1861. Lister TA, Crowther D, Sutcliffe SB, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol 1989;7:1630–1636. Castellino RA. Hodgkin disease: practical concepts for the diagnostic radiologist. Radiology 1986;159:305–310. Morton LM, Wang SS, Devesa SS, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006;107:265–276. Turner JJ, Hughes AM, Kricker A, et al. WHO non-Hodgkin’s lymphoma classification by criterion-based report review followed by targeted pathology review: an effective strategy for epidemiology studies. Cancer Epidemiol Biomarkers Prev 2005;14:2213–2219. White KS. Thoracic imaging of pediatric lymphomas. J Thorac Imaging 2001; 16:224–237. Smith SD, Rubin CM, Horvath A, et al. Non-Hodgkin’s lymphoma in children. Semin Oncol 1990;17:113–119. Ng YY, Healy JC, Vincent JM, et al. The radiology of non-Hodgkin’s lymphoma in childhood: a review of 80 cases. Clin Radiol 1994;49:594–600. Murphy SB. Childhood non-Hodgkin’s lymphoma. N Engl J Med 1978;299: 1446–1448. Filly R, Bland N, Castellino RA. Radiographic distribution of intrathoracic disease in previously untreated patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Radiology 1976;120:277–281. Castellino RA, Blank N, Hoppe RT, et al. Hodgkin disease: contributions of chest CT in the initial staging evaluation. Radiology 1986;160:603–605. Grossman H, Winchester PH, Bragg DG, et al. Roentgenographic changes in childhood Hodgkin’s disease. Am J Roentgenol Radium Ther Nucl Med 1970;108:354–364. Hopper KD, Diehl LF, Cole BA, et al. The significance of necrotic mediastinal lymph nodes on CT in patients with newly diagnosed Hodgkin disease. AJR Am J Roentgenol 1990;155:267–270. Samuels TH, Margolis M, Hamilton PA, et al. Mediastinal large-cell lymphoma. Can Assoc Radiol J 1992;43:120–126. Shaffer K, Smith D, Kirn D, et al. Primary mediastinal large-B-cell lymphoma: radiologic findings at presentation. AJR Am J Roentgenol 1996;167:425–430. Strijk SP. Lymph node calcification in malignant lymphoma. Presentation of nine cases and a review of the literature. Acta Radiol Diagn (Stockh) 1985;26:427–431. Wycoco D, Raval B. An unusual presentation of mediastinal Hodgkin’s lymphoma on computed tomography. J Comput Tomogr 1983;7:187–188. Negendank WG, al Katib AM, Karanes C, et al. Lymphomas: MR imaging contrast characteristics with clinical-pathologic

634.

635.

636.

637.

638.

639.

640.

641.

642.

643.

644. 645. 646. 647.

648. 649.

650.

651.

correlations. Radiology 1990;177: 209–216. Spiers AS, Husband JE, MacVicar AD. Treated thymic lymphoma: comparison of MR imaging with CT. Radiology 1997;203: 369–376. Radford JA, Cowan RA, Flanagan M, et al. The significance of residual mediastinal abnormality on the chest radiograph following treatment for Hodgkin’s disease. J Clin Oncol 1988;6:940–946. Shah N, Hoskin P, McMillan A, et al. The impact of FDG positron emission tomography imaging on the management of lymphomas. Br J Radiol 2000;73:482– 487. Maisey NR, Hill ME, Webb A, et al. Are 18fluorodeoxyglucose positron emission tomography and magnetic resonance imaging useful in the prediction of relapse in lymphoma residual masses? Eur J Cancer 2000;36:200–206. Rahmouni A, Divine M, Lepage E, et al. Mediastinal lymphoma: quantitative changes in gadolinium enhancement at MR imaging after treatment. Radiology 2001; 219:621–628. Rahmouni A, Tempany C, Jones R, et al. Lymphoma: monitoring tumor size and signal intensity with MR imaging. Radiology 1993;188:445–451. Baron RL, Sagel SS, Baglan RJ. Thymic cysts following radiation therapy for Hodgkin disease. Radiology 1981;141: 593–597. Kim HC, Nosher J, Haas A, et al. Cystic degeneration of thymic Hodgkin’s disease following radiation therapy. Cancer 1985; 55:354–356. Lewis ER, Caskey CI, Fishman EK. Lymphoma of the lung: CT findings in 31 patients. AJR Am J Roentgenol 1991; 156:711–714. Diederich S, Link TM, Zuhlsdorf H, et al. Pulmonary manifestations of Hodgkin’s disease: radiographic and CT findings. Eur Radiol 2001;11:2295–2305. North LB, Libshitz HI, Lorigan JG. Thoracic lymphoma. Radiol Clin North Am 1990;28:745–762. Shuman LS, Libshitz HI. Solid pleural manifestations of lymphoma. AJR Am J Roentgenol 1984;142:269–273. Lee KS, Kim Y, Primack SL. Imaging of pulmonary lymphomas. AJR Am J Roentgenol 1997;168:339–345. Cartier Y, Johkoh T, Honda O, et al. Primary pulmonary Hodgkin’s disease: CT findings in three patients. Clin Radiol 1999; 54:182–184. Ferraro P, Trastek VF, Adlakha H, et al. Primary non-Hodgkin’s lymphoma of the lung. Ann Thorac Surg 2000;69:993–997. Isaacson P, Wright DH. Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma. Cancer 1983;52:1410–1416. Holland EA, Ghahremani GG, Fry WA, et al. Evolution of pulmonary pseudolymphomas: clinical and radiologic manifestations. J Thorac Imaging 1991; 6:74–80. O’Donnell PG, Jackson SA, Tung KT, et al. Radiological appearances of lymphomas arising from mucosa-associated lymphoid tissue (MALT) in the lung. Clin Radiol 1998;53:258–263.

References 652. Kennedy JL, Nathwani BN, Burke JS, et al. Pulmonary lymphomas and other pulmonary lymphoid lesions. A clinicopathologic and immunologic study of 64 patients. Cancer 1985;56:539–552. 653. King LJ, Padley SP, Wotherspoon AC, et al. Pulmonary MALT lymphoma: imaging findings in 24 cases. Eur Radiol 2000;10: 1932–1938. 654. Kradin RL, Mark EJ. Benign lymphoid disorders of the lung, with a theory regarding their development. Hum Pathol 1983;14:857–867. 655. Lee DK, Im JG, Lee KS, et al. B-cell lymphoma of bronchus-associated lymphoid tissue (BALT): CT features in 10 patients. J Comput Assist Tomogr 2000;24: 30–34. 656. Knisely BL, Mastey LA, Mergo PJ, et al. Pulmonary mucosa-associated lymphoid tissue lymphoma: CT and pathologic findings. AJR Am J Roentgenol 1999;172: 1321–1326. 657. McCulloch GL, Sinnatamby R, Stewart S, et al. High-resolution computed tomographic appearance of MALToma of the lung. Eur Radiol 1998;8:1669–1673. 658. Guinee DG Jr, Perkins SL, Travis WD, et al. Proliferation and cellular phenotype in lymphomatoid granulomatosis: implications of a higher proliferation index in B cells. Am J Surg Pathol 1998;22: 1093–1100. 659. Liebow AA, Carrington CR, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol 1972;3:457–558. 660. Pisani RJ, DeRemee RA. Clinical implications of the histopathologic diagnosis of pulmonary lymphomatoid granulomatosis. Mayo Clin Proc 1990;65: 151–163. 661. Lee JS, Tuder R, Lynch DA. Lymphomatoid granulomatosis: radiologic features and pathologic correlations. AJR Am J Roentgenol 2000;175:1335–1339. 662. Wechsler RJ, Steiner RM, Israel HL, et al. Chest radiograph in lymphomatoid granulomatosis: comparison with Wegener granulomatosis. AJR Am J Roentgenol 1984;142:79–83. 663. Dee PM, Arora NS, Innes DJ Jr. The pulmonary manifestations of lymphomatoid granulomatosis. Radiology 1982;143:613–618. 664. Benamore RE, Weisbrod GL, Hwang DM, et al. Reversed halo sign in lymphomatoid granulomatosis. Br J Radiol 2007;80: e162–e166. 665. Mason AC, White CS. CT appearance of endobronchial non-Hodgkin lymphoma. J Comput Assist Tomogr 1994;18:559–561. 666. Gollub MJ, Castellino RA. Diffuse endobronchial non-Hodgkin’s lymphoma: CT demonstration. AJR Am J Roentgenol 1995;164:1093–1094. 667. Kim KI, Lee JW, Lee MK, et al. Polypoid endobronchial Hodgkin’s disease with pneumomediastinum. Br J Radiol 1999; 72:392–394. 668. MacDonald JB. Lung involvement in Hodgkin’s disease. Thorax 1977;32:664– 667. 669. Whitcomb ME, Schwarz MI, Keller AR, et al. Hodgkin’s disease of the lung. Am Rev Respir Dis 1972;106:79–85. 670. Aquino SL, Chen MY, Kuo WT, et al. The CT appearance of pleural and extrapleural

671.

672.

673.

674.

675.

676.

677.

678.

679.

680. 681.

682.

683.

684. 685.

686.

687.

688.

disease in lymphoma. Clin Radiol 1999;54:647–650. Nakatsuka S, Yao M, Hoshida Y, et al. Pyothorax-associated lymphoma: a review of 106 cases. J Clin Oncol 2002;20: 4255–4260. Kim Y, Lee SW, Choi HY, et al. A case of pyothorax-associated lymphoma simulating empyema necessitatis. Clin Imaging 2003;27:162–165. Brun V, Revel MP, Danel C, et al. Case report. Pyothorax-associated lymphoma: diagnosis at percutaneous core biopsy with CT guidance. AJR Am J Roentgenol 2003; 180:969–971. Ansari MQ, Dawson DB, Nador R, et al. Primary body cavity-based AIDS-related lymphomas. Am J Clin Pathol 1996;105: 221–229. Nador RG, Cesarman E, Chadburn A, et al. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi’s sarcoma-associated herpes virus. Blood 1996;88:645–656. Castellino RA, Hilton S, O’Brien JP, et al. Non-Hodgkin lymphoma: contribution of chest CT in the initial staging evaluation. Radiology 1996;199:129–132. Cohen MD, Siddiqui A, Weetman R, et al. Hodgkin disease and non-Hodgkin lymphomas in children: utilization of radiological modalities. Radiology 1986; 158:499–505. Bergin CJ, Healy MV, Zincone GE, et al. MR evaluation of chest wall involvement in malignant lymphoma. J Comput Assist Tomogr 1990;14:928–932. Tesoro-Tess JD, Balzarini L, Ceglia E, et al. Magnetic resonance imaging in the initial staging of Hodgkin’s disease and non-Hodgkin lymphoma. Eur J Radiol 1991;12:81–90. Rehm PK. Radionuclide evaluation of patients with lymphoma. Radiol Clin North Am 2001;39:957–978. Bar-Shalom R, Mor M, Yefremov N, et al. The value of Ga-67 scintigraphy and F-18 fluorodeoxyglucose positron emission tomography in staging and monitoring the response of lymphoma to treatment. Semin Nucl Med 2001;31:177–190. Fiche M, Caprons F, Berger F, et al. Primary pulmonary non-Hodgkin’s lymphomas. Histopathology 1995;26: 529–537. Abbondanzo SL, Rush W, Bijwaard KE, et al. Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases. Am J Surg Pathol 2000;24:587–597. Travis WD, Galvin JR. Non-neoplastic pulmonary lymphoid lesions. Thorax 2001;56:964–971. Klatte EC, Yardley J, Smith EB, et al. The pulmonary manifestations and complications of leukemia. AJR Am J Roentgenol 1963;89:598–609. Maile CW, Moore AV, Ulreich S, et al. Chest radiographic-pathologic correlation in adult leukemia patients. Invest Radiol 1983;18:495–499. Winer-Muram HT, Rubin SA, Fletcher BD, et al. Childhood leukemia: diagnostic accuracy of bedside chest radiography for severe pulmonary complications. Radiology 1994;193:127–133. Seynaeve P, Mathijs R, Kockx M, et al. Case report: the air crescent sign in pulmonary

689.

690.

691. 692.

693.

694.

695.

696.

697.

698.

699.

700. 701.

702.

703.

704.

705.

706.

leukaemic infiltrate. Clin Radiol 1992;45:40–41. Heyneman LE, Johkoh T, Ward S, et al. Pulmonary leukemic infiltrates: highresolution CT findings in 10 patients. AJR Am J Roentgenol 2000;174:517–521. Tanaka N, Matsumoto T, Miura G, et al. CT findings of leukemic pulmonary infiltration with pathologic correlation. Eur Radiol 2002;12:166–174. Takasugi JE, Godwin JD, Marglin SI, et al. Intrathoracic granulocytic sarcomas. J Thorac Imaging 1996;11:223–230. Ooi GC, Chim CS, Khong PL, et al. Radiologic manifestations of granulocytic sarcoma in adult leukemia. AJR Am J Roentgenol 2001;176:1427–1431. Vernant JP, Brun B, Mannoni P, et al. Respiratory distress of hyperleukocytic granulocytic leukemias. Cancer 1979;44: 264–268. van Buchem MA, Wondergem JH, Kool LJ, et al. Pulmonary leukostasis: radiologicpathologic study. Radiology 1987;165: 739–741. Myers TJ, Cole SR, Klatsky AU, et al. Respiratory failure due to pulmonary leukostasis following chemotherapy of acute nonlymphocytic leukemia. Cancer 1983;51:1808–1813. England DM, Hochholzer L, McCarthy MJ. Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases. Am J Surg Pathol 1989;13:640–658. Briselli M, Mark EJ, Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature. Cancer 1981;47:2678–2689. Cardillo G, Facciolo F, Cavazzana AO, et al. Localized (solitary) fibrous tumors of the pleura: an analysis of 55 patients. Ann Thorac Surg 2000;70:1808–1812. Hill JK, Heitmiller RF, Askin FB, et al. Localized benign pleural mesothelioma arising in a radiation field. Clin Imaging 1997;21:189–194. Ellis K, Wolff M. Mesotheliomas and secondary tumors of the pleura. Semin Roentgenol 1977;12:303–311. Saifuddin A, Da Costa P, Chalmers AG, et al. Primary malignant localized fibrous tumours of the pleura: clinical, radiological and pathological features. Clin Radiol 1992;45:13–17. de Perrot M, Kurt AM, Robert JH, et al. Clinical behavior of solitary fibrous tumors of the pleura. Ann Thorac Surg 1999;67: 1456–1459. Aufiero TX, McGary SA, Campbell DB, et al. Intrapulmonary benign fibrous tumor of the pleura. J Thorac Cardiovasc Surg 1995;110:549–551. Spizarny DL, Gross BH, Shepard JA. CT findings in localized fibrous mesothelioma of the pleural fissure. J Comput Assist Tomogr 1986;10:942–944. Rosado-de-Christenson ML, Abbott GF, McAdams HP, et al. From the archives of the AFIP: localized fibrous tumors of the pleura. RadioGraphics 2003;23:759– 783. Moran CA, Hochholzer L, Rush W, et al. Primary intrapulmonary meningiomas. A clinicopathologic and immunohistochemical study of ten cases. Cancer 1996;78:2328–2333.

877

Chapter 13 • Neoplasms of the Lungs, Airways, and Pleura 707. Scharifker D, Kaneko M. Localized fibrous ‘mesothelioma’ of pleura (submesothelial fibroma): a clinicopathologic study of 18 cases. Cancer 1979;43:627–635. 708. Kinoshita T, Ishii K, Miyasato S. Localized pleural mesothelioma: CT and MR findings. Magn Reson Imaging 1997;15:377–379. 709. Chamberlain MH, Taggart DP. Solitary fibrous tumor associated with hypoglycemia: an example of the Doege-Potter syndrome. J Thorac Cardiovasc Surg 2000;119:185–187. 710. Karabulut N, Goodman LR. Pedunculated solitary fibrous tumor of the interlobar fissure: a wandering chest mass. AJR Am J Roentgenol 1999;173:476–477. 711. Soulen MC, Greco-Hunt VT, Templeton P. Cases from A3CR2. Migratory chest mass. Invest Radiol 1990;25:209–211. 712. Desser TS, Stark P. Pictorial essay: solitary fibrous tumor of the pleura. J Thorac Imaging 1998;13:27–35. 713. Ferretti GR, Chiles C, Choplin RH, et al. Localized benign fibrous tumors of the pleura. AJR Am J Roentgenol 1997;169: 683–686. 714. Lee KS, Im JG, Choe KO, et al. CT findings in benign fibrous mesothelioma of the pleura: pathologic correlation in nine patients. AJR Am J Roentgenol 1992;158: 983–986. 715. Tublin ME, Tessler FN, Rifkin MD. US case of the day. Solitary fibrous tumor of the pleura (SFTP). RadioGraphics 1998;18: 523–525. 716. Harris GN, Rozenshtein A, Schiff MJ. Benign fibrous mesothelioma of the pleura: MR imaging findings. AJR Am J Roentgenol 1995;165:1143–1144. 717. Lee KS, Im JG. Benign fibrous mesothelioma of the pleura: MR findings (letter). AJR Am J Roentgenol 1993;160: 204–205. 718. George JC. Benign fibrous mesothelioma of the pleura: MR findings. AJR Am J Roentgenol 1993;160:204–205. 719. Padovani B, Mouroux J, Raffaelli C, et al. Benign fibrous mesothelioma of the pleura: MR study and pathologic correlation. Eur Radiol 1996;6:425–428. 720. Tateishi U, Nishihara H, Morikawa T, et al. Solitary fibrous tumor of the pleura: MR appearance and enhancement pattern. J Comput Assist Tomogr 2002;26:174–179. 721. Kawashima A, Libshitz HI. Malignant pleural mesothelioma: CT manifestations in 50 cases. AJR Am J Roentgenol 1990;155: 965–969. 722. Brenner J, Sordillo PP, Magill GB, et al. Malignant mesothelioma of the pleura: review of 123 patients. Cancer 1982;49: 2431–2435. 723. Antman KH, Corson JM. Benign and malignant pleural mesothelioma. Clin Chest Med 1985;6:127–140. 724. Hillerdal G. Malignant mesothelioma 1982: review of 4710 published cases. Br J Dis Chest 1983;77:321–343. 725. Aisner J, Wiernik PH. Malignant mesothelioma. Current status and future prospects. Chest 1978;74:438–444. 726. Erzen C, Eryilmaz M, Kalyoncu F, et al. CT findings in malignant pleural mesothelioma related to nonoccupational exposure to asbestos and fibrous zeolite (erionite). J Comput Assist Tomogr 1991;15:256–260.

878

727. Behling CA, Wolf PL, Haghighi P. AIDS and malignant mesothelioma: is there a connection? Chest 1993;103:1268– 1269. 728. Anderson KA, Hurley WC, Hurley BT, et al. Malignant pleural mesothelioma following radiotherapy in a 16-year-old boy. Cancer 1985;56:273–276. 729. Legha SS, Muggia FM. Pleural mesothelioma: clinical features and therapeutic implications. Ann Intern Med 1977;87:613–621. 730. Adams VI, Unni KK, Muhm JR, et al. Diffuse malignant mesothelioma of pleura. Diagnosis and survival in 92 cases. Cancer 1986;58:1540–1551. 731. Sugarbaker DJ, Garcia JP, Richards WG, et al. Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients. Ann Surg 1996;224: 288–294. 732. Otis CN, Carter D, Cole S, et al. Immunohistochemical evaluation of pleural mesothelioma and pulmonary adenocarcinoma. A bi-institutional study of 47 cases. Am J Surg Pathol 1987;11: 445–456. 733. Raizon A, Schwartz A, Hix W, et al. Calcification as a sign of sarcomatous degeneration of malignant pleural mesotheliomas: a new CT finding. J Comput Assist Tomogr 1996;20:42–44. 734. Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group. Chest 1995; 108:1122–1128. 735. Rusch VW, Venkatraman E. The importance of surgical staging in the treatment of malignant pleural mesothelioma. J Thorac Cardiovasc Surg 1996;111:815–825. 736. Patz EF Jr, Rusch VW, Heelan R. The proposed new international TNM staging system for malignant pleural mesothelioma: application to imaging. AJR Am J Roentgenol 1996;166:323–327. 737. Heelan R. Staging and response to therapy of malignant pleural mesothelioma. Lung Cancer 2004;45(suppl 1):S59–S61. 738. Van Schil P. Malignant pleural mesothelioma: staging systems. Lung Cancer 2005;49(suppl 1):S45–S48. 739. Antman KH. Clinical presentation and natural history of benign and malignant mesothelioma. Semin Oncol 1981;8:313– 320. 740. Grant DC, Seltzer SE, Antman KH, et al. Computed tomography of malignant pleural mesothelioma. J Comput Assist Tomogr 1983;7:626–632. 741. Law MR, Gregor A, Husband JE, et al. Computed tomography in the assessment of malignant mesothelioma of the pleura. Clin Radiol 1982;33:67–70. 742. Leung AN, Müller NL, Miller RR. CT in differential diagnosis of diffuse pleural disease. AJR Am J Roentgenol 1990;154: 487–492. 743. Libshitz HI. Malignant pleural mesothelioma: the role of computed tomography. J Comput Tomogr 1984;8:15– 20. 744. Lorigan JG, Libshitz HI. MR imaging of malignant pleural mesothelioma. J Comput Assist Tomogr 1989;13:617–620.

745. Miller BH, Rosado-de-Christenson ML, Mason AC, et al. From the archives of the AFIP. Malignant pleural mesothelioma: radiologic-pathologic correlation. RadioGraphics 1996;16:613–644. 746. Mirvis S, Dutcher JP, Haney PJ, et al. CT of malignant pleural mesothelioma. AJR Am J Roentgenol 1983;140:665–670. 747. Patz EF Jr, Shaffer K, Piwnica-Worms DR, et al. Malignant pleural mesothelioma: value of CT and MR imaging in predicting resectability. AJR Am J Roentgenol 1992; 159:961–966. 748. Wechsler RJ, Rao VM, Steiner RM. The radiology of thoracic malignant mesothelioma. Crit Rev Diagn Imaging 1984;20:283–310. 749. Ng CS, Munden RF, Libshitz HI. Malignant pleural mesothelioma: the spectrum of manifestations on CT in 70 cases. Clin Radiol 1999;54:415–421. 750. Knuuttila A, Kivisaari L, Kivisaari A, et al. Evaluation of pleural disease using MR and CT. With special reference to malignant pleural mesothelioma. Acta Radiol 2001;42:502–507. 751. Rusch VW, Godwin JD, Shuman WP. The role of computed tomography scanning in the initial assessment and the follow-up of malignant pleural mesothelioma. J Thorac Cardiovasc Surg 1988;96:171–177. 752. Heelan RT, Rusch VW, Begg CB, et al. Staging of malignant pleural mesothelioma: comparison of CT and MR imaging. AJR Am J Roentgenol 1999;172:1039–1047. 753. Gerbaudo VH, Sugarbaker DJ, BritzCunningham S, et al. Assessment of malignant pleural mesothelioma with (18) F-FDG dual-head gamma-camera coincidence imaging: comparison with histopathology. J Nucl Med 2002;43: 1144–1149. 754. Rabinowitz JG, Efremidis SC, Cohen B, et al. A comparative study of mesothelioma and asbestosis using computed tomography and conventional chest radiography. Radiology 1982;144:453– 460. 755. Carretta A, Landoni C, Melloni G, et al. 18-FDG positron emission tomography in the evaluation of malignant pleural diseases: a pilot study. Eur J Cardiothorac Surg 2000;17:377–383. 756. Kruger S, Pauls S, Mottaghy FM, et al. Integrated FDG PET-CT imaging improves staging in malignant pleural mesothelioma. Nuklearmedizin 2007;46:239–243. 757. Otsuka H, Terazawa K, Morita N, et al. Is FDG-PET/CT useful for managing malignant pleural mesothelioma? J Med Invest 2009;56:16–20. 758. Benard F, Sterman D, Smith RJ, et al. Prognostic value of FDG PET imaging in malignant pleural mesothelioma. J Nucl Med 1999;40:1241–1245. 759. Evans AR, Wolstenholme RJ, Shettar SP, et al. Primary pleural liposarcoma. Thorax 1985;40:554–555. 760. Buxton RC, Tan CS, Khine NM, et al. Atypical transmural thoracic lipoma: CT diagnosis. J Comput Assist Tomogr 1988; 12:196–198. 761. Epler GR, McLoud TC, Munn CS, et al. Pleural lipoma. Diagnosis by computed tomography. Chest 1986;90:265–268. 762. Gramiak R, Koerner HJ. A roentgen diagnostic observation in subpleural

References

763.

764. 765.

766.

767.

768.

769.

770.

771.

772.

773.

774.

775.

776. 777.

lipoma. Am J Roentgenol Radium Ther Nucl Med 1966;98:465–467. Iqbal M, Posen J, Bhuiya TA, et al. Lymphocyte – rich pleural liposarcoma mimicking pericardial cyst. J Thorac Cardiovasc Surg 2000;120:610–612. Shanley DJ, Mulligan ME. Osteosarcoma with isolated metastases to the pleura. Pediatr Radiol 1991;21:226. Kravis MM, Hutton LC. Solitary plasma cell tumor of the pleura manifested as massive hemothorax. AJR Am J Roentgenol 1993;161:543–544. Lin BT, Colby T, Gown AM, et al. Malignant vascular tumors of the serous membranes mimicking mesothelioma. A report of 14 cases. Am J Surg Pathol 1996; 20:1431–1439. Crotty EJ, McAdams HP, Erasmus JJ, et al. Epithelioid hemangioendothelioma of the pleura: clinical and radiologic features. AJR Am J Roentgenol 2000;175:1545–1549. Coppage L, Shaw C, Curtis AM. Metastatic disease to the chest in patients with extrathoracic malignancy. J Thorac Imaging 1987;2:24–37. Hirakata K, Nakata H, Nakagawa T. CT of pulmonary metastases with pathological correlation. Semin Ultrasound CT MR 1995;16:379–394. Kundu S, Murphy J, Towers M, et al. Computed tomographic demonstration of very-low-density pulmonary nodules in metastatic gastric carcinoma: case report. Can Assoc Radiol J 1999;50:198–201. Yousem DM, Scatarige JC, Fishman EK, et al. Low-attenuation thoracic metastases in testicular malignancy. AJR Am J Roentgenol 1986;146:291–293. Seo JB, Im JG, Goo JM, et al. Atypical pulmonary metastases: spectrum of radiologic findings. RadioGraphics 2001;21: 403–417. Ren H, Hruban RH, Kuhlman JE, et al. Computed tomography of inflation-fixed lungs: the beaded septum sign of pulmonary metastases. J Comput Assist Tomogr 1989;13:411–416. Murata K, Takahashi M, Mori M, et al. Pulmonary metastatic nodules: CT-pathologic correlation. Radiology 1992; 182:331–335. Chan DP, Griffith JF, Lee TW, et al. Cystic pulmonary metastases from epithelioid cell sarcoma. Ann Thorac Surg 2003;75: 1652–1654. Davis SD. CT evaluation for pulmonary metastases in patients with extrathoracic malignancy. Radiology 1991;180:1–12. Jimenez JM, Casey SO, Citron M, et al. Calcified pulmonary metastases from

778. 779.

780. 781.

782.

783.

784.

785.

786.

787.

788.

789.

790.

medullary carcinoma of the thyroid. Comput Med Imaging Graph 1995;19: 325–328. Maile CW, Rodan BA, Godwin JD, et al. Calcification in pulmonary metastases. Br J Radiol 1982;55:108–113. Toye R, Jones DK, Armstrong P, et al. Numerous pulmonary metastases from renal cell carcinoma confined to the middle lobe. Clin Radiol 1990;42:443–444. Charig MJ, Williams MP. Pulmonary lacunae: sequelae of metastases following chemotherapy. Clin Radiol 1990;42:93–96. Panicek DM, Toner GC, Heelan RT, et al. Nonseminomatous germ cell tumors: enlarging masses despite chemotherapy. Radiology 1990;175:499–502. MacMahon H. Improvement in detection of pulmonary nodules: digital image processing and computer-aided diagnosis. RadioGraphics 2000;20:1169–1177. Grampp S, Bankier AA, Zoubek A, et al. Spiral CT of the lung in children with malignant extra-thoracic tumors: distribution of benign vs malignant pulmonary nodules. Eur Radiol 2000;10: 1318–1322. Gross BH, Glazer GM, Bookstein FL. Multiple pulmonary nodules detected by computed tomography: diagnostic implications. J Comput Assist Tomogr 1985;9:880–885. Williams MP, Husband JE, Heron CW. Intrathoracic manifestations of metastatic testicular seminoma: a comparison of chest radiographic and CT findings. AJR Am J Roentgenol 1987;149:473–475. Chalmers N, Best JJ. The significance of pulmonary nodules detected by CT but not by chest radiography in tumour staging. Clin Radiol 1991;44:410–412. Heaston DK, Putman CE, Rodan BA, et al. Solitary pulmonary metastases in high-risk melanoma patients: a prospective comparison of conventional and computed tomography. AJR Am J Roentgenol 1983; 141:169–174. Kostrubiak I, Whitley NO, Aisner J, et al. The use of computed body tomography in malignant melanoma. JAMA 1988;259: 2896–2897. Feuerstein IM, Jicha DL, Pass HI, et al. Pulmonary metastases: MR imaging with surgical correlation – a prospective study. Radiology 1992;182:123–129. Bruegel M, Gaa J, Woertler K, et al. MRI of the lung: value of different turbo spin-echo, single-shot turbo spin-echo, and 3D gradient-echo pulse sequences for the detection of pulmonary metastases. J Magn Reson Imaging 2007;25:73–81.

791. Bohdiewicz PJ, Juni JE, Ball D, et al. Krukenberg tumor and lung metastases from colon carcinoma diagnosed with F-18 FDG PET. Clin Nucl Med 1995;20:419–420. 792. Connolly LP, Bloom DA, Kozakewich H, et al. Localization of Tc-99m MDP in neuroblastoma metastases to the liver and lung. Clin Nucl Med 1996;21:629–633. 793. Pevarski DJ, Drane WE, Scarborough MT. The usefulness of bone scintigraphy with SPECT images for detection of pulmonary metastases from osteosarcoma. AJR Am J Roentgenol 1998;170:319–322. 794. Braman SS, Whitcomb ME. Endobronchial metastasis. Arch Intern Med 1975;135: 543–547. 795. Baumgartner WA, Mark JB. Metastatic malignancies from distant sites to the tracheobronchial tree. J Thorac Cardiovasc Surg 1980;79:499–503. 796. Carlin BW, Harrell JH, Olson LK, et al. Endobronchial metastases due to colorectal carcinoma. Chest 1989;96:1110–1114. 797. Heitmiller RF, Marasco WJ, Hruban RH, et al. Endobronchial metastasis. J Thorac Cardiovasc Surg 1993;106:537–542. 798. Plavsic BM, Robinson AE, Freundlich IM, et al. Melanoma metastatic to the bronchus: radiologic features in two patients. J Thorac Imaging 1994;9:67–70. 799. Albertini RE, Ekberg NL. Endobronchial metastasis in breast cancer. Thorax 1980;35:435–440. 800. Boiselle PM. Imaging of the large airways. Clin Chest Med 2008;29:181–193, vii. 801. Boiselle PM, Lee KS, Ernst A. Multidetector CT of the central airways. J Thorac Imaging 2005;20:186–195. 802. Johkoh T, Ikezoe J, Tomiyama N, et al. CT findings in lymphangitic carcinomatosis of the lung: correlation with histologic findings and pulmonary function tests. AJR Am J Roentgenol 1992;158:1217–1222. 803. Matthay RA, Coppage L, Shaw C, et al. Malignancies metastatic to the pleura. Invest Radiol 1990;25:601–619. 804. Anderson CB, Philpott GW, Ferguson TB. The treatment of malignant pleural effusions. Cancer 1974;33:916–922. 805. Sahn SA. Malignant pleural effusions. Clin Chest Med 1985;6:113–125. 806. Hough DM. Multifocal osteosarcoma with extensive pleural metastatic disease. Australas Radiol 1992;36:147–149. 807. Light RW. Pleural disease. Lippincott Williams and Wilkins, 1995. 808. Meyer PC. Metastatic carcinoma of the pleura. Thorax 1966;21:437–443. 809. Chernow B, Sahn SA. Carcinomatous involvement of the pleura: an analysis of 96 patients. Am J Med 1977;63:695–702.

879

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14

Mediastinal and aortic disease

MEDIASTINAL DISEASES Imaging techniques Frequency of mediastinal masses Differential diagnosis of mediastinal masses Prevascular masses Paracardiac masses Paratracheal, subcarinal, and paraesophageal masses Paravertebral masses SPECIFIC MEDIASTINAL LESIONS Cysts or cystlike lesions Bronchogenic cysts Esophageal duplication cysts Pericardial cysts Neurenteric cysts Mediastinal pancreatic pseudocyst Lateral thoracic meningocele Lymphoceles and thoracic duct cysts Desmoid tumor of the mediastinum Diaphragmatic hernia Hiatal hernia Esophageal lesions Fat-containing lesions of the mediastinum Mediastinal lipomatosis Fatty tumors of the mediastinum Herniation of abdominal fat Extramedullary hematopoiesis Germ cell tumors of the mediastinum Teratoma Malignant nonteratomatous germ cell tumors Lymphadenopathy Causes of lymphadenopathy Castleman disease Diagnosis of lymphadenopathy Lymph node calcification Low attenuation on CT Contrast enhancement on CT Chest radiographic signs of mediastinal lymph node enlargement CT of mediastinal lymph node enlargement MRI of mediastinal lymph node enlargement PET imaging of mediastinal lymph node enlargement Chest radiographic findings of hilar lymph node enlargement CT of hilar node enlargement MRI of hilar node enlargement Pitfalls in the diagnosis of intrathoracic lymph node enlargement

MEDIASTINAL DISEASES Imaging techniques The chest radiograph is usually the first imaging study obtained in a patient with a known or suspected mediastinal or hilar mass. Furthermore, mediastinal or hilar abnormalities are often discovered serendipitously on chest radiographs obtained for other purposes. Thus, the role of chest radiography for detection of hilar and mediastinal abnormalities remains essential, and thorough knowl-

Lymphovascular tumors of the mediastinum Lymphangioma Blood vessel tumors Mediastinal hemorrhage Mediastinitis Acute mediastinitis Fibrosing mediastinitis Mediastinal panniculitis Neurogenic tumors of the mediastinum Imaging of neurogenic tumors Mediastinal paragangliomas Parathyroid lesions of the mediastinum Pneumomediastinum Radiographic findings of pneumomediastinum Sarcomas of the mediastinum Superior vena cava syndrome Thymic lesions Normal thymus Thymic hyperplasia Thymic epithelial neoplasm Neuroendocrine tumors of the thymus Thymolipoma Thymic cysts Thyroid lesions DISEASES OF THE THORACIC AORTA Atherosclerotic aortic aneurysm Traumatic aortic injury and pseudoaneurysm Mycotic aneurysm of the aorta Cystic medial necrosis Aortic dissection, intramural hematoma and penetrating atherosclerotic ulcer Aortic dissection Intramural hematoma Penetrating atherosclerotic ulcer Imaging of aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer Optimal imaging of a patient with a suspected acute (nontraumatic) aortic syndrome Congenital aortic aneurysms Aortic aneurysms resulting from aortitis Aortic anomalies that may simulate a mediastinal mass Right aortic arch Double aortic arch Pseudocoarctation of the aorta

edge of the relevant radiographic anatomy is of utmost importance to the practicing radiologist. Despite the advent of cross-sectional imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI), the chest radiograph remains important for localization of the mass (useful for formulating an appropriate differential diagnosis) and, in some instances, for characterization of the lesion. Some abnormalities, such as vascular lesions or mediastinal lipomatosis, may have a sufficiently characteristic appearance on the chest radiograph to obviate further evaluation. Findings of calcification within the mass on chest radiography can also be a clue to the correct

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Chapter 14 • Mediastinal and Aortic Disease diagnosis. However, in most cases, once a mediastinal or hilar abnormality is detected, or at least suspected, on the chest radiograph, cross-sectional imaging is performed. CT or MRI are used to assess the location and extent of the lesion and, because of their superior contrast resolution, are also used to characterize the tissue components of the mass. CT or MRI are also quite useful for distinguishing vascular lesions or benign processes of the mediastinum such as lipomatosis from pathologic conditions that warrant further investigation. Ultrasonography can also be useful for imaging mediastinal abnormalities in selected patients. Because it does not use ionizing radiation, ultrasonography may be preferred to CT for evaluation of some mediastinal masses in children, such as mediastinal cysts.1 If the lesion is thought to arise from the heart or great vessels, either transthoracic or endoscopic ultrasonography may be the first line of investigation. Furthermore, ultrasonography can be useful for guiding biopsy of mediastinal masses.2 Although cross-sectional imaging is primarily used to evaluate abnormalities detected by radiography, it may also be performed in certain situations when the chest radiograph is normal. For example, CT may be performed in patients with myasthenia gravis even if the chest radiograph is normal, because of the association between myasthenia gravis and thymoma. Furthermore, malignancies such as lung cancer have a predilection to metastasize to mediastinal lymph nodes. These metastases may not be visible on the chest radiograph and CT is used to further assess the mediastinal nodes in such patients. CT is now the mainstay for the evaluation of known or suspected mediastinal or hilar abnormalities. However, MRI is sometimes used to further evaluate the location and extent of mediastinal or hilar disease because of its high contrast resolution compared with CT and lack of ionizing radiation. Further, MRI may be the method of choice for imaging suspected neurogenic tumors because it not only shows the size, location, and internal features of the lesions, but because it more clearly depicts spinal involvement.3 MRI is also useful for confirming the cystic nature of mediastinal lesions that appear solid on CT, such as bronchogenic cysts, and for demonstrating vascular structures in patients for whom administration of iodinated intravenous contrast is contraindicated.3 Two potential disadvantages of MRI compared with CT are its poor depiction of calcification and comparatively poorer spatial resolution. Multidetector spiral CT has further improved the ability of CT to image the mediastinum.3 By markedly shortening scan time, respiratory motion artifacts are limited and the dose of iodinated contrast can be reduced.4 Multidetector CT datasets can also be effectively reconstructed in a variety of nonaxial planes, often facilitating interpretation of mediastinal abnormalities. The application of nonaxial two- and three-dimensional reconstruction techniques has proved most useful for imaging abnormalities of the central airways and great vessels.5 By presenting anatomic information in a context more familiar to referring clinicians, these reconstructed images may show the location and extent of an abnormality in a way that imaging reports and axial CT images do not. Positron emission tomography (PET) is a physiologic imaging technique that uses metabolic markers labeled with positron-emitting radionuclides such as fluorine-18, carbon-11, or oxygen-15.6 [18F]2-fluoro-2-deoxy-d-glucose (FDG), a d-glucose analog labeled with fluorine-18, is ideally suited for tumor imaging.7 PET performed with this agent (FDG-PET) exploits the differences in glucose metabolism between normal and neoplastic cells. After intravenous administration, FDG preferentially accumulates in neoplastic cells allowing accurate, noninvasive differentiation of benign from malignant abnormalities by PET imaging.8 FDG-PET imaging has proved quite useful for staging patients with a variety of systemic malignancies that affect the mediastinum, including lymphoma and lung cancer, and has become a mainstay for evaluation of such lesions.9,10 FDG-PET imaging can also play an important role in staging patients with primary mediastinal malignancies such as thymic epithelial neoplasm and nonseminomatous germ cell tumors.11–13 However, FDG-PET has had a more limited role in evaluation of localized mediastinal processes such as neurogenic tumors. In these tumors,

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accurate information about the location and anatomic extent of disease, as provided by MRI or CT, is likely of greater importance than the assessment of metabolic activity of the tumor.

Frequency of mediastinal masses The relative frequency of various mediastinal lesions is difficult to ascertain because most published series are biased toward patients whose lesions undergo biopsy or resection. Some common medi­ astinal masses such as thyroid goiter, aortic aneurysms, or lymphadenopathy in patients with previously established diagnoses such as lymphoma or sarcoidosis are underrepresented in many surgical reviews. The relative frequency of lesions in several large series is shown in Table 14.1. In the Mayo Clinic series,14 about 75% of mediastinal masses in both adults and children were benign and completely resectable and 25% were malignant. The authors14 highlighted the significant differences in the relative frequencies of mediastinal lesions in children and adults. Neurogenic tumors, germ cell neoplasms, and foregut cysts accounted for almost 80% of the masses seen in children. Conversely, primary thymic neoplasms, pericardial cysts, and thoracic goiters were rare in childhood.14 Another retrospective series, however, found that the only significant differences between the adult and pediatric populations were a higher frequency of lymphoma in adults and of neurogenic tumors in children.15 Surprisingly, the frequency of thymic tumors in adults and children was not significantly different in that series.15 Temes et al.16 and Takeda et al.,17 however, reported a significantly lower frequency of thymic tumors and a higher frequency of neurogenic tumors in children. Although all of these series were limited by the biases inherent in retrospective, single-institution, surgical studies, a few trends emerge:18–20 • Neurogenic tumors are more frequent in children than in adults, perhaps reflecting the prevalence of neuroblastoma in that population. • Thymic and thyroid tumors are more common in adults. • Lymphoma tends to occur as a mediastinal mass with roughly equal frequency in adults and children, as do benign cysts of the mediastinum.

Differential diagnosis of mediastinal masses Mediastinal masses are classically defined and discussed according to their location in the anterior, middle, or posterior mediastinal compartments. This classification is primarily a matter of descriptive convenience because there are no anatomic boundaries that limit growth between these various compartments. Indeed, many radiologists do not use these terms in the manner defined by anatomy textbooks. As Heitzman21 noted, apart from being useful for remembering that thymic lesions, thyroid masses, and germ cell tumors are found in the anterior mediastinum and that most neurogenic tumors are posteriorly situated, this simple classification ‘tends to constrict thinking and minimizes more detailed anatomic analysis’. Much more important is the accurate assessment of the location of the mass, together with a description of its size, shape, and characteristics such as CT attenuation, magnetic resonance (MR) signal intensity, or metabolic activity on PET. Cross-sectional imaging techniques, notably CT, provide the best information with which to refine the differential diagnosis and, on occasion, suggest a specific diagnosis.22,23 The differential diagnosis of a mediastinal mass depends on the age of the patient, the location of the mass, the imaging technique used to evaluate the mass, and findings on that imaging examination. For example, Ahn et al.24 analyzed chest radiographs and CT of 128 patients with anterior mediastinal masses and showed that, using the chest radiograph, the first-choice diagnosis was correct in 36% of cases; using CT, the first-choice diagnosis was correct in 48%. Using chest radiographs, the correct diagnosis was included among the top three choices in 59% of cases; using CT, the correct diagnosis was included among the top three choices in 73% of cases. This serves to emphasize that CT can not only help narrow the

Mediastinal Diseases Table 14.1  Frequency (%) of mediastinal masses Series

Wychulis et al.14

Benjamin et al.18

Cohen et al.19

Azarow et al.15

Whooley et al.20

Temes et al.16*

Takeda et al.17

Population

All

All

All

Pediatric

Adult

All

Adult

Pediatric

Adult

Pediatric

Number Neurogenic Thymic Lymphoma Germ cell Benign cyst Thyroid Granuloma Mesenchymal Primary carcinoma Vascular tumor/ malformation Miscellaneous

1064 20 19 10 9 18 5 6 6 2

214 23 21 15 13 7 11

230 17 24 16 10 20 2 0 4

62 32 33 6 6 23 0 0 0 0

195 12 26 21 12 16

124 12 33 19 23 4 0 0 5 0

197 1 16 55 15 NA NA NA 6 0

22 23 0 55 18 NA NA NA 4 0

676 11 36 12 16 14 4

130 46 4 13 19 10

†

3

† † † †

†

†

†

†

†

†

†

†

†

†

7

2

0

†

0

NA

NA

†

†

5

†

5

0

13

4

7

0

7

8

*Only mediastinal malignancies were included. † Not reported as a separate category.

differential diagnosis, but may also reflect the rather limited range of pathologies encountered in the anterior mediastinum. The first step in the differential diagnosis of a mediastinal mass is to be sure that the mass arises from the mediastinum rather than from contiguous lung, pleura, spine or sternum. Masses that lie deep to mediastinal vessels are certainly mediastinal in origin and masses that arise from the sternum or spine should be obvious at CT. The interface with the adjacent lung is a most useful sign, particularly at CT. With few exceptions, a mass with spiculated, nodular, or irregular borders arises in the lung; likewise, a wellmarginated mass with a broad base against the mediastinum arises either from the mediastinum or from the mediastinal pleura.25 Masses arising from the mediastinal pleura project into the lung and usually have obtuse rather than acute angles at their margins. Some general comments regarding patient age, CT attenuation, or MR signal intensity and multiplicity are made here, since all three features are relevant, whatever the location of the mass: • Lymphoma, benign thymic enlargement, germ cell tumors, foregut cysts and neurogenic tumors of ganglion cell origin make up 80% of mediastinal masses in children.26 In adults, lymphoma, metastatic carcinoma to lymph nodes, intrathoracic goiter, thymoma, neurogenic tumors of nerve sheath origin, aortic aneurysms, germ cell tumors, and foregut cysts are the prime considerations. • Lesions that are of higher attenuation than muscle on noncontrast CT scans are usually calcified, have high iodine content (indicating thyroid tissue), or contain areas of acute hemorrhage.27 Furthermore: • Irregular, granular, or eggshell calcification within multiple small mediastinal masses limits the differential diagnosis, for practical purposes, to lymphadenopathy due to such benign conditions as granulomatous infection, coal worker pneumoconiosis, silicosis, and sarcoidosis. Amyloidosis, treated lymphoma, metastasis, and Castleman disease may be an occasional cause. • Calcification in a solitary mass has a broader differential diagnosis. Neurogenic tumors may calcify, as may thymoma and germ cell tumors. • Curvilinear calcification is seen in the walls of foregut cysts, mature teratoma, and, occasionally, pericardial cysts. Untreated lymphoma almost never calcifies. Aneurysms of the aorta or its major branches frequently have curvilinear

•

•

•

•

• •

calcification in their walls or in thrombus lining the aneurysm. This pattern of calcification, along with the observation that the mass arises from, or is in intimate contact with, the aorta or branch vessels, suggests the correct diagnosis. Lesions that are of homogeneous water attenuation on CT or have characteristics of water on MRI, and have a thin wall of uniform thickness are most likely congenital cysts, pericardial recesses, meningoceles, or lymphangiomas. Necrotic malignant or benign neoplasms are usually heterogeneous and have thick or irregular walls.28 Some neurogenic tumors may be of low attenuation on CT; however, they are typically of higher attenuation than water, occur in characteristic locations, and enhance after administration of contrast material. Lesions that contain fat on CT or MRI include collections of normal fat (epicardial fat pads, lipomatosis, and herniated abdominal fat), lipomas, lipoblastomas, liposarcomas, extramedullary hematopoiesis, teratomas, thymolipoma, and fat-replaced lymph nodes.29 A fat–fluid level within a cystic mass is pathognomonic of mature teratoma. Benign lipomas and thymolipomas are composed almost entirely of fat and should contain but a few thin strands of soft tissue. Liposarcomas are rare and usually manifest as mixed fat and soft tissue masses. Contrast enhancement, either by iodinated contrast material at CT or by gadolinium-based contrast material at MRI, is an important feature and can be diagnostic of a vascular lesion such as an aneurysm. A minor degree of enhancement of the soft tissue component of a mass is a nonspecific finding. However, marked enhancement suggests thyroid tissue, vascular tumors such as paragangliomas, or Castleman disease.30 The finding of multiple small masses within the mediastinum is suggestive of lymphadenopathy. The nodes may be separated by fat or may conglomerate into multiple larger lobulated masses. At MRI, most mediastinal masses are of low-to-intermediate signal on T1-weighted images and relatively high signal on T2-weighted images. Those that contain water, or fluid similar to water, have uniformly low signal on T1-weighted images and uniformly very high signal on T2-weighted or short tau inversion recovery (STIR) images. • Lesions that contain fat or subacute hemorrhage have substantially higher signal intensity than muscle on T1-weighted images.31 The differential diagnosis of masses with areas of

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Chapter 14 • Mediastinal and Aortic Disease high signal intensity on T1-weighted images is extensive, because many primary and secondary mediastinal tumors occasionally contain such foci even in the absence of fat or recent hemorrhage. • Furthermore, cysts that contain proteinaceous debris may be of high signal intensity on T1-weighted MRI. Thus, mediastinal masses that may have signal intensity similar to or near that of fat on T1-weighted images include neurogenic tumors, lipomas, teratomas, foregut cysts, lymphangioma, paraganglioma, carcinoid tumors, and a variety of primary and secondary carcinomas.31,32 Finally, location is clearly of great importance for differentiating mediastinal masses. Cross-sectional imaging, particularly CT, is the mainstay for evaluation of known or suspected mediastinal masses. Thus, the differential diagnosis is best discussed by location on cross-sectional imaging.

Prevascular masses Prevascular masses (Box 14.1) are located anterior to the ascending aorta and branch vessels. Almost all masses in this location33 are thyroid or thymic masses, germ cell tumors, or lymphadenopathy. Thyroid masses can usually be specifically diagnosed or excluded based on their contiguity with the thyroid gland in the neck and their high CT attenuation on both pre- and postcontrast scans. In addition, most thyroid lesions are heterogeneous and have focal cysts as well as one or more areas of discrete calcification. A mass located superiorly in the anterior mediastinum that causes lateral deviation of the trachea is likely to be of thyroid origin. Thymic masses and germ cell tumors can have a similar appearance on cross-sectional imaging. Clinical and laboratory features may help distinguish them. For example, myasthenia gravis, red cell aplasia, and hypogammaglobulinemia are associated with thymoma, whereas high α-fetoprotein (AFP) or human chorionic gonadotropin (hCG) levels are associated with malignant germ cell tumors. If there is an associated pleural mass, then lymphoma or intrapleural spread of thymoma becomes a strong possibility. If fat, cartilaginous calcification, or teeth are present in the mass, mature teratoma is the most likely diagnosis. More unusual causes of masses anterior to the aorta and branch vessels are parathyroid adenoma, lymphangioma (cystic hygroma), pericardial cyst, aortic body paraganglioma, lipoma, liposarcoma or other mesenchymal tumors, or aneurysms. Many of these masses have features that permit a specific diagnosis to be made. Parathyroid adenomas are usually associated with clinical features of hyperparathyroidism and are discovered in the quest for an ectopic

parathyroid gland. Lymphangiomas, because they are composed largely of lymph-filled spaces, show numerous cysts on CT. Cystic hygroma should be a serious consideration for a prevascular mass that extends into the neck in a child. Lipomas may be indistinguishable from normal fat collections but are readily distinguished from more significant fat-containing mediastinal masses. Liposarcomas show a mixture of fat and irregular strands or masses of soft tissue. Pericardial cysts are, in general, of uniform water density with a thin, uniform thickness wall, and they need only be considered when the mass in question is in contact with the pericardium. It should be remembered, however, that the pericardium extends to the level of the junction between the proximal and middle thirds of the ascending aorta. Mesenchymal tumors such as sarcomas often have no distinguishing features.

Paracardiac masses The likely diagnoses for paracardiac masses (Box 14.2) that contact the diaphragm are pericardial cyst, diaphragmatic hernia, fat pad, lymphadenopathy, or, in patients with portal hypertension, cardiophrenic varices.34,35 Most pericardial cysts are diagnosable by their uniform water attenuation on CT and their thin walls. Morgagni hernias are recognized by the omental fat within the hernia and sometimes by opacified bowel either within the mass or leading into it. If the mass is not in contact with the diaphragm, the differential diagnosis broadens to include germ cell tumors, mesenchymal and pericardial tumors, and thymic masses. Approximately 20% of thymomas are found in a paracardiac location, though contact with the diaphragm is very unusual. Lack of contact with the diaphragm excludes diaphragmatic hernia.

Paratracheal, subcarinal, and paraesophageal masses Paratracheal, subcarinal, and paraesophageal masses (Box 14.3) are considered together because the trachea, central bronchi, and esophagus are contained within a common fascial sheath. This compartment continues into the neck around the airway, the esophagus, and pharynx. Prime considerations for nonvascular masses in these locations are lymphadenopathy, intrathoracic thyroid mass, foregut cysts, esophageal tumors, hiatal hernias, and paraspinal masses encroaching on the middle mediastinum. In terms of frequency, lymphadenopathy is by far the most frequent. Masses deep to the azygos vein in either the right paratracheal area or in the pretracheal or precarinal space are almost invariably enlarged lymph nodes. For masses arising in the aortopulmonary window, the only

Box 14.1  Prevascular masses

Common • • • •

Thyroid masses Thymic lesions Germ cell tumors Lymphadenopathy

Uncommon • • • • • •

Parathyroid adenoma Lymphangioma (cystic hygroma) Pericardial cyst Aortic body paraganglioma Mesenchymal tumor Aneurysm

Mass V

V

V

T

V E

Prevascular T, trachea; E, esophagus; V, great vessel.

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Mediastinal Diseases Box 14.2  Paracardiac masses

Common • • • •

Pericardial cyst Morgagni hernia Epicardial (anterior) fat pad Lymphadenopathy

Mass RV LV

Uncommon • • • •

RA IVC

Thymoma Germ cell tumor Mesenchymal tumor Varices

E

Ao

Paracardiac RV, right ventricle; LV, left ventricle; RA, right atrium; IVC, inferior vena cava; E, esophagus; Ao, aorta. Box 14.3  Paratracheal, subcarinal, and paraesophageal masses • • • • • • • •

Lymphadenopathy Foregut malformations/cysts Esophageal tumors Thyroid lesions Hiatal hernia Aneurysms Vascular anomalies Pancreatic pseudocyst

Mass

AA SVC

PA

T E

DA

Paratracheal

AA

PA

SVC RM Mass

E

LM DA

Subcarinal

Mass

E DA

Paraesophageal

Ao, aorta; SVC, superior vena cava; AA, ascending aorta; PA, pulmonary artery; T, trachea; E, esophagus; DA, descending aorta; RM, right main bronchus; LM, left main bronchus; RV, right ventricle; LV, left ventricle.

other alternative is aortic aneurysm – a diagnosis that can be readily confirmed or excluded with contrast-enhanced CT or MRI. As mentioned earlier, lymphadenopathy is frequently multifocal and, in the case of metastatic carcinoma, the primary tumor is usually already known. Bronchogenic cyst can be diagnosed with confi-

dence if the criteria of a simple cyst are met. But many bronchogenic cysts do not meet these criteria and these, therefore, are included in the differential diagnosis of a solid mediastinal mass.36 Thyroid masses that pass lateral to or posterior to the trachea are distinctive, partly because of the signs discussed below, but also because

885

Chapter 14 • Mediastinal and Aortic Disease thyroid masses show far greater contact, displacement, and compression of the trachea than do lymph nodes. Separation of the trachea from the esophagus is a characteristic shared only by thyroid masses, bronchogenic cysts, esophageal tumors, and an aberrant origin of the left pulmonary artery. Aortic arch anomalies, though they deform the trachea and esophagus in various ways, do not pass between these two structures. Esophageal tumors very rarely present as unexpected mediastinal masses. Patients with esophageal carcinoma, the most common esophageal tumor, nearly always present with dysphagia at a time when the tumor mass is relatively small. Although the tumor can sometimes be seen as a mass on plain chest radiographs and may be recognized at CT, the diagnosis of esophageal carcinoma is usually made at endoscopy or barium swallow examination. Leiomyoma or other mesenchymal tumors of the esophagus may grow to a considerable size without causing dysphagia and may, on occasion, present as a mediastinal mass on chest radiography or CT. Hiatal hernia is an exceedingly common cause of a mediastinal mass in the region of the lower esophagus. The diagnosis from chest radiographs is so straightforward and reliable that barium swallow or CT should rarely be required to confirm the diagnosis. As discussed below, a number of vascular anomalies may mimic a paratracheal mass on chest radiographs and sometimes even on CT.

Paravertebral masses Strictly speaking, masses situated on either side of the vertebral column (Box 14.4) are outside the mediastinum since, according to anatomists’ definitions, the mediastinum lies anterior to the spine. However, it is standard practice among radiologists and thoracic surgeons to label paraspinal masses as posterior mediastinal masses. Neurogenic lesions and lymphadenopathy dominate the differential diagnosis for paraspinal masses. Lymphadenopathy is rarely confined to the paraspinal areas; usually it is accompanied by enlarged lymph nodes in adjacent mediastinal or retroperitoneal areas. The most common causes of posterior mediastinal lymph node enlargement are lymphoma and metastatic carcinoma from genitourinary primary tumors. Other, less common, causes of para­ spinal masses include metastases from other sites, extramedullary hematopoiesis, pancreatic pseudocyst, mesenchymal tumors such as lipoma, fibroma, chordoma, and hemangioma, and lesions arising from the esophagus, pharynx, spine, or aorta. The esophageal or pharyngeal lesions that may project posteriorly include leiomyoma, foregut cyst, and congenital or acquired diverticula of the esophagus. The spinal origin of lesions such as paraspinal abscess,

tumors of the vertebral body that have spread into the adjacent paravertebral space, or hematomas from trauma to the spine, are usually readily diagnosed by observing corresponding changes in the spine. Aneurysms of the descending aorta that truly mimic mediastinal masses are uncommon. Most large aneurysms in this location are usually obvious. Saccular aneurysms that could be confused with a mass show a broad base on the aorta and almost always have curvilinear calcification in their walls. The diagnosis is readily made on CT or MRI when opacification of the lumen can be demonstrated.

SPECIFIC MEDIASTINAL LESIONS Cysts or cystlike lesions True mediastinal cysts or cystlike lesions (Box 14.5) are usually developmental in origin and include bronchogenic cysts, esophageal duplication cysts, neurenteric cysts, and pericardial cysts. In one series of 105 patients with mediastinal cysts, 45% were bronchogenic, 28% were thymic, and 11% were pericardial cysts.37 The remainder were esophageal duplication cysts, meningoceles, or thoracic duct cysts. Bronchogenic cysts are discussed in Chapter 16 (p 1089). Parathyroid cysts, thymic cysts, and lymphangioma are discussed on pages 938, 955, and 1087, respectively. Distinguishing between the various cysts and cystlike lesions of the mediastinum is not always straightforward. For example, a cyst deep in the wall in the esophagus, and unquestionably by all anatomic criteria an esophageal duplication cyst, may contain respiratory epithelium. In order to emphasize their origin from the embryological foregut, bronchogenic, esophageal, and neurenteric cysts are often collectively referred to as foregut duplication cysts.38,39 Foregut duplication cysts account for approximately 20% of all mediastinal masses.37,40,41 Bronchogenic cysts are the most common mediastinal foregut cysts; esophageal duplication and neurenteric cysts are less common. Mediastinal cysts that contain cartilage are classified as bronchogenic cysts and those that contain gastric epithelium are classified as enteric duplication cysts. Those cysts with seromucinous glands are considered as probably, although not definitely, respiratory in origin. Most congenital mediastinal cysts are lined by respiratory epithelium and these are usually labeled bronchogenic cysts even though their precise origin can only be conjectured.39

Bronchogenic cysts Bronchogenic cysts are discussed on page 1089–1093.

Box 14.4  Paravertebral lesions

Common • Neurogenic tumors • Lymphadenopathy

Uncommon • • • • • •

Extramedullary hematopoiesis Pancreatic pseudocyst Mesenchymal tumors Esophageal lesions Paraspinal abscess or hematoma Aneurysm

RV LV

E DA Mass

Paravertebral DA, descending aorta; E, esophagus; RV, right ventricle; LV, left ventricle.

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Specific Mediastinal Lesions Box 14.5  Cyst or cystlike lesions of the mediastinum • Foregut duplication cysts – Bronchogenic cysts – Esophageal duplication cysts – Neurenteric cysts • Pericardial cysts • Thymic cysts • Parathyroid cysts • Pancreatic pseudocysts • Lymphangiomas (cystic hygromas) • Lymphoceles • Thoracic duct cysts • Meningoceles

Esophageal duplication cysts Esophageal duplication cysts are uncommon. They may present in adults or children.42 The cysts are located in the middle or posterior mediastinum, have muscular coats, and contain mucosa that resembles esophagus, stomach, or small intestine. Esophageal duplication cysts usually occur within the wall, or are adherent to the wall, of the esophagus, are either spherical or tubular in shape, and are usually located along the lateral aspect of the distal esophagus.43,44 Many cysts are clinically silent and are first discovered as asymptomatic masses on chest imaging. The remainder manifest with symptoms of dysphagia or chest pain or symptoms due to compression of adjacent structures.42 Ectopic gastric mucosa in the cyst may cause bleeding into the cyst or perforation of the cyst and the cyst may become infected. On chest radiographs, esophageal duplication cysts manifest as well-defined round or lobular masses in the middle or posterior mediastinum (Figs 14.1 and 14.2).43,44 The masses are usually solid, unless they are infected and contain air. Calcification is rarely detected in the cyst walls. On CT, the cysts manifest as round or tubular water attenuation masses, usually in close proximity to the esophageal wall. These features are similar to those seen in cases of bronchogenic cysts, except that the wall of the esophageal duplication cyst may appear thicker and the mass may have more of a tubular shape than the typical bronchogenic cyst (Fig. 14.2).42,45–47 On barium swallow examination, the cyst may manifest as either an intramural or extrinsic mass.42 Although esophageal duplication cysts are usually of water attenuation on CT (Fig. 14.1), some contain proteinaceous fluid or blood and thus appear as soft tissue masses.43,44 On MRI, the cysts have similar signal intensity characteristics to bronchogenic cysts, being of variable signal intensity on T1-weighted images, depending on intracystic content, and of markedly increased signal intensity on T2-weighted images (Figs 14.1 and 14.2).48 Endoscopic ultrasonography can be used to diagnose and treat esophageal duplication cysts.49

A

B

Fig. 14.1  Esophageal duplication cyst. A, Frontal chest radiograph shows a lobulated left retrocardiac mass (arrow). B, Contrastenhanced CT (left panel) shows a well-marginated water attenuation mass (yellow arrow) that is closely associated with the distal esophagus (red arrow). Note that the lesion is homogeneous and of high signal intensity on the T2-weighted MR image (B, right panel).

Pericardial cysts Pericardial cysts are anomalous outpouchings of parietal pericardium, but only rarely have an identifiable communication with the pericardial sac. Pericardial diverticula are related anomalies of the visceral pericardium that communicate with the pericardial space.50 Rapid change in size, particularly a decrease in size, suggests a pericardial diverticulum rather than a pericardial cyst.51 The cysts contain clear yellow fluid. The interior is usually unilocular but can be trabeculated. In one series, 20% of cases examined pathologically were multilocular,52 though in another large series of 72 patients, only one pericardial cyst was truly loculated.53 The wall of the cyst is composed of collagen and scattered elastic fibers lined by a single layer of mesothelial cells.52 Most affected patients are asymptomatic at presentation, but in series derived from surgical case material, symptoms such as chest pain, cough, and dyspnea are reported in up to a third of patients.38,52,53 There is a strong predilection for the anterior cardiophrenic angles and the cysts typically contact the heart, the diaphragm, and

Fig. 14.2  Esophageal duplication cyst. Coronal T1-weighted MR images shows a tubular mass (*) extending into the abdomen. The mass is of high signal intensity consistent with proteinaceous fluid. (Courtesy of M Rosado-de-Christenson, MD, Columbus, OH, USA.)

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Chapter 14 • Mediastinal and Aortic Disease

A

B

Fig. 14.3  Pericardial cyst. A, Frontal and B, lateral chest radiographs show a large well-marginated mass in the right cardiophrenic angle.

Fig. 14.4  Pericardial cyst in a patient with chest pain. Contrastenhanced CT (upper panels) shows a large water attenuation mass along the right heart border. Noncontrast CT obtained after percutaneous aspiration and drainage (bottom panels) shows only minimal residual fluid in the cyst (arrow) and a new small right pleural effusion. the anterior chest wall. They are more frequent on the right than on the left. In one large series of 72 patients with pericardial cysts, 37 (51%) were in the right cardiophrenic angle (Figs 14.3 and 14.4) and 17 were in the left.53 The remaining 18 arose higher in the mediastinum (Fig. 14.5), and 11 extended into the superior mediastinum. In a review of chest radiographs of 41 patients with pericardial cysts, the right-to-left ratio was 4 : 3.52 On radiographic studies, the cysts are seen as smooth round or oval well-defined masses in contact with the heart (Figs 14.3–14.6). Occasionally, the cysts may be large enough to compress adjacent structures such as heart.54 A pointed oval shape has been observed in some cases.52,55,56 Calcification is exceptional on chest radiographs.

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Fig. 14.5  Pericardial cyst. Contrast-enhanced CT shows a homogeneous water attenuation mass C, along the left pulmonary artery L. A, ascending aorta. On CT, the cysts are usually homogeneous water attenuation masses with thin or imperceptible walls (Figs 14.4 and 14.5). The cyst contents should not enhance after administration of intravenous contrast.57 Soft tissue attenuation pericardial cysts are quite rare.55 The size of the cysts is quite variable, with very large cysts occasionally reported (Figs 14.3 and 14.4).52,53 Ultrasonography can be used to demonstrate the cystic nature of these lesions. MRI shows the mass to be homogeneous and of low signal intensity on T1-weighted images and of high signal intensity on T2-weighted images (Fig. 14.6), similar to water.32 Cyst puncture and aspiration can be diagnostic in difficult cases or therapeutic in symptomatic patients, although the frequency of recurrence after such intervention is unknown (Fig. 14.4).58

Specific Mediastinal Lesions

Neurenteric cysts Neurenteric cysts result from incomplete separation of endoderm from notochord, resulting in a diverticulum of endoderm. Neur­ enteric cysts are pathologically identical to esophageal duplication cysts and usually have either a fibrous connection to the spine or an intraspinal component.59 These cysts are typically associated

with vertebral body anomalies such as hemivertebra, butterfly vertebra or spina bifida that occur at or above the level of the cyst. Most neurenteric cysts occur in the posterior, rather than middle, mediastinum, and usually above the level of the carina.38 Neurenteric cysts are quite rare.14,38,60 Radiographically (Fig. 14.7),61,62 neurenteric cysts are round, oval, or lobulated masses of water density situated in the posterior mediastinum or paravertebral region. Their cystic nature can be demonstrated by ultrasonography. The CT and MRI appearance of these lesions (Fig. 14.7) is similar to that of other foregut cysts.44 MRI is useful for optimally demonstrating the extent of spinal abnormality and degree of intraspinal involvement. Because the cysts may communicate with the subarachnoid space, CT myelography can also be diagnostic.

Mediastinal pancreatic pseudocyst

Fig. 14.6  Pericardial cyst. T1- (left panel) and T2-weighted (right panel) MR images show a small right-sided cyst with signal characteristics of water. Note that the cyst wall is imperceptible.

A

On rare occasions, a pancreatic pseudocyst extends into the mediastinum.63,64 Most affected patients are adults and have clinical features of chronic pancreatitis. In children, the usual etiology is trauma.65 Radiographically, most patients have either bilateral or left-sided pleural effusions.66 The mediastinal component of the pseudocyst is almost always in the middle and posterior mediasti-

B

Fig. 14.7  Neurenteric cyst in an infant with stridor. A, Lateral chest radiograph shows a large retrotracheal mass that anteriorly displaces and narrows the trachea (yellow arrow). Note also the vertebral body clefts (red arrows). B, Axial T1- (upper panel) and T2-weighted (lower panel) MR images show the cyst, C, between the vertebral body and trachea. Note anterior displacement and narrowing of the trachea (yellow arrows on top panel). (Courtesy of Lane Donnelly, MD, Cincinnati, OH, USA.)

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Fig. 14.8  Mediastinal pseudocyst. CT shows a water attenuation middle mediastinal mass, C, that traverses the esophageal hiatus and is associated with a pseudocyst in the tail of the pancreas (arrow). Note the close association with the intrathoracic esophagus (*) and descending thoracic aorta, A. (Courtesy of May Lesar, MD, Bethesda, MD.) multiple or bilateral intrathoracic meningoceles are encountered.76,77 On chest radiographs,78 these lesions manifest as well-defined paravertebral masses, usually associated with scalloping and deformity of the adjacent ribs, pedicles, or vertebral bodies. Enlargement of the adjacent intervertebral foramen is an important diagnostic feature. Kyphoscoliosis is often present. These findings are identical to those seen in patients with so-called ‘dumbbell’ nerve sheath tumors – a diagnostic problem that is complicated by the fact that both conditions are so frequently associated with neurofibromatosis. CT79,80 better demonstrates these features and also shows that the ‘mass’ is of water attenuation, since the bulk of the lesion consists of cerebrospinal fluid (Fig. 14.9). If CT is performed with intrathecal contrast medium, the contrast will enter the meningocele, confirming the diagnosis. Similarly, uniform cerebrospinal fluid (CSF) signal is seen throughout the lesion on MRI.79

Fig. 14.9  Lateral thoracic meningocele. Noncontrast CT shows a well-marginated water attenuation mass arising from the spinal canal. Note the marked widening of the neural foramen. num, having gained access to the chest via the esophageal or aortic hiatus. The pseudocyst in many instances, therefore, deforms the esophagus. CT is the optimum method of demonstrating the full extent of these pseudocysts.67 CT shows a thin-walled cyst containing fluid within the mediastinum in continuity with the pancreas (Fig. 14.8), as well as any peripancreatic fluid collections.68 Magnetic resonance cholangiopancreaticography (MRCP) has been used to successfully diagnose a mediastinal pancreatic pseudocyst.69 The cyst may, on rare occasion, rupture into the pericardium resulting in tamponade.70 Hemothorax and esophagobronchial fistula have also been reported as complications of mediastinal pseudocyst.71 Mediastinal pseudocysts have been successfully treated by endoscopic ultrasonography.72,73

Lateral thoracic meningocele Intrathoracic meningoceles are protrusions of spinal meninges through the intervertebral foramina.74 They are usually detected in patients between 30 and 60 years of age as asymptomatic masses on chest radiographs. They are rarely associated with pain or neurological abnormalities.75 Approximately two-thirds of cases occur in association with neurofibromatosis.75 On rare occasions,

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Lymphoceles and thoracic duct cysts Thoracic lymphoceles are usually due to trauma and are discussed on page 1140. Mediastinal thoracic duct cysts are extremely rare lesions that may be due to either congenital or degenerative weaknesses in the wall of the thoracic duct.37 The cysts can occur anywhere along the course of the thoracic duct, but have also been reported in the neck.81 Very large cysts are reported.82 In a review of 30 reported cases, approximately half of affected patients were asymptomatic.83 The remainder presented with symptoms such as chest pain, dysphagia, and dyspnea due to compression of adjacent structures.83–85 CT usually shows a homogeneous mass of water attenuation along the course of the thoracic duct (Fig. 14.10).83

Desmoid tumor of the mediastinum Desmoid tumors, also known as aggressive fibromatosis, are locally invasive tumors of fibrous origin that primarily involve the soft tissues of the extremities, neck, and trunk. Histopathologically, they are characterized by a proliferation of fibrous tissue that falls within a spectrum that ranges from benign scar tissue to high-grade fibrosarcoma.86 The tumors frequently show extensive local invasion, have a high rate of local recurrence after treatment, and can result in significant morbidity.86 Distant metastases are, however, rare.87 Desmoid tumors may arise in areas of previous trauma or surgery.88 Desmoid tumors of the mediastinum and chest wall are rare (Fig. 14.11).88–95 On chest radiographs, thoracic desmoid tumors manifest

Specific Mediastinal Lesions

A

Fig. 14.10  Thoracic duct cyst. Noncontrast CT shows a water attenuation mass (yellow arrow) anterior to the thoracic vertebral body. The inferior aspect of the lesion (red arrow) is closely associated with the thoracic duct. Aspiration showed chylous fluid. as soft tissue masses that may cause a localized periosteal reaction or cortical erosion of adjacent bone. On noncontrast CT, the mass is usually homogeneous and of the same attenuation as skeletal muscle.93 On enhanced CT, the lesions are often more heterogeneous and may become hyperattenuating to muscle or show areas of necrosis.92 Desmoids are usually heterogeneous and of variable signal intensity compared with muscle on both T1- and T2-weighted MR images.96 As such, there are no particular imaging features to distinguish desmoid tumors from other soft tissue masses in the mediastinum or chest wall.97,98 The lesions may be quite invasive, however, infiltrating in and around the great vessels or extending through the diaphragm to involve the abdomen, making complete resection impossible.99,100 The lesions are frequently hypervascular at angiography.101 FDG-PET characteristics of desmoid tumors are not well described. In one small series, the degree of FDG uptake seemed to correlate with aggressiveness of the lesion and propensity for recurrence after resection.102

Diaphragmatic hernia Herniation of mesenteric fat or abdominal viscera through congenital or acquired defects in the diaphragm is a common cause of a mediastinal abnormality on chest radiograph or CT. Only hernias through the esophageal hiatus are discussed here. Hernias through the foramina of Bochdalek and Morgagni are discussed on pages 1104–1112.

Hiatal hernia Hiatal hernias are frequent incidental findings on chest radiographs and CT. Pain as a result of gastroesophageal reflux or anemia due to upper gastrointestinal bleeding may be presenting complaints. On chest radiography, they produce a smooth, focal widening of the posterior junction anatomy extending down to the diaphragm. Varying amounts of fat surround the hernia itself, and in most instances some air can be appreciated within the hernia and there may be a visible air–fluid level (Fig. 14.12). When air is present within the hernia, a definitive diagnosis can be made by chest radiography. In the absence of air, however, the differential diagnosis includes other lower paraesophageal masses including lymphadenopathy, and CT or barium swallow examination may be required for confirmation. At CT, the esophagus can be traced down into the hernia, and air (and contrast material) within the lumen usually enables the diagnosis to be made without difficulty (Fig. 14.12). The fat surrounding the hernia may be a striking feature. Hiatus hernias can be huge

B

Fig. 14.11  Recurrent desmoid tumor. A, Contrast-enhanced CT shows an enhancing paraaortic mass (arrow). Note findings of previous left chest wall resection for desmoid tumor. B, T1-weighted MR image shows homogeneous mass (top panel; arrow) that is isointense to skeletal muscle and enhances (middle panel) after gadolinium administration. On T2-weighted sequence (bottom panel), the mass is hyperintense. and may contain a major portion of the stomach. With large paraesophageal hernias, the stomach not infrequently undergoes organoaxial rotation.103 On occasion, ascitic fluid under tension may herniate into the mediastinum at the gastroesophageal junction, usually contained by the parietal peritoneum.104 This so-called ‘communicating thoracic hydrocele’ can occur in the absence of a hiatal hernia and manifests as a mass on chest radiographs.104 Because the fluid freely communicates with the abdominal cavity, the ‘mass’ may spontaneously disappear. CT shows a water-attenuation middle mediastinal mass closely associated with the esophageal hiatus in a patient with ascites (Fig. 14.13).105

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A

B

C

Fig. 14.12  Hiatal hernia. A, Frontal and B, lateral chest radiographs show a retrocardiac mass with an air–fluid level (arrows). C, CT shows the contrast-filled stomach, S, in the middle mediastinum.

Esophageal lesions Various lesions of the esophagus (Box 14.6) can manifest as mediastinal masses, including esophageal dilatation (including achalasia), esophageal duplication cysts (see above), esophageal diverticula, mucoceles,106 and esophageal neoplasms.107,108

Diffuse dilatation of the esophagus can occur as a result of motility disorders, distal obstruction, or destruction of the myenteric plexus by tumor at the esophagogastric junction.109 Massive, radiographically evident, esophageal dilatation is most often caused by achalasia or, in some parts of the world, Chagas disease.110 Achalasia is caused by failure of relaxation of the lower esophageal sphincter. The esophagus can dilate to enormous size in affected patients.

Box 14.6  Esophageal lesions that can manifest as mediastinal masses

Diffuse dilatation • Motility disorder – Achalasia – Postvagotomy syndrome – Chagas disease – Scleroderma – Systemic lupus erythematosus – Presbyesophagus – Diabetic neuropathy – Esophagitis

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• Distal obstruction – Carcinoma – Stricture – Extrinsic compression – Mucocele (after distal and proximal exclusion) • Destruction of the myenteric plexus by tumor (pseudoachalasia)

Esophageal duplication cysts Esophageal diverticula Esophageal neoplasms • Carcinoma • Stromal tumors

Specific Mediastinal Lesions

A

Carcinoma of the esophagus, the most common neoplasm of the esophagus, is only occasionally detected as a focal mediastinal mass on chest radiography (Fig. 14.16). Instead, the most frequent finding in affected patients is proximal dilatation of the esophagus, which may be accompanied by recognizable thickening of the esophageal wall. Esophageal dilatation due to an obstructing lesion such as carcinoma is rarely as severe as that seen in patients with achalasia. Submucosal esophageal neoplasms (gastrointestinal stromal tumors, leiomyomas, leiomyosarcomas) may grow to substantial size without causing dysphagia and may, therefore, present first as an asymptomatic mediastinal mass.116 Leiomyomas are the most common esophageal stromal tumor (Fig. 14.17).117 The esophagus is an uncommon location for gastrointestinal stromal tumors (Fig. 14.18). Less than 10% of gastrointestinal stromal tumors are found in the esophagus.117–120 The diagnosis of an esophageal stromal tumor is suggested at barium swallow examination by observing the characteristic signs of an intramural extramucosal mass. On CT, esophageal leiomyomas manifest as smooth, round or ovoid, homogeneous masses (Fig. 14.17) that enhance following administration of intravenous contrast material. The mass is typically inseparable from the esophagus. The esophagus is usually not dilated above the level of the tumor. The absence of proximal esophageal dilatation is an important feature that helps differentiate a stromal tumor such as a leiomyoma from esophageal carcinoma. Leiomyosarcomas and large gastrointestinal stromal tumors (Fig. 14.18) tend to be more heterogeneous on CT.121 FDG-PET-CT imaging has been primarily used to evaluate known or suspected esophageal mucosal malignancies,122 but may also be useful for assessment of malignant stromal tumors.123

B

Fig. 14.13  Communicating thoracic hydrocele in a patient with cirrhosis. A, Frontal chest radiograph shows a well-marginated right retrocardiac mass (arrows). B, CT shows a water attenuation mass, H, in the mediastinum that communicates with the ascitic fluid, A, in the abdomen through the esophageal hiatus (arrow).

Esophageal dilatation is usually best appreciated on the lateral view where the fluid-filled, dilated esophagus displaces the trachea and carina forward (Fig. 14.14).111 In healthy individuals, the lung usually invaginates posterior to the right half of the trachea, resulting in a thin stripe of soft tissue along the posterior tracheal wall (the posterior tracheal stripe, see Chapter 2).112 When the esophagus is dilated, the esophagus displaces this lung and the posterior tracheal stripe may appear thickened on the lateral radiograph (Fig. 14.15). This thickened stripe is due to the combined thickness of the trachea and esophageal walls, contained fluid in the dilated esophagus, and, sometimes, periesophageal lymphatic involvement by tumor.113 The specificity of this finding in isolation is poor, as the stripe can appear thickened in normal patients due to interposition of collapsed normal esophagus between lung and trachea. However, if this sign is seen in association with anterior bowing of the trachea and anterior displacement of the carina, then esophageal dilatation or mass can be confidently diagnosed. The diagnosis of achalasia is further suggested by absence of air in the expected location of the stomach bubble on the frontal radiograph and an air–fluid level within the dilated esophagus. Double exclusion of the esophagus (distal and proximal) with either colonic or gastric bypass is a surgical procedure occasionally used to treat patients with severe congenital, inflammatory, or neoplastic conditions when esophageal resection is not possible (e.g. lye-induced stricture). In rare cases, the excluded esophageal remnant fills with mucus and dilates, often to large size, resulting in compressive symptoms.106,114,115 The diagnosis is made when a tubular mass containing either fluid or proteinaceous material is seen on CT in the characteristic location of the esophagus, in a patient with a history of esophageal exclusion.

Fat-containing lesions of the mediastinum There are many fat-containing lesions of the mediastinum (Box 14.7), including lipomatosis, mature teratoma (see section on germ cell tumors), thymolipoma (see section on thymic lesions), fatty neoplasms, hernias, and extramedullary hematopoiesis.124

Mediastinal lipomatosis Excessive deposition of fat may result in mediastinal widening, a condition known as mediastinal lipomatosis.125,126 When associated with generalized obesity, mediastinal lipomatosis does not usually pose a diagnostic problem. However, in patients on steroid therapy or in those with Cushing disease, focal collections of histopathologically normal, but unencapsulated, fat can deposit in many sites, including the mediastinum, and simulate mass lesions on chest radiographs.127–129 Furthermore, a similar phenomenon is

Box 14.7  Fat-containing lesions of the mediastinum • Mediastinal lipomatosis – Obesity – Cushing disease – Corticosteroid therapy • Neoplasms of fat tissue – Lipoma – Lipoblastoma – Hibernoma – Liposarcoma • Fat-containing tumors – Teratoma – Thymolipoma • Herniation of abdominal fat • Extramedullary hematopoiesis

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A

C

B

Fig. 14.14  Achalasia. A, Frontal and B, lateral chest radiographs show massive esophageal dilatation (arrows on A). Note anterior bowing of the trachea (arrows on B) on the lateral view. C, Barium swallow examination shows typical findings of achalasia with marked esophageal dilatation.

A

Fig. 14.15  Achalasia. Lateral chest radiograph shows an air–fluid level in the mid-esophagus (yellow arrow) and thickening of the posterior tracheal stripe (red arrows).

B

Fig. 14.16  Esophageal cancer. A, Frontal chest radiograph shows lateral convexity (arrows) along the mid-aspect of the azygoesophageal interface. B, CT shows a soft tissue attenuation mass (arrow) in the middle mediastinum. Biopsy revealed squamous cell carcinoma of the esophagus.

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Specific Mediastinal Lesions

Fig. 14.18  Gastrointestinal stromal tumor of the esophagus. Contrast-enhanced CT shows a large soft tissue attenuation mediastinal mass that encases and distorts the distal esophagus (arrows). Note that the mass is quite heterogeneous with a large low-attenuation region.

A

A

B

Fig. 14.17  Esophageal leiomyoma. A, Frontal chest radiograph shows a large lobulated retrocardiac mass (arrows). B, CT shows a homogeneous, soft tissue attenuation mass, M. Note the eccentric contrast-filled esophageal lumen (arrow). occasionally encountered in patients with normal steroid hormone levels.130,131 On chest radiographs, mediastinal lipomatosis usually manifests as smooth, diffuse widening of the superior mediastinum (Fig. 14.19). There is usually no mass effect upon the trachea or other mediastinal structures. In addition to findings of mediastinal fat deposition, chest radiographs also usually show a symmetric increase in extrapleural fat and the costophrenic angle fat pads may be enlarged as well. When mediastinal fat deposition is symmetric

B

Fig. 14.19  Mediastinal lipomatosis in a renal transplant recipient. A, Frontal chest radiograph shows bilateral upper mediastinal widening (yellow arrows). Note extrapleural fat deposition (red arrows) and prominent epicardial fat pad (blue arrow). B, Contrast-enhanced CT shows diffuse deposition of fat in the mediastinum and pleural spaces.

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Fig. 14.21  Metabolically active fat (brown fat). CT (top left panel) shows supraclavicular fat but no lymphadenopathy. FDG PET image (top right panel) shows focally increased FDG activity in fat, consistent with brown fat. Combined PET-CT images (bottom) help localize activity to regions of adipose tissue. (Courtesy of Terry Wong, MD, Durham, NC, USA.)

A

Fatty tumors of the mediastinum

B

Fig. 14.20  Mediastinal lipomatosis. A, Frontal chest radiograph shows focal left upper mediastinal mass with straight lateral margin (arrow). B, CT shows focal mediastinal lipomatosis on the left side of the superior mediastinum.

and diffuse, the radiographic appearance is characteristic enough to pose no significant diagnostic difficulty (Fig. 14.19). On the other hand, when deposition is asymmetric or more focal, CT may be required to exclude a soft tissue mass (Fig. 14.20). This may be the case in patients with lymphoma who are being treated with corticosteroids. At CT, the uniform low attenuation of fat is diagnostic (Figs 14.19 and 14.20).130,132,133 A rare inherited condition termed multiple symmetric lipomatosis, also known as Madelung disease or Lanois–Bensaude syndrome, radiologically resembles mediastinal lipomatosis. In this condition, multiple masses of benign fat tissue proliferate at various sites including the mediastinum.134 Unlike mediastinal lipomatosis, however, these masses occasionally compress mediastinal structures such as the trachea135 or larynx.136 Although the pathogenesis is unclear, the disease may be due to defective regulation of brown fat.137–140 Increased use of combined FDG-PET-CT imaging in oncology patients has led to the recognition that metabolically active fat, known as brown fat, can accumulate FDG and lead to false-positive interpretations.141 Brown fat is more commonly found in young patients and in women. It is most commonly seen in the neck and paravertebral regions, but can also be found in the mediastinum.142 Careful correlation between the CT image and foci of FDG uptake should prevent misinterpretation (Fig. 14.21).

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Mediastinal tumors of fatty origin are uncommon, accounting for less than 1% of 1064 surgically proved mediastinal masses.14 On chest radiographs, both benign and malignant fat-containing tumors manifest as well-defined, round or oval, mediastinal masses.143 Benign lipomas usually do not compress surrounding structures unless they are very large. Quinn et al.144 reported one unusual case where a mediastinal lipoma extended into the spinal canal and caused pressure deformity of the adjacent bones. Large mediastinal lipomas may mold so completely to mediastinal contours as to simulate the appearance of an enlarged heart.145 CT of mediastinal lipomas usually shows a homogeneous mass of fat attenuation. The lesion may contain a very few strands of soft tissue or septa, but these should be quite thin (10.0  cm), male sex, fat content less than 75% of the lesion, thick internal septa (>1.0 mm), and nodular or globular soft tissue components favor liposarcoma.162–165 Areas of high signal intensity on fluid-sensitive MRI sequences are also a suggestive feature of liposarcoma.162 FDG-PET-CT imaging features of mediastinal liposarcomas have not been reported. Based on experience with extremity tumors, however, the degree of FDG uptake likely correlates with likelihood of malignancy, histopathologic grade,

Herniation of omental or perigastric fat is a common cause of a localized fatty mass in the mediastinum. The fat may herniate through the esophageal hiatus, the foramen of Morgagni, or the foramen of Bochdalek. Such herniations are usually readily diagnosed on chest radiographs because of their characteristic locations. The masses are of fat attenuation or signal intensity on CT29 or MRI168 and may contain linear or nodular foci due to contained omental vessels (Fig. 14.25).

Extramedullary hematopoiesis Extramedullary hematopoiesis in potential blood-forming organs such as the liver, spleen, and lymph nodes is common in patients with severe anemia. Thoracic manifestations are rare and usually consist of paravertebral soft tissue masses, although pulmonary parenchymal involvement has been described.169 The masses are caused by extrusion of the marrow through the thinned cortex of the posterior ribs. Histopathologically the masses resemble splenic tissue with hematopoietic elements mixed with fat. The masses themselves are usually asymptomatic, though paraplegia from cord compression may occur.170,171 Massive hemothorax secondary to rupture of the hematopoietic masses has been described.172 The most common conditions that result in extramedullary hematopoiesis are the congenital hemolytic anemias, notably thalassemia, hereditary spherocytosis, and sickle cell disease.173 However, it may rarely occur in other anemias and may even occur in patients without anemia.174

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A

B

Fig. 14.24  Liposarcoma. Combined FDG-PET-CT images show large mixed attenuation mass. Note fatty component (yellow arrow) and focus of significantly increased FDG uptake (red arrow), likely representing an area of high-grade sarcoma. Thoracic extramedullary hematopoiesis manifests on chest radiographs,171,174,175 CT,175,176 and MRI177 as focal paravertebral masses, usually in the lower half of the thorax (Fig. 14.26). The masses are usually well marginated because they are covered by pleura, are bilateral in distribution, contain no calcification, and show no rib destruction. Further foci of extramedullary hematopoiesis can also be seen as subpleural masses adjacent to ribs. These subpleural masses may be continuous or discontinuous with the paravertebral masses. The adjacent bone is usually normal or shows findings of marrow expansion; pressure erosions or bone destruction do not occur.174 CT is particularly useful for demonstrating the lacelike marrow expansion in the adjacent bones (Fig. 14.26).175 On CT, the lesions manifest as heterogeneous or homogeneous soft tissue attenuation masses (Figs 14.26 and 14.27). There may be some fat within the mass (Fig. 14.27),178 but calcification is uncommon.179 On MRI, the masses are usually heterogeneous with increased signal intensity on T1-weighted images because of contained fat.177 Radionuclide studies using agents that show erythropoiesis or the reticuloendothelial system may demonstrate activity in the mass,175,180–182 but can be negative.175,183 Diagnosis can also be established by fine needle aspiration biopsy.184

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Fig. 14.25  Herniation of intraabdominal fat. A, Frontal chest radiograph shows a well-marginated retrocardiac mass (arrows). B, Contrast-enhanced CT shows a well-circumscribed fatty mass (arrows) in the posterior mediastinum. Note the thin wisps of soft tissue that likely represent mesenteric blood vessels.

Germ cell tumors of the mediastinum Germ cell tumors (Boxes 14.8 and 14.9) account for 10–15% of anterior mediastinal masses and are thought to arise from mediastinal remnants left behind after embryonal cell migration.185–188 The mediastinum is the most common primary site for extragonadal germ cell tumors and mediastinal lesions account for about 60% of all germ cell tumors in adults. Germ cell tumors usually occur in young adults; the mean age at presentation is 27 years.185–187 Most malignant germ cell tumors (>90%) occur in men. Benign lesions (mature teratoma) occur with equal frequency in men and women. Histopathologic types of germ cell tumors that occur in the mediastinum include teratoma, seminoma, embryonal carcinoma, endodermal sinus tumor, choriocarcinoma, and mixed tumors.189 Malignant germ cell tumors frequently secrete tumor markers such as hCG, AFP, or lactate dehydrogenase (LDH). These serum markers can be used to diagnose and monitor the progress of the disease.190 Poor prognostic factors include mediastinal location, metastases at presentation, and degree of elevation of serum tumor markers.191

Specific Mediastinal Lesions

A

Fig. 14.27  Extramedullary hematopoiesis in a patient with sickle cell anemia. CT shows bilateral paraspinal masses. Note that the masses are of mixed attenuation and contain punctate areas of fat.

Teratoma

B

Fig. 14.26  Extramedullary hematopoiesis in a patient with thalassemia. A, Frontal chest radiograph shows a well-marginated right paravertebral mass (arrows). B, CT shows bilateral soft tissue masses (arrows) in the posterior mediastinum. Note the typical osseous changes in the posterior ribs.

Teratomas are the most common mediastinal germ cell tumors and are derived from more than one embryonic germ layer. Most mediastinal teratomas arise in cell rests within, or in intimate contact with, the thymus.192,193 Teratomas are classified histopathologically as mature or immature. Immature teratomas are further subclassified as immature teratoma, immature teratoma – malignant, or immature teratoma with additional malignant components.194 The term teratocarcinoma is now discouraged.190 Mature teratomas are composed of different tissue types (ectoderm, endoderm, mesoderm), with ectodermal derivatives predominating.195 The term dermoid cyst is commonly used when the tumor contains primarily ectodermal components such as skin, sebaceous material, hair and calcification.189,196 Such lesions are typically unilocular; multilocular lesions with intervening solid portions are less common.14 Tumors with more than 10% immature elements are classified as immature teratoma and are considered potentially malignant.190 Immature teratoma – malignant is such a lesion that develops metastases after

Box 14.8  Germ cell tumors of the mediastinum

Location • Usually anterior • Rarely middle or posterior

– Embryonal cell carcinoma – Choriocarcinoma • Mixed tumors

Demographics

Clinical

• • • •

• May be asymptomatic • Malignant more likely to present with symptoms • Malignant associated with serologic markers – AFP – hCG – Lactate dehydrogenase (LDH)

Young adults 15% of anterior mediastinal masses 90% occur in men (malignant form) Mature teratomas occur with equal frequency in men and women

Histopathology • Teratoma – Mature teratoma – Immature teratoma – Immature teratoma – malignant – Teratoma with additional malignant components • Seminoma – Most common pure histology • Nonseminomatous germ cell malignancy – Yolk-sac tumor

Poor prognostic factors • • • • •

Nonseminomatous histology Mediastinal location Nonpulmonary metastases at presentation AFP >10 000 ng/mL hCG >50 000 IU/L

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Chapter 14 • Mediastinal and Aortic Disease Box 14.9  Germ cell tumors of the mediastinum: imaging features

Mature teratoma • Chest radiography – Well-circumscribed mediastinal mass – Typically unilateral – May contain calcification • CT – Appear as uni- or multilocular cystic mass – Fat • Seen in 75% • Predominant feature in 15% • Fat–fluid level rare, but diagnostic – Calcification common • Rimlike • Internal coarse – Rupture – Lesions are more heterogeneous – Fat in pleural space, pericardium, lung • MRI – Complex signal patterns depending on proportion of water, soft tissue, fat, and calcification

occur in the posterior mediastinum or the lung parenchyma itself.14,186,199–202 The lesions tend to grow very slowly, but may increase in size rapidly if intratumoral hemorrhage occurs. Calcification, ossification, or even teeth199,200 may be visible on chest radiographs (Fig. 14.29) and, occasionally, sufficient fat is present within the lesion to be detectable radiographically. The CT appearance of mature teratoma is quite variable because it depends upon the content of the lesion (Figs 14.28 and 14.29).203,204 Almost all lesions have some areas of water attenuation on CT. Regions of fat attenuation are seen on CT in up to three-quarters of lesions and are the predominant tissue type in 15%.199 Fat–fluid levels within the lesion, while uncommon, are virtually diagnostic of teratoma (Fig. 14.30).205,206 More often, however, the fat is interspersed with regions of water and soft tissue attenuation. A definite cyst wall, which may have curvilinear calcification, may be visible on CT (Fig. 14.28), as is characteristic intralesional calcification (Fig. 14.29).199 On rare occasions, the lesions rupture into the airway, pleural space, or pericardium. When the tumor ruptures into the airway, air may enter the cyst and become visible on imaging examination; severe chemical pneumonitis or lung abscess can also result.38 In a

Immature teratoma/malignant elements • • • •

Large bulky tumors Heterogeneous on CT/MRI Invasive May or may not contain fat/calcification

Malignant nonteratomatous germ cell tumors • Seminoma – Large, lobulated, homogeneous – May have prominent cystic component – Fat or calcification rare – Indistinguishable from lymphoma – Nodal metastases • Nonseminomatous – Larger and more ill-defined borders – May be bilateral – Frequently invasive – Very heterogeneous with areas of necrosis or cysts – Fat or calcification rare A

diagnosis. Teratomas that contain malignant components such as other malignant germ cell neoplasia, sarcoma, or adenocarcinoma, are termed immature teratoma with additional malignant components and are frequently metastatic at presentation.190,194,197 Such tumors have a very poor prognosis. Mature teratomas account for 70% of germ cell tumors in childhood and 60% of mediastinal germ cell tumors in adults. Mature teratomas occur most frequently in children and young adults.14,185,198 About half of affected patients are asymptomatic at presentation, with the lesion being detected on chest radiographs obtained for other purposes. In the remainder, symptoms due to local compression, rupture, or infection occur. The most common presenting complaints are chest pain, productive cough, dyspnea, or fever.199 Rarely, affected patients present with pneumonia, hemoptysis, or the superior vena cava syndrome. Trichoptysis (the expectoration of hair) is a dramatic, but extremely rare, symptom that occurs when the lesion ruptures into the airway.14,189 Patients with mature teratoma usually have normal serum levels of β-hCG and AFP. Complete resection is the treatment for mature teratomas and usually results in a complete cure. Despite a benign histology, these tumors may be difficult to remove when they are adherent to local structures. On chest radiographs, mature teratomas manifest as well-defined, rounded, or lobulated masses that usually project to one side of the midline (Fig. 14.28).14 They most commonly occur in the anterior mediastinum, typically in the prevascular space. On occasion, they

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Fig. 14.28  Mature teratoma. A, Frontal chest radiograph shows a large, well-circumscribed right anterior mediastinal mass. B, CT shows that the mass is predominantly of water attenuation, although there are a few small posterior foci of fat. Note the thin uniform cyst wall (arrow).

Specific Mediastinal Lesions

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Fig. 14.29  Mediastinal teratoma in an infant with dyspnea. A, Frontal chest radiograph shows a large left thoracic mass with linear calcification (arrow). B, Contrast-enhanced CT (left panel), T1- (center panel), and T2-weighted (right panel) MR images shows that the mass contains fluid, fat, and calcium. Note that the calcification is not easily appreciated on the MR images. (Courtesy of Lane Donnelly, MD, Cincinnati, OH, USA.)

Fig. 14.30  Mature teratoma. Contrast-enhanced CT shows a well-circumscribed anterior mediastinal mass that contains a fat–fluid level, a diagnostic feature. The low-attenuation mass (arrow) at the interface was a hairball. (Courtesy of M. Rosado-de-Christenson, MD, Columbus, OH, USA.)

review of 17 patients with seven ruptured and 10 unruptured teratomas, those lesions that ruptured were noted to be more internally heterogeneous on CT than were those that were not ruptured.207 Additional findings suggestive of rupture were adjacent consolidation, atelectasis, pleural, or pericardial effusion.207 In two cases, fat was seen in the lung parenchyma. Rupture into the pericardium208 or pleura can result in the appearance of a fat–fluid level within these spaces on imaging examinations.209 As is the case with CT, the MRI appearance of mature mediastinal teratomas is quite variable (Fig. 14.29). Because the contents of the cyst are typically rich in proteinaceous fluid, the cystic component of the lesion may be of high signal intensity on T1-weighted

images.32,199,210 Furthermore, the lesion may be of high signal on T1-weighted images because of fat or hemorrhage. On ultrasonography, the lesions may appear as completely cystic or solid masses or as mixed cystic and solid masses.211 The pattern on ultrasonography is often quite complex because of intralesional calcification (densely echogenic), hair (hyperechoic dots), and fat (dense echo pattern).212 One case that showed echogenic floating spherules in the mass has been described.213 Information regarding FDG-PET imaging features of mediastinal mature teratoma is scant. Based upon limited experience with germ cell tumors in other sites, it is likely that these lesions, unless complicated, show little or no FDG accumulation.214 Any foci of

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Chapter 14 • Mediastinal and Aortic Disease increased FDG accumulation should suggest a more aggressive lesion, such as immature teratoma, until proven otherwise. Imaging features of immature teratoma or teratoma with malignant components are less well-described.190 Masses are typically described as large, invasive, and quite heterogeneous on CT or MRI, and may or may not contain areas of fat or calcification (Fig. 14.31).190

Malignant nonteratomatous germ cell tumors In addition to teratomas with malignant features, other types of malignant germ cell tumors that occur in the mediastinum include seminoma, embryonal cell carcinoma, endodermal sinus tumor,

Fig. 14.31  Immature teratoma with malignant components. Contrast-enhanced CT shows large heterogeneous mass with extensive calcification and single minute focus of fat (arrow).

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choriocarcinoma, and mixed germ cell tumors.215,216 Seminoma is the most common pure histopathologic type in men and accounts for 40% of such tumors.216 However, tumors of mixed histology are more common than pure seminoma.215 Malignant mediastinal germ cell tumors are usually encountered in young adults and are much more common in men than women.192 In a review of 103 cases of primary mediastinal seminoma, only five occurred in women.217 Even mediastinal choriocarcinoma in adults is more common in men than women; in children, the male–female ratio is more evenly distributed.192 Because of marked differences in prognosis and treatment, nonteratomatous malignant germ cell tumors are frequently grouped as seminoma and nonseminomatous germ cell malignancies.191 Malignant mediastinal germ cell tumors are more frequently symptomatic than mature teratomas.187,190,192 Common presenting complaints include cough, dyspnea, and chest pain.217 Superior venal cava obstruction is reported in up to 10% of affected patients.217,218 Weight loss may also be a notable feature. However, between 10% and 30% of affected patients are asymptomatic at presentation, with the mass discovered on routine chest radiographs.191 Serum levels of hCG and AFP are useful for diagnosis and monitoring of some mediastinal germ cell malignancies.187,190 Both hCG and AFP levels are typically normal in cases of pure seminoma; slight elevation in hCG levels are occasionally encountered; elevation of AFP indicates a nonseminomatous component of the tumor. Up to 80% of patients with nonseminomatous germ cell malignancies have elevated levels of AFP and 54% have elevated levels of hCG.187,190 There is an association between malignant nonseminomatous germ cell tumors of the mediastinum and hematologic malignancies219,220 and up to 20% of affected patients may have Klinefelter syndrome.221,222 Seminomas typically manifest on chest radiographs as focal, unilateral or bilateral, mediastinal masses (Fig. 14.32). On CT or MRI, they are usually large lobulated masses of homogeneous attenua-

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Fig. 14.32  Mediastinal seminoma. A, Frontal chest radiograph shows a large, well-marginated right anterior mediastinal mass. Note the small left lower lobe nodule (arrow) consistent with a metastasis. The left central venous catheter is looped in the left subclavian vein. B, Contrast-enhanced CT shows that the mass is homogeneous, of soft tissue attenuation, and has ill-defined borders. C, Axial MR images show numerous internal septations. (Courtesy of Jeremy Erasmus, MD, Houston, TX, USA.)

Specific Mediastinal Lesions tion or signal intensity, often indistinguishable from lymphoma (Fig. 14.32).187,190 Cysts or areas of necrosis may also be seen in association with mediastinal seminoma.187,190 Invasion of adjacent structures may occur but calcification is rare. Metastases to regional nodes or lung can occur (Fig. 14.32). Nonseminomatous germ cell malignancies usually manifest as large lobular or ill-defined anterior mediastinal masses (Figs 14.33 and 14.34).190 The mass is typically asymmetric and projects to one side of the thorax.185,223,224 Calcification is an exceptional finding on chest radiographs. On CT or MRI, the mass may be quite heterogeneous and may contain cysts or areas of necrosis and hemorrhage (Figs 14.33 and 14.34).225,226 These features may be accentuated following administration of intravenous contrast. Coarse tumor calcification is rarely seen on CT.225,227 Adjacent mediastinal fat planes are often obliterated and extensive local invasion may be identified.228 Invasion of the adjacent mediastinal structures, chest wall, and lung, as well as metastases to the regional lymph nodes and distant sites, is common (Figs 14.33 and 14.34).190 The FDG-PET imaging features of mediastinal germ cell malignancies are not well described. Most of the literature on the subject describes findings in patients with testicular or ovarian primary tumors.11,229–232 Extrapolation of such results to patients with mediastinal primary tumors is difficult, as the nonseminomatous mediastinal tumors tend to behave quite differently from their testicular or ovarian counterparts. Nevertheless, it is likely, based upon these results, that pure teratoma will show little if any increased metabolic activity.230 Malignant tumors (seminoma or nonseminomatous), on the other hand, should show metabolic activity (Figs 14.33 and 14.35). Results of staging studies with testicular primary tumors

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are mixed, with one multicenter randomized trial showing only a slight positive benefit for FDG-PET over CT.229 Marked FDG uptake in a residual mass after treatment, however, does seem to predict viable tumor.232 A residual mediastinal mass is sometimes seen on CT after successful treatment of a primary mediastinal nonseminomatous germ cell malignancy or after treatment of metastatic disease from a gonadal primary (Fig. 14.36). This mass may be cystic in nature, contain residual mature teratoma, and enlarge with time.233,234 This

Fig. 14.34  Nonseminomatous germ cell tumor. CT shows heterogeneous mass with large area of central necrosis. Note ill-defined margins suggesting invasion and metastatic nodule in right lower lobe (arrow).

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Fig. 14.33  Nonseminomatous germ cell tumor. A, Contrastenhanced CT shows a large heterogeneous mass. Note invasion of the superior vena cava (arrow). B, Combined FDG-PET CT image shows marked increase the metabolic activity in the periphery of mass, with necrotic center.

Fig. 14.35  Mediastinal seminoma. Combined FDG-PET-CT image shows large left-sided mediastinal mass with multifocal regions of marked increased metabolic activity.

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Chapter 14 • Mediastinal and Aortic Disease phenomenon is known as the ‘growing teratoma’ syndrome.235–238 The benign or malignant nature of the residual mass cannot be confidently determined based upon the CT appearance alone. However, elevation of serum tumor markers suggests a malignant component. Andre et al.236 followed 30 patients with growing teratoma syndrome. All 30 lesions were biopsied or resected and 86% of lesions were found to have a mature teratoma component. All but one patient who underwent curative resection survived disease-free. Five of the six patients who had only partial resection

Fig. 14.36  Growing teratoma in a patient previously treated for a nonseminomatous germ cell malignancy of the testis. CT shows a partially calcified subcarinal mass that contains a small cystic region (arrow). (Courtesy of M Rosado-de Christenson, MD, Columbus, OH.)

developed recurrent disease and one died of progressive tumor. These authors and others233 concluded that complete surgical resection was the treatment of choice.

Lymphadenopathy Causes of lymphadenopathy Lymphadenopathy (Box 14.10) can be caused by a variety of infectious, inflammatory, and neoplastic conditions. Neoplastic causes include lymphoma, leukemia, and metastatic carcinoma. Lymph node metastases frequently occur in the setting of thoracic malignancies such as lung (Fig. 14.37), esophagus, and breast cancer. Extrathoracic tumors that frequently spread to intrathoracic lymph nodes include renal, testicular, and head and neck malignancies.239,240 The most common infections that result in intrathoracic lymphadenopathy are tuberculosis (Fig. 14.38) and fungal disease (particularly histoplasmosis and coccidioidomycosis). Lymph node enlargement is frequent in acquired immune deficiency syndrome (AIDS) patients (see Chapter 6) and can be caused by lymphoma or granulomatous infection. Rare infections such as tularemia, anthrax, and plague can also cause lymphadenopathy. Enlarged nodes in patients with anthrax are characteristically of high attenuation on CT due to extensive hemorrhage.241 Significant lymphadenopathy is quite uncommon in other infections, particularly bacterial pneumonia, and, when present, suggests an unusual organism or alternative diagnosis. Sarcoidosis is a particularly frequent cause of intrathoracic lymph node enlargement in young adults (Fig. 14.39). When multiple lymph node groups in the hila and mediastinum are symmetrically enlarged in a young patient, sarcoid is the most likely diagnosis. Lymph nodes in patients with sarcoidosis are frequently positive on FDG-PET scans (Fig. 14.40).242 Lymphoma is the most important differential diagnosis in such patients, but lymphoma is rarely so symmetrically distributed with equal involvement of the hilar and mediastinal lymph node groups (Fig. 14.41). Isolated paracardiac node enlargement is unusual in cases of sarcoid or infection, and are often due to lymphoma or metastatic carcinoma.243,244 Lymphoma and sarcoidosis are discussed further in Chapters 13 and 11, respectively. Reactive hyperplasia is a term used to describe an acute or chronic nonspecific inflammatory response in which both inflammation and hyperplasia are present. Lymph nodes undergo reactive changes whenever challenged by infection, cell debris, or foreign substances. Thus, nodal enlargement due to reactive hyperplasia is

Box 14.10  Causes of mediastinal and hilar lymph node enlargement

Infection • Common – Primary tuberculosis258 – Fungal infection (esp. histoplasmosis)259 • Uncommon – Viral (especially Ebstein–Barr virus)260 – Bacterial: anthrax,241,261 tularemia,262 pneumonic plague (Yersinia pestis)263

Inflammatory • • • • • • • •

Sarcoidosis264 Silicosis265 Coal worker’s pneumoconiosis266 Asbestos exposure257 Chronic beryllium disease267–269 Wegener granulomatosis270 Interstitial pneumonia245,253–255 Collagen vascular disease271–273

Neoplasm • Primary – Lymphoma

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– Leukemia (especially chronic lymphocytic leukemia) – Myeloma274 • Metastatic239,240 – Lung – Breast – Melanoma – Renal – Testicular – Unknown primary275

Other • • • • • • •

Reactive hyperplasia Castleman disease276 Amyloidosis277–280 Whipple disease281–283 Chronic eosinophilic pneumonia284 Chronic congestive heart failure250–252 Drug-induced lymphadenopathy (see Chapter 9)

Specific Mediastinal Lesions

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Fig. 14.39  Sarcoidosis. Frontal chest radiograph shows bilateral hilar, right paratracheal, aortopulmonary window and subcarinal lymphadenopathy. This symmetric pattern of lymphadenopathy is typical of sarcoidosis.

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Fig. 14.37  Nonsmall cell lung cancer. A, Frontal chest radiograph shows a right hilar mass. Note splaying of the right upper and lower lobe bronchi. B, Contrast-enhanced CT confirms metastatic lymphadenopathy.

Fig. 14.38  Mediastinal tuberculosis. Contrast-enhanced CT shows a conglomerate mass of enlarged prevascular lymph nodes, as well as subcarinal lymphadenopathy. Note subtle rim enhancement (arrow) of some of the nodes. Biopsy showed Mycobacterium tuberculosis.

Fig. 14.40  Sarcoidosis in a patient with breast cancer. Combined FDG-PET-CT images show metabolically active right paratracheal (yellow arrow, top panel), left axillary (red arrow, top panel), bilateral hilar (yellow arrow, bottom panel), and subcarinal (red arrow, bottom panel) lymphadenopathy. Biopsy of the right paratracheal lymph nodes showed sarcoidosis.

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Fig. 14.41  Non-Hodgkin lymphoma. Frontal chest radiograph shows unilateral right paratracheal (yellow arrow) and subcarinal (red arrow) lymphadenopathy. Note mass effect on medial wall of bronchus intermedius (blue arrows).

seen in nodes draining areas of pulmonary infection, bronchiectasis, and a variety of inflammatory and chronic interstitial lung diseases,245,246 and also in nodes draining neoplasms. Reactive hyperplasia is a common cause of false-positive lymph nodes on FDG-PET scans in patients with nonsmall cell carcinoma.247 In such cases, high FDG uptake has been attributed to overexpression of the glucose transporter-1 enzyme in regions of follicular lymphoid hyperplasia.248,249 Chronic left heart failure is an important and perhaps underrecognized cause of mediastinal lymphadenopathy.250–253 Between 42% and 66% of patients with left heart failure will have enlarged lymph nodes (>1  cm short axis, see below) on CT.250,252,253 Most (63%) are in the pretracheal regions and the mean short axis diameter in one series was 1.3 cm.252 Node margins may be ill-defined and mediastinal fat may be of increased attenuation (‘hazy’) in up to 33%.250 Presence of enlarged nodes has been shown to correlate with decreased left ventricular ejection fraction.252,253 Node enlargement may resolve after treatment for heart failure.253 The etiology for lymph node enlargement in this setting is unknown. Histopathologic sampling in three patients with congestive heart failure and mediastinal lymphadenopathy showed only sinus histiocytosis.251 It has been speculated, however, that mediastinal lymph nodes hypertrophy in response to chronic mediastinal edema and lymphatic congestion.251 Mediastinal lymph node enlargement is also common in patients with pulmonary fibrosis that occurs either idiopathically254,255 or in the setting of collagen vascular disease (Fig. 14.42)245,256 or asbestos exposure.257 In one series, 13 (93%) of 14 patients with usual interstitial pneumonia had enlarged mediastinal lymph nodes on CT.255 Nodes larger than 2  cm in short axis diameter were seen in three (21%).255 In another series, enlarged nodes were found on CT in 67% of 175 patients with diffuse infiltrative lung disease.245 These authors noted that the vast majority of patients had only a few enlarged nodes and that they rarely exceeded 15  mm in short axis diameter.245 Jung et  al.254 reported enlarged nodes on CT in 86% of 30 patients with pulmonary fibrosis and also found that the number of enlarged nodes correlated with disease severity. Histopathologic analysis of enlarged lymph nodes in patients with fibrosis usually shows reactive change or sinus histiocytosis.245

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Fig. 14.42  Patient with scleroderma and pulmonary fibrosis. A, CT shows multiple enlarged lymph nodes in the prevascular and right paratracheal regions. The largest node measures 1.5 cm in short axis dimension. B, HRCT shows diffuse ground-glass and irregular linear opacities consistent with nonspecific interstitial pneumonia.

Castleman disease Castleman disease (Box 14.11), also known as giant lymph node hyperplasia or angiofollicular lymph node hyperplasia, is a rare cause of often massive lymph node enlargement in the chest.285 Although intrathoracic lymph nodes are most commonly affected, nodes at any location can be involved.276,286 Extranodal involvement, including spleen and lung parenchyma, can also occur.287–289 There are two major histopathologic variants of Castleman disease: hyaline-vascular and plasma cell. The hyaline-vascular type is the most common (80–90%) and shows a follicular structure with tumor nodules composed predominantly of small lymphocytes and with large numbers of blood vessels in the interfollicular areas. The plasma cell type (10%) shows sheets of interfollicular cells and fewer blood vessels.290 Mixed hyaline-vascular and plasma cell types can also occur, particularly in patients with multifocal disease.287–289 Furthermore, hyaline-vascular and plasma cell lesions can occur concomitantly at separate sites.285 The pathogenesis of Castleman disease remains a subject of investigation. Although clonal expansion of certain lymphocyte populations is seen in some cases, Castleman disease is generally regarded as a reactive process that can eventually lead to lym-

Specific Mediastinal Lesions Box 14.11  Thoracic Castleman disease

Etiology • Unknown • Abnormal production of B lymphocyte growth factor (interleukin [IL]-6) • Associated with human herpes-8 virus (HHV-8) in human immunodeficiency virus (HIV+) individuals

Histopathology • Hyaline-vascular – 80% • Plasma cell – 10% • Mixed lesions

Location • Middle mediastinum (subcarinal or paratracheal) • Hila • Other mediastinal, chest wall, lung parenchyma

Current clinical classification • Focal – Usually hyaline-vascular – Asymptomatic or symptoms due to mass effect – Good prognosis with resection • Multifocal – Usually plasma cell or mixed – Constitutional symptoms (fever, weight loss, night sweats) – Chemotherapy, radiation – Poorer prognosis • HIV-associated – Usually multifocal – HHV-8 association – High rate progression to lymphoma – Also associated with Kaposi sarcoma – Poor prognosis

Imaging • Localized Castleman disease (hyaline-vascular) – Large solitary mass – May be locally invasive – Heterogeneous soft tissue attenuation – Intense contrast enhancement, large feeding vessels – Flow voids on MRI – FDG-avid on PET imaging • Multifocal Castleman disease (plasma cell, mixed) – Diffuse lymphadenopathy – Less intense enhancement – FDG-avid on PET imaging

Lung parenchymal Castleman disease • • • •

Rare Usually in setting of multifocal disease Histopathology: lymphoid interstitial pneumonitis CT – Centrilobular nodules – Septal thickening – Thin-walled cysts

phoma, particularly in patients with multifocal disease. There is evidence that some cases may be mediated by abnormal production of B lymphocyte growth factors, such as interleukin 6, leading to abnormal lymphoid proliferation.285 There is also an association with infection by human herpes-8 virus (HHV-8), also known as the Kaposi sarcoma associated virus, particularly in HIV-positive individuals.291,292 Castleman disease is currently best classified as unifocal, multi­ focal or HIV-associated disease.287–289 Patients with unifocal Castleman disease typically present in the fourth decade of life with a mass detected either incidentally or by virtue of symptoms related to mass-effect on neighboring mediastinal structures.276,286 Systemic symptoms, laboratory abnormalities, peripheral lymphadenopathy,

or organomegaly are rare. About 90% of cases of unifocal Castleman disease are of the hyaline vascular variant. Unifocal disease is usually resected in toto and patients typically have a benign course thereafter. Patients with multifocal Castleman disease typically present in the sixth decade of life with diffuse lymphadenopathy and systemic complaints such as fever, night sweats, and weight loss.287–289,293,294 Organomegaly, peripheral neuropathy, anemia, gamma globulin abnormalities, and elevated lactic dehydrogenase are common.290 About 80% of cases of multifocal Castleman disease are of the plasma cell or mixed variants. Some patients with multifocal Castleman disease are infected with HHV-8, an association that increases in the HIV-positive population.287–289 Affected patients are usually treated with chemotherapy or radiation therapy with mixed results. Disease usually pursues an aggressive course, and development of frank lymphoma can occur. Castleman disease that develops in HIV-positive individuals is almost always multifocal and pursues a very aggressive course.295 There is a strong association with HHV-8 viral infection, and affected individuals may also develop Kaposi sarcoma.287–289,296–298 HIV-positive patients with multifocal Castleman disease have a very high risk of developing lymphoma as well. Prognosis is poor. On chest radiographs, localized Castleman disease usually manifests as a focal, well-defined, smooth or lobular mediastinal or hilar mass (Fig. 14.43). The mass is typically quite large and most commonly occurs in the middle mediastinum or hila.276,299,300 Occasionally, the lesion is found in other sites, including the posterior mediastinum and chest wall.276,286,300 On noncontrast-enhanced CT, the mass is usually homogeneous and of soft tissue attenuation (Fig. 14.44). Calcification is uncommon (5–10%) and, when it occurs, is typically coarse and central in location (Fig. 14.45). Multifocal Castleman disease usually manifests on chest radiographs with diffuse mediastinal widening. On CT or MRI, multifocal lymph node enlargement is noted. Because of its highly vascular nature, hyaline-vascular Castleman disease usually enhances intensely following administration of intravenous iodinated or gadolinium-based contrast material (Fig. 14.45)276,286,293,301–306 – a distinctive feature that helps differentiate Castleman disease from many other mediastinal lesions including lymphoma. The lesions are also found to be highly vascular at angiography.299,301,307 Plasma cell Castleman disease is less vascular, and typically shows less enhancement after contrast administration.258 On MRI, hyaline-vascular Castleman disease lesions are typically heterogeneous and have increased signal intensity compared with skeletal muscle on T1-weighted sequences (Figs 14.43 and 14.45).307–309 They become markedly hyperintense on T2-weighted sequences (Fig. 14.45). Low signal intensity septa are occasionally visible within the lesions. In larger lesions, flow voids in and around the mass may be identified and are important clues to the hypervascular nature of the mass. Because the lesions are hypervascular, diffuse enhancement following administration of intravenous gadolinium is common (Fig. 14.45). The FDG-PET imaging findings of Castleman disease have been described only in small series or case reports.310–313 In these reports, the lesions are usually quite metabolically active, whether uni- or multifocal in nature (Fig. 14.46). Castleman disease may, very rarely, involve the lung parenchyma (Fig. 14.44). Reported manifestations include a pulmonary mass,290,314 centrilobular nodules,315 septal thickening,315 and thinwalled cysts.315 Most patients with diffuse lung involvement have multifocal disease and the lung findings are usually due to associated lymphoid interstitial pneumonitis.315

Diagnosis of lymphadenopathy Important clues to the presence and sometimes the cause of mediastinal or hilar lymph node disease include enlargement and abnormal density on chest radiographs, attenuation on CT, or signal intensity on MRI. It is important to remember, however, that lymph

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Fig. 14.43  Unifocal hyaline-vascular Castleman disease. A, Frontal and B, lateral chest radiographs show a large, well-marginated subcarinal mass. C, Axial T1-weighted MR image shows that the mass is of slightly increased signal intensity compared with skeletal muscle. (With permission from McAdams HP, Rosado-de-Christenson M, Fishback NF, et al. Castleman disease of the thorax: radiologic features with clinical and histopathologic correlation. Radiology 1998;209:221–228.)

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Fig. 14.44  Multifocal hyaline-vascular Castleman disease. A, Noncontrast CT shows a homogeneous soft tissue mass (arrow) in the subcarinal region. B, Contrast-enhanced CT shows marked enhancement within the mass (arrow). C, CT coned to the left lung shows tiny centrilobular nodules in the lower lobe. Biopsy showed lymphoid interstitial pneumonia.

nodes of normal size and attenuation or signal intensity can harbor disease, including malignancy.

Lymph node calcification Calcification of intrathoracic lymph nodes (Box 14.12) is a common sequela of certain infections, particularly tuberculosis and histoplasmosis (Fig. 14.47). It can also be seen in other benign conditions such as sarcoidosis, silicosis, coal worker’s pneumoconiosis, amyloidosis, and Castleman disease. Lymph node calcification is very rarely due to neoplastic disease. Lymph node metastases from calcifying primary malignancies such as osteosarcoma, chondrosarcoma, carcinoid tumors, and mucinous colorectal and ovarian carcinomas (Fig. 14.48) may calcify.316,317 Lymph node calcification can occur after treatment of mediastinal lymphoma (Fig. 14.49), but

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is quite rare prior to treatment.318,319 CT clearly demonstrates lymph node calcification to better advantage than chest radiographs. MRI is limited, however, in its ability to show calcification, a notable disadvantage.320 Various patterns of lymph node calcification can be seen. Coarse irregular clumplike calcification of a part of the node and homogeneous calcification of the entire node are the two most common patterns. Lymph node calcification due to tuberculosis tends to involve the entire node whereas calcification due to sarcoid tends to be more punctate. Further, calcified lymph nodes due to tuberculosis tend to involve the mediastinum asymmetrically (usually unilateral), corresponding to the drainage patterns of primary infection; whereas diffuse, bilateral nodal involvement is more common in sarcoidosis.321 A strikingly foamy pattern of calcification is described in AIDS patients with disseminated Pneumocystis jirovecii

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Fig. 14.45  Unifocal hyaline-vascular Castleman disease. A, Contrast-enhanced CT shows an enhancing subcarinal mass. Note mass effect upon the bronchus intermedius (*) and two small foci of calcification (arrow). Axial T1-weighted MR images obtained B, before and C, after administration of gadolinium-based contrast material shows that the mass is heterogeneous and intensely enhances. D, T2-weighted MR image shows marked increase signal intensity within the mass. (With permission from McAdams HP, Rosado-deChristenson M, Fishback NF, et al. Castleman disease of the thorax: radiologic features with clinical and histopathologic correlation. Radiology 1998;209:221–228.)

Box 14.12  Causes of lymph node calcification

Benign disease • Tuberculosis and fungal disease* (notably histoplasmosis) • Pneumocystis jirovecii infection in patients with acquired immune deficiency syndrome (AIDS) • Sarcoidosis* • Silicosis and coal worker’s pneumoconiosis* • Amyloidosis* • Castleman disease

Malignant disease • Treated lymphoma and other neoplasms* (calcification in untreated lymphoma almost never occurs) • Metastases from primary tumor Osteosarcoma Chondrosarcoma Mucinous adenocarcinoma

other conditions, but has been reported in patients with amyloidosis, histoplasmosis, blastomycosis, and treated lymphoma.277

Low attenuation on CT Areas of low CT attenuation within enlarged nodes, likely due to necrosis (Fig. 14.51), is seen in a variety of conditions, including tuberculosis,326,327 nontuberculous mycobacterial infection, metastatic disease, particularly testicular tumor,328,329 and lymphoma. In one series, 16 of 76 patients with Hodgkin disease had low-attenuation lymphadenopathy on CT at presentation.330 Some nodes have a prominent fatty hilum on CT. This feature is associated with benign disease and is usually thought to be the result of previous inflammation. Conversely, obliteration of the fatty hilum has been associated with metastatic disease.331 Low-attenuation or even fatty nodes have also been described in patients with Whipple disease.283

Contrast enhancement on CT *Eggshell calcification is reported.

infection322,323 and in patients with metastatic mucinous neoplasms. Thin peripheral calcification – so-called ‘eggshell calcification’ (Fig. 14.50) – is seen in patients with coal worker’s pneumoconiosis, silicosis, and sarcoidosis.321,324,325 In one series, eggshell calcification was seen on chest radiographs in 3% of coal workers with greater than 30 years’ experience.325 Eggshell calcification is rarely seen in

Contrast enhancement in enlarged nodes, when moderate in degree, is nonspecific and seen in patients with tuberculosis,327,332 fungal infection,326 sarcoidosis, and metastatic neoplasm. When enhancement is dramatic, however, it suggests metastatic neoplasm from a highly vascular primary tumor such as melanoma, renal or thyroid carcinoma, carcinoid tumor, or leiomyosarcoma. Castleman disease is a further, though rare, cause of markedly enhancing lymph nodes (see Fig. 14.44). Peripheral, or rim, enhancement and central necrosis are features of tuberculosis (see Fig. 14.38)327 and can be of

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Chapter 14 • Mediastinal and Aortic Disease

Fig. 14.47  Histoplasmosis. Noncontrast CT shows a densely calcified nodal mass in the subcarinal region as well as a small calcified right hilar node.

Fig. 14.46  Hyaline-vascular Castleman disease. Combined FDG-PET-CT image shows matted anterior mediastinal lymphadenopathy with focal areas of increased metabolic activity.

Fig. 14.48  Metastatic mucinous adenocarcinoma of the ovary. Noncontrast CT shows multiple calcified lymph nodes within the right mediastinum and hilum. Note also the partially calcified pleural nodules.

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Fig. 14.49  Treated Hodgkin lymphoma. Coned view of a lateral chest radiograph shows calcified nodal masses (arrows) in the anterior mediastinum.

Specific Mediastinal Lesions diagnostic value in situations where tuberculosis is likely and metastatic carcinoma is not.332

Chest radiographic signs of mediastinal lymph node enlargement How large a mediastinal or hilar node has to be in order to be detected on chest radiographs is not easily established. It is likely that this size threshold depends upon the location of the node in the mediastinum, the presence of other mediastinal abnormalities such as tortuous great vessel or lipomatosis, and radiographic technique. Most nodes with a short-axis diameter of 2 cm or greater in the right paratracheal region, the aortopulmonary window, the hilar or the paravertebral regions should be detected on appropriately exposed posteroanterior chest radiographs. However, nodes in the pretracheal, left paratracheal, subcarinal, and paracardiac regions may be considerably larger than 2 cm in diameter and yet not be identified on chest radiographs.243,333 Upper right paratracheal node enlargement (Fig. 14.52) (station 2R of the AJCC/UICC nomenclature)334 (see p 69) manifests as uniform or lobular widening of the right paratracheal stripe.335

Fig. 14.50  Sarcoidosis. Noncontrast CT shows multiple slightly enlarged mediastinal lymph nodes with thin rim (‘egg-shell’) calcification.

When the paratracheal nodes become substantially enlarged, the lateral border of the superior vena cava may become convex rather than flat or concave. The apparent density of the superior vena cava may be increased and equal that of the aortic arch (normally the density of the superior vena cava in the right paratracheal area is less than that of the aortic arch). When the lower right paratracheal (azygos) nodes (station 4R) enlarge, they displace the azygos vein laterally so that the diameter of the combined shadow of the azygos node and vein enlarges (the normal diameter on an upright chest film should be 7 mm or less).336 Enlargement of the upper left paratracheal nodes (station 2L) is frequently obscured by the shadows of the left carotid and subclavian arteries. These nodes have to be quite large to be detected on chest radiographs. If the aortopulmonary nodes (station 5) are substantially enlarged, they project beyond the aortopulmonary window and appear as a mass in the angle between the aortic arch and the main pulmonary artery (Fig. 14.53).337 Enlargement of the anterior mediastinal nodes, i.e. nodes anterior to the aorta (station 6), the brachiocephalic artery (station 3), and the trachea (stations 2 and 4), must be substantial to be recognizable on chest radiographs. The resulting mediastinal abnormality is frequently bilateral and lobulated in contour (Fig. 14.54). Sometimes, the only finding of lymph node enlargement in these areas is increased opacity of the retrosternal area on the lateral view. Enlargement of the anterior intercostal, or internal mammary, nodes is best recognized on the lateral chest radiograph as well-marginated, retrosternal soft tissue masses along the course of the internal mammary arteries. Significant enlargement may result in upper parasternal opacities on the frontal radiograph.338 The most useful sign of subcarinal node (station 7) enlargement on chest radiographs is a change from the normally concave contour of the superior portion of the azygoesophageal interface (Fig. 14.55) into a convex bulge.339 Alteration of the contour of the azygoesophageal interface is, unfortunately, a relatively insensitive sign of subcarinal lymphadenopathy. It was noted in only 23% of the patients with subcarinal lymph node enlargement reported by Müller et  al.333 Effacement of the interface, without a focal bulge, can be seen with smaller volume nodes, but is a less specific finding for subcarinal pathology, particularly in children.340,341 Other chest radiographic findings of subcarinal node enlargement include increased opacity in the subcarinal region342 and obscuration of the

Fig. 14.51  Tuberculosis. Noncontrast CT shows multiple enlarged lymph nodes with low-attenuation centers.

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Fig. 14.52  Mycobacterium avium complex infection in an AIDS patient. A, Frontal chest radiograph shows right paratracheal and right hilar lymphadenopathy. B, Contrast-enhanced CT confirms lymphadenopathy in the right paratracheal region.

medial margin of the bronchus intermedius.333 Since the esophagus passes immediately behind the carina, subcarinal node enlargement may cause posterior displacement of the esophagus. Enlarged paraesophageal nodes (station 8) and posterior medi­ astinal nodes result in displacement of the azygoesophageal and paraspinal interfaces.

CT of mediastinal lymph node enlargement CT more readily demonstrates lymph node enlargement than chest radiography. The optimal CT technique for detection of enlarged mediastinal lymph nodes remains a subject of debate and is related to the rapidly changing nature of CT technology. In general, the thinner the slice collimation used, the better individual nodes will be shown. Thin-collimation images obtained on a multidetector spiral CT scanner will likely show more nodes than relatively thickcollimation images on a single-slice spiral or non-spiral scanner. However, whether this improvement in node detection makes a significant clinical difference to the patient is less certain and

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Fig. 14.53  Chronic lymphocytic leukemia. A, Frontal chest radiograph shows convexity in the aortopulmonary window (arrow). B, Contrast-enhanced CT confirms aortopulmonary window lymphadenopathy. Note also the enlarged nodes in the right paratracheal region and both axilla.

depends upon the specific clinical circumstances. Furthermore, although CT images are traditionally reviewed in axial format, several studies have shown that coronal reformat images from multidetector CT datasets obtained using thin slice collimation (0.5 mm or 2 mm collimation) performed better for the detection of enlarged lymph nodes than conventional 5  mm postcontrast scans.343,344 Again, whether this improvement translates into improved patient outcome is uncertain. Whether or not intravenous contrast is necessary for detection of mediastinal lymphadenopathy also remains a subject of debate and is, for the most part, a decision that rests upon the experience of the interpreter and individual preference. One group compared contrast-enhanced with noncontrast CT for staging lung cancer and found that contrast-enhanced CT revealed more enlarged lymph nodes, particularly at the 2R station.345 However, they also reported excellent overall agreement between the two studies for the presence and total number of enlarged lymph nodes, suggesting that

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the observed differences might not be clinically relevant. Another study compared contrast-enhanced with noncontrast CT for staging lung cancer and found that contrast-enhanced CT rarely changed the tumor stage determined by noncontrast CT.346 These authors concluded that intravenous contrast was not needed for routine CT for lung cancer staging. A more recent study compared noncontrast with contrast-enhanced FDG-PET-CT for lung cancer staging, and found no difference for assessment of nodal metastases.347 CT findings of mediastinal lymphadenopathy (Figs 14.50–14.56) include: an increase in size of individual nodes; focal mediastinal contour abnormalities or lobulations of the interface between the mediastinum and lung; invasion of surrounding mediastinal fat; coalescence of adjacent and enlarged nodes to form larger masses; and diffuse soft tissue attenuation throughout the mediastinum obliterating the mediastinal fat. Individually enlarged nodes are seen as round or oval soft tissue lesions in the mediastinum. Distinguishing enlarged nodes from normal vascular structures requires thorough knowledge of the normal arrangement of blood vessels and an understanding of the various anomalies and variations in the arrangement of the mediastinal vessels. Intravenous contrast enhancement may be needed to help distinguish vessels from lymph nodes in problematic cases.

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Fig. 14.54  Multiple myeloma. A, Frontal chest radiograph shows lateral displacement and convexity of the aortopulmonary reflection (arrow) as well as widening of the right mediastinum. These findings suggest prevascular lymphadenopathy. B, Lateral chest radiograph shows increased soft tissue opacity in the retrosternal region. C, Contrast-enhanced CT confirms matted lymphadenopathy in the prevascular space. Note also the lytic sternal lesion.

Many authors have studied CT scans in normal patients in order to establish normal size criteria for mediastinal or hilar lymph nodes (see p 68).348–351 These studies suggest that the upper limit of normal for short-axis lymph node diameter is about 1 cm. Short-axis diameter is considered the standard for diagnosis because it is the most reproducible measurement and has the best correlation with lymph node volume at autopsy.352 These studies must be interpreted with caution, however, as the importance of both ‘enlarged’ and ‘nonenlarged’ nodes varies depending upon node location, the clinical scenario, and the presence or absence of known or suspected malignancy. For example, nodes between 10 mm and 15 mm in short-axis diameter may be normally found in certain areas, such as the subcarinal region. Furthermore, nodes considerably smaller than 10  mm can harbor metastatic disease in patients with lung cancer.353 Use of size alone to predict presence or absence of nodal malignancy is fraught with error, particularly in patients with lung cancer.354 It is easier to identify and measure right-sided mediastinal lymph nodes than to evaluate the left-sided nodes, because of the more abundant mediastinal fat and less complex vascular anatomy on the right.352 Subcarinal lymph node enlargement may be difficult to recognize at noncontrast CT. Important signs include: a soft tissue

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Fig. 14.55  Subcarinal mass. A, Frontal chest radiograph shows a smooth subcarinal mass (arrow). Note displacement of the right main bronchus. B, CT shows that the mass (arrow) is homogeneous and of soft tissue attenuation. Resection showed bronchogenic cyst filled with proteinaceous debris. mass between the esophagus and either the left atrium or the intramediastinal portions of the right or left pulmonary arteries; or a soft tissue mass that extends into the azygoesophageal recess, posterior to the bronchus intermedius and the left lower lobe bronchus.

MRI of mediastinal lymph node enlargement For the most part, MRI and CT provide comparable information regarding enlarged mediastinal nodes. However, MRI is frequently more time-consuming, more difficult for patients, and more limited in availability than CT at many centers. It can also be difficult to distinguish a cluster of small normal nodes from a single enlarged node or to detect intranodal calcification at MRI.320 Furthermore, differences in signal intensity at spin-echo MRI have not proved to be a reliable method for differentiating benign from malignant lymphadenopathy. For these reasons, MRI is currently used primarily for patients for whom the use of iodinated intravenous contrast material is contraindicated.247,355 There has been considerable recent interest, however, in developing new MR techniques for imaging nodal metastases from a variety of malignancies including lung cancer. One group reported increased accuracy for differentiating benign from malignant nodes at 3.0 T field strength.331 Others have reported positive results with contrast agents such as gadolinium-DTPA356,357 or molecular

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Fig. 14.56  Chronic lymphocytic leukemia. A, Frontal chest radiograph shows subtle lobulation of the right hilum (arrows). Note the normal appearance of the left hilum and the enlarged descending thoracic aorta. B, Noncontrast CT confirms right hilar (arrows) and subcarinal (*) lymphadenopathy. imaging techniques such as small superparamagnetic iron oxide (USPIO) particles.358–360 In a recent series, USPIO-enhanced MRI was shown to be more accurate that FDG-PET for detection of nodal metastases in a rabbit model.360 Furthermore, new pulse sequences such as diffusion-weighted MRI are being investigated and have also been recently shown to be more accurate than FDG-PET for mediastinal nodal staging in patients with lung cancer.361 While these results are promising, their impact and eventual role in staging patients with suspected mediastinal nodal metastases remains to be seen.

PET imaging of mediastinal lymph node enlargement PET imaging, using a variety of positron-emitting agents, most commonly FDG, has assumed a dominant role in the assessment of mediastinal lymph nodes, especially in patients with known or suspected malignancy. The role and influence of FDG-PET imaging in this regard very much depends upon the clinical scenario and source of primary malignancy and is considered in more detail in sections dealing with specific conditions. However, a few caveats

Specific Mediastinal Lesions are appropriate. First, while FDG-PET greatly improves the accuracy of assessment of suspected mediastinal nodal metastases, it is not perfect; false positives and negatives occur and are not infrequent.354 Second, a variety of benign causes of lymph node enlargement also show increased metabolic activity on FDG-PET imaging, including sarcoidosis, tuberculosis, and histoplasmosis (see Fig. 14.40).242,362,363 Third, combined PET-CT is probably more accurate for assessment of medi­astinal lymph nodes than either CT or PET alone, especially in patients with lung cancer.363–365

Chest radiographic findings of hilar lymph node enlargement The findings of hilar node enlargement on chest radiographs are enlargement of the hilum, increased lobulation of the hilar contours, a rounded mass in a portion of the hilum that does not contain major vessels (Fig. 14.56; see also Figs 14.37 and 14.39), and increased density of the hilum.366 In certain highly vascular regions of the hila (e.g. the intersection of the right superior pulmonary vein and interlobar artery and the inferior aspect of the hilum where the inferior pulmonary veins intersect the lower lobe segmental arteries), nodal enlargement must be substantial to be recognized radiographically. Enlarged nodes adjacent to the lower lobe arteries increase the overall diameter of the hilum (the transverse diameter of each lower lobe artery should be no greater than 16  mm) and result in a lobular rather than the normal tubular configuration. Lymph node enlargement in the upper portions of the hila is often easily detected because the vessels in these regions are normally small. Even mild nodal enlargement can be recognized on the lateral view when the enlarged nodes lie posterior to the right main bronchus and bronchus intermedius (Fig. 14.57), because lung nor-

mally contacts the posterior wall of the airway in this region. Another important region to evaluate for hilar lymphadenopathy on the lateral view is the angle formed by the lower lobe bronchi and the middle lobe or lingular bronchus (Fig. 14.58) – the so-called inferior hilar window.367 It may, at times, be very difficult to distinguish enlarged hilar lymph nodes from enlargement of the hilar arteries due to pulmonary hypertension (Fig. 14.59). Correct diagnosis depends on determining that the abnormality is truly centered on the pulmonary arteries and on evaluating the degree of lobulation. A hilar mass in a location that is normally devoid of vessels clearly favors nodal enlargement. Enlarged central pulmonary arteries usually retain their tubular configuration. Lobulated hilar enlargement favors lymphadenopathy. If needed, contrast-enhanced CT will answer the question.

CT of hilar node enlargement The recognition of hilar node enlargement at CT is facilitated by intravenous contrast opacification of the hilar vessels (see Fig. 14.37).368 Lymph nodes generally do not enhance to the same degree

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Fig. 14.57  Sarcoidosis. Lateral chest radiograph shows typical finding of hilar lymphadenopathy. Note the abnormal opacity posterior to the bronchus intermedius (yellow arrow) and anterior to the lower lobe bronchus (red arrow), two areas normally devoid of opacity on the lateral view.

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Fig. 14.58  Metastatic adenocarcinoma. A, Lateral chest radiograph shows a mass (arrows) in the ‘inferior hilar window’. B, Noncontrast CT confirms left hilar lymphadenopathy (arrow).

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Fig. 14.60  Normal CT appearance of the right hilum. A, Axial contrast-enhanced CT shows volume-averaged small lymph nodes and hilar fat pad simulating lymphadenopathy (yellow arrow), medial to the right superior pulmonary vein (red arrow). B, Coronal reformat image more clearly shows small nodes and fat pad (yellow arrow) at the bifurcation of the right upper lobe (*) and right interlobar (IL) pulmonary arteries. Note the right superior pulmonary vein (red arrow). A, aorta; R, right main pulmonary artery; M, main pulmonary artery; LA, left atrium. B

Fig. 14.59  Pulmonary arterial hypertension. A, Frontal and B, lateral chest radiographs show enlarged central pulmonary arteries. Note the typical tubular configuration of the enlarged pulmonary arteries and the evidence of right heart enlargement on the lateral view, a finding that supports the diagnosis. as blood vessels. The majority of nodes in the hilum, except those around the lower hilum, are normally less than 3 mm in short-axis diameter.369 Nonenhancing hilar tissue that is up to 7 mm in shortaxis diameter is commonly seen in the lower hila, however.369 If the examination is performed without contrast, then the recognition of nodal enlargement depends on demonstrating rounded soft tissue densities that are too large to be blood vessels (see Figs 14.56 and 14.58).370–373 The smallest node that can be reliably detected on noncontrast CT varies with location. Some portions of the hilum are normally devoid of vessels greater than 5 mm in diameter and thus relatively small nodes may be detected as contour abnormalities in these regions. In other regions of the hila, however, the vessel diameters may be 15 mm, or greater if there is increased pulmonary blood flow or pulmonary arterial hypertension, limiting detection

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of all but the largest nodes. Perhaps the most sensitive area for detection of hilar lymphadenopathy on noncontrast CT is the region immediately behind the right main bronchus and its divisions – the right upper lobe bronchus and the bronchus intermedius – because, in these regions, the lung normally contacts the posterior wall of the airway.374 Increased soft tissue opacity, especially if it is lobulated, in this region is suggestive of lymphadenopathy. The equivalent area in the left hilum is occupied by the descending aorta and left descending pulmonary artery; therefore, only a small portion of lung contacts the posterior wall of the left main bronchus,375 limiting detection of lymphadenopathy in this region. The most difficult, and therefore the least sensitive, area for detection of hilar lymphadenopathy is the central portion of the right hilum, where the right superior pulmonary vein crosses directly anterior to the right pulmonary artery and its major divisions. Additionally, there are fat pads at the bifurcation of the right pulmonary artery that can resemble lymph node enlargement on axial CT (Fig. 14.60). It can be difficult to recognize the fatty nature of these pads because of partial volume averaging with the adjacent arteries and lung.376

Specific Mediastinal Lesions

MRI of hilar node enlargement As is the case with imaging mediastinal lymph node enlargement, MRI and CT provides comparable information regarding enlarged hilar nodes. However, hilar node enlargement may be more easily recognized with MRI than with noncontrast CT.320,326,377,378 For the most part, MRI is used primarily in patients for whom the use of iodinated intravenous contrast material is contraindicated.247,355

as lymphadenopathy. Some of these pitfalls are illustrated in Figs 14.61–14.63.

Lymphovascular tumors of the mediastinum Lymphangioma Mediastinal lymphangioma (cystic hygroma) is discussed in Chapter 16.

Pitfalls in the diagnosis of intrathoracic lymph node enlargement

Blood vessel tumors

A variety of anatomic structures can be confused with mediastinal lymph node enlargement,379–381 including enlarged blood vessels and vascular variants such as aortic anomalies (p 979), azygos continuation of the inferior vena cava, varices of the azygos or pulmonary vein,382–385 and aneurysmal dilatation of the brachiocephalic vein or superior vena cava.385–387 Fluid in the various pericardial recesses can occasionally mimic lymphadenopathy or other mediastinal masses.388,389 Choi et al.388 described a series of patients with posterior superior pericardial recesses that extended cephalad to the level of the aortic arch (‘high-riding’) and were misdiagnosed

Blood vessel tumors in the mediastinum are rare and frequently benign. Capillary or cavernous hemangiomas390 are the most common lesions. Hemangioendothelioma,391 hemangiosarcoma, hemangiopericytoma,392 hemangioendothelioma,393 and mixed lymphatic and blood vessel lesions, such as lymphangiohemangiomas,394–396 are very rare. Hemangiomas are rare mediastinal tumors that account for less than 0.5% of all mediastinal masses.397 Mediastinal hemangiomas usually occur in the anterior (68%) or posterior mediastinum (22%), although multicompartment involvement is found in up to 14% of

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Fig. 14.61  ‘High-riding’ pericardial recess. A, CT shows possible lymphadenopathy (yellow arrow) in the paratracheal region, posterior to the right brachiocephalic vein (red arrow) and artery (asterisk). Note, however, that the lesion is of water attenuation. B, CT at a more inferior level shows the typical crescent shape of a superior pericardial recess (arrow). C, Coronal reformat image shows continuity typical of the so-called ‘high-riding’ recess (arrows). A, aorta; S, superior vena cava; P, pulmonary artery.

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Fig. 14.62  Persistent left superior vena cava. A, Noncontrast CT shows a round soft tissue attenuation structure in the left prevascular space (arrow). The anomalous vein enhances following administration of intravenous contrast, B.

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Fig. 14.63  Azygos continuation of the inferior vena cava. A, Frontal chest radiograph shows a right tracheobronchial angle mass (arrow), concerning for lymphadenopathy. B, C, CT confirms that the opacity is a dilated azygos vein (Az) due to interruption of the inferior vena cava.

Specific Mediastinal Lesions cases.398–401 Most mediastinal lesions are cavernous hemangiomas and are composed of large interconnecting vascular spaces with varying amounts of interposed stromal elements such as fat and fibrous tissue. Focal areas of organized thrombus can calcify as phleboliths. Affected patients are usually asymptomatic. On chest radiographs, hemangiomas manifest as sharp, wellmarginated mediastinal masses (Fig. 14.64). Phleboliths are seen in less than 10% of cases but, when present, are diagnostic. CT typically reveals a heterogeneous mass with intense central and peripheral rim-like enhancement after administration of intravenous contrast.391,397,398,402,403 Hemangiomas typically have heterogeneous signal intensity on T1-weighted images. In lesions with significant stromal fat, linear areas of increased signal intensity on T1-weighted images can occasionally be identified. The central vascular spaces typically become markedly hyperintense on T2-weighted images, a suggestive feature (Fig. 14.64).404 Mixed lymphangioma/hemangioma is a variant of hemangioma seen most frequently in children and young adults.405 The lesion may be localized to the thorax or occur as a more systemic process. When it occurs in the chest, the lesion may involve the mediastinum, pleura, and chest wall as a single process causing widespread lobular soft tissue swelling, bone destruction, and chylous pleural effusion. This destructive form of the disease is known as Gorham disease.406,407 Cystic angiomatosis is another, probably distinct form of widespread lymphangiomatosis408 in which lymphangiomas and hemangiomas may coexist. Many different sites in the body are involved, including the mediastinum, pericardium, and pleura. Multiple lytic lesions may be seen in the bones.409 The condition is most frequently seen in children and young adults. Lymphangiomatosis is discussed further in Chapter 16.

Mediastinal hemorrhage Trauma to the aorta, branch vessels, or spine is a frequent cause of mediastinal hemorrhage (see p 1121, Chapter 17). Common causes of spontaneous mediastinal hemorrhage include aortic dissection

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(see p 967), rupture of an aneurysm, misplacement of central catheters (Fig. 14.65), bleeding disorders, or anticoagulant therapy. Other less common causes of mediastinal hemorrhage include chronic hemodialysis,410 bleeding into preexisting mediastinal tumors, such as thymic masses and thyroid goiter, radiation vasculitis,411,412 and severe vomiting.413,414 Patients with mediastinal hemorrhage can be asymptomatic or present with substernal chest pain that may radiate to the back. Its investigation depends on the probable cause. CT is usually the first line of investigation after chest radiography to confirm the presence of hemorrhage and occasionally to elucidate its cause. The chest radiographic findings of mediastinal hemorrhage depend upon the cause and source of the bleeding. Blood may affect one mediastinal compartment and manifest as a focal mass (Fig. 14.65), or may dissect freely throughout the mediastinum and manifest as diffuse mediastinal widening.415 Blood may also dissect extrapleurally over the lung apices, giving rise to the important sign of apical capping.416 When the hemorrhage is severe, blood may rupture into the pleural cavity or dissect into the lung along perivascular and peribronchial sheaths, resulting in opacities that resemble pulmonary edema.417 The appearance of mediastinal hemorrhage on CT can be fairly characteristic (Fig. 14.65). Linear bands of soft tissue attenuation are seen interspersed with mediastinal fat in affected regions of the mediastinum. On occasion, it is possible to appreciate the high attenuation values of fresh thrombus on noncontrast CT images. A focal hematoma may, however, be difficult to distinguish from a solid mediastinal mass on CT. The appearance of hemorrhage on MRI varies with the age of the hemorrhage (Fig. 14.66). In the hyperacute phase, there is low signal on T1-weighted and high signal on T2-weighted images. Over the ensuing days, the signal on the T1-weighted images rises and there is a period during the sub­ acute phase in which high signal is seen on both T1- and T2-weighted images. Thereafter, complex signal patterns are seen in which the signal intensity depends on the amount of water in the area of hemorrhage and the degree of conversion from methemoglobin to ferritin and hemosiderin.418

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Fig. 14.64  Mediastinal hemangioma. A, Frontal chest radiograph shows left mediastinal widening (arrows). B, Coned view shows phleboliths (arrows) in the left supraclavicular fossa.

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Fig. 14.64  Continued C, Contrast-enhanced CT shows a heterogeneous enhancing mass extending from the neck into the left upper mediastinum. D, Coronal T1-weighted MR images show an infiltrative, heterogeneous mass with signal intensity similar to skeletal muscle. E, On T2-weighted MR images the majority of the mass is of very high signal intensity, consistent with hemangioma.

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Specific Mediastinal Lesions

Fig. 14.66  Mediastinal hematoma after cardiac surgery. Coronal T1-weighted MR images show a large prevascular mass (arrows) that compresses the pulmonary outflow tract. Note the high signal intensity rim and isointense center, consistent with acute hemorrhage.

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Fig. 14.65  Mediastinal hematoma after inadvertent arterial puncture during line placement. A, Frontal chest radiograph shows marked widening of the right mediastinum. Note shift of the extrathoracic trachea (arrow) to the left. B, Contrast-enhanced CT shows that portions of the hematoma are of high attenuation and that it diffusely infiltrates the right side of the mediastinum. Note extrinsic narrowing of the right and left main bronchi.

Mediastinitis Acute mediastinitis Acute mediastinitis is a potentially life-threatening, but fortunately rare, condition that requires prompt diagnosis and treatment. Spontaneous or iatrogenic esophageal rupture is the most common cause, accounting for up to 90% of cases.419,420 Other causes of acute mediastinitis include necrosis of neoplasm, extension of infection from the neck, pharynx, teeth,421–425 retroperitoneum, lungs, pleura, or adjacent bones and joints,426 and mediastinitis after cardiac surgery.427 Acute mediastinitis may also be associated with empyema or subphrenic abscess. Clinically, affected patients are often very ill with chills, high fever, tachycardia, and chest pain. Circulatory shock is frequent. Dysphagia is common in those patients in whom the mediastinitis is caused by perforation of the esophagus. Diffuse mediastinitis has a particularly high mortality.

Esophageal perforation is usually caused by penetrating trauma, particularly from surgery, endoscopy, or swallowing sharp objects such as chicken bones. In young children, the possibility of child abuse as a cause of pharyngeal or esophageal perforation must be considered.428 Spontaneous perforation may occur, as in the Boerhaave syndrome, when forceful vomiting causes a tear in the esophageal wall. The tear in the esophagus is usually just above the gastroesophageal junction. It may be of any depth, but is usually confined to the mucosa, in which case bleeding may occur but there is no immediate danger of mediastinitis. If the tear is complete, however, air, alimentary juices, and food leak into the mediastinum resulting in mediastinitis. The primary imaging features of acute mediastinitis are medi­ astinal widening, pneumomediastinum, obliteration of fat planes, localized fluid collections, and abscess formation (Figs 14.67 and 14.68).429 Mediastinal widening is the result of inflammatory swelling or abscess formation within the mediastinum. Because so many cases of acute mediastinitis are secondary to esophageal perforation, an important clue to the diagnosis is air within the mediastinum, a feature that may be difficult to appreciate on chest radiographs. The air may be bubbly or streaky and may be localized or widespread in distribution. As with all types of pneumomediastinum, the air may extend into the neck or retroperitoneum. Accompanying pleural effusions in one or both pleural cavities are also common. Pleural effusion tends to be right sided in patients with iatrogenic, mid-esophageal perforation and left sided in patients with spontaneous, distal esophageal perforation (Boerhaave syndrome). In patients with Boerhaave syndrome, the effusion is particularly striking on the left and is often accompanied by consolidation of the left lower lobe (Fig. 14.67).430 All these features are better demonstrated on CT than on chest radiographs.429,431,432 Findings of esophageal perforation on CT include periesophageal fluid collections (100%), extra-luminal mediastinal air (100%), esophageal wall thickening (82%), and pleural effusion (82%).433 The site of perforation is rarely identifiable on CT (18%).433 Contrast esophagography can be critical in determining the presence and precise location of esophageal perforation.430 In cases of acute mediastinitis without discrete abscess formation, CT may show diffuse obliteration of normal fat planes, and gas bubbles may be scattered throughout the mediastinum (Fig. 14.69). When a walled-off abscess develops, the gas may be seen in discrete rounded collections or as air–fluid levels (Fig. 14.70). Mediastinal abscesses may be solitary, but are frequently multiple. CT is an invaluable guide should percutaneous drainage be indicated.429,434 CT may also show important associated abnormalities such as jugular vein thrombosis, pericardial effusion, or rupture of the hypopharynx or esophagus. Descending cervical mediastinitis is an uncommon, but potentially life-threatening, cause of mediastinitis.423–425,435 These infections begin in the head and neck region and spread via fascial

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Fig. 14.67  Spontaneous esophageal rupture after vomiting (Boerhaave syndrome). A, Supine chest radiograph shows pneumomediastinum (yellow arrows), air in neck (red arrow), left lower lobe atelectasis and layering left pleural effusion. B, Contrast esophogram shows rupture (arrow) into left pleural space.

planes (usually in the prevertebral space) into the middle and posterior mediastinum. Typical causes include odontogenic infection, suppurative tonsillitis, and retropharyngeal abscess. CT in cases of descending cervical mediastinitis shows fluid collections in the mediastinum that may be contiguous with a fluid collection in the cervical region.435 CT is essential for confirming the diagnosis, assisting in fluid aspiration to confirm infection, and for monitoring response to therapy. Mediastinitis after cardiac surgery is uncommon, occurring in only 0.5–3% of patients.427,429,436–440 Mediastinitis often occurs in the setting of sternal dehiscence. Radiographic features of sternal dehiscence include the midsternal stripe and the wandering wire signs (Fig. 14.71). A very thin vertical lucency (midsternal stripe) in the upper third of the sternum can often be seen on well-centered radiographs of patients after uncomplicated sternotomy. This lucent line should not exceed 2  mm in thickness, nor extend below the first sternal wire. Progressive mid-sternal lucency or a mid-sternal stripe greater than 3  mm in thickness after sternotomy suggests possible dehiscence.441 Changes in position or orientation of sternal wires (wandering wire sign) also suggest dehiscence.442 However, neither sign is predictive of mediastinitis complicating dehiscence.443 CT is therefore frequently performed in patients with clinically suspected mediastinitis but can be difficult to interpret since fluid and air collections, hematomas, pleural effusions, and increased attenuation of anterior mediastinal fat, all potential findings of mediastinitis, are common expected findings in the immediate postoperative period (Fig. 14.72). These findings generally resolve, however, in the first days and weeks after median sternotomy. One study found that mediastinal air or fluid collections seen on CT in the first 2 weeks after sternotomy were not specific for mediastini-

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tis.437 However, such findings were highly indicative of mediastinitis after 2 weeks. Air or fluid collections that appear de novo or that progressively increase without other explanation are also suggestive of mediastinitis (Figs 14.70 and 14.73).444 Needle aspiration of fluid collections may be necessary to rule out infection when mediastinitis is suspected (Fig. 14.72). CT is most useful for distinguishing patients with substantial retrosternal fluid collections that require open drainage from those that have only superficial wound infections. CT has limited ability for detecting early changes of sternal osteomyelitis. As noted above, minor degrees of sternal separation are common in asymptomatic patients after uncomplicated operations.436,438 However, gross sternal destruction, indicative of osteomyelitis, is occasionally seen on CT (Fig. 14.73). Radiolabeled leukocyte scanning (indium-111, 99mTc-hexamethylpropylene amine oxime [HMPAO]) can also be used to help diagnose sternal osteomyelitis in the setting of mediastinitis.445,446

Fibrosing mediastinitis Fibrosing mediastinitis (sclerosing mediastinitis or mediastinal fibrosis; Box 14.13) is a rare disorder caused by proliferation of acellular collagen and fibrous tissue within the mediastinum.447 It is thought that most cases in the USA are caused by an abnormal immunologic response to Histoplasma capsulatum antigens in genetically susceptible individuals.448–450 However, fibrosing mediastinitis is rare, even in areas where histoplasmosis is endemic, and recovery of organisms in affected specimens is unusual. Other etiologies that are likely more important in other parts of the world where H. capsulatum is rare include M. tuberculosis, autoimmune disease,

Specific Mediastinal Lesions Box 14.13  Fibrosing mediastinitis

Etiology • Infection – H. capsulatum (in USA) – Other fungi – M. tuberculosis • Radiation, autoimmune disease, drug therapy • Idiopathic

Clinical – symptoms related to mediastinal structures involved • Airway – Recurrent pneumonia – Persistent atelectasis – Hemoptysis • Pulmonary vein – Mimics mitral stenosis – Dyspnea, hemoptysis • Superior vena cava – Distended neck veins – Facial swelling and edema

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Imaging • When related to infection – Focal invasive mediastinal mass – Typically unilateral – Calcification in most • When idiopathic – Focal or diffuse mediastinal soft tissue mass – Calcification uncommon • Caveats – Chest radiograph frequently underestimates extent of mediastinal disease – CT best for showing calcification, mediastinal invasion – CT angiography/MRI good for showing vascular involvement • Differential diagnosis – Lymphoma – Calcifying mediastinal metastases

Behçet disease, radiation therapy, trauma, and drugs such as methy­ sergide.451–453 Importantly, an idiopathic form of fibrosing mediastinitis is also now recognized.454,455 A rare familial form associated with retroperitoneal fibrosis, sclerosing cholangitis, Riedel thyroiditis, and pseudotumor of the orbit has also been reported.456 Fibrosing mediastinitis is characterized by progressive proliferation of fibrous tissue within the mediastinum that encases and eventually obstructs vital structures such as the vena cava, the pulmonary arteries and veins, and the airways. Fibrosis due to histoplasmosis is often focal in nature. In older reports, idiopathic disease was described as more diffuse in distribution.457 However, more recent reports describe more focal mediastinal involvement in cases of idiopathic fibrosis.454,455 In areas where histoplasmosis is endemic, affected patients usually present in the second through fifth decades of life with signs and symptoms of cough, recurrent pulmonary infection, hemoptysis, or chest pain.449 Pulmonary venous obstruction may result in symptoms that mimic mitral stenosis. Patients with superior vena cava obstruction may present with swelling of the face and distension of the neck veins.458 In other parts of the world where histoplasmosis is unusual, the age range at presentation is much broader.451 Chest radiographs frequently underestimate the extent of mediastinal disease (Fig. 14.74) and can be normal.459–467 When abnormal, chest radiographic findings vary somewhat depending on the etiology of fibrosis and the site and nature of the mediastinal abnormal-

P

P B

Fig. 14.68  Esophageal rupture after vomiting. A, Frontal chest radiograph shows large right hydropneumothorax. B, CT performed after oral contrast administration shows extravasation into mediastinum and right pleural space, P, with multiple sites of potential rupture (arrows).

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Chapter 14 • Mediastinal and Aortic Disease

Fig. 14.69  Esophageal rupture. CT shows extensive pneumomediastinum surrounding the esophagus. Rupture was confirmed by esophogram (not shown).

ity. Disease due to infection, usually histoplasmosis, typically results in focal or diffuse calcified mediastinal masses that may be evident radiographically (Fig. 14.75). Idiopathic fibrosis results in either a focal454,455 or diffuse mediastinal abnormality without evident calcification (Fig. 14.76).468 In either setting, the secondary effects of mediastinal fibrosis may also be evident on chest radiographs. These include findings of airway narrowing, parenchymal consolidation or atelectasis due to airway obstruction, oligemia due to pulmonary artery obstruction, or septal thickening and pleural effusion due to pulmonary venous obstruction (Fig. 14.77). CT or MRI are most useful for evaluation of fibrosing mediastinitis.259,449,451,465,469–471 When disease is due to histoplasmosis or tuberculosis, CT usually shows a focal, infiltrative mediastinal or hilar mass that is often extensively calcified (Figs 14.74, 14.75, and 14.77). When disease occurs idiopathically, CT may show either a focal masslike opacity454,455 or more diffuse encasement of mediastinal structures by soft tissue attenuation masses that obliterate normal fat planes (Fig. 14.76). Calcification is uncommon in lesions due to idiopathic fibrosis. In either setting, CT is also useful for demonstrating airway, pulmonary arterial and venous involvement. On MRI, the process is typically of heterogeneous signal intensity on T1- and T2-weighted images.447 Markedly decreased signal intensity on T2-weighted images is occasionally seen and is suggestive of the fibrotic or calcific nature of the process.472,473 MRI can demonstrate the infiltrative nature of the fibrosis and the narrowing of the major vessels and bronchi as well as, if not better than, CT.460,470,472,474,475 However, CT is better for demonstrating calcification within the lesion, a finding that is critical for differentiating fibrosing mediastinitis from other infiltrative disorders of the mediastinum such as metastatic carcinoma or lymphoma. Radionuclide ventilation–perfusion scanning can be used to diagnose pulmonary arterial or airway obstruction (Fig. 14.77).473,476 Venography, pulmonary arteriography (Fig. 14.74), or CT angiography may show smooth, tapered narrowing of the superior vena cava and brachiocephalic veins, together with numerous dilated collateral veins, and may also show narrowing of the central pulmonary arteries.449,467 Lesions can be either metabolically active477,478 or negative479 on FDG-PET imaging. Barium swallow may show narrowing of the esophagus and, in rare instances, may show varices resulting from esophageal venous collaterals, so-called downhill varices. The prognosis for affected patients is often unpredictable; disease may progress, remain stable for many years, or even spontaneously regress.447 Mortality rates up to 30% are reported.449 Patients with subcarinal or bilateral fibrosis may have a slightly higher mortality than patients with more localized disease.449 Causes of death include recurrent pneumonia, hemoptysis, or cor pulmonale.447 Because many cases in the USA are caused by an inflammatory reaction to H. capsulatum infection, some patients have been treated with systemic antifungal agents or corticosteroids, with variable success.447 If disease is localized, surgical resection can be curative or result in symptomatic improvement. Bilateral mediastinal involvement may preclude surgery, however. Symptomatic patients may also be treated by percutaneous therapies directed at occluded or severely stenosed airways, pulmonary arteries, or vena cava.480,481 Laser therapy, balloon dilation, and intravascular or endobronchial stent placement have all been used with success to treat affected patients (Fig. 14.78).447

Mediastinal panniculitis

Fig. 14.70  Mediastinal abscess in heart transplant recipient. Contrast-enhanced CT shows large anterior mediastinal fluid collection. Note gas bubbles and rim enhancement. Aspiration confirmed bacterial infection.

924

Panniculitis is an inflammatory process of fat leading to focal fat necrosis. It is most commonly encountered in subcutaneous mesenteric fat. Mediastinal panniculitis is a very rare condition that is usually seen in patients with Weber–Christian disease, it may cause focal mediastinal widening, and may therefore be mistaken for neoplasm. CT in one case showed masslike accumulations of soft tissue (shown to be fibrosis and inflammation on histopathologic examination) interspersed with fat in the mediastinum.482 On MRI, the mass was very heterogeneous.482

Specific Mediastinal Lesions

A

B

C

Fig. 14.71  Mediastinal dehiscence after heart transplant. A, Frontal chest radiograph obtained 1 week after surgery shows normally aligned sternal wires. B, Chest radiograph obtained 1 month later now shows misalignment of wires (‘wandering wire sign’) (arrows). C, Coronal reconstruction from CT confirms dehiscence.

A

Fig. 14.72  Mediastinal hematoma after bypass surgery. Contrastenhanced CT shows a well-defined fluid collection (arrow) with punctate collections of gas in the prevascular space. Needle aspiration confirmed hematoma; all cultures were negative.

B

Fig. 14.73  Acute mediastinitis in a heart transplant recipient. A, CT shows soft tissue opacity in the prevascular space and destruction of the right clavicular head. B, CT at a lower level shows sternal osteomyelitis and substernal phlegmon.

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Chapter 14 • Mediastinal and Aortic Disease

B

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C

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Fig. 14.74  Fibrosing mediastinitis due to histoplasmosis. A, Frontal chest radiograph shows a calcified right upper lobe nodule (arrow). B, Contrast-enhanced CT shows an infiltrating subcarinal mass with punctate calcification. Note smooth narrowing of proximal right pulmonary artery (yellow arrow), encasement and narrowing of the distal superior vena cava (*), and dilatation of the azygos vein (red arrow). C, Arteriogram confirms marked stenosis of the right pulmonary artery (arrows). D, Superior vena cavagram confirms near-complete occlusion of the distal superior vena cava (arrow). (With permission from Rossi SE, McAdams HP, Rosado-de-Christenson ML, et al. Fibrosing mediastinitis. RadioGraphics 2001;21:737–757.)

926

Specific Mediastinal Lesions

A

B

Fig. 14.75  Fibrosing mediastinitis due to histoplasmosis. A, Frontal chest radiograph shows right hilar, paratracheal, and subcarinal lymph node enlargement. Note small calcified nodules in the lungs. B, Contrast-enhanced CT shows a calcified infiltrative mediastinal mass that surrounds and narrows the bronchus intermedius and right pulmonary artery.

A

C

B

Fig. 14.76  Fibrosing mediastinitis in a patient with sickle cell anemia. A, Frontal chest radiograph shows diffuse mediastinal widening. B, C, Contrast-enhanced CT shows diffuse encasement of the mediastinum by an infiltrating, non-calcified soft tissue mass. C, Note narrowing of the proximal right and left pulmonary arteries and encasement of the descending thoracic aorta.

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Chapter 14 • Mediastinal and Aortic Disease

B

A

D

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Fig. 14.77  Fibrosing mediastinitis due to histoplasmosis. A, Frontal chest radiograph shows volume loss in the right hemithorax and diffuse septal thickening in the right lung. B, Contrast-enhanced CT shows an infiltrative, partially calcified mass that narrows the right pulmonary artery and bronchus intermedius. Note complete obstruction of the superior pulmonary vein (arrow). C, CT shows diffuse septal thickening in the right lung due to pulmonary venous obstruction. D, Perfusion scintigraphy shows complete absence of perfusion to the right lung. The ventilation scan (not shown) was normal. (With permission from Rossi SE, McAdams HP, Rosado-de-Christenson ML, et al. Fibrosing mediastinitis. RadioGraphics 2001;21:737–757.)

Fig. 14.78  Fibrosing mediastinitis due to histoplasmosis. Contrast-enhanced CT shows a calcified mass (yellow arrow) obstructing the superior vena cava. A conduit (red arrow) that bypasses the obstructed vena cava is seen anterior to the ascending aorta. Note also the stent in the distal left pulmonary artery.

928

Specific Mediastinal Lesions

Neurogenic tumors of the mediastinum For purposes of discussion, the neurogenic tumors (Boxes 14.14– 14.16) can be classified as tumors of nerve sheath origin, those of ganglion cell origin, and tumors of the paraganglionic cells.483–485 The nerve sheath tumors include schwannomas, neurofibromas, and malignant tumors of nerve sheath origin. They account for up to 65% of mediastinal neurogenic tumors.486 Schwannomas are the most common intrathoracic nerve sheath tumors.487 Neurofibromas, particularly when multiple, and malignant nerve sheath tumors are strongly associated with neurofibromatosis. Patients with neurofibromatosis may develop large plexiform masses of neurofibromatous tissue in the mediastinum (Fig. 14.79).488–490 Granular cell myoblastomas, which are believed to be of Schwann cell origin, are rarely found in the mediastinum.491,492 Almost all intrathoracic nerve sheath tumors arise either from the intercostal (Fig. 14.80) or from sympathetic nerves, the rare exceptions being neurofibromas or schwannomas of the phrenic or vagus nerves. Many arise adjacent to the spine and, in about 5% of cases,14,493 extend through the neural foramina into the spinal canal (the so-called ‘dumbbell tumor’) (Fig. 14.81). Most nerve sheath tumors of the mediastinum are benign. Affected patients are typically asymptomatic and the tumors are

Box 14.14  Neurogenic tumors of the mediastinum • Nerve sheath tumors – Schwannoma – Neurofibroma – Malignant tumor of nerve sheath origin • Ganglion cell tumors – Ganglioneuroma – Ganglioneuroblastoma – Neuroblastoma • Paragangliomas

Box 14.15  Imaging of neurogenic tumors

Tumors of nerve sheath origin • Chest radiography – Round or oval – Enlarged neural foramina – Pressure erosion on bone – Rarely calcify • CT – Neurofibroma – homogeneous soft tissue mass, can be near-water attenuation and mimic a cyst – Schwannoma – usually more heterogeneous, calcification – Both enhance heterogeneously – Malignant nerve sheath tumor – heterogeneous, bone destruction, metastases • MRI – Intraspinal extension (‘dumbbell’ lesion) in 5% – Neurofibroma – target lesion on T1, T2

Tumors of ganglion cell origin • Chest radiography – Elongated along axis of spine – May also cause bone changes – May calcify • CT – Ganglioneuroma – homogeneous soft tissue mass – Neuroblastoma – heterogeneous, invasive – Calcification is common • MRI – Intraspinal extension

Box 14.16  Mediastinal paraganglioma • Histopathology – Arise from chromaffin cells – Benign or malignant • Terminology – Within adrenal = pheochromocytoma – Outside adrenal = paraganglioma • Location (mediastinal) – Two-thirds near aortic arch (aortic body tumors) – One-third paravertebral – Rarely within heart • Mediastinal paragangliomas usually nonfunctional • CT findings – Homogeneous or heterogeneous, central necrosis – Hyperenhancing • MRI – Isointense T1 signal – Hyperintense T2 signal – Intratumoral flow voids due to vessels • FDG-PET findings – Metabolically active

often discovered as incidental findings on chest imaging studies. In contrast to the ganglion cell tumors, nerve sheath tumors are rare in patients under the age of 20 and virtually nonexistent in patients who are less than 10 years old, except in patients with neurofibromatosis. Malignant tumors of nerve sheath origin are uncommon and almost always occur in patients with neurofibromatosis.483,485 Affected patients typically present with pain. The tumors of ganglion cell origin comprise a spectrum from benign ganglioneuroma to malignant neuroblastoma; ganglioneuroblastoma is an intermediate form of low malignant potential.494 Neuroblastoma and ganglioneuroblastoma may occasionally mature into the more benign form.495 The mediastinum is the second most common primary site (after the adrenal gland) for tumors of ganglion cell origin.496 Approximately one-third to one-half of mediastinal neuroblastomas arise primarily in the mediastinum.497,498 The remainder occur secondary to either lymph node metastases or intrathoracic spread from a tumor arising primarily in the adrenal gland. Neuroblastoma and ganglioneuroblastoma are essentially tumors of childhood.497,499 Less than 10% occur in patients older than 20 years of age.487,500 In children less than 1 year of age, a neurogenic tumor is virtually certain to be one of these two types.501 Ganglio­ neuroma has a broader and more even age distribution, ranging from 1 to 50 years.487,501 Urinary vanillylmandelic acid and homovanillylmandelic acid levels may be elevated in patients with neuro­ blastoma and ganglioneuroblastoma and are useful diagnostic markers.502

Imaging of neurogenic tumors (Box 14.15) Most neurogenic tumors manifest as well-defined masses with smooth or lobulated contours (Figs 14.82–14.84).487,500,503 When localized, it is not possible to distinguish benign from malignant lesions. The tumors may be almost any size and some are very large, occupying most of a hemithorax. Except for vagal and phrenic nerve tumors, and the occasional neuroblastoma, neurogenic tumors are typically situated in the posterior mediastinum501 or grow along intercostal nerves. Those that arise adjacent to the upper thoracic spine may occupy the lung apex and appear as a well-marginated apical mass (Fig. 14.84). Most neurogenic tumors are spherical in nature, but some ganglion cell tumors are elongated along the spine, paralleling the vertical orientation of the sympathetic chain (Fig. 14.85). It may be possible to distinguish between a ganglion cell tumor and a nerve

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D

Fig. 14.79  Neurofibromatosis. A, Frontal chest radiograph shows lobulated masses in both apices and along both sides of the superior mediastinum. Note nodular opacities overlying both lower lung zones, consistent with neurofibromas of intercostal nerves. B, Coned view shows extensive rib-notching (arrows). C, D, Coronal T1-weighted MR images confirm multiple mediastinal, apical, and axillary plexiform neurofibromas (arrows). Note the central regions of low signal intensity (‘target sign’). (With permission from Rossi SE, Erasmus JJ, McAdams HP, et al. Thoracic manifestations of neurofibromatosis-I. AJR Am J Roentgenol 1999;173:1631–1638.)

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Specific Mediastinal Lesions

A

A

C

Fig. 14.80  Intercostal nerve schwannoma. A, CT shows a wellmarginated soft tissue mass (arrow) arising from an intercostal nerve. Coned view of a frontal B, chest radiograph shows a smooth, wellcorticated pressure erosion of the adjacent rib (arrow).

B

B

Fig. 14.81  ‘Dumbbell’ neurofibroma. A, Coned view of a lateral chest radiograph shows a well-marginated paraspinal mass (yellow arrows). Note pressure erosion along the posterior surface of the vertebral body (red arrows). B, CT shows marked widening of the neural foramen by a soft tissue mass. C, Coronal T1-weighted MR image shows extension of the mass through the foramen into the spinal canal.

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Chapter 14 • Mediastinal and Aortic Disease

B

A

C

Fig. 14.82  Mediastinal schwannoma. A, Coned scout view from CT shows a well-marginated right paraspinal mass (arrow). B, CT shows that the mass is homogeneous and of soft tissue attenuation. C, Combined FDG-PET image shows focally increased metabolic activity in mass.

932

Specific Mediastinal Lesions

A

A

B

Fig. 14.83  Mediastinal schwannoma. A, Frontal chest radiograph shows a large well-marginated mass in the right upper thorax. B, Noncontrast CT shows a homogeneous, low-attenuation 20 HU mass with no evidence of extension into the spinal canal.

B

Fig. 14.84  Apical schwannoma. A, Frontal chest radiograph shows a well-marginated left apical mass without rib or bone erosion. B, Noncontrast CT shows a slightly heterogeneous mediastinal mass

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Fig. 14.85  Ganglioneuroma in 7-year-old girl with cough. A, Frontal chest radiograph shows an oblong mass in the right paraspinal region. The lateral margins of the mass are indistinct and there is right lower lobe pneumonia. B, Coned view shows minimal pressure erosion (arrow) of the posterior ribs. C, Contrast-enhanced CT shows that the mass is heterogeneous and contains punctate and chunk-like calcification. D, Axial T2-weighted MR image shows that the mass is of high signal intensity.

934

Specific Mediastinal Lesions

Fig. 14.86  Calcified nerve sheath tumor. Frontal chest radiograph shows a large calcified right-sided mediastinal mass. sheath tumor by observing: (1) the shape of the tumor mass, since the ganglion cell tumors are frequently elongated along the mediastinum with tapered superior and inferior margins, whereas nerve sheath tumors are more spherical in shape with more acute angles at their margins; and (2) that ganglion cell tumors arise slightly more anteriorly with their center alongside the vertebral body, whereas nerve sheath tumors are centered on the neural foramen, or are closely adherent to the chest wall. Calcification can be seen in all types of neurogenic tumors (Figs 14.85 and 14.86). Approximately 10% of primary mediastinal neuroblastomas are visibly calcified on chest radiographs,487,497 a figure considerably lower than that reported for neuroblastomas arising in the abdomen. The frequency of calcification detectable at CT is substantially higher. In neuroblastoma, the calcification is usually finely stippled, whereas in ganglioneuroblastoma and ganglioneuroma (Fig. 14.85), it is denser and coarser, occurring most frequently in the larger, more benign lesions. Nerve sheath tumors rarely calcify.487,488 When present, calcification is typically curvilinear and peripheral in nature and is seen in only very large masses. Because neurogenic tumors tend to arise adjacent to bone and grow slowly, they can cause pressure erosions of adjacent ribs and vertebrae (Figs 14.81, 14.83, and 14.85) – an important diagnostic feature. The bone in immediate contact with the tumor shows a scalloped edge; usually the bony cortex is preserved, and frequently it is thickened. The ribs may be thinned and splayed apart, and the intervertebral foramina may appear enlarged. With larger lesions, the absence of changes in the adjacent bones argues against the diagnosis of a neurogenic tumor. Bone changes are most frequently seen with the tumors of ganglion cell origin, perhaps because these tumors are frequently large at presentation and occur in pediatric patients with a rapidly growing skeleton. Large tumors may be associated with scoliosis.488 Frank destruction of bone appears to be a sign of malignancy,487,488,504 as is associated pleural effusion.501 On noncontrast CT, schwannomas are often of mixed attenuation, and may have regions that are close to water attenuation485,500,504–507 due either to hypocellularity or to cystic degeneration (Fig. 14.83).508,509 Neurofibromas tend to be more homogeneous on noncontrast CT.485,506 Nerve sheath tumors are typically vascular and enhance after administration of intravascular contrast. A variety of enhancement patterns have been described including homogeneous, diffuse heterogeneous (with cystlike regions of nonenhancement), rim enhancement, and central enhancement with a hypoattenuating rim.485,504 Malignant nerve sheath tumors are typically heterogeneous on both contrast-enhanced and noncontrast CT; local invasion and bone destruction as well as metastatic foci to the pleura or lungs suggest the diagnosis (Fig. 14.87).485,509 Ganglioneuromas usually manifest as homogeneous or heterogeneous masses of low-attenuation lesions on both contrast-enhanced and

Fig. 14.87  Malignant nerve sheath tumor in a patient with neurofibromatosis. Frontal chest radiograph obtained 1 year after resection of a right-sided malignant nerve sheath tumor (note surgical clips) shows a new mass (arrow) in the left hemithorax. Biopsy confirmed metastatic disease.

Fig. 14.88  Neuroblastoma. Contrast-enhanced CT shows an infiltrative posterior mediastinal mass that encases the descending thoracic aorta. (Courtesy of Donald Frush, MD, Durham, NC.) noncontrast CT (Fig. 14.85).485 Neuroblastomas manifest as heterogeneous soft tissue masses that show extensive local invasion (Fig. 14.88).485 CT can show spinal and intraspinal involvement (Fig. 14.81),510,511 particularly if intrathecal contrast has been administered (rarely performed). However, MRI is considered the standard for imaging neurogenic tumors because it better demonstrates spinal and intraspinal involvement (Fig. 14.81).404,512 The signal pattern at MRI is variable (Figs 14.89–14.91). Neurogenic tumors may show uniform signal intensity similar to muscle on T1-weighted sequences and signal intensity considerably higher than muscle on T2-weighted

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Chapter 14 • Mediastinal and Aortic Disease

Fig. 14.91  Neuroblastoma. Axial gadolinium-enhanced MR images show invasion of the chest wall and extension into the neural foramen (arrow).

A

B

Fig. 14.89  Neurofibroma. A, Axial T1-wieghted MR image shows a small well-circumscribed mass (arrow) of intermediate signal intensity in the right paraspinal region. B, The mass enhances intensely after administration of gadolinium-based contrast material.

Fig. 14.90  Ganglioneuroma in a young woman. Coronal MR images show a well-circumscribed oblong mass of intermediate signal intensity in the left paraspinal region. Note limited extension into the neural foramen (arrows).

936

sequences. Neurofibromas, on occasion, show the so-called ‘target pattern’ with different signal in the central portion of the lesion compared with the periphery (see Fig. 14.79).507,513–515 On T1-weighted images, the central portion is of higher signal, whereas on T2-weighted spin-echo images, the periphery is of higher intensity than the center, corresponding to the histopathologic finding of central nerve tissue and peripheral myxoid degeneration.516 Schwannomas and ganglioneuromas may show heterogeneous high signal intensity throughout the lesion on T2-weighted images, and low to intermediate signal intensity on T1-weighted images.32 In these cases, the signal high intensity on T2-weighted images is probably due to cystic degeneration.507,516 Ganglioneuromas may have a whorled appearance on MRI, corresponding to whorls of collagenous fibrous tissue and neural tissue. Because most neurogenic tumors in adults are benign, the role of imaging is to facilitate differential diagnosis and to evaluate local extent prior to resection. MRI is probably the technique of choice for imaging neurogenic tumors because it best shows intraspinal extension. For malignant tumors, notably neuroblastoma, chest radiography and MRI appear to be the best imaging techniques for staging (Fig. 14.91).502,517 Radionuclide imaging with agents such as meta-iodobenzylguanidine (MIBG) or FDG-PET scanning can also be used to assess the extent of tumor and for staging.518,519 FDG-PET imaging is likely of little benefit for differentiation of benign from malignant nerve sheath tumors, as benign schwannomas may show increased metabolic activity (Fig. 14.82).520,521

Mediastinal paragangliomas Paragangliomas (Box 14.16) are rare tumors that arise from chromaffin cells and may be either benign or malignant.522–524 Most such tumors arise in the adrenal glands and are known as pheochromocytomas. Those that arise elsewhere are known collectively as paragangliomas.523 Mediastinal paragangliomas are rare, constituting less than 2% of thoracic neurogenic tumors in one large series.487 In a review of 51 mediastinal paragangliomas, two-thirds arose in the region of the aortic arch (aortic body tumors) and one-third arose in the paravertebral region (Figs 14.92 and 14.93).525 Aortic body tumors may occur in one of four locations: lateral to the brachiocephalic artery; anterolateral to the aortic arch; at the angle of the ductus arteriosus; or above and to the right of the right pulmonary artery.524,525 Tumors may also arise in the wall of the left atrium or the interatrial septum (Fig. 14.94).526–528 Multifocal lesions are also reported.529 Most mediastinal paragangliomas are nonfunctional and are detected either incidentally or because of signs and symptoms related to compression or invasion of mediastinal structures.524 Mediastinal paragangliomas manifest as round soft tissue masses on CT that, because they are highly vascular, can enhance intensely after administration of intravenous contrast.30,524 Smaller lesions tend to be of homogeneous attenuation, while larger lesions may be more heterogeneous, due to necrosis (Fig. 14.92).524 Arteriography demonstrates enlarged feeding vessels, pathologic vessels within the tumor, and an intense tumor blush.530 Radioiodine MIBG

Specific Mediastinal Lesions

A

B

Fig. 14.92  Mediastinal paraganglioma. A, Contrast-enhanced CT shows medial anteroposterior window mass. Note peripheral enhancement. B, Coronal FDG-PET-CT image shows markedly increased metabolic activity within the periphery of the lesion and decreased activity centrally, likely due to necrosis.

A

B

Fig. 14.93  Mediastinal paraganglioma. CT performed after myelography A, shows a well-marginated right paravertebral mass. B, MIBG scan shows increased activity in the mass, but no other sites of tumor.

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Chapter 14 • Mediastinal and Aortic Disease

A

Fig. 14.94  Intracardiac paraganglioma arising from the wall of the left atrium. Axial MR image shows a mass of intermediate signal intensity that occupies most of the lumen of the left atrium. Note that the mass contains foci of decreased signal, typical of paraganglionic tumors. (Fig. 14.93) and somatostatin receptor scintigraphy all show increased activity in paragangliomas.526,531–534 The MR findings of thoracic paragangliomas are the subjects of case reports only.535–537 Based on these reports, it seems that the MR appearance of thoracic lesions is similar to that of lesions more commonly encountered in the head and neck: the masses are iso­ intense to muscle on T1-weighted images and are of substantially higher signal than muscle on T2-weighted images (Fig. 14.95).538 Numerous serpiginous vascular channels may also be seen coursing through the larger lesions. MRI is particularly advantageous for showing intracardiac paragangliomas (Fig. 14.94). Lesions can be metabolically active on FDG-PET scans (Fig. 14.92).

Parathyroid lesions of the mediastinum Primary hyperparathyroidism is usually caused by a parathyroid adenoma (Box 14.17) in the neck. Surgeons frequently do not obtain preoperative imaging studies to localize the parathyroid glands because neck exploration is curative in over 90% of affected patients.539 However, about 10% of adenomas arise in ectopic para­ thyroid glands in the mediastinum, usually in or around the thymus gland.540,541 In one large series, the two most common ectopic locations were intrathymic and paraesophageal.542 Affected patients may have four parathyroid glands in the normal position in addition to the ectopic mediastinal adenoma. Although the ectopic adenoma is usually solitary, at least one patient with multiple mediastinal adenomas has been reported.543 As ectopic adenomas can be missed at surgical exploration, preoperative localization with imaging studies can reduce operative time, postoperative morbidity, and requirement for repeat surgery.404 Imaging techniques for localizing ectopic mediastinal parathyroid glands include radionuclide imaging (99mTc-MIBI, 99m Tc-tetrofosmin),544,545 CT, and MRI.546–548 Mediastinal parathyroid glands are probably best demonstrated using 99mTc-sestamibi radionuclide imaging.544–547,549–551 Sensitivities of over 90% are reported, especially with use of SPECT.552 CT or MRI are usually reserved for anatomic localization of an abnormality detected on the 99mTc-sestamibi scan.404 However, combined CT/SPECT imaging can also be used to improve localization of mediastinal lesions.553

938

B

Fig. 14.95  Mediastinal paraganglioma. MRI shows a small mediastinal mass (arrows) of intermediate signal intensity on A, the T1-weighted image and of very high signal intensity on B, the T2-weighted image. Box 14.17  Mediastinal parathyroid lesions

Ectopic parathyroid glands • 10% parathyroid adenoma • Arise near thymus gland, paraesophageal • 99mTc-sestamibi findings – Technique of choice for detection – Sensitivity 90%, especially with single photon emission computed tomography (SPECT) • CT findings – Homogeneous soft tissue attenuation – 50  mm, wall thickness >11  mm and presence or development of ulcer-like projections in the hematoma.867,869 The optimal treatment of aortic intramural hematoma continues to evolve. Traditionally, type A lesions have been treated by open surgical repair, whereas type B lesions are managed medically, unless complications develop.810,869,870 However, Motoyoshi et al.865 studied 36 patients with acute type A intramural hematoma. All 10 patients with intramural hematoma and cardiac tamponade or aortic rupture received surgery; 26 patients without complications were initially treated medically, but seven eventually required surgery due to complications. These authors concluded that patients with type A intramural hematoma without complications such as cardiac tamponade or aortic rupture could be managed medically, but that up to half would eventually require surgical repair of the ascending aorta.865 Endoluminal stent-graft repair is now becoming the treatment of choice for complicated type B hematomas.810

Penetrating atherosclerotic ulcer Penetrating atherosclerotic ulcers (PAUs) result from progressive ulceration of an atheromatous plaque.857,871–875 The ulcer, which is most frequent in the descending aorta, penetrates the internal elastic lamina of the aorta and causes intramural hematoma that may then resolve or progress to aortic rupture or classic dissection.876 Unlike classic dissection, the hematoma may dissect between the aortic media and adventitia.864 The clinical features of penetrating atherosclerotic ulcer are similar to those of classic aortic dissection, except that affected patients are usually older, there is a marked male predominance, there is a stronger association with severe atherosclerosis, and the ulcerated aorta may be more prone to rupture than is a typical dissection.877–880 The optimal management of these patients is debated, but frequently involves endovascular stent grafting, particularly in the setting of complications.810,874,881 Ulcerlike projections are common in the setting of intramural hematoma, may be present on initial imaging or develop on followup, and have been reported to portend a worse outcome.843,869,882–884 Thus, there can be confusion regarding diagnosis of penetrating atherosclerotic ulcer syndrome and intramural hematoma. Classic PAU syndrome is probably best thought of as a focal disease of the aorta with a substantial risk of aortic rupture or saccular or pseudo­ aneurysm formation. Intramural hematoma in the setting of PAU is usually quite limited in longitudinal extent. Classic aortic intramural hematoma, with or without ulcerlike projections, involves the aorta in a more diffuse fashion.843

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Chapter 14 • Mediastinal and Aortic Disease

Imaging of aortic dissection, intramural hematoma, and penetrating atherosclerotic ulcer (Boxes 14.27–14.29)

Aortic dissection

Aortic dissection

• Noncontrast CT – Displaced intimal calcification – ± Aortic dilatation – ± Complications – Mediastinal, pericardial, pleural hemorrhage • Contrast CT – Opacification of two (or more) lumens separated by thin intimal flap • Pitfalls – Thrombosed false lumen – Pulsation artifacts in ascending aorta – Periaortic atelectasis, tumor

Chest radiography

Intramural hematoma

The role of imaging in patients with symptoms of an acute nontraumatic aortic syndrome is to: confirm the presence of a dissection, intramural hematoma, or penetrating ulcer; and differentiate between type A and B lesions – information used not only for major management decisions (surgery versus medical therapy), but also for surgical planning. Identification of complications such as associated aortic regurgitation, pericardial, mediastinal or pleural hemorrhage, aortic rupture or coronary artery involvement is also important.841,885,886

The primary role of chest radiography in patients with suspected aortic dissection is to exclude other conditions. Though chest radiographic findings may suggest the diagnosis in up to half of affected patients,889 these findings are usually not specific enough for definitive diagnosis.890 While unusual, the chest radiograph can be completely normal in patients with acute aortic dissection. A major diagnostic problem is that affected patients are often critically ill and that portable radiographs obtained in this situation are frequently suboptimal. Furthermore, dissections confined to the aortic root are often hidden on chest radiographs. The arch and descending aorta are, however, border-forming structures and dissections involving these portions of the aorta usually produce recognizable findings on chest radiographs (Figs 14.147 and 14.148). Enlargement of the aorta, the most frequent finding, tends to involve long segBox 14.27  Diagnostic information required in patients with acute nontraumatic aortic syndromes* • Confirm presence of aortic dissection, intramural hematoma, or penetrating ulcer • Evaluate extent of disease – Involvement of the ascending aorta – Sites of entry and reentry tears – Branch vessel involvement – Coronary artery involvement – Thrombus in the false lumen • Diagnose complications – Aortic dilatation – Aortic rupture – Integrity of aortic valve – Severity of aortic regurgitation – Pericardial, mediastinal, or pleural hemorrhage *Modified from Cigarroa et al.887 and Treasure.888

Box 14.28  Chest radiographic findings of acute aortic dissection* • • • • • • • • •

Enlarged ascending aorta Enlarged descending aorta Enlarged aortic arch Indistinct aortic arch Widened paraspinal reflection Tracheal shift Displacement of left main bronchus Displaced intimal calcification Pleural effusion, notably on left side

*None is specific. Modified from Dee et al.891 and Ide et al.894

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Box 14.29  CT of aortic dissection, intramural hematoma, and penetrating ulcer

• Noncontrast CT – Crescentic high-attenuation rim – ± Aortic dilatation • Contrast CT – No intimal flap or false lumen – No enhancement of rim

Penetrating ulcer • Noncontrast CT – Extensive, calcified atheromatous plaque – ± Aortic dilatation • Contrast CT – Focal contrast collection penetrating into media – Associated intramural hematoma – No intimal flap or false lumen

ments, although focal dilatation is occasionally seen. Sometimes the aorta is distinctly undulating in appearance (Fig. 14.148), and, occasionally, the dissection may manifest as a focal aneurysm of the aorta.891 It is often impossible to distinguish aortic dissection from atherosclerotic disease on chest radiographs.892 However, progressive enlargement of the aorta over a few hours or days is a fairly specific sign and is therefore a most important observation. In appropriate clinical circumstances, atheromatous calcification that projects more than 1 cm inside the lateral aortic contour on the frontal chest radiograph is suggestive of aortic dissection (Fig. 14.149). Displacement of intimal calcification to this degree is not a common finding, however, being seen in only 4% of cases in one large series.890 This sign must be used with caution. The calcification must be unequivocally seen in profile along the lateral aortic contour. This sign is therefore of limited utility in the region of the aortic arch where the frontal projection shows a foreshortened view of the obliquely curving aorta (Fig. 14.150). Furthermore, this sign is not specific because the lateral wall of the aorta may be substantially thickened in patients with severe atherosclerosis or aortitis. Additionally, a soft tissue mass that abuts the lateral margin of the aorta may give rise to a false-positive finding. Absence of this sign cannot be used to exclude aortic dissection, as intimal calcification may not be visibly displaced on chest radiographs of patients with acute aortic dissection.893 Hemorrhage from acute aortic dissection may also cause recognizable well- or ill-defined mediastinal widening on chest radiographs. Perihilar pulmonary opacities may also be seen due to dissection of mediastinal blood into the lungs. Pleural effusions due to leakage of blood from the mediastinum are common; they are usually left-sided or, if bilateral, are often worse on the left than the right. Rupture into the pericardium is an extremely serious, often fatal, complication. The presence of pericardial blood can rarely be diagnosed on chest radiographs but is suggested by a rapid increase in the diameter of the cardiopericardial silhouette (Fig. 14.151).

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Fig. 14.147  Acute type B aortic dissection. A, Frontal chest radiograph shows bilateral mediastinal widening, elevation of the left diaphragm, and perihilar heterogeneous opacity in the right lower lobe. B, Noncontrast CT shows displaced intimal calcification (arrows) in the lumen of the descending thoracic aorta. C, Contrast-enhanced CT shows a complex type B dissection with at least two false lumens (*). T, true lumen.

C

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Fig. 14.148  Acute type B aortic dissection. A, Frontal chest radiograph shows dilatation and tortuosity of the descending thoracic aorta. Note that the lateral contour of the aorta is undulating. B, Oblique coronal reformat image from a contrast-enhanced CT shows a limited type B aortic dissection. Note that the reformat image clearly shows the communication between the true, T, and false lumens (*) and that the majority of the false lumen is filled with thrombus.

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Aortography For many years, catheter-based aortography was the standard for diagnosis of aortic dissection. The reported sensitivity of aortography for diagnosis of aortic dissection varies from 88% in a large multicenter study895 up to 97%.896 The principal angiographic finding is a false lumen separated from the true lumen by an intimal flap (Fig. 14.152). False-negative results occur when the false lumen is thrombosed,897 in patients with intramural hematoma, and when the true and false channels opacify equally and the intimal flap is not tangential to the X-ray beam.898 Conversely, aortic wall thickening may mimic an unopacified false lumen. Aortography can also diagnose aortic regurgitation and, if necessary, the coronary arteries can be evaluated at the same time. The major disadvantage to aortography is that it can delay surgery with possibly deleterious effect and that it can have potentially disastrous complications.899 A

Computed tomography

B

Fig. 14.149  Type B aortic dissection. A, Coned view of frontal chest radiograph (left panel) shows enlarged descending aorta and displaced intimal calcification (arrows), in contrast to appearance on chest radiograph obtained 1 year earlier (A, right panel). B, Contrast-enhanced CT shows intramural hematoma in mid-aorta (left panel, arrow) and dissection flap (right panel, arrow) in the distal descending thoracic aorta. Note left pleural effusion (*).

Fig. 14.150  Frontal chest radiograph in asymptomatic woman with apparently displaced intimal calcification (arrow) due to the normal obliquity of the transverse aortic arch.

970

Multidetector CT is a highly sensitive and specific technique for diagnosis of aortic dissection.841,843,885 It is as accurate as, if not more accurate than, aortography for demonstrating the presence and extent of dissection.900–906 Neinaber et  al.,907 in a multicenter study with 110 patients, showed conventional CT to have a sensitivity of 94% and a specificity of 87%. Studies using multidetector CT report sensitivities approaching 100% and specificities greater than 95%.908,909 CT also allows rapid detection of complications such as mediastinal, pericardial, or pleural hemorrhage. Optimal CT technique for evaluation of acute aortic dissection, or other acute aortic syndromes, is rapidly evolving, varies from center to center, depends upon the type of CT machine available, and is the subject of a recent review.845 Although a detailed discussion of CT technique is beyond the scope of this discussion, the following caveats apply: • Brisk administration of contrast material is required, but method, timing, and dose of contrast administered depends upon the type of CT scanner used. • Most centers use relatively thin sections (2.5 or 1.25 mm collimation) and maximum table speed to image the aorta from the thoracic inlet to the upper abdomen. If dissection is identified in the descending aorta, the scan should continue into the abdomen to identify the distal extent of the dissection. These parameters will allow multiplanar reconstructions as needed (Fig. 14.153). • Many, if not most, centers also obtain noncontrast scans to facilitate diagnosis of intramural hematoma (see below). • Whether electrocardiographic (ECG)-gating should be routinely used is a subject of debate. While retrospective ECG-gating can add to the overall time of the examination and increases radiation dose, there are a number of positives, including reduction or elimination of pulsation artifact in the ascending aorta and important additional information regarding status of the coronary arteries. And gated CT can provide useful information regarding the integrity of the aortic valve and functional information regarding the left ventricle.900–906 Furthermore, because acute aortic syndromes can be clinically confused with acute coronary syndrome, or even pulmonary embolism, ECGgated multidetector CT may become the test of choice for patients with acute chest pain in the emergency department.906 The diagnostic features of aortic dissection on contrast-enhanced CT scans are similar to those seen at aortography: namely, the recognition of two lumens separated by an intimal flap (Fig. 14.153; see Box 14.29). The intimal flap is seen as a curvilinear lucency within the opacified aorta in some three-quarters of cases. Sometimes, particularly in the aortic arch, the intimal flap may assume a serpiginous course. Plaques of calcification are sometimes seen along the intimal flap (Fig. 14.153). It is sometimes possible to see the intimal flap on noncontrast scans,910 particularly when the flap is calcified (Fig. 14.147) or in patients who are anemic.911 The false

Diseases of the Thoracic Aorta

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Fig. 14.151  Type A intramural hematoma (dissection variant). A, Frontal chest radiograph obtained on admission shows enlarged cardiopericardial silhouette, a marked change from B, a radiograph obtained 1 year earlier. C, Contrast-enhanced CT confirms large pericardial effusion and intramural hematoma (arrow) in ascending aorta.

Fig. 14.152  Acute type B aortic dissection. Lateral projection from an aortogram shows an obvious intimal flap (arrow) separating the true from the false lumen.

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lumen may be partially filled with thrombus (Fig. 14.153). It usually fills and empties in a delayed fashion compared with the true lumen. Differential opacification can be a very useful sign in cases where the intimal flap is invisible or uncertain. Equal opacification of both lumina along with failure to see an intimal flap is one of the causes of false-negative interpretations using CT. It should be remembered that the false lumen may not enhance, either because it is totally filled by thrombus or because there is very slow flow. The affected portions of the aorta are often, though not always, enlarged. In some reports,912 aortic dilatation was always present, but in the series of Vasile et  al.,910 almost 60% of patients with dissection showed no aortic dilatation. The appearance of two lumens separated by an intimal flap is specific for aortic dissection, but care must be taken not to misdiagnose an extraaortic structure as a false lumen. The left brachiocephalic vein, the superior vena cava, the left superior intercostal vein, the left superior pulmonary vein, and the superior pericardial recesses can all mimic a false channel, as can adjacent pleural or pericardial thickening and adjacent atelectasis of the lung (Fig. 14.154). Other potential mimics of a false lumen are: apparent asymmetrical thickening of the wall of the aorta caused by motion artifact due to systolic aortic motion, or adjacent atelectasis (Fig. 14.155).913–915 and partial volume averaging of densities in the section above or below that may closely resemble a false lumen and give the impression of displaced intimal calcification.916 These artifacts can be overcome with the use of thinner collimation, changing the CT reconstruction algorithm (partial reconstruction), or use of ECGgating.917 Streak artifacts can mimic an intimal flap (Fig. 14.155).918

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Fig. 14.153  Acute type A aortic dissection. A, B, Contrastenhanced axial CT shows an intimal flap within the right brachiocephalic artery (arrow on A) and aortic arch. Note extension of the dissection flap into the celiac artery (arrow on B). C, Sagittal reformat image clearly shows the full extent of the dissection. Furthermore, note that a considerable portion of the false lumen (*) is thrombosed. T, true lumen.

Fig. 14.154  Atelectasis simulating aortic dissection. Contrastenhanced CT shows enhancing atelectatic lung (arrow) adjacent to the descending thoracic aorta, simulating the appearance of aortic dissection.

Diseases of the Thoracic Aorta

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Fig. 14.156  Acute type A aortic dissection. Contrast-enhanced CT shows entry site (yellow arrow, top left) in ascending aorta. Note distal extension of flap into the proximal superior mesenteric artery (SMA) (red arrow, top right), left renal infarct (blue arrow, bottom left) and distal SMA occlusion (white arrow, bottom right). Intimal flaps are gently curved structures of uniform thickness conforming to the configuration of the aorta. Streak artifacts are straight and vary in thickness. Also, their orientation may change markedly from one CT section to the next, and they often extend outside the aorta. In addition to confirming the diagnosis of aortic dissection, imaging is required to assess extent (particularly for differentiating type A from B dissection), branch vessel involvement, and site of entry or reentry tears, information required for treatment planning (Fig. 14.156). Distinguishing the true from false lumen is also of

Fig. 14.155  Various artifacts that may simulate aortic dissection on CT. A, Pulsation artifact in the ascending aorta (arrow) may simulate aortic dissection. Image obtained 1 mm cephalad (right panel) shows a normal aortic contour. B, Streak artifact from the superior vena cava simulates a dissection flap in the ascending aorta. C, Enhancement of the closely applied right atrial appendage (yellow arrow) may also simulate the appearance of a dissection flap in the ascending aorta. Streak artifact in the same patient (red arrow) simulates a dissection flap in the descending aorta. importance for treatment planning. In most instances, the false lumen can be confidently identified by its characteristic location within the aorta (see above). The cross-sectional surface area of the false lumen is frequently larger than that of the true lumen (Fig. 14.157).919 Thin strands of tissue, so-called cobwebs, can sometimes be seen crossing the false lumen. These are better identified by MRI or intravascular ultrasound than CT.920,921 The false lumen may also show a ‘beak’ sign as blood in the false channel undermines the intimal flap (Fig. 14.157).919 Finally, flow in the false lumen is often slower than in the true lumen, a finding again better demonstrated by MRI than CT. Differentiating a thrombosed aortic dissection from severe atherosclerotic disease of the aorta can be difficult. Classically, dissection displaces intimal calcification into the lumen of the aorta, whereas atherosclerotic disease does not. However, calcification may, on occasion, occur along the inner surface of the thrombus in an atherosclerotic aneurysm,816,922 simulating the appearance of a thrombosed dissection. The shape of the opacified lumen can be a useful differentiating feature. In atherosclerotic aneurysm, the lumen is almost always round (Fig. 14.158), whereas in aortic dissection the true lumen is frequently flattened because of compression by the false lumen (Fig. 14.159).816,923

Magnetic resonance imaging MRI can also be used to evaluate known or suspected aortic dissection.924,925 Advantages of MRI over CT include the ability to better recognize differential flow within the true and false lumen and the lack of ionizing radiation. The latter makes MRI the test of choice for imaging younger patients or those for whom administration of iodinated contrast material is contraindicated. The sensitivity and specificity of MRI for diagnosis of aortic dissection is at least as good as that of CT.885,909,926,927 MRI has been reported to have sensitivities as high as 95–100% for diagnosing aortic dissection.928 Nienaber et  al.929 prospectively studied 53 patients with possible aortic dissection with MRI and reported 100% sensitivity and

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Chapter 14 • Mediastinal and Aortic Disease

Fig. 14.159  Acute type A aortic dissection. Contrast-enhanced CT shows crescentic soft tissue opacity surrounding the ascending aorta (arrows), dilatation of the descending thoracic aorta, and marked compression the true lumen (*). Note that the opacified true lumen in the descending aorta has a flattened contour. These findings suggest acute type A aortic dissection with near complete thrombosis of (or very slow flow in) the false lumen.

Fig. 14.157  Acute type A aortic dissection. Contrast-enhanced CT shows intimal flap in ascending aorta separating true, T, from false, F, lumen. Note that the true lumen is smaller and that the false lumen shows a ‘beak’ sign (yellow arrows) at leading edge of dissection. Note also that mediastinal hematoma dissects around and narrows right pulmonary artery (red arrows).

Fig. 14.158  Atherosclerotic aneurysm. Contrast-enhanced CT show a fusiform saccular aneurysm of the descending thoracic aorta lined by thrombus. Note that the opacified aortic lumen remains round in contour. specificity for the diagnosis. These optimistic numbers dropped slightly to a sensitivity of 98% and a specificity of 97% in a later report.907 As with CT, MRI techniques for evaluating the thoracic aorta continue to evolve, depend upon the type of MR machine available, are the subject of a recent review, and details are beyond the scope of this discussion.924,925 In general, ECG-gated conventional or fast spin-echo images show fast-flowing blood as a signal void (‘blackblood’ imaging). When the blood flow is above a critical rate an

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intimal flap and the aortic wall are readily demonstrated as separately definable curvilinear structures. For the most part, blood in the true lumen of the aorta flows at a rate above this threshold.818 Slow-flowing blood in the false lumen produces a variety of signal patterns which can be difficult to distinguish from thrombus (Figs 14.160 and 14.161), but gradient-echo and magnetic resonance angiographic sequences (‘white blood’ images) can usually help resolve this problem. Gradient-echo techniques also allow faster imaging, including breath-hold sequences, and three-dimensional gradient-echo sequences with intravenous gadolinium enhancement permit high-quality images without flow-related loss of signal.796–798,924,925 The basic signs of aortic dissection at MRI (Figs 14.160 and 14.161) are the same as those described for CT: an intimal flap separating true and false lumina. Eccentric or concentric aortic wall thickening may, on occasion, be the only MR finding.930 In approximately onequarter of cases, cords or bands of soft tissue intensity (cobwebs) may be seen traversing the false lumen, a useful marker that the lumen in question is indeed the false lumen.920 Oblique sagittal and coronal planes may be the optimal imaging planes to demonstrate the entry site,931 extent of dissection, and the relationship of the dissection to the major aortic branches, particularly those arising from the aortic arch.887,898 MRI can also be used to evaluate the integrity of the aortic valve in patients with type A dissections and to quantify associated aortic regurgitation. Disadvantages of MR include lack of access in an emergency setting, the time required to image the patient, and difficulty with monitoring very sick patients in the magnet.887 Many of these difficulties are not insurmountable, though.794,926 As with CT there are a number of diagnostic pitfalls using MRI.932–934 Adjacent structures, such as the left brachiocephalic vein (Fig. 14.162), the left superior intercostal vein, left superior pulmonary vein, hemiazygos or azygos vein, may mimic a false lumen, as may the origins of the arteries arising from the aortic arch and the superior pericardial recesses. Apparent thickening of the aortic wall due to motion artifact, atherosclerotic plaques, aortitis (Fig. 14.163), or fibrosing mediastinitis may also be confused with a thrombosed false lumen.

Echocardiography Echocardiography, particularly transesophageal echocardiography (TEE), has proved useful for diagnosis of aortic dissection. Standard transthoracic echocardiography935,936 can show ascending aortic dissection, the aortic valve, and hemopericardium. Color-flow Doppler ultrasonography can diagnose and grade aortic regurgitation. For the diagnosis of aortic dissection, regardless of type, transthoracic

Diseases of the Thoracic Aorta

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Fig. 14.160  Type B aortic dissection. A, Axial T1-weighted MR images show typical findings of aortic dissection on MR. Note that it is difficult to distinguish thrombus from slowly flowing blood in the false lumen (*) on this pulse sequence. B, Images obtained after dynamic administration of gadolinium-based contrast material clearly show flow in the false lumen (*) on both the sagittal image (left panel) and MIP reconstruction (right panel).

A

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Fig. 14.161  Type A aortic dissection. A, B, Paired axial T1-weighted and bright blood GRE images at two different levels clearly show a dissection flap in both the ascending and descending thoracic aorta. Note differential flow within the true and false lumen in the aortic arch and possible thrombosis of the false lumen at the aortic root (A). C, Sagittal MR images obtained following dynamic administration of gadolinium-based contrast material show flow in the false lumen with no evidence of thrombus.

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Fig. 14.162  Pitfalls in the diagnosis of aortic dissection on spin-echo MR imaging. A, Dissection mimicked by the anterior portion of superior pericardial recess. Pericardial fluid is typically of low signal intensity because it is moving due to cardiac pulsation. B, Aortic dissection mimicked by the left brachiocephalic vein passing anterior to the aortic arch.

cardiac ultrasonography has been shown to be 60% sensitive and 83% specific, the sensitivity for dissections of the descending aorta being particularly poor.794 Transesophageal echocardiography, which allows examination of the aorta at multiple levels, can provide an extensive view of the ascending and descending aorta, and can also show the aortic arch and proximal coronary arteries. Reports suggest sensitivities above 95%, which can be increased to close to 100% for combined trans­ thoracic and transesophageal ultrasonography.895,897,929,937–939 One problem with ultrasonography is the inability to see through the air in the trachea; thus, if the dissection is confined to the ascending aorta, it may not be visible from the transducer in the esophagus.794,927 The reported specificities for diagnosis are more variable with one large series showing specificities well above 95%940 but another equally large study794 showing a specificity of 80%, mainly because of false-positive findings in the ascending aorta. High frequency ultrasonography probes mounted on the tips of intraarterial catheters have been tested and shown to be accurate in diagnosing aortic dissection.941 The basic signs of dissection at ultrasonography are the same as those described for CT/MRI and aortography, namely a double lumen separated by an intimal flap. If the false lumen is thrombosed, central displacement of intimal calcification or separation of intimal layers are looked for. The entry tear can be identified at ultrasonography as interruption in the continuity of the intimal flap with associated fluttering of the edges. A major advantage of transthoracic/transesophageal ultrasonography is that it can be performed at the patient’s bedside and in operating rooms. Fig. 14.163  Aortic dissection mimicked by aortitis. Axial T1-weighted MR images show diffuse aortic wall thickening simulating the appearance of a thrombosed aortic dissection. However, note that the aortic lumen remains round in shape.

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Intramural hematoma The principal CT finding of intramural hematoma859,861,862,942,943 is a crescent-shaped rim of high attenuation in the wall of the aorta (Fig. 14.164; see Box 14.29). The diameter of the aorta may also be enlarged, but the lumen is not usually compressed. The hyperattenuating rim is best appreciated on noncontrast CT; it can be misdiagnosed as crescentic thrombus on contrast-enhanced CT scans. The attenuation of the hematoma typically declines with time. Unless complicated by classic dissection, the hematoma should not opacify on contrast-enhanced CT scans. It can be difficult to dif-

Diseases of the Thoracic Aorta

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Fig. 14.164  Intramural aortic hematoma. A, Noncontrast CT shows crescentic high attenuation in the wall of the aorta, extending from ascending to descending aorta. B, Contrast-enhanced CT shows no dissection flap. Note ulcer-like projection (arrow) in the descending thoracic aorta. C, Follow-up contrast-enhanced CT after placement of an aortic stent graft shows near complete resolution of the intramural hematoma.

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Chapter 14 • Mediastinal and Aortic Disease ferentiate intramural hematoma from atherosclerotic disease. Helpful findings include: atherosclerotic wall thickening is rare in the ascending aorta; atherosclerosis causes an irregular inner margin whereas the aortic wall is smooth with intramural hematoma; and atherosclerosis is patchy, whereas intramural hematoma extends smoothly up and down the affected part of the aorta (Fig. 14.164). Differentiating intramural hematoma from a thrombosed aortic dissection can also be problematic because, in both cases, neither a double contrast-enhanced channel nor an intimal flap is seen on CT. In this circumstance, the spiral shape of the thrombosed false channel and displaced intimal calcification suggests the diagnosis of dissection with a thrombosed lumen. Conversely, crescentic high attenuation in the wall of the aorta on noncontrast CT suggests intramural hematoma (Fig. 14.164). The features of intramural hematoma on MRI859–862,942,944 are similar to those seen on CT: a crescent-shaped rim with signal characteristics of hematoma (Fig. 14.165). Intramural hematoma is readily diagnosed by transesophageal echocardiography as circular or crescentic thickening of the aortic wall showing a partial or complete ‘thrombus-like echo pattern’ with displacement of intimal calcification and some differential movement between the layers of the aortic wall.861,945 As noted earlier, ulcerlike projections are commonly seen within aortic intramural hematoma, either on initial imaging or at followup (Figs 14.164 and 14.166).869,884 These ulcers are more common in the descending aorta and their presence is associated with a worse

outcome, as they can lead to development of a saccular aneurysm, pseudoaneurysm, or frank aortic rupture.869,884 Other poor prognostic factors include aortic diameter >50 mm and hematoma thickness >11 mm.867

Penetrating atherosclerotic ulcer Penetrating ulcers are diagnosed on imaging studies (Figs 14.167 and 14.168) such as aortography, CT, or MRI by the presence of a focal contrast-filled outpouching through the aortic wall with limited intramural hematoma842 (see Box 14.29). Unless the ulcer is complicated by classic dissection, an intimal flap is not seen.872,874,946–949 Ulcers typically occur in the setting of extensive atheromatous plaque, which may be calcified. Displacement of intimal calcification, similar to that seen with classic aortic dissection, is a common finding on CT.

Optimal imaging of a patient with a suspected acute (nontraumatic) aortic syndrome The four primary imaging methods, CT, MRI, TEE, and aortography, each have advantages and disadvantages in the evaluation of suspected acute nontraumatic aortic syndromes.887,909 The ideal examination should confirm or exclude the diagnosis, correctly evaluate the extent of the lesion, and identify all possible complica-

Fig. 14.166  Intramural aortic hematoma. Noncontrast CT (left panel) shows crescentic high-attenuation focus in aortic wall. Contrast-enhanced CT (right panel) shows a focal ulcerlike projection (arrow) in the hematoma.

Fig. 14.165  Intramural aortic hematoma. Cardiac-gated T1-weighted spin-echo MR shows fairly uniform high signal in the aortic wall consistent with maturing hematoma (arrows). (With permission from Oliver TB, Murchison JT, Reid JH. Spiral CT in acute non-cardiac chest pain. Clin Radiol 1999;54:38–45. [Courtesy of TB Oliver, MD, Edinburgh, UK]).

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Fig. 14.167  Penetrating atherosclerotic ulcer. Contrast-enhanced CT (left panel) shows a large penetrating ulcer (arrows) in the descending thoracic aorta. Note the large associated hematoma. Repeat CT after stent-grafting (right panel) shows resolution of the ulcer.

Diseases of the Thoracic Aorta

Fig. 14.168  Penetrating atherosclerotic ulcer. Axial T1-weighted MR images show a focal ulceration in the descending thoracic aorta (arrow), focal dilatation of the descending thoracic aorta, and high signal intensity in the aortic wall consistent with intramural hematoma.

tions, including aortic regurgitation and coronary artery involvement (see Box 14.27), all with 100% accuracy. Furthermore, the ideal test should be performed in a rapid and timely fashion and be applicable to even the most sick and critically ill patients. Unfortunately, no single such test exists.888 Instead, the choice of imaging technique used in a given patient depends upon institutional experience, availability of certain services such as TEE or emergency MRI, and the status of the patient.887,888 Furthermore, the minimum diagnostic information that a treating physician requires varies.888 Some surgeons require detailed knowledge about the status of the aortic valve, coronary arteries, and branch vessels before proceeding to surgery, whereas others do not. In many instances, therefore, multiple studies (CT and TEE, for example) may be required. Aortography was for many years regarded as the best diagnostic test for patients with suspected acute aortic dissection, but aortography is time-consuming, invasive and, very importantly, has lower sensitivity than CT or MRI. Transesophageal ultrasonography has a high sensitivity, but its specificity only becomes as good as CT or MRI when strict criteria are applied to the diagnosis of dissection – criteria which lower its overall sensitivity. MRI is not available on an emergency basis in all hospitals, and the need for patient transport together with the length of the procedure may make it less desirable for patients who are unstable or those requiring particularly close monitoring. TEE is readily available and fast; it can be performed at the bedside, making it ideal for use in patients who are unstable. It is, however, very operator dependent. Many authors have opined that TEE, when available, should be considered first in cases of suspected dissection, because of its accuracy, safety, speed, and convenience. As MR-compatible monitoring and life-support systems become available, the use of MRI as the primary imaging technique for acute aortic dissection is likely to increase because of its excellent accuracy and high-quality images. However, in many, and perhaps most, hospitals, CT scanning, particularly multidetector CT, is the first choice for the rapid screening of patients with suspected acute aortic dissection. Both echocardiography and MRI are excellent techniques for following up patients with known or treated acute aortic syndromes950,951 because they are noninvasive and do not involve ionizing radiation.

Congenital aortic aneurysms Congenital aneurysms of the aorta are rare.952 Almost all of those encountered in clinical practice are sinus of Valsalva aneurysms.952 Normally, the media of the wall of the proximal aorta is firmly

attached to the fibrous annulus of the aortic valve. In patients with congenital sinus of Valsalva aneurysm, the media avulses from its attachment to the annulus and an aneurysm results.953,954 These aneurysms most commonly arise from the posterior noncoronary or right aortic sinus. An aneurysm of the posterior aortic sinus bulges into the right atrium, and if it ruptures the result is an aortic to right atrial shunt. An aneurysm of the right aortic sinus bulges into the right ventricle and rupture, therefore, causes an aortic to right ventricular shunt. The aortic valve lies deep within the mediastinal shadow and congenital sinus of Valsalva aneurysms must, therefore, reach substantial size to be recognizable on chest radiographs. Occasionally, they do reach such a size. Calcification may be visible in the wall of the aneurysm. The signs of left-to-right shunt may be visible if rupture has occurred. CT and MRI can show the aneurysm to advantage.955–957 Very occasionally, congenital aneurysms are associated with coarctation of the aorta (Fig. 14.169) or other aortic anomalies, such as right-sided aortic arch.958 Whether the aneurysms in patients with coarctation are truly congenital or acquired secondary to prolonged hypertension is debated.959

Aortic aneurysms resulting from aortitis Aortic aneurysm as a result of aortitis is rare now that tertiary syphilis is so uncommon.452,960 Most cases are due to giant cell arteritis,961,962 Behçet disease,963 or Takayasu arteritis.964,965 Takayasu arteritis is a large vessel vasculitis that affects the aorta, the branch vessels, and the pulmonary arteries. It occurs most commonly in South East Asia, but has a worldwide distribution. Though more often a stenosing disease, Takayasu arteritis may, on occasion, cause saccular or fusiform aortic aneurysms.966–970 Aneurysms in this condition may be single or multiple and may be seen anywhere in the aorta. Involvement of the ascending aorta can lead to annulo­ aortic ectasia and aortic regurgitation971 and aortic dissection can be a complication.972 On CT or MR angiography, aortic wall thickening, which may be calcified, is seen in cases of aortitis (Fig. 14.163).973 Wall thickening due to aortitis can, on occasion, be difficult to differentiate from that due to intramural hematoma. In general, however, wall thickening is eccentric in cases of hematoma and concentric in cases of aortitis. High attenuation within the wall on noncontrast scans favors hematoma as well. FDG-PET imaging has been used both to diagnose aortitis and to follow patients after treatment.974–977 PET may not be helpful, however, for differentiating aortitis from intramural hematoma, as the latter can also show increased metabolic activity.978,979

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Fig. 14.169  Slowly enlarging aortic aneurysm in a young woman with aortic coarctation. A, Frontal chest radiograph shows a saccular aneurysm of the proximal descending thoracic aorta. B, Early phase of the aortogram shows the coarctation (arrows). C, Later phase of the aortogram shows opacification of the aneurysm (arrows).

Aortic involvement in patients with giant cell arteritis may be more common than generally believed. In a prospective case– control trial that included 22 patients with biopsy-proven giant-cell arteritis, 23% had thickening of the wall of the ascending aorta (mean 3.3 mm).962,980

Aortic anomalies that may simulate a mediastinal mass At least three congenital aortic variants can simulate a mediastinal mass981 on chest radiographs or noncontrast CT: right aortic arch, double aortic arch, and pseudocoarctation of the aorta.

Right aortic arch (Box 14.30) A right aortic arch is commonly mistaken for a mediastinal mass on chest radiographs and patients may be referred for CT. Most asymptomatic adults with a right-sided aortic arch (about 1 in 1000 patients) have an aberrant left subclavian artery. Other anatomic configurations such as mirror image branching of the great vessels are less common and are associated with congenital heart disease. This discussion will be confined to right aortic arch in patients without cardiac malformation. In these patients, the right arch passes to the right of the trachea and usually descends in the right posterior mediastinum; only rarely is the descending aorta on the left. In the usual branching pattern, the left carotid artery arises first, followed by the right carotid and right subclavian arteries. The left subclavian artery, which arises as the fourth and most distal branch of the aortic arch, is known as an ‘aberrant subclavian artery’. The aberrant left subclavian artery passes behind the esophagus to reach the root of the neck on the left side. The left subclavian artery may take origin from a diverticulum (diverticulum of Kommerell) in the proximal descending aorta, which embryologically represents a remnant of the left arch. On frontal chest radiographs, the right arch appears as a round mass in the right paratracheal region that indents the right lateral margin of the trachea, and may deviate the trachea to the left (Fig. 14.170). There may, however, be a small round density in the expected location of the left arch, caused either by the diverticulum

980

Box 14.30  Right aortic arch

Frequency • 0.1% of population

Symptoms • Usually asymptomatic • Usually only if associated with a left patent ductus arteriosus or a tight ductus ligament (stridor, dysphagia)

Types • Aberrant left subclavian artery – Most common – Usually isolated finding – Minimal (5–10%) association with congenital heart disease • Mirror image branching – Less common – Strong association with cyanotic congenital heart disease • Other types – Isolated left subclavian artery

Imaging • Right paratracheal mass, indents tracheal air column • Absent left arch • Retrotracheal (retroesophageal) mass – Present = aberrant left subclavian artery – Absent = mirror image branching pattern – Best seen on lateral radiograph • Diverticulum of Kommerell – Focal dilatation at the origin of the aberrant subclavian artery – May mimic a left aortic arch – typically retrotracheal; does not indent tracheal air column

Diseases of the Thoracic Aorta

A

B

Fig. 14.170  Right aortic arch. A, Frontal chest radiograph shows a round opacity that indents the right side of the intrathoracic trachea (arrow). Note absence of the normal left-sided aortic impression. B, Lateral radiograph shows a retrotracheal opacity with slight anterior bowing of the trachea (arrows), consistent with an aberrant left subclavian artery.

or by leftward displacement of the aorta. An important clue to the correct diagnosis is the absence of the normal left-sided tracheal indentation that is seen when the arch is normally situated. The descending aorta is to the right of the midline in almost all cases. On lateral chest radiographs, a density posterior to the esophagus that is variable in size will be seen (Fig. 14.170).982 This density is sometimes due to the aortic diverticulum and aberrant left subclavian artery and sometimes to medial displacement of the proximal descending aorta. The posterior impression on the esophagus at barium swallow examination and on the trachea on chest radiography and CT is often striking. For the most part, the findings of a right arch on chest radiographs are distinctive enough to suggest the correct diagnosis. In difficult cases, or in patients with symptoms of a vascular ring, CT or MRI may be performed (Fig. 14.171). CT or MRI easily identifies the aortic arch to the right of the trachea. The aberrant right subclavian artery arises as the last and most posterior vessel off the rightsided aortic arch, crosses the mediastinum behind the trachea and esophagus and continues into the neck and axilla along the left side of the trachea. Frequently, a diverticulum (diverticulum of Kommerell) is seen at the origin of the aberrant left subclavian artery from the aorta.

Double aortic arch Most patients with double aortic arch present early in life with tracheal obstruction and swallowing difficulties. Occasionally, the condition remains undetected until later in childhood or adult life. The two aortic arches pass to either side of the trachea and join posteriorly, at which point they often displace the trachea and esophagus forward, thus potentially causing confusion with a middle mediastinal mass. The descending aorta is usually in the midline. On chest radiographs, the features of double aortic arch are similar to those of a right arch with aberrant subclavian artery.

The diagnostic features of double aortic arch on cross-sectional imaging studies (Fig. 14.172)982 are: • The right arch is almost always larger and higher than the left arch. This observation is particularly important at barium swallow, where the arches indent the esophagus from either side. Furthermore, the tracheal indentation from the right arch is almost always more pronounced than that of the left arch. • The branching pattern of the vessels to the head and neck is distinctive. Each arch gives rise to two vessels – a carotid and a subclavian artery – each artery of the pair lying one in front of the other. • The arches fuse posterior to the esophagus and trachea and may create a masslike density in the middle mediastinum.

Pseudocoarctation of the aorta Pseudocoarctation of the aorta is a congenital anomaly that many authorities believe to be in the spectrum of true coarctation, but without a gradient producing narrowing of the aorta. The aorta is kinked at the level of the ligamentum arteriosum, the same position as the usual site of coarctation (Fig. 14.173). The ascending aorta is typically more vertical in orientation, the arch higher, and the curve of the arch tighter than normal. This results in a very high aortic arch that may simulate a mass on chest radiographs. Pseudocoarctation, like true coarctation, is associated with an increased tendency to aneurysm formation and aortic dissection. Thus, the aorta above or below the kink may be significantly enlarged, leading to the possibility of even greater confusion with a mass lesion.983,984 CT or MRI can be diagnostic.838,985–987 Absence of significant collateral vessels suggests pseudocoarctation as opposed to true coarctation. However, pressure gradient measurements across the area of kinking or narrowing must be obtained to exclude a hemodynamically significant coarctation.

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B

A

C

E

D

F

Fig. 14.171  CT and MRI of a right aortic arch. A–C, Contrast-enhanced CT clearly shows the right aortic arch R, the retrotracheal aortic diverticulum D, the aberrant left subclavian artery S, right-sided ascending aorta AA, and the midline descending thoracic aorta DA. D–F, Coronal T1-weighted MR images also clearly show the right-sided ascending aorta AA, the high right aortic arch R, the retrotracheal and left-sided aortic diverticulum D, the left subclavian artery (*), and the midline descending thoracic aorta DA.

982

Diseases of the Thoracic Aorta Fig. 14.172  Double aortic arch. A, Frontal chest radiograph shows a high right-sided aorta. B, Coronal reformat images from a contrast-enhanced CT shows, from anterior to posterior, the ascending aorta A, the larger right and smaller left aortic arches R, L, and the midline descending thoracic aorta D. C, These relationships are shown to better advantage by three-dimensional shaded surface display reconstructions.

A

B

C

983

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A

B

Fig. 14.173  Pseudocoarctation of the aorta. A, Frontal chest radiograph shows findings suggestive of either an enlarged pulmonary artery or a mediastinal mass (arrow). B, Aortogram shows typical features of pseudocoarctation including a high aortic arch, proximal kinking of the aorta, and absence of collateral vessels.

REFERENCES 1. Williams HJ, Alton HM. Imaging of paediatric mediastinal abnormalities. Paediatr Respir Rev 2003;4:55–66. 2. Chhieng DC, Jhala D, Jhala N, et al. Endoscopic ultrasound-guided fine-needle aspiration biopsy: a study of 103 cases. Cancer 2002;96:232–239. 3. McAdams HP, Erasmus JJ, Tarver RD, et al. The mediastinum. In: Haaga JR, Lanzieri CF, Gilkeson RC (eds). CT and MR imaging of the whole body, 4th ed. St. Louis, MO: Mosby, 2003:937–996. 4. Brink JA, Heiken JP, Forman HP, et al. Hepatic spiral CT: reduction of dose of intravenous contrast material. Radiology 1995;197:83–88. 5. Boiselle PM, Dippolito G, Copeland J, et al. Multiplanar and 3D imaging of the central airways: comparison of image quality and radiation dose of single-detector row CT and multi-detector row CT at differing tube currents in dogs. Radiology 2003;228: 107–111. 6. Brady F, Luthra SK, Brown GD, et al. Radiolabelled tracers and anticancer drugs for assessment of therapeutic efficacy using PET. Curr Pharm Des 2001;7: 1863–1892. 7. Jerusalem G, Hustinx R, Beguin Y, et al. PET scan imaging in oncology. Eur J Cancer 2003;39:1525–1534. 8. Patz EF Jr, Lowe VJ, Hoffman JM, et al. Focal pulmonary abnormalities: evaluation with F-18 fluorodeoxyglucose PET scanning. Radiology 1993;188:487–490.

984

9. Verboom P, Van Tinteren H, Hoekstra OS, et al. Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: the PLUS study. Eur J Nucl Med Mol Imaging 2003;30:1444–1449. 10. Friedberg JW, Chengazi V. PET scans in the staging of lymphoma: current status. Oncologist 2003;8:438–447. 11. Huddart RA, O’Doherty MJ, Padhani A, et al. 18fluorodeoxyglucose positron emission tomography in the prediction of relapse in patients with high-risk, clinical stage I nonseminomatous germ cell tumors: preliminary report of MRC Trial TE22 – the NCRI Testis Tumour Clinical Study Group. J Clin Oncol 2007;25:3090–3095. 12. Endo M, Nakagawa K, Ohde Y, et al. Utility of 18DG-PET for differentiating the grade of malignancy in thymic epithelial tumors. Lung Cancer 2008;61:350–355. 13. Sung YM, Lee KS, Kim BT, et al. 18F-FDG PET/CT of thymic epithelial tumors: usefulness for distinguishing and staging tumor subgroups. J Nucl Med 2006;47: 1628–1634. 14. Wychulis AR, Payne WS, Clagett OT, et al. Surgical treatment of mediastinal tumors: a 40 year experience. J Thorac Cardiovasc Surg 1971;62:379–392. 15. Azarow KS, Pearl RH, Zurcher R, et al. Primary mediastinal masses. A comparison of adult and pediatric populations. J Thorac Cardiovasc Surg 1993;106:67–72. 16. Temes R, Allen N, Chavez T, et al. Primary mediastinal malignancies in children:

17.

18. 19.

20. 21. 22.

23.

24.

25.

report of 22 patients and comparison to 197 adults. Oncologist 2000;5:179–184. Takeda S, Miyoshi S, Akashi A, et al. Clinical spectrum of primary mediastinal tumors: a comparison of adult and pediatric populations at a single Japanese institution. J Surg Oncol 2003;83:24–30. Benjamin SP, McCormack LJ, Effler DB, et al. Primary tumors of the mediastinum. Chest 1972;62:297–303. Cohen AJ, Thompson L, Edwards FH, et al. Primary cysts and tumors of the mediastinum. Ann Thorac Surg 1991;51: 378–384, discussion 385–376. Whooley BP, Urschel JD, Antkowiak JG, et al. Primary tumors of the mediastinum. J Surg Oncol 1999;70:95–99. Heitzman ER. The mediastinum: radiologic correlations with anatomy and pathology. Berlin: Springer-Verlag, 1988. Rendina EA, Venuta F, Ceroni L, et al. Computed tomographic staging of anterior mediastinal neoplasms. Thorax 1988;43: 441–445. Whitten CR, Khan S, Munneke GJ, et al. A diagnostic approach to mediastinal abnormalities. RadioGraphics 2007;27: 657–671. Ahn JM, Lee KS, Goo JM, et al. Predicting the histology of anterior mediastinal masses: comparison of chest radiography and CT. J Thorac Imaging 1996;11:265–271. Woodring JH, Johnson PJ. Computed tomography distinction of central thoracic masses. J Thorac Imaging 1991;6:32–39.

References 26. Merten DF. Diagnostic imaging of mediastinal masses in children. AJR Am J Roentgenol 1992;158:825–832. 27. Glazer HS, Molina PL, Siegel MJ, et al. High-attenuation mediastinal masses on unenhanced CT. AJR Am J Roentgenol 1991;156:45–50. 28. Glazer HS, Siegel MJ, Sagel SS. Lowattenuation mediastinal masses on CT. AJR Am J Roentgenol 1989;152:1173–1177. 29. Glazer HS, Wick MR, Anderson DJ, et al. CT of fatty thoracic masses. AJR Am J Roentgenol 1992;159:1181–1187. 30. Spizarny DL, Rebner M, Gross BH. CT evaluation of enhancing mediastinal masses. J Comput Assist Tomogr 1987;11: 990–993. 31. Barakos JA, Brown JJ, Brescia RJ, et al. High signal intensity lesions of the chest in MR imaging. J Comput Assist Tomogr 1989;13:797–802. 32. Suster S, Rosai J. Multilocular thymic cyst: an acquired reactive process. Study of 18 cases. Am J Surg Pathol 1991;15:388–398. 33. Tecce PM, Fishman EK, Kuhlman JE. CT evaluation of the anterior mediastinum: spectrum of disease. RadioGraphics 1994; 14:973–990. 34. Wachsberg RH, Yaghmai V, Javors BR, et al. Cardiophrenic varices in portal hypertension: evaluation with CT. Radiology 1995;195:553–556. 35. Pineda V, Andreu J, Caceres J, et al. Lesions of the cardiophrenic space: findings at cross-sectional imaging. RadioGraphics 2007;27:19–32. 36. McAdams HP, Kirejczyk WM, Rosado-deChristenson ML, et al. Bronchogenic cyst: imaging features with clinical and histopathologic correlation. Radiology 2000;217:441–446. 37. Takeda S, Miyoshi S, Minami M, et al. Clinical spectrum of mediastinal cysts. Chest 2003;124:125–132. 38. Sasaka K, Kurihara Y, Nakajima Y, et al. Spontaneous rupture: a complication of benign mature teratomas of the mediastinum. AJR Am J Roentgenol 1998; 170:323–328. 39. Reed JC, Sobonya RE. Morphologic analysis of foregut cysts in the thorax. Am J Roentgenol Radium Ther Nucl Med 1974; 120:851–860. 40. Snyder ME, Luck SR, Hernandez R, et al. Diagnostic dilemmas of mediastinal cysts. J Pediatr Surg 1985;20:810–815. 41. Sirivella S, Ford WB, Zikria EA, et al. Foregut cysts of the mediastinum. Results in 20 consecutive surgically treated cases. J Thorac Cardiovasc Surg 1985;90:776–782. 42. Salo JA, Ala-Kulju KV. Congenital esophageal cysts in adults. Ann Thorac Surg 1987;44:135–138. 43. Jang KM, Lee KS, Lee SJ, et al. The spectrum of benign esophageal lesions: imaging findings. Korean J Radiol 2002;3: 199–210. 44. Jeung MY, Gasser B, Gangi A, et al. Imaging of cystic masses of the mediastinum. RadioGraphics 2002;22:S79– S93. 45. Kuhlman JE, Fishman EK, Wang KP, et al. Esophageal duplication cyst: CT and transesophageal needle aspiration. AJR Am J Roentgenol 1985;145:531–532. 46. Weiss LM, Fagelman D, Warhit JM. CT demonstration of an esophageal

47. 48. 49.

50. 51. 52.

53.

54.

55. 56.

57. 58. 59.

60. 61. 62. 63.

64.

65. 66.

67. 68.

duplication cyst. J Comput Assist Tomogr 1983;7:716–718. Whitaker JA, Deffenbaugh LD, Cooke AR. Esophageal duplication cyst. Case report. Am J Gastroenterol 1980;73:329–332. LeBlanc J, Guttentag AR, Shepard JA, et al. Imaging of mediastinal foregut cysts. Can Assoc Radiol J 1994;45:381–386. Will U, Meyer F, Bosseckert H. Successful endoscopic treatment of an esophageal duplication cyst. Scand J Gastroenterol 2005;40:995–999. Pader E, Kirschner PA. Pericardial diverticulum. Dis Chest 1969;55:344–346. Kittredge RD, Finby N. Pericardial cysts and diverticula. Am J Roentgenol Radium Ther Nucl Med 1967;99:668–673. Feigin DS, Fenoglio JJ, McAllister HA, et al. Pericardial cysts. A radiologic-pathologic correlation and review. Radiology 1977; 125:15–20. Wychulis AR, Connolly DC, McGoon DC. Pericardial cysts, tumors, and fat necrosis. J Thorac Cardiovasc Surg 1971;62: 294–300. Lesniak-Sobelga AM, Olszowska M, Tracz W, et al. Giant pericardial cyst compressing the right ventricle. Ann Thorac Surg 2008; 85:1811. Brunner DR, Whitley NO. A pericardial cyst with high CT numbers. AJR Am J Roentgenol 1984;142:279–280. Demos TC, Budorick NE, Posniak HV. Benign mediastinal cysts: pointed appearance on CT. J Comput Assist Tomogr 1989;13:132–133. Pugatch RD, Braver JH, Robbins AH, et al. CT diagnosis of pericardial cysts. AJR Am J Roentgenol 1978;131:515–516. Klatte EC, Yune HY. Diagnosis and treatment of pericardial cysts. Radiology 1972;104:541–544. Singhal BS, Parekh HN, Ursekar M, et al. Intramedullary neurenteric cyst in mid thoracic spine in an adult: a case report. Neurol India 2001;49:302–304. Boyd DP, Midell AI. Mediastinal cysts and tumors. An analysis of 96 cases. Surg Clin North Am 1968;48:493–505. Madewell JE, Sobonya RE, Reed JC. Clinical conference: RPC from the AFIP. Radiology 1973;109:707–712. Wilson ES Jr. Neurenteric cyst of the mediastinum. Am J Roentgenol Radium Ther Nucl Med 1969;107:641–646. Zeilender S, Turner MA, Glauser FL. Mediastinal pseudocyst associated with chronic pleural effusions. Chest 1990;97: 1014–1016. Gupta R, Munoz JC, Garg P, et al. Mediastinal pancreatic pseudocyst: a case report and review of the literature. Med Gen Med 2007;9:8. Kirchner SG, Heller RM, Smith CW. Pancreatic pseudocyst of the mediastinum. Radiology 1977;123:37–42. Herrmann F, Reichenberger F, Leupold U, et al. Recurrent pleural effusion and a mediastinal mass. Respiration 2000;67:471– 472. Owens GR, Arger PH, Mulhern CB Jr, et al. CT evaluation of mediastinal pseudocyst. J Comput Assist Tomogr 1980;4:256–259. Ito H, Matsubara N, Sakai T, et al. Two cases of thoracopancreatic fistula in alcoholic pancreatitis: clinical and CT findings. Radiat Med 2002;20:207–211.

69. Geier A, Lammert F, Gartung C, et al. Magnetic resonance imaging and magnetic resonance cholangiopancreaticography for diagnosis and pre-interventional evaluation of a fluid thoracic mass. Eur J Gastroenterol Hepatol 2003;15:429–431. 70. Tan MH, Kirk G, Archibold P, et al. Cardiac compromise due to a pancreatic mediastinal pseudocyst. Eur J Gastroenterol Hepatol 2002;14:1279–1282. 71. Tanaka A, Takeda R, Utsunomiya H, et al. Severe complications of mediastinal pancreatic pseudocyst: report of esophagobronchial fistula and hemothorax. J Hepatobiliary Pancreat Surg 2000;7:86–91. 72. Saftoiu A, Ciurea T, Dumitrescu D, et al. Endoscopic ultrasound-guided transesophageal drainage of a mediastinal pancreatic pseudocyst. Endoscopy 2006;38:538–539. 73. Komtong S, Chanatrirattanapan R, Kongkam P, et al. Mediastinal pseudocyst with pericardial effusion and dysphagia treated by endoscopic drainage. JOP 2006; 7:405–410. 74. Strollo DC, Rosado-de-Christenson ML, Jett JR. Primary mediastinal tumors: part II. Tumors of the middle and posterior mediastinum. Chest 1997;112:1344–1357. 75. Miles J, Pennybacker J, Sheldon P. Intrathoracic meningocele. Its development and association with neurofibromatosis. J Neurol Neurosurg Psychiatry 1969;32: 99–110. 76. Chen SS, Shao KN, Feng RJ, et al. Multiple bilateral thoracic meningoceles without neurofibromatosis: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1998;61:736–740. 77. Haddad R. Multiple asymptomatic lateral thoracic meningocele. Eur J Cardiothorac Surg 2008;33:113. 78. Edeiken J, Lee KF, Libshitz H. Intrathoracic meningocele. Am J Roentgenol Radium Ther Nucl Med 1969;106:381–384. 79. Nakasu Y, Minouchi K, Hatsuda N, et al. Thoracic meningocele in neurofibromatosis: CT and MR findings. J Comput Assist Tomogr 1991;15:1062–1064. 80. Weinreb JC, Arger PH, Grossman R, et al. CT metrizamide myelography in multiple bilateral intrathoracic meningoceles. J Comput Assist Tomogr 1984;8:324–326. 81. Wax MK, Treloar ME. Thoracic duct cyst: an unusual supraclavicular mass. Head Neck 1992;14:502–505. 82. Karajiannis A, Krueger T, Stauffer E, et al. Large thoracic duct cyst: a case report and review of the literature. Eur J Cardiothorac Surg 2000;17:754–756. 83. Mattila PS, Tarkkanen J, Mattila S. Thoracic duct cyst: a case report and review of 29 cases. Ann Otol Rhinol Laryngol 1999;108: 505–508. 84. Pramesh CS, Deshpande MS, Pantvaidya GH, et al. Thoracic duct cyst of the mediastinum. Ann Thorac Cardiovasc Surg 2003;9:264–265. 85. Turkyilmaz A, Eroglu A. A giant thoracic duct cyst: an unusual cause of dysphagia. J Thorac Cardiovasc Surg 2007;134:1082– 1083. 86. Kotiligam D, Lazar AJ, Pollock RE, et al. Desmoid tumor: a disease opportune for molecular insights. Histol Histopathol 2008;23:117–126. 87. Shankwiler RA, Athey PA, Lamki N. Aggressive infantile fibromatosis.

985

Chapter 14 • Mediastinal and Aortic Disease

88. 89.

90. 91.

92.

93.

94.

95.

96.

97.

98.

99.

100.

101.

102.

103.

104. 105.

986

Pulmonary metastases documented by plain film and computed tomography. Clin Imaging 1989;13:127–129. Kaplan J, Davidson T. Intrathoracic desmoids: report of two cases. Thorax 1986;41:894–895. Black WC, Armstrong P, Daniel TM, et al. Computed tomography of aggressive fibromatosis in the posterior mediastinum. J Comput Assist Tomogr 1987;11:153–155. Casillas J, Sais GJ, Greve JL, et al. Imaging of intra- and extraabdominal desmoid tumors. RadioGraphics 1991;11:959–968. Ko SF, Ng SH, Hsiao CC, et al. Juvenile fibromatosis of the posterior mediastinum with intraspinal extension. AJNR Am J Neuroradiol 1996;17:522–524. Peled N, Babyn PS, Manson D, et al. Aggressive fibromatosis simulating congenital lung malformation. Can Assoc Radiol J 1993;44:221–223. Tam CG, Broome DR, Shannon RL. Desmoid tumor of the anterior mediastinum: CT and radiologic features. J Comput Assist Tomogr 1994;18:499–501. Dosios TJ, Angouras DC, Floros DG. Primary desmoid tumor of the posterior mediastinum. Ann Thorac Surg 1998;66: 2098–2099. Wilhelm A, Jolles HI, Krishna M. Anterior mediastinal desmoid tumor with CT and MR imaging. J Thorac Imaging 2007;22: 252–255. Cyrlak D, Milne EN, Imray TJ. Pneumomediastinum: a diagnostic problem. Crit Rev Diagn Imaging 1984;23: 75–117. Quinn SF, Erickson SJ, Dee PM, et al. MR imaging in fibromatosis: results in 26 patients with pathologic correlation. AJR Am J Roentgenol 1991;156:539–542. Sundaram M, McGuire MH, Schajowicz F. Soft-tissue masses: histologic basis for decreased signal (short T2) on T2-weighted MR images. AJR Am J Roentgenol 1987; 148:1247–1250. Cardoso PF, da Silva LC, Bonamigo TP, et al. Intrathoracic desmoid tumor with invasion of the great vessels. Eur J Cardiothorac Surg 2002;22:1017–1019. Kocak Z, Adli M, Erdir O, et al. Intrathoracic desmoid tumor of the posterior mediastinum with transdiaphragmatic extension. Report of a case. Tumori 2000;86:489–491. Hudson TM, Vandergriend RA, Springfield DS, et al. Aggressive fibromatosis: evaluation by computed tomography and angiography. Radiology 1984;150: 495–501. Basu S, Nair N, Banavali S. Uptake characteristics of fluorodeoxyglucose (FDG) in deep fibromatosis and abdominal desmoids: potential clinical role of FDG-PET in the management. Br J Radiol 2007;80:750–756. Maziak DE, Todd TR, Pearson FG. Massive hiatus hernia: evaluation and surgical management. J Thorac Cardiovasc Surg 1998;115:53–60, discussion 61–62. Hartley WS, Schabel SI, Scruggs MC, et al. Communicating intrathoracic hydrocele. Clin Imaging 1991;15:280–282. Godwin JD, MacGregor JM. Extension of ascites into the chest with hiatal hernia: visualization on CT. AJR Am J Roentgenol 1987;148:31–32.

106. Erasmus JJ, McAdams HP, Goodman PC. Diagnosis please. Case 5: esophageal mucocele after surgical bypass of the esophagus. Radiology 1998;209:757–760. 107. Rabushka LS, Fishman EK, Kuhlman JE. CT evaluation of achalasia. J Comput Assist Tomogr 1991;15:434–439. 108. Levine MS. Benign tumors of the esophagus: radiologic evaluation. Semin Thorac Cardiovasc Surg 2003;15:9–19. 109. Donner MW, Saba GP, Martinez CR. Diffuse diseases of the esophagus: a practical approach. Semin Roentgenol 1981;16:198–213. 110. Gonlachanvit S, Fisher RS, Parkman HP. Diagnostic modalities for achalasia. Gastrointest Endosc Clin N Am 2001;11: 293–310, vi. 111. Raider L, Landry BA, Brogdon BG. The retrotracheal triangle. RadioGraphics 1990;10:1055–1079. 112. Franquet T, Erasmus JJ, Gimenez A, et al. The retrotracheal space: normal anatomic and pathologic appearances. RadioGraphics 2002;22:S231–S246. 113. Putman CE, Curtis AM, Westfried M, et al. Thickening of the posterior tracheal stripe: a sign of squamous cell carcinoma of the esophagus. Radiology 1976;121:533–536. 114. Lee SY. Tracheal compression by esophageal mucocele after surgical exclusion of the esophagus. Eur J Cardiothorac Surg 2005;27:706. 115. Haddad R, Lima RT, Boasquevisque CH, et al. Symptomatic mucocele after esophageal exclusion. Interact Cardiovasc Thorac Surg 2008;7:742–744. 116. Cohen AM, Cunat JS. Giant esophageal leiomyoma as a mediastinal mass. J Can Assoc Radiol 1981;32:129–130. 117. Miettinen M, Sarlomo-Rikala M, Sobin LH, et al. Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol 2000;24:211–222. 118. Greenson JK. Gastrointestinal stromal tumors and other mesenchymal lesions of the gut. Mod Pathol 2003;16:366–375. 119. Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): definition, occurrence, pathology, differential diagnosis and molecular genetics. Pol J Pathol 2003;54:3–24. 120. Miettinen M, Lasota J. Gastrointestinal stromal tumors: definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001;438:1–12. 121. Ghanem N, Altehoefer C, Furtwangler A, et al. Computed tomography in gastrointestinal stromal tumors. Eur Radiol 2003;13:1669–1678. 122. Bruzzi JF, Munden RF, Truong MT, et al. PET/CT of esophageal cancer: its role in clinical management. RadioGraphics 2007; 27:1635–1652. 123. van Kouwen MC, Oyen WJ, Nagengast FM, et al. FDG-PET scanning in the diagnosis of gastrointestinal cancers. Scand J Gastroenterol Suppl 2004;241:85–92. 124. Gaerte SC, Meyer CA, Winer-Muram HT, et al. Fat-containing lesions of the chest. RadioGraphics 2002;22:S61–S78. 125. Heitzman ER. Radiological diagnosis of mediastinal lymph node enlargement.

126.

127.

128. 129. 130. 131. 132.

133.

134.

135.

136.

137.

138.

139.

140.

141.

142.

143.

144.

J Can Assoc Radiol 1987;39: 151–157. Homer MJ, Wechsler RJ, Carter BL. Mediastinal lipomatosis. CT confirmation of a normal variant. Radiology 1978;128: 657–661. Koerner HJ, Sun DI. Mediastinal lipomatosis secondary to steroid therapy. Am J Roentgenol Radium Ther Nucl Med 1966;98:461–464. Price JE Jr, Rigler LG. Widening of the mediastinum resulting from fat accumulation. Radiology 1970;96:497–500. Teates CD. Steroid-induced mediastinal lipomatosis. Radiology 1970;96:501–502. Glickstein MF, Miller WT, Dalinka MK, et al. Paraspinal lipomatosis: a benign mass. Radiology 1987;163:79–80. Lee WJ, Fattal G. Mediastinal lipomatosis in simple obesity. Chest 1976;70:308–309. Bein ME, Mancuso AA, Mink JH, et al. Computed tomography in the evaluation of mediastinal lipomatosis. J Comput Assist Tomogr 1978;2:379–383. Streiter ML, Schneider HJ, Proto AV. Steroid-induced thoracic lipomatosis: paraspinal involvement. AJR Am J Roentgenol 1982;139:679–681. Zhang XY, Li NY, Xiao WL. Madelung disease: manifestations of CT and MR imaging. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:e57–e64. Enzi G, Biondetti PR, Fiore D, et al. Computed tomography of deep fat masses in multiple symmetrical lipomatosis. Radiology 1982;144:121–124. Borges A, Torrinha F, Lufkin RB, et al. Laryngeal involvement in multiple symmetric lipomatosis: the role of computed tomography in diagnosis. Am J Otolaryngol 1997;18:127–130. Smith PD, Stadelmann WK, Wassermann RJ, et al. Benign symmetric lipomatosis (Madelung’s disease). Ann Plast Surg 1998;41:671–673. Ahuja AT, King AD, Chan ES. Ultrasound, CT and MRI in patients with multiple symmetric lipomatosis. Clin Radiol 2000; 55:79. Pandzic Jaksic V, Sucic M. Multiple symmetric lipomatosis: a reflection of new concepts about obesity. Med Hypotheses 2008;71:99–101. Nisoli E, Regianini L, Briscini L, et al. Multiple symmetric lipomatosis may be the consequence of defective noradrenergic modulation of proliferation and differentiation of brown fat cells. J Pathol 2002;198:378–387. Yeung HW, Grewal RK, Gonen M, et al. Patterns of (18)F-FDG uptake in adipose tissue and muscle: a potential source of false-positives for PET. J Nucl Med 2003; 44:1789–1796. Truong MT, Erasmus JJ, Munden RF, et al. Focal FDG uptake in mediastinal brown fat mimicking malignancy: a potential pitfall resolved on PET/CT. AJR Am J Roentgenol 2004;183:1127–1132. Schweitzer DL, Aguam AS. Primary liposarcoma of the mediastinum. Report of a case and review of the literature. J Thorac Cardiovasc Surg 1977;74:83–97. Quinn SF, Monson M, Paling M. Spinal lipoma presenting as a mediastinal mass: diagnosis by CT. J Comput Assist Tomogr 1983;7:1087–1089.

References 145. Shub C, Parkin TW, Lie JT. An unusual mediastinal lipoma simulating cardiomegaly. Mayo Clin Proc 1979;54:60– 62. 146. Mendez G Jr, Isikoff MB, Isikoff SK, et al. Fatty tumors of the thorax demonstrated by CT. AJR Am J Roentgenol 1979;133: 207–212. 147. Federici S, Cuoghi D, Sciutti R. Benign mediastinal lipoblastoma in a 14months-old infant. Pediatr Radiol 1992;22: 150–151. 148. Moholkar S, Sebire NJ, Roebuck DJ. Radiological-pathological correlation in lipoblastoma and lipoblastomatosis. Pediatr Radiol 2006;36:851–856. 149. Black WC, Burke JW, Feldman PS, et al. CT appearance of cervical lipoblastoma. J Comput Assist Tomogr 1986;10:696–698. 150. Whyte AM, Powell N. Mediastinal lipoblastoma of infancy. Clin Radiol 1990;42:205–206. 151. Seidel FG, Magill HL, Burton EM, et al. Cases of the day. Pediatric. Lipoblastoma. RadioGraphics 1990;10:728–731. 152. Burdick MJ, Jolles PR, Grimes MM, et al. Mediastinal hibernoma simulates a malignant lesion on dual time point FDG imaging. Lung Cancer 2008;59:391–394. 153. Udwadia ZF, Kumar N, Bhaduri AS. Mediastinal hibernoma. Eur J Cardiothorac Surg 1999;15:533–535. 154. Santambrogio L, Cioffi U, De Simone M, et al. Cervicomediastinal hibernoma. Ann Thorac Surg 1997;64:1160–1162. 155. Smith CS, Teruya-Feldstein J, Caravelli JF, et al. False-positive findings on 18F-FDG PET/CT: differentiation of hibernoma and malignant fatty tumor on the basis of fluctuating standardized uptake values. AJR Am J Roentgenol 2008;190:1091–1096. 156. Kline ME, Patel BU, Agosti SJ. Noninfiltrating angiolipoma of the mediastinum. Radiology 1990;175:737–738. 157. Kim K, Koo BC, Davis JT, et al. Primary myelolipoma of mediastinum. J Comput Tomogr 1984;8:119–123. 158. Eisenstat R, Bruce D, Williams LE, et al. Primary liposarcoma of the mediastinum with coexistent mediastinal lipomatosis. AJR Am J Roentgenol 2000;174:572–573. 159. Hahn HP, Fletcher CD. Primary mediastinal liposarcoma: clinicopathologic analysis of 24 cases. Am J Surg Pathol 2007;31:1868–1874. 160. Paci M, De Franco S, Cavazza A, et al. Well-differentiated giant ‘lipoma-like’ liposarcoma of the posterior mediastinum: a case report. Chir Ital 2003;55:101–104. 161. Jung JI, Kim H, Kang SW, et al. Radiological findings in myxoid liposarcoma of the anterior mediastinum. Br J Radiol 1998;71:975–976. 162. Doyle AJ, Pang AK, Miller MV, et al. Magnetic resonance imaging of lipoma and atypical lipomatous tumour/welldifferentiated liposarcoma: observer performance using T1-weighted and fluid-sensitive MRI. J Med Imaging Radiat Oncol 2008;52:44–48. 163. Ohguri T, Aoki T, Hisaoka M, et al. Differential diagnosis of benign peripheral lipoma from well-differentiated liposarcoma on MR imaging: is comparison of margins and internal characteristics useful? AJR Am J Roentgenol 2003;180: 1689–1694.

164. Kransdorf MJ, Bancroft LW, Peterson JJ, et al. Imaging of fatty tumors: distinction of lipoma and well-differentiated liposarcoma. Radiology 2002;224:99–104. 165. Einarsdottir H, Soderlund V, Larsson O, et al. 110 subfascial lipomatous tumors. MR and CT findings versus histopathological diagnosis and cytogenetic analysis. Acta Radiol 1999;40:603–609. 166. Brenner W, Eary JF, Hwang W, et al. Risk assessment in liposarcoma patients based on FDG PET imaging. Eur J Nucl Med Mol Imaging 2006;33:1290–1295. 167. Suzuki R, Watanabe H, Yanagawa T, et al. PET evaluation of fatty tumors in the extremity: possibility of using the standardized uptake value (SUV) to differentiate benign tumors from liposarcoma. Ann Nucl Med 2005;19: 661–670. 168. Yeager BA, Guglielmi GE, Schiebler ML, et al. Magnetic resonance imaging of Morgagni hernia. Gastrointest Radiol 1987;12:296–298. 169. Wyatt SH, Fishman EK. Diffuse pulmonary extramedullary hematopoiesis in a patient with myelofibrosis: CT findings. J Comput Assist Tomogr 1994;18:815–817. 170. Long JA Jr, Doppman JL, Nienhuis AW. Computed tomographic studies of thoracic extramedullary hematopoiesis. J Comput Assist Tomogr 1980;4:67–70. 171. Papavasiliou C, Gouliamos A, Andreou J. The marrow heterotopia in thalassemia. Eur J Radiol 1986;6:92–96. 172. Xiros N, Economopoulos T, Papageorgiou E, et al. Massive hemothorax due to intrathoracic extramedullary hematopoiesis in a patient with hereditary spherocytosis. Ann Hematol 2001;80:38–40. 173. Leong CS, Stark P. Thoracic manifestations of sickle cell disease. J Thorac Imaging 1998;13:128–134. 174. Ross P, Logan W. Roentgen findings in extramedullary hematopoiesis. Am J Roentgenol Radium Ther Nucl Med 1969; 106:604–613. 175. Gumbs RV, Higginbotham-Ford EA, Teal JS, et al. Thoracic extramedullary hematopoiesis in sickle-cell disease. AJR Am J Roentgenol 1987;149:889–893. 176. Martin J, Palacio A, Petit J, et al. Fatty transformation of thoracic extramedullary hematopoiesis following splenectomy: CT features. J Comput Assist Tomogr 1990;14:477–478. 177. Savader SJ, Otero RR, Savader BL. MR imaging of intrathoracic extramedullary hematopoiesis. J Comput Assist Tomogr 1988;12:878–880. 178. Yamato M, Fuhrman CR. Computed tomography of fatty replacement in extramedullary hematopoiesis. J Comput Assist Tomogr 1987;11:541–542. 179. Hines GL. Paravertebral extramedullary hematopoiesis (as a posterior mediastinal tumor) associated with congenital dyserythropoietic anemia. J Thorac Cardiovasc Surg 1993;106:760–761. 180. Stebner FC, Bishop CR. Bone marrow scan and radioiron uptake of an intrathoracic mass. Clin Nucl Med 1982;7:86–87. 181. Adams BK, Jacobs P, Byrne MJ, et al. Fe-52 imaging of intrathoracic extramedullary hematopoiesis in a patient with betathalassemia. Clin Nucl Med 1995;20: 619–622.

182. Chen YW, Sheu RS, Chiou SS, et al. Tc99m sulfur colloid scintigraphy for detection of intrathoracic extramedullary hematopoiesis in patient with beta-thalassemia major: a case report. Kaohsiung J Med Sci 2000;16: 319–324. 183. Harnsberger HR, Datz FL, Knochel JQ, et al. Failure to detect extramedullary hematopoiesis during bone-marrow imaging with indium-111 or technetium99m sulfur colloid. J Nucl Med 1982;23: 589–591. 184. Al-Marzooq YM, Al-Bahrani AT, Chopra R, et al. Fine-needle aspiration biopsy diagnosis of intrathoracic extramedullary hematopoiesis presenting as a posterior mediastinal tumor in a patient with sickle-cell disease: case report. Diagn Cytopathol 2004;30:119–121. 185. Rosado-de-Christenson ML, Templeton PA, Moran CA. From the archives of the AFIP. Mediastinal germ cell tumors: radiologic and pathologic correlation. RadioGraphics 1992;12:1013–1030. 186. Dulmet EM, Macchiarini P, Suc B, et al. Germ cell tumors of the mediastinum. A 30-year experience. Cancer 1993;72: 1894–1901. 187. Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest 1997;112:511–522. 188. Drevelegas A, Palladas P, Scordalaki A. Mediastinal germ cell tumors: a radiologicpathologic review. Eur Radiol 2001;11: 1925–1932. 189. Sham JS, Chan FL, Lau WH, et al. Primary mediastinal endodermal sinus tumors: CT evaluation. Clin Imaging 1989;13:299–304. 190. Strollo DC, Rosado-de-Christenson ML. Primary mediastinal malignant germ cell neoplasms: imaging features. Chest Surg Clin N Am 2002;12:645–658. 191. Hartmann JT, Nichols CR, Droz JP, et al. Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors. Ann Oncol 2002;13:1017– 1028. 192. Nichols CR. Mediastinal germ cell tumors. Clinical features and biologic correlates. Chest 1991;99:472–479. 193. Levine GD, Rosai J. Thymic hyperplasia and neoplasia: a review of current concepts. Hum Pathol 1978;9:495–515. 194. Moran CA, Suster S. Primary germ cell tumors of the mediastinum: I. Analysis of 322 cases with special emphasis on teratomatous lesions and a proposal for histopathologic classification and clinical staging. Cancer 1997;80:681–690. 195. Allen MS. Presentation and management of benign mediastinal teratomas. Chest Surg Clin N Am 2002;12:659–664, vi. 196. Lewis BD, Hurt RD, Payne WS, et al. Benign teratomas of the mediastinum. J Thorac Cardiovasc Surg 1983;86:727–731. 197. Dominguez Malagon H, Perez Montiel D. Mediastinal germ cell tumors. Semin Diagn Pathol 2005;22:230–240. 198. Lyons HA, Calvy GL, Sammons BP. The diagnosis and classification of mediastinal masses. A study of 782 cases. Ann Intern Med 1959;51:897–932. 199. Moeller KH, Rosado-de-Christenson ML, Templeton PA. Mediastinal mature teratoma: imaging features. AJR Am J Roentgenol 1997;169:985–990.

987

Chapter 14 • Mediastinal and Aortic Disease 200. Dobranowski J, Martin LF, Bennett WF. CT evaluation of posterior mediastinal teratoma. J Comput Assist Tomogr 1987; 11:156–157. 201. Sidani AH, Oberson R, Deleze G, et al. Infected teratoma of lower posterior mediastinum in a six-year-old boy. Pediatr Radiol 1991;21:438–439. 202. Kurosaki Y, Tanaka YO, Itai Y. Mature teratoma of the posterior mediastinum. Eur Radiol 1998;8:100–102. 203. Brown LR, Muhm JR, Aughenbaugh GL, et al. Computed tomography of benign mature teratomas of the mediastinum. J Thorac Imaging 1987;2:66–71. 204. Suzuki M, Takashima T, Itoh H, et al. Computed tomography of mediastinal teratomas. J Comput Assist Tomogr 1983; 7:74–76. 205. Fulcher AS, Proto AV, Jolles H. Cystic teratoma of the mediastinum: demonstration of fat/fluid level. AJR Am J Roentgenol 1990;154:259–260. 206. Seltzer SE, Herman PG, Sagel SS. Differential diagnosis of mediastinal fluid levels visualized on computed tomography. J Comput Assist Tomogr 1984;8:244–246. 207. Choi SJ, Lee JS, Song KS, et al. Mediastinal teratoma: CT differentiation of ruptured and unruptured tumors. AJR Am J Roentgenol 1998;171:591–594. 208. Ochsner JL, Ochsner SF. Congenital cysts of the mediastinum: 20-year experience with 42 cases. Ann Surg 1966;163:909–920. 209. Yeoman LJ, Dalton HR, Adam EJ. Fat-fluid level in pleural effusion as a complication of a mediastinal dermoid: CT characteristics. J Comput Assist Tomogr 1990;14:307–309. 210. Ikezoe J, Takeuchi N, Johkoh T, et al. MRI of anterior mediastinal tumors. Radiat Med 1992;10:176–183. 211. Ikezoe J, Morimoto S, Arisawa J, et al. Ultrasonography of mediastinal teratoma. J Clin Ultrasound 1986;14:513–520. 212. Wu TT, Wang HC, Chang YC, et al. Mature mediastinal teratoma: sonographic imaging patterns and pathologic correlation. J Ultrasound Med 2002;21:759–765. 213. Shih JY, Wang HC, Chang YL, et al. Echogenic floating spherules as a sonographic sign of cystic teratoma of mediastinum: correlation with CT and pathologic findings. J Ultrasound Med 1996;15:603–605. 214. Sugawara Y, Zasadny KR, Grossman HB, et al. Germ cell tumor: differentiation of viable tumor, mature teratoma, and necrotic tissue with FDG PET and kinetic modeling. Radiology 1999;211:249–256. 215. Moran CA, Suster S, Koss MN. Primary germ cell tumors of the mediastinum: III. Yolk sac tumor, embryonal carcinoma, choriocarcinoma, and combined nonteratomatous germ cell tumors of the mediastinum: a clinicopathologic and immunohistochemical study of 64 cases. Cancer 1997;80:699–707. 216. Moran CA, Suster S, Przygodzki RM, et al. Primary germ cell tumors of the mediastinum. II. Mediastinal seminomas: a clinicopathologic and immunohistochemical study of 120 cases. Cancer 1997;80:691–698. 217. Polansky SM, Barwick KW, Ravin CE. Primary mediastinal seminoma. AJR Am J Roentgenol 1979;132:17–21.

988

218. Holbert BL, Libshitz HI. Superior vena caval syndrome in primary mediastinal germ cell tumors. Can Assoc Radiol J 1986; 37:182–183. 219. deMent SH. Association between mediastinal germ cell tumors and hematologic malignancies: an update. Hum Pathol 1990;21:699–703. 220. Nichols CR, Roth BJ, Heerema N, et al. Hematologic neoplasia associated with primary mediastinal germ-cell tumors. N Engl J Med 1990;322:1425–1429. 221. Cohen D, Weintrob N. Case 9–2003: mediastinal germ-cell tumor. N Engl J Med 2003;348:2469–2470, author reply 2469–2470. 222. Hainsworth JD, Greco FA. Germ cell neoplasms and other malignancies of the mediastinum. Cancer Treat Res 2001;105: 303–325. 223. Blomlie V, Lien HH, Fossa SD, et al. Computed tomography in primary non-seminomatous germ cell tumors of the mediastinum. Acta Radiol 1988;29:289–292. 224. Lee KS, Im JG, Han CH, et al. Malignant primary germ cell tumors of the mediastinum: CT features. AJR Am J Roentgenol 1989;153:947–951. 225. Levitt RG, Husband JE, Glazer HS. CT of primary germ-cell tumors of the mediastinum. AJR Am J Roentgenol 1984;142:73–78. 226. el-Khatib M, Chew FS. Embryonal carcinoma of the anterior mediastinum. AJR Am J Roentgenol 1998;170:722. 227. Mori K, Eguchi K, Moriyama H, et al. Computed tomography of anterior mediastinal tumors. Differentiation between thymoma and germ cell tumor. Acta Radiol 1987;28:395–398. 228. Cox JD. Primary malignant germinal tumors of the mediastinum. A study of 24 cases. Cancer 1975;36:1162–1168. 229. de Wit M, Brenner W, Hartmann M, et al. [18F]-FDG-PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial. Ann Oncol 2008;19:1619–1623. 230. De Giorgi U, Pupi A, Fiorentini G, et al. FDG-PET in the management of germ cell tumor. Ann Oncol 2005;16(suppl 4):iv90– iv94. 231. De Santis M, Pont J. The role of positron emission tomography in germ cell cancer. World J Urol 2004;22:41–46. 232. Kollmannsberger C, Oechsle K, Dohmen BM, et al. Prospective comparison of [18F]fluorodeoxyglucose positron emission tomography with conventional assessment by computed tomography scans and serum tumor markers for the evaluation of residual masses in patients with nonseminomatous germ cell carcinoma. Cancer 2002;94:2353–2362. 233. Panicek DM, Toner GC, Heelan RT, et al. Nonseminomatous germ cell tumors: enlarging masses despite chemotherapy. Radiology 1990;175:499–502. 234. Afifi HY, Bosl GJ, Burt ME. Mediastinal growing teratoma syndrome. Ann Thorac Surg 1997;64:359–362. 235. Iyoda A, Hiroshima K, Yusa T, et al. The primary mediastinal growing teratoma syndrome. Anticancer Res 2000;20: 3723–3726. 236. Andre F, Fizazi K, Culine S, et al. The growing teratoma syndrome: results of

237. 238.

239.

240.

241.

242.

243.

244. 245.

246.

247.

248.

249.

250.

251.

252.

253.

therapy and long-term follow-up of 33 patients. Eur J Cancer 2000;36:1389– 1394. Nimkin K, Gupta P, McCauley R, et al. The growing teratoma syndrome. Pediatr Radiol 2003. Coscojuela P, Llauger J, Perez C, et al. The growing teratoma syndrome: radiologic findings in four cases. Eur J Radiol 1991; 12:138–140. Daly BD, Leung SF, Cheung H, et al. Thoracic metastases from carcinoma of the nasopharynx: high frequency of hilar and mediastinal lymphadenopathy. AJR Am J Roentgenol 1993;160:241–244. McLoud TC, Kalisher L, Stark P, et al. Intrathoracic lymph node metastases from extrathoracic neoplasms. AJR Am J Roentgenol 1978;131:403–407. Earls JP, Cerva D Jr, Berman E, et al. Inhalational anthrax after bioterrorism exposure: spectrum of imaging findings in two surviving patients. Radiology 2002; 222:305–312. Prabhakar HB, Rabinowitz CB, Gibbons FK, et al. Imaging features of sarcoidosis on MDCT, FDG PET, and PET/CT. AJR Am J Roentgenol 2008;190:S1–S6. Sussman SK, Halvorsen RA Jr, Silverman PM, et al. Paracardiac adenopathy: CT evaluation. AJR Am J Roentgenol 1987;149:29–34. Vock P, Hodler J. Cardiophrenic angle adenopathy: update of causes and significance. Radiology 1986;159:395–399. Niimi H, Kang EY, Kwong JS, et al. CT of chronic infiltrative lung disease: prevalence of mediastinal lymphadenopathy. J Comput Assist Tomogr 1996;20:305–308. Thomas RD, Blaquiere RM. Reactive mediastinal lymphadenopathy in bronchiectasis assessed by CT. Acta Radiol 1993;34:489–491. Boiselle PM, Patz EF Jr, Vining DJ, et al. Imaging of mediastinal lymph nodes: CT, MR, and FDG PET. RadioGraphics 1998; 18:1061–1069. Chung JH, Cho KJ, Lee SS, et al. Overexpression of Glut1 in lymphoid follicles correlates with false-positive18-FDG PET results in lung cancer staging. J Nucl Med 2004;45:999–1003. Nakagawa T, Yamada M, Suzuki Y. 18F-FDG uptake in reactive neck lymph nodes of oral cancer: relationship to lymphoid follicles. J Nucl Med 2008;49: 1053–1059. Slanetz PJ, Truong M, Shepard JA, et al. Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure. AJR Am J Roentgenol 1998;171:1307–1309. Ngom A, Dumont P, Diot P, et al. Benign mediastinal lymphadenopathy in congestive heart failure. Chest 2001;119: 653–656. Erly WK, Borders RJ, Outwater EK, et al. Location, size, and distribution of mediastinal lymph node enlargement in chronic congestive heart failure. J Comput Assist Tomogr 2003;27:485–489. Chabbert V, Canevet G, Baixas C, et al. Mediastinal lymphadenopathy in congestive heart failure: a sequential CT evaluation with clinical and echocardiographic correlations. Eur Radiol 2004;14:881–889.

References 254. Jung JI, Kim HH, Jung YJ, et al. Mediastinal lymphadenopathy in pulmonary fibrosis: correlation with disease severity. J Comput Assist Tomogr 2000;24:706–710. 255. Bergin C, Castellino RA. Mediastinal lymph node enlargement on CT scans in patients with usual interstitial pneumonitis. AJR Am J Roentgenol 1990;154:251–254. 256. Garber SJ, Wells AU, duBois RM, et al. Enlarged mediastinal lymph nodes in the fibrosing alveolitis of systemic sclerosis. Br J Radiol 1992;65:983–986. 257. Sampson C, Hansell DM. The prevalence of enlarged mediastinal lymph nodes in asbestos-exposed individuals: a CT study. Clin Radiol 1992;45:340–342. 258. McAdams HP, Erasmus J, Winter JA. Radiologic manifestations of pulmonary tuberculosis. Radiol Clin North Am 1995; 33:655–678. 259. McAdams HP, Rosado-de-Christenson ML, Lesar M, et al. Thoracic mycoses from endemic fungi: radiologic-pathologic correlation. RadioGraphics 1995;15: 255–270. 260. Archibald N, Dalzell KG, Fernando CC, et al. Infectious mononucleosis complicated by mediastinal lymphadenopathy causing transient pulmonary artery stenosis. Intern Med J 2003;33:324–325. 261. Jernigan JA, Stephens DS, Ashford DA, et al. Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States. Emerg Infect Dis 2001;7: 933–944. 262. Bryant KA. Tularemia: lymphadenitis with a twist. Pediatr Ann 2002;31:187–190. 263. Krishna G, Chitkara RK. Pneumonic plague. Semin Respir Infect 2003;18: 159–167. 264. Thomas KW, Hunninghake GW. Sarcoidosis. JAMA 2003;289:3300–3303. 265. Baldwin DR, Lambert L, Pantin CF, et al. Silicosis presenting as bilateral hilar lymphadenopathy. Thorax 1996;51: 1165–1167. 266. Kinoshita T, Itoh H. Coal worker’s pneumoconiosis mimicking pulmonary sarcoidosis. Clin Nucl Med 1994;19: 544–545. 267. Zinck SE, Schwartz E, Berry GJ, et al. CT of noninfectious granulomatous lung disease. Radiol Clin North Am 2001;39:1189–1209, vi. 268. Rossman MD, Kreider ME. Is chronic beryllium disease sarcoidosis of known etiology? Sarcoidosis Vasc Diffuse Lung Dis 2003;20:104–109. 269. Fireman E, Haimsky E, Noiderfer M, et al. Misdiagnosis of sarcoidosis in patients with chronic beryllium disease. Sarcoidosis Vasc Diffuse Lung Dis 2003;20:144–148. 270. George TM, Cash JM, Farver C, et al. Mediastinal mass and hilar adenopathy: rare thoracic manifestations of Wegener’s granulomatosis. Arthritis Rheum 1997;40: 1992–1997. 271. Prakash UB. Respiratory complications in mixed connective tissue disease. Clin Chest Med 1998;19:733–746, ix. 272. Wechsler RJ, Steiner RM, Spirn PW, et al. The relationship of thoracic lymphadenopathy to pulmonary interstitial disease in diffuse and limited systemic sclerosis: CT findings. AJR Am J Roentgenol 1996;167:101–104.

273. Yoshioka K. Mediastinal lymphadenopathy preceding skin and lung fibrosis in systemic sclerosis. Respiration 1994;61: 169–171. 274. Kaplan JO, Morillo G, Weinfeld A, et al. Mediastinal adenopathy in myeloma. J Can Assoc Radiol 1980;31:48–49. 275. Pavlidis N, Briasoulis E, Hainsworth J, et al. Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer 2003;39:1990–2005. 276. McAdams HP, Rosado-de-Christenson M, Fishback NF, et al. Castleman disease of the thorax: radiologic features with clinical and histopathologic correlation. Radiology 1998;209:221–228. 277. Gross BH, Schneider HJ, Proto AV. Eggshell calcification of lymph nodes: an update. AJR Am J Roentgenol 1980;135: 1265–1268. 278. Urschel JD, Urschel DM. Mediastinal amyloidosis. Ann Thorac Surg 2000;69: 944–946. 279. Takeshita K, Yamada S, Sato N, et al. An unusual case of mediastinal lymphadenopathy caused by amyloidosis. Intern Med 2000;39:839–842. 280. Hiller N, Fisher D, Shmesh O, et al. Primary amyloidosis presenting as an isolated mediastinal mass: diagnosis by fine needle biopsy. Thorax 1995;50:908–909. 281. Kubaska SM, Shepard JA, Chew FS, et al. Whipple’s disease involving the mediastinum. AJR Am J Roentgenol 1998; 171:364. 282. Wolfert AL, Wright JE. Whipple’s disease presenting as sarcoidosis and valvular heart disease. South Med J 1999;92:820–825. 283. Samuels T, Hamilton P, Shaw P. Whipple disease of the mediastinum. AJR Am J Roentgenol 1990;154:1187–1188. 284. Mayo JR, Müller NL, Road J, et al. Chronic eosinophilic pneumonia: CT findings in six cases. AJR Am J Roentgenol 1989;153: 727–730. 285. Palestro G, Turrini F, Pagano M, et al. Castleman’s disease. Adv Clin Path 1999;3:11–22. 286. Kim JH, Jun TG, Sung SW, et al. Giant lymph node hyperplasia (Castleman’s disease) in the chest. Ann Thorac Surg 1995;59:1162–1165. 287. Dham A, Peterson BA. Castleman disease. Curr Opin Hematol 2007;14:354–359. 288. Dispenzieri A. Castleman disease. Cancer Treat Res 2008;142:293–330. 289. Dispenzieri A, Gertz MA. Treatment of Castleman’s disease. Curr Treat Options Oncol 2005;6:255–266. 290. Keller AR, Hochholzer L, Castleman B. Hyaline-vascular and plasma-cell types of giant lymph node hyperplasia of the mediastinum and other locations. Cancer 1972;29:670–683. 291. Rimar D, Rimar Y, Keynan Y. Human herpesvirus-8: beyond Kaposi’s. Isr Med Assoc J 2006;8:489–493. 292. Carbone A, Gloghini A. KSHV/HHV8associated lymphomas. Br J Haematol 2008;140:13–24. 293. Kirsch CF, Webb EM, Webb WR. Multicentric Castleman’s disease and POEMS syndrome: CT findings. J Thorac Imaging 1997;12:75–77. 294. Gossios K, Nikolaides C, Bai M. Widespread Castleman disease: CT findings. Eur Radiol 1995;6:95–98.

295. Guihot A, Couderc LJ, Rivaud E, et al. Thoracic radiographic and CT findings of multicentric Castleman disease in HIV-infected patients. J Thorac Imaging 2007;22:207–211. 296. Chen KT. Multicentric Castleman’s disease and Kaposi’s sarcoma. Am J Surg Pathol 1984;8:287–293. 297. Frizzera G, Banks PM, Massarelli G, et al. A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease. Pathological findings in 15 patients. Am J Surg Pathol 1983;7:211–231. 298. Naresh KN, Rice AJ, Bower M. Lymph nodes involved by multicentric Castleman disease among HIV-positive individuals are often involved by Kaposi Sarcoma. Am J Surg Pathol 2008;32:1006–1012. 299. Olscamp G, Weisbrod G, Sanders D, et al. Castleman disease: unusual manifestations of an unusual disorder. Radiology 1980; 135:43–48. 300. Phelan MS. Castleman’s giant lymph node hyperplasia. Br J Radiol 1982;55:158–160. 301. Samuels TH, Hamilton PA, Ngan B. Mediastinal Castleman’s disease: demonstration with computed tomography and angiography. Can Assoc Radiol J 1990; 41:380–383. 302. Aalbers R, vd Jagt E, Poppema S, et al. Left paravertebral mass: giant lymph node hyperplasia. Chest 1987;91:889–890. 303. Fiore D, Biondetti PR, Calabro F, et al. CT demonstration of bilateral Castleman tumors in the mediastinum. J Comput Assist Tomogr 1983;7:719–720. 304. Meisel S, Rozenman J, Yellin A, et al. Castleman’s disease. An uncommon computed tomographic feature. Chest 1988;93:1306–1307. 305. Onik G, Goodman PC. CT of Castleman disease. AJR Am J Roentgenol 1983;140: 691–692. 306. Charig MJ. Mediastinal Castleman’s disease: a missed pre-operative diagnosis? Clin Radiol 1990;42:440–442. 307. Walter JF, Rottenberg RW, Cannon WB, et al. Giant mediastinal lymph node hyperplasia (Castleman’s disease): angiographic and clinical features. AJR Am J Roentgenol 1978;130:447–450. 308. Moon WK, Im JG, Han MC. Castleman’s disease of the mediastinum: MR imaging features. Clin Radiol 1994;49:466–468. 309. Hsieh ML, Quint LE, Faust JM, et al. Enhancing mediastinal mass at MR: Castleman disease. Magn Reson Imaging 1993;11:599–601. 310. Park JB, Hwang JH, Kim H, et al. Castleman disease presenting with jaundice: a case with the multicentric hyaline vascular variant. Korean J Intern Med 2007;22:113–117. 311. Halac M, Ergul N, Sager S, et al. PET/CT findings in a multicentric form of Castleman’s disease. Hell J Nucl Med 2007; 10:172–174. 312. Enomoto K, Nakamichi I, Hamada K, et al. Unicentric and multicentric Castleman’s disease. Br J Radiol 2007;80:e24–e26. 313. Dieval C, Bonnet F, Mauclere S, et al. Multicentric Castleman disease: use of HHV8 viral load monitoring and positron emission tomography during follow-up. Leuk Lymphoma 2007;48:1881–1883. 314. Ferrozzi F, Tognini G, Spaggiari E, et al. Focal Castleman disease of the lung: MRI

989

Chapter 14 • Mediastinal and Aortic Disease

315.

316.

317.

318.

319. 320.

321.

322.

323.

324.

325. 326. 327.

328.

329.

330.

331.

332.

990

findings. Clin Imaging 2001;25: 400–402. Johkoh T, Müller NL, Ichikado K, et al. Intrathoracic multicentric Castleman disease: CT findings in 12 patients. Radiology 1998;209:477–481. Mallens WM, Nijhuis-Heddes JM, Bakker W. Calcified lymph node metastases in bronchioloalveolar carcinoma. Radiology 1986;161:103–104. Oguchi M, Higashi K, Taniguchi M, et al. Calcified mediastinal metastases from ovarian cancer imaged with Tc-99m MDP SPECT. Clin Nucl Med 1998;23:479–481. Lautin EM, Rosenblatt M, Friedman AC, et al. Calcification in non-Hodgkin lymphoma occurring before therapy: identification on plain films and CT. AJR Am J Roentgenol 1990;155:739–740. Panicek DM, Harty MP, Scicutella CJ, et al. Calcification in untreated mediastinal lymphoma. Radiology 1988;166:735–736. Levitt RG, Glazer HS, Roper CL, et al. Magnetic resonance imaging of mediastinal and hilar masses: comparison with CT. AJR Am J Roentgenol 1985;145:9–14. Gawne-Cain ML, Hansell DM. The pattern and distribution of calcified mediastinal lymph nodes in sarcoidosis and tuberculosis: a CT study. Clin Radiol 1996; 51:263–267. Groskin SA, Massi AF, Randall PA. Calcified hilar and mediastinal lymph nodes in an AIDS patient with Pneumocystis carinii infection. Radiology 1990;175:345–346. Radin DR, Baker EL, Klatt EC, et al. Visceral and nodal calcification in patients with AIDS-related Pneumocystis carinii infection. AJR Am J Roentgenol 1990;154: 27–31. Israel HL, Lenchner G, Steiner RM. Late development of mediastinal calcification in sarcoidosis. Am Rev Respir Dis 1981;124: 302–305. Jacobson G, Fleson B, Pendergrass EP. Eggshell calcifications in coal and metal miners. Semin Roentgenol 1967;2:276–282. Landay MJ, Rollins NK. Mediastinal histoplasmosis granuloma: evaluation with CT. Radiology 1989;172:657–659. Pombo F, Rodriguez E, Mato J, et al. Patterns of contrast enhancement of tuberculous lymph nodes demonstrated by computed tomography. Clin Radiol 1992; 46:13–17. Scatarige JC, Fishman EK, Kuhajda FP, et al. Low attenuation nodal metastases in testicular carcinoma. J Comput Assist Tomogr 1983;7:682–687. Yousem DM, Scatarige JC, Fishman EK, et al. Low-attenuation thoracic metastases in testicular malignancy. AJR Am J Roentgenol 1986;146:291–293. Hopper KD, Diehl LF, Cole BA, et al. The significance of necrotic mediastinal lymph nodes on CT in patients with newly diagnosed Hodgkin disease. AJR Am J Roentgenol 1990;155:267–270. Kim HY, Yi CA, Lee KS, et al. Nodal metastasis in non-small cell lung cancer: accuracy of 3.0-T MR imaging. Radiology 2008;246:596–604. Im JG, Song KS, Kang HS, et al. Mediastinal tuberculous lymphadenitis: CT manifestations. Radiology 1987;164: 115–119.

333. Müller NL, Webb WR, Gamsu G. Subcarinal lymph node enlargement: radiographic findings and CT correlation. AJR Am J Roentgenol 1985;145:15–19. 334. Cymbalista M, Waysberg A, Zacharias C, et al. CT demonstration of the 1996 AJCCUICC regional lymph node classification for lung cancer staging. RadioGraphics 1999;19:899–900 poster. 335. Müller NL, Webb WR, Gamsu G. Paratracheal lymphadenopathy: radiographic findings and correlation with CT. Radiology 1985;156:761–765. 336. Keats TE, Lipscomb GE, Betts CS 3rd. Mensuration of the arch of the azygos vein and its application to the study of cardiopulmonary disease. Radiology 1968;90:990–994. 337. Blank N, Castellino RA. Patterns of pleural reflections of the left superior mediastinum. Normal anatomy and distortions produced by adenopathy. Radiology 1972;102:585–589. 338. Patz EF Jr, Stark P, Shaffer K, et al. Identification of internal mammary lymph nodes: value of the frontal chest radiograph. J Thorac Imaging 1993;8: 81–84. 339. Ravenel JG, Erasmus JJ. Azygoesophageal recess. J Thorac Imaging 2002;17:219–226. 340. Yoon HK, Jung KJ, Han BK, et al. Mediastinal interfaces and lines in children: radiographic-CT correlation. Pediatr Radiol 2001;31:406–412. 341. Miller FH, Fitzgerald SW, Donaldson JS. CT of the azygoesophageal recess in infants and children. RadioGraphics 1993;13: 623–634. 342. Hammersley JR, Grum CM, Green RA. The correlation of subcarinal density visualized on plain chest roentgenograms with computed tomographic scans. Chest 1990; 97:869–872. 343. Kozuka T, Tomiyama N, Johkoh T, et al. Coronal multiplanar reconstruction view from isotropic voxel data sets obtained with multidetector-row CT: assessment of detection and size of mediastinal and hilar lymph nodes. Radiat Med 2003;21:23–27. 344. Nambu A, Kato S, Saito A, et al. Appearances of mediastinal and pulmonary hilar lymph nodes on thin-section CT: comparison with 5 mm slice thickness CT. Clin Imaging 2007;31: 375–378. 345. Cascade PN, Gross BH, Kazerooni EA, et al. Variability in the detection of enlarged mediastinal lymph nodes in staging lung cancer: a comparison of contrast – enhanced and unenhanced CT. AJR Am J Roentgenol 1998;170:927–931. 346. Patz EF Jr, Erasmus JJ, McAdams HP, et al. Lung cancer staging and management: comparison of contrast: enhanced and nonenhanced helical CT of the thorax. Radiology 1999;212:56–60. 347. Pfannenberg AC, Aschoff P, Brechtel K, et al. Low dose non-enhanced CT versus standard dose contrast-enhanced CT in combined PET/CT protocols for staging and therapy planning in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 2007;34:36–44. 348. Genereux GP, Howie JL. Normal mediastinal lymph node size and number: CT and anatomic study. AJR Am J Roentgenol 1984;142:1095–1100.

349. Glazer GM, Gross BH, Quint LE, et al. Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping. AJR Am J Roentgenol 1985;144:261–265. 350. Ingram CE, Belli AM, Lewars MD, et al. Normal lymph node size in the mediastinum: a retrospective study in two patient groups. Clin Radiol 1989;40:35–39. 351. Schnyder PA, Gamsu G. CT of the pretracheal retrocaval space. AJR Am J Roentgenol 1981;136:303–308. 352. Quint LE, Glazer GM, Orringer MB, et al. Mediastinal lymph node detection and sizing at CT and autopsy. AJR Am J Roentgenol 1986;147:469–472. 353. Nomori H, Watanabe K, Ohtsuka T, et al. The size of metastatic foci and lymph nodes yielding false-negative and false-positive lymph node staging with positron emission tomography in patients with lung cancer. J Thorac Cardiovasc Surg 2004;127:1087–1092. 354. Gould MK, Kuschner WG, Rydzak CE, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med 2003;139: 879–892. 355. Platt JF, Glazer GM, Orringer MB, et al. Radiologic evaluation of the subcarinal lymph nodes: a comparative study. AJR Am J Roentgenol 1988;151:279–282. 356. Kono M, Adachi S, Kusumoto M, et al. Clinical utility of Gd-DTPA-enhanced magnetic resonance imaging in lung cancer. J Thorac Imaging 1993;8:18–26. 357. Crisci R, Di Cesare E, Lupattelli L, et al. MR study of N2 disease in lung cancer: contrast-enhanced method using gadolinium-DTPA. Eur J Cardiothorac Surg 1997;11:214–217. 358. Nguyen BC, Stanford W, Thompson BH, et al. Multicenter clinical trial of ultrasmall superparamagnetic iron oxide in the evaluation of mediastinal lymph nodes in patients with primary lung carcinoma. J Magn Reson Imaging 1999;10:468–473. 359. Pannu HK, Wang KP, Borman TL, et al. MR imaging of mediastinal lymph nodes: evaluation using a superparamagnetic contrast agent. J Magn Reson Imaging 2000;12:899–904. 360. Choi SH, Moon WK, Hong JH, et al. Lymph node metastasis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging versus PET/CT in a rabbit model. Radiology 2007;242:137–143. 361. Nomori H, Mori T, Ikeda K, et al. Diffusion-weighted magnetic resonance imaging can be used in place of positron emission tomography for N staging of non-small cell lung cancer with fewer false-positive results. J Thorac Cardiovasc Surg 2008;135:816–822. 362. Mackie GC, Pohlen JM. Mediastinal histoplasmosis: F-18 FDG PET and CT findings simulating malignant disease. Clin Nucl Med 2005;30:633–635. 363. Yen RF, Chen KC, Lee JM, et al. (18)F-FDG PET for the lymph node staging of non-small cell lung cancer in a tuberculosis-endemic country: is dual time point imaging worth the effort? Eur J Nucl Med Mol Imaging 2008;35:1305– 1315.

References 364. Shim SS, Lee KS, Kim BT, et al. Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology 2005;236:1011–1019. 365. von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and future directions. Radiology 2006;238: 405–422. 366. Müller NL, Webb WR. Imaging of the pulmonary hila. Invest Radiol 1985;20:661– 671. 367. Park CK, Webb WR, Klein JS. Inferior hilar window. Radiology 1991;178:163–168. 368. Glazer GM, Francis IR, Shirazi KK, et al. Evaluation of the pulmonary hilum: comparison of conventional radiography, 55 degrees posterior oblique tomography, and dynamic computed tomography. J Comput Assist Tomogr 1983;7:983–989. 369. Remy-Jardin M, Duyck P, Remy J, et al. Hilar lymph nodes: identification with spiral CT and histologic correlation. Radiology 1995;196:387–394. 370. Armstrong P. Tomographic evaluation of the questionably enlarged pulmonary hilum. In: Armstrong P, ed. Critical problems in diagnostic radiology. Philadelphia: JB Lippincott, 1983. 371. Naidich DP, Khouri NF, Scott WW Jr, et al. Computed tomography of the pulmonary hila: 1. normal anatomy. J Comput Assist Tomogr 1981;5:459–467. 372. Naidich DP, Khouri NF, Stitik FP, et al. Computed tomography of the pulmonary hila: 2. abnormal anatomy. J Comput Assist Tomogr 1981;5:468–475. 373. Webb WR, Gamsu G, Glazer G. Computed tomography of the abnormal pulmonary hilum. J Comput Assist Tomogr 1981;5: 485–490. 374. Webb WR, Hirji M, Gamsu G. Posterior wall of the bronchus intermedius: radiographic-CT correlation. AJR Am J Roentgenol 1984;142:907–911. 375. Webb WR, Gamsu G. Computed tomography of the left retrobronchial stripe. J Comput Assist Tomogr 1983;7: 65–69. 376. Gotway MB, Patel RA, Webb WR. Helical CT for the evaluation of suspected acute pulmonary embolism: diagnostic pitfalls. J Comput Assist Tomogr 2000;24:267–273. 377. Webb WR, Gamsu G, Stark DD, et al. Magnetic resonance imaging of the normal and abnormal pulmonary hila. Radiology 1984;152:89–94. 378. Baker HL Jr, Berquist TH, Kispert DB, et al. Magnetic resonance imaging in a routine clinical setting. Mayo Clin Proc 1985;60: 75–90. 379. Buirski G, Jordan SC, Joffe HS, et al. Superior vena caval abnormalities: their occurrence rate, associated cardiac abnormalities and angiographic classification in a paediatric population with congenital heart disease. Clin Radiol 1986;37:131–138. 380. Glazer HS, Aronberg DJ, Sagel SS. Pitfalls in CT recognition of mediastinal lymphadenopathy. AJR Am J Roentgenol 1985;144:267–274. 381. Proto AV, Rost RC. CT of the thorax: pitfalls in interpretation. RadioGraphics 1985;5:693–712. 382. Kurihara Y, Nakajima Y, Ishikawa T. Case report: saccular aneurysm of the azygos

383.

384. 385.

386. 387.

388.

389.

390.

391.

392.

393.

394.

395.

396. 397.

398. 399.

400.

401.

402.

vein simulating a paratracheal tumour. Clin Radiol 1993;48:427–428. Mehta M, Towers M. Computed tomography appearance of idiopathic aneurysm of the azygos vein. Can Assoc Radiol J 1996;47:288–290. Podbielski FJ, Sam AD 2nd, Halldorsson AO, et al. Giant azygos vein varix. Ann Thorac Surg 1997;63:1167–1169. Burkill GJ, Burn PR, Padley SP. Aneurysm of the left brachiocephalic vein: an unusual cause of mediastinal widening. Br J Radiol 1997;70:837–839. Pasic M, Schopke W, Vogt P, et al. Aneurysm of the superior mediastinal veins. J Vasc Surg 1995;21:505–509. Rappaport DC, Ros PR, Moser RP Jr. Idiopathic dilatation of the thoracic venous system. Can Assoc Radiol J 1992;43: 385–387. Choi YW, McAdams HP, Jeon SC, et al. The ‘High-Riding’ superior pericardial recess: CT findings. AJR Am J Roentgenol 2000;175:1025–1028. Kodama F, Fultz PJ, Wandtke JC. Comparing thin-section and thick-section CT of pericardial sinuses and recesses. AJR Am J Roentgenol 2003;181:1101–1108. Davis J, Mark G, Green R. Benign blood vascular tumors of the mediastinum: report of four cases and review of the literature. Radiology 1987;126:581–587. Tarr RW, Page DL, Glick AG, et al. Benign hemangioendothelioma involving posterior mediastinum: CT findings. J Comput Assist Tomogr 1986;10:865–867. Hayashi A, Takamori S, Tayama K, et al. Primary hemangiopericytoma of the superior mediastinum: a case report. Ann Thorac Cardiovasc Surg 1998;4:283–285. Rubinowitz AN, Moreira AL, Naidich DP. Mediastinal hemangioendothelioma: radiologic–pathologic correlation. J Comput Assist Tomogr 2000;24:721–723. Angtuaco EJ, Jimenez JF, Burrows P, et al. Lymphatic-venous malformation (lymphangiohemangioma) of mediastinum. J Comput Assist Tomogr 1983;7:895–897. Riquet M, Briere J, Le Pimpec-Barthes F, et al. Lymphangiohemangioma of the mediastinum. Ann Thorac Surg 1997;64: 1476–1478. Toye R, Armstrong P, Dacie JE. Lymphangiohaemangioma of the mediastinum. Br J Radiol 1991;64:62–64. McAdams HP, Rosado-de-Christenson ML, Moran CA. Mediastinal hemangioma: radiographic and CT features in 14 patients. Radiology 1994;193:399–402. Cohen AJ, Sbaschnig RJ, Hochholzer L, et al. Mediastinal hemangiomas. Ann Thorac Surg 1987;43:656–659. Bedros AA, Munson J, Toomey FE. Hemangioendothelioma presenting as posterior mediastinal mass in a child. Cancer 1980;46:801–803. Kronthal AJ, Heitmiller RF, Fishman EK, et al. Mediastinal seroma after esophagogastrectomy. AJR Am J Roentgenol 1991;156:715–716. Buckner S, McAllister J, D’Altorio R. Case of the season. Hemangioma of the middle mediastinum. Semin Roentgenol 1994;29: 98–99. Schurawitzki H, Stiglbauer R, Klepetko W, et al. CT and MRI in benign mediastinal haemangioma. Clin Radiol 1991;43:91–94.

403. Seline TH, Gross BH, Francis IR. CT and MR imaging of mediastinal hemangiomas. J Comput Assist Tomogr 1990;14:766–768. 404. Erasmus JJ, McAdams HP, Donnelly LF, et al. MR imaging of mediastinal masses. Magn Reson Imaging Clin N Am 2000;8: 59–89. 405. Fishman SJ. Vascular anomalies of the mediastinum. Semin Pediatr Surg 1999;8: 92–98. 406. Yoo SY, Hong SH, Chung HW, et al. MRI of Gorham’s disease: findings in two cases. Skeletal Radiol 2002;31:301–306. 407. Yoo SY, Goo JM, Im JG. Mediastinal lymphangioma and chylothorax: thoracic involvement of Gorham’s disease. Korean J Radiol 2002;3:130–132. 408. Brown LR, Reiman HM, Rosenow EC 3rd, et al. Intrathoracic lymphangioma. Mayo Clin Proc 1986;61:882–892. 409. Halliday DR, Dahlin DC, Pugh DG. Massive osteolysis and angiomatosis. Radiology 1964;82:637–643. 410. Ellison RT 3rd, Corrao WM, Fox MJ, et al. Spontaneous mediastinal hemorrhage in patients on chronic hemodialysis. Ann Intern Med 1981;95:704–706. 411. Aalbers R, Piers B, Eygelaar A, et al. Sudden superior mediastinal enlargement. Chest 1991;99:209–210. 412. Bethancourt B, Pond GD, Jones SE, et al. Mediastinal hematoma simulating recurrent hodgkin disease during systemic chemotherapy. AJR Am J Roentgenol 1984;142:1119–1120. 413. Pezzulli FA, Aronson D, Goldberg N. Computed tomography of mediastinal hematoma secondary to unusual esophageal laceration: a Boerhaave variant. J Comput Assist Tomogr 1989;13:129–131. 414. Stilwell ME, Weisbrod GL, Ilves R. Spontaneous mediastinal hematoma. J Can Assoc Radiol 1981;32:60–61. 415. Woodring JH, Loh FK, Kryscio RJ. Mediastinal hemorrhage: an evaluation of radiographic manifestations. Radiology 1984;151:15–21. 416. Simeone JF, Minagi H, Putman CE. Traumatic disruption of the thoracic aorta: significance of the left apical extrapleural cap. Radiology 1975;117:265–268. 417. Panicek DM, Ewing DK, Markarian B, et al. Interstitial pulmonary hemorrhage from mediastinal hematoma secondary to aortic rupture. Radiology 1987;162:165–166. 418. Bradley WG Jr. MR appearance of hemorrhage in the brain. Radiology 1993; 189:15–26. 419. Burnett CM, Rosemurgy AS, Pfeiffer EA. Life-threatening acute posterior mediastinitis due to esophageal perforation. Ann Thorac Surg 1990;49:979–983. 420. Payne WS, Larson RH. Acute mediastinitis. Surg Clin North Am 1969;49:999–1009. 421. Levine TM, Wurster CF, Krespi YP. Mediastinitis occurring as a complication of odontogenic infections. Laryngoscope 1986;96:747–750. 422. Marty-Ane CH, Alauzen M, Alric P, et al. Descending necrotizing mediastinitis. Advantage of mediastinal drainage with thoracotomy. J Thorac Cardiovasc Surg 1994;107:55–61. 423. Novellas S, Kechabtia K, Chevallier P, et al. Descending necrotizing mediastinitis: a rare pathology to keep in mind. Clin Imaging 2005;29:138–140.

991

Chapter 14 • Mediastinal and Aortic Disease 424. Singhal P, Kejriwal N, Lin Z, et al. Optimal surgical management of descending necrotising mediastinitis: our experience and review of literature. Heart Lung Circ 2008;17:124–128. 425. Cirino LM, Elias FM, Almeida JL. Descending mediastinitis: a review. Sao Paulo Med J 2006;124:285–290. 426. Pollack MS. Staphylococcal mediastinitis due to sternoclavicular pyarthrosis: CT appearance. J Comput Assist Tomogr 1990;14:924–927. 427. Sjogren J, Malmsjo M, Gustafsson R, et al. Poststernotomy mediastinitis: a review of conventional surgical treatments, vacuum-assisted closure therapy and presentation of the Lund University Hospital mediastinitis algorithm. Eur J Cardiothorac Surg 2006;30:898–905. 428. Ablin DS, Reinhart MA. Esophageal perforation with mediastinal abscess in child abuse. Pediatr Radiol 1990;20: 524–525. 429. Breatnach E, Nath PH, Delany DJ. The role of computed tomography in acute and subacute mediastinitis. Clin Radiol 1986; 37:139–145. 430. Rogers LF, Puig AW, Dooley BN, et al. Diagnostic considerations in mediastinal emphysema: a pathophysiologicroentgenologic approach to Boerhaave’s syndrome and spontaneous pneumomediastinum. Am J Roentgenol Radium Ther Nucl Med 1972;115:495–511. 431. Carrol CL, Jeffrey RB, Federle MP. CT evaluation of mediastinal infections. J Comput Assist Tomog 1989;11:449–454. 432. Fields JM, Schwartz DS, Gosche J, et al. Idiopathic bilateral anterior mediastinal abscesses. Pediatr Radiol 1997;27:596–597. 433. White CS, Templeton PA, Attar S. Esophageal perforation: CT findings. AJR Am J Roentgenol 1993;160:767–770. 434. Gobien RP, Stanley JH, Gobien BS, et al. Percutaneous catheter aspiration and drainage of suspected mediastinal abscesses. Radiology 1984;151:69–71. 435. Kiernan PD, Hernandez A, Byrne WD, et al. Descending cervical mediastinitis. Ann Thorac Surg 1998;65:1483–1488. 436. Goodman LR, Kay HR, Teplick SK, et al. Complications of median sternotomy: computed tomographic evaluation. AJR Am J Roentgenol 1983;141:225–230. 437. Jolles H, Henry DA, Roberson JP, et al. Mediastinitis following median sternotomy: CT findings. Radiology 1996; 201:463–466. 438. Kay HR, Goodman LR, Teplick SK, et al. Use of computed tomography to assess mediastinal complications after median sternotomy. Ann Thorac Surg 1983;36:706–714. 439. Bitkover CY, Cederlund K, Aberg B, et al. Computed tomography of the sternum and mediastinum after median sternotomy. Ann Thorac Surg 1999;68:858–863. 440. Robicsek F. Postoperative sternomediastinitis. Am Surg 2000;66:184–192. 441. Boiselle PM, Mansilla AV. A closer look at the midsternal stripe sign. AJR Am J Roentgenol 2002;178:945–948. 442. Boiselle PM, Mansilla AV, Fisher MS, et al. Wandering wires: frequency of sternal wire abnormalities in patients with sternal dehiscence. AJR Am J Roentgenol 1999; 173:777–780.

992

443. Boiselle PM, Mansilla AV, White CS, et al. Sternal dehiscence in patients with and without mediastinitis. J Thorac Imaging 2001;16:106–110. 444. Carter AR, Sostman HD, Curtis AM, et al. Thoracic alterations after cardiac surgery. AJR Am J Roentgenol 1983;140:475–481. 445. Browdie DA, Bernstein RV, Agnew R, et al. Diagnosis of poststernotomy infection: comparison of three means of assessment. Ann Thorac Surg 1991;51:290–292. 446. Quirce R, Carril JM, GutierrezMendiguchia C, et al. Assessment of the diagnostic capacity of planar scintigraphy and SPECT with 99mTc-HMPAO-labelled leukocytes in superficial and deep sternal infections after median sternotomy. Nucl Med Commun 2002;23:453–459. 447. Rossi SE, McAdams HP, Rosado-deChristenson ML, et al. Fibrosing mediastinitis. RadioGraphics 2001;21: 737–757. 448. Goodwin RA, Nickell JA, Des Prez RM. Mediastinal fibrosis complicating healed primary histoplasmosis and tuberculosis. Medicine (Baltimore) 1972;51:227–246. 449. Loyd JE, Tillman BF, Atkinson JB, et al. Mediastinal fibrosis complicating histoplasmosis. Medicine (Baltimore) 1988; 67:295–310. 450. Davis AM, Pierson RN, Loyd JE. Mediastinal fibrosis. Semin Respir Infect 2001;16:119–130. 451. Mole TM, Glover J, Sheppard MN. Sclerosing mediastinitis: a report on 18 cases. Thorax 1995;50:280–283. 452. Hofmann-Wellenhof R, Domej W, Schmid C, et al. Mediastinal mass caused by syphilitic aortitis. Thorax 1993;48:568–569. 453. Kanne JP, Mohammed TL. Fibrosing mediastinitis associated with Behcet’s disease: CT findings. Clin Radiol 2007;62: 1124–1126. 454. Worrell JA, Donnelly EF, Martin JB, et al. Computed tomography and the idiopathic form of proliferative fibrosing mediastinitis. J Thorac Imaging 2007;22: 235–240. 455. Devaraj A, Griffin N, Nicholson AG, et al. Computed tomography findings in fibrosing mediastinitis. Clin Radiol 2007; 62:781–786. 456. Light AM. Idiopathic fibrosis of mediastinum: a discussion of three cases and review of the literature. J Clin Pathol 1978;31:78–88. 457. Flieder DB, Suster S, Moran CA. Idiopathic fibroinflammatory (fibrosing/sclerosing) lesions of the mediastinum: a study of 30 cases with emphasis on morphologic heterogeneity. Mod Pathol 1999;12: 257–264. 458. Ramakantan R, Shah P. Dysphagia due to mediastinal fibrosis in advanced pulmonary tuberculosis. AJR Am J Roentgenol 1990;154:61–63. 459. Goodwin RA, Loyd JE, Des Prez RM. Histoplasmosis in normal hosts. Medicine (Baltimore) 1981;60:231–266. 460. Kirchner SG, Hernanz-Schulman M, Stein SM, et al. Imaging of pediatric mediastinal histoplasmosis. RadioGraphics 1991;11: 365–381. 461. Christoforidis AJ. Radiologic manifestations of histoplasmosis. Am J Roentgenol Radium Ther Nucl Med 1970; 109:478–490.

462. Conces DJ Jr. Histoplasmosis. Semin Roentgenol 1996;31:14–27. 463. Connell JV, Muhm JR. Radiographic manifestations of pulmonary histoplasmosis: a 10-year review. Radiology 1976;121:281–285. 464. Feigin DS, Eggleston JC, Siegelman SS. The multiple roentgen manifestations of sclerosing mediastinitis. Johns Hopkins Med J 1979;144:1–8. 465. Kountz PD, Molina PL, Sagel SS. Fibrosing mediastinitis in the posterior thorax. AJR Am J Roentgenol 1989;153:489–490. 466. Wieder S, Rabinowitz JG. Fibrous mediastinitis: a late manifestation of mediastinal histoplasmosis. Radiology 1977;125:305–312. 467. Wieder S, White TJ 3rd, Salazar J, et al. Pulmonary artery occlusion due to histoplasmosis. AJR Am J Roentgenol 1982;138:243–251. 468. Sherrick AD, Brown LR, Harms GF, et al. The radiographic findings of fibrosing mediastinitis. Chest 1994;106:484–489. 469. Barnett SM. CT findings in tuberculous mediastinitis. J Comput Assist Tomogr 1986;10:165–166. 470. Rodriguez E, Soler R, Pombo F, et al. Fibrosing mediastinitis: CT and MR findings. Clin Radiol 1998;53:907–910. 471. Weinstein JB, Aronberg DJ, Sagel SS. CT of fibrosing mediastinitis: findings and their utility. AJR Am J Roentgenol 1983;141: 247–251. 472. Rholl KS, Levitt RG, Glazer HS. Magnetic resonance imaging of fibrosing mediastinitis. AJR Am J Roentgenol 1985;145:255–259. 473. Mallin WH, Silberstein EB, Shipley RT, et al. Fibrosing mediastinitis causing nonvisualization of one lung on pulmonary scintigraphy. Clin Nucl Med 1993;18: 594–596. 474. David RA, Weiner MA, Rakow JI. Chronic active mediastinitis in a 7-year-old boy: MRI findings. Pediatr Radiol 1996;26: 669–671. 475. Farmer DW, Moore E, Amparo E, et al. Calcific fibrosing mediastinitis: demonstration of pulmonary vascular obstruction by magnetic resonance imaging. AJR Am J Roentgenol 1984;143: 1189–1191. 476. Moreno AJ, Weismann I, Billingsley JL, et al. Angiographic and scintigraphic findings in fibrosing mediastinitis. Clin Nucl Med 1983;8:167–169. 477. Lee KY, Yi JG, Park JH, et al. Fibrosing mediastinitis manifesting as thoracic prevertebral thin band-like mass on MRI and PET-CT. Br J Radiol 2007;80:e141–e144. 478. Takalkar AM, Bruno GL, Makanjoula AJ, et al. A potential role for F-18 FDG PET/ CT in evaluation and management of fibrosing mediastinitis. Clin Nucl Med 2007;32:703–706. 479. Chong S, Kim TS, Kim BT, et al. Fibrosing mediastinitis mimicking malignancy at CT: negative FDG uptake in integrated FDG PET/CT imaging. Eur Radiol 2007;17: 1644–1646. 480. Thiessen R, Matzinger FR, Seely J, et al. Fibrosing mediastinitis: successful stenting of the pulmonary artery. Can Respir J 2008;15:41–44. 481. Pompeo E, Stella F, Ippoliti A, et al. Extra-anatomic bypass of the superior vena

References

482.

483. 484.

485.

486. 487. 488.

489. 490.

491.

492. 493. 494.

495. 496. 497. 498.

499.

500.

501. 502.

cava after successful stenting for fibrosing mediastinitis. J Thorac Cardiovasc Surg 2008;135:220–221, 221, e221. Ashizawa K, Hayashi K, Minami K, et al. CT and MR findings of posterior mediastinal panniculitis. J Comput Assist Tomogr 1997;21:324–326. Reeder LB. Neurogenic tumors of the mediastinum. Semin Thorac Cardiovasc Surg 2000;12:261–267. Topcu S, Alper A, Gulhan E, et al. Neurogenic tumours of the mediastinum: a report of 60 cases. Can Respir J 2000;7: 261–265. Lee JY, Lee KS, Han J, et al. Spectrum of neurogenic tumors in the thorax: CT and pathologic findings. J Comput Assist Tomogr 1999;23:399–406. Duwe BV, Sterman DH, Musani AI. Tumors of the mediastinum. Chest 2005; 128:2893–2909. Reed JC, Hallet KK, Feigin DS. Neural tumors of the thorax: subject review from the AFIP. Radiology 1978;126:9–17. Carey LS, Ellis FH, Good CA. Neurogenic tumors of the mediastinum: a clinicopathologic study. AJR Am J Roentgenol 1960;84:189–205. Chalmers AH, Armstrong P. Plexiform mediastinal neurofibromas. A report of two cases. Br J Radiol 1977;50:215–217. Gossios KJ, Guy RL. Case report: imaging of widespread plexiform neurofibromatosis. Clin Radiol 1993;47: 211–213. Aisner SC, Chakravarthy AK, Joslyn JN, et al. Bilateral granular cell tumors of the posterior mediastinum. Ann Thorac Surg 1988;46:688–689. Machida E, Haniuda M, Eguchi T, et al. Granular cell tumor of the mediastinum. Intern Med 2003;42:178–181. Gale AW, Jelihovsky T, Grant AF, et al. Neurogenic tumors of the mediastinum. Ann Thorac Surg 1974;17:434–443. Lonergan GJ, Schwab CM, Suarez ES, et al. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. RadioGraphics 2002;22:911– 934. Alterman K, Shueller EF. Maturation of neuroblastoma to ganglioneuroma. Am J Dis Child 1970;120:217–222. Alexander F. Neuroblastoma. Urol Clin North Am 2000;27:383–392, vii. Eklof O, Gooding CA. Intrathoracic neuroblastoma. Am J Roentgenol Radium Ther Nucl Med 1967;100:202–207. Bar-Ziv J, Nogrady MB. Mediastinal neuroblastoma and ganglioneuroma. The differentiation between primary and secondary involvement on the chest roentgenogram. Am J Roentgenol Radium Ther Nucl Med 1975;125:380–390. Filler RM, Traggis DG, Jaffe N, et al. Favorable outlook for children with mediastinal neuroblastoma. J Pediatr Surg 1972;7:136–143. Feinstein RS, Gatewood OM, Fishman EK, et al. Computed tomography of adult neuroblastoma. J Comput Assist Tomogr 1984;8:720–726. Ribet ME, Cardot GR. Neurogenic tumors of the thorax. Ann Thorac Surg 1994;58: 1091–1095. Tanabe M, Yoshida H, Ohnuma N, et al. Imaging of neuroblastoma in patients

503.

504.

505.

506.

507.

508.

509. 510.

511.

512.

513.

514.

515.

516.

517.

518.

519.

520.

identified by mass screening using urinary catecholamine metabolites. J Pediatr Surg 1993;28:617–621. Barrett AF, Toye DKM. Sympathicoblastoma: radiological findings in forty-three cases. Clin Radiol 1960; 14:33–42. Ko SF, Lee TY, Lin JW, et al. Thoracic neurilemomas: an analysis of computed tomography findings in 36 patients. J Thorac Imaging 1998;13:21–26. Coleman BG, Arger PH, Dalinka MK, et al. CT of sarcomatous degeneration in neurofibromatosis. AJR Am J Roentgenol 1983;140:383–387. Pilavaki M, Chourmouzi D, Kiziridou A, et al. Imaging of peripheral nerve sheath tumors with pathologic correlation: pictorial review. Eur J Radiol 2004;52:229– 239. Tanaka O, Kiryu T, Hirose Y, et al. Neurogenic tumors of the mediastinum and chest wall: MR imaging appearance. J Thorac Imaging 2005;20:316–320. Cohen LM, Schwartz AM, Rockoff SD. Benign schwannomas: pathologic basis for CT inhomogeneities. AJR Am J Roentgenol 1986;147:141–143. Moon WK, Im JG, Han MC. Malignant schwannomas of the thorax: CT findings. J Comput Assist Tomogr 1993;17:274–276. Armstrong EA, Harwood-Nash DC, Ritz CR, et al. CT of neuroblastomas and ganglioneuromas in children. AJR Am J Roentgenol 1982;139:571–576. Faerber EN, Carter BL, Sarno RC, et al. Computed tomography of neuroblastic tumors in children. Clin Pediatr (Phila) 1984;23:17–21. Ricci C, Rendina EA, Venuta F, et al. Diagnostic imaging and surgical treatment of dumbbell tumors of the mediastinum. Ann Thorac Surg 1990;50:586–589. Burk DL Jr, Brunberg JA, Kanal E, et al. Spinal and paraspinal neurofibromatosis: surface coil MR imaging at 1.5 T1. Radiology 1987;162:797–801. Freundlich IM, Chasen MH, Varma DG. Magnetic resonance imaging of pulmonary apical tumors. J Thorac Imaging 1996;11: 210–222. Suh JS, Abenoza P, Galloway HR, et al. Peripheral (extracranial) nerve tumors: correlation of MR imaging and histologic findings. Radiology 1992;183:341–346. Sakai F, Sone S, Kiyono K, et al. Intrathoracic neurogenic tumors: MR-pathologic correlation. AJR Am J Roentgenol 1992;159:279–283. Slovis TL, Meza MP, Cushing B, et al. Thoracic neuroblastoma: what is the best imaging modality for evaluating extent of disease? Pediatr Radiol 1997;27: 273–275. Shulkin BL, Hutchinson RJ, Castle VP, et al. Neuroblastoma: positron emission tomography with 2-[fluorine-18]-fluoro-2deoxy-D-glucose compared with metaiodobenzylguanidine scintigraphy. Radiology 1996;199:743–750. Boubaker A, Bischof Delaloye A. Nuclear medicine procedures and neuroblastoma in childhood. Their value in the diagnosis, staging and assessment of response to therapy. Q J Nucl Med 2003;47:31–40. Hamada K, Ueda T, Higuchi I, et al. Peripheral nerve schwannoma: two cases

521.

522.

523. 524.

525.

526.

527.

528.

529.

530.

531.

532.

533.

534.

535.

536.

537.

exhibiting increased FDG uptake in early and delayed PET imaging. Skeletal Radiol 2005;34:52–57. Beaulieu S, Rubin B, Djang D, et al. Positron emission tomography of schwannomas: emphasizing its potential in preoperative planning. AJR Am J Roentgenol 2004;182:971–974. Herrera MF, van Heerden JA, Puga FJ, et al. Mediastinal paraganglioma: a surgical experience. Ann Thorac Surg 1993;56:1096–1100. Suster S, Moran CA. Neuroendocrine neoplasms of the mediastinum. Am J Clin Pathol 2001;115 Suppl:S17–S27. Balcombe J, Torigian DA, Kim W, et al. Cross-sectional imaging of paragangliomas of the aortic body and other thoracic branchiomeric paraganglia. AJR Am J Roentgenol 2007;188:1054–1058. Olson JL, Salyer WR. Mediastinal paragangliomas (aortic body tumor): a report of four cases and a review of the literature. Cancer 1978;41:2405–2412. Banzo J, Prats E, Velilla J, et al. Functioning intrapericardial paraganglioma diagnosed by I-123 MIBG imaging. Clin Nucl Med 1991;16:860–861. Shapiro B, Sisson J, Kalff V, et al. The location of middle mediastinal pheochromocytomas. J Thorac Cardiovasc Surg 1984;87:814–820. Shirkhoda A, Wallace S. Computed tomography of juxtacardiac pheochromocytoma. J Comput Tomogr 1984;8:207–209. Habe RS. Retroperitoneal and mediastinal chemodectoma: report of a case and review of the literature. AJR Am J Roentgenol 1964;92:1029–1041. Castanon J, Gil-Aguado M, de la Llana R, et al. Aortopulmonary paraganglioma, a rare aortic tumor: a case report. J Thorac Cardiovasc Surg 1993;106:1232– 1233. Cornford EJ, Wastie ML, Morgan DA. Malignant paraganglioma of the mediastinum: a further diagnostic and therapeutic use of radiolabelled mIBG. Br J Radiol 1992;65:75–78. Francis IR, Glazer GM, Shapiro B, et al. Complementary roles of CT and 131IMIBG scintigraphy in diagnosing pheochromocytoma. AJR Am J Roentgenol 1983;141:719–725. Krenning EP, Kwekkeboom DJ, Bakker WH, et al. Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993;20:716–731. van Gils AP, Falke TH, van Erkel AR, et al. MR imaging and MIBG scintigraphy of pheochromocytomas and extraadrenal functioning paragangliomas. RadioGraphics 1991;11:37–57. Blandino A, Salvi L, Faranda C, et al. Unusual malignant paraganglioma of the anterior mediastinum: CT and MR findings. Eur J Radiol 1992;15:1–3. Andrade CF, Camargo SM, Zanchet M, et al. Nonfunctioning paraganglioma of the aortopulmonary window. Ann Thorac Surg 2003;75:1950–1951. Spector JA, Willis DN, Ginsburg HB. Paraganglioma (pheochromocytoma) of the posterior mediastinum: a case report and

993

Chapter 14 • Mediastinal and Aortic Disease

538. 539.

540.

541. 542.

543.

544.

545.

546.

547.

548.

549.

550.

551. 552.

553.

994

review of the literature. J Pediatr Surg 2003;38:1114–1116. Olsen WL, Dillon WP, Kelly WM, et al. MR imaging of paragangliomas. AJR Am J Roentgenol 1987;148:201–204. Satava RM Jr, Beahrs OH, Scholz DA. Success rate of cervical exploration for hyperparathyroidism. Arch Surg 1975;110: 625–628. Russell CF, Edis AJ, Scholz DA, et al. Mediastinal parathyroid tumors: experience with 38 tumors requiring mediastinotomy for removal. Ann Surg 1981;193:805–809. Norris EH. The parathyroid adenoma: a study of 322 cases. Int Abst Surg 1947;84: 1–41. Kang YS, Rosen K, Clark OH, et al. Localization of abnormal parathyroid glands of the mediastinum with MR imaging. Radiology 1993;189:137–141. Lossef SV, Ziessman HA, Alijani MR, et al. Multiple hyperfunctioning mediastinal parathyroid glands in a patient with tertiary hyperparathyroidism. AJR Am J Roentgenol 1993;161:285–286. Kaczirek K, Prager G, Kienast O, et al. Combined transmission and (99m) Tc-sestamibi emission tomography for localization of mediastinal parathyroid glands. Nuklearmedizin 2003;42:220–223. Itoh K, Ishizuka R. Tc-99m-MIBI scintigraphy for recurrent hyperparathyroidism after total parathyroidectomy with autograft. Ann Nucl Med 2003;17:315–320. Ishibashi M, Nishida H, Hiromatsu Y, et al. Localization of ectopic parathyroid glands using technetium-99m sestamibi imaging: comparison with magnetic resonance and computed tomographic imaging. Eur J Nucl Med 1997;24:197–201. Ishibashi M, Nishida H, Hiromatsu Y, et al. Comparison of technetium-99m-MIBI, technetium-99m-tetrofosmin, ultrasound and MRI for localization of abnormal parathyroid glands. J Nucl Med 1998;39: 320–324. Kelly JD, Forster AM, Higley B, et al. Technetium-99m-tetrofosmin as a new radiopharmaceutical for myocardial perfusion imaging. J Nucl Med 1993;34: 222–227. Lee VS, Spritzer CE, Coleman RE, et al. The complementary roles of fast spin-echo MR imaging and double-phase 99m Tc-sestamibi scintigraphy for localization of hyperfunctioning parathyroid glands. AJR Am J Roentgenol 1996;167: 1555–1562. Mariani G, Gulec SA, Rubello D, et al. Preoperative localization and radioguided parathyroid surgery. J Nucl Med 2003;44: 1443–1458. Singh N, Krishna BA. Role of radionuclide scintigraphy in the detection of parathyroid adenoma. Indian J Cancer 2007;44:12–16. Ansquer C, Mirallie E, Carlier T, et al. Preoperative localization of parathyroid lesions. Value of 99mTc-MIBI tomography and factors influencing detection. Nuklearmedizin 2008;47:158–162. Ruf J, Seehofer D, Denecke T, et al. Impact of image fusion and attenuation correction by SPECT-CT on the scintigraphic detection of parathyroid adenomas. Nuklearmedizin 2007;46:15–21.

554. Doppman JL, Skarulis MC, Chen CC, et al. Parathyroid adenomas in the aortopulmonary window. Radiology 1996; 201:456–462. 555. Spritzer CE, Gefter WB, Hamilton R, et al. Abnormal parathyroid glands: highresolution MR imaging. Radiology 1987; 162:487–491. 556. Shields TW, Immerman SC. Mediastinal parathyroid cysts revisited. Ann Thorac Surg 1999;67:581–590. 557. Hauet EJ, Paul MA, Salu MK. Compression of the trachea by a mediastinal parathyroid cyst. Ann Thorac Surg 1997;64:851–852. 558. Landau O, Chamberlain DW, Kennedy RS, et al. Mediastinal parathyroid cysts. Ann Thorac Surg 1997;63:951–953. 559. Soler R, Bargiela A, Cordido F. MRI of mediastinal cystic adenoma causing hyperparathyroidism. J Comput Assist Tomogr 1995;20:166–167. 560. Gray JM, Hanson GC. Mediastinal emphysema: aetiology, diagnosis, and treatment. Thorax 1966;21:325–332. 561. Munsell WP. Pneumomediastinum. A report of 28 cases and review of the literature. JAMA 1967;202:689–693. 562. Damore DT, Dayan PS. Medical causes of pneumomediastinum in children. Clin Pediatr (Phila) 2001;40:87–91. 563. Bejvan SM, Godwin JD. Pneumomediastinum: old signs and new signs. AJR Am J Roentgenol 1996;166: 1041–1048. 564. Hedlund GL, Wiatrak BJ, Pranikoff T. Pneumomediastinum as an early radiographic sign in membranous croup. AJR Am J Roentgenol 1998;170:55–56. 565. Sullivan TP, Pierson DJ. Pneumomediastinum after freebase cocaine use. AJR Am J Roentgenol 1997;168:84. 566. Gotway MB, Marder SR, Hanks DK, et al. Thoracic complications of illicit drug use: an organ system approach. RadioGraphics 2002;22:S119–S135. 567. LiPuma JP, Wellman J, Stern HP. Nitrous oxide abuse: a new cause of pneumomediastinum. Radiology 1982; 145:602. 568. Pauw RG, van der Werf TS, van Dullemen HM, et al. Mediastinal emphysema complicating diabetic ketoacidosis: plea for conservative diagnostic approach. Neth J Med 2007;65:368–371. 569. Fujiwara T. Pneumomediastinum in pulmonary fibrosis: detection by computed tomography. Chest 1993;104:44–46. 570. Jamadar DA, Kazerooni EA, Hirschl RB. Pneumomediastinum: elucidation of the anatomic pathway by liquid ventilation. J Comput Assist Tomogr 1996;20:309–311. 571. Girard DE, Carlson V, Natelson EA, et al. Pneumomediastinum in diabetic ketoacidosis: comments on mechanism, incidence, and management. Chest 1971; 60:455–459. 572. Chon KS, vanSonnenberg E, D’Agostino HB, et al. CT-guided catheter drainage of loculated thoracic air collections in mechanically ventilated patients with acute respiratory distress syndrome. AJR Am J Roentgenol 1999;173:1345–1350. 573. Dondelinger RF, Coulon M, Kurdziel JC, et al. Tension mediastinal emphysema: emergency percutaneous drainage with CT guidance. Eur J Radiol 1992;15:7–10.

574. Rohlfing BM, Webb WR, Schlobohm RM. Ventilator-related extra-alveolar air in adults. Radiology 1976;121:25–31. 575. Astigarraga E, Saez F, Canteli B, et al. Postmediastinoscopy changes in chest CT. J Comput Assist Tomogr 1994;18: 566–568. 576. Parker GS, Mosborg DA, Foley RW, et al. Spontaneous cervical and mediastinal emphysema. Laryngoscope 1990;100: 938–940. 577. Takahashi T, Hoshino Y, Nakamura T, et al. Mediastinal emphysema with Pneumocystis carinii pneumonia in AIDS. AJR Am J Roentgenol 1997;169:1465–1466. 578. Sutherland FW, Ho SY, Campanella C. Pneumomediastinum during spontaneous vaginal delivery. Ann Thorac Surg 2002;73: 314–315. 579. Sandler CM, Libshitz HI, Marks G. Pneumoperitoneum, pneumomediastinum and pneumopericardium following dental extraction. Radiology 1975;115:539–540. 580. Tomsick TA. Dental surgical subcutaneous and mediastinal emphysema: a case report. J Can Assoc Radiol 1974;25:49–51. 581. Stahl JD, Goldman SM, Minkin SD, et al. Perforated duodenal ulcer and pneumomediastinum. Radiology 1977;124: 23–25. 582. Beerman PJ, Gelfand DW, Ott DJ. Pneumomediastinum after double-contrast barium enema examination: a sign of colonic perforation. AJR Am J Roentgenol 1981;136:197–198. 583. Levin B. The continuous diaphragm sign. A newly-recognized sign of pneumomediastinum. Clin Radiol 1973;24: 337–338. 584. Friedman AC, Lautin EM, Rothenberg L. Mach bands and pneumomediastinum. J Can Assoc Radiol 1981;32:232–235. 585. Stark P, Eber CD, Jacobson F. Primary intrathoracic malignant mesenchymal tumors: pictorial essay. J Thorac Imaging 1994;9:148–155. 586. Gladish GW, Sabloff BM, Munden RF, et al. Primary thoracic sarcomas. RadioGraphics 2002;22:621–637. 587. Stark P, Smith DC, Watkins GE, et al. Primary intrathoracic extraosseous osteogenic sarcoma: report of three cases. Radiology 1990;174:725–726. 588. Ratto GB, Costa R, Alloisio A, et al. Mediastinal chondrosarcoma. Tumori 2004;90:151–153. 589. McDermott VG, Mackenzie S, Hendry GM. Case report: primary intrathoracic rhabdomyosarcoma: a rare childhood malignancy. Br J Radiol 1993;66:937–941. 590. Kaira K, Ishizuka T, Sunaga N, et al. Primary mediastinal synovial sarcoma: a report of 2 cases. J Comput Assist Tomogr 2008;32:238–241. 591. Leipsic JA, McAdams HP, Sporn TA. Follicular dendritic cell sarcoma of the mediastinum. AJR Am J Roentgenol 2007; 188:W554–W556. 592. Hirai S, Hamanaka Y, Mitsui N, et al. Surgical resection of primary liposarcoma of the anterior mediastinum. Ann Thorac Cardiovasc Surg 2008;14:38–41. 593. Phillips GW, Choong M. Chondrosarcoma presenting as an anterior mediastinal mass. Clin Radiol 1991;43:63–64. 594. Taki S, Kakuda K, Kakuma K, et al. Posterior mediastinal chordoma: MR

References

595. 596.

597. 598. 599.

600. 601.

602.

603.

604.

605.

606.

607.

608.

609.

610.

611.

612.

613.

614.

imaging findings. AJR Am J Roentgenol 1996;166:26–27. Murphy JM, Wallis F, Toland J, et al. CT and MRI appearances of a thoracic chordoma. Eur Radiol 1998;8:1677–1679. Parish JM, Marschke RF Jr, Dines DE, et al. Etiologic considerations in superior vena cava syndrome. Mayo Clin Proc 1981;56: 407–413. Wudel LJ Jr, Nesbitt JC. Superior vena cava syndrome. Curr Treat Options Oncol 2001;2:77–91. Zojer N, Ludwig H. Hematological emergencies. Ann Oncol 2007;18(suppl 1): i45–i48. Wilson LD, Detterbeck FC, Yahalom J. Clinical practice. Superior vena cava syndrome with malignant causes. N Engl J Med 2007;356:1862–1869. Mahajan V, Strimlan V, Ordstrand HS, et al. Benign superior vena cava syndrome. Chest 1975;68:32–35. Burney K, Young H, Barnard SA, et al. CT appearances of congential and acquired abnormalities of the superior vena cava. Clin Radiol 2007;62:837–842. Carter MM, Tarr RW, Mazer MJ, et al. The ‘aortic nipple’ as a sign of impending superior vena caval syndrome. Chest 1985; 87:775–777. Brown G, Husband JE. Mediastinal widening: a valuable radiographic sign of superior vena cava thrombosis. Clin Radiol 1993;47:415–420. Rice TW. Pleural effusions in superior vena cava syndrome: prevalence, characteristics, and proposed pathophysiology. Curr Opin Pulm Med 2007;13:324–327. Cihangiroglu M, Lin BH, Dachman AH. Collateral pathways in superior vena caval obstruction as seen on CT. J Comput Assist Tomogr 2001;25:1–8. Barek L, Lautin R, Ledor S, et al. Role of CT in the assessment of superior vena caval obstruction. J Comput Tomogr 1982;6:121–126. Bechtold RE, Wolfman NT, Karstaedt N, et al. Superior vena caval obstruction: detection using CT. Radiology 1985;157: 485–487. Moncada R, Cardella R, Demos TC, et al. Evaluation of superior vena cava syndrome by axial CT and CT phlebography. AJR Am J Roentgenol 1984;143:731–736. Eren S, Karaman A, Okur A. The superior vena cava syndrome caused by malignant disease. Imaging with multi-detector row CT. Eur J Radiol 2006;59:93–103. McMurdo KK, de Geer G, Webb WR, et al. Normal and occluded mediastinal veins: MR imaging. Radiology 1986;159: 33–38. Weinreb JC, Mootz A, Cohen JM. MRI evaluation of mediastinal and thoracic inlet venous obstruction. AJR Am J Roentgenol 1986;146:679–684. Li W, David V, Kaplan R, et al. Threedimensional low dose gadoliniumenhanced peripheral MR venography. J Magn Reson Imaging 1998;8: 630–633. Kim CY, Mirza RA, Bryant JA, et al. Central veins of the chest: evaluation with time-resolved MR angiography. Radiology 2008;247:558–566. Lin J, Zhou KR, Chen ZW, et al. Vena cava 3D contrast-enhanced MR venography: a

615. 616. 617.

618.

619. 620. 621.

622. 623.

624.

625.

626.

627.

628. 629. 630.

631. 632.

633.

pictorial review. Cardiovasc Intervent Radiol 2005;28:795–805. FitzGerald JM, Mayo JR, Miller RR, et al. Tuberculosis of the thymus. Chest 1992; 102:1604–1605. Freundlich IM, McGavran MH. Abnormalities of the thymus. J Thorac Imaging 1996;11:58–65. Hara M, McAdams HP, Vredenburgh JJ, et al. Thymic hyperplasia after high-dose chemotherapy and autologous stem cell transplantation: incidence and significance in patients with breast cancer. AJR Am J Roentgenol 1999;173:1341–1344. Francis IR, Glazer GM, Bookstein FL, et al. The thymus: reexamination of age-related changes in size and shape. AJR Am J Roentgenol 1985;145:249–254. Baron RL, Lee JK, Sagel SS, et al. Computed tomography of the normal thymus. Radiology 1982;142:121–125. de Geer G, Webb WR, Gamsu G. Normal thymus: assessment with MR and CT. Radiology 1986;158:313–317. Boothroyd AE, Hall-Craggs MA, Dicks-Mireaux C, et al. The magnetic resonance appearances of the normal thymus in children. Clin Radiol 1992;45: 378–381. Molina PL, Siegel MJ, Glazer HS. Thymic masses on MR imaging. AJR Am J Roentgenol 1990;155:495–500. Siegel MJ, Glazer HS, Wiener JI, et al. Normal and abnormal thymus in childhood: MR imaging. Radiology 1989; 172:367–371. Brink I, Reinhardt MJ, Hoegerle S, et al. Increased metabolic activity in the thymus gland studied with 18F-FDG PET: age dependency and frequency after chemotherapy. J Nucl Med 2001;42: 591–595. Lemaitre L, Marconi V, Avni F, et al. The sonographic evaluation of normal thymus in infants and children. Eur J Radiol 1987; 7:130–136. Carty H. Ultrasound of the normal thymus in the infant: a simple method of resolving a clinical dilemma. Br J Radiol 1990;63: 737–738. Han BK, Babcock DS, Oestreich AE. Normal thymus in infancy: sonographic characteristics. Radiology 1989;170: 471–474. Baron RL, Lee JK, Sagel SS, et al. Computed tomography of the abnormal thymus. Radiology 1982;142:127–134. Franken EA. Radiologic evidence of thymic enlargement in Grave’s disease. Radiology 1969;91:20–22. Wortsman J, McConnachie P, Baker JR Jr, et al. Immunoglobulins that cause thymocyte proliferation from a patient with Graves’ disease and an enlarged thymus. Am J Med 1988;85:117–121. Rosenow EC 3rd, Hurley BT. Disorders of the thymus. A review. Arch Intern Med 1984;144:763–770. Arliss J, Scholes J, Dickson PR, et al. Massive thymic hyperplasia in an adolescent. Ann Thorac Surg 1988;45: 220–222. Nicolaou S, Müller NL, Li DK, et al. Thymus in myasthenia gravis: comparison of CT and pathologic findings and clinical outcome after thymectomy. Radiology 1996;201:471–474.

634. Batra P, Herrmann C Jr, Mulder D. Mediastinal imaging in myasthenia gravis: correlation of chest radiography, CT, MR, and surgical findings. AJR Am J Roentgenol 1987;148:515–519. 635. Goldberg RE, Haaga JR, Yulish BS. Serial CT scans in thymic hyperplasia. J Comput Assist Tomog 1988;11:539–540. 636. Brown LR, Muhm JR, Sheedy PF 2nd, et al. The value of computed tomography in myasthenia gravis. AJR Am J Roentgenol 1983;140:31–35. 637. Fon GT, Bein ME, Mancuso AA, et al. Computed tomography of the anterior mediastinum in myasthenia gravis. A radiologic-pathologic correlative study. Radiology 1982;142:135–141. 638. Liu RS, Yeh SH, Huang MH, et al. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of thymoma: a preliminary report. Eur J Nucl Med 1995;22:1402–1407. 639. El-Bawab H, Al-Sugair AA, Rafay M, et al. Role of flourine-18 fluorodeoxyglucose positron emission tomography in thymic pathology. Eur J Cardiothorac Surg 2007; 31:731–736. 640. Ferdinand B, Gupta P, Kramer EL. Spectrum of thymic uptake at 18F-FDG PET. RadioGraphics 2004;24:1611–1616. 641. Choyke PL, Zeman RK, Gootenberg JE, et al. Thymic atrophy and regrowth in response to chemotherapy: CT evaluation. AJR Am J Roentgenol 1987;149:269–272. 642. Hendrickx P, Dohring W. Thymic atrophy and rebound enlargement following chemotherapy for testicular cancer. Acta Radiol 1989;30:263–267. 643. Abildgaard A, Lien HH, Fossa SD, et al. Enlargement of the thymus following chemotherapy for non-seminomatous testicular cancer. Acta Radiol 1989;30: 259–262. 644. Kissin CM, Husband JE, Nicholas D, et al. Benign thymic enlargement in adults after chemotherapy: CT demonstration. Radiology 1987;163:67–70. 645. Due W, Dieckmann KP, Stein H. Thymic hyperplasia following chemotherapy of a testicular germ cell tumor. Immunohistological evidence for a simple rebound phenomenon. Cancer 1989;63: 446–449. 646. Willich E. Clinical features of thymic hyperplasia. In: Willich E, Webb WR (eds). The thymus: diagnostic imaging, functions and pathologic anatomy. Berlin: SpringerVerlag, 1992. 647. Chertoff J, Barth RA, Dickerman JD. Rebound thymic hyperplasia five years after chemotherapy for Wilms’ tumor. Pediatr Radiol 1991;21:596–597. 648. Caffey J, Silbey R. Regrowth and overgrowth of the thymus after atrophy induced by the oral administration of adrenocorticosteroids to human infants. Pediatrics 1960;26:762–770. 649. Doppman JL, Oldfield EH, Chrousos GP, et al. Rebound thymic hyperplasia after treatment of Cushing’s syndrome. AJR Am J Roentgenol 1986;147:1145–1147. 650. Gelfand DW, Goldman AS, Law EJ, et al. Thymic hyperplasia in children recovering from thermal burns. J Trauma 1972;12: 813–817. 651. Rizk G, Cueto L, Amplatz K. Rebound enlargement of the thymus after successful

995

Chapter 14 • Mediastinal and Aortic Disease

652.

653.

654. 655. 656.

657.

658.

659.

660.

661. 662. 663.

664.

665. 666.

667.

668. 669.

996

corrective surgery for transposition of the great vessels. Am J Roentgenol Radium Ther Nucl Med 1972;116:528–530. Wenger MC, Cohen AJ, Greensite F. Thymic rebound in a patient with scrotal mesothelioma. J Thorac Imaging 1994;9:145–147. Cohen M, Hill CA, Cangir A, et al. Thymic rebound after treatment of childhood tumors. AJR Am J Roentgenol 1980;135: 151–156. Luker GD, Siegel MJ. Mediastinal Hodgkin disease in children: response to therapy. Radiology 1993;189:737–740. Foulner D. Case report: transient thymic calcification: association with rebound enlargement. Clin Radiol 1991;44:428–429. Small EJ, Venook AP, Damon LE. Galliumavid thymic hyperplasia in an adult after chemotherapy for Hodgkin disease. Cancer 1993;72:905–908. Rettenbacher L, Galvan G. Differentiation between residual cancer and thymic hyperplasia in malignant non-Hodgkin’s lymphoma with somatostatin receptor scintigraphy. Clin Nucl Med 1994;19: 64–65. Ford EG, Lockhart SK, Sullivan MP, et al. Mediastinal mass following chemotherapeutic treatment of Hodgkin’s disease: recurrent tumor or thymic hyperplasia? J Pediatr Surg 1987;22: 1155–1159. Wittram C, Fischman AJ, Mark E, et al. Thymic enlargement and FDG uptake in three patients: CT and FDG positron emission tomography correlated with pathology. AJR Am J Roentgenol 2003;180: 519–522. Marchevsky AM, Gupta R, McKenna RJ, et al. Evidence-based pathology and the pathologic evaluation of thymomas: the World Health Organization classification can be simplified into only 3 categories other than thymic carcinoma. Cancer 2008; 112:2780–2788. Detterbeck FC. Clinical value of the WHO classification system of thymoma. Ann Thorac Surg 2006;81:2328–2334. Suster S, Moran CA. Thymoma classification: current status and future trends. Am J Clin Pathol 2006;125:542–554. Jeong YJ, Lee KS, Kim J, et al. Does CT of thymic epithelial tumors enable us to differentiate histologic subtypes and predict prognosis? AJR Am J Roentgenol 2004;183:283–289. Masaoka A, Monden Y, Nakahara K, et al. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48:2485–2492. Strollo DC, Rosado-de-Christenson ML. Tumors of the thymus. J Thorac Imaging 1999;14:152–171. Rosado-de-Christenson ML, Galobardes J, Moran CA. Thymoma: radiologicpathologic correlation. RadioGraphics 1992;12:151–168. Tan A, Holdener GP, Hecht A, et al. Malignant thymoma in an ectopic thymus: CT appearance. J Comput Assist Tomogr 1991;15:842–844. Cooper GN Jr, Narodick BG. Posterior mediastinal thymoma: case report. J Thorac Cardiovasc Surg 1972;63:561–563. Souadjian JV, Enriquez P, Silverstein MN, et al. The spectrum of diseases associated

670.

671.

672.

673.

674.

675. 676.

677.

678.

679. 680.

681. 682. 683.

684.

685.

686. 687.

with thymoma. Coincidence or syndrome? Arch Intern Med 1974;134:374–379. Papatestas AE, Alpert LI, Osserman KE, et al. Studies in myasthenia gravis: effects of thymectomy. Results on 185 patients with nonthymomatous and thymomatous myasthenia gravis, 1941–1969. Am J Med 1971;50:465–474. Moore AV, Korobkin M, Powers B, et al. Thymoma detection by mediastinal CT: patient with myasthenia gravis. AJR Am J Roentgenol 1982;138:217–222. Monden Y, Nakahara K, Kagotani K, et al. Myasthenia gravis with thymoma: analysis of and postoperative prognosis for 65 patients with thymomatous myasthenia gravis. Ann Thorac Surg 1984;38:46–52. Fox MA, Lynch DA, Make BJ. Thymoma with hypogammaglobulinemia (Good’s syndrome): an unusual cause of bronchiectasis. AJR Am J Roentgenol 1992;158:1229–1230. Tsai YG, Lai JH, Kuo SY, et al. Thymoma and hypogammaglobulinemia (Good’s syndrome): a case report. J Microbiol Immunol Infect 2005;38:218–220. Morgenthaler TI, Brown LR, Colby TV, et al. Thymoma. Mayo Clin Proc 1993;68: 1110–1123. Sakai F, Sone S, Kiyono K, et al. MR imaging of thymoma: radiologic-pathologic correlation. AJR Am J Roentgenol 1992; 158:751–756. Sadohara J, Fujimoto K, Müller NL, et al. Thymic epithelial tumors: comparison of CT and MR imaging findings of low-risk thymomas, high-risk thymomas, and thymic carcinomas. Eur J Radiol 2006;60: 70–79. Moran CA, Travis WD, Rosado-deChristenson M, et al. Thymomas presenting as pleural tumors. Report of eight cases. Am J Surg Pathol 1992;16: 138–144. Lee JD, Choe KO, Kim SJ, et al. CT findings in primary thymic carcinoma. J Comput Assist Tomogr 1991;15:429–433. Hsu CP, Chen CY, Chen CL, et al. Thymic carcinoma. Ten years’ experience in twenty patients. J Thorac Cardiovasc Surg 1994; 107:615–620. Lewis JE, Wick MR, Scheithauer BW, et al. Thymoma. A clinicopathologic review. Cancer 1987;60:2727–2743. Wick MR, Scheithauer BW, Weiland LH, et al. Primary thymic carcinomas. Am J Surg Pathol 1982;6:613–630. Negron-Soto JM, Cascade PN. Squamous cell carcinoma of the thymus with paraneoplastic hypercalcemia. Clin Imaging 1995;19:122–124. Do YS, Im JG, Lee BH, et al. CT findings in malignant tumors of thymic epithelium. J Comput Assist Tomogr 1995;19:192– 197. Kushihashi T, Fujisawa H, Munechika H. Magnetic resonance imaging of thymic epithelial tumors. Crit Rev Diagn Imaging 1996;37:191–259. Spedini P, D’Adda M, Blanzuoli L. Thymoma and pancytopenia: a very rare association. Haematologica 2002;87:EIM18. Tuncer Elmaci N, Ratip S, Ince-Gunal D, et al. Myasthenia gravis with thymoma and autoimmune haemolytic anaemia. A case report. Neurol Sci 2003;24:34–36.

688. Newsom-Davis J. Therapy in myasthenia gravis and Lambert-Eaton myasthenic syndrome. Semin Neurol 2003;23:191–198. 689. Vernino S, Cheshire WP, Lennon VA. Myasthenia gravis with autoimmune autonomic neuropathy. Auton Neurosci 2001;88:187–192. 690. Evoli A, Lo Monaco M, Marra R, et al. Multiple paraneoplastic diseases associated with thymoma. Neuromuscul Disord 1999;9:601–603. 691. Weissel M, Mayr N, Zeitlhofer J. Clinical significance of autoimmune thyroid disease in myasthenia gravis. Exp Clin Endocrinol Diabetes 2000;108:63–65. 692. Bosch EP, Reith PE, Granner DK. Myasthenia gravis and Schmidt syndrome. Neurology 1977;27:1179–1180. 693. Christensen PB, Jensen TS, Tsiropoulos I, et al. Associated autoimmune diseases in myasthenia gravis. A population-based study. Acta Neurol Scand 1995;91: 192–195. 694. Barbosa RE, Cordova S, Cajigas JC. Coexistence of systemic lupus erythematosus and myasthenia gravis. Lupus 2000;9:156–157. 695. Mais DD, Mulhall BP, Adolphson KR, et al. Thymoma-associated autoimmune enteropathy. A report of two cases. Am J Clin Pathol 1999;112:810–815. 696. Lowry PW, Myers JD, Geller A, et al. Graft-versus-host-like colitis and malignant thymoma. Dig Dis Sci 2002;47:1998–2001. 697. Lasseur C, Combe C, Deminiere C, et al. Thymoma associated with myasthenia gravis and minimal lesion nephrotic syndrome. Am J Kidney Dis 1999;33:e4. 698. Di Cataldo A, Villari L, Milone P, et al. Thymic carcinoma, systemic lupus erythematosus, and hypertrophic pulmonary osteoarthropathy in an 11-year-old boy: a novel association. Pediatr Hematol Oncol 2000;17:701–706. 699. Tomiyama N, Johkoh T, Mihara N, et al. Using the World Health Organization Classification of thymic epithelial neoplasms to describe CT findings. AJR Am J Roentgenol 2002;179:881–886. 700. Lastoria S, Palmieri G, Muto P, et al. Functional imaging of thymic disorders. Ann Med 1999;31(suppl 2):63–69. 701. Ohta H, Taniguchi T, Watanabe H. T1-201 and Tc-99m HMPAO SPECT in a patient with recurrent thymoma. Clin Nucl Med 1996;21:902–903. 702. Hashimoto T, Goto K, Hishinuma Y, et al. Uptake of 99mTc-tetrofosmin, 99mTc-MIBI and 201Tl in malignant thymoma. Ann Nucl Med 2000;14:293–298. 703. Hashimoto T, Takahashi K, Goto M, et al. Tc-99m tetrofosmin uptake of malignant thymoma in primary tumor and metastatic lesions. Clin Nucl Med 2001;26:562–564. 704. Kubota K, Yamada S, Kondo T, et al. PET imaging of primary mediastinal tumours. Br J Cancer 1996;73:882–886. 705. Sasaki M, Kuwabara Y, Ichiya Y, et al. Differential diagnosis of thymic tumors using a combination of 11C-methionine PET and FDG PET. J Nucl Med 1999;40: 1595–1601. 706. Lastoria S, Vergara E, Palmieri G, et al. In vivo detection of malignant thymic masses by indium-111-DTPA-D-Phe1-octreotide scintigraphy. J Nucl Med 1998;39: 634–639.

References 707. Srirajaskanthan R, Toubanakis C, Dusmet M, et al. A review of thymic tumours. Lung Cancer 2008;60:4–13. 708. Kurup A, Loehrer PJ Sr. Thymoma and thymic carcinoma: therapeutic approaches. Clin Lung Cancer 2004;6:28–32. 709. Evans TL, Lynch TJ. Role of chemotherapy in the management of advanced thymic tumors. Semin Thorac Cardiovasc Surg 2005;17:41–50. 710. Heron CW, Husband JE, Williams MP. Hodgkin disease: CT of the thymus. Radiology 1988;167:647–651. 711. Wernecke K, Vassallo P, Rutsch F, et al. Thymic involvement in Hodgkin disease: CT and sonographic findings. Radiology 1991;181:375–383. 712. Federle MP, Callen PW. Cystic Hodgkin’s lymphoma of the thymus: computed tomography appearance. J Comput Assist Tomogr 1979;3:542–544. 713. Spiers AS, Husband JE, MacVicar AD. Treated thymic lymphoma: comparison of MR imaging with CT. Radiology 1997;203: 369–376. 714. Jerusalem G, Beguin Y, Fassotte MF, et al. Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin’s disease. Ann Oncol 2003;14:123–130. 715. Bangerter M, Kotzerke J, Griesshammer M, et al. Positron emission tomography with 18-fluorodeoxyglucose in the staging and follow-up of lymphoma in the chest. Acta Oncol 1999;38:799–804. 716. Rosado de Christenson ML, Abbott GF, Kirejczyk WM, et al. Thoracic carcinoids: radiologic-pathologic correlation. RadioGraphics 1999;19:707–736. 717. Klemm KM, Moran CA. Primary neuroendocrine carcinomas of the thymus. Semin Diagn Pathol 1999;16:32–41. 718. Klemm KM, Moran CA, Suster S. Pigmented thymic carcinoids: a clinicopathological and immunohistochemical study of two cases. Mod Pathol 1999;12:946–948. 719. Chaer R, Massad MG, Evans A, et al. Primary neuroendocrine tumors of the thymus. Ann Thorac Surg 2002;74: 1733–1740. 720. Blunt SB, Sandler LM, Burrin JM, et al. An evaluation of the distinction of ectopic and pituitary ACTH dependent Cushing’s syndrome by clinical features, biochemical tests and radiological findings. Q J Med 1990;77:1113–1133. 721. Doppman JL, Nieman L, Miller DL, et al. Ectopic adrenocorticotropic hormone syndrome: localization studies in 28 patients. Radiology 1989;172:115–124. 722. Jex RK, van Heerden JA, Carpenter PC, et al. Ectopic ACTH syndrome. Diagnostic and therapeutic aspects. Am J Surg 1985; 149:276–282. 723. Vincent JM, Trainer PJ, Reznek RH, et al. The radiological investigation of occult ectopic ACTH-dependent Cushing’s syndrome. Clin Radiol 1993;48:11–17. 724. Gibril F, Chen YJ, Schrump DS, et al. Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 2003;88: 1066–1081. 725. Teh BT. Thymic carcinoids in multiple endocrine neoplasia type 1. J Intern Med 1998;243:501–504.

726. de Montpreville VT, Macchiarini P, Dulmet E. Thymic neuroendocrine carcinoma (carcinoid): a clinicopathologic study of fourteen cases. J Thorac Cardiovasc Surg 1996;111:134–141. 727. Wang DY, Chang DB, Kuo SH, et al. Carcinoid tumours of the thymus. Thorax 1994;49:357–360. 728. Brown LR, Aughenbaugh GL, Wick MR, et al. Roentgenologic diagnosis of primary corticotropin-producing carcinoid tumors of the mediastinum. Radiology 1982;142: 143–148. 729. Cadigan DG, Hollett PD, Collingwood PW, et al. Imaging of a mediastinal thymic carcinoid tumor with radiolabeled somatostatin analogue. Clin Nucl Med 1996;21:487–488. 730. Hirano T, Otake H, Watanabe N, et al. Presurgical diagnosis of a primary carcinoid tumor of the thymus with MIBG. J Nucl Med 1995;36:2243–2245. 731. Tonami N, Yokoyama K, Nonomura A, et al. Intense accumulation of Tl-201 in carcinoid tumor of the thymus. Clin Nucl Med 1994;19:408–412. 732. Markou A, Manning P, Kaya B, et al. [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography imaging of thymic carcinoid tumor presenting with recurrent Cushing’s syndrome. Eur J Endocrinol 2005;152:521–525. 733. Whitaker D, Dussek J. PET scanning in thymic neuroendocrine tumors. Chest 2004;125:2368–2369. 734. Casullo J, Palayew MJ, Lisbona A. General case of the day. Thymolipoma. RadioGraphics 1992;12:1250–1254. 735. Rosado-de-Christenson ML, Pugatch RD, Moran CA, et al. Thymolipoma: analysis of 27 cases. Radiology 1994;193: 121–126. 736. Otto HF, Loning T, Lachenmayer L, et al. Thymolipoma in association with myasthenia gravis. Cancer 1982;50: 1623–1628. 737. Pan CH, Chiang CY, Chen SS. Thymolipoma in patients with myasthenia gravis: report of two cases and review. Acta Neurol Scand 1988;78:16–21. 738. Damadoglu E, Salturk C, Takir HB, et al. Mediastinal thymolipoma: an analysis of 10 cases. Respirology 2007;12:924–927. 739. Shirkhoda A, Chasen MH, Eftekhari F, et al. MR imaging of mediastinal thymolipoma. J Comput Assist Tomogr 1987;11:364–365. 740. Haddad H, Joudeh A, El-Taani H, et al. Thymoma and thymic carcinoma arising in a thymolipoma: report of a unique case. Int J Surg Pathol 2009;17:55–59. 741. Chew FS, Weissleder R. Mediastinal thymolipoma. AJR Am J Roentgenol 1991;157:468. 742. Teplick JG, Nedwich A, Haskin ME. Roentgenographic features of thymolipoma. Am J Roentgenol Radium Ther Nucl Med 1973;117:873–880. 743. Moran CA, Rosado-de-Christenson M, Suster S. Thymolipoma: clinicopathologic review of 33 cases. Mod Pathol 1995;8: 741–744. 744. Kim JH, Goo JM, Lee HJ, et al. Cystic tumors in the anterior mediastinum. Radiologic-pathological correlation. J Comput Assist Tomogr 2003;27: 714–723.

745. Sltzer RA, Mills DS, Baddock SS, et al. Mediastinal thymic cyst. Dis Chest 1968;53: 186–196. 746. Gonullu U, Gungor A, Savas I, et al. Huge thymic cysts. J Thorac Cardiovasc Surg 1996;112:835–836. 747. Barrick B, O’Kell RT. Thymic cysts and remnant cervical thymus. J Pediatr Surg 1969;4:355–358. 748. Graeber GM, Thompson LD, Cohen DJ, et al. Cystic lesion of the thymus. An occasionally malignant cervical and/or anterior mediastinal mass. J Thorac Cardiovasc Surg 1984;87:295–300. 749. Sirivella S, Gielchinsky I, Parsonnet V. Mediastinal thymic cysts: a report of three cases. J Thorac Cardiovasc Surg 1995;110: 1771–1772. 750. Chalaoui J, Samson L, Robillard P, et al. Cases of the day. General. Benign thymic cyst complicated by hemorrhage. RadioGraphics 1990;10:957–958. 751. Moskowitz PS, Noon MA, McAlister WH, et al. Thymic cyst hemorrhage: a cause of acute, symptomatic mediastinal widening in children with aplastic anemia. AJR Am J Roentgenol 1980;134:832–836. 752. Gouliamos A, Striggaris K, Lolas C, et al. Thymic cyst. J Comput Assist Tomogr 1982;6:172–174. 753. Merine DS, Fishman EK, Zerhouni EA. Computed tomography and magnetic resonance imaging diagnosis of thymic cyst. J Comput Tomogr 1988;12:220–222. 754. Murayama S, Murakami J, Watanabe H, et al. Signal intensity characteristics of mediastinal cystic masses on T1-weighted MRI. J Comput Assist Tomogr 1995;19: 188–191. 755. Lindfors KK, Meyer JE, Dedrick CG, et al. Thymic cysts in mediastinal Hodgkin disease. Radiology 1985;156:37–41. 756. Dyer NH. Cystic thymomas and thymic cysts. A review. Thorax 1967;22:408–421. 757. Baron RL, Sagel SS, Baglan RJ. Thymic cysts following radiation therapy for Hodgkin disease. Radiology 1981;141: 593–597. 758. Wong-You-Cheong J, Radford JA. Case report: enlargement of a mediastinal mass during treatment for Hodgkin’s disease may be due to accumulation of fluid within thymic cysts. Clin Radiol 1995;50:61–62. 759. Veeze-Kuijpers B, Van Andel JG, Stiegelis WF, et al. Benign thymic cyst following mantle radiotherapy for Hodgkin’s disease. Clin Radiol 1987;38:289–290. 760. Kim HC, Nosher J, Haas A, et al. Cystic degeneration of thymic Hodgkin’s disease following radiation therapy. Cancer 1985;55:354–356. 761. Avila NA, Mueller BU, Carrasquillo JA, et al. Multilocular thymic cysts: imaging features in children with human immunodeficiency virus infection. Radiology 1996;201:130–134. 762. Leonidas JC, Berdon WE, Valderrama E, et al. Human immunodeficiency virus infection and multilocular thymic cysts. Radiology 1996;198:377–379. 763. Mercado-Deane MG, Sabio H, Burton EM, et al. Cystic thymic hyperplasia in a child with HIV infection: imaging findings. AJR Am J Roentgenol 1996;166:171–172. 764. Mishalani SH, Lones MA, Said JW. Multilocular thymic cyst. A novel thymic lesion associated with human

997

Chapter 14 • Mediastinal and Aortic Disease

765.

766.

767.

768. 769.

770. 771. 772.

773.

774.

775.

776.

777. 778. 779.

780.

781.

782. 783.

998

immunodeficiency virus infection. Arch Pathol Lab Med 1995;119:467–470. Shalaby-Rana E, Selby D, Ivy P, et al. Multilocular thymic cyst in a child with acquired immunodeficiency syndrome. Pediatr Infect Dis J 1996;15:83–86. Jaramillo D, Perez-Atayde A, Griscom NT. Apparent association between thymic cysts and prior thoracotomy. Radiology 1989; 172:207–209. Choi YW, McAdams HP, Jeon SC, et al. Idiopathic multilocular thymic cyst: CT features with clinical and histopathologic correlation. AJR Am J Roentgenol 2001; 177:881–885. Glazer GM, Axel L, Moss AA. CT diagnosis of mediastinal thyroid. AJR Am J Roentgenol 1982;138:495–498. Morris UL, Colletti PM, Ralls PW, et al. CT demonstration of intrathoracic thyroid tissue. J Comput Assist Tomogr 1982;6: 821–824. Bashist B, Ellis K, Gold RP. Computed tomography of intrathoracic goiters. AJR Am J Roentgenol 1983;140:455–460. Higgins CB, McNamara MT, Fisher MR, et al. MR imaging of the thyroid. AJR Am J Roentgenol 1986;147:1255–1261. Gefter WB, Spritzer CE, Eisenberg B, et al. Thyroid imaging with high-field-strength surface-coil MR. Radiology 1987;164: 483–490. Higgins CB, Auffermann W. MR imaging of thyroid and parathyroid glands: a review of current status. AJR Am J Roentgenol 1988;151:1095–1106. Hall TS, Caslowitz P, Popper C, et al. Substernal goiter versus intrathoracic aberrant thyroid: a critical difference. Ann Thorac Surg 1988;46:684–685. Sand J, Pehkonen E, Mattila J, et al. Pulsating mass at the sternum: a primary carcinoma of ectopic mediastinal thyroid. J Thorac Cardiovasc Surg 1996;112:833–835. Sussman SK, Silverman PM, Donnal JF. CT demonstration of isolated mediastinal goiter. J Comput Assist Tomogr 1986;10: 863–864. Komolafe F. Radiological patterns and significance of thyroid calcification. Clin Radiol 1981;32:571–575. Holtz S, Powers WE. Calcification in papillary carcinoma of the thyroid. AJR Am J Roentgenol 1958;80:997–1000. Margolin FR, Winfield J, Steinbach HL. Patterns of thyroid calcification. Roentgenologic-histologic study of excised specimens. Invest Radiol 1967;2:208–212. Park CH, Rothermel FJ, Judge DM. Unusual calcification in mixed papillary and follicular carcinoma of the thyroid gland. Radiology 1976;119:554. Binder RE, Pugatch RD, Faling LJ, et al. Diagnosis of posterior mediastinal goiter by computed tomography. J Comput Assist Tomogr 1980;4:550–552. Bryk D. Venous compression and obstruction by intrathoracic goiter. J Can Assoc Radiol 1974;25:300–302. Tunca F, Giles Y, Salmaslioglu A, et al. The preoperative exclusion of thyroid carcinoma in multinodular goiter: dynamic contrast-enhanced magnetic resonance imaging versus ultrasonography-guided fine-needle aspiration biopsy. Surgery 2007;142:992–1002, discussion 1002, e1001–1002.

784. Tezelman S, Giles Y, Tunca F, et al. Diagnostic value of dynamic contrast medium enhanced magnetic resonance imaging in preoperative detection of thyroid carcinoma. Arch Surg 2007;142: 1036–1041. 785. von Schulthess GK, McMurdo K, Tscholakoff D, et al. Mediastinal masses: MR imaging. Radiology 1986;158:289–296. 786. Noma S, Nishimura K, Togashi K, et al. Thyroid gland: MR imaging. Radiology 1987;164:495–499. 787. Irwin RS, Braman SS, Arvanitidis AN, et al. 131I thyroid scanning in preoperative diagnosis of mediastinal goiter. Ann Intern Med 1978;89:73–74. 788. Chen YK, Chen YL, Cheng RH, et al. The significance of FDG uptake in bilateral thyroid glands. Nucl Med Commun 2007;28:117–122. 789. Kresnik E, Gallowitsch HJ, Mikosch P, et al. Fluorine-18-fluorodeoxyglucose positron emission tomography in the preoperative assessment of thyroid nodules in an endemic goiter area. Surgery 2003; 133:294–299. 790. Chu QD, Connor MS, Lilien DL, et al. Positron emission tomography (PET) positive thyroid incidentaloma: the risk of malignancy observed in a tertiary referral center. Am Surg 2006;72:272–275. 791. Keene RJ, Steiner RE, Olsen EJ, et al. Aortic root aneurysm: radiographic and pathologic features. Clin Radiol 1971;22: 330–340. 792. Szamosi A. Radiological detection of aneurysms involving the aortic root. Radiology 1981;138:551–555. 793. Krinsky GA, Rofsky NM, DeCorato DR, et al. Thoracic aorta: comparison of gadolinium-enhanced three-dimensional MR angiography with conventional MR imaging. Radiology 1997;202:183–193. 794. Boxerman JL, Mosher TJ, McVeigh ER, et al. Advanced MR imaging techniques for evaluation of the heart and great vessels. RadioGraphics 1998;18:543–564. 795. Prince MR, Narasimham DL, Jacoby WT, et al. Three-dimensional gadoliniumenhanced MR angiography of the thoracic aorta. AJR Am J Roentgenol 1996;166: 1387–1397. 796. Ho VB, Prince MR. Thoracic MR aortography: imaging techniques and strategies. RadioGraphics 1998;18:287–309. 797. Krinsky G, Weinreb J. Gadoliniumenhanced three-dimensional MR angiography of the thoracoabdominal aorta. Semin Ultrasound CT MR 1996;17: 280–303. 798. Leung DA, Debatin JF. Three-dimensional contrast-enhanced magnetic resonance angiography of the thoracic vasculature. Eur Radiol 1997;7:981–989. 799. Chung JW, Park JH, Im JG, et al. Spiral CT angiography of the thoracic aorta. RadioGraphics 1996;16:811–824. 800. Kimura F, Shen Y, Date S, et al. Thoracic aortic aneurysm and aortic dissection: new endoscopic mode for three-dimensional CT display of aorta. Radiology 1996;198: 573–578. 801. Kopecky KK, Gokhale HS, Hawes DR. Spiral CT angiography of the aorta. Semin Ultrasound CT MR 1996;17:304–315. 802. Quint LE, Francis IR, Williams DM, et al. Evaluation of thoracic aortic disease with

803. 804.

805.

806.

807.

808.

809.

810.

811.

812. 813. 814. 815. 816.

817.

818. 819.

820.

the use of helical CT and multiplanar reconstructions: comparison with surgical findings. Radiology 1996;201:37–41. Rubin GD. Helical CT angiography of the thoracic aorta. J Thorac Imaging 1997;12: 128–149. Zeman RK, Berman PM, Silverman PM, et al. Diagnosis of aortic dissection: value of helical CT with multiplanar reformation and three-dimensional rendering. AJR Am J Roentgenol 1995;164:1375–1380. Cramer M, Foley WD, Palmer TE, et al. Compression of the right pulmonary artery by aortic aneurysms: CT demonstration. J Comput Assist Tomogr 1985;9:310–314. Duke RA, Barrett MR 2nd, Payne SD, et al. Compression of left main bronchus and left pulmonary artery by thoracic aortic aneurysm. AJR Am J Roentgenol 1987;149: 261–263. Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical versus nonsurgical risks. Ann Thorac Surg 2002;74:S1877–S1880, discussion S1892–S1878. Davies RR, Goldstein LJ, Coady MA, et al. Yearly rupture or dissection rates for thoracic aortic aneurysms: simple prediction based on size. Ann Thorac Surg 2002;73:17–27. Coady MA, Rizzo JA, Hammond GL, et al. What is the appropriate size criterion for resection of thoracic aortic aneurysms? J Thorac Cardiovasc Surg 1997;113:476–491, discussion 489–491. Svensson LG, Kouchoukos NT, Miller DC, et al. Expert consensus document on the treatment of descending thoracic aortic disease using endovascular stent-grafts. Ann Thorac Surg 2008;85:S1–S41. Smith TR, Khoury PT. Aneurysm of the proximal thoracic aorta simulating neoplasm: the role of CT and angiography. AJR Am J Roentgenol 1985;144:909–910. Posniak HV, Olson MC, Demos TC, et al. CT of thoracic aortic aneurysms. RadioGraphics 1990;10:839–855. Rubin GD. MDCT imaging of the aorta and peripheral vessels. Eur J Radiol 2003; 45(suppl 1):S42–S49. Rubin GD. CT angiography of the thoracic aorta. Semin Roentgenol 2003;38:115–134. Kalender WA, Prokop M. 3D CT angiography. Crit Rev Diagn Imaging 2001;42:1–28. Heiberg E, Wolverson MK, Sundaram M, et al. CT characteristics of aortic atherosclerotic aneurysm versus aortic dissection. J Comput Assist Tomogr 1985;9:78–83. Bural GG, Torigian DA, Chamroonrat W, et al. FDG-PET is an effective imaging modality to detect and quantify age-related atherosclerosis in large arteries. Eur J Nucl Med Mol Imaging 2008;35:562–569. White RD, Higgins CB. Magnetic resonance imaging of thoracic vascular disease. J Thorac Imaging 1989;4:34–50. Gundry SR, Burney RE, Mackenzie JR, et al. Traumatic pseudoaneurysms of the thoracic aorta. Anatomic and radiologic correlations. Arch Surg 1984;119:1055–1060. Heystraten FM, Rosenbusch G, Kingma LM, et al. Chronic posttraumatic aneurysm of the thoracic aorta: surgically correctable occult threat. AJR Am J Roentgenol 1986; 146:303–308.

References 821. Hirsch JH, Carter SJ, Chikos PM. Traumatic pseudoaneurysms of the thoracic aorta: two unusual cases. AJR Am J Roentgenol 1978;130:157–160. 822. Gabbieri D, Dohmen PM, Linneweber J, et al. Mycotic pseudoaneurysm of the ascending aorta at site of aortic cannulation. Asian Cardiovasc Thorac Ann 2008;16:e15–e17. 823. Reed DH. Mycotic pseudoaneurysm of the descending thoracic aorta associated with vertebral osteomyelitis. Clin Radiol 1990; 41:427–429. 824. Betancourt MC, Mena R, Colon M. Mycotic aneurysm: a rare complication of vertebral osteomyelitis. P R Health Sci J 2007;26: 233–236. 825. Manzi SV, Fultz PJ, Sickel JZ, et al. Chest mass in a patient with leukemia with hemoptysis. Invest Radiol 1994;29: 940–943. 826. Feltis BA, Lee DA, Beilman GJ. Mycotic aneurysm of the descending thoracic aorta caused by Pseudomonas aeruginosa in a solid organ transplant recipient: case report and review. Surg Infect (Larchmt) 2002;3: 29–33. 827. Feigl D, Feigl A, Edwards JE. Mycotic aneurysms of the aortic root. A pathologic study of 20 cases. Chest 1986;90:553–557. 828. Moriarty JA, Edelman RR, Tumeh SS. CT and MRI of mycotic aneurysms of the abdominal aorta. J Comput Assist Tomogr 1992;16:941–943. 829. Lee MH, Chan P, Chiou HJ, et al. Diagnostic imaging of Salmonella-related mycotic aneurysm of aorta by CT. Clin Imaging 1996;20:26–30. 830. Ben-Haim S, Seabold JE, Hawes DR, et al. Leukocyte scintigraphy in the diagnosis of mycotic aneurysm. J Nucl Med 1992;33: 1486–1493. 831. Haug A, Schmidt G, Hacker M, et al. Mycotic aneurysm of the thoracic aorta detected by FDG-PET. Nuklearmedizin 2007;46:N43. 832. Davison JM, Montilla-Soler JL, Broussard E, et al. F-18 FDG PET-CT imaging of a mycotic aneurysm. Clin Nucl Med 2005;30: 483–487. 833. Gufler H, Buitrago-Tellez CH, Nesbitt E, et al. Mycotic aneurysm rupture of the descending aorta. Eur Radiol 1998;8: 295–297. 834. Yong D, Roake JA, Buckenham T, et al. Endovascular repair of mycotic aortic aneurysms. N Z Med J 2008;121:64–67. 835. Kan CD, Lee HL, Yang YJ. Outcome after endovascular stent graft treatment for mycotic aortic aneurysm: a systematic review. J Vasc Surg 2007;46:906–912. 836. Edwards JE. Manifestations of acquired and congenital diseases of the aorta. Curr Probl Cardiol 1979;3:1–62. 837. Gelsomino S, Morocutti G, Frassani R, et al. Long-term results of Bentall composite aortic root replacement for ascending aortic aneurysms and dissections. Chest 2003;124:984–988. 838. Pacini D, Ranocchi F, Angeli E, et al. Aortic root replacement with composite valve graft. Ann Thorac Surg 2003;76:90–98. 839. Gelsomino S, Masullo G, Morocutti G, et al. Sixteen-year results of composite aortic root replacement for non-dissecting chronic aortic aneurysms. Ital Heart J 2003;4:454–459.

840. Carlson RG, Lillehei CW, Edwards JE. Cystic medial necrosis of the ascending aorta in relation to age and hypertension. Am J Cardiol 1970;25:411–415. 841. Castaner E, Andreu M, Gallardo X, et al. CT in nontraumatic acute thoracic aortic disease: typical and atypical features and complications. RadioGraphics 2003;23: S93–S110. 842. Macura KJ, Corl FM, Fishman EK, et al. Pathogenesis in acute aortic syndromes: aortic dissection, intramural hematoma, and penetrating atherosclerotic aortic ulcer. AJR Am J Roentgenol 2003;181:309–316. 843. Smith AD, Schoenhagen P. CT imaging for acute aortic syndrome. Cleve Clin J Med 2008;75:7–9, 12, 15–17 passim. 844. Weissmann-Brenner A, Schoen R, Divon MY. Aortic dissection in pregnancy. Obstet Gynecol 2004;103:1110–1113. 845. Avila WS, Dias R, Yamada RT, et al. Acute aortic dissection during pregnancy. Arq Bras Cardiol 2006;87:e112–e115. 846. Carlson M, Silberbach M. Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature. J Med Genet 2007;44:745–749. 847. Ince H, Nienaber CA. Diagnosis and management of patients with aortic dissection. Heart 2007;93:266–270. 848. Crawford ES. The diagnosis and management of aortic dissection. JAMA 1990;264:2537–2541. 849. DeBakey ME, McCollum CH, Crawford ES, et al. Dissection and dissecting aneurysms of the aorta: twenty-year follow-up of five hundred twenty-seven patients treated surgically. Surgery 1982;92:1118–1134. 850. DeBakey ME, Henly WS, Cooley DA. Surgical management of dissecting aneurysms of the aorta. J Thorac Cardiovasc Surg 1965;49:130–149. 851. Appelbaum A, Karp RB, Kirklin JW. Ascending vs descending aortic dissections. Ann Surg 1976;183:296–300. 852. Miller DG, Stinson EB, Oyer PB. Operative treatment of aortic dissection: experience with 125 patients over a sixteen-year period. J Thorac Cardiovasc Surg 1979;78: 365–382. 853. Wheat MW Jr. Acute dissection of the aorta. Cardiovasc Clin 1987;17:241–262. 854. Apaydin AZ, Buket S, Posacioglu H, et al. Perioperative risk factors for mortality in patients with acute type A aortic dissection. Ann Thorac Surg 2002;74:2034– 2039, discussion 2039. 855. Umana JP, Lai DT, Mitchell RS, et al. Is medical therapy still the optimal treatment strategy for patients with acute type B aortic dissections? J Thorac Cardiovasc Surg 2002;124:896–910. 856. Umana JP, Miller DC, Mitchell RS. What is the best treatment for patients with acute type B aortic dissections: medical, surgical, or endovascular stent-grafting? Ann Thorac Surg 2002;74:S1840–S1843, discussion S1857–S1863. 857. Elefteriades JA, Lovoulos CJ, Coady MA, et al. Management of descending aortic dissection. Ann Thorac Surg 1999;67:2002– 2005, discussion 2014–2009. 858. Spittell PC, Spittell JA Jr, Joyce JW, et al. Clinical features and differential diagnosis of aortic dissection: experience with 236 cases (1980 through 1990). Mayo Clin Proc 1993;68:642–651.

859. Yamada T, Tada S, Harada J. Aortic dissection without intimal rupture: diagnosis with MR imaging and CT. Radiology 1988;168:347–352. 860. Erbel R, Oelert H, Meyer J, et al. Effect of medical and surgical therapy on aortic dissection evaluated by transesophageal echocardiography. Implications for prognosis and therapy. The European Cooperative Study Group on Echocardiography. Circulation 1993;87: 1604–1615. 861. Nienaber CA, von Kodolitsch Y, Petersen B, et al. Intramural hemorrhage of the thoracic aorta. Diagnostic and therapeutic implications. Circulation 1995;92: 1465–1472. 862. Robbins RC, McManus RP, Mitchell RS, et al. Management of patients with intramural hematoma of the thoracic aorta. Circulation 1993;88:II1–II10. 863. Murray JG, Manisali M, Flamm SD, et al. Intramural hematoma of the thoracic aorta: MR image findings and their prognostic implications. Radiology 1997;204:349–355. 864. Svensson LG. Acute aortic syndromes: time to talk of many things. Cleve Clin J Med 2008;75:25–26, 29. 865. Motoyoshi N, Moizumi Y, Komatsu T, et al. Intramural hematoma and dissection involving ascending aorta: the clinical features and prognosis. Eur J Cardiothorac Surg 2003;24:237–242, discussion 242. 866. Sueyoshi E, Matsuoka Y, Sakamoto I, et al. Fate of intramural hematoma of the aorta: CT evaluation. J Comput Assist Tomogr 1997;21:931–938. 867. Evangelista A, Dominguez R, Sebastia C, et al. Long-term follow-up of aortic intramural hematoma: predictors of outcome. Circulation 2003;108:583–589. 868. Kaji S, Akasaka T, Katayama M, et al. Long-term prognosis of patients with type B aortic intramural hematoma. Circulation 2003;108(suppl 1):II307–II311. 869. Lee YK, Seo JB, Jang YM, et al. Acute and chronic complications of aortic intramural hematoma on follow-up computed tomography: incidence and predictor analysis. J Comput Assist Tomogr 2007; 31:435–440. 870. Shimokawa T, Ozawa N, Takanashi S, et al. Intermediate-term results of surgical treatment of acute intramural hematoma involving the ascending aorta. Ann Thorac Surg 2008;85:982–986. 871. Cooke JP, Kazmier FJ, Orszulak TA. The penetrating aortic ulcer: pathologic manifestations, diagnosis, and management. Mayo Clin Proc 1988;63: 718–725. 872. Harris JA, Bis KG, Glover JL, et al. Penetrating atherosclerotic ulcers of the aorta. J Vasc Surg 1994;19:90–98, discussion 98–99. 873. Hussain S, Glover JL, Bree R, et al. Penetrating atherosclerotic ulcers of the thoracic aorta. J Vasc Surg 1989;9: 710–717. 874. Kazerooni EA, Bree RL, Williams DM. Penetrating atherosclerotic ulcers of the descending thoracic aorta: evaluation with CT and distinction from aortic dissection. Radiology 1992;183:759–765. 875. Stanson AW, Kazmier FJ, Hollier LH, et al. Penetrating atherosclerotic ulcers of the thoracic aorta: natural history and

999

Chapter 14 • Mediastinal and Aortic Disease

876.

877. 878. 879.

880.

881.

882.

883.

884.

885.

886.

887.

888. 889.

890.

891. 892.

893.

1000

clinicopathologic correlations. Ann Vasc Surg 1986;1:15–23. Primack SL, Mayo JR, Fradet G. Perforated atherosclerotic ulcer of the aorta presenting with upper airway obstruction. Can Assoc Radiol J 1995;46:209–211. Troxler M, Mavor AI, Homer-Vanniasinkam S. Penetrating atherosclerotic ulcers of the aorta. Br J Surg 2001;88:1169–1177. Toda R, Moriyama Y, Iguro Y, et al. Penetrating atherosclerotic ulcer. Surg Today 2001;31:32–35. Hayashi H, Matsuoka Y, Sakamoto I, et al. Penetrating atherosclerotic ulcer of the aorta: imaging features and disease concept. RadioGraphics 2000;20:995–1005. Coady MA, Rizzo JA, Elefteriades JA. Pathologic variants of thoracic aortic dissections. Penetrating atherosclerotic ulcers and intramural hematomas. Cardiol Clin 1999;17:637–657. Coady MA, Rizzo JA, Hammond GL, et al. Penetrating ulcer of the thoracic aorta: what is it? How do we recognize it? How do we manage it? J Vasc Surg 1998;27: 1006–1015. Ganaha F, Miller DC, Sugimoto K, et al. Prognosis of aortic intramural hematoma with and without penetrating atherosclerotic ulcer: a clinical and radiological analysis. Circulation 2002;106: 342–348. Quint LE, Williams DM, Francis IR, et al. Ulcerlike lesions of the aorta: imaging features and natural history. Radiology 2001;218:719–723. Jang YM, Seo JB, Lee YK, et al. Newly developed ulcer-like projection (ULP) in aortic intramural haematoma on follow-up CT: is it different from the ULP seen on the initial CT? Clin Radiol 2008;63:201–206. Macura KJ, Szarf G, Fishman EK, et al. Role of computed tomography and magnetic resonance imaging in assessment of acute aortic syndromes. Semin Ultrasound CT MR 2003;24:232–254. Levy JR, Heiken JP, Gutierrez FR. Imaging of penetrating atherosclerotic ulcers of the aorta. AJR Am J Roentgenol 1999;173: 151–154. Cigarroa JE, Isselbacher EM, DeSanctis RW, et al. Diagnostic imaging in the evaluation of suspected aortic dissection. Old standards and new directions. N Engl J Med 1993;328:35–43. Treasure T. Imaging the dissected aorta. Br Heart J 1993;70:497–498. Luker GD, Glazer HS, Eagar G, et al. Aortic dissection: effect of prospective chest radiographic diagnosis on delay to definitive diagnosis. Radiology 1994;193: 813–819. Hartnell GG, Wakeley CJ, Tottle A, et al. Limitations of chest radiography in discriminating between aortic dissection and myocardial infarction: implications for thrombolysis. J Thorac Imaging 1993;8: 152–155. Dee P, Martin R, Oudkerk M, et al. The diagnosis of aortic dissection. Curr Probl Diagn Radiol 1983;12:3–56. Jagannath AS, Sos TA, Lockhart SH, et al. Aortic dissection: a statistical analysis of the usefulness of plain chest radiographic findings. AJR Am J Roentgenol 1986;147: 1123–1126. Hachiya J, Nitatori T, Yoshino A, et al. CT

894.

895. 896. 897.

898. 899.

900.

901.

902. 903.

904.

905. 906.

907.

908. 909.

910.

911.

of calcified chronic aortic dissection simulating atherosclerotic aneurysm. J Comput Assist Tomogr 1993;17:374–378. Ide K, Uchida H, Otsuji H, et al. Acute aortic dissection with intramural hematoma: possibility of transition to classic dissection or aneurysm. J Thorac Imaging 1996;11:46–52. Erbel R, Engberding R, Daniel W, et al. Echocardiography in diagnosis of aortic dissection. Lancet 1989;1:457–461. Demos TC, Posniak HV, Marsan RE. CT of aortic dissection. Semin Roentgenol 1989; 24:22–37. Bansal RC, Chandrasekaran K, Ayala K, et al. Frequency and explanation of false negative diagnosis of aortic dissection by aortography and transesophageal echocardiography. J Am Coll Cardiol 1995;25:1393–1401. Petasnick JP. Radiologic evaluation of aortic dissection. Radiology 1991;180: 297–305. Rizzo RJ, Aranki SF, Aklog L, et al. Rapid noninvasive diagnosis and surgical repair of acute ascending aortic dissection. Improved survival with less angiography. J Thorac Cardiovasc Surg 1994;108:567–574. Manghat NE, Rachapalli V, Van Lingen R, et al. Imaging the heart valves using ECG-gated 64-detector row cardiac CT. Br J Radiol 2008;81:275–290. Vogel-Claussen J, Pannu H, Spevak PJ, et al. Cardiac valve assessment with MR imaging and 64-section multi-detector row CT. RadioGraphics 2006;26:1769–1784. Alkadhi H, Desbiolles L, Husmann L, et al. Aortic regurgitation: assessment with 64-section CT. Radiology 2007;245:111–121. Scheffel H, Leschka S, Plass A, et al. Accuracy of 64-slice computed tomography for the preoperative detection of coronary artery disease in patients with chronic aortic regurgitation. Am J Cardiol 2007; 100:701–706. Gaemperli O, Schepis T, Koepfli P, et al. Accuracy of 64-slice CT angiography for the detection of functionally relevant coronary stenoses as assessed with myocardial perfusion SPECT. Eur J Nucl Med Mol Imaging 2007;34:1162–1171. Johnson TR, Nikolaou K, Becker A, et al. Dual-source CT for chest pain assessment. Eur Radiol 2008;18:773–780. Johnson TR, Nikolaou K, Wintersperger BJ, et al. ECG-gated 64-MDCT angiography in the differential diagnosis of acute chest pain. AJR Am J Roentgenol 2007;188:76–82. Nienaber CA, von Kodolitsch Y, Nicolas V, et al. The diagnosis of thoracic aortic dissection by noninvasive imaging procedures. N Engl J Med 1993;328:1–9. Small JH, Dixon AK, Coulden RA, et al. Fast CT for aortic dissection. Br J Radiol 1996;69:900–905. Sommer T, Fehske W, Holzknecht N, et al. Aortic dissection: a comparative study of diagnosis with spiral CT, multiplanar transesophageal echocardiography, and MR imaging. Radiology 1996;199:347–352. Vasile N, Mathieu D, Keita K, et al. Computed tomography of thoracic aortic dissection: accuracy and pitfalls. J Comput Assist Tomogr 1986;10:211–215. Demos TC, Posniak HV, Churchill RJ. Detection of the intimal flap of aortic dissection on unenhanced CT images. AJR

Am J Roentgenol 1986;146:601–603. 912. Larde D, Belloir C, Vasile N, et al. Computed tomography of aortic dissection. Radiology 1980;136:147–151. 913. Duvernoy O, Coulden R, Ytterberg C. Aortic motion: a potential pitfall in CT imaging of dissection in the ascending aorta. J Comput Assist Tomogr 1995;19: 569–572. 914. Burns MA, Molina PL, Gutierrez FR, et al. Motion artifact simulating aortic dissection on CT. AJR Am J Roentgenol 1991;157: 465–467. 915. Posniak HV, Olson MC, Demos TC. Aortic motion artifact simulating dissection on CT scans: elimination with reconstructive segmented images. AJR Am J Roentgenol 1993;161:557–558. 916. Godwin JD. Conventional CT of the aorta. J Thorac Imaging 1990;5:18–31. 917. Loubeyre P, Angelie E, Grozel F, et al. Spiral CT artifact that simulates aortic dissection: image reconstruction with use of 180 degrees and 360 degrees linearinterpolation algorithms. Radiology 1997; 205:153–157. 918. Gallagher S, Dixon AK. Streak artefacts of the thoracic aorta: pseudodissection. J Comput Assist Tomogr 1984;8:688–693. 919. LePage MA, Quint LE, Sonnad SS, et al. Aortic dissection: CT features that distinguish true lumen from false lumen. AJR Am J Roentgenol 2001;177:207–211. 920. Williams DM, Joshi A, Dake MD, et al. Aortic cobwebs: an anatomic marker identifying the false lumen in aortic dissection: imaging and pathologic correlation. Radiology 1994;190:167–174. 921. Lee DY, Williams DM, Abrams GD. The dissected aorta. Part II. Differentiation of the true from the false lumen with intravascular US. Radiology 1997;203: 32–36. 922. White RD, Lipton MJ, Higgins CB, et al. Noninvasive evaluation of suspected thoracic aortic disease by contrastenhanced computed tomography. Am J Cardiol 1986;57:282–290. 923. Williams DM, Lee DY, Hamilton BH, et al. The dissected aorta. Part III. Anatomy and radiologic diagnosis of branch-vessel compromise. Radiology 1997;203:37–44. 924. Liu Q, Lu JP, Wang F, et al. Threedimensional contrast-enhanced MR angiography of aortic dissection: a pictorial essay. RadioGraphics 2007;27:1311–1321. 925. Gebker R, Gomaa O, Schnackenburg B, et al. Comparison of different MRI techniques for the assessment of thoracic aortic pathology: 3D contrast enhanced MR angiography, turbo spin echo and balanced steady state free precession. Int J Cardiovasc Imaging 2007;23:747–756. 926. Panting JR, Norell MS, Baker C, et al. Feasibility, accuracy and safety of magnetic resonance imaging in acute aortic dissection. Clin Radiol 1995;50:455–458. 927. Laissy JP, Blanc F, Soyer P, et al. Thoracic aortic dissection: diagnosis with transesophageal echocardiography versus MR imaging. Radiology 1995;194: 331–336. 928. Kersting-Sommerhoff BA, Higgins CB, White RD, et al. Aortic dissection: sensitivity and specificity of MR imaging. Radiology 1988;166:651–655. 929. Nienaber CA, Spielmann RP, von

References

930.

931.

932.

933.

934.

935.

936.

937.

938.

939.

940.

941.

942. 943. 944.

945.

946.

Kodolitsch Y, et al. Diagnosis of thoracic aortic dissection. Magnetic resonance imaging versus transesophageal echocardiography. Circulation 1992;85: 434–447. Wolff KA, Herold CJ, Tempany CM, et al. Aortic dissection: atypical patterns seen at MR imaging. Radiology 1991;181: 489–495. Chung JW, Park JH, Kim HC, et al. Entry tears of thoracic aortic dissections: MR appearance on gated SE imaging. J Comput Assist Tomogr 1994;18:250–255. Lotan CS, Cranney GB, Doyle M, et al. Fat-shift artifact simulating aortic dissection on MR images. AJR Am J Roentgenol 1989;152:385–386. Solomon SL, Brown JJ, Glazer HS, et al. Thoracic aortic dissection: pitfalls and artifacts in MR imaging. Radiology 1990;177:223–228. Savit RM, Panico RA. Case report: simulated thoracic aortic dissection on magnetic resonance in a patient with interruption of the inferior vena cava. Br J Radiol 1995;68:425–427. Granato JE, Dee P, Gibson RS. Utility of two-dimensional echocardiography in suspected ascending aortic dissection. Am J Cardiol 1985;56:123–129. Tottle AJ, Wilde P, Hartnell GG, et al. Diagnosis of acute thoracic aortic dissection using combined echocardiography and computed tomography. Clin Radiol 1992; 45:104–108. Ballal RS, Nanda NC, Gatewood R, et al. Usefulness of transesophageal echocardiography in assessment of aortic dissection. Circulation 1991;84:1903–1914. Chirillo F, Cavallini C, Longhini C, et al. Comparative diagnostic value of transesophageal echocardiography and retrograde aortography in the evaluation of thoracic aortic dissection. Am J Cardiol 1994;74:590–595. Hashimoto S, Kumada T, Osakada G, et al. Assessment of transesophageal Doppler echography in dissecting aortic aneurysm. J Am Coll Cardiol 1989;14:1253–1262. Erbel R, Borner N, Steller D, et al. Detection of aortic dissection by transoesophageal echocardiography. Br Heart J 1987;58:45–51. Yamada E, Matsumura M, Kyo S, et al. Usefulness of a prototype intravascular ultrasound imaging in evaluation of aortic dissection and comparison with angiographic study, transesophageal echocardiography, computed tomography, and magnetic resonance imaging. Am J Cardiol 1995;75:161–165. Wambeek ND, Cameron DC, Holden A. Intramural aortic dissection. Australas Radiol 1996;40:442–446. Oliver TB, Murchison JT, Reid JH. Spiral CT in acute non-cardiac chest pain. Clin Radiol 1999;54:38–45. Oliver TB, Murchison JT, Reid JH. Serial MRI in the management of intramural haemorrhage of the thoracic aorta. Br J Radiol 1997;70:1288–1290. Mohr-Kahaly S, Erbel R, Kearney P, et al. Aortic intramural hemorrhage visualized by transesophageal echocardiography: findings and prognostic implications. J Am Coll Cardiol 1994;23:658–664. Yucel EK, Steinberg FL, Egglin TK, et al.

947.

948.

949. 950.

951.

952. 953.

954. 955. 956.

957.

958.

959.

960.

961.

962.

963. 964.

965.

Penetrating aortic ulcers: diagnosis with MR imaging. Radiology 1990;177:779–781. Patel NH, Mann FA, Jurkovich GJ. Penetrating ulcer of the descending aorta mimicking a traumatic aortic laceration. AJR Am J Roentgenol 1996;166:20. Welch TJ, Stanson AW, Sheedy PF 2nd, et al. Radiologic evaluation of penetrating aortic atherosclerotic ulcer. RadioGraphics 1990;10:675–685. Williams MP, Farrow R. Atypical patterns in the CT diagnosis of aortic dissection. Clin Radiol 1994;49:686–689. Deutsch HJ, Sechtem U, Meyer H, et al. Chronic aortic dissection: comparison of MR Imaging and transesophageal echocardiography. Radiology 1994;192:645–650. Gaubert JY, Moulin G, Mesana T, et al. Type A dissection of the thoracic aorta: use of MR imaging for long-term follow-up. Radiology 1995;196:363–369. Goldberg N, Krasnow N. Sinus of valsalva aneurysms. Clin Cardiol 1990;13:831–836. Zannis K, Tzvetkov B, Deux JF, et al. Unruptured congenital aneurysms of the right and left sinuses of Valsalva. Eur Heart J 2007;28:1565. Ott DA. Aneurysm of the sinus of valsalva. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2006;81:165–176. Gomes AS, Lois JF, George B, et al. Congenital abnormalities of the aortic arch: MR imaging. Radiology 1987;165:691–695. Soler R, Rodriguez E, Requejo I, et al. Magnetic resonance imaging of congenital abnormalities of the thoracic aorta. Eur Radiol 1998;8:540–546. Azarine A, Lions C, Koussa M, et al. Rupture of an aneurysm of the coronary sinus of Valsalva: diagnosis by helical CT angiography. Eur Radiol 2001;11: 1371–1373. Holland P, Fitzpatrick JD. Case report: magnetic resonance imaging of a rightsided cervical aortic arch with a congenital aneurysm. Clin Radiol 1991;43:352–355. Kenny D, Margey R, Turner MS, et al. Self-expanding and balloon expandable covered stents in the treatment of aortic coarctation with or without aneurysm formation. Catheter Cardiovasc Interv 2008;72:65–71. Tavora F, Burke A. Review of isolated ascending aortitis: differential diagnosis, including syphilitic, Takayasu’s and giant cell aortitis. Pathology 2006;38:302–308. Evans JM, Bowles CA, Bjornsson JB, et al. Thoracic aortic aneurysm and rupture in giant cell arteritis: descriptive study of 41 cases. Ann Intern Med 1995;122:502–507. Erratum in: Arthritis Rheum 1995;38:290. Agard C, Barrier JH, Dupas B, et al. Aortic involvement in recent-onset giant cell (temporal) arteritis: a case-control prospective study using helical aortic computed tomodensitometric scan. Arthritis Rheum 2008;59:670–676. Chau EM. Aortitis. Curr Treat Options Cardiovasc Med 2007;9:109–114. Park JH. Conventional and CT angiographic diagnosis of Takayasu arteritis. Int J Cardiol 1996;54(suppl):} S165–S171. Angeli E, Vanzulli A, Venturini M, et al. The role of radiology in the diagnosis and management of Takayasu’s arteritis. J

Nephrol 2001;14:514–524. 966. Lui YQ. Radiology of aortoarteritis. Radiol Clin North Am 1985;23:671–688. 967. Matsunaga N, Hayashi K, Sakamoto I, et al. Takayasu arteritis: protean radiologic manifestations and diagnosis. RadioGraphics 1997;17:579–594. 968. Peterson IM, Guthaner DF. Aortic pseudoaneurysm complicating Takayasu disease: CT appearance. J Comput Assist Tomogr 1986;10:676–678. 969. Sharma S, Rajani M, Kamalakar T, et al. The association between aneurysm formation and systemic hypertension in Takayasu’s arteritis. Clin Radiol 1990;42: 182–187. 970. Yamato M, Lecky JW, Hiramatsu K, et al. Takayasu arteritis: radiographic and angiographic findings in 59 patients. Radiology 1986;161:329–334. 971. Chau EM, Wang E, Chiu CS, et al. Non-infectious aortitis: an important cause of severe aortic regurgitation. Asian Cardiovasc Thorac Ann 2006;14:177–182. 972. Agard C, Ponge T, Fradet G, et al. Giant cell arteritis presenting with aortic dissection: two cases and review of the literature. Scand J Rheumatol 2006;35: 233–236. 973. Yamada I, Nakagawa T, Himeno Y, et al. Takayasu arteritis: evaluation of the thoracic aorta with CT angiography. Radiology 1998;209:103–109. 974. Ceriani L, Oberson M, Marone C, et al. F-18 FDG PET-CT imaging in the care-management of a patient with pan-aortitis and coronary involvement. Clin Nucl Med 2007;32:562–564. 975. Takahashi M, Momose T, Kameyama M, et al. Abnormal accumulation of [18F]fluorodeoxyglucose in the aortic wall related to inflammatory changes: three case reports. Ann Nucl Med 2006;20:361–364. 976. Kobayashi Y, Ishii K, Oda K, et al. Aortic wall inflammation due to Takayasu arteritis imaged with 18F-FDG PET coregistered with enhanced CT. J Nucl Med 2005;46:917–922. 977. Blockmans D. The use of (18F)fluorodeoxyglucose positron emission tomography in the assessment of large vessel vasculitis. Clin Exp Rheumatol 2003;21:S15–S22. 978. Kuehl H, Eggebrecht H, Boes T, et al. Detection of inflammation in patients with acute aortic syndrome: comparison of FDG-PET/CT imaging and serologic markers of inflammation. Heart 2007;94: 1472–1477. 979. Ryan A, McCook B, Sholosh B, et al. Acute intramural hematoma of the aorta as a cause of positive FDG PET/CT. Clin Nucl Med 2007;32:729–731. 980. Slobodin G, Naschitz JE, Zuckerman E, et al. Aortic involvement in rheumatic diseases. Clin Exp Rheumatol 2006;24: S41–S47. 981. Cole TJ, Henry DA, Jolles H, et al. Normal and abnormal vascular structures that simulate neoplasms on chest radiographs: clues to the diagnosis. RadioGraphics 1995;15:867–891. 982. VanDyke CW, White RD. Congenital abnormalities of the thoracic aorta presenting in the adult. J Thorac Imaging 1994;9:230–245. 983. Kessler RM, Miller KB, Pett S, Wernly JA.

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Chapter 14 • Mediastinal and Aortic Disease Pseudocoarctation of the aorta presenting as a mediastinal mass with dysphagia. Ann Thorac Surg 1993;55: 1003–1005. 984. Safir J, Kerr A, Morehouse H, et al. Magnetic resonance imaging of dissection in pseudocoarctation of the aorta. Cardiovasc Intervent Radiol 1993;16:

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180–182. 985. Sebastia C, Quiroga S, Boye R, et al. Aortic stenosis: spectrum of diseases depicted at multisection CT. RadioGraphics 2003;23: S79–S91. 986. Taneja K, Kawlra S, Sharma S, et al. Pseudocoarctation of the aorta: complementary findings on plain film

radiography, CT, DSA, and MRA. Cardiovasc Intervent Radiol 1998;21: 439–441. 987. Munjal AK, Rose WS, Williams G. Magnetic resonance imaging of pseudocoarctation of the aorta: a case report. J Thorac Imaging 1994;9:88–91.

CHAPTER

15

Pleura and pleural disorders

PLEURAL PHYSIOLOGY AND PLEURAL EFFUSIONS Imaging of pleural effusion Subpulmonic effusion Large pleural effusion Loculated pleural effusion Pleural effusion in the supine patient CT of pleural fluid Ultrasonography and pleural fluid MRI and pleural fluid Specific causes of pleural effusion Pregnancy-related pleural effusion Adjacent infection Cardiovascular disease Pericardial disease Ascitic effusion Pancreatic disease Renal disease Splenic disease Abdominal surgery Radiation Drugs and the pleura Ovarian hyperstimulation syndrome Miscellaneous causes of pleural effusion Myxedema Pleural effusion with yellow nails and primary lymphedema Familial Mediterranean fever Atelectasis, trapped lung, and pneumothorax ex vacuo CHYLOTHORAX Anatomy of the thoracic duct and its tributaries Mechanisms of chylothorax formation Physiology of chyle Causes of chylothorax Neoplastic causes Trauma Idiopathic causes Miscellaneous Imaging of chylothorax Pseudochylothorax Hemothorax

RADIOGRAPHIC APPEARANCE FOLLOWING PLEURODESIS PLEURAL CALCIFICATION THORACIC SPLENOSIS PNEUMOTHORAX Primary spontaneous pneumothorax Secondary spontaneous pneumothorax Airflow obstruction Interstitial lung disease Primary and secondary neoplasm Radiation Pulmonary infarction Endometriosis and catamenial pneumothorax Pleurodiaphragmatic endometriosis Bronchopulmonary endometriosis Heritable disorders causing pneumothorax Marfan syndrome Ehlers–Danlos syndromes Cutis laxa (generalized elastolysis) Other familial conditions Mechanical ventilation Radiographic signs of pneumothorax Free pneumothorax Pneumothorax in the supine patient Ultrasonographic detection of pneumothorax Loculated and localized pneumothorax Subpulmonic pneumothorax Loculated pneumothorax ‘Pulmonary ligament pneumatocele’ Complications of pneumothorax Tension pneumothorax Reexpansion pulmonary edema Buffalo chest Following progress and management BRONCHOPLEURAL FISTULA

PLEURAL THICKENING Mimics of pleural thickening Extrapleural fat Apical pleural cap

PLEURAL PHYSIOLOGY AND PLEURAL EFFUSIONS (Box 15.1) The outward pull of the chest wall and the inward recoil of the lung tend to separate the parietal and visceral pleura. These membranes are permeable to both gases and liquid, and are kept in apposition only because of mechanisms that keep the pleural space essentially free of gas and liquid. Gas is removed from the pleural space by systemic venous blood because the total gas pressure in venous blood is about 70 cmH2O subatmospheric, and this provides a steep

absorption gradient. The mechanisms governing the formation and absorption of pleural fluid are more complex. The pleural space is lubricated by a small amount of pleural fluid. This liquid coupling provides instantaneous transmission of perpendicular forces between pleural surfaces and allows the pleural membranes to slide in response to shear forces.1 The volume of pleural fluid in the human pleural space, determined by urea dilution, is 0.26 mL/kg.2 This means that normal individuals may have 8–10 mL of fluid in each pleural space. Using lateral decubitus chest radiographs to detect pleural fluid, a technique that has a threshold sensitivity of about 5  mL,3 Hessen4 found a 10% prevalence of

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Chapter 15 • Pleura and Pleural Disorders Box 15.1  Pleural effusions • Up to 10 mL of fluid may be found in the pleural space of normal subjects • Pleural effusions develop when the rate of formation of fluid and its resorption are mismatched • Transudative effusions are usually due to systemic disease causing increased formation of pleural fluid • Exudative effusions are typically due to pleural inflammation or malignancy • Biochemical markers may help in diagnosis of a pleural effusion but none is entirely specific

definite or probable pleural fluid in healthy adults. In humans, it is estimated that 10–20  mL of pleural fluid is formed each day.5–7 Normal pleural fluid has a protein concentration of 1–2 g/dL, a cell count of 1500–4500/mL (60–70% monocytes) and less than half the serum concentration of large protein macromolecules such as lactate dehydrogenase (LDH).8 Pleural fluid originates as extracellular interstitial fluid in parietal pleural tissue, and leaks from there into the pleural space through nontight mesothelial junctions. Physiologically, the pleural space is best considered as part of the parietal pleural extracellular space.6,9 Under physiologic conditions, the rate of fluid formation by the visceral pleura is low because the bronchial arteries which supply the pleura are relatively deep to the surface, and the pleural capillaries, draining into pulmonary veins, have low pressure.10 Removal of pleural fluid is primarily through parietal pleural lymphatics. Lymphatic drainage of the pleural space allows removal of proteins, particulates, and cells in addition to water and crystalloids. Protein is also removed by active transport by mesothelial cells.10 Protein removal is particularly important in pathologic states, but even under normal conditions some protein leaks into the pleural space. Were this not removed, the subsequent rise in oncotic pressure in the pleural fluid would lead to progressive pleural fluid accumulation. Pleural effusions develop when the rate of entry and exit of pleural fluid is mismatched, because of increased microvascular hydrostatic pressure, reduced oncotic pressures, impaired lymphatic drainage, and increased mesothelial or vascular permeability.6,10 Less common mechanisms include reduced pressure in the pleural space (seen with major atelectasis), and transdiaphragmatic passage of fluid from the peritoneum. A variety of liquids may accumulate in the pleural space: transudate, exudate, blood, chyle, and occasionally bile, urine, cerebrospinal fluid, peritoneal dialysate, and intravenous infusions. Because the character of pleural fluid is often unknown, liquid in the pleural space is usually called pleural effusion. Alternative and more specific terms such as hemothorax, pyothorax, and chylothorax may be used as appropriate. Distinction between transudative and exudative pleural fluid is pivotal for diagnosis and management of effusions. The standard criteria for distinguishing transudates from exudates were defined by Light et  al.5,11 (Box 15.2). In a multicenter metaanalysis, the overall diagnostic accuracy of the three-test Light criteria was 92%.12 However, they appear to be more accurate for diagnosis of exudates than for transudates. For example, in a study by Romero et  al.,13 98% of exudates and 77% of transudates were correctly classified Box 15.2  Features distinguishing transudates from exudates • • • • •

Underlying condition likely to cause transudate (see Box 15.3) Pleural fluid to serum protein ratio 0.25 at this level • Obscuration of the aortic arch • Shift of trachea to the right • Shift of orogastric tube (esophagus) to the right • Left apical pleural cap • Widened left paraspinal reflection • Widened right paraspinal reflection • Opacification of the aortopulmonary window • Widened right paratracheal stripe • Displaced superior vena cava • Depressed left main bronchus • Evidence of significant chest trauma – Multiple rib fractures (especially first rib) – Lung contusion – Hemothorax – Pneumothorax

B

Fig. 17.4  Blunt aortic injury after a motor vehicle accident. A, Frontal chest radiograph shows an abnormal mediastinum. Note that the aortic arch (yellow arrow) is obscured, the left main bronchus (*) is inferiorly displaced, and there is a left apical cap (red arrows). The endotracheal and orogastric tubes are not displaced, however. B, Aortogram shows complete aortic transection with a large pseudoaneurysm (arrow) at the isthmus.

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Injury to the Aorta or Great Vessels

Fig. 17.5  Blunt aortic injury after a motor vehicle accident. Frontal chest radiograph shows an abnormal mediastinum and left lung contusion. Note that both the aortic arch and descending thoracic aorta are obscured, there is a left apical cap, and both the endotracheal and orogastric tubes (arrows) are displaced to the right. Aortogram (not shown) confirmed aortic injury at the isthmus.

the setting of blunt chest trauma. More reproducible criteria for diagnosis of ‘mediastinal widening’ have been difficult to establish, however, due to variations in radiographic technique (source-todetector distance), patient positioning, patient size, obesity, and age. Proposed criteria have included a mediastinal width exceeding 8 cm just above the aortic arch26 or a ratio of the width of the mediastinum to the width of the chest exceeding 0.25 at the same level.27 However, BAI is occasionally found in patients with normal mediastinal measurements.28 Obscuration of the normal contours of the aortic arch and descending aorta and opacification of the AP window are important findings that suggest perivascular mediastinal hematoma and BAI (Figs 17.4 and 17.5). Mirvis et al.20 found these signs to be among the best radiographic discriminators for BAI. Furthermore, these signs may be more specifically applied to interpretation of trauma chest radiographs. Displacement of normal structures such as the trachea, left main bronchus, and esophagus are also important radiographic findings of perivascular hematoma. Hematoma at the aortic isthmus can displace the left main bronchus downward (Fig. 17.4) and the trachea and esophagus to the right (Fig. 17.5). Marnocha and Maglinte29 found that depression of the left main bronchus to below 40° off horizontal was a specific finding of BAI. Tracheal deviation is more difficult to diagnose because the trachea normally deviates to the right at the level of the aortic arch, and minor degrees of patient rotation can either artificially accentuate or minimize the finding. Because the esophagus descends adjacent to the right lateral wall of the aorta at the isthmus, lateral deviation of the esophagus (as indicated by the position of an orogastric tube) is a good indicator of perivascular hematoma (Fig. 17.5).30,31 Hemorrhage into anatomically contiguous regions such as the pleural space, paravertebral soft tissues, or apex of the thorax can result in further important radiographic findings that suggest BAI. Hemothorax, particularly on the left, should immediately suggest the possibility of BAI. Widening of the paravertebral reflections (Figs 17.3 and 17.6)32 also suggests mediastinal hemorrhage. Care must be taken not to confuse paraspinal hematoma due to vertebral fractures with mediastinal hematoma due to BAI (Fig. 17.7).33 Mirvis et al.20 found that widening of the left paraspinal reflection (Fig. 17.3) without associated spine fracture was a discriminating radiographic finding for BAI. Mediastinal hematomas may dissect over the lung apices in the extrapleural space, forming so-called

apical ‘caps’ which are more common on the left (Fig. 17.4).34 This finding is particularly important when there are no associated fractures of the upper ribs. Other radiographic findings such as upper rib or scapular fractures, pulmonary contusion, or pneumothorax can indicate significant chest trauma.7 The importance of such findings in isolation, particularly upper rib and scapular fractures, and in the context of suspected BAI, is controversial. Most authors have concluded that isolated first rib fractures with an otherwise normal chest radiograph are unlikely to be indicative of BAI.35–39 There is an extensive literature on the role of chest radiography for diagnosis of BAI. While a correctly performed chest radiograph can be a sensitive test for mediastinal hematoma, it is very nonspecific.40 Mirvis et  al.,20 for example, reported that a normal chest radiograph had a 98% negative predictive value for BAI.20 There are many dissenting opinions, however. Woodring23 reviewed 52 published studies of patients with BAI and found that 7% of patients with proved BAI had normal chest radiographs, and concluded that a normal chest radiograph does not confidently exclude BAI. Fabian et  al.41 reported that 2% of patients with BAI had a normal chest radiograph. Dyer et al.42 prospectively evaluated over 1500 patients with suspected BAI and found that 4/30 (13%) patients with BAI had normal chest radiographs. Cook et  al.43 and Ho et  al.25 also concluded that the chest radiograph was of limited value in excluding BAI. There are thus contradictory results regarding the utility of chest radiographs for diagnosing BAI. Many of these results can be explained by inconsistent standards for diagnosis of an ‘abnormal’ mediastinum and a variable ‘gold standard’ for diagnosis of BAI. Many authors, however, conclude that the chest radiograph, properly performed, remains a useful screening test for BAI, but that negative results must be interpreted with caution in patients with a high risk of BAI.40 Many such patients will, and should, be referred for CT. For example, Exadaktylos et  al.44 have recommended that all patients undergo CT if there is a history of motor vehicle accident at a speed of more than 16 km/h (unrestrained) or 48 km/h (restrained), or a fall from a height of 7 m or more. Interpretation of a ‘positive’ chest radiograph result remains controversial as well. Algorithms that send all patients with a ‘positive’ chest radiograph to CT may result in considerable overutilization and overexposure of the population to ionizing radiation, with little added benefit.45 Strategies to decrease the ‘overuse’ of CT in this setting, while maintaining a high sensitivity for diagnosis of BAI, have been proposed and have met with variable success.40,46–48

Computed tomography Many now consider multidetector CT the ‘gold standard’ for diagnosis of BAI42,49,50 (see Box 17.3). Current generation multidetector CT scanners allow rapid acquisition of very thin-slice axial images with isotropic voxel sampling through the thorax. These datasets can be reconstructed in multiple two-dimensional planes, and isotropic three-dimensional images that simulate those of conventional aortography can be produced. High-quality CT angiography of the thoracic aorta requires rapid-bolus administration of intravenous contrast (typically between 3 mL and 5 mL per second), thin slice collimation (2.5  mm or less) and overlapping reconstruction intervals. Cardiac-gating can improve visualization of the ascending aorta,51 but increases acquisition time, a potential limitation for trauma imaging. The signs of BAI on CT may be classified as indirect or direct.52 The most important indirect sign of BAI is mediastinal hematoma. As noted previously, however, this finding is relatively nonspecific as it can also be caused by venous bleeding, rib, spine, or sternal fractures. Location of mediastinal hematoma is thus important and has been recently classified into four types depending on proximity to the aorta or other sites of injury such as the spine, preservation of periaortic fat planes, etc.53 It is generally accepted that only hematoma that directly contacts the margins of the aorta or great

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Chapter 17 • Chest Trauma

A

C

Fig. 17.6  Blunt aortic injury after a high-speed motor vehicle accident. A, Frontal chest radiograph shows subtle obscuration of the contour of the descending thoracic aorta (yellow arrow) and widening of the left paraspinal reflection (red arrows). The mediastinum is otherwise normal. The orogastric tube appears displaced, but this finding is due to rotation. Note the subtle right basal pneumothorax and right lung contusion. B, CT shows perivascular (yellow arrows) and paraspinal hematoma (red arrows). Note the small, anterior pseudoaneurysm (*) at the isthmus, confirmed at aortography (C, yellow arrows).

B

Box 17.3  CT for diagnosis of blunt aortic injury

Indirect signs of BAI • Periaortic or perivascular hematoma

Direct signs of BAI • • • •

Focal disruption of the wall Extravasation of contrast Intimal flap Pseudoaneurysm

Diagnosis • Direct signs more sensitive and specific than indirect signs • Direct signs have less intraobserver variability • Negative predictive value >98% (100% for significant injury) when: – No periaortic hematoma – No direct signs of injury

Pitfalls in diagnosis • • • • •

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Streak artifacts Thymic tissue simulating hematoma Atheromatous disease Ductus diverticulum or bump Difficulty in identifying injury to the great vessels

vessels (perivascular or periaortic) is of importance for predicting the presence or absence of BAI (see discussion below). The direct signs of BAI include intimal flaps and/or intraluminal thrombus, aortic contour irregularities and/or caliber changes and contrast extravasation11 (Figs 17.6, 17.8–17.10). Much data support the very high sensitivity of CT for diagnosis of BAI and the very high negative predictive value of a normal study7,42,52,54–61 (Figs 17.11 and 17.12). Dyer et al.7,42 reported a sensitivity of 95% for BAI and a 99.9% negative predictive value using only direct signs for diagnosis on CT. When they included peri­ aortic hematoma as an additional positive finding, both their sensitivity and negative predictive value improved to 100%. Fabian et al.56 prospectively evaluated 494 patients with suspected BAI and reported that the sensitivity and negative predictive value of CT was 100% and 100%, respectively. In the same group of patients, the sensitivity and negative predictive value of angiography was 92% and 97%, respectively. Parker et  al.58 prospectively evaluated 142 patients with both CT and angiography and reported 100% sensitivity and 100% negative predictive value for both methods. Ellis and Mayo62 studied 278 consecutive patients who received contrast-enhanced CT for blunt chest trauma and reported a negative predictive value for BAI of 100%.

Injury to the Aorta or Great Vessels

A A

B B

Fig. 17.7  Suspected blunt aortic injury after a motor vehicle accident. A, Frontal chest radiograph shows widening of the right paratracheal stripe (arrow). Note that the contours of the aortic arch and descending thoracic aorta are preserved and that the orogastric tube is in normal position. B, CT shows an anterior vertebral body fracture (yellow arrow). Note that the paravertebral hematoma displaces the trachea (T) anteriorly and dissects (red arrows) along the right side of the mediastinum. The aorta was normal (not shown).

Fig. 17.8  Blunt aortic injury after a motor vehicle accident. A, Frontal chest radiograph shows apparent enlargement of proximal descending thoracic aorta and subtle lateral displacement of the orogastric tube. Note the right pneumothorax and right lower lobe contusion. B, CT shows a perivascular hematoma, a complex intimal flap (yellow arrows), focal dilatation of the proximal descending aorta (pseudoaneurysm, red arrow), and apparent narrowing of the distal descending aorta (pseudocoarctation). These features are diagnostic of BAI. An aortogram (not shown) was performed which confirmed the aortic injury, but wasted potentially valuable time.

Table 17.1  Guidelines for trauma-related aortic imaging, adapted from Dyer et al.42 Clinical suspicion based on severity of trauma and mechanism of injury

Findings on chest radiography

Medium–high Medium–high Low Low

Suspect mediastinal hematoma Normal Suspect mediastinal hematoma Normal

Several authors have debated the merits of using direct versus indirect signs for diagnosis or exclusion of BAI.52,55,59 Fishman et al.52 found that, when they used direct signs for diagnosis alone, not only did their accuracy of diagnosis improve (with no loss of sensitivity), but the intraobserver variability for diagnosis improved as well. Cleverley et al.59 found that using direct signs enabled diag-

Recommended imaging To detect significant aortic injury

To detect all (including intimal) aortic injuries

CT None CT None

CT CT CT None

nosis of all surgically proved cases of BAI. Interestingly, 9% of patients with BAI in their series had no periaortic hematoma. There is thus a large body of evidence that suggests that highquality helical CT angiography has both a very high sensitivity (close to 100%) and a high negative predictive value (also close to 100%) for diagnosis or exclusion of BAI (Table 17.1). Furthermore,

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Chapter 17 • Chest Trauma

Fig. 17.9  Blunt aortic injury (BAI) after a motor vehicle accident. CT shows perivascular hematoma (yellow arrow) in the left superior mediastinum, focal dilatation of the proximal descending aorta (pseudoaneurysm, red arrows), and an intimal flap at the isthmus. These CT features are diagnostic of BAI. Angiography was not performed and the injury was promptly repaired.

Fig. 17.10  Fatal aortic injury after a motor vehicle accident. CT shows extensive mediastinal hematoma and active contrast extravasation at site of injury (arrow).

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Injury to the Aorta or Great Vessels

B A

Fig. 17.11  Normal aorta after a motor vehicle accident. A, Frontal chest radiograph shows an abnormal mediastinum. B, CT shows soft tissue in the anterior mediastinum that likely represents residual thymus. The periaortic fat planes are preserved and there are no specific direct or indirect (perivascular hematoma) signs of aortic injury.

A B

C

Fig. 17.12  Normal aorta after a motor vehicle accident. A, CT shows an isolated anterior mediastinal hematoma (arrows). There are no direct signs of aortic injury. B, Sagittal reconstruction shows a fracture-dislocation at the sternomanubrial joint (yellow arrow) and associated hematoma (red arrows). C, Sagittal reconstruction confirms a normal aortic isthmus and descending thoracic aorta. Note aortic pulsation artifact.

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Chapter 17 • Chest Trauma evidence suggests that if the criteria for diagnosis of BAI are restricted to the direct signs of aortic injury (intimal flaps, aortic contour irregularities, caliber changes, and pseudoaneurysm formation) or periaortic hematoma, specificity can be substantially improved without an adverse effect on either sensitivity or negative predictive value. In summary, current evidence suggests that patients with a normal-appearing aorta and no periaortic hematoma on CT need not undergo further evaluation. Furthermore, patients with a normal-appearing aorta and only isolated anterior mediastinal hematoma need not undergo further evaluation53 (Fig. 17.12). Dyer et al.,7,42 for example, found that no patient with an isolated anterior mediastinal hematoma had BAI. There remains the problem of the equivocal or indeterminate CT. Equivocal results derive from either anatomic variants (‘ductus bump’, bronchial arteries), CT artifacts (motion, stairstep), or, most importantly, perivascular or periaortic hematoma without direct signs of injury. In such cases, aortography is frequently recommended.7,40,42,56 While anatomic variants or CT artifacts may exclude definitive interpretation and necessitate aortography, perivascular or periaortic hematoma in the absence of direct signs of injury remains a point of significant controversy. Many authorities40,63 continue to recommend aortography in this setting. Sammer et  al.53 reached a different conclusion by reviewing CT, aortography, and outcome data in 107 patients with mediastinal hematoma and no direct signs of BAI on CT, of whom over 50% had periaortic hematoma. In their series, no patients were found to have aortic or great vessel injury. The further management of patients with evidence of BAI on CT angiography remains controversial. There are several important questions that await definitive answers. The first has to do with the management of a positive result. Bruckner et al.63 reported a positive predictive value for CT of only 15%. However, CTs that were either interpreted as equivocal or nondiagnostic were included in the positive pool. Of those scans read as definitively positive, the positive predictive value (PPV) was 100%. Further, the majority of their scans were performed on a single slice scanner with 5–7 mm collimation. Nevertheless, as recently as 2006,63 these authors recommended follow-on aortography to confirm all positive CT results (Fig. 17.8). Ng et al.11 found that the number and type of direct signs present on CT was an important factor in regard to false positives; in their series, three patients with only a single positive direct sign were found not to have BAI at aortography or surgery. Intimal flaps or intraluminal thrombus had the highest specificity for diagnosis. On the other hand, patients with three or more direct signs, including extravasation, were shown to have a high risk of immediate rupture and death. They would thus recommend proceeding immediately to repair in patients with multiple direct signs or with an intimal flap evident on CT, but proceeding to aortography when only one sign such as luminal irregularity was present. While this decision ultimately rests on the experience of the operating surgeon, a number of other studies support proceeding directly to operative repair based on CT alone.7,42,54,56,58,64 Multiplanar reconstruction techniques can yield images that are quite similar to those obtained at conventional angiography; in particular, sagittal reconstructions are usually adequate for surgical planning (Fig. 17.13).42 Downing et al.64 reviewed their experience with treatment of 54 patients with BAI and found that operating on the basis of the CT alone was both safe and expeditious. Traditionally, BAI has been treated by open thoracotomy and direct aortic repair. More recently, endovascular stent grafting is being used to treat such injuries.65–69 While immediate and ‘mid-term’ results for endovascular repair are promising, the issue has not been definitively resolved. A further interesting question is the concept of minimal aortic injury (MAI). With the increasing use of high-quality CT angiography (or endoscopic ultrasound), more and more subtle aortic intimal injuries are being diagnosed. Frequently, these injuries are detected in the absence of significant periaortic hematoma (Figs 17.14 and 17.15).7,42,59,70–72 Malhotra et  al.72 defined MAI as a small (less than 1 cm) intimal flap with no other aortic abnormality and no or minimal periaortic hematoma. In their series of 189 patients

1130

Fig. 17.13  Blunt aortic injury after a motor vehicle accident. Sagittal CT reconstruction clearly demonstrate a traumatic pseudoaneurysm (arrow) and its relationship to the aortic branch vessels, information needed for surgical planning.

with BAI, 10% were found to have MAI by CT. Aortography was normal in half the patients with MAI; in those, the diagnosis was confirmed either by surgery or by endovascular ultrasound. Follow-up studies in six of the nine patients with MAI showed that the lesion resolved in half and that a small pseudoaneurysm developed in the other half. Malhotra et al.,72 and others,70 have suggested that MAI, in hemodynamically stable patients, can be managed conservatively, but followed carefully until resolution of the lesion is documented. Furthermore, Malhotra et al.72 found that intravascular ultrasound was useful for confirming such limited injuries.

Aortography Aortography has long been considered the ‘gold standard’ for diagnosis of BAI (see Box 17.4, Figs 17.2–17.4, 17.6). Prior to the widespread application of multidetector CT, aortography was performed liberally for evaluation of patients with suspected BAI. Consequently, a large number of negative angiograms were performed; up to 90% of aortograms performed on the basis of an abnormal chest radiograph are negative.20,24,73–76 One of the great advantages of CT is to reduce the number of negative angiograms performed. In centers where high-quality helical CT is available, aortography is more often reserved for patients with either nondiagnostic scans or minimal periaortic hematoma without aortic contour abnormalities. As discussed above, some centers may also perform aortography in patients with clearly abnormal CT scans. With experience, the need for aortography should occur less and less.

Injury to the Aorta or Great Vessels

Fig. 17.14  Minimal aortic injury after a motor vehicle accident. CT shows minimal right paratracheal hematoma (yellow arrow) and an intimal flap (red arrows). There is also evidence of atheromatous plaque in the arch and questionable irregularity of the aortic contour (blue arrows) at the isthmus. There is no perivascular hematoma. Aortography (not shown) suggested blunt aortic injury. At surgery, however, the external surface of the aorta was intact and the contour abnormality was reported to be a ‘ductus bump’. Follow-up imaging showed resolution of the intimal flap. Box 17.4  Aortographic findings of blunt aortic injury

Features on aortography • • • • •

Pseudoaneurysm Frank rupture with extravasation of contrast Intimal tear with intravasation of contrast into the wall Posttraumatic coarctation Concomitant great vessel injury

Pitfalls in diagnosis • • • •

Ductus bump or diverticulum Ulcerated atheromatous plaque Preexistent aortic dissection Congenital abnormalities of the arch and the great vessels

The angiographic diagnosis of BAI is occasionally difficult and both false-positive and false-negative examinations (Fig. 17.16) are reported.77,78 Angiographic diagnosis depends on identifying a disruption of the aortic contour that ranges from a subtle contour irregularity to a focal pseudoaneurysm and even to evidence of extravasation. The two main pitfalls are ulcerated atheromatous plaque and the ductus diverticulum (ductus bump). Ulcerated

plaque can simulate an intimal flap whereas the ductus diverticulum resembles a pseudoaneurysm. Particular care, therefore, needs to be taken in the older individual with other evidence of atheromatous disease. However, this is not a problem with the younger patient and it should be noted that in one large series the mean age of the patients with BAI was 40 years.79 The appearance of a ductus diverticulum (bump) can be especially problematic. This outpouching of the aorta occurs at the attachment of the ligamentum arteriosum at the isthmus and may closely resemble a pseudoaneurysm. Other diagnostic difficulties include BAI in unusual locations, preexistent nontraumatic aortic dissection and congenital abnormalities of the aorta or great vessels. A detailed review of the problems in the angiographic diagnosis of BAI is beyond the scope of this text, but the subject is well reviewed with copious illustrations by Mirvis et al.77 and Fisher et al.80 One potential advantage of aortography over CT and transesophageal echocardiography (TEE) is that it clearly demonstrates injury to the great vessels (see Box 17.5).

Ultrasonography TEE has shown promise in the diagnosis of BAI (see Box 17.5).81–92 Smith et al.93 reported a sensitivity of 100% and a specificity of 98% for TEE in the examination of over 90 patients with suspected aortic

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Chapter 17 • Chest Trauma

A

B

Fig. 17.15  Minimal aortic injury and spine fracture after a motor vehicle accident. A, Axial and reconstructed B, sagittal CT images show a complex intimal flap in the descending thoracic aorta at the diaphragm (yellow arrows). The aortic contours are normal and there is only minimal periaortic hematoma. Note the retropulsed vertebral body fragment in the spinal canal (red arrows) at the same level. The aortic injury was managed conservatively and resolved on follow-up imaging (not shown). Box 17.5  Transesophageal echocardiography in blunt aortic injury

Advantages • • • •

Bedside examination Rapidly performed Highly sensitive and specific with skilled, experienced operator Accurate in assessing myocardial and valve function and detecting pericardial effusions

Disadvantages • Cannot be performed on all patients • Operator dependent • Difficult to provide the necessary continuous emergency department coverage • Does not adequately assess the great vessels and the descending aorta

injury. Buckmaster et  al.94 reported comparable results. In their series of 160 patients, TEE was 100% sensitive and specific, whereas aortography had a sensitivity of 73% and a specificity of 99%. On the other hand, Saletta et al.95 and Minard and Lang96 reported more modest results with sensitivities of 63% and 57% and specificities of 84% and 91%, respectively. Vignon and Lang90 reviewed the literature to 1999 and concluded that the sensitivity and specificity of TEE for BAI was 88% (range 57–100%) and 96% (range 84–100%), respectively. In another study, Goarin et al.87 reported that TEE was more sensitive than either angiography or CT for diagnosis of BAI, primarily because it detected more limited (MAI) intimal injuries. When they compared diagnostic sensitivity for ‘significant’ injuries (those requiring surgical repair), all three methods were equivalent. There are certain disadvantages with TEE. It may not be possible to perform the examination because of lack of patient cooperation or maxillofacial trauma.93 TEE is not suited to diagnosing injury to the arch vessels or distal descending aorta.90,97 TEE performance is quite dependent on the skill and experience of the operator and it can be difficult to provide continuous TEE coverage with immediate availability by skilled operators. Nevertheless, in experienced hands, TEE seems to be an excellent test for diagnosing BAI.

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Although it is not commonly used as first-line imaging, it may be quite useful for assessment of patients with indeterminate or inconclusive CT scans or aortograms.88,89 While TEE is clearly an examination of great utility, the role of intravascular ultrasound is less clear. Some authors have reported success in diagnosing BAI with this method.72,88,98 This technique is probably too invasive and time consuming to be of value as a primary investigative test. However, like TEE, its greatest value may be in the assessment of patients with indeterminate or inconclusive CT scans or aortograms.

Magnetic resonance imaging Magnetic resonance imaging (MRI) has not, to date, played a great role in the acute evaluation of suspected BAI.4,99,100 There have been, however, considerable recent advances in the quality and speed of high-resolution MRI of the aorta.101,102 It is now possible to image the aorta with the same clarity and nearly the same speed as helical CT. However, MRI of an acutely traumatized patient remains a daunting task. MRI is now currently used, and will likely continue to be used, as a problem-solving tool for diagnosis of BAI, once the patient has been stabilized.

Injury to the aortic branch vessels As has already been noted, injuries to the aortic branch vessels (subclavian, brachiocephalic, and intrathoracic carotid arteries) are less common than injuries to the aorta itself in the setting of blunt thoracic trauma.103 Branch vessel injury due to penetrating trauma is, for instance, far more common. Chen et  al.104 retrospectively reviewed 166 arteriograms performed in the setting of blunt trauma to exclude aortic or branch vessel injury. They identified 24 vascular injuries overall; 15 had isolated aortic injury, seven had isolated branch vessel injury, and two had both aortic and branch vessel injuries. They emphasized that the arteriographic features of the injuries were often quite subtle. The spectrum of branch vessel injuries reported ranges from limited intimal flaps to marked arterial dissection to complete transection with pseudoaneurysm formation.103–112

Injury to the Aorta or Great Vessels

A

B

C

D E

Fig. 17.16  False-negative aortogram after blunt aortic injury. A, Initial CT shows an intimal flap and small anterior pseudoaneurysm (arrow). B, The aortogram was interpreted as normal. C, Repeat CT performed 8 days later shows a persistent pseudoaneurysm (arrow). D, Oblique sagittal reconstruction clearly shows the relationship of injury (arrow) to the left subclavian artery (L). E, Repeat aortogram now also shows the lesion (arrow), which was surgically repaired.

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A

B

Fig. 17.17  Aortic branch vessel injury after a motor vehicle accident. A, CT shows extensive perivascular hematoma in the superior mediastinum. There is a subtle intimal flap (arrows) in the right carotid artery, confirmed at aortography (B, arrow). The aorta was normal.

Numerous authors have emphasized the difficulties in diagnosing aortic branch vessel injury.103,105–112 Chest radiographs in affected patients are frequently (usually) abnormal, although the sensitivity of the chest radiograph for branch vessel injury has not been studied in detail, perhaps due to the infrequency of these injuries. The role of CT in this regard is even less studied and concerns have been raised regarding the use of CT for diagnosis of branch vessel injury. Certainly, CT can diagnose such injuries (Figs 17.17 and 17.18), but its sensitivity and specificity in the absence of direct signs of vascular injury is unknown. In our practice, patients with significant mediastinal hematoma on CT but who have no direct signs of arterial injury frequently undergo arteriography in order to exclude great vessel injury. Furthermore, arteriography is performed if there are suggestive physical examination findings, such as diminished arm blood pressures or pulses or evidence of neurovascular compromise.

Injury to the pulmonary artery Injuries to the pulmonary arteries in the setting of blunt trauma are quite rare.113–117 Penetrating trauma to the pulmonary arteries is much more common. Blunt injury to the pulmonary arteries is often fatal, as intrapericardial rupture may lead to cardiac tamponade. Chest radiographs in all reported cases have been abnormal. CT has been used successfully to diagnose pulmonary artery laceration in the setting of blunt trauma.113,114,116,117 However, given the rarity of the injury, the sensitivity of CT for pulmonary arterial injury in this setting is unknown. Avulsion of pulmonary veins is also a rare, sometimes lethal, complication of blunt thoracic trauma.118,119

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INJURY TO THE PULMONARY PARENCHYMA (Box 17.6) Contusion of the lung parenchyma is quite common in patients with major blunt thoracic trauma and can occur at the site of injury Box 17.6  Pulmonary parenchymal injuries due to blunt chest trauma

Contusions • • • •

Appear rapidly (within a few hours) Resolve within a few days Opacities do not respect anatomic boundaries (e.g. fissures) Peripheral clearing may be noted on CT

Hematoma • • • •

May result from focal laceration Solitary or multiple nodules or masses Margins initially ill-defined but become well-defined with time May cavitate

Posttraumatic lung cysts • • • • •

Due to parenchymal laceration Solitary or multiple May be quite large Resolve slowly Residual pneumatocele may occur

Secondary injuries • Pneumothorax • Hemothorax

Injury to the Pulmonary Parenchyma

A

C

B

(coup) or in other parts of the lung (contrecoup injury).120,121 Contusion results from laceration of the pulmonary parenchyma by sudden compression and shear forces.122 Lung injury may be further compounded by fractured ribs or tearing of pleural adhesions. Alveolar hemorrhage and parenchymal destruction are usually greatest during the first 24 hours after injury.6,120,121 Nevertheless, radiographs obtained within the first few hours of injury may not show findings of contusion. Radiographs obtained shortly there­ after, however, will show either focal or diffuse homogeneous opacities (Figs 17.19 and 17.20). Because the interlobar fissures do not impede the shock wave, lung contusion does not usually localize in a lobar (or segmental) pattern. Although the opacities may appear to progress on chest radiographs for a day or 2, they tend to stabilize and then clear fairly rapidly, usually within 7 days (Fig. 17.19).120,121 Lung contusion can result in considerable respiratory distress leading to mechanical ventilation, acute respiratory distress syndrome (ARDS), and, in some cases, long-term respiratory disability.120,121 CT is clearly more sensitive for lung contusion than chest radiography (Fig. 17.21).120,123–126 Schild et  al.127 imaged experimentally induced pulmonary contusions in an animal model with CT and chest radiographs. CT detected 100% of contusions immediately after the trauma, whereas radiographs failed to detect 20% of contusions even on sequential examinations. Miller et  al.126 used CT to quantify the volume of contusion and found a correlation between contusion volume and risk for ARDS. Donnelly et  al.124 reported that lung contusion in children very frequently (95% of cases) showed subpleural sparing on CT, a finding of potential utility for differentiating contusion from infection and aspiration. Pulmonary laceration can also result in formation of posttraumatic lung cysts (pneumatoceles, Figs 17.21 and 17.22) or focal hematomas (Figs 17.23 and 17.24).128 Such lesions may be solitary or multiple. Most range from 2 cm to 5 cm in diameter, but extremely

Fig. 17.18  Aortic branch vessel injury after a high-speed motor vehicle accident. A, Frontal chest radiograph shows an abnormal mediastinum, multiple left rib fractures, and a left apical cap (arrow). B, CT shows extensive perivascular hematoma in the superior mediastinum. No direct signs of aortic or great vessel injury are seen. C, Aortogram shows nonfilling of the right subclavian artery (arrow), consistent with avulsion. large hematomas, up to 14 cm in diameter, are reported. Pneumatoceles or hematomas may be radiographically apparent within a few hours of injury. However, the lesions may not be apparent on initial chest radiographs because of associated parenchymal contusion. In such instances, the lesions will become more visible as the surrounding pulmonary parenchymal contusion clears. As is the case with lung contusion, CT is more sensitive than chest radiography for detection of posttraumatic lung cysts and parenchymal hematomas. Both lesions tend to resolve with time; pneumatoceles tend to resolve faster than hematomas. Hematomas may take many months to resolve completely and for a considerable period of time may be the only visible sequela of previous injury. Since by this stage a hematoma is a circumscribed lung mass, the lesion may be mistaken for a neoplasm (Fig. 17.23). In such a case, Takahashi et al.129 were able to identify the lesion as a hematoma by its signal characteristics on MRI. During resolution, a hematoma may communicate with the airway and manifest as a cavitary mass (Fig. 17.24). Awareness of these features is important to avoid confusion with more serious pulmonary processes such as lung cancer. Cavitating hematomas resolve without treatment. Pneumothoraces (Fig. 17.25) and pleural effusions (Fig. 17.19) commonly accompany lung parenchymal injury and may require prompt chest tube drainage. Severely injured patients are usually radiographed in the supine position, which can make detecting air and fluid in the pleural space difficult, unless the fluid or air is localized to the minor fissure, the subpulmonic spaces, or the mediastinal pleural space. In the supine position air tends to collect anteriorly and fluid tends to layer posteriorly. Anterior pneumothoraces can be detected on frontal projections taken with the patient supine, but the findings are subtle and easily overlooked.130,131 The mediastinal contours on the affected side may be seen with unusual clarity, and the anterior portion of the diaphragm may be depressed, revealing more of the base of the heart on that side.130,132 The lateral

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Chapter 17 • Chest Trauma

A A

B

Fig. 17.19  Pulmonary contusion after a fall from 6 m (20 ft). A, Initial chest radiograph shows homogeneous right upper lobe opacity consistent with contusion. B, Radiograph obtained 72 hours later shows partial resolution of right upper lobe opacity and an increasing right pleural effusion.

Fig. 17.21  Pulmonary contusion after a motor vehicle accident. CT performed to exclude aortic injury shows subtle, scattered groundglass opacities and parenchymal lung cysts (arrows) consistent with contusion and laceration. These findings were not seen on the chest radiograph (not shown).

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B

Fig. 17.20  Pulmonary contusion after a motorcycle accident and right chest wall trauma. A, Frontal chest radiograph shows an abnormal mediastinum, multiple right rib fractures, a right pleural chest tube, and a right lower lobe opacity consistent with contusion. B, CT shows homogeneous opacity consistent with contusion in the right lower lobe and possible contrecoup injury in the left lung (arrow).

Fig. 17.22  Pulmonary contusion and traumatic lung cysts after a motor vehicle accident. CT shows bilateral lower lobe contusions and traumatic lung cysts. (Courtesy of Dr. P Goodman, Durham, NC, USA.)

Injury to the Central Airways

A

B

Fig. 17.23  Pulmonary hematomas after a motor vehicle accident. A, Initial chest radiograph shows an abnormal mediastinum and left lung contusion. B, Follow-up radiograph obtained 2 weeks later shows well-defined masses in the left lower lobe consistent with hematomas. (Courtesy of Dr. P Goodman, Durham, NC, USA.)

Fig. 17.24  Pulmonary hematoma in an asymptomatic man with a history of recent chest trauma. Frontal chest radiograph shows a cavitary mass in the left lung. The lesion resolved on follow-up, consistent with cavitary hematoma. (Courtesy of Dr. P Goodman, Durham, NC, USA.) costophrenic sulcus may also be seen with unusual clarity and appear asymmetrically deep – the so-called ‘deep sulcus sign’.132 Pleural effusions may cause a diffuse haze over the lungs resulting from the filtering effect of the posteriorly positioned fluid layer (Fig. 17.19B). If the effusion is large enough, it may extend around the lung and produce a band of density along the lateral chest wall and over the apex. Cross-table lateral views can be helpful for detecting both pneumothoraces and pleural effusions. CT is highly accurate for both, and the lung bases should always be covered during the abdominal CT examination for visceral injury.133 One study showed that CT detected 100% of pneumothoraces, whereas supine frontal chest radiographs detected only 40%.134 Two other studies found that supine chest radiographs detected only about 50% of pneumo­ thoraces in trauma patients.135,136 However, Holmes et  al.136 also found that many of the pneumothoraces detected only by abdomi-

Fig. 17.25  Pulmonary contusion and pneumothorax after a motor vehicle accident. Frontal chest radiograph shows homogeneous opacity in the right lung consistent with contusion and a subtle anteromedial lucency (arrow) indicative of a small anterior pneumothorax.

nal CT did not require tube thoracostomy. Wolfman et  al.137 used CT to grade the size of such incidental pneumothoraces and found that very small ones did not require tube thoracostomy.

INJURY TO THE CENTRAL AIRWAYS (Box 17.7) Tracheal or bronchial rupture most frequently results from penetrating thoracic injuries or instrumentation.138 Injury due to blunt trauma is rare and, because of the significant force required, is frequently associated with injuries to other structures such as the aorta and great vessels, thoracic cage, and lungs.139–142 The imaging findings of airway rupture are often subtle and may be overshad-

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Chapter 17 • Chest Trauma Box 17.7  Central airway injury due to blunt chest trauma

Location • • • •

80% occur in main bronchi Right bronchus > left bronchus 15% occur in trachea Most occur within 2.5 cm of the carina

Radiographic findings • • • • •

Persistent pneumothorax despite adequate chest tube drainage Pneumomediastinum ‘Fallen lung’ sign (rare) Abnormal endotracheal tube position Endotracheal tube balloon overinflation

CT findings • Mediastinal air adjacent to airways • Airway disruption • CT ‘fallen lung’ sign

owed by other injuries. A considerable proportion of cases may go undetected until complications develop either at the site of rupture, such as bronchial stenosis, or in the lung distal to the rupture, such as septic complications or persistent atelectasis.143–146 Definitive diagnosis frequently requires fiberoptic bronchoscopy.140 There are two major indirect manifestations of tracheal or bronchial rupture – evidence of air leak and abnormal lung ventilation distal to the injury. Evidence of air leak is the more crucial finding and is seen in up to 90% of cases of tracheobronchial injury.147 However, in up to 10% of cases, the adventitial sleeve remains intact and air leak may not occur, making the diagnosis of airway injury more difficult. The most common imaging finding of air leak is pneumothorax, seen in 60–100% of cases.148,149 Pneumothoraces due to major airway injury are frequently large and persistent despite insertion of multiple pleural tubes (Figs 17.26 and 17.27); they may also be under tension. Pneumomediastinum is another important indicator of airway injury (Figs 17.27 and 17.28)149,150 and is a more specific sign than pneumothorax. Pneumomediastinum may be the only sign of air leak in patients with tracheal or intramediastinal bronchial rupture (particularly the left main bronchus).151 Pneumomediastinum due to airway injury typically manifests on chest radiographs with streaky lucencies around the carina and these extend superiorly as the air dissects in the tissue planes around the trachea, aorta, and great vessels. At the margins of the mediastinum, air dissects and elevates the mediastinal parietal pleura from the aorta and heart. On lateral radiographs, pneumomediastinum is best appreciated in the retrosternal space. Pneumothorax and pneumomediastinum seen on chest radiographs obtained after severe blunt thoracic trauma are highly suggestive of airway injury. The second major indirect manifestation of major airway injury is abnormal ventilation of the affected lung.152 This can result in ventilation–perfusion mismatch with hypoxia and cyanosis. Loss of bronchial continuity combined with intraairway hemorrhage and edema can also result in significant atelectasis. The diagnostic problems in these cases are numerous. In severely traumatized patients, atelectasis may develop for reasons other than bronchial rupture. Furthermore, significant associated pulmonary abnormalities such as lung contusion or aspiration may also be present. Collapse of a lung is expected in the presence of a pneumothorax, particularly if the pneumothorax is large and under tension. Atelectasis in patients with bronchial rupture is usually persistent and unresponsive to normal therapeutic maneuvers. Bronchial stenosis or occlusion at the site of rupture can occur if the injury is not promptly diagnosed and repaired. Septic complications including pneumonia and abscess can also be encountered in the affected lung. Further important, but infrequently observed, indirect findings of major airway injury include abnormally positioned endotracheal

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Fig. 17.26  Left main bronchus fracture after motor vehicle accident. Frontal chest radiograph shows a large persistent left pneumothorax despite adequate chest tube drainage. Note that the left lung has collapsed inferiorly away from the hilum – the ‘fallen lung’ sign. Fiberoptic bronchoscopy showed complete transection of the left main bronchus. (Courtesy of Dr. Jud Gurney, Omaha, NE, USA.)

tubes or overdistended endotracheal tube balloons.153,154 Chen et  al.155 reported that balloon overinflation occurred in 71% and balloon herniation through the defect in 29% of cases of tracheal rupture. The overinflated balloon may also assume a more rounded configuration than is normally seen. Tracheal perforation due to traumatic intubation can result in the tip of the endotracheal tube projecting too far to the right of the tracheal air column on supine chest radiographs.138 A rare but characteristic feature of bronchial rupture is the socalled ‘fallen lung’ sign, which can be seen on chest radiographs or CT139,156 (Fig. 17.26). This finding occurs in the setting of a complete bronchial transection and a large pneumothorax that allows the lung to sag away from the hilum inferiorly and laterally and, on supine CT, posteriorly. The vascular pedicle remains intact and the lung remains perfused but underventilated.157 The consequent ventilation–perfusion mismatch can result in hypoxia and cyanosis. CT has been used with success to diagnose airway injuries (Figs 17.27 and 17.28).139,155,156,158–163 CT is clearly more sensitive than chest radiography for detecting small air-leaks in the mediastinum that suggest the presence of airway injury. However, the sensitivity of CT for direct visualization of the site of injury is not 100%. Chen et  al.155 studied a group of patients with tracheal rupture and reported that CT identified the direct site of injury in 71%, whereas, in another study, direct CT evidence of tracheal rupture was seen in only 10% of patients.160 Thus, the primary role of CT in diagnosis of airway injuries is probably to suggest the possibility of injury when extraluminal air is identified adjacent to major airways. Ultimately, the diagnosis depends on awareness of the possibility of airway injury in cases of severe thoracic trauma. In a considerable number of instances the diagnosis is missed in the acute phase and is detected only because of persistent lung or lobar atelectasis. Bronchoscopy should be performed in any case in which the radiographic or CT findings suggest airway rupture.

Injury to the Central Airways

A

B

C

Fig. 17.27  Right main bronchus fracture after a sports accident. A, Frontal chest radiograph shows large right pneumothorax despite chest tube drainage and a completely collapsed right lung. Note left lung contusion. B, CT shows pneumomediastinum, a collapsed right lung (‘CT fallen lung sign’) and complete transection of distal right main bronchus (arrow). C, Coronal reformatted images show bronchial transection (yellow arrow) and intact vascular pedicle (red arrow).

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A

B

Fig. 17.28  Tracheal injury after a motor vehicle accident. A, CT shows extensive mediastinal emphysema and marked focal enlargement and irregularity of the apparent tracheal lumen (arrow). B, Coronal reconstruction shows complete transaction of the trachea (arrow) with marked separation of the proximal (P) and distal (D) portions.

INJURY TO THE ESOPHAGUS OR THORACIC DUCT (Box 17.8) Instrumentation is the most common cause of traumatic esophageal rupture.164,165 Most noniatrogenic traumatic esophageal injuries are due to gunshot wounds.166 Esophageal rupture due to blunt thoracic trauma is quite rare, accounting for only 10% of all noniatrogenic cases.167,168 The radiographic features of esophageal rupture are more fully discussed elsewhere (see p. 921) and include pneumo­ mediastinum, pneumothorax, or pleural effusion, most commonly on the left side, and evidence of mediastinitis, including abscess formation. Diagnosis of esophageal rupture in the trauma patient can be quite difficult because these findings may be attributed to other injuries and considerable delay in diagnosis is common.165,167 Unfortunately, this delay in diagnosis results in a higher incidence of infectious complications. The majority of esophageal ruptures due to blunt trauma occur in the cervical and upper thoracic region (Fig. 17.29) but distal esophageal rupture following blunt external trauma has been described.169,170 In many cases, particularly with

Box 17.8  Thoracic duct injuries

Mechanism • Penetrating >> blunt trauma

Imaging appearances • Chylothorax • Lymphocele

Location • Left – injuries above T6 • Right – injuries below T6

Diagnosis • • • •

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Lymphangiography Lymphoscintigraphy Percutaneous aspiration Magnetic resonance lymphangiography

gunshot wounds, the diagnosis is made by surgical exploration. Otherwise, an esophagram using water-soluble contrast will readily confirm the injury. Injuries to the thoracic duct are usually due either to penetrating trauma or to surgical injury during thoracic exploration (Figs 17.30 and 17.31).171,172 Thoracic duct injury from blunt external trauma is exceedingly rare.173 Rupture of the thoracic duct can result in chylothorax (Fig. 17.30) or, occasionally, a localized lymphocele (Fig. 17.31).174 Fluid accumulation is characteristically slow and many days may pass before considerable quantities of fluid accumulate. Definitive diagnosis rests on determining that the fluid collection is chylous or that it communicates with the thoracic duct.174–176 The site of injury to the thoracic duct determines the side on which the fluid accumulates. The duct enters the thorax through the aortic hiatus in the diaphragm and ascends along the right anterolateral aspect of the spine. In the midthoracic region (about the level of the sixth thoracic vertebral body), the duct crosses the midline and ascends along the left anterolateral aspect of the spine. Finally, it arches forward to enter the venous system in the region of the left jugular and subclavian vein junction. As the duct arches into the left cervical region, it is particularly vulnerable to penetrating injury. Worthington et al.177 described eight cases of rupture involving the upper portion of the thoracic duct above the level of the aortic arch, seven of which were caused by knife wounds. All seven were associated with left chylothorax. On the other hand, injuries to the duct below the level of the sixth thoracic vertebral body usually result in right-sided chylothorax or lymphocele formation. Because the duct lies in close proximity to the spine, there is a significant association between thoracic duct injury and fracture-dislocation injuries of the thoracic spine.178 Large persistent pleural effusions in patients with such fractures suggest the possibility of thoracic duct injury. Lymphangiography has been used successfully to determine the site of leakage prior to surgical intervention. Sachs et al.179 studied 12 patients with chylous ascites or chylothorax following surgery and found abnormal lymphangiograms in seven. Lymphoscintigraphy (Fig. 17.31),174 CT-guided needle aspiration,176 and magnetic resonance (MR) Lymphangiography have also been used to successfully diagnose chylothoraces and lymphoceles180,181 due to thoracic duct trauma.

Injury to the Esophagus or Thoracic Duct

A

C

B

Fig. 17.29  Esophageal injury in a man with dysphagia after recent automobile accident. A, Frontal chest radiograph shows air in the proximal esophagus (arrow). B, CT performed after administration of thick-barium paste shows a dilated esophagus (e) and extraluminal barium (arrow). C, Esophagram shows a mucosal flap (arrow) in the proximal esophagus.

Fig. 17.30  Chylothorax in a man with chest pain after a recent esophagectomy with gastric bypass for esophageal carcinoma. CT shows a large fluid collection in the mediastinum and right pleural space. Aspiration confirmed chylothorax.

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A

C

B

INJURY TO THE DIAPHRAGM (Boxes 17.9 and 17.10) Acute diaphragm rupture can result from either penetrating injury or blunt thoracoabdominal trauma182 (see Box 17.9). Rupture can result in herniation of abdominal contents into the chest, either acutely or in a delayed fashion. Herniated viscera can cause respiratory distress because of heart or lung compression. Herniated bowel can also strangulate, sometimes years after the initial injury.183 Penetrating injuries to the diaphragm are usually caused by knife or bullet wounds (Fig. 17.32). These injuries usually cause shorter diaphragmatic tears than those seen after blunt trauma.184 Because the tear is usually so small, herniation of abdominal contents is uncommon. Furthermore, because adjacent lung is frequently injured, the contours of the diaphragm may be obscured on the frontal chest radiograph, making detection of small hernias (if present) difficult. Thus, definitive diagnosis may be delayed. For example, Demetriades et al.185 found herniation of abdominal contents in only 15% of 150 patients with penetrating injuries of the diaphragm. Diagnosis was delayed in almost half of the affected patients. Because associated abdominal injuries that require exploratory laparotomy (e.g. liver, spleen, or bowel laceration) occur in at least 75% of affected patients, diaphragmatic injuries due to penetrating trauma are usually detected by direct inspection. Diaphragm rupture due to blunt thoracoabdominal trauma is usually the result

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Fig. 17.31  Thoracic lymphocele after a motor vehicle accident complicated by aortic transection and left diaphragm and spleen rupture. A, Frontal chest radiograph shows a well-circumscribed left periaortic mass (arrow). Note findings of prior left rib, scapular, and clavicular trauma. B, CT shows that the mass is of fluid attenuation. C, Frontal view of chest from a technetium-99m antimony sulfur colloid lymphoscintigram shows activity within the mass (arrow), confirming the diagnosis of thoracic lymphocele. S, markers on shoulders; L, liver activity. (With permission from Perusse KR, McAdams HP, Earls JP, et al. General case of the day. Posttraumatic thoracic lymphocele. RadioGraphics 1994;14:192– 195. Copyright Radiological Society of North America.)

Box 17.9  Clinical features of diaphragmatic rupture

Mechanism of injury • Penetrating injury • Blunt trauma, usually high-speed motor vehicle accidents or fall from height

Incidence • Seen in 3–5% of patients admitted to major trauma centers

Mortality • Approximately 20–25%, mainly due to associated injuries

Associated injuries • Over 90% have solid abdominal organ injury • 10% have associated blunt aortic injury • Pelvic fractures, spinal fractures, and closed head injuries common

Diagnostic peritoneal lavage • Left-sided ruptures – a small number (15–30%) may have a negative lavage (lesser sac sequestration of blood) • Right-sided ruptures – almost invariably positive

Injury to the Diaphragm Box 17.10  Imaging findings of acute diaphragmatic rupture

Chest radiography • • • • • •

85–90% show abnormalities of some type Pleural fluid ± pulmonary contusion ‘Elevated’ hemidiaphragm Stomach and bowel loops high in the chest Diaphragm obscured by atelectasis and pleural fluid Abnormal course of the orogastric tube

CT • High position of the liver or the stomach in the chest with contra­lateral shift of the heart • Diaphragmatic defect may be directly shown – focal or complete discontinuity • Diaphragm thickening • Sagittal and coronal reconstructions – diaphragmatic defect. • Collar or gathering effect on herniated liver or bowel (‘collar’ or ‘waist’ sign) • ‘Dependent viscera’ sign • ‘Hump’ and ‘band’ signs – specific to right diaphragm ruptures

Ultrasonography • Disrupted diaphragm • ‘Floating’ portion of diaphragm • Demonstration of liver or bowel herniation

MRI • Diaphragm shown with clarity – either intact or disrupted • Herniation of liver, stomach, or bowel clearly shown

Fig. 17.32  Right diaphragm laceration due to gunshot wound to the right chest. CT shows a large right pleural hemothorax, parenchymal lung injury, and hepatic laceration (arrow). The diaphragm injury is not directly visualized, but is inferred from the injury pattern; a small tear was visualized and repaired at laparoscopy.

of a high-speed motor vehicle accident or a fall from a considerable height. The high incidence of associated injury is reflected in reported mortality rates of up to 25%.186–188 Over 80% of patients with traumatic rupture of the diaphragm have concomitant intra­ abdominal injuries, typically liver and spleen lacerations.189 Pelvic and spinal fractures are frequent, as is closed head injury. Further, up to 10% of patients with diaphragm rupture due to blunt trauma also have aortic injury190 (Fig. 17.33). Diaphragm rupture due to

blunt trauma is more commonly seen on the left, possibly because the liver acts as a buffer on the right. In several large series, 67–88% of ruptures were left sided (Fig. 17.33), 12–28% were right sided (Fig. 17.34) and 5% were either bilateral or central in location.184,187,191 While this left-sided predominance may be due to the protective effect of the liver, it may also reflect difficulties in diagnosis of rightsided injuries and that patients with right-sided injuries may have more associated and severe injuries. Autopsy studies of trauma victims who died at the accident site or before hospitalization report an equal frequency of right and left-sided ruptures,189 in marked contrast to the left-sided predominance noted in surgical series.184,187,191 This finding suggests that patients with right-sided ruptures are more likely to die acutely, due to other severe injuries. For example, Boulanger et  al.189 found that 100% of patients with right-sided ruptures had associated intraabdominal injuries whereas only 77% of patients with left-sided rupture had such injuries. Preoperative diagnosis of diaphragmatic rupture after blunt trauma can be difficult. Diagnosis by chest radiography depends on demonstration of herniated abdominal contents within the thorax (see below). However, herniation of abdominal contents does not always occur in cases of traumatic rupture, particularly if positive-pressure ventilation is used (Fig. 17.34).192,193 Prior to widespread use of CT in the setting of trauma, a significant number of diaphragmatic injuries were discovered at exploratory laparotomy.186,187,192 Shah et al.194 reviewed 980 reported cases of traumatic rupture and found that only 44% were diagnosed prior to exploratory surgery. Over 40% of the ruptures were diagnosed during surgery or at autopsy and, in 15% of cases, the injury was not diagnosed during the initial hospitalization. Beal and McKennan,195 also using chest radiography, suggested the correct preoperative diagnosis in only 12 of 37 patients. These authors emphasized the diagnostic problems caused by associated lung contusion or laceration, hemothoraces, pneumothoraces, and rib fractures. Left-sided ruptures appear to be more easily diagnosed than right-sided ruptures. In cases of left-sided rupture, there are often distinct radiographic findings of herniation such as identifiable gastrointestinal gas patterns within the thorax or an abnormally positioned orogastric tube. On the other hand, right diaphragmatic ruptures with liver herniation often lack such distinctive radiographic features. Right diaphragmatic rupture may manifest as an ‘elevated’ diaphragm196 and associated right basal pulmonary opacities or pleural fluid may not elicit particular concern in a severely injured patient. In the series of Boulanger et al.,189 37% of the left-sided ruptures were diagnosed by chest radiography whereas none of the right-sided ruptures were so diagnosed. Thus, delayed diagnosis is particularly likely when the right diaphragm is ruptured.191,197 What is clear from review of the literature is that diagnosis of diaphragmatic rupture by chest radiography first and foremost requires a high index of suspicion for the possibility of such an injury.184 This is particularly true in regard to the difficult-to-diagnose right-sided ruptures. As noted above, confident radiographic diagnosis of diaphragmatic rupture depends upon identifying herniated abdominal contents in the thorax (see Box 17.10). Herniation of hollow viscera is recognized by the characteristic gas patterns of herniated stomach or bowel (Figs 17.33, 17.35, and 17.36). Continuity of these loops of bowel with infradiaphragmatic bowel may be apparent, possibly with some constriction or gathering of loops at the site of the rupture. Normal diaphragmatic contours are usually obscured on the chest radiograph and there may be associated pleural fluid or basal atelectasis. Diagnosis can be difficult if the herniated stomach forms an arc-like contour simulating a paralyzed or eventrated diaphragm (Fig. 17.35). Furthermore, if only a small amount of bowel herniates, it may be obscured by pleural fluid and contused or collapsed lung. Placement of an orogastric tube can be helpful with gastric herniation into the left chest; the gastric tube either is held up at the esophageal hiatus or curves upward beyond the hiatus into the left chest (Fig. 17.36).198 Contrast studies of the gastrointestinal tract are rarely necessary or even appropriate in the acute setting. However, such examinations can be useful for

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A

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Fig. 17.33  Blunt aortic injury and left diaphragm rupture after a motor vehicle accident. A, Frontal chest radiograph shows an abnormal mediastinum, rightward shift of endotracheal and orogastric tubes, and apparent elevation of left diaphragm. B, CT shows intimal flap and pseudoaneurysm indicative of aortic injury (arrows) and air–fluid-filled stomach (*) herniated into left thorax. C, Coronal reformatted images show left diaphragm discontinuity (yellow arrow), a ‘collar sign’ (red arrow) with herniated stomach (*), and aortic injury (blue arrow).

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Injury to the Diaphragm

A

B

D

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Fig. 17.34  Right diaphragm rupture after a motor vehicle accident. A, Initial frontal chest radiograph shows right lung contusion and an elevated right diaphragm. B, Repeat radiograph obtained after intubation and institution of positive-pressure ventilation shows right diaphragm in normal position. A right hemothorax has been drained. C, Chest radiograph obtained at discharge again shows an elevated right diaphragm and an apparent right pleural effusion. D, CT showing that the apparent pleural fluid is actually herniated omentum (*) and bowel and that the apparently elevated diaphragm is due to herniated liver (L). evaluation of patients presenting in a delayed fashion.199–201 Radiographic diagnosis of herniation of solid viscera or omentum is more difficult and accounts in large part for the delays in diagnosis of right diaphragm rupture (Fig. 17.34, see also Fig. 17.1).202 Diaphragm rupture can be confused with posttraumatic diaphragmatic paralysis or posttraumatic pneumatoceles.203 As the rent in the diaphragm allows free passage of fluid or air between the abdominal and pleural cavities, the diagnosis is sometimes suggested by seemingly inappropriate passage of air or fluid across this barrier. For example, peritoneal lavage fluid may be detected in the pleural cavity at a subsequent CT examination. An otherwise inexplicable association between pneumothorax and pneumoperitoneum suggests the diagnosis.

CT is now widely performed in patients with blunt thoraco­ abdominal trauma and has assumed an increasingly important role in preoperative diagnosis of diaphragmatic injuries.182,204–208 This is particularly true since the advent of high-speed multidetector helical CT with sagittal and coronal reformatted images. Although CT is clearly useful for demonstrating rupture in the presence of herniation, it can also show ruptures in the absence of herniation.209 The CT findings of diaphragmatic rupture are well described (Figs 17.33, 17.34, and 17.37–17.40).193,209–216 Typical findings include direct visualization of the diaphragmatic defect, retraction and thickening of the ruptured diaphragm, and herniation of peritoneal fat or abdominal viscera into the chest. Herniated gut may show a focal constriction at the site of the rupture; this is known as the ‘collar’

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Chapter 17 • Chest Trauma

A

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Fig. 17.35  Left diaphragm rupture after blunt abdominal trauma. A, Frontal and B, lateral chest radiographs show herniated stomach in the left lower hemithorax. The upper margin of the gastric wall simulates the normal appearance of the diaphragm. However, the anterior margin of the stomach (yellow arrows) curves down to the actual level of the diaphragm (red arrow).

Fig. 17.37  Left diaphragm rupture after a motor vehicle accident. CT shows the contrast-filled stomach (S) in the left hemithorax. Note the ‘collar sign’ (arrows) as the stomach herniates through the rent in the diaphragm. Fig. 17.36  Left diaphragm rupture after blunt abdominal trauma. Frontal chest radiograph shows herniated stomach in the left hemithorax. Note that the orogastric tube turns upwards into the intrathoracic stomach. or ‘waist sign’. Rees et al.207 reported two variants of the collar sign suggestive of right diaphragm injury: the ‘hump sign’, a round portion of liver herniating through the diaphragm to form a humpshaped mass, seen in 10/12 (83%) patients, and the ‘band sign’, a linear lucency across the liver along the torn edges of the diaphragm, seen in four (33%). Both signs were seen to much better advantage on sagittal and coronal reformatted CT images. Bergin et al.217 described the ‘dependent viscera’ sign when the upper third of the liver abuts the posterior right ribs or the bowel or stomach lies in contact with the posterior left ribs on CT. In their experience217 this sign was seen in 100% of left-sided ruptures and 83% of

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right-sided ruptures. Common associated findings on CT include rib fractures, pleural effusions, basal atelectasis or contusion, pneumothorax, or pneumomediastinum. While CT is now regarded as a very good test for diagnosis or exclusion of diaphragm rupture, it is not perfect.208 In an early study, Shapiro et al.193 diagnosed only five of 12 ruptures by CT and emphasized the difficulty of diagnosing right diaphragm injuries. Nau et al.218 reported their experience with diaphragmatic injuries (20 blunt, 11 penetrating) over a 10-year period and found that chest radiography and CT diagnosed only a minority of tears. Surprisingly, they reported no significant difference between the diagnostic sensitivity of chest radiography and CT. However, it should be noted that neither group used the most up-to-date CT scanners with multiplanar reformat capabilities.193,218 Other authors have reached different conclusions regarding the accuracy of CT. Worthy et al.216 reported findings diagnostic of rupture in nine of 11 patients.

Injury to the Diaphragm

Fig. 17.38  Left diaphragm rupture after blunt abdominal trauma. CT shows herniation of the stomach and omental fat through a small diaphragmatic defect (yellow arrow). Note again the classic ‘collar’ sign (red arrows).

A

Murray et  al.214 reported sensitivity of 61% and specificity of 87% for diagnosis of rupture in a series of 32 patients with suspected diaphragmatic injury. Nchimi et al. reported sensitivities for diagnosis of diaphragm rupture by CT that ranged from 56% to 88% among four reviewers.208 When, however, two additional interpreters based diagnosis on the presence or absence of 11 specific CT signs, sensitivity increased to 100%. In this study, diaphragmatic discontinuity, diaphragmatic thickening, segmental nonvisualization of the diaphragm, intrathoracic herniation of abdominal viscera, elevation of the diaphragm, and combined hemothorax and hemoperitoneum were the best predictors of diaphragm rupture.208 Thus, while the sensitivity of CT is clearly not 100%, it is widely used for evaluation of seriously injured patients and should detect the majority of diaphragmatic ruptures.204,205 MRI can be a useful adjunct to CT for diagnosis of traumatic diaphragmatic injuries (Figs 17.41 and 17.42).191,204,205,219–226 Because MRI can directly image multiple planes and identify the entire diaphragm as a distinct and separate structure, it has some advantages compared with conventional CT. Shanmuganathan et  al.221 found that MRI was often more definitively positive than CT in diagnosing rupture in seven patients and also correctly excluded rupture in nine others by clearly showing total continuity of the diaphragm. However, the latest generation multidetector CT scanners with multiplanar reformatted images obviate many of the putative advantages of MRI.227 Furthermore, it remains quite difficult to image acutely injured patients with MRI. Thus, CT remains the mainstay for diagnosis of traumatic diaphragm rupture; MRI is reserved for the more difficult cases (particularly suspected rightsided ruptures) in more stable patients. There has been little interest in using ultrasonography to diagnose traumatic rupture of the diaphragm in humans. However, animal data suggest that ultrasound can be quite sensitive for detecting ruptures.188 Because both bowel and diaphragm are readily identifiable on ultrasound, diagnosis of visceral herniation in this setting is relatively straightforward.202,228,229 The edges of the torn diaphragm and actual site of disruption are also frequently detectable by ultrasonography.188,229

B

Fig. 17.39  Right diaphragm rupture after blunt abdominal trauma. A, Frontal chest radiograph shows apparent elevation of the right diaphragm and right lower lobe partial atelectasis. B, CT shows focal herniation of the medial portion of the right hepatic lobe into the thorax. Note the indentation of the hepatic contour at the site of herniation (‘hump’ sign, yellow arrows) and associated liver laceration (red arrow).

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Chapter 17 • Chest Trauma • Myocardial contusion or infarction231–233 • Myocardial rupture, resulting in hemopericardium and tamponade234,235 • Septal rupture236,237 • True and false myocardial aneurysms238,239 • Coronary artery rupture, resulting in hemopericardium, false aneurysm formation, and infarction240,241 • Rupture of chordae tendineae, resulting in valve insufficiency (most commonly the tricuspid valve)242,243 • Pneumopericardium244,245 • Postpericardiectomy syndrome and constrictive pericarditis as late sequelae246,247 • Herniation of the heart through a pericardial tear (Fig. 17.45).248–250

Fig. 17.40  Right diaphragm rupture after blunt abdominal trauma. CT shows herniation of liver into the right hemithorax. Note the dependent viscera sign (arrows) and associated hepatic lacerations.

Most of these conditions have clinical and imaging features that are similar to their nontraumatic counterparts and are beyond the scope of this discussion. Myocardial contusion is probably the most common cardiac injury caused by blunt trauma238 and can cause life-threatening arrhythmias and heart failure.230,231 Diagnosis is difficult, however, because symptoms are nonspecific and there are few specific tests for myocardial injury. Traditional diagnosis has rested upon the finding of electrocardiographic changes in the setting of blunt thoracic trauma. Studies have shown that elevated levels of cardiac troponin I and T are highly sensitive for myocardial injury.231 Collins et al.,251 however, found that elevated troponin levels did not necessarily correlate with the clinical significance of the contusion. On imaging, severe cardiac contusions manifest with pulmonary edema that may be misattributed to overvigorous fluid resuscitation. Cardiac herniation through a pericardial tear is a rare but dramatic form of injury.248–250,252–256 In the acute setting, this injury is associated with high mortality because torsion of the great vessels results in severely compromised venous return and cardiogenic shock. In the majority of described cases, the diagnosis was made on chest radiography by noting the displaced and distorted cardiac contour (Fig. 17.45). Traumatic pericardial rupture with cardiac herniation has also been diagnosed using CT.257,258 CT has also been used to diagnose traumatic ruptures of the heart itself.234,235

INJURY TO THE THORACIC CAGE Some of the more important aspects of this topic as they apply to chest imaging are summarized below.

Rib fractures

Fig. 17.41  Left diaphragm rupture after blunt abdominal trauma. Coronal T1-weighted MR image clearly demonstrates herniation of stomach (S) and omental fat into the left chest. Note that the ends of the torn diaphragm (arrows) are well visualized by MRI.

INJURY TO THE HEART OR PERICARDIUM The heart and pericardium are fairly well protected from the effects of blunt thoracic trauma injury. Cardiac and pericardial injuries due to blunt trauma, other than cardiac contusion, are uncommon.230 Penetrating trauma, on the other hand, is usually the result of a felonious assault, and the mortality is high (Figs 17.43 and 17.44). The following injuries may be encountered following blunt chest trauma:

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Rib fractures are very common in clinical practice and most are of limited clinical significance.259 Occasionally, however, the fractured rib ends lacerate the pleura or lung causing bleeding or pneumo­ thorax. Thus, the primary indication for radiography in patients with suspected rib fractures is to exclude such complications. For this reason, a single frontal upright chest radiograph will usually suffice. Rib detail studies are usually not required, but may be driven by medicolegal considerations. Danher et  al.260 studied radiographs from over 1100 cases of chest trauma and found that only 17 patients were admitted to the hospital for reasons related exclusively to rib trauma. In only two of these cases did oblique views give additional information, and even this information was clinically inconsequential. Other authors have reached similar conclusions.261–263 In the absence of significant associated pain, pneumothorax, or hemothorax (Fig. 17.46), fractures of single ribs are usually not of major importance. However, fractures of multiple contiguous ribs can result in a flail chest deformity that has significant morbidity and mortality (Fig. 17.47).264–268 This injury causes paradoxical retraction of the affected hemithorax during inspiration, impairing ventilation.269 Affected patients often require mechanical ventila-

Injury to the Thoracic Cage

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D

Fig. 17.42  Pneumopericardium and right diaphragm rupture after blunt abdominal trauma. A, Frontal chest radiograph shows an elevated right diaphragm, a right pneumothorax, and air in the pericardial sac (arrows). B, CT shows a large right pneumothorax and pneumopericardium (*) and the position of the liver suggests a ruptured right diaphragm. C, D, Sagittal T1-weighted MR images show lateral herniation of liver into the right hemithorax. Note that the diaphragm is well visualized medially (C, arrow) and posteriorly (D, arrow), but is absent over the lateral dome of the liver. L, liver.

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Fig. 17.43  Hemopericardium after a stab wound to the right chest. A, CT shows soft tissue attenuation pericardial fluid consistent with hemorrhage. B, Oblique axial maximum intensity projection reconstruction more clearly demonstrates knife track (arrow) in anterior chest wall. (Courtesy of Dr. Santiago Martinez, Durham, NC, USA.)

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Fig. 17.44  Intracardiac air after a fatal stab wound to the right chest. Frontal chest radiograph shows a large right pneumothorax, right pleural effusion, and air in the heart due to a bronchus-topulmonary vein fistula. Note that the intracardiac air outlines the intraventricular trabeculations, distinguishing it from pneumopericardium.

Fig. 17.45  Cardiac herniation after pericardial window placement for uremic pericarditis. Frontal chest radiograph shows marked lateral displacement of the cardiac apex (arrow) due to herniation of the heart through the pericardial window.

tion and may require surgical stabilization.265 Although the definition of flail chest varies, contiguous fractures of four or more ribs make it a distinct clinical possibility. Thin-section CT with threedimensional reconstructions has been used to assess the flail segment prior to surgical stabilization.264,270 Although rib fractures are, of themselves, often of little clinical import (except in the setting of a flail segment), the number or location of fractures can be a marker for the severity of thoracic injury.271 This is particularly true in the setting of motor vehicle accidents. Generally speaking, the greater the number of rib fractures, the greater the likelihood of severe intrathoracic injury and morbidity and mortality.267 Furthermore, fractures of certain ribs indicate severe trauma and may suggest increased likelihood of injury to specific organs. For example, considerable force is required to

fracture the first, second, and third ribs because they are well protected by the shoulder girdle and associated musculature.39 Patients with fractures of these ribs may be at greater risk for injury to important structures such as the aorta and great vessels.272 Lee et al.,35 in a review of 548 patients with suspected blunt aortic injury, found a higher incidence of rib fractures in patients with aortic injury than in those without. However, the positive predictive value of fractures for blunt aortic injury was only 14%, a rate similar to the incidence of aortic injury at major trauma centers. Lee et al.,35 and others,36–39 have concluded that first rib fractures seen in isolation, without other evidence for aortic or great vessel injury (e.g. mediastinal hematoma), are not a sufficient indication for angiography. Fractures of the tenth, eleventh, or twelfth ribs raise the possibility of injury to the liver, kidneys, or spleen. It should be

Injury to the Thoracic Cage

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Fig. 17.46  Rib fracture and hemothorax due to intercostal artery laceration. A, CT shows mixed attenuation left pleural effusion (*) consistent with hemothorax, displaced rib fracture (yellow arrow), and focus of contrast extravasation (red arrow). B, Oblique axial maximum intensity projection reconstruction shows contrast extravasation (arrow) to better advantage. Arteriography (not shown) confirmed intercostal artery laceration, which was successfully embolized. (Courtesy of Dr. Santiago Martinez, Durham, NC, USA.)

Fig. 17.47  Flail chest deformity in a man with severe dyspnea after a motorcycle accident. Frontal chest radiograph shows an abnormal mediastinum, and multiple contiguous right rib fractures (arrows). Note also fractures of the scapula and clavicle. CT (not shown) showed only fat in the anterior mediastinum; the aorta was normal. remembered, however, that major internal thoracic injuries can occur in the absence of rib fractures, particularly in younger individuals.273 Rib fractures are commonly seen in children subject to physical abuse.274,275 Indeed the finding of occult rib fractures may be a critical clue to the fact that the child has been abused. Rib fractures are uncommon in infants and young children and, when present, should be attributable to a known episode of significant trauma.276 Underlying conditions that may predispose to rib fractures such as rickets or osteogenesis imperfecta must be excluded. Rib fractures in abused children are often bilateral and at varying stages of healing. Callus formation may be prominent, a feature that makes the fractures more readily visible. Certain rib fractures may have distinct or noteworthy features:

• Stress fractures. Fractures of the first or second ribs may be stress fractures as a result of activities such as backpacking. The bony reaction and callus formation may give a spurious appearance of an apical pulmonary parenchymal process. Apical lordotic and rib detail views plus the clinical circumstances should clarify the diagnosis. • Cough fractures. These may also be stress fractures but occur in older patients, usually in the posterolateral aspects of the lower ribs. The patient may experience localized rib pain. Callus formation around the fractures may be conspicuous. • Excessive callus formation in cushingoid patients. Patients with Cushing syndrome or who are receiving intensive steroid therapy are frequently osteoporotic and have an increased tendency to develop fractures. An interesting and characteristic feature of fractures in these patients is the exuberant callus formation that occurs in relation to the fractures.277 This exuberant callus may simulate a pulmonary parenchymal process. • Multiple rib fractures in alcoholic patients. Hard-core alcoholic patients frequently have multiple bilateral rib fractures in varying stages of healing.278 Such fractures may be an indicator of other medical consequences of alcohol misuse. • Pseudoarthroses of ribs. On occasion, rib fractures evolve into pseudoarthroses, since ribs are difficult to immobilize. As with stress fractures or excessive callus formation, an unwary or unobservant physician may diagnose a parenchymal lesion on chest radiographs. • Pathologic fractures are clearly of the utmost clinical significance. The diagnosis hinges on identifying a fracture through a destructive process. Obtaining detailed views or tomography may be necessary to confirm the suspicion of focal bone destruction. The majority of such fractures relate to metastatic neoplasm or myeloma, but on occasion they are due to a benign process such as eosinophilic granuloma.

Sternal fractures Up to 8% of patients admitted with blunt chest trauma have sternal fractures.279,280 These fractures cannot be seen on frontal chest radiographs and may be difficult to diagnose on lateral chest

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Fig. 17.48  Sternal fracture after a motorcycle accident. A, CT shows anterior mediastinal hematoma. The periaortic fat planes are preserved and the aorta is normal in contour. Note displaced sternal fracture (arrows), shown to better advantage on B, sagittal reconstruction.

A

B

Fig. 17.49  Sternoclavicular joint dislocation after a motorcycle accident. A, Frontal chest radiograph was interpreted as normal. Note, however, slight asymmetry of clavicular heads. B, CT shows posterior dislocation of left proximal clavicle (arrows), with potential for great vessel impingement or injury. (Courtesy of Dr. Santiago Martinez, Durham, NC, USA.) radiographs. In appropriate circumstances, careful attention should be paid to the sternal contours on the lateral view (Fig. 17.48). Sternal fractures as such do not generally cause problems either in healing or by direct damage to adjacent structures. Costochondral separation may occur in younger individuals, and this usually also indicates significant trauma. The diagnosis of costochondral separation, however, is essentially based on clinical findings. The presence of a sternal fracture usually indicates significant chest trauma, and the radiologist should be alert to the possibility of a deceleration injury to the aorta, the great vessels, or the myocardium.272,279–282 On the other hand, Chiu et  al.283 could not find any evidence of myocardial injury in over 30 patients with sternal fracture, nor could Sturm et al.73 detect any increase in the incidence of aortic rupture in patients with sternal fracture as opposed to those without.

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Sternoclavicular joint and scapula Dislocation of the sternoclavicular joint with posterior displacement of the inner end of the clavicle may cause compression of the trachea and the adjacent great vessels with important clinical consequences.284,285 Dislocation of a sternoclavicular joint may be difficult or impossible to detect on chest radiographs (Fig. 17.49), particularly in a patient with major trauma in whom the radiographic examination is restricted. However, tracheal deviation may be noted and paratracheal soft tissue thickening may be apparent. The diagnosis of dislocation of the sternoclavicular joint is readily made with CT.286–288 Clinical awareness of the possibility of such an injury is the key to its recognition, with radiographs often helping to confirm the diagnosis.

Miscellaneous Injuries

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Fig. 17.50  Scapulothoracic dissociation after a motorcycle accident. Patient presented with a diminished right radial pulse. A, Frontal chest radiograph shows lateral dislocation of the right clavicle with widening of the sternoclavicular joint (yellow arrow). Note also that the medial scapular border (red arrows) is laterally displaced when compared with the left (blue arrows). These findings suggest scapulothoracic dissociation. B, Selective right subclavian arteriogram shows complete transection of the right subclavian artery (arrow) with abundant collateral vessels. The patient also sustained a significant right brachial plexus injury.

Traumatic scapulothoracic dissociation occurs when the attachments of the scapula to the axial skeleton are completely disrupted when a severe rotational force is placed on the shoulder.289,290 It most commonly occurs in the setting of a motorcycle crash. Scapulothoracic dissociation typically results in injury to the subclavian or axillary vessels, lateral displacement of the scapula, disruption of the clavicular articulations with or without a clavicular fracture, and cervical nerve root avulsion or brachial plexus injury.289,291–295 On chest radiographs, the finding of either a clavicular fracture or disruption of either the sternomanubrial or the acromioclavicular joint in combination with lateral displacement of the scapula suggests scapulothoracic dissociation (Fig. 17.50).

Vertebral fractures Fractures of the thoracic spine are not usually of much direct consequence to the respiratory system. Paravertebral hematoma adjacent to these fractures, however, may be conspicuous on chest radiography (Fig. 17.51, see also Fig. 17.7), and due allowance should be made when diagnosing lower lobe collapse or aortic injury.33,296 Nevertheless, when studying the initial chest radiographs on trauma victims, it is important to study the thoracic spine with care. The signs of thoracic spine fracture may not be obvious. Lawrason et al.,297 in a study of 34 patients with thoracic spine injury, found that only 18 patients (53%) were initially reported as having fractures, whereas on review fractures were seen in 27 patients (79%). The signs they reported included widening of the paraspinal reflections and apical pleural caps, decreased vertebral body height, lateral offset of vertebral bodies, increased interpediculate and interspinous distances, and rib disarticulation.

MISCELLANEOUS INJURIES Injury due to gunshot, blast, or stab wounds Most gunshot wounds to the lungs in civilian practice are the result of low-velocity missiles. Although the missiles may fragment, the

devastating fragmentation of a high-velocity missile is not seen. In addition, the shock waves of low-velocity missiles are not nearly so severe or extensive in their effects. The lung is a low-density structure of high elasticity, and the degree of damage is much less than in high-density, low-elasticity structures such as liver or brain.298 A low-velocity missile traversing the lung forms a distinct track that may be air-filled or occupied by hematoma (Figs 17.52–17.54).299 Surrounding this track is a variable zone of lung contusion. On occasion the track itself is visible, and gauging the thickness and extent of the surrounding contusion may be possible. This observation applies particularly to cases with an air-filled track radiographed in the axis of the track. Shotgun injuries are generally severe because of the intermediate muzzle velocity of these weapons and the large mass of the shot. Shotgun injuries to the chest are said to be nearly 10 times more lethal than wounds from other weapons.300 The pleura is inevitably involved in pulmonary damage from gunshots and thus hemothorax or pneumothorax is common. The chest radiographic appearance is a critical factor in determining whether or not the pleural space should be drained. In damage confined to the lungs and pleura, drainage may be the only direct intervention required. Stab wounds do not generate shock waves, and the resultant contusion of lung parenchyma is less. As with gunshot wounds the impact of stab wounds relates to the extent and severity of damage to major vascular structures and the pleura or pericardium. Blast injuries are still relatively uncommon in civilian practice, although clearly of major importance in wartime and in settings of terroristrelated activity.301,302 Cohn120 comprehensively reviewed the subject of pulmonary contusion in blast injuries and found that pulmonary hemorrhage was the dominant pathologic finding in such cases. In described cases, the radiographic changes are typically bilateral and centered on the major airways with perihilar edema and contusion.120,303,304

Lung torsion (Box 17.11) Torsion of a lung or a lobe of lung is an extremely rare but serious condition that rarely results from blunt chest trauma.305,306 Such victims are frequently children who have been run over by a car. In adults, torsion of the lung is usually associated with thoracic surgery, spontaneous pneumothorax, or pneumothorax induced by

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Chapter 17 • Chest Trauma

B A

Fig. 17.51  Vertebral fractures after a motor vehicle accident. A, Frontal chest radiograph shows widening of the right paratracheal stripe (arrow). B, CT shows bilateral paraspinal hematomas and comminuted vertebral body fractures shown to better advantage on C, sagittal reconstructions. The aorta was normal.

C

Box 17.11  Lung torsion

Causes • • • • •

Blunt chest trauma (rare) Thoracic surgery including lobectomy, lung transplantation Pneumothorax Pleural effusion Heavy neoplasm

Imaging appearances • Twisting of airways and lung vessels – Bronchial (cutoff) – Distal lobar opacification, overexpansion, or atelectasis – Hemorrhagic infarction • Anatomic malpositioning – Hilar vessels or interlobar fissures rotated away from normal position – Otherwise unexplained movement of lung nodules or surgical sutures – CT with intravenous contrast material is particularly useful for showing changes in vascular orientation (Fig. 17.55)313–315

Diagnosis • Difficult • Requires high index of suspicion • Suspect with persistent consolidation of lung or lung remnant after thoracic surgery

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needle biopsy, pleural effusion or neoplasm.307–316 Predisposing mechanical factors include transection or underdevelopment of the inferior pulmonary ligament, the presence of complete fissures or accessory lobes, the freedom of movement allowed by pneumothoraces or pleural effusions, and the presence of a heavy mass in the lung. The condition may be more common than is realized following thoracic surgery. Wong and Goldstraw,317 in a survey of thoracic surgeons in the UK, found that 30% had encountered at least one case. Diagnosis of lung torsion is very difficult.318 A key factor is awareness of the possibility of torsion and the circumstances under which it occurs. The radiographic findings may be subdivided: • Twisting of the airways and lung vessels. Airway twisting may result in abrupt cutoff in the bronchus at the hilum with development of distal atelectasis. Twisting of the hilar vessels may result in hemorrhagic infarction of lung. Thus a spectrum of lung parenchymal findings ranging from normal aeration to varying degrees of lobar or whole lung atelectasis to expansile consolidation of lung is possible. In the immediate period after thoracic surgery (when torsion is most likely to occur), the development of dense consolidation of all or part of the lung or lung remnant should raise the possibility of torsion (Fig. 17.55). • Anatomic malpositioning. By identifying malpositioning of normal anatomic structures, the radiologist can suggest the diagnosis of lung torsion prior to surgical exploration. Hilar vessels or interlobar fissures may be rotated away from their

Miscellaneous Injuries

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Fig. 17.52  Gunshot wound to the chest. A, Initial frontal chest radiograph shows severe right lung contusion, hemothorax, and metallic bullet fragments overlying the right chest. B, Radiograph obtained 4 days later shows resolution of the contusion into a focal hematoma (arrow). C, Radiograph obtained 3 days later shows apparent cavitation in the hematoma. This appearance is typical of a ‘bullet-track’ in the lung.

B

Fig. 17.53  Gunshot wound to the chest. A, B, CT shows the typical appearance of a bullet track in the lung. The linear nature of the abnormality helps distinguish this lesion from other cavitary lung lesions such as abscess.

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Chapter 17 • Chest Trauma Chest radiographs can easily diagnose lung hernias if they can be shown in profile. However, diagnosis is more commonly made by CT (Figs 17.56 and 17.57).

INDIRECT EFFECTS OF TRAUMA ON THE LUNGS Trauma can have indirect effects on the lungs that can severely complicate the patient’s clinical course and affect outcome. Three processes require consideration: fat embolism, acute respiratory distress syndrome, and neurogenic pulmonary edema. Only fat embolism is discussed here; the other two conditions are discussed in Chapter 7.

Fat embolism (Box 17.12)

Fig. 17.54  Gunshot wound to the chest. Frontal chest radiograph shows an oblong cavitary mass (yellow arrows) in the left upper lobe, an appearance typical of a ‘bullet-track’. Note the position of the bullet (red arrow). normal position (Fig. 17.55). If previous films are available, an identifiable structure such as a lung nodule or surgical sutures may be shifted in position in an otherwise inexplicable fashion. CT with intravenous contrast material can be particularly useful for diagnosing torsion by demonstrating alterations in vascular orientation (Fig. 17.55).313–315 In summary, lung torsion should be suspected when chest radiographs show persistent atelectasis or consolidation of a lobe or lung after prior partial pulmonary resection or in the setting of trauma or a large pneumothorax. CT can help confirm the diagnosis by demonstrating airway occlusion and alteration of normal vascular anatomy.318

Lung herniation Most lung hernias occur in the cervical region and are not associated with trauma.319 Intercostal lung herniation is usually the result of direct trauma or previous surgical intervention such as chest tube placement, open thoracotomy, or minimally invasive thoracic or cardiac surgery.320–324 Clinically, a chest wall deformity or palpable crepitant mass may be encountered often varying in size with respiration, cough, or Valsalva maneuver. In one recent series, 16 patients developed anterior intercostal hernias after minimally invasive thoracic or cardiac surgery.323 All presented with a persistent bulge at the surgical site, 75% complained of pain, and all underwent successful chest wall reconstruction with mesh grafts.

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Skeletal trauma, particularly pelvic and long-bone fractures, can cause neutral fat droplets to enter the bloodstream.325 These droplets likely enter via lacerated veins in the area of trauma, possibly aided by increased intraosseous pressure or bone fragment movement. Rapid immobilization of fractures, particularly by early operative fixation, decreases the incidence of fat embolization.326 The fat droplets are typically 20–40  µm in diameter and occlude vascular beds in the lungs and other organs. Autopsy and clinical studies indicate that subclinical fat embolization is more common than is generally realized.327–329 The term ‘fat embolism syndrome’ is reserved for patients who have overt clinical findings attributable to fat embolization in the lungs and other organs such as the brain, kidneys, and skin. Fat embolization may be detected by examination of the blood and urine in as many as 90% of patients following major trauma, whereas the incidence of fat embolism syndrome is approximately 3%.330 The incidence of fat embolism syndrome increases with the number of long-bone fractures.331 Trauma is the major cause of fat embolism syndrome. However, fat embolization can occur in the absence of trauma in many conditions, including diabetes mellitus, acute decompression sickness,

Box 17.12  Fat embolism syndrome

Clinical setting • • • • • • • •

Long-bone fractures Orthopedic fixation with intramedullary rod placement Acute decompression sickness Pancreatitis Alcoholism Burns Severe infection Sickle cell anemia (crisis)

Clinical features (usually appear 24–72 hours after trauma) • • • •

Severe dyspnea Hypoxemia CNS symptoms (delirium, obtundation) Petechial skin and retinal hemorrhages

Chest radiography • Scattered or diffuse heterogeneous or homogeneous opacities • Initially may be peripheral

CT • • • •

Centrilobular and/or subpleural nodules (early finding) Scattered or diffuse ground-glass opacities May progress to consolidation Septal thickening

Outcome • Usually resolves within 7–14 days (good prognosis) • May progress to ARDS (poor prognosis)

Indirect Effects of Trauma on the Lungs

A

C

Fig. 17.55  Lung torsion in a man with chest pain and hemoptysis 3 days after a lingula-sparing left upper lobectomy. A, Frontal and B, lateral chest radiographs show a large homogeneous opacity in the left upper hemithorax. The fissure between the lower lobe and lingula (arrows) is rotated in a clockwise fashion. C, CT (lung window) shows homogeneous opacification of the posteriorly displaced lingula. Note narrowing of the bronchi (arrow). D, E, Contrast-enhanced CT (mediastinal window) shows partial vascular occlusion at the arterial stump (D, arrow) and unusual curvature of the lingular vessels (E, arrow). Torsion of the lingula was found at surgical exploration.

B

D

E

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A

Fig. 17.56  Lung hernia in a woman with a crepitant mass over the left upper chest after a motor vehicle accident. A, Frontal and B, coned chest radiographs show a well-circumscribed lucency (B, arrows) consistent with a post-traumatic lung hernia.

Fig. 17.57  Lung hernia in a woman with a crepitant mass over the right upper chest after a motor vehicle accident. CT shows focal anterior lung herniation at the point of costochondral separation.

chronic pancreatitis, alcoholism, burns, severe infections, sickle cell disease, inhalational anesthesia, and renal infarction.332 The origin of fat emboli in such nontraumatic cases is debated.331,333 One theory suggests that the embolic fat is derived from circulating blood lipids and from mobilization of fat depots. Neutral fat in the blood is normally emulsified in the form of chylomicrons that are less than 1 µm in diameter. During periods of stress, chylomicrons may coalesce to form fat globules up to 40 µm in diameter that may cause

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B

capillary occlusion.332 Fat embolism due to bone marrow infarction is believed to be a major cause of acute chest syndrome in patients with sickle cell anemia.334–337 The deleterious effects of fat embolization are not simply the result of vascular occlusion.332,338,339 Hydrolysis of neutral fat by tissue lipase forms free fatty acids that have a toxic effect on the vascular endothelium and lung parenchyma. Plasma phospho­ lipase A(2), nitric oxide, free radicals, and proinflammatory cytokines play an important role in pathogenesis as well.339 Resulting endothelial damage leads to increased capillary permeability, damage to the alveolar lining cells, loss of surfactant activity, and formation of hyaline membranes (ARDS). In rare cases, acute cor pulmonale occurs within hours of injury, attributable to significant pulmonary vascular occlusion.340 A latent period of 12–48 hours before fat embolism syndrome occurs is much more common.341 This latent period is explained by the time required to hydrolyze neutral fat and for the secondary endothelial damage to develop. The chief clinical manifestations of fat embolism syndrome involve the lungs, central nervous system, and skin.325,339 The pulmonary manifestations are generally the first to appear and include dyspnea, tachypnea, and cyanosis, which develop within 72 hours of trauma. Arterial oxygen tension decreases to 50 mmHg or less. At the same time, generalized cerebral symptoms may develop, ranging from headache and irritability to delirium, stupor, seizures, and coma. Focal neurologic signs are generally absent. Funduscopic examination may reveal petechial retinal hemorrhages. Petechial skin rash distributed over the neck and trunk appears in many, but not all, cases after 2–3 days. Chest radiographic findings reflect the severity of fat embolization syndrome. The chest radiograph can remain normal in mild cases. In more severe cases, radiographic findings develop after a 12–72-hour latent period. The classic appearance is either that of multifocal scattered homogeneous opacities or more diffuse heterogeneous or homogeneous opacities (pulmonary edema pattern). Pleural effusions are not a typical feature. The degree of opacifica-

Indirect Effects of Trauma on the Lungs tion can become remarkably severe, yet clearing generally occurs in 7–14 days. On the other hand, ARDS can develop with prolongation of the clinical course and markedly increased mortality (Fig. 17.58). Curtis et  al.342 reported that one-third of patients with fat embolization syndrome developed ARDS and that the mortality in the subset with ARDS was substantially higher than that in the subset without ARDS. The radiographic features of ARDS are discussed further on p. 429. CT findings of pulmonary fat embolism syndrome have been well reported.343–348 Arakawa et  al.345 reported CT findings in six patients. They saw focal consolidation or ground-glass opacity and

A

C

nodules in the upper lobes in all six patients and more diffuse ground-glass opacities in five (Fig. 17.59). They also found that the extent of CT abnormalities correlated with respiratory impairment as assessed by PaO2 measurements and that follow-up CT scans showed rapid improvement in three of six patients. Malagari et al.343 reviewed thin-section CT scans in nine patients with mild disease. They reported ground-glass opacities in seven patients, thickened interlobular septa in five, and centrilobular nodules in two. In four, the distribution of opacities was quite patchy and geographic in nature. Follow-up CT showed resolution of opacities from 7 to 25 days post-trauma (mean 16 days). Several authors have emphasized

B

Fig. 17.58  Fat embolism syndrome in a man with severe dyspnea 48 hours after major pelvic trauma. A, Frontal chest radiograph obtained on admission shows partial right upper lobe atelectasis and an abnormal mediastinum. CT (not shown) showed no evidence of a vascular injury. B, Radiograph obtained at the time of symptoms now shows bilateral scattered pulmonary opacities. C, Radiograph obtained 2 days later shows progression to diffuse pulmonary opacities. By this time, characteristic retinal hemorrhages and a petechial skin rash were evident. The patient eventually died of respiratory failure.

Fig. 17.59  Fat embolism in a man with dyspnea and hypoxemia after intramedullary nailing of a femur fracture. Axial CT images show scattered nondependent ground-glass opacities, likely due to fat embolism. The patient did not develop further stigmata of fat embolism syndrome and his symptoms improved gradually over the next few days.

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Fig. 17.60  Fat embolism in a man with dyspnea and hypoxemia after a recent orthopedic procedure. Perfusion (P) and ventilation (V) radionuclide scans show multiple peripheral subsegmental perfusion defects suggestive of fat embolism.

that centrilobular or subpleural nodules can be early findings of pulmonary fat embolism on CT, likely corresponding to areas of hemorrhage and edema.346–349 In very rare cases, intravascular fatcontaining thromboemboli are seen by CT.344,346 On occasion, patients with symptoms of pulmonary fat embolism syndrome and a normal or near-normal chest radiograph may be referred for ventilation–perfusion scintigraphy to exclude pulmonary embolism. Ventilation scans are typically normal. Perfusion scans, however, may show multiple peripheral subsegmental defects that result in a diffusely mottled appearance341,350 (Fig. 17.60). This is quite unlike the larger and more focal defects commonly associated with bland thromboemboli. The diagnosis of fat embolism syndrome depends on correlation of clinical features, chest radiographic or CT findings, and labora-

tory results, especially the results of blood gas analysis. On imaging, findings are not specific and can be seen in other conditions that affect traumatized patients, including pulmonary contusion, massive aspiration of gastric contents, thermal damage, toxic gas inhalation, transfusion reactions, neurogenic and other causes of pulmonary edema, and bacterial sepsis. The characteristic latent period before the imaging appearances and clinical findings of fat embolism syndrome develop has great diagnostic importance. In many of these other conditions, clinical symptoms and imaging abnormalities are more acute in onset. ARDS may develop in any severely traumatized patient and fat embolization as the precipitating cause may go unrecognized. Although a number of strategies to minimize the severity of fat embolism syndrome have been proposed, treatment is usually supportive.333

REFERENCES 1. Heron M. Deaths: leading causes for 2004. Natl Vital Stat Rep 2007;56:1–95. 2. Minino AM, Heron MP, Murphy SL, et al. Deaths: final data for 2004. Natl Vital Stat Rep 2007;55:1–119. 3. Wicky S, Wintermark M, Schnyder P, et al. Imaging of blunt chest trauma. Eur Radiol 2000;10:1524–1538. 4. Gavelli G, Canini R, Bertaccini P, et al. Traumatic injuries: imaging of thoracic injuries. Eur Radiol 2002;12:1273–1294. 5. Mirvis SE. Imaging of acute thoracic injury: the advent of MDCT screening. Semin Ultrasound CT MR 2005;26:305–331. 6. Sangster GP, Gonzalez-Beicos A, Carbo AI, et al. Blunt traumatic injuries of the lung parenchyma, pleura, thoracic wall, and intrathoracic airways: multidetector computer tomography imaging findings. Emerg Radiol 2007;14:297–310. 7. Dyer DS, Moore EE, Mestek MF, et al. Can chest CT be used to exclude aortic injury? Radiology 1999;213:195–202. 8. Rivas LA, Fishman JE, Munera F, et al. Multislice CT in thoracic trauma. Radiol Clin North Am 2003;41:599–616. 9. Wintermark M, Schnyder P. Imaging of patients post blunt trauma to the chest. J Radiol 2002;83:123–132. 10. Primack SL, Collins J. Blunt nonaortic chest trauma: radiographic and CT findings. Emerg Radiol 2002;9:5–12. 11. Ng CJ, Chen JC, Wang LJ, et al. Diagnostic value of the helical CT scan for traumatic aortic injury: correlation with mortality and early rupture. J Emerg Med 2006;30: 277–282. 12. Gundry SR, Burney RE, Mackenzie JR, et al. Traumatic pseudoaneurysms of the

1160

13.

14.

15.

16. 17.

18.

19.

20.

21.

thoracic aorta. Anatomic and radiologic correlations. Arch Surg 1984;119: 1055–1060. Feczko JD, Lynch L, Pless JE, et al. An autopsy case review of 142 nonpenetrating (blunt) injuries of the aorta. J Trauma 1992; 33:846–849. Lundell CJ, Quinn MF, Finck EJ. Traumatic laceration of the ascending aorta: angiographic assessment. AJR Am J Roentgenol 1985;145:715–719. Rabinsky I, Sidhu GS, Wagner RB. Mid-descending aortic traumatic aneurysms. Ann Thorac Surg 1990;50: 155–160. Nucifora G, Hysko F, Vasciaveo A. Blunt traumatic abdominal aortic rupture: CT imaging. Emerg Radiol 2008;15:211–213. Cohen AM, Crass JR, Thomas HA, et al. CT evidence for the ‘osseous pinch’ mechanism of traumatic aortic injury. AJR Am J Roentgenol 1992;159:271–274. Crass JR, Cohen AM, Motta AO, et al. A proposed new mechanism of traumatic aortic rupture: the osseous pinch. Radiology 1990;176:645–649. Javadpour H, O’Toole JJ, McEniff JN, et al. Traumatic aortic transection: evidence for the osseous pinch mechanism. Ann Thorac Surg 2002;73:951–953. Mirvis SE, Bidwell JK, Buddemeyer EU, et al. Value of chest radiography in excluding traumatic aortic rupture. Radiology 1987;163:487–493. Mirvis SE, Bidwell JK, Buddemeyer EU, et al. Imaging diagnosis of traumatic aortic rupture. A review and experience at a major trauma center. Invest Radiol 1987;22: 187–196.

22. Sefczek DM, Sefczek RJ, Deeb ZL. Radiographic signs of acute traumatic rupture of the thoracic aorta. AJR Am J Roentgenol 1983;141:1259–1262. 23. Woodring JH. The normal mediastinum in blunt traumatic rupture of the thoracic aorta and brachiocephalic arteries. J Emerg Med 1990;8:467–476. 24. Williams S, Burney RE, MacKenzie JR, et al. Indications for aortography. Radiography after blunt chest trauma: a reassessment of the radiographic findings associated with traumatic rupture of the aorta. Invest Radiol 1983;18:230–237. 25. Ho RT, Blackmore CC, Bloch RD, et al. Can we rely on mediastinal widening on chest radiography to identify subjects with aortic injury? Emerg Radiol 2002;9:183–187. 26. Marsh DG, Sturm JT. Traumatic aortic rupture: roentgenographic indications for angiography. Ann Thorac Surg 1976;21: 337–340. 27. Seltzer SE, D’Orsi C, Kirshner R, et al. Traumatic aortic rupture: plain radiographic findings. AJR Am J Roentgenol 1981;137:1011–1014. 28. Fisher RG, Chasen MH, Lamki N. Diagnosis of injuries of the aorta and brachiocephalic arteries caused by blunt chest trauma: CT vs aortography. AJR Am J Roentgenol 1994;162:1047–1052. 29. Marnocha KE, Maglinte DD. Plain-film criteria for excluding aortic rupture in blunt chest trauma. AJR Am J Roentgenol 1985;144:19–21. 30. Gerlock AJ Jr, Muhletaler CA, Coulam CM, et al. Traumatic aortic aneurysm: validity of esophageal tube displacement sign. AJR Am J Roentgenol 1980;135:713–718.

References 31. Tisnado J, Tsai FY, Als A, et al. A new radiographic sign of acute traumatic rupture of the thoracic aorta: displacement of the nasogastric tube to the right. Radiology 1977;125:603–608. 32. Peters DR, Gamsu G. Displacement of the right paraspinous interface: a radiographic sign of acute traumatic rupture of the thoracic aorta. Radiology 1980;134:599–603. 33. Dennis LN, Rogers LF. Superior mediastinal widening from spine fractures mimicking aortic rupture on chest radiographs. AJR Am J Roentgenol 1989; 152:27–30. 34. Simeone JF, Deren MM, Cagle F. The value of the left apical cap in the diagnosis of aortic rupture: a prospective and retrospective study. Radiology 1981;139: 35–37. 35. Lee J, Harris JH Jr, Duke JH Jr, et al. Noncorrelation between thoracic skeletal injuries and acute traumatic aortic tear. J Trauma 1997;43:400–404. 36. Fisher RG, Ward RE, Ben-Menachem Y, et al. Arteriography and the fractured first rib: too much for too little? AJR Am J Roentgenol 1982;138:1059–1062. 37. Poole GV. Fracture of the upper ribs and injury to the great vessels. Surg Gynecol Obstet 1989;169:275–282. 38. Woodring JH, Fried AM, Hatfield DR, et al. Fractures of first and second ribs: predictive value for arterial and bronchial injury. AJR Am J Roentgenol 1982;138: 211–215. 39. Gupta A, Jamshidi M, Rubin JR. Traumatic first rib fracture: is angiography necessary? A review of 730 cases. Cardiovasc Surg 1997;5:48–53. 40. Nagy K, Fabian T, Rodman G, et al. Guidelines for the diagnosis and management of blunt aortic injury: an EAST Practice Management Guidelines Work Group. J Trauma 2000;48:1128–1143. 41. Fabian TC, Richardson JD, Croce MA, et al. Prospective study of blunt aortic injury: Multicenter Trial of the American Association for the Surgery of Trauma. J Trauma 1997;42:374–380. 42. Dyer DS, Moore EE, Ilke DN, et al. Thoracic aortic injury: how predictive is mechanism and is chest computed tomography a reliable screening tool? A prospective study of 1,561 patients. J Trauma 2000;48:673–682. 43. Cook AD, Klein JS, Rogers FB, et al. Chest radiographs of limited utility in the diagnosis of blunt traumatic aortic laceration. J Trauma 2001;50:843–847. 44. Exadaktylos AK, Duwe J, Eckstein F, et al. The role of contrast-enhanced spiral CT imaging versus chest X-rays in surgical therapeutic concepts and thoracic aortic injury: a 29-year Swiss retrospective analysis of aortic surgery. Cardiovasc J S Afr 2005;16:162–165. 45. Plurad D, Green D, Demetriades D, et al. The increasing use of chest computed tomography for trauma: is it being overutilized? J Trauma 2007;62:631–635. 46. Blackmore CC, Zweibel A, Mann FA. Determining risk of traumatic aortic injury: how to optimize imaging strategy. AJR Am J Roentgenol 2000;174:343–347. 47. Ungar TC, Wolf SJ, Haukoos JS, et al. Derivation of a clinical decision rule to exclude thoracic aortic imaging in patients

48.

49.

50. 51.

52.

53.

54.

55.

56.

57. 58.

59.

60. 61. 62.

63.

64.

with blunt chest trauma after motor vehicle collisions. J Trauma 2006;61:1150–1155. Kirkham JR, Blackmore CC. Screening for aortic injury with chest radiography and clinical factors. Emerg Radiol 2007;14: 211–217. Alkadhi H, Wildermuth S, Desbiolles L, et al. Vascular emergencies of the thorax after blunt and iatrogenic trauma: multi-detector row CT and threedimensional imaging. RadioGraphics 2004;24:1239–1255. Sinclair DS. Traumatic aortic injury: an imaging review. Emerg Radiol 2002;9: 13–20. Schertler T, Glucker T, Wildermuth S, et al. Comparison of retrospectively ECG-gated and nongated MDCT of the chest in an emergency setting regarding workflow, image quality, and diagnostic certainty. Emerg Radiol 2005;12:19–29. Fishman JE, Nunez D Jr, Kane A, et al. Direct versus indirect signs of traumatic aortic injury revealed by helical CT: performance characteristics and interobserver agreement. AJR Am J Roentgenol 1999;172:1027–1031. Sammer M, Wang E, Blackmore CC, et al. Indeterminate CT angiography in blunt thoracic trauma: is CT angiography enough? AJR Am J Roentgenol 2007;189: 603–608. Wicky S, Capasso P, Meuli R, et al. Spiral CT aortography: an efficient technique for the diagnosis of traumatic aortic injury. Eur Radiol 1998;8:828–833. Scaglione M, Pinto A, Pinto F, et al. Role of contrast-enhanced helical CT in the evaluation of acute thoracic aortic injuries after blunt chest trauma. Eur Radiol 2001; 11:2444–2448. Fabian TC, Davis KA, Gavant ML, et al. Prospective study of blunt aortic injury: helical CT is diagnostic and antihypertensive therapy reduces rupture. Ann Surg 1998;227:666–676. Fishman JE. Imaging of blunt aortic and great vessel trauma. J Thorac Imaging 2000;15:97–103. Parker MS, Matheson TL, Rao AV, et al. Making the transition: the role of helical CT in the evaluation of potentially acute thoracic aortic injuries. AJR Am J Roentgenol 2001;176:1267–1272. Cleverley JR, Barrie JR, Raymond GS, et al. Direct findings of aortic injury on contrast-enhanced CT in surgically proven traumatic aortic injury: a multi-centre review. Clin Radiol 2002;57:281–286. Wintermark M, Wicky S, Schnyder P. Imaging of acute traumatic injuries of the thoracic aorta. Eur Radiol 2002;12:431–442. Gavant ML, Flick P, Menke P, et al. CT aortography of thoracic aortic rupture. AJR Am J Roentgenol 1996;166:955–961. Ellis JD, Mayo JR. Computed tomography evaluation of traumatic rupture of the thoracic aorta: an outcome study. Can Assoc Radiol J 2007;58:22–26. Bruckner BA, DiBardino DJ, Cumbie TC, et al. Critical evaluation of chest computed tomography scans for blunt descending thoracic aortic injury. Ann Thorac Surg 2006;81:1339–1346. Downing SW, Sperling JS, Mirvis SE, et al. Experience with spiral computed tomography as the sole diagnostic method

65.

66.

67.

68.

69.

70.

71.

72.

73.

74.

75.

76. 77.

78.

79.

80.

81.

82.

for traumatic aortic rupture. Ann Thorac Surg 2001;72:495–501. Karmy-Jones R, Nicholls S, Gleason TG. The endovascular approach to acute aortic trauma. Thorac Surg Clin 2007;17: 109–128. McPhee JT, Asham EH, Rohrer MJ, et al. The midterm results of stent graft treatment of thoracic aortic injuries. J Surg Res 2007;138:181–188. Tehrani HY, Peterson BG, Katariya K, et al. Endovascular repair of thoracic aortic tears. Ann Thorac Surg 2006;82:873–877, discussion 877–878. Schumacher H, Bockler D, von TenggKobligk H, et al. Acute traumatic aortic tear: open versus stent-graft repair. Semin Vasc Surg 2006;19:48–59. Stampfl P, Greitbauer M, Zimpfer D, et al. Mid-term results of conservative, conventional and endovascular treatment for acute traumatic aortic lesions. Eur J Vasc Endovasc Surg 2006;31:475–480. Pate JW, Gavant ML, Weiman DS, et al. Traumatic rupture of the aortic isthmus: program of selective management. World J Surg 1999;23:59–63. Gavant ML. Helical CT grading of traumatic aortic injuries. Impact on clinical guidelines for medical and surgical management. Radiol Clin North Am 1999; 37:553–574, vi. Malhotra AK, Fabian TC, Croce MA, et al. Minimal aortic injury: a lesion associated with advancing diagnostic techniques. J Trauma 2001;51:1042–1048. Sturm JT, Luxenberg MG, Moudry BM, et al. Does sternal fracture increase the risk for aortic rupture? Ann Thorac Surg 1989;48:697–698. Miller FB, Richardson JD, Thomas HA, et al. Role of CT in diagnosis of major arterial injury after blunt thoracic trauma. Surgery 1989;106:596–602. Madayag MA, Kirshenbaum KJ, Nadimpalli SR, et al. Thoracic aortic trauma: role of dynamic CT. Radiology 1991;179:853–855. Raptopoulos V. Chest CT for aortic injury: maybe not for everyone. AJR Am J Roentgenol 1994;162:1053–1055. Mirvis SE, Pais SO, Shanmuganathan K. Atypical results of thoracic aortography performed to exclude aortic injury. Emerg Radiol 1994;1:24–31. Morse SS, Glickman MG, Greenwood LH, et al. Traumatic aortic rupture: falsepositive aortographic diagnosis due to atypical ductus diverticulum. AJR Am J Roentgenol 1988;150:793–796. Gavant ML, Menke PG, Fabian T, et al. Blunt traumatic aortic rupture: detection with helical CT of the chest. Radiology 1995;197:125–133. Fisher RG, Sanchez-Torres M, Thomas JW, et al. Subtle or atypical injuries of the thoracic aorta and brachiocephalic vessels in blunt thoracic trauma. RadioGraphics 1997;17:835–849. Brooks SW, Cmolik BL, Young JC, et al. Transesophageal echocardiographic examination of a patient with traumatic aortic transection from blunt chest trauma: a case report. J Trauma 1991;31:841–845. Davis GA, Sauerisen S, Chandrasekaran K, et al. Subclinical traumatic aortic injury diagnosed by transesophageal

1161

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83.

84.

85.

86.

87.

88.

89.

90.

91.

92.

93.

94.

95.

96.

97. 98.

99.

1162

echocardiography. Am Heart J 1992;123:534–536. Goarin JP, Le Bret F, Riou B, et al. Early diagnosis of traumatic thoracic aortic rupture by transesophageal echocardiography. Chest 1993;103:618–620. Shapiro MJ, Yanofsky SD, Trapp J, et al. Cardiovascular evaluation in blunt thoracic trauma using transesophageal echocardiography (TEE). J Trauma 1991;31:835–839, discussion 839–840. Sparks MB, Burchard KW, Marrin CA, et al. Transesophageal echocardiography. Preliminary results in patients with traumatic aortic rupture. Arch Surg 1991;126:711–713, discussion 713–714. Vignon P, Lagrange P, Boncoeur MP, et al. Routine transesophageal echocardiography for the diagnosis of aortic disruption in trauma patients without enlarged mediastinum. J Trauma 1996;40:422–427. Goarin JP, Cluzel P, Gosgnach M, et al. Evaluation of transesophageal echocardiography for diagnosis of traumatic aortic injury. Anesthesiology 2000;93:1373–1377. Patel NH, Hahn D, Comess KA. Blunt chest trauma victims: role of intravascular ultrasound and transesophageal echocardiography in cases of abnormal thoracic aortogram. J Trauma 2003;55: 330–337. Lee DE, Arslan B, Queiroz R, et al. Assessment of inter- and intraobserver agreement between intravascular US and aortic angiography of thoracic aortic injury. Radiology 2003;227:434–439. Vignon P, Lang RM. Use of transesophageal echocardiography for the assessment of traumatic aortic injuries. Echocardiography 1999;16:207–219. Goarin JP, Catoire P, Jacquens Y, et al. Use of transesophageal echocardiography for diagnosis of traumatic aortic injury. Chest 1997;112:71–80. Hainer C, Bockler D, Bernhard M, et al. Blunt traumatic aortic injury: importance of transesophageal echocardiography. Anaesthesist 2008;57:262–268. Smith MD, Cassidy JM, Souther S, et al. Transesophageal echocardiography in the diagnosis of traumatic rupture of the aorta. N Engl J Med 1995;332:356–362. Buckmaster MJ, Kearney PA, Johnson SB, et al. Further experience with transesophageal echocardiography in the evaluation of thoracic aortic injury. J Trauma 1994;37:989–995. Saletta S, Lederman E, Fein S, et al. Transesophageal echocardiography for the initial evaluation of the widened mediastinum in trauma patients. J Trauma 1995;39:137–141. Minard G, Schurr MJ, Croce MA, et al. A prospective analysis of transesophageal echocardiography in the diagnosis of traumatic disruption of the aorta. J Trauma 1996;40:225–230. Ahrar K, Smith DC, Bansal RC, et al. Angiography in blunt thoracic aortic injury. J Trauma 1997;42:665–669. Williams DM, Simon HJ, Marx MV, et al. Acute traumatic aortic rupture: intravascular US findings. Radiology 1992;182:247–249. Hughes JP, Ruttley MS, Musumeci F. Case report: traumatic aortic rupture:

100.

101.

102. 103. 104.

105. 106.

107. 108. 109.

110.

111. 112.

113.

114.

115. 116.

117.

118. 119.

demonstration by magnetic resonance imaging. Br J Radiol 1994;67:1264–1267. Cohn SM, Pollak JS, McCarthy S, et al. Detection of aortic tear in the acute trauma patient using MRI. Magn Reson Imaging 1994;12:963–967. Nakanishi T, Hata R, Tamura A, et al. Breath-hold gadolinium-enhanced three-dimensional MR thoracic aortography: higher spatial resolution imaging with phased-array coil and three-dimensional surface display. Hiroshima J Med Sci 2000;49:129–133. Nienaber CA, Fattori R. Aortic diseases – do we need MR techniques? Herz 2000; 25:331–341. Pretre R, Chilcott M, Murith N, et al. Blunt injury to the supra-aortic arteries. Br J Surg 1997;84:603–609. Chen MY, Regan JD, D’Amore MJ, et al. Role of angiography in the detection of aortic branch vessel injury after blunt thoracic trauma. J Trauma 2001;51:1166– 1171, discussion 1172. Nunnink L. Blunt carotid artery injury. Emerg Med (Fremantle) 2002;14:412–421. Chomel A, Vernet M, Lile A, et al. Traumatic bilateral dissections of the internal carotid artery: an infrequent diagnosis not to be missed. J Neurosurg Anesthesiol 2002;14:309–312. Stover S, Holtzman RB, Lottenberg L, et al. Blunt innominate artery injury. Am Surg 2001;67:757–759. Klein S, Munshi IA, Engelman D, et al. Innominate artery transection secondary to blunt trauma. J Trauma 2003;54:202. Karkos CD, Thomson GJ. Combined subclavian artery and brachial plexus injury following blunt trauma to the shoulder. Injury 1998;29:395–396. Cox CS Jr, Allen GS, Fischer RP, et al. Blunt versus penetrating subclavian artery injury: presentation, injury pattern, and outcome. J Trauma 1999;46:445–449. Katras T, Baltazar U, Rush DS, et al. Subclavian arterial injury associated with blunt trauma. Vasc Surg 2001;35:43–50. Anastasiadis K, Channon KM, Ratnatunga C. Traumatic innominate artery transection. J Cardiovasc Surg (Torino) 2002;43: 697–700. Donaldson B, Ngo-Nonga B. Traumatic pseudoaneurysm of the pulmonary artery: case report and review of the literature. Am Surg 2002;68:414–416. Kanani N, Ting P, Weber B, et al. Blunt trauma resulting in systemic arterial and pulmonary artery injury: case report. Can Assoc Radiol J 2002;53:141–143. Hawkins ML, Carraway RP, Ross SE, et al. Pulmonary artery disruption from blunt thoracic trauma. Am Surg 1988;54:148–152. Weltman DI, Baykal A, Zhang D. CT diagnosis of laceration of the main pulmonary artery after blunt trauma. AJR Am J Roentgenol 1999;173:1361–1362. Ambrose G, Barrett LO, Angus GL, et al. Main pulmonary artery laceration after blunt trauma: accurate preoperative diagnosis. Ann Thorac Surg 2000;70: 955–957. Fang R, Miller OL, Cai T, et al. Blunt avulsion of the right inferior pulmonary vein. J Trauma 2004;56:191–193. Varghese D, Patel H, Cameron EW, et al. Repair of pulmonary vein rupture after

120. 121.

122. 123.

124. 125.

126.

127.

128.

129.

130.

131. 132. 133.

134.

135.

136.

137.

138.

deceleration injury. Ann Thorac Surg 2000; 70:656–658. Cohn SM. Pulmonary contusion: review of the clinical entity. J Trauma 1997;42:973–979. Sutyak JP, Wohltmann CD, Larson J. Pulmonary contusions and criti cal care management in thoracic trauma. Thorac Surg Clin 2007;17:11–23, v. Wagner RB, Crawford WO Jr, Schimpf PP. Classification of parenchymal injuries of the lung. Radiology 1988;167:77–82. Blostein PA, Hodgman CG. Computed tomography of the chest in blunt thoracic trauma: results of a prospective study. J Trauma 1997;43:13–18. Donnelly LF, Klosterman LA. Subpleural sparing: a CT finding of lung contusion in children. Radiology 1997;204:385–387. Guerrero-Lopez F, Vazquez-Mata G, Alcazar-Romero PP, et al. Evaluation of the utility of computed tomography in the initial assessment of the critical care patient with chest trauma. Crit Care Med 2000;28: 1370–1375. Miller PR, Croce MA, Bee TK, et al. ARDS after pulmonary contusion: accurate measurement of contusion volume identifies high-risk patients. J Trauma 2001;51:223–228, discussion 229–230. Schild HH, Strunk H, Weber W, et al. Pulmonary contusion: CT vs plain radiograms. J Comput Assist Tomogr 1989;13:417–420. Athanassiadi K, Gerazounis M, Kalantzi N, et al. Primary traumatic pulmonary pseudocysts: a rare entity. Eur J Cardiothorac Surg 2003;23:43–45. Takahashi N, Murakami J, Murayama S, et al. MR evaluation of intrapulmonary hematoma. J Comput Assist Tomogr 1995; 19:125–127. Chiles C, Ravin CE. Radiographic recognition of pneumothorax in the intensive care unit. Crit Care Med 1986;14: 677–680. Ziter FM Jr, Westcott JL. Supine subpulmonary pneumothorax. AJR Am J Roentgenol 1981;137:699–701. Gordon R. The deep sulcus sign. Radiology 1980;136:25–27. Wall SD, Federle MP, Jeffrey RB, et al. CT diagnosis of unsuspected pneumothorax after blunt abdominal trauma. AJR Am J Roentgenol 1983;141:919–921. McGonigal MD, Schwab CW, Kauder DR, et al. Supplemental emergent chest computed tomography in the management of blunt torso trauma. J Trauma 1990;30:1431–1434, discussion 1434–1435. Tocino IM, Miller MH, Frederick PR, et al. CT detection of occult pneumothorax in head trauma. AJR Am J Roentgenol 1984; 143:987–990. Holmes JF, Brant WE, Bogren HG, et al. Prevalence and importance of pneumothoraces visualized on abdominal computed tomographic scan in children with blunt trauma. J Trauma 2001;50: 516–520. Wolfman NT, Myers WS, Glauser SJ, et al. Validity of CT classification on management of occult pneumothorax: a prospective study. AJR Am J Roentgenol 1998;171:1317–1320. Rollins RJ, Tocino I. Early radiographic signs of tracheal rupture. AJR Am J Roentgenol 1987;148:695–698.

References 139. Wintermark M, Schnyder P, Wicky S. Blunt traumatic rupture of a mainstem bronchus: spiral CT demonstration of the ‘fallen lung’ sign. Eur Radiol 2001;11:409–411. 140. Karmy-Jones R, Wood DE. Traumatic injury to the trachea and bronchus. Thorac Surg Clin 2007;17:35–46. 141. Mussi A, Ambrogi MC, Ribechini A, et al. Acute major airway injuries: clinical features and management. Eur J Cardiothorac Surg 2001;20:46–51, discussion 51–52. 142. Cassada DC, Munyikwa MP, Moniz MP, et al. Acute injuries of the trachea and major bronchi: importance of early diagnosis. Ann Thorac Surg 2000;69:1563–1567. 143. Harvey-Smith W, Bush W, Northrop C. Traumatic bronchial rupture. AJR Am J Roentgenol 1980;134:1189–1193. 144. Lotz PR, Martel W, Rohwedder JJ, et al. Significance of pneumomediastinum in blunt trauma to the thorax. AJR Am J Roentgenol 1979;132:817–819. 145. Mahboubi S, O’Hara AE. Bronchial rupture in children following blunt chest trauma. Report of five cases with emphasis on radiologic findings. Pediatr Radiol 1981;10: 133–138. 146. Richardson JD. Outcome of tracheobronchial injuries: a long-term perspective. J Trauma 2004;56:30–36. 147. Chesterman JT, Satsangi PN. Rupture of the trachea and bronchi by closed injury. Thorax 1966;21:21–27. 148. Hood RM, Sloan HE. Injuries of the trachea and major bronchi. J Thorac Cardiovasc Surg 1959;38:458–480. 149. Taskinen SO, Salo JA, Halttunen PE, et al. Tracheobronchial rupture due to blunt chest trauma: a follow-up study. Ann Thorac Surg 1989;48:846–849. 150. Unger JM, Schuchmann GG, Grossman JE, et al. Tears of the trachea and main bronchi caused by blunt trauma: radiologic findings. AJR Am J Roentgenol 1989;153: 1175–1180. 151. Stark P. Imaging of tracheobronchial injuries. J Thorac Imaging 1995;10:206–219. 152. Hartley C, Morritt GN. Bronchial rupture secondary to blunt chest trauma. Thorax 1993;48:183–184. 153. Millham FH, Rajii-Khorasani A, Birkett DF, et al. Carinal injury: diagnosis and treatment – case report. J Trauma 1991;31: 1420–1422. 154. Rao PM, Novelline RA, Dobbins JM. The spherical endotracheal tube cuff: a plain radiographic sign of tracheal injury. Emerg Radiol 1996;3:87–90. 155. Chen JD, Shanmuganathan K, Mirvis SE, et al. Using CT to diagnose tracheal rupture. AJR Am J Roentgenol 2001;176: 1273–1280. 156. Tack D, Defrance P, Delcour C, et al. The CT fallen-lung sign. Eur Radiol 2000;10: 719–721. 157. Oh KS, Fleischner FG, Wyman SM. Characteristic pulmonary finding in traumatic complete transection of a main-stem bronchus. Radiology 1969;92:371–372. 158. Wan YL, Tsai KT, Yeow KM, et al. CT findings of bronchial transection. Am J Emerg Med 1997;15:176–177. 159. Epelman M, Ofer A, Klein Y, et al. CT diagnosis of traumatic bronchial rupture in children. Pediatr Radiol 2002;32:888–891.

160. Kunisch-Hoppe M, Hoppe M, Rauber K, et al. Tracheal rupture caused by blunt chest trauma: radiological and clinical features. Eur Radiol 2000;10:480–483. 161. Karmy-Jones R, Avansino J, Stern EJ. CT of blunt tracheal rupture. AJR Am J Roentgenol 2003;180:1670. 162. Nakamori Y, Hayakata T, Fujimi S, et al. Tracheal rupture diagnosed with virtual bronchoscopy and managed nonoperatively: a case report. J Trauma 2002;53:369–371. 163. Marom EM, Goodman PC, McAdams HP. Focal abnormalities of the trachea and main bronchi. AJR Am J Roentgenol 2001; 176:707–711. 164. Plott E, Jones D, McDermott D, et al. A state-of-the-art review of esophageal trauma: where do we stand? Dis Esophagus 2007;20:279–289. 165. Bryant AS, Cerfolio RJ. Esophageal trauma. Thorac Surg Clin 2007;17:63–72. 166. Weiman DS, Walker WA, Brosnan KM, et al. Noniatrogenic esophageal trauma. Ann Thorac Surg 1995;59:845–849, discussion 849–850. 167. Beal SL, Pottmeyer EW, Spisso JM. Esophageal perforation following external blunt trauma. J Trauma 1988;28:1425–1432. 168. Bladergroen MR, Lowe JE, Postlethwait RW. Diagnosis and recommended management of esophageal perforation and rupture. Ann Thorac Surg 1986;42:235–239. 169. Cordero JA, Kuehler DH, Fortune JB. Distal esophageal rupture after external blunt trauma: report of two cases. J Trauma 1997;42:321–322. 170. Micon L, Geis L, Siderys H, et al. Rupture of the distal thoracic esophagus following blunt trauma: case report. J Trauma 1990; 30:214–217. 171. Vallieres E, Shamji FM, Todd TR. Postpneumonectomy chylothorax. Ann Thorac Surg 1993;55:1006–1008. 172. Guzman AE, Rossi L, Witte CL, et al. Traumatic injury of the thoracic duct. Lymphology 2002;35:4–14. 173. Dulchavsky SA, Ledgerwood AM, Lucas CE. Management of chylothorax after blunt chest trauma. J Trauma 1988;28:1400–1401. 174. Perusse KR, McAdams HP, Earls JP, et al. General case of the day. Posttraumatic thoracic lymphocele. RadioGraphics 1994; 14:192–195. 175. Allen SJ, Koch SM, Tonnesen AS, et al. Tracheal compression caused by traumatic thoracic duct leak. Chest 1994;106:296–297. 176. Hom M, Jolles H. Traumatic mediastinal lymphocele mimicking other thoracic injuries: case report. J Thorac Imaging 1992;7:78–80. 177. Worthington MG, de Groot M, Gunning AJ, et al. Isolated thoracic duct injury after penetrating chest trauma. Ann Thorac Surg 1995;60:272–274. 178. Silen ML, Weber TR. Management of thoracic duct injury associated with fracture-dislocation of the spine following blunt trauma. J Trauma 1995;39:1185–1187. 179. Sachs PB, Zelch MG, Rice TW, et al. Diagnosis and localization of laceration of the thoracic duct: usefulness of lymphangiography and CT. AJR Am J Roentgenol 1991;157:703–705. 180. Lohrmann C, Foeldi E, Speck O, et al. High-resolution MR lymphangiography in patients with primary and secondary

181.

182. 183.

184.

185. 186. 187.

188.

189.

190.

191.

192. 193.

194. 195. 196.

197.

198.

199.

200.

lymphedema. AJR Am J Roentgenol 2006;187:556–561. Lohrmann C, Felmerer G, Speck O, et al. Postoperative lymphoceles: detection with high-resolution MR lymphangiography. J Vasc Interv Radiol 2006;17:1057–1062. Sliker CW. Imaging of diaphragm injuries. Radiol Clin North Am 2006;44:199–211, vii. Aronchick JM, Epstein DM, Gefter WB, et al. Chronic traumatic diaphragmatic hernia: the significance of pleural effusion. Radiology 1988;168:675–678. Mueller CF, Pendarvis RW. Traumatic injury of the diaphragm: report of seven cases and extensive literature review. Emerg Radiol 1994;1:118–132. Demetriades D, Kakoyiannis S, Parekh D, et al. Penetrating injuries of the diaphragm. Br J Surg 1988;75:824–826. Morgan AS, Flancbaum L, Esposito T, et al. Blunt injury to the diaphragm: an analysis of 44 patients. J Trauma 1986;26:565–568. Rodriguez-Morales G, Rodriguez A, Shatney CH. Acute rupture of the diaphragm in blunt trauma: analysis of 60 patients. J Trauma 1986;26:438–444. Simpson J, Lobo DN, Shah AB, et al. Traumatic diaphragmatic rupture: associated injuries and outcome. Ann R Coll Surg Engl 2000;82:97–100. Boulanger BR, Milzman DP, Rosati C, et al. A comparison of right and left blunt traumatic diaphragmatic rupture. J Trauma 1993;35:255–260. Rizoli SB, Brenneman FD, Boulanger BR, et al. Blunt diaphragmatic and thoracic aortic rupture: an emerging injury complex. Ann Thorac Surg 1994;58:1404–1408. Gelman R, Mirvis SE, Gens D. Diaphragmatic rupture due to blunt trauma: sensitivity of plain chest radiographs. AJR Am J Roentgenol 1991; 156:51–57. Arendrup HC, Jensen BS. Traumatic rupture of the diaphragm. Surg Gynecol Obstet 1982;154:526–530. Shapiro MJ, Heiberg E, Durham RM, et al. The unreliability of CT scans and initial chest radiographs in evaluating blunt trauma induced diaphragmatic rupture. Clin Radiol 1996;51:27–30. Shah R, Sabanathan S, Mearns AJ, et al. Traumatic rupture of diaphragm. Ann Thorac Surg 1995;60:1444–1449. Beal SL, McKennan M. Blunt diaphragm rupture. A morbid injury. Arch Surg 1988; 123:828–832. Baron B, Daffner RH. Traumatic rupture of the right hemidiaphragm: diagnosis by chest radiography. Emerg Radiol 1994;1: 231–235. Ball T, McCrory R, Smith JO, et al. Traumatic diaphragmatic hernia: errors in diagnosis. AJR Am J Roentgenol 1982;138: 633–637. Perlman SJ, Rogers LF, Mintzer RA. Abnormal course of nasogastric tube in traumatic rupture of left diaphragm. AJR Am J Roentgenol 1985;142:85–88. McHugh K, Ogilvie BC, Brunton FJ. Delayed presentation of traumatic diaphragmatic hernia. Clin Radiol 1991;43: 246–250. Schulman A, van Gelderen F. Bowel herniation through the torn diaphragm: I. Gastric herniation. Abdom Imaging 1996; 21:395–399.

1163

Chapter 17 • Chest Trauma 201. Schulman A, van Gelderen F. Bowel herniation through the torn diaphragm: II. Intestinal herniation. Abdom Imaging 1996; 21:400–403. 202. Somers JM, Gleeson FV, Flower CD. Rupture of the right hemidiaphragm following blunt trauma: the use of ultrasound in diagnosis. Clin Radiol 1990; 42:97–101. 203. Allbery SM, Swischuk LE, John SD. Posttraumatic pneumatoceles mimicking diaphragmatic hernia. Emerg Radiol 1997; 4:94–96. 204. Shanmuganathan K, Killeen K, Mirvis SE, et al. Imaging of diaphragmatic injuries. J Thorac Imaging 2000;15:104–111. 205. Iochum S, Ludig T, Walter F, et al. Imaging of diaphragmatic injury: a diagnostic challenge? Radiographics 2002;22: S103–116. 206. Eren S, Kantarci M, Okur A. Imaging of diaphragmatic rupture after trauma. Clin Radiol 2006;61:467–477. 207. Rees O, Mirvis SE, Shanmuganathan K. Multidetector-row CT of right hemidiaphragmatic rupture caused by blunt trauma: a review of 12 cases. Clin Radiol 2005;60:1280–1289. 208. Nchimi A, Szapiro D, Ghaye B, et al. Helical CT of blunt diaphragmatic rupture. AJR Am J Roentgenol 2005;184:24–30. 209. Holland DG, Quint LE. Traumatic rupture of the diaphragm without visceral herniation: CT diagnosis. AJR Am J Roentgenol 1991;157:17–18. 210. Demos TC, Solomon C, Posniak HV, et al. Computed tomography in traumatic defects of the diaphragm. Clin Imaging 1989;13:62–67. 211. Catasca JV, Siegel MJ. Posttraumatic diaphragmatic herniation: CT findings in two children. Pediatr Radiol 1995;25: 262–264. 212. Heiberg E, Wolverson MK, Hurd RN, et al. CT recognition of traumatic rupture of the diaphragm. AJR Am J Roentgenol 1980; 135:369–372. 213. McCarroll KA, Weintraub J. Traumatic intrapericardial diaphragmatic hernia. Emerg Radiol 1995;2:376–379. 214. Murray JG, Caoili E, Gruden JF, et al. Acute rupture of the diaphragm due to blunt trauma: diagnostic sensitivity and specificity of CT. AJR Am J Roentgenol 1996;166:1035–1039. 215. Toombs BD, Sandler CM, Lester RG. Computed tomography of chest trauma. Radiology 1981;140:733–738. 216. Worthy SA, Kang EY, Hartman TE, et al. Diaphragmatic rupture: CT findings in 11 patients. Radiology 1995;194:885–888. 217. Bergin D, Ennis R, Keogh C, et al. The ‘dependent viscera’ sign in CT diagnosis of blunt traumatic diaphragmatic rupture. AJR Am J Roentgenol 2001;177:1137–1140. 218. Nau T, Seitz H, Mousavi M, et al. The diagnostic dilemma of traumatic rupture of the diaphragm. Surg Endosc 2001;15: 992–996. 219. Mirvis SE, Shanmuganathan K. MR imaging of thoracic trauma. Magn Reson Imaging Clin N Am 2000;8:91–104. 220. Pomerantz SM, Shanmuganathan K, Siegel EL. Liver herniation through an occult diaphragmatic injury presenting as a solitary pulmonary nodule: value of helical computed tomography and magnetic

1164

221.

222.

223.

224.

225.

226.

227.

228.

229.

230. 231. 232.

233. 234.

235.

236.

237.

238.

239.

resonance imaging. Emerg Radiol 1996;3:205–208. Shanmuganathan K, Mirvis SE, White CS, et al. MR imaging evaluation of hemidiaphragms in acute blunt trauma: experience with 16 patients. AJR Am J Roentgenol 1996;167:397–402. Boulanger BR, Mirvis SE, Rodriguez A. Magnetic resonance imaging in traumatic diaphragmatic rupture: case reports. J Trauma 1992;32:89–93. Carter EA, Cleverley JR, Delany DJ, et al. Case report: cine MRI in the diagnosis of a ruptured right hemidiaphragm. Clin Radiol 1996;51:137–140. Daum-Kowalski R, Shanley DJ, Murphy T. MRI diagnosis of delayed presentation of traumatic diaphragmatic hernia. Gastrointest Radiol 1991;16:298–300. Lawrason JN, Novelline RA, Rhea JT. The magnetic resonance diagnosis of diaphragmatic rupture: a report of two cases. Emerg Radiol 1996;3:137–141. Mirvis SE, Keramati B, Buckman R, et al. MR imaging of traumatic diaphragmatic rupture. J Comput Assist Tomogr 1988;12: 147–149. Israel RS, Mayberry JC, Primack SL. Diaphragmatic rupture: use of helical CT scanning with multiplanar reformations. AJR Am J Roentgenol 1996;167:1201–1203. Ammann AM, Brewer WH, Maull KI, et al. Traumatic rupture of the diaphragm: real-time sonographic diagnosis. AJR Am J Roentgenol 1983;140:915–916. Kim HH, Shin YR, Kim KJ, et al. Blunt traumatic rupture of the diaphragm: sonographic diagnosis. J Ultrasound Med 1997;16:593–598. El-Chami MF, Nicholson W, Helmy T. Blunt Cardiac Trauma. J Emerg Med 2008; 35:127–133. Sybrandy KC, Cramer MJ, Burgersdijk C. Diagnosing cardiac contusion: old wisdom and new insights. Heart 2003;89:485–489. Holanda MS, Dominguez MJ, LopezEspadas F, et al. Cardiac contusion following blunt chest trauma. Eur J Emerg Med 2006;13:373–376. Elie MC. Blunt cardiac injury. Mt Sinai J Med 2006;73:542–552. Sliker CW, Mirvis SE, Shanmuganathan K, et al. Blunt cardiac rupture: value of contrast-enhanced spiral CT. Clin Radiol 2000;55:805–808. Wintermark M, Delabays A, Bettex D, et al. Blunt trauma of the heart: CT pattern of atrial appendage ruptures. Eur Radiol 2001; 11:113–116. Amorim MJ, Almeida J, Santos A, et al. Atrioventricular septal defect following blunt chest trauma. Eur J Cardiothorac Surg 1999;16:679–682. Thors A, Guarneri R, Costantini EN, et al. Atrial septal rupture, flail tricuspid valve, and complete heart block due to nonpenetrating chest trauma. Ann Thorac Surg 2007;83:2207–2210. RuDusky BM. Myocardial contusion culminating in a ruptured pseudoaneurysm of the left ventricle – a case report. Angiology 2003;54:359–362. Moen J, Hansen W, Chandrasekaran K, et al. Traumatic aneurysm and pseudoaneurysm of the right ventricle: a diagnosis by echocardiography. J Am Soc Echocardiogr 2002;15:1025–1026.

240. Sugimoto S, Yamauchi A, Kudoh K, et al. A successfully treated case of blunt traumatic right coronary ostium rupture. Ann Thorac Surg 2003;75:1001–1003. 241. Straub A, Beierlein W, Kuttner A, et al. Isolated coronary artery rupture after blunt chest trauma. Thorac Cardiovasc Surg 2003;51:97–98. 242. Dounis G, Matsakas E, Poularas J, et al. Traumatic tricuspid insufficiency: a case report with a review of the literature. Eur J Emerg Med 2002;9:258–261. 243. van Son JA, Danielson GK, Schaff HV, et al. Traumatic tricuspid valve insufficiency. Experience in thirteen patients. J Thorac Cardiovasc Surg 1994; 108:893–898. 244. Roth TC, Schmid RA. Pneumopericardium after blunt chest trauma: a sign of severe injury? J Thorac Cardiovasc Surg 2002;124: 630–631. 245. Gould JC, Schurr MA. Tension pneumopericardium after blunt chest trauma. Ann Thorac Surg 2001;72: 1728–1730. 246. Loughlin V, Murphy A, Russell C. The post-pericardiotomy syndrome and penetrating injury of the chest. Injury 1987;18:412–414. 247. Rashid MA, Wikstrom T, Ortenwall P. Cardiac injuries: a ten-year experience. Eur J Surg 2000;166:18–21. 248. Janson JT, Harris DG, Pretorius J, et al. Pericardial rupture and cardiac herniation after blunt chest trauma. Ann Thorac Surg 2003;75:581–582. 249. Sharma OP. Pericardio-diaphragmatic rupture: five new cases and literature review. J Emerg Med 1999;17:963–968. 250. Wall MJ Jr, Mattox KL, Wolf DA. The cardiac pendulum: blunt rupture of the pericardium with strangulation of the heart. J Trauma 2005;59:136–141. 251. Collins JN, Cole FJ, Weireter LJ, et al. The usefulness of serum troponin levels in evaluating cardiac injury. Am Surg 2001;67:821–825, discussion 825–826. 252. Carrillo EH, Heniford BT, Dykes JR, et al. Cardiac herniation producing tamponade: the critical role of early diagnosis. J Trauma 1997;43:19–23. 253. Fulda G, Brathwaite CE, Rodriguez A, et al. Blunt traumatic rupture of the heart and pericardium: a ten-year experience (1979–1989). J Trauma 1991;31:167–172. 254. Kermond AJ. The dislocated heart: an unusual complication of major chest injury. Radiology 1976;119:59–60. 255. Furusawa T, Fukaya Y, Amano J. Herniation of the heart due to traumatic rupture of the pericardium. Eur J Cardiothorac Surg 2000;17:752–753. 256. De Amicis V, Rossi M, Monaco M, et al. Right luxation of the heart after pericardial rupture caused by blunt trauma. Tex Heart Inst J 2003;30:140–142. 257. Kirsch JD, Escarous A. CT diagnosis of traumatic pericardium rupture. J Comput Assist Tomogr 1989;13:523–524. 258. Place RJ, Cavanaugh DG. Computed tomography to diagnose pericardial rupture. J Trauma 1995; 38:822–823. 259. Miller LA. Chest wall, lung, and pleural space trauma. Radiol Clin North Am 2006;44:213–224, viii. 260. Danher J, Eyes BE, Kumar K. Oblique rib views after blunt chest trauma: an

References

261. 262.

263.

264. 265.

266.

267.

268. 269. 270.

271. 272.

273. 274. 275.

276. 277.

278.

279. 280.

unnecessary routine? BMJ (Clin Res Ed) 1984;289:1271. DeLuca SA, Rhea JT, O’Malley TO. Radiographic evaluation of rib fractures. AJR Am J Roentgenol 1982;138:91–92. Thompson BM, Finger W, Tonsfeldt D, et al. Rib radiographs for trauma: useful or wasteful? Ann Emerg Med 1986;15: 261–265. Verma SM, Hawkins HH, Colglazier S. The clinical utility of rib detail films in the evaluation of trauma. Emerg Radiol 1995;2: 264–266. Liman ST, Kuzucu A, Tastepe AI, et al. Chest injury due to blunt trauma. Eur J Cardiothorac Surg 2003;23:374–378. Tanaka H, Yukioka T, Yamaguti Y, et al. Surgical stabilization of internal pneumatic stabilization? A prospective randomized study of management of severe flail chest patients. J Trauma 2002;52:727–732. Velmahos GC, Vassiliu P, Chan LS, et al. Influence of flail chest on outcome among patients with severe thoracic cage trauma. Int Surg 2002;87:240–244. Sirmali M, Turut H, Topcu S, et al. A comprehensive analysis of traumatic rib fractures: morbidity, mortality and management. Eur J Cardiothorac Surg 2003;24:133–138. Pettiford BL, Luketich JD, Landreneau RJ. The management of flail chest. Thorac Surg Clin 2007;17:25–33. Laghi F, Tobin MJ. Disorders of the respiratory muscles. Am J Respir Crit Care Med 2003;168:10–48. Weyant MJ, Bleier JI, Naama H, et al. Severe crushed chest injury with large flail segment: computed tomographic three-dimensional reconstruction. J Trauma 2002;52:605. Ziegler DW, Agarwal NN. The morbidity and mortality of rib fractures. J Trauma 1994;37:975–979. Ben-Menachem Y. Avulsion of the innominate artery associated with fracture of the sternum. AJR Am J Roentgenol 1988;150:621–622. Vyas PK, Sivit CJ. Imaging of blunt pediatric thoracic trauma. Emerg Radiol 1997;4:16–25. Kleinman PK. Bony thoracic trauma. In: Kleinman PK (ed). Diagnostic imaging of child abuse, 2nd ed. New York: Mosby, 1998. Lonergan GJ, Baker AM, Morey MK, et al. From the archives of the AFIP. Child abuse: radiologic-pathologic correlation. RadioGraphics 2003;23:811–845. Garcia VF, Gotschall CS, Eichelberger MR, et al. Rib fractures in children: a marker of severe trauma. J Trauma 1990;30:695–700. Resnick D. Disorders of other endocrine glands and of pregnancy. In: Resnick D, Niwayama G (eds). Diagnosis of bone and joint disorders. Philadelphia: WB Saunders, 1988. Lindsell DR, Wilson AG, Maxwell JD. Fractures on the chest radiograph in detection of alcoholic liver disease. BMJ (Clin Res Ed) 1982;285:597–599. Harley DP, Mena I. Cardiac and vascular sequelae of sternal fractures. J Trauma 1986;26:553–555. Potaris K, Gakidis J, Mihos P, et al. Management of sternal fractures: 239 cases. Asian Cardiovasc Thorac Ann 2002;10: 145–149.

281. Athanassiadi K, Gerazounis M, Moustardas M, et al. Sternal fractures: retrospective analysis of 100 cases. World J Surg 2002;26: 1243–1246. 282. Rashid MA, Ortenwall P, Wikstrom T. Cardiovascular injuries associated with sternal fractures. Eur J Surg 2001;167: 243–248. 283. Chiu WC, D’Amelio LF, Hammond JS. Sternal fractures in blunt chest trauma: a practical algorithm for management. Am J Emerg Med 1997;15:252–255. 284. Hidalgo Ovejero AM, Garcia Mata S, Sanchez Villares JJ, et al. Posterior sternoclavicular dislocation. Report of two cases. Acta Orthop Belg 2003;69:188–192. 285. Gove N, Ebraheim NA, Glass E. Posterior sternoclavicular dislocations: a review of management and complications. Am J Orthop 2006;35:132–136. 286. Brooks AP, Olson LK. Computed tomography of the chest in the trauma patient. Clin Radiol 1989;40:127–132. 287. Ernberg LA, Potter HG. Radiographic evaluation of the acromioclavicular and sternoclavicular joints. Clin Sports Med 2003;22:255–275. 288. Burnstein MI, Pozniak MA. Computed tomography with stress maneuver to demonstrate sternoclavicular joint dislocation. J Comput Assist Tomogr 1990; 14:159–160. 289. Clements RH, Reisser JR. Scapulothoracic dissociation: a devastating injury. J Trauma 1996;40:146–149. 290. Brucker PU, Gruen GS, Kaufmann RA. Scapulothoracic dissociation: evaluation and management. Injury 2005;36: 1147–1155. 291. Oreck SL, Burgess A, Levine AM. Traumatic lateral displacement of the scapula: a radiographic sign of neurovascular disruption. J Bone Joint Surg (Am) 1984;66:758–763. 292. Lange RH, Noel SH. Traumatic lateral scapular displacement: an expanded spectrum of associated neurovascular injury. J Orthop Trauma 1993;7:361–366. 293. Tsai DW, Swiontkowski MF, Kottra CL. A case of sternoclavicular dislocation with scapulothoracic dissociation. AJR Am J Roentgenol 1996;167:332. 294. Katsamouris AN, Kafetzakis A, Kostas T, et al. The initial management of scapulothoracic dissociation: a challenging task for the vascular surgeon. Eur J Vasc Endovasc Surg 2002;24:547–549. 295. Damschen DD, Cogbill TH, Siegel MJ. Scapulothoracic dissociation caused by blunt trauma. J Trauma 1997;42:537–540. 296. Woodring JH, Lee C, Jenkins K. Spinal fractures in blunt chest trauma. J Trauma 1988;28:789–793. 297. Lawrason JN, Novelline RA, Rhea JT. Early detection of thoracic spine fracture in multiple trauma patient: role of the initial portable chest radiograph. Emerg Radiol 1997;4:309–319. 298. Hollerman JJ, Fackler ML, Coldwell DM, et al. Gunshot wounds. 1. Bullets, ballistics, and mechanisms of injury. AJR Am J Roentgenol 1990;155:685–690. 299. George PY, Goodman P. Radiographic appearance of bullet tracks in the lung. AJR Am J Roentgenol 1992;159:967–970. 300. Shafer N, Wilkenfeld M, Shafer R. Gunshot wounds. Leg Med 1982:1–19.

301. Sasser SM, Sattin RW, Hunt RC, et al. Blast lung injury. Prehosp Emerg Care 2006;10:165–172. 302. Avidan V, Hersch M, Armon Y, et al. Blast lung injury: clinical manifestations, treatment, and outcome. Am J Surg 2005; 190:927–931. 303. Martin N, Bollaert PE, Bauer P, et al. 2 case reports of pulmonary blast injuries. Cah Anesthesiol 1987;35:133–137. 304. Williams JR, Stembridge VA. Pulmonary contusion secondary to nonpenetrating chest trauma. AJR Am J Roentgenol 1964; 91:284–290. 305. Felson B. Lung torsion: radiographic findings in nine cases. Radiology 1987;162:631–638. 306. Selmonosky CA, Flege JB Jr, Ehrenhaft JL. Torsion of a lobe of the lung due to blunt thoracic trauma. Ann Thorac Surg 1967;4: 166–170. 307. Graham RJ, Heyd RL, Raval VA, et al. Lung torsion after percutaneous needle biopsy of lung. AJR Am J Roentgenol 1992; 159:35–37. 308. Moser ES Jr, Proto AV. Lung torsion: case report and literature review. Radiology 1987;162:639–643. 309. Munk PL, Vellet AD, Zwirewich C. Torsion of the upper lobe of the lung after surgery: findings on pulmonary angiography. AJR Am J Roentgenol 1991;157:471–472. 310. Andresen R, Meyer DR, Kniffert T, et al. Lung torsion – a rare postoperative complication. A case report. Acta Radiol 1997;38:243–245. 311. Chan MC, Scott JM, Mercer CD, et al. Intraoperative whole-lung torsion producing pulmonary venous infarction. Ann Thorac Surg 1994;57:1330–1331. 312. Fogarty JP, Dudek G. An unusual case of lung torsion. Chest 1995;108:575–578. 313. Gilkeson RC, Lange P, Kirby TJ. Lung torsion after lung transplantation: evaluation with helical CT. AJR Am J Roentgenol 2000;174:1341–1343. 314. Spizarny DL, Shetty PC, Lewis JW Jr. Lung torsion: preoperative diagnosis with angiography and computed tomography. J Thorac Imaging 1998;13:42–44. 315. Trotter MC, McFadden PM, Ochsner JL. Spontaneous torsion of the right lung: a case report. Am Surg 1995;61:306–309. 316. Farkas EA, Detterbeck FC. Airway complications after pulmonary resection. Thorac Surg Clin 2006;16:243–251. 317. Wong PS, Goldstraw P. Pulmonary torsion: a questionnaire survey and a survey of the literature. Ann Thorac Surg 1992;54: 286–288. 318. Kim EA, Lee KS, Shim YM, et al. Radiographic and CT findings in complications following pulmonary resection. RadioGraphics 2002;22:67–86. 319. McAdams HP, Gordon DS, White CS. Apical lung hernia: radiologic findings in six cases. AJR Am J Roentgenol 1996;167:927–930. 320. Bhalla M, Leitman BS, Forcade C, et al. Lung hernia: radiographic features. AJR Am J Roentgenol 1990;154:51–53. 321. Sadler MA, Shapiro RS, Wagreich J, et al. CT diagnosis of acquired intercostal lung herniation. Clin Imaging 1997;21: 104–106. 322. Seibel DG, Hopper KD, Ghaed N. Mammographic and CT detection of

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323.

324.

325.

326. 327.

328.

329. 330. 331. 332.

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extrathoracic lung herniation. J Comput Assist Tomogr 1987;11:537–538. Athanassiadi K, Bagaev E, Simon A, et al. Lung herniation: a rare complication in minimally invasive cardiothoracic surgery. Eur J Cardiothorac Surg 2008;33:774–776. Khalil MW, Masala N, Waller DA, et al. Surgical repair of post-traumatic lung hernia using a video-assisted open technique. Interact Cardiovasc Thorac Surg 2008;7:506–507. Memtsoudis SG, Rosenberger P, Walz JM. Critical care issues in the patient after major joint replacement. J Intensive Care Med 2007;22:92–104. Riska EB, Myllynen P. Fat embolism in patients with multiple injuries. J Trauma 1982;22:891–894. Chan KM, Tham KT, Chiu HS, et al. Post-traumatic fat embolism – its clinical and subclinical presentations. J Trauma 1984;24:45–49. McCarthy B, Mammen E, Leblanc LP, et al. Subclinical fat embolism: a prospective study of 50 patients with extremity fractures. J Trauma 1973;13:9–16. Palmovic V, McCarroll JR. Fat embolism in trauma. Arch Pathol 1965;80:630–635. Feldman F, Ellis K, Green WM. The fat embolism syndrome. Radiology 1975;114: 535–542. Parisi DM, Koval K, Egol K. Fat embolism syndrome. Am J Orthop 2002;31: 507–512. Batra P. The fat embolism syndrome. J Thorac Imaging 1987;2:12–17.

333. Mellor A, Soni N. Fat embolism. Anaesthesia 2001;56:145–154. 334. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med 2000;342:1855–1865. 335. Maitre B, Habibi A, Roudot-Thoraval F, et al. Acute chest syndrome in adults with sickle cell disease. Chest 2000;117: 1386–1392. 336. Platt OS. The acute chest syndrome of sickle cell disease. N Engl J Med 2000;342:1904–1907. 337. Rucknagel DL. The role of rib infarcts in the acute chest syndrome of sickle cell diseases. Pediatr Pathol Mol Med 2001;20: 137–154. 338. Alho A. Fat embolism syndrome: etiology, pathogenesis and treatment. Acta Chir Scand Suppl 1980;499:75–85. 339. Kao SJ, Yeh DY, Chen HI. Clinical and pathological features of fat embolism with acute respiratory distress syndrome. Clin Sci (Lond) 2007;113:279–285. 340. Mayron R, Ruiz E, Mestitz ST, et al. Tissue-fat pulmonary embolism occurring in a patient with a severe pelvic fracture. J Emerg Med 1985;2:251–256. 341. Williams AG Jr, Mettler FA Jr, Christie JH, et al. Fat embolism syndrome. Clin Nucl Med 1986;11:495–497. 342. Curtis AM, Knowles GD, Putman CE, et al. The three syndromes of fat embolism: pulmonary manifestations. Yale J Biol Med 1979;52:149–157.

343. Malagari K, Economopoulos N, Stoupis C, et al. High-resolution CT findings in mild pulmonary fat embolism. Chest 2003;123: 1196–1201. 344. Ravenel JG, Heyneman LE, McAdams HP. Computed tomography diagnosis of macroscopic pulmonary fat embolism. J Thorac Imaging 2002;17:154–156. 345. Arakawa H, Kurihara Y, Nakajima Y. Pulmonary fat embolism syndrome: CT findings in six patients. J Comput Assist Tomogr 2000;24:24–29. 346. Nucifora G, Hysko F, Vit A, et al. Pulmonary fat embolism: common and unusual computed tomography findings. J Comput Assist Tomogr 2007;31: 806–807. 347. Van den Brande FG, Hellemans S, De Schepper A, et al. Post-traumatic severe fat embolism syndrome with uncommon CT findings. Anaesth Intensive Care 2006;34: 102–106. 348. Gallardo X, Castaner E, Mata JM, et al. Nodular pattern at lung computed tomography in fat embolism syndrome: a helpful finding. J Comput Assist Tomogr 2006;30:254–257. 349. Heyneman LE, Müller NL. Pulmonary nodules in early fat embolism syndrome: a case report. J Thorac Imaging 2000;15: 71–74. 350. Park HM, Ducret RP, Brindley DC. Pulmonary imaging in fat embolism syndrome. Clin Nucl Med 1986;11: 521–522.

Index Page numbers in italics indicate figures, tables and boxes. CT, computed tomography; MRI, magnetic resonance imaging.

A line, 1046 AA see amyloid A ABCA3 (ATP-binding cassette A3) gene mutation/deficiency, 581, 582, 677 abdominal surgery, pleural effusions following, 1024 aberrant origin of left pulmonary artery, 886 aberrant subclavian artery, 61, 980, 981 abscess aspergillosis, immunocompromised patient, 324 cerebral, 1081, 1084 hepatic, 1020 mediastinal see mediastinal abscess paraspinal, 886 pulmonary see lung abscess splenic, 1023 subphrenic, 1020 upper abdominal, pleural effusions association, 1020, 1023 absent lung/lobes of lung, 1073–1074 Absidia, 329 accelerated deterioration, usual interstitial pneumonia, 570 accelerated interstitial pneumonitis see acute interstitial pneumonia accessory cardiac bronchus, 41 accessory diaphragm, 1107 accessory fissures, 56–58, 57, 58, 59, 60 accessory lobes, pulmonary edema, 426 acebutolol toxicity, 1025 acetylcysteine, 564 achalasia, 892, 893, 894 Achromobacter xylosoxidans, 733 acinar shadows, 90, 140 pulmonary edema, 426 Acinetobacter pneumonia, 214 acinus, 50, 51 Fleischner Society glossary definition, 155 high-resolution CT, 153 nodules, 176 Actinomyces, 218 Actinomyces israelii, 248 actinomycin D, 542 actinomycosis, 97, 218, 248–250, 249, 250, 251, 420, 740 hypersensitivity pneumonitis, 457 solitary pulmonary nodule, 131 acute eosinophilic pneumonia, 660–662 clinical features, 661 imaging features, 661, 662 acute exacerbation of usual interstitial pneumonia, 570 acute inhalational injury, 488–490 causes, 488 reactive airways disease syndrome, 490

smoke/fire injury, 488, 488, 489 toxic fume inhalation, 489 acute interstitial pneumonia, 562, 562, 579–580 acute exudative phase, 579, 580 clinical features, 580–581 diagnosis, 583 fibrotic phase, 579, 580 Fleischner Society glossary definition, 155, 155 imaging findings, 580, 580 CT, 583 organizing phase, 579, 580 acute leukemia, 525 acute lung injury, 247, 432 acute lupus pneumonia, 592–593, 593 acute lymphoid leukemia, 529 acute mediastinitis, 921–922 acute promyelocytic leukemia, 520 acute radiation pneumonitis, 542 acute respiratory distress syndrome (ARDS), 186, 187, 210, 427–433, 429, 430, 431, 573 acute eosinophilic pneumonia, 661 air bronchogram, 100 airspace opacities, 100, 101 aspiration of gastric contents, 492 causes, 248 clinical uses of chest radiography, 430 complications, 432–433, 433 CT, 195, 430–432, 432 fat embolism, 1158, 1159, 1160 HIV/AIDS patients, 298 miliary tuberculosis, 235 mitomycin toxicity, 515 pneumothorax, 1045, 1046 pulmonary contusion, 1135 residual changes in survivors, 433, 433 smoke/fire inhalational injury, 488 stages, 429 toxic fume inhalation, 490 acute reversible hypoxemia, sytemic lupus erythematosus, 595 adalimumab toxicity, 591 Addison disease, 947 adenocarcinoma, 569, 787, 788, 820 imaging features, 789, 791, 792, 793, 794, 794 metastatic, hilar lymphadenopathy, 915 solitary pulmonary nodule, 130 ground-glass opacity, 127 trachea, 829 adenoid cystic carcinoma, trachea, 716, 829, 831 adenovirus infection, 751 constrictive bronchiolitis, 741 pneumonia, 271, 274–275 hematopoietic stem cell transplantation patients, 337, 339 lung transplantation patients, 357

adrenal gland metastases, 813, 813 aggressive fibromatosis see desmoid tumor AIDS-related conditions airway disease, 312, 312 lymphoma, 312–313, 314, 315, 319 neoplasms, 295, 296 see also HIV/AIDS air alveologram, 90, 91 pulmonary edema, 426 air bronchogram, 85–86, 87, 88, 89, 90, 91, 100 acute interstitial pneumonia, 580 acute respiratory distress syndrome, 429, 432 with airspace opacity, 92, 95 bronchioloalveolar carcinoma, 814, 815 causes, 85, 88 consolidation, 180 diffuse alveolar (pulmonary) hemorrhage, 621 Fleischner Society glossary definition, 155, 155 lobar atelectasis/collapse, 104 lung cancer, 794, 795, 795 lymphoma, 841, 842, 844 pneumonia (infective), 206 pulmonary edema, 426 round atelectasis, 119 septic pulmonary emboli, 222 silicoproteinosis, 466, 467 solitary pulmonary nodule, 130 air crescent (air meniscus) sign aspergillosis angioinvasive, 266, 268 mycetoma, 264 Fleischner Society glossary definition, 156, 156 hydatid disease, 280, 280 lung cancer, 793 mucormycosis, 330 solitary pulmonary nodules, 130–131 air gap, high-kilovoltage radiography, 1 air-bubble sign, hydatid cyst rupture, 280–281 air–fluid level aspergilloma, 264 cystic fibrosis, 733 empyema, 223, 225 esophageal dilatation, 893, 894 hiatal hernia, 891, 892 pneumothorax with pleural effusion, 1046 pulmonary sequestration, 1098 tuberculosis, reactivation (postprimary), 232, 234 air-trapping asthma, 754 bronchopulmonary dysplasia, 537 constrictive obliterative bronchiolitis, 22

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Index CT, 24 expiratory sections, 23, 24 high-resolution CT, 190, 191 decreased attenuation lung, 185–186 foreign body inhalation, 494, 495 hypersensitivity pneumonitis, 460, 460, 747, 748 pulmonary surfactant deficiencies, 582 sarcoidosis, 656, 748, 748 silicosis, 463–464 Swyer–James (McLeod) syndrome, 751, 751 tuberculosis, 230 ventilation scanning, 27 airspace opacities, 89–101, 91 alveolar edema, 426 definition, 89 differential diagnosis, 91–92 drug-induced eosinophilic lung disease, 673 multifocal, 91, 97, 97, 98, 102 bat’s wing/butterfly pattern, 96, 97–98, 99 causes, 95 differential diagnosis, 97–99, 98 solitary, 91, 91, 92, 93, 94, 95 differential diagnosis, 91, 96 see also pulmonary opacities airway stents, CT, 15 airways anomalous bronchial branching, 41 injury, 1137–1139, 1138 normal, 39 airways disease, 715–768 CT, 24 high-resolution CT, 187–192 techniques, 21–22 increased transradiancy of lung, 147 relapsing polychondritis, 605 rheumatoid arthritis, 590, 590 sarcoidosis, 653, 653, 656–657, 656 Wegener granulomatosis, 611–612 AL see amyloid light chain (AL) aliasing artifact, high-resolution CT, 21 ALK-1 gene defect, 1081 all-trans-retinoic acid, lung toxicity, 515, 520, 621 pleural effusions/thickening, 1025 allergic bronchopulmonary aspergillosis, 182, 323, 664–673 airspace opacities, 99 allergic fungal sinusitis association, 665 asthma association, 665, 666, 753 atelectasis, 670, 671 bronchiectasis, 665, 666, 668, 670, 670, 671, 672, 673, 725, 729, 732 bronchocele (mucoid impaction), 136, 667, 669, 670, 670 clinical features, 665–666 consolidation, 666, 667, 668 cystic fibrosis patients, 670–671, 671, 673, 733, 737 diagnostic criteria, 666 imaging features, 666, 666, 667, 668, 669, 670, 670, 671, 672 permanent changes, 670 transient changes, 666–667, 670 immunology, 665 antigen-specific IgE levels, 666 mycetomas, 670

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allergic bronchopulmonary mycosis, 664–673 allergic fungal sinusitis, 665 allergic granulomatosis and angiitis see Churg–Strauss syndrome alpha1-antitrypsin (antiprotease) deficiency, 344, 731, 756, 763–764 bronchiectasis, 732, 763 genetic aspects, 763 panacinar emphysema, 746, 759, 763, 764 alpha-fetoprotein, 884, 898, 900, 902 aluminosis, 483, 484 alveolar adenoma, 833 alveolar cell carcinoma see bronchioloalveolar carcinoma alveolar disease, lung opacities, 140 alveolar ducts, 51 alveolar edema, 426–427, 428 acute inhalational injury, 488 alveolar fibrosis, acute radiation pneumonitis, 542 alveolar hemorrhage, drug-induced, 515–516 alveolar microlithiasis, 143, 146, 176, 679–680 alveolar proteinosis see pulmonary alveolar proteinosis alveolar rupture, pneumomediastinum, 939 alveolus, 51 amebiasis, 276, 277 aminorex fumarate, 411, 516 amiodarone toxicity, 182, 509, 510, 519, 520–522, 520, 521, 521, 522, 523 pleural effusions/thickening, 1025 amniotic fluid embolism, 436 amosite, 472, 477, 851 amphotericin B toxicity, 515 amyloid A (AA), 692 amyloid beta2-microglobulin, 692–693 amyloid light chain (AL), 692 amyloidosis, 694 imaging features, 694, 695, 696 parenchymal nodular, 697 tracheobronchial, 696 amyloid proteins, 692–693 generalized/localized deposition, 693 amyloid transthyretin, 692 amyloidoma, 696, 835, 836 amyloidosis, 692–699, 883 amyloidoma, 696, 835, 836 clinical forms, 693 diffuse pulmonary ossification, 681 intrathoracic lymph node calcification, 908, 909 localized, 696, 696 parenchymal alveolar septal, 698–699 parenchymal nodular, 697–698, 698, 699 tracheobronchial, 696, 697 systemic, 694–696 imaging features, 694, 695 amyopathic dermatomyositis, 600 anaerobic infection empyema, 223 pulmonary, 207, 208, 209, 210, 218–219, 219 pyopneumothorax, 1048 anaphylactoid purpura (Henoch–Schönlein purpura), 615–616 ANCA see antineutrophilic cytoplasmic antibodies Ancylostoma braziliense (creeping eruption), 674, 674 Ancylostoma duodenale, 276, 674

angiocentric immunoproliferative lesion see lymphomatoid granulomatosis angiofollicular lymph node hyperplasia see Castleman disease angiolipoma, 896 angiomyolipoma, 686, 687, 689 angiosarcoma, 830 ankylosing spondylitis, 142, 606, 607 annuloaortic ectasia, 966 anomalous bronchi, 41 antenatal diagnosis bronchial obstruction with fluid retention, 1098 bronchogenic cyst, 1098 congenital cystic adenomatoid malformation, 1100, 1103 congenital diaphragmatic hernia, 1097, 1106 esophageal duplication cysts, 1098 fetal chest masses, 1097, 1098 intrathoracic neoplasms, 1098 neurenteric cysts, 1098 pulmonary hypoplasia, 1078 with diaphragmatic abnormalities, 1106–1107 pulmonary sequestration, 1096, 1097, 1100 anterior extrapleural line, 74 anterior junction line, 72, 73 anterior junction (prevascular space), 65, 67, 70 anterior (Morgagni) hernia, 884, 1107, 1111, 1112 anthophyllite, 471, 477 see also asbestos-related disease anthrax, 213–214, 214 mediastinal lymphadenopathy, 904 anti-double-stranded DNA antibodies, 592, 622 anti-glomerular basement membrane antibodies, 619, 620, 622 anti-glomerular basement membrane disease, diffuse pulmonary hemorrhage, 619 anti-Jo-1 antibodies, 600 anti-La antibodies, 592 anti-Ro antibodies, 592 anti-Sm antibodies, 592 antiarrhythmic drugs, pleural effusions/ thickening, 1025 antibacterial drugs, pleural effusions/ thickening, 1025 antimigraine drugs, pleural effusions/ thickening, 1025 antimony pneumoconiosis, 483, 484 antineutrophilic cytoplasmic antibodies, 622 Churg–Strauss syndrome, 613, 614 Goodpasture syndrome, 620 microscopic polyangiitis, 613 vasculitis, 608, 608, 609–615 diffuse pulmonary hemorrhage, 620 somatostatin receptor scintigraphy, 613 Wegener granulomatosis, 609, 611, 613 antinuclear antibodies, 596, 622 interstitial pneumonia, 563 Sjögren syndrome, 602 systemic lupus erythematosus, 592 antiphospholipid syndrome, 621 systemic lupus erythematosus, 595, 595 antiretroviral therapy, 520 AIDS-related lymphoma, 313

Index immune restoration inflammatory syndrome, 312, 313 lung toxicity, 295 pulmonary manifestations of HIV/AIDS, 295 antisynthetase syndrome, 600, 601, 601 aorta, 39, 61 aortic aneurysm, 10, 883 aortitis, 979 atherosclerotic, 960–962, 961, 974 congenital, 979, 980 cystic medial necrosis, 966 descending aorta, 886 fusiform, 960, 964, 974 mycotic, 965–966 rupture, 919, 960, 962, 963 saccular, 960, 964, 965 aortic anomalies, simulating mediastinal mass, 980 aortic arch, 61, 74 aortic arch anomalies, 886, 980, 981 aortic body paraganglioma, 884 aortic body tumors, 936 aortic branch vessel injury, 1132, 1134, 1135 aortic disease, 959–984, 959 aortic dissection, 11, 919, 966, 967 classification, 967 imaging, 968, 968, 979 aortography, 970, 971 chest radiography, 968, 969, 970 CT, 24, 968, 969, 970, 970, 972–973, 972, 973, 974, 979 echocardiography, 974, 976, 979 MRI, 973–974, 975, 976, 979 aortic hiatus, 61, 75 aortic injury, blunt, 962, 1121–1134, 1122, 1123 aortography, 1123, 1124, 1130–1131, 1131, 1133 chest radiography, 1122, 1123, 1124–1125, 1124, 1125, 1126, 1127, 1129 aortic arch contours obscuration, 1125 tracheal displacement, 1125 CT, 1122, 1123, 1125–1127, 1126, 1127, 1128, 1129, 1130, 1130, 1132 diaphragmatic rupture association, 1143, 1144 imaging guidelines, 1127 mediastinal widening, 1124–1125 minimal, 1130, 1131, 1132, 1132 MRI, 1132 posttraumatic pseudoaneurysm, 1121, 1122, 1124, 1130 transesophageal echocardiography, 1131– 1132, 1132 aortic intramural hematoma, 966, 967 imaging, 968, 968, 971, 976, 977, 978, 978 aortic nipple, 942, 944 aortic penetrating atherosclerotic ulcer, 966, 967 imaging, 968, 968, 978, 979 aortic pseudoaneurysm, 962, 962, 963, 965, 966 posttraumatic, 1121, 1122, 1124, 1130 aortic pseudocoarctation, 981, 984 aortic syndromes, acute nontraumatic diagnostic information required, 968 optimal imaging, 978–979 aortitis, aortic aneurysm, 979

aortography, 969 aortic dissection, 970, 971, 979 aortic injury, 1123, 1130–1131, 1131, 1133 penetrating atherosclerotic ulcer, 978 aortopulmonary window, 65, 66–67 Fleischner Society glossary definition, 156, 156 lymph nodes, 68 apical capping mediastinal hemorrhage, 919 mimicking pleural thickening, 1034–1035, 1034 superior sulcus tumors, 806, 806 arc-welder’s lung, 482–483, 483 architectural distortion Fleischner Society glossary definition, 156, 156 tuberculosis, reactivation (postprimary), 229 usual interstitial pneumonia, 564, 572 arterial thrombosis, antiphospholipid syndrome, 595 arteriovenous malformation, pulmonary, 1079, 1081, 1083, 1084, 1085, 1086, 1086 clinical features, 1081, 1081 genetic aspects, 1081 multiple pulmonary nodules, 133 arthropathy, interstitial pneumonia association, 563 ARTICLE±V complex, 1065 artificial intelligence, computer-aided diagnosis, 6 asbestos, 470, 471 adverse effects of exposure, 471 amphiboles, 470–471 serpentine, 470 asbestos-related disease, 470–482, 1032 benign pleural effusion, 471–472, 471 diffuse pleural thickening, 472, 472, 473–474, 476, 477 frequency, 471 interstitial pneumonia, 563 latency, 471 lung cancer risk, 482, 788 mesothelioma see mesothelioma pericardial fibrosis, 472 pleural calcification, 1036 pleural effusion, 1004 pleural plaques, 472–473, 473, 474, 475, 476, 856, 857 pulmonary fibrosis see asbestosis rounded atelectasis, 474, 476–477, 476 usual interstitial pneumonia, 564 asbestosis, 142, 471, 477–478, 477, 481, 482 high-resolution CT, 193 interlobular septum thickening, 172 latency period, 477 lung cancer association, 482 ascariasis, simple eosinophilic pneumonia (Löffler syndrome), 663 Ascaris lumbricoides, 276, 674 Ascaris suum, 674 ascites pleural effusion, 1022 pleural fluid differentiation, 1015 Askin tumors, 832 aspergilloma, 263–264, 263, 264, 265, 266, 323 allergic bronchopulmonary aspergillosis, 670

complicating sarcoidosis, 653, 658, 658 complicating usual interstitial pneumonia, 569, 571 see also mycetoma aspergillosis, 262–268 allergic bronchopulmonary see allergic bronchopulmonary aspergillosis angioinvasive, 266–267, 324, 326, 327, 328, 329 chronic necrotizing, 311 hematopoietic stem cell transplantation patients, 336, 337 HIV/AIDS patients, 310–311, 311 obstructing bronchopulmonary, 311, 311 hyperimmunoglobulin E syndrome, 676 hypersensitivity pneumonitis, 457 immunocompromised patients, 322–324, 323, 324, 324, 325, 326, 327, 328, 329 imaging findings, 324, 324, 334 invasive, 263, 264, 267, 269, 323–324, 325, 520 airway acute, 265, 267 airway chronic, necrotizing, or semi-invasive, 266, 268 solitary pulmonary nodule, CT halo sign, 131, 132 lung transplantation patients, 352, 357, 359 airways infection, 354 overlap manifestations, 267–268, 268, 270 pneumonia, 208 Aspergillus, 250, 593, 595 Aspergillus flavus, 664 Aspergillus fumigatus, 262, 606 allergic bronchopulmonary aspergillosis, 664, 666 pneumonia, 131 immunocompromised patients, 322 Aspergillus nidulans, 664 Aspergillus niger, 664 Aspergillus ochraceus, 664 Aspergillus oryzae, 664 Aspergillus terreus, 664 aspiration of gastric contents, 98 aspiration pneumonia, 142, 182, 207, 210 bat’s wing airspace opacities, 98 mixed connective tissue disease, 604 polymyositis/dermatomyositis, 602 scleroderma, 598, 599 aspirin-induced asthma, 511 asthma, 752–754 airspace opacities, 99 allergic bronchopulmonary aspergillosis, 665, 666 bronchial obstruction (mucus plug obstruction), 101 bronchial wall thickening, 752–753, 752, 754 chronic eosinophilic pneumonia, 663, 664 Churg–Strauss syndrome, 613, 615 drug-induced, 511 eosinophilia, 676 imaging findings, 752–753, 752, 753 complications detectable on chest radiograph, 753, 753 high-resolution CT, 734, 753–753 increased transradiancy of lung, 147 ventilation/perfusion (V/Q) scan, 399 pathology, 752 pneumothorax, 1039

1169

Index spontaneous pneumomediastinum, 939, 942 work-related (reactive airways disease syndrome), 490 asymmetric film–screen combinations, 1 atelectasis, 86, 89, 101–119 airspace opacities, 91 allergic bronchopulmonary aspergillosis, 670, 671 asthma, 753 bronchial carcinoid, 823 bronchial obstruction, 101 bronchial rupture, 1138 bronchopulmonary dysplasia, 537 compressive, 101 cystic fibrosis, 733 discoid (Fleischner lines), 101–103, 102 pulmonary embolism, 386, 387 fibrosing mediastinitis, 924 Fleischner Society glossary definitions, 157, 157, 162, 162, 168, 169 foreign body inhalation complication, 493, 494 heart transplantation patients, 342 lobar, 103–104, 103 bronchial dilatation/air bronchograms, 104, 105 bronchiectasis, 117, 118 combined lower and middle lobe, 115, 117 combined upper and middle lobe, 115, 116 distinguishing lower lobe collapse from pleural fluid, 115, 117, 117 Golden S sign, 103, 105, 106, 109 left upper lobe, 105, 108–109, 108, 109 lower lobe, 111–115, 112, 113, 115 mediastinal shift, 103 middle lobe, 114 peripheral, 104, 107, 109 right middle lobe, 109–111, 110, 111 right upper lobe, 104, 106, 107 silhouette sign, 83, 105, 110 lung cancer, 788 mechanisms, 101–102 middle lobe syndrome, 101, 110, 111, 111 passive, 101 pleural effusion imaging, 1006 pulmonary surfactant deficiencies, 582 round/rounded, 117–119, 118, 119, 130, 169, 169 asbestos-related, 474, 476–477, 476, 478, 479, 480 comet-tail sign, 119, 119 drug-induced, 531 smoke/fire injury, 488 systemic lupus erythematosus, 595 torsion of lung/lobe, 1154, 1156 trapped lung, 1026 tuberculosis, 230 endobronchial, 235 whole lung, 115, 116 see also collapse atelectatic pseudotumor see atelectasis, round/rounded atherosclerosis aortic aneurysm, 960–962, 961, 974 penetrating aortic ulcer, 966, 967, 968 atrial myxoma, 416 atrial natriuretic factor, 693

1170

atrial septal defect, Eisenmenger reaction, 415 atypical adenomatous hyperplasia, 818, 819 atypical mycobacteria see nontuberculous mycobacterial infection atypical pneumonia, 216 autoantibodies collagen vascular disease, 584, 585 Goodpasture syndrome, 619, 620 interstitial pneumonia, 563 mixed connective tissue disease, 604 polymyositis/dermatomyositis, 600 relapsing polychondritis, 605 scleroderma (systemic sclerosis), 596 systemic lupus erythematosus, 592 autoimmune hemolytic anemia, 947 avian antigens, hypersensitivity pneumonitis, 457 avian influenza A virus (H5N1), 272, 273 azygoesophageal line, 71, 73, 74 azygoesophageal recess, 67, 71, 73 Fleischner Society glossary definition, 157, 157 herniation, pleural effusion, 1008 azygos aneurysm, 1086–1087 azygos continuation of inferior vena cava, 917, 918 azygos lobe fissure, 56, 57, 58, 61 azygos vein, 56, 57, 61, 75

bacillary angiomatosis, 298 bacille Calmette Guérin (BCG), complications of therapy, 522, 523 Bacillus anthracis, 213 bacterial pneumonia, 87, 91, 97, 98, 98, 206, 207, 210–222 consolidation, 182 hematopoietic stem cell transplantation patients, 337 HIV/AIDS, 295, 296, 297, 319 immunocompromised patients, 321–322 lung transplantation patients, 352 sickle cell disease with acute chest syndrome, 421 smoking-related risk, 455 spherical, 97, 98 systemic lupus erythematosus, 595 bacterial (pyogenic) infections hematopoietic stem cell transplantation patients, 336 HIV/AIDS, 295, 296–298, 297 Bacteroides, 218 BALT lymphoma, 183 band, parenchymal, Fleischner Society glossary definition, 166, 166 band sign, 1146 bandlike opacities, 135–137 allergic bronchopulmonary aspergillosis, 667, 668, 669, 670 causes, 136 lung cancer (pleural tail sign), 789, 790 organizing pneumonia, 575, 577 pneumothorax, 1038, 1043, 1044, 1045 polymyositis/dermatomyositis, 601 subpleural edema, 424, 425, 426, 426 see also linear opacities baritosis, 143, 483 barium halide phosphors, 4 barrel chest deformity, cystic fibrosis, 735 Bartonella, 298

Basidiospores, hypersensitivity pneumonitis, 457 bat’s wing (butterfly) airspace opacities, 96, 97–98, 99 pulmonary edema, 426 beaded septum sign, 858 Fleischner Society glossary definition, 157, 157 Behçet disease, 420, 609, 616–618, 923, 947, 979 benign asbestos-related pleural effusion, 471–472, 471 benign clear cell tumor, 833 benign intrapulmonary teratomas, 834, 834 benign lung neoplasms, 833–835 benign mesothelioma see localized fibrous tumor of pleura benign multinodular goiter, 957 beryllium-related disease, 485–486, 485, 486, 487, 642 beta2-microglobulin, amyloid, 692–693 beta-adrenergic blockers drug-induced asthma, 511 pleural effusions/thickening, 1025 bevacizumab toxicity, 532 pulmonary thromboembolism, 518, 518 Bipolaris, allergic fungal sinusitis, 665 bird fancier’s lung, 144, 458 Birt–Hogg–Dubé syndrome, 687, 690 cystic airspaces, 183 pneumothorax, 1042 black bronchus sign, 177, 178 bladder cancer, 522 blast injury, 1153 blastoma pleuropulmonary, 831 pulmonary, 830–831, 832 Blastomyces dermatitidis, 259, 309 blastomycosis, 131, 210, 259–261, 262 HIV/AIDS, 309–310 immunocompromised patients, 330 intrathoracic lymph node calcification (egg shell calcification), 909 bleb Fleischner Society glossary definition, 157 pneumothorax, 1038, 1038 apical, 1044 bleomycin toxicity, 507, 508, 509, 522, 523, 524, 524, 525, 526, 527, 579 hypersensitivity reactions, 509, 524 pleural effusions/thickening, 1025 radiation therapy potentiation (recall pneumonitis), 542 Blesovsky syndrome see atelectasis, round/ rounded Bochdalek (posterior) hernia, 1107, 1110, 1111 Boerhaave syndrome, 921, 922 bolus-tracking technique CT, 18 CT angiography, 24 pulmonary, 391, 391 bone destruction blastomycosis, 261 lung cancer, 804, 804 Pancoast tumors, 806, 806 lymphoma, 845 neurogenic tumors (mediastinum), 931, 934, 935 bone lesions, radiation-induced, 552

Index bone marrow transplantation patients constrictive bronchiolitis, 743 diffuse alveolar (pulmonary) hemorrhage, 619 bone metastases, 813, 814 bone scintigraphy, Pancoast/superior sulcus tumors, 806 Bordetella (Haemophilus) pertussis, 216 bosetan, 564 botryomycosis, 250, 252 brachiocephalic (innominate) artery, 39, 61, 74 injury, 1132 brachiocephalic veins, 56, 61, 74 brain abscess, 1081, 1084 brain metastases, 813, 814 Branhamella catarrhalis pneumonia, 207 breast cancer, 526, 531, 539, 542, 543, 546, 546, 578, 579 metastasis, smoking-related risk, 456 bridging bronchus, 41, 45 bromocriptine toxicity, 519, 524 pleural effusions/thickening, 1025 bronchi anomalous, 41 branching pattern, 41, 43, 44 bridging, 41, 45 normal, 39, 41 pulmonary hila, 45, 47 subcarinal angle, 39 bronchial atresia pneumothorax, 1039 segmental, 1069–1070, 1069, 1070, 1071 bronchial carcinoid, 822–826, 823, 829 atypical, 823 ectopic adrenocorticotrophic hormone syndrome, 823, 823 imaging features, 823–824, 823, 824, 825, 827 solitary pulmonary nodule, 122 typical, 823 bronchial carcinoma, 85 bronchial obstruction, lobar atelectasis/ collapse, 103, 104–107, 109, 112, 113 multiple pulmonary nodules, 134 obstructive pneumonia (‘drowned lung’), 97 solitary pulmonary nodules, 119, 121, 122, 124 size, 130 V/Q scan mismatched perfusion defect, 403, 404 see also lung cancer bronchial obstruction, 101 causes, 101 with fluid retention, antenatal detection, 1098 lobar atelectasis/collapse, 103 bronchial carcinoma, 103, 104, 106, 107, 109 ‘rat tail’ narrowing, 104 bronchial rupture, 1137, 1138, 1138, 1139 bronchial stenosis bronchial obstruction, 101 central airways injury, 1138 congenital, 1066, 1067 CT, 14 lung transplantation patients, 354 sarcoidosis, 656, 657 Wegener granulomatosis, 612

bronchial wall thickening, 137, 139 asthma, 752–753, 752, 754 bronchiectasis, 729, 730, 730 chronic bronchitis, 755, 756 ciliary dyskinesia syndrome, 737 constrictive bronchiolitis, 743, 744, 744 cystic fibrosis, 729, 730, 730, 733, 734 pulmonary edema, 424 bronchiectasis, 85, 154, 187, 188, 724–732, 752 allergic bronchopulmonary aspergillosis, 665, 666, 668, 670, 670, 671, 672, 673, 725 alpha1-antitrypsin deficiency, 763 atelectasis, 101 lobar, 117, 118 bronchial wall thickening, 729, 730, 730, 733, 734 causes/associated conditions, 727 ciliary dyskinesia syndrome, 736–737 clinical features, 725 congenital (Williams–Campbell syndrome), 1068, 1069 CT, 21–22, 22, 670 cylindrical, 725, 726, 729, 729, 731, 736 asthma, 754 cystic fibrosis, 671, 673, 733, 734, 735, 736, 736, 738, 739 cystic (saccular), 140, 183, 184, 725, 726, 729, 730, 736 decreased bronchoarterial ratio, 727, 729 disease-specific patterns, 732 Fleischner Society glossary definition, 157, 157 foreign body inhalation, 494 high-resolution CT, 187–188, 188, 189, 190, 193, 725, 731–732, 731 HIV/AIDS, 312 nontuberculous mycobacterial infection, 243 Mycobacterium avium–intracellulare, 244, 245, 245, 246 overinflation, 725, 727 pathogenesis, 725 radiation-induced lung injury, 546 radiographic features, 725, 727, 728 Reid classification, 725 reversibility of changes, 724 rheumatoid arthritis, 585, 587, 590 scimitar (venolobular) syndrome, 1079 smoke/fire inhalational injury, 489 tracheobronchomegaly, 721, 721, 722 traction see traction bronchiectasis tuberculosis, reactivation (postprimary), 233, 234 varicose, 725, 726, 729, 729 bronchiolar carcinoma see bronchioloalveolar carcinoma bronchiolectasis, Fleischner Society glossary definition, 157–158, 158 bronchioles Fleischner Society glossary definition, 157 high-resolution CT, 153 normal, 50 respiratory, 51 terminal, 50 bronchioliths, tuberculosis, 235, 236, 240 bronchiolitis, 740, 741 chronic/recurrent aspiration, 492 Fleischner Society glossary definition, 158 follicular, 748, 749

high-resolution CT, 190, 191, 192 hypersensitivity pneumonitis, 458, 460 Swyer–James (McLeod) syndrome, 750 Wegener granulomatosis, 609 see also constrictive bronchiolitis; obliterative bronchiolitis (bronchiolitis obliterans) bronchiolitis obliterans organizing pneumonia (BOOP) see cryptogenic organizing pneumonia bronchiolitis obliterans syndrome, 361, 743 classification, 360 imaging features, 361–362, 361, 362 lung transplantation patients, 359–362, 360, 361, 362, 363 bronchioloalveolar carcinoma, 569, 788, 814–817 air bronchograms, 85, 88 airspace opacities, 91, 94, 98 CT angiography, 91 epidemiology, 814 imaging features, 793, 794, 814–815, 815, 816, 817 pathology, 814 prognosis, 814 pseudocavitation, 814–816 solitary pulmonary nodule, 130 ground-glass opacity, 127, 127 bronchitis, 752, 754–756 acute exacerbations, 755 coal worker’s pneumoconiosis, 469 definition, 754 epidemiology, 754–755 hyperimmunoglobulin E syndrome, 676 pathologic changes, 755 radiographic features, 755, 755, 756 bronchial pits, 755, 756 rheumatoid arthritis, 590 silica exposure-related, 468 Swyer–James (McLeod) syndrome, 750 bronchoalveolar lavage eosinophilic pneumonia acute, 662 chronic, 663 pulmonary alveolar microlithiasis, 680 pulmonary alveolar proteinosis, 678 bronchocele see mucoid impaction bronchocentric disease, Fleischner Society glossary definition, 158, 158 bronchocentric granulomatosis, 674–675, 675 rheumatoid arthritis, 590 bronchogenic cyst, 885, 886, 1089–1093, 1090 antenatal detection, 1098 clinical manifestations, 1090 diagnosis, 1093 imaging features, 1090–1092, 1091, 1092, 1093 pulmonary sequestration association, 1089, 1098 broncholithiasis, 23, 740, 740 actinomycosis, 249 bronchial obstruction, lobar atelectasis, 103 Fleischner Society glossary definition, 158, 158 bronchomalacia, lung transplantation patients, 354 bronchopathia osteo(chondro)plastica, 718 bronchopleural fistula, 223, 237, 239, 1051, 1051 causes, 1051

1171

Index bronchopneumonia, 205, 206, 206 aspergillosis in immunocompromised patient, 323 intravenous drug users, 532 tuberculosis, 233–235, 240 bronchopulmonary dysplasia, 537, 538, 539 decreased attenuation lung, 185 bronchopulmonary endometriosis, 1040–1041, 1041 bronchopulmonary segments, 50 bronchoscopic lung volume reduction, preoperative, 764, 765, 766 bronchoscopy, lung cancer staging, 800 bronchovascular bundle, high-resolution CT, 153 bronchovascular interstitial thickening high-resolution CT, 171 nodular, 176 bronchus suis (tracheal bronchus), 41, 45, 1067 brown fat, 896, 896 brucellosis, 217 Brugia malayi, 673 bubblelike lucencies (pseudocavitation) bronchioloalveolar carcinoma, 814, 815, 816 solitary pulmonary nodule, 130 buffalo chest, 1049 lung transplantation, 365, 365 bullae complications, 767–768 cutis laxa (generalized elastolysis), 1042 Ehlers–Danlos syndrome, 1042 emphysema, 158, 759, 765–767, 767 alpha1-antitrypsin deficiency, 763 paraseptal, 757 enlargement (vanishing lung syndrome), 767 Fleischner Society glossary definition, 158, 158 Marfan syndrome, 1042 simulating pneumothorax, 1043, 1044 Burkholderia cystic fibrosis patients, 733 lung transplantation recipients, 345 Burkholderia cepacia, 733 Burkholderia pseudomallei, 217 ‘bush tea’, 411, 518 busulfan toxicity, 507, 524, 528 pleural effusions/thickening, 1025 butterfly shadowing see bat’s wing airspace opacities byssinosis, 462

calcification amyloidosis, 696 alveolar septal disease, 698 parenchymal nodular disease, 697–698 aortic aneurysm (atherosclerotic), 960, 962 aortic dissection, 968, 970, 970 aortitis, 979 asbestos-related pleural plaques, 472, 473, 473, 474 atheromatous pulmonary artery with pulmonary hypertension, 410, 411 bronchial carcinoid, 823, 824, 826, 827 bronchogenic cyst, 1091 broncholithiasis, 740, 740 concentric (laminated), 121, 124

1172

dermatomyositis, 585 diffuse pulmonary, differential diagnosis, 680–681, 681 drug-induced, 519 fibrosing mediastinitis, 924 hamartomas, 827, 828, 829 histoplasmosis, 251, 252, 254, 255, 256 ligamentum arteriosum, 65–66 lung cancer, 791, 792, 793 lymph nodes, 647, 647, 908–909 causes, 909 mediastinal lesions, 881, 883 metastases, 519, 519, 858, 859, 859, 860 multiple pulmonary nodules, 133 neurogenic tumors (mediastinum), 935 nodular opacities, 143, 144 nonseminomatous germ cell malignancies, 903 pleural, 1036–1037, 1036 polymyositis/dermatomyositis, 600, 601 popcorn, 121, 124, 125, 827, 828 pulmonary alveolar microlithiasis, 679–680, 680 punctate, 99–100, 101, 121 sarcoidosis, 643, 647, 647 scleroderma, 585 silicoproteinosis, 466, 467 silicosis, 463, 464, 465 solitary pulmonary nodule, 121, 124, 125, 132 teratoma, mature, 900, 901 thymoma, 950 thyroid goiter, intrathoracic, 957 tracheal cartilages, 39 tuberculosis primary, 230, 232, 240 reactivation (postprimary), 229, 233 usual interstitial pneumonia, 566 calcispherites (microliths), 679 camalote sign, 280 Candida infection, 250, 595 allergic bronchopulmonary mycosis, 665 hematopoietic stem cell transplantation patients, 336, 337 HIV/AIDS patients, 296 immunocompromised patients, 326, 329 pneumonia, 324, 326, 329, 330 lung transplantation patients, 352, 357, 359 airways infection, 354 capillary hemangioma, mediastinum, 917 Caplan syndrome, 590, 591 multiple pulmonary nodules, 133 carbemazapine hypersensitivity reactions, 509, 673 carcinoid syndrome, 823 carcinoid tumors mediastinum, 884 pulmonary sequestration, 1093 thymus, 955 carcinosarcoma, 830 cardiac amyloidosis, 694 cardiac arrhythmias, 520 cardiac enlargement see cardiomegaly cardiac herniation, 1148, 1150 cardiac surgery, complications acute mediastinitis, 922, 925 chylothorax, 1029 pleural effusions, 1021 postpericardiotomy syndrome, 1021

cardiogenic pulmonary edema, 142, 423, 424, 425 alveolar edema, 426–427, 428 differentiation from noncardiogenic, 432 radiographic signs, 424 resolution, 426 cardiomegaly Churg–Strauss syndrome, 615, 615 congenital systemic-to-pulmonary shunts, 415 heart transplantation patients, 342 polymyositis/dermatomyositis, 600 pulmonary arterial hypertension, 408, 408, 409 chronic thromboembolism, 418 sickle cell disease, 422 cardiophrenic fat pad, 111, 114 cardiophrenic varices, 884 carina, 39 carmustine (BCNU) toxicity, 507, 508, 509, 535–536, 535, 536, 537 Carney triad, 826–827 carotid artery injury, 1132 cartilage tumors, solitary pulmonary nodule, 121 Castleman disease, 845, 847, 883, 906–907, 907, 909 HIV-related, 907 hyaline–vascular, 906, 907, 908, 909, 910 lung parenchymal involvement, 907 lymph node calcification, 908 lymphoid interstitial pneumonia, 580, 581 plasma cell, 906 catamenial hemothorax, 1040 catamenial pneumothorax, 1040, 1040, 1041 cavernous hemangioma, mediastinum, 917, 919 cavitation, 91, 92 aspergillosis, 310–311, 311, 326, 329 blastomycosis, 261, 262 bronchioloalveolar carcinoma, 814, 815 coccidioidomycosis, 258, 260, 261 cryptococcosis, 257, 257 cryptogenic organizing pneumonia, 575 definition, 90, 130 Fleischner Society glossary, 159, 159 histoplasmosis, 253, 255 HIV/AIDS-related infections, 297, 297, 299, 299, 310–311, 311 lymphoma, 841 mucormycosis, 330, 331 multiple pulmonary nodules, 133 nocardiosis, 248, 248 nontuberculous mycobacterial infection, 243, 244, 244 Mycobacterium avium–intracellulare, 246, 246 pneumonia, 205, 207–208, 209, 212, 213, 213 progressive massive fibrosis coal worker’s pneumoconiosis, 469 silicosis, 464 pulmonary embolism with infarction, 387, 389, 394 pulmonary metastases, 858, 859 sarcoidosis, 653, 655 solitary pulmonary nodules, 130–131 tuberculosis, 238, 240, 241, 299, 299 primary, 230, 231 reactivation (postprimary), 229, 232, 233, 233, 234

Index vasculitis, 608 Wegener granulomatosis, 610, 611, 611 within airspace opacities/consolidations, 90, 91 CCNU toxicity, 535 CD4 counts, HIV/AIDS, 295, 314 antiretroviral therapy response, 312 immune restoration inflammatory syndrome, 312 influence on pulmonary manifestations, 297, 298, 299, 304, 308, 309, 310, 311 cell-mediated (type IV) hypersensitivity, drug-induced vasculitis, 513 cement, pulmonary embolism, 518, 518 central airways disease see airways disease injury, 1137–1139, 1138 normal, 39 centrilobular emphysema, 747, 759, 760, 760, 761, 1038 Fleischner Society glossary definition, 159 high-resolution CT, 183 centrilobular nodules, 176 associated conditions, 178 centrilobular structures, Fleischner Society glossary definition, 159 cerebral glioma, 535 Chagas disease, 892 charge-coupled device (CCD) cameras, 4 chemicals exposure hypersensitivity pneumonitis, 457 pulmonary alveolar proteinosis, 677 chemodectoma, 833 chest radiography, 1 basic patterns of lung disease, 83–148 air bronchograms, 85–86, 87, 88, 89 airspace opacities, 89–101 atelectasis/collapse, 101–119 pulmonary opacity, 88–89, 89, 90 silhouette sign, 83–85, 84, 85, 86 solitary pulmonary nodule/mass, 119–132 digital see digital chest radiography extra radiographic views, 2–3 inspiratory/expiratory film, 1, 2 limitations, 3 mediastinal contours frontal view, 69–74, 69, 70, 71, 72, 73, 74 lateral view, 74–75, 74, 75 normal chest, 40, 41 portable, 3 standard views, 1–2, 2 systematic approach to analysis, 89 technique, 1–2 chest wall actinomycosis invasion, 250, 251 lung cancer invasion, 803–805, 804 lung interface, 53 neurofibromatosis, 682 structures causing diagnostic problems, 76 chickenpox pneumonia see varicella pneumonia child abuse, rib fractures, 1151 Chlamydia pneumoniae chronic bronchitis acute exacerbations, 755 pneumonia, 221 Chlamydia psittaci infection (ornithosis; psittacosis), 210, 221

Chlamydia trachomatis, 221 chlamydial pneumonia, 207, 210, 221–222 chlorambucil, lung toxicity, 509 chloroma (granulocytic sacroma), 848 chlorpropamide hypersensitivity, 673 chondroma, 833 chondrosarcoma, 829, 941, 943 chordoma, 886, 941 choriocarcinoma, 831, 902 chronic eosinophilic pneumonia, 660, 663–664 consolidation, 181 imaging features, 663, 664, 665, 666 chronic granulomatous disease, 322 chronic myelogenous leukemia, 524 chronic obstructive pulmonary disease, 207, 752–768 aspergillosis, 263 lung transplantation, 344 pneumothorax, 1039 pulmonary hypertension, 416, 417, 417 saber-sheath trachea, 715–716 ventilation/perfusion (V/Q) scan, 399 chronic/recurrent aspiration, 492, 493, 494 chrysotile, 470, 471, 472, 477 see also asbestos-related disease Churg–Strauss syndrome, 513, 608, 609, 613–615, 613, 664 allergic phase, 613 diagnostic criteria, 613 eosinophilic phase, 613–614, 615 imaging features, 613, 614, 615, 615 vasculitic phase, 613, 614, 615 chyle, physiology, 1027–1028 chyloma, 1027, 1028 chylothorax, 1015, 1022, 1027–1031, 1030, 1031 causes, 1029, 1029 idiopathic, 1028, 1029–1039 imaging, 1030–1031 lung transplantation patients, 365 lymphangioleiomyomatosis, 685, 686, 686, 687 lymphangiomatosis, 1088 lymphoma, 844 mechanisms of formation, 1027 neoplastic, 1029 postsurgical, 1029, 1029 traumatic, 1029 thoracic duct injury, 1140, 1141 tuberous sclerosis, 684 chylous effusion see chylothorax ciliary dyskinesia syndrome (immobile cilia syndrome), 736–737, 736, 739, 740 bronchiectasis, 736–737 cisterna chyli, 1027 Cladosporium, 358 clofibrate hypersensitivity, 673 cloudlike calcification, 143 solitary pulmonary nodule, 121 coagulopathy, diffuse pulmonary hemorrhage, 621 coal dust exposure, 468–469, 469 coal macule, 469, 469 coal workers, focal dust emphysema, 757 coal worker’s pneumoconiosis, 142, 468–470, 470, 883 clinical manifestations, 469 imaging features, 469–470 intrathoracic lymph node calcification (egg-shell calcification), 908, 909

multiple pulmonary nodules, 133 nodular pattern, 176 progressive massive fibrosis, 464, 466, 469 rapidly progressive, 469–470 simple (coal macule), 469, 469 coarctation of aorta, aortic aneurysm, 979, 980 cocaine misuse, 967 granulomatous pneumonitis, 514 lung injury, 533, 534, 534, 621 spontaneous pneumomediastinum, 939 coccidioidal nodules (coccidioidoma), 258, 259 Coccidioides immitis, 258 coccidioidomycosis, 210, 258–259, 260, 261, 740, 904 immunocompromised patients, 330 persistent pulmonary, 258–259, 259 primary, 258 cognitive errors, chest radiograph interpretation, 3 COL3A1 gene mutations, 1042 collagen vascular disease, 584–585 associated lung disease, 584–585, 584 patterns of involvement, 586 autoantibodies, 584, 585 diffuse pulmonary hemorrhage, 620 interstitial pneumonia, 562, 563 nonspecific, 573 usual, 564 mediastinal lymphadenopathy, 906 secondary organizing pneumonia, 578 collapse asthma, 753, 753 loculated pleural fluid differentiation, 1014, 1015 lung cancer, 795–796, 795, 796, 801 sarcoidosis, 656 see also atelectasis collar sign, 1144, 1145–1146, 1146, 1147 collateral air drift, 50, 54 collimation, 12, 13, 16 aliasing artifact, 21 emphysema extent quantification, 762 mediastinal lymphadenopathy detection, 912 multiplanar reconstructions, 14 narrow, 20, 21, 22, 175 pulmonary embolism detection, 389 colorectal cancer, 539 comet-tail sign, 119, 119, 1046 rounded atelectasis, 476 common cold, smoking-related risk, 455 common variable immunodeficiency bronchiectasis, 732 lymphoid interstitial pneumonia, 580 communicating thoracic hydrocele, 891, 893 computed radiography, 4 computer-aided detection (CAD), 6, 8, 9 concentric (laminated) calcification, solitary pulmonary nodule, 121, 123 congenital anomalies, 1065–1112 classification, 1065, 1066 congenital aortic aneurysm, 979, 980 congenital bronchiectasis (Williams– Campbell syndrome), 1068, 1069 congenital chylothorax, 1029 congenital cystic adenomatoid malformation, 1097, 1099–1104, 1099, 1100 antenatal diagnosis, 1100, 1103

1173

Index clinical manifestations, 1100 imaging features, 1100, 1101, 1102, 1103, 1104, 1104 pathologic types, 1100 pulmonary sequestration association, 1098, 1099, 1100 congenital diaphragmatic hernia, 1096, 1097, 1100, 1104–1107, 1105, 1106, 1108 antenatal detection, 1097 diagnostic pitfalls, 1106 prognostic features, 1105–1106 pulmonary hypoplasia association, 1075, 1078, 1105 congenital heart disease, 1065 congenital diaphragmatic hernia, 1106 left superior vena cava, 61 scimitar (venolobular) syndrome, 1079 congenital lobar overinflation (emphysema), 1070, 1072, 1073, 1073 congenital lymphatic development disorders, 1087–1089, 1087 congenital pulmonary alveolar proteinosis, 677 congenital systemic-to-pulmonary shunts classification, 414 pulmonary arterial hypertension, 414–416, 415 congenital thymic cysts, 955–956, 956 connective tissue disease constrictive bronchiolitis, 742 heritable, 1041 pneumothorax, 1041–1042 immune complex vasculitis, 616 nonspecific interstitial pneumonia, 573 overlap syndromes, 603–604 consolidation, 86, 87, 91 actinomycosis, 249, 250 acute eosinophilic pneumonia, 662, 662 acute interstitial pneumonia, 580 airspace opacities, 91, 94, 97 allergic bronchopulmonary aspergillosis, 666, 667, 668 aspergillosis, 311, 324, 326, 329 Behçet disease, 616, 617 blastomycosis, 261, 262 bronchioloalveolar carcinoma, 814, 815, 816, 817 bronchocentric granulomatosis, 674, 675 chronic eosinophilic pneumonia, 663, 664, 664, 665, 666 Churg–Strauss syndrome, 615, 615 CT angiogram sign, 91, 92 cryptococcosis, 257, 257 cryptogenic organizing pneumonia, 575, 577, 577, 578 cystic fibrosis, 733 definition, 89 diffuse alveolar hemorrhage, 621 fat embolism syndrome, 1159 Fleischner Society glossary definition, 159, 159 high-resolution CT, 180–182, 181, 182 associated conditions, 181 histoplasmosis, 253 leptospirosis, 220 leukemic infiltration of lungs, 848 lung cancer, 795, 795 Mycoplasma pneumonia, 269, 270, 271 nocardiosis, 248, 248 non-Hodgkin lymphoma, 842

1174

nontuberculous mycobacterial infection, 243 organizing pneumonia, 583 pertussis, 217, 217 Pneumocystis jirovecii pneumonia, 305 pneumonia, 97, 205, 206, 207, 209, 210, 212, 213 anaerobic organisms, 219 lobar, 211 pulmonary alveolar proteinosis, 678 pulmonary embolism with infarction, 387 pulmonary surfactant deficiencies, 582 radiation-induced lung injury, 544, 544, 546 sarcoidosis, 648 sickle cell disease, acute chest syndrome, 421, 422 silicoproteinosis, 466–467, 467 simple eosinophilic pneumonia, 662 tuberculosis, reactivation (postprimary), 231, 233, 234 Wegener granulomatosis, 610, 610, 611, 613 constrictive (obliterative) bronchiolitis, 17, 22, 741–742, 742, 743, 743, 744, 744, 745, 746 causes, 742 high-resolution CT, 189–190, 191, 191, 192 increased transradiancy of lung, 147 pathology, 741, 741 radiographic features, 743–744, 743, 744 Swyer–James (McLeod) syndrome, 750 see also obliterative bronchiolitis (bronchiolitis obliterans) continuous diaphragm sign, 940, 942 contrast enhancement CT, 17–19, 19 angiography, 24 bolus-tracking technology, 18 pulmonary angiography, 389–390, 390 saline flush technique, 18 streak artifact, 18 hilar lymphadenopathy, 915 lung cancer, 794 mediastinal lymphadenopathy, 912, 914 mediastinal mass, 883 MRI, 29, 128, 794, 914 solitary pulmonary nodule, 127–128, 128 contusion, lung parenchyma, 1121, 1125, 1125, 1126, 1134–1135, 1134, 1136, 1145 blast injury, 1153 gunshot wounds, 1153, 1155 stab wounds, 1153 contusion, myocardial, 1148 cor pulmonale bronchiectasis, 725 chronic bronchitis, 755 cutis laxa (generalized elastolysis), 1042 fat embolism, 1158 Marfan syndrome, 1042 sarcoidosis, 653 usual interstitial pneumonia, 564 cor triatriatum, pulmonary arterial hypertension, 416 corona radiata, lung cancer peripheral tumor imaging, 789, 790 solitary pulmonary nodules, 130 coronary arteriography, transplant graft vasculopathy, 343

coronary artery bypass surgery chylothorax, 1029 pleural effusions, 1021 corticosteroids, 520 Pneumocystis jirovecii pneumonia, 331 costochondral junction, simulating solitary pulmonary nodule, 120 costophrenal sulcus, 53 cough fracture of rib, 1151 Coxiella burnettii, 210, 220 crack lung, 534 crazy-paving pattern, 174, 195 acute respiratory distress syndrome, 431 cryptococcosis, 257 diffuse alveolar hemorrhage, 621 exogenous lipid pneumonia, 515, 517 Fleischner Society glossary definition, 159, 159 pulmonary alveolar microlithiasis, 680 pulmonary alveolar proteinosis, 678, 678, 679 silicoproteinosis, 467 creeping eruption (Ancylostoma braziliense), 674, 674 CREST syndrome, 597, 599 pulmonary hypertension, 599 thoracic findings, 596 crocidolite, 471, 472, 477, 851 see also asbestos-related disease Crohn disease, pulmonary complications, 688, 689, 690 Crotolaria fulva, 411 cryoablation therapy, 552 cryptococcosis, 131, 210, 254–258, 256, 520, 595, 740 heart transplantation patients, 342 HIV/AIDS patients, 296, 308, 309, 310 immunocompromised patients, 330 lung transplantation patients, 357 nodules/masses, 255–256, 257 patchy consolidation, 257, 257 pleural effusion, 258 pulmonary alveolar proteinosis, 679 widespread small nodular/irregular shadows, 257 Cryptococcus neoformans, 254, 256 cryptogenic bilateral fibrosing pleuritis, 1034, 1034 cryptogenic fibrosing alveolitis, 563 cryptogenic organizing pneumonia, 100, 561, 562, 563, 575–577, 741 clinical features, 575 epidemiology, 575 histology, 575 imaging appearances, 181, 575–577, 576, 577, 578 progression, 577 see also organizing pneumonia Cryptosporidium, 311 CT angiography aortic injury see aortic injury, CT indications, 24 see also CT pulmonary angiography CT, 1 acquisition parameters, 11–12 air bronchogram, 85, 87, 88, 89, 91 airspace opacities, 91, 92 airways disease, 21–22, 24 angiogram sign, 91, 92, 94

Index contrast enhancement, intravenous, 17–19, 19 field of view size, 11 Fleischner Society glossary of terms, 155–171 halo sign, 97, 131, 132 image reconstruction, 14–15 indications, 19–20, 20 lung density measurement technique, 762, 762 lung–chest wall interface, 53, 54 maximum intensity projections, 16–17, 17 minimum intensity projections, 17, 17, 18 multiplanar reformations pitch, 11–12 pixels, 11 positron emission tomography combined examination see positron emission tomography–CT (PET-CT) protocols, 19–20 radiation dose, 12–13, 13, 19 detector efficiency, 13–14 electronic noise, 14 focal spot tracking, 13 geometric efficiency, 13 measurement, 13, 13 noise filtering, 14 reduction, 14 scanner geometry, 13 tube current modulation, 14 section thickness, 11, 12, 12, 13 spatial resolution, 11 narrow collimation, 20 surface shaded display, 14, 15, 16 targeted reconstruction, 11 technical considerations, 6–7, 11 volumetric (spiral/helical), 6, 11 continuous scanning, 7 voxels, 11 density, 19 window settings, 19, 19 see also CT angiography; CT pulmonary angiography; high-resolution CT; multidetector CT (MDCT) CT densitometry, 762, 762 solitary pulmonary nodules, 121, 125, 126 CT pulmonary angiography bolus-tracking, 391, 391 chronic thromboembolism, 419 contrast enhancement, 389–390, 390 CT venography combined examination, 397–398 image reconstruction, 391 patient-related problems, 391–392 pulmonary embolism, 387, 389–390, 389, 390, 391 accuracy, 394–398 acute embolism, 392–393, 392, 393 chronic/recurrent embolism, 393–394, 393 false negative/false positive, 394, 395, 396 Takayasu arteritis, 420 technical aspects, 389–392 window settings, 391, 392 CT venography, pulmonary embolism diagnosis, 397–398 Cunninghamella, 329 curvilinear calcification goiter, intrathoracic, 957 mediastinal mass, 883 neurogenic tumors, 935

curvilinear subpleural lines, asbestosis, 477 Curvularia allergic bronchopulmonary mycosis, 665 allergic fungal sinusitis, 665 Cushing syndrome (ectopic adrenocorticotrophic hormone syndrome), 823, 823, 948, 955 rib fracture with excessive callus, 1151 cutis laxa (generalized elastolysis), 756, 1042 cyclophosphamide toxicity, 507, 508, 509, 515, 524–525, 525, 528 radiation therapy potentiation (recall pneumonitis), 542 cystic airspaces, high-resolution CT, 183–184, 183, 184, 185, 186 associated conditions, 183 cystic angiomatosis, 919 cystic fibrosis, 139, 143, 147, 190, 193, 207, 733–736 allergic bronchopulmonary aspergillosis, 670–671, 673, 733, 737 diagnostic criteria, 671 bronchial obstruction (mucus plug obstruction), 101 bronchiectasis, 725, 732, 733, 734, 735, 736, 736, 738, 739 clinical features, 733 genetic aspects, 733 hilar lymphadenopathy, 733, 734, 738 lung transplantation, 344, 346, 347, 354, 359, 361, 363, 368 nocardiosis, 247 nontuberculous mycobacterial infection, 243, 244 pneumothorax, 733, 736, 739, 1039 catamenial hemoptysis, 1041 loculated, 1047 pulmonary hyperinflation, 733, 734, 735, 736 pulmonary infections, 733 radiographic features, 733, 734, 735, 736, 736 CT, 733, 735, 736, 736, 738, 739 signet ring sign, 728 cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations, 733 cystic hygroma see lymphangioma cystic medial necrosis, 966 cystic opacities, 140, 140 cystinuria, 537 cysts, 135 ankylosing spondylitis, 606 Birt–Hogg–Dubé syndrome, 687, 690 bronchiectasis, 729 bronchogenic see bronchogenic cyst causes, 135 congenital cystic adenomatoid malformation see congenital cystic adenomatoid malformation dermoid, 899 emphysema, 761, 761 see also bullae enteric duplication, 886 esophageal duplication, 886, 887, 887, 892, 1098 fat–fluid level, 883 Fleischner Society glossary definition, 159, 159 foregut, 882, 883, 884, 886

hyperimmunoglobulin E syndrome, 676 hypersensitivity pneumonitis, 460, 461 Langerhans cell histiocytosis, 454, 455 lung cancer, 794 lymphangioleiomyomatosis, 685, 686, 686, 687, 688, 689 lymphoid interstitial pneumonia, 581, 581 Marfan syndrome, 1042 mediastinal, 883, 884, 886–890, 887 neurenteric, 889, 889, 1098 neurofibromatosis type I, 683, 683 paratracheal, 724 pericardial, 882, 883, 884, 887–888, 888, 889 posttraumatic lung, 1134, 1135, 1136 pulmonary alveolar microlithiasis, 680 pulmonary lacunae (air cysts) in treated metastases, 859 pulmonary surfactant deficiencies, 582 sarcoidosis, 653, 655 simulating pneumothorax, 1043 Sjögren syndrome, 603, 604 thymic, 950, 955–956, 956, 957 tuberous sclerosis, 684, 685 usual interstitial pneumonia, 565 acute exacerbation, 572 see also cystic airspaces; cystic opacities; honeycomb pattern; pneumatocele cytomegalovirus infection, 595 heart transplantation patients, 342–343, 343 hematopoietic stem cell transplantation patients, 338 HIV/AIDS-related, 296, 312 immunocompromised patients, 331–332, 333 lung transplantation patients, 355, 357, 357, 358 obliterative bronchiolitis, 360 lung transplantion donor screening, 345 cytosine arabinoside toxicity, 512, 515, 517, 525 cytotoxic drugs hematopoietic stem cell transplantation regimens, 336 lung injury, 338, 522, 524, 525, 526, 527, 529, 531, 535, 539, 541 pleural effusions/thickening, 1024–1025 radiation therapy potentiation (recall pneumonitis), 542

3D conformational radiation therapy, lung injury, 546–547, 549 D-dimer tests, pulmonary embolism, 386, 397 dantrolene, pleural effusions/thickening, 1025 daptomycin toxicity, 511 dendriform pulmonary ossification, 176, 681 dependent viscera sign, 1146, 1148 dermatomyositis, 142, 585 see also polymyositis/dermatomyositis dermoid cyst, 899 desipramine hypersensitivity reaction, 511 desmoid tumor, 890–891, 891 desquamative interstitial pneumonia, 178, 452, 453, 453, 562, 562, 563 Fleischner Society glossary definition, 160, 160 imaging features, 584 CT, 583

1175

Index prognosis, 584 rheumatoid arthritis, 588 dexfenfluramine toxicity, 526 dextran, intraperitoneal, 1022 diaphragm congenital abnormalities, 1104–1112 crura, 75 dysfunction polymyositis/dermatomyositis, 601 systemic lupus erythematosus (‘shrinking lungs’), 594–595 eventration, 76 normal, 75, 77 range of movement, 76 diaphragmatic elevation diaphragmatic injury, 1143, 1145, 1147 lung cancer, 801 pleural effusion, 1008, 1009, 1010, 1011 subpulmonic, 1007, 1009 scleroderma, 596 diaphragmatic hernia, 884, 891 congenital see congenital diaphragmatic hernia traumatic pleural effusion, 1024 diaphragmatic injury/rupture, 1121, 1142–1147, 1149 aortic injury, 1143, 1144 blunt trauma, 1143, 1144 clinical features, 1142 herniation of abdominal contents, 1142, 1143, 1144, 1145, 1146, 1147, 1148 imaging features, 1143, 1143, 1145–1147 band sign, 1146 collar sign, 1144, 1145–1146, 1146, 1147 dependent viscera sign, 1146, 1148 hump sign, 1146, 1147 intra-abdominal injuries, 1143 penetrating injuries, 1143 preoperative diagnosis, 1143 diaphyseal aclasia, 679 diffuse alveolar damage acute interstitial pneumonia, 579 drug-induced, 507–508, 508, 524, 534, 536, 537 polymyositis/dermatomyositis, 601 diffuse alveolar (pulmonary) hemorrhage, 618–622 Churg–Strauss syndrome, 615, 615 coagulopathy, 621 collagen vascular disease, 620 differential diagnosis, 621–622 drug-induced, 621 Goodpasture syndrome, 619 hematopoietic stem cell transplantation patients, 338, 338 idiopathic (primary) pulmonary siderosis, 620 imaging features, 621 high-resolution CT, 196 immune complex disorders, 620 microscopic polyangiitis, 613, 613, 620 vasculitis, 608 Wegener granulomatosis, 609, 611, 611 diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH), 749–750, 750, 823 diffuse (Japanese) panbronchiolitis, 746 high-resolution CT, 190, 191 pathology, 746

1176

diffuse lung disease high-resolution CT, 171 conditions with ‘diagnostic’ appearance, 194, 194 cystic airspaces, 183–184 decreased attenuation lung, 184–186 nodular pattern, 175–177 parenchymal opacification, 177–182 reticular pattern, 171–175 sensitivity, 193 specificity, 193–194 lung opacities, descriptive terms, 139–140 diffuse malignant mesothelioma see mesothelioma diffuse panbronchiolitis, 746–747, 746 CT, 22 recurrence following lung transplantation, 364 rheumatoid arthritis, 590 diffuse pleural thickening asbestos-related, 472, 472, 473–474, 476, 477 pleural metastases, 1034 diffuse pulmonary hemorrhage see diffuse alveolar (pulmonary) hemorrhage diffuse pulmonary ossification, 681–682 dendriform, 681, 682, 682 nodular, 681–682 usual interstitial pneumonia, 566, 567 diffusion capacity for carbon monoxide (DLCO) reduction drug-induced lung disease, 505, 506, 536, 539 bleomycin toxicity, 524 scleroderma, 596 digital chest radiography, 4–5 computer-aided diagnosis, 6 digital tomosynthesis, 4, 6, 8 dual-energy subtraction imaging, 4, 5, 5, 6 image display, 4 image processing, 4 radiographic data acquisition, 4 temporal subtraction imaging, 4, 5–6, 7 digital subtraction angiography pulmonary embolism, 405, 406 radiation dose, 406 digital tomosynthesis, 4, 6, 8 diphenylhydantoin toxicity, 520, 526, 621 DIPNECH see diffuse idiopathic pulmonary neuroendocrine cell hyperplasia Dirofilaria immitis, 278 docetaxel, lung toxicity, 509, 526, 539, 540 dopamine receptor stimulants, pleural effusions/thickening, 1025 double aortic arch, 981, 983 double diaphragm sign, 1045 double wall sign, 1043 emphysema, 767 Down syndrome, subpleural cystic airspaces, 183 doxorubicin, lung toxicity, 509, 539 radiation therapy effects accentuation, 542 Dressler syndrome, 1021 drowned lobe, lung cancer, 796, 797 drug abuse, intravenous, thoracic complications, 532–533, 532 drug-induced lung disease, 505–541 alveolar hemorrhage, 515–516 autoimmune mechanisms, 512–513 lupus, 512–513, 513, 519 vasculitis, 513, 513

clinicopathologic manifestations, 506 diffuse pulmonary hemorrhage, 621 direct toxic action on lung tissues, 507–509 diffuse alveolar damage, 507–508, 508 interstitial pneumonia, 508–509, 509 organizing pneumonia, 509 eosinophilic, 673, 673 hematopoietic stem cell transplantation patients, 336, 338 histopathologic manifestations, 506 hypersensitivity reactions, 509, 510, 511 imaging findings, 406 infections, 520 lung fibrosis, 563 lymphadenopathy, 519, 520 neural/humoral mechanisms, 511 nonspecific interstitial pneumonia, 573 obliterative bronchiolitis, 518–519 online database, 507 pleural effusion/fibrosis, 519, 1024–1025, 1025 pneumothorax, 1048 pulmonary alveolar proteinosis, 677 pulmonary calcification, 519 pulmonary edema, 511, 512 pulmonary granulomatosis, 513–515, 513 pulmonary hypertension, 516 pulmonary thromboembolism, 518 rheumatoid arthritis, 591 secondary organizing pneumonia, 578 usual interstitial pneumonia, 564 dual-energy subtraction imaging, 4, 5, 5, 6 dumbell neurofibroma, 929, 931 dust exposure acute eosinophilic pneumonia, 660 focal dust emphysema, 757 lung fibrosis, 563 pulmonary alveolar proteinosis, 677 dysgammaglobulinemia, 842 dysproteinemias, 580

Ebstein anomaly, 1075 ECG-gating CT aortic dissection, 970, 972 high-resolution CT, 21 MRI, 29 Echinococcus granulosus, 279 Echinococcus multilocularis (alveolaris), 279, 674 ectopic adrenocorticotrophic hormone syndrome see Cushing syndrome ectopic thyroid, tracheal filling defects, 723–724 edge enhancement, digital chest radiography, 4 egg-shell calcification, 908, 909, 911 Ehlers–Danlos syndrome, 1042 Eisenmenger syndrome, 147, 409, 410, 411, 415–416, 415 embryonal cell carcinoma, 898, 902 emphysema, 17, 18, 31, 32, 73, 752, 756–763 bullae, 158, 757, 759, 763, 765–767, 767 causes, 756 centrilobular/centriacinar, 159, 183, 747, 759, 760, 760, 761, 1038 chest radiography, 747, 758–759, 758 classification, 756–757 clinical features, 757

Index coal worker’s pneumoconiosis, 469, 469 CT, 759–763, 760, 761 high-resolution CT, 183, 184 cutis laxa (generalized elastolysis), 1042 definition, 756 Fleischner Society glossary, 159, 160 HIV/AIDS, 295, 312 hyperinflation, 758, 758, 759 hypersensitivity pneumonitis, 460, 461, 461 increased transradiancy of lung, 147, 148, 184 interstitial acute respiratory distress syndrome, 432 bronchopulmonary dysplasia, 537 lung scintigraphy, 763 lung transplantation, 344, 349, 352, 353, 356, 357, 358, 365 postoperative native lung overinflation, 364, 364 lung volume reduction surgery, 764–765, 765, 766 Marfan syndrome, 1042 measurement of extent (CT quantification), 762, 762 volumetric reconstructions, 763 mediastinal/chest wall in pneumomediastinum, 940, 941 panacinar/panlobular, 757, 759, 761, 761, 762, 765 alpha1-antitrypsin deficiency, 746, 763, 763, 764 paraseptal, 757, 761, 761, 1038 pathogenesis, 756 peripheral, 761 pneumothorax, 1038 pulmonary function tests, 762 pulmonary hypertension, 417 pulmonary sequestration association, 1098 silica exposure-related, 468 silicosis, 463, 464 spurious interlobular septum thickening/ remnant interlobular septa, 174, 175 Swyer–James (McLeod) syndrome, 750, 751 usual interstitial pneumonia, 565, 566 vascular signs, 758–759, 759 empyema, 210, 222–227, 224, 225, 226, 1017, 1028 actinomycosis, 249, 250 anaerobic pneumonia, 219 development exudative stage, 222 fibropurulent stage, 222–223 organization stage, 223 hemorrhagic, 1011 lung abscess differentiation, 225, 226, 227 lung transplantation patients, 365, 366 malignant neoplasms association, 226 necessitatis, 223, 237 pleural calcification following, 1037 pleural peel, 223, 223 Staphylococcus aureus pneumonia, 213 tuberculosis, 237, 238 endarteritis obliterans, usual interstitial pneumonia, 564 endobronchial metastases, 862, 862 endocarditis, infective, 1023 intravenous drug users, 532

endodermal sinus tumor, 898, 902 endometriosis bronchopulmonary, 834, 1040–1041, 1041 catamenial hemothorax, 1040 catamenial pneumothorax, 1040, 1040 endoscopic retrograde pancreatography, 1023 ENG gene defect, 1081 engraftment syndrome, 337–338 Entamoeba histolytica, 276 enteric duplication cyst, 886 Enterobacter pneumonia, 214 lung transplantation patients, 352 Enterobacteriaceae, pneumonia, 214 environmental opportunistic mycobacteria see nontuberculous mycobacteria eosinophilia, 659 associated conditions, 676, 676 Churg–Strauss syndrome, 613, 615 tropical pulmonary, 673 eosinophilic granuloma of lung see Langerhans cell histiocytosis eosinophilic lung disease, 659–677 classification, 661 worm infestations, 673, 674, 674 eosinophilic pneumonia, 98, 99, 100, 659–664 acute, smoking-related risk, 456 airspace opacities, 98, 99 drug-induced hypersensitivity reactions, 509 epirubicin, lung toxicity, 539 epithelioid hemangioendothelioma (intravascular bronchioloalveolar tumor), 833 pleura, 857 Epstein–Barr virus, 274, 366 B cell lymphoproliferative disorders, 843 HIV/AIDS patients, 316 AIDS-related lymphoma, 312 lung transplantation donor screening, 345 posttransplant lymphoproliferative disorder, 368 Erasmus syndrome, 596 Erdheim–Chester disease, 690–691, 691 ergonovine maleate toxicity, 519 pleural effusions/thickening, 1025 ergot alkaloid toxicity, 531 pleural effusions/thickening, 1025 ergotamine toxicity, 519, 531 pleural effusions/thickening, 1025 erionite, 472, 851 erlotinib toxicity, 541 Escherichia coli pneumonia, 214 esophageal atresia, 1065, 1073 esophageal candidiasis, 296 esophageal carcinoma, 886, 893, 894 esophageal dilatation, 892–893, 894 scleroderma, 596, 597, 598–599 esophageal diverticula, 886, 892 esophageal double exclusion procedure, 893 esophageal duplication cysts, 886, 887, 887, 892 antenatal detection, 1098 esophageal dysmotility, scleroderma, 596, 598–599 esophageal hiatus, 75 esophageal injury/rupture, 923, 1121, 1140, 1141 acute mediastinitis, 921 Boerhaave syndrome, 922

esophageal lesions, mediastinal masses, 892–893, 892 esophageal neoplasms, 884, 885, 886, 892, 893 esophagectomy, chylothorax complicating, 1029 esophagitis, radiation-induced, 552, 552 esophagus, 64, 74, 75, 75 etanercept, 520, 591 etoposide, lung toxicity, 507, 509, 539 European Guidelines for Quality in Computed Tomography (EUR16262), 12 everolimus, 538 exogenous lipid pneumonia, 514–515, 516, 517 extramedullary hematopoiesis, 883, 886, 897–898 extrinsic allergic alveolitis see hypersensitivity pneumonitis

18

F-fluorodeoxyglucose positron emission tomography (FDG-PET), 24, 26, 27 aortic aneurysm, 962, 965 aortitis, 979 bleomycin toxicity, 524 bronchioloalveolar carcinoma, 817 Castleman disease, 907, 910 desmoid tumors, 891 diffuse malignant mesothelioma, 856, 857 esophageal neoplasms, 893 germ cell tumors malignant nonteratomatous, 903, 903 mature teratoma, 901–902 lung cancer extrathoracic metastases, 812–813, 813, 814 nodal metastases staging, 810 pleural invasion, 811, 811 recurrence, 817, 818 lung transplantation recipient screening, 347 lymphoma, 847 posttreatment residual masses, 839 mediastinal disease, 882 mediastinal lymphadenopathy, 914–915 neuroendocrine thymic tumors, 955 neurogenic tumors, mediastinum, 936 paraganglioma, mediastinum, 937 pleural thickening, 1033, 1033 pleurodesis-related changes, 1036 rebound thymic hyperplasia, 949 rheumatoid arthritis nodules, 590 pleural effusions, 587 round atelectasis, 119 sarcoidosis, 659, 660, 904 secondary organizing pneumonia, 579 silicosis with progressive massive fibrosis, 467 solitary pulmonary nodules, 128, 128, 132 thymoma, 954, 954 thymus (normal), 947, 947 thyroid mass, intrathoracic, 959 tuberculomas, 235 tumor recurrence detection, 550 usual interstitial pneumonia, 569, 569 Fabry disease, 691 factor V Leiden, 518

1177

Index fallen lung sign, 1138, 1139 Fallot tetralogy, 147 familial emphysema, 756 familial lung fibrosis, 581–582 usual interstitial pneumonia, 564 familial Mediterranean fever, pleural effusions, 1026 familial pulmonary alveolar proteinosis, 677 familial pulmonary hypertension, 411 farmer’s lung, 457, 458, 459, 460 fat embolism, 1156, 1156, 1158–1160, 1159, 1160 clinical features, 1158 imaging findings, 1158 fat, extrapleural differentiation from pleural plaques, 473, 475 mimicking pleural thickening, 1034, 1034, 1035 fat herniation, intraabdominal, 897, 898 fat pads, pericardial, 1045 paracardiac mediastinal mass, 884 fat tissue, at bifurcation of pulmonary arteries, 45, 50 fat-containing lesions, mediastinum, 883, 884, 893, 893, 895–898 abdominal fat herniations, 897, 898 fat–fluid levels, mature teratoma, 900, 901 feeding vessel sign, 130 septic pulmonary emboli, 222 fenfluramine toxicity, 516, 526 fetal chest masses, 1097, 1098 fetal hydrops, 1096, 1106 congenital cystic adenomatoid malformation, 1100 fibrillin gene mutations, 1042 fibrin body (pleural mouse), 1048 fibroblastic foci, usual interstitial pneumonia, 564 fibrocystic disease see cystic fibrosis fibroleiomyosarcoma, 829 fibroma, 829, 833, 886 fibrosarcoma, 829, 941 fibrosing mediastinitis, 922–924, 923, 926, 927, 928, 1079 chylothorax, 1030 fibrothorax, lung transplantation patients, 366 fibrous mesothelioma see localized fibrous tumor of pleura fibroxanthoma (plasma cell granuloma), 835, 836 filariasis, 278 chylothorax, 1030 tropical pulmonary eosinophilia, 673 fire, acute inhalational injury, 488, 488 fissures, 54, 54 accessory, 56–58, 57, 58, 59, 60 Fleischner Society glossary definition, 160 incomplete, 54, 59, 61, 62 intrusion of fluid with pleural effusion, 1006 loculated effusions, 1011–1012, 1011, 1012, 1013, 1014 middle lobe step, 1006, 1007 major, 54, 54, 55, 55, 56, 56 minor, 54, 55, 55, 56, 56, 57 flail chest deformity, 1148, 1150, 1151 flat waist sign, 111

1178

flat-panel detectors, digital chest radiography, 4 flavor worker’s lung, 487, 487 Fleischner lines (discoid atelectasis), 101–102, 102 Fleischner Society glossary of terms for thoracic imagimg, 155–171 Fleischner Society guidelines, 12 acute pulmonary embolism, 397 solitary pulmonary nodules management, 133, 134, 135 flock worker’s lung, 486–487, 487 focal organizing pneumonia, 578–579 focal spot tracking, 13 folded lung see atelectasis, round/rounded follicular bronchiolitis, 748, 749, 847 rheumatoid arthritis, 590 follicular dendritic sarcoma, 941 foregut cysts, 882, 883, 884, 886 foreign body inhalation, 493–494, 495, 496 bronchial obstruction lobar atelectasis, 103 mucus plug, 101 pulmonary sequestration, 1093 Francisella tularensis, 218 fungal granuloma, solitary pulmonary nodule, 123 calcification, 121 fungal infection, 250–269 ankylosing spondylitis with cystic lung disease, 606 apical pleural thickening, 1035 heart transplantation patients, 342 hematopoietic stem cell transplantation patients, 336 HIV/AIDS, 295, 296, 302, 304–311, 308 hypersensitivity pneumonitis, 457 immunocompromised patients, 322–331 lung transplantation patients, 357, 359 mediastinal lymphadenopathy, 904, 909 pneumonia, 97, 143, 210 cavities/cavitation, 131 Fusarium angioinvasive, 324 lung transplantation patients, 357 Fusobacterium, 218

gallium-67 scintigraphy radiation-induced lung injury, 544 sarcoidosis, 659 ganglion cell tumors, 929, 935 ganglioneuroblastoma, 929, 935 ganglioneuroma, 929, 934, 935, 936, 936 gastrointestinal stromal tumor, esophagus, 893, 894 Gaucher disease, 691 gefitinib, lung toxicity, 507, 541, 541 gemcitabine toxicity, 507, 509, 526, 529 generalized elastolysis (cutis laxa), 756, 1042 germ cell tumors benign, 898 imaging features, 900 malignant, 884, 898 nonteratomatous, 902–904 mediastinum, 882, 883, 884, 898, 899 pneumothorax, 1039 Ghon focus, 229 giant cell arteritis (temporal arteritis), 608, 608, 979

giant cell interstitial pneumonia, 483, 561 recurrence following lung transplantation, 364 giant lymph node hyperplasia see Castleman disease glomerulonephritis, 525 GM-CSFR gene mutation, 677 goiter, intrathoracic, 957, 958, 958, 959, 960 gold salts, lung toxicity, 507, 509, 527, 529, 590, 591, 673 Golden S sign, 103, 105, 106, 109, 795, 796, 801 Good syndrome, 950 Goodpasture syndrome, 456, 537, 609, 619–620, 619 Gorham syndrome, 919, 1030 graft-versus-host disease, 336 hematopoietic stem cell transplantation, 341 acute, 338, 339 chronic, 339, 340 Gram-negative bacteria empyema, 223 pneumonia, 207, 210, 214–215 lung transplantation patients, 352 granular cell myoblastoma (granular cell tumor), 829, 833, 929 granulocyte–macrophage colony-stimulating factor deficiency, pulmonary alveolar proteinosis, 677 granulocytic sarcoma (chloroma), 848 granulomas bronchocentric granulomatosis, 674–675, 675 Churg–Strauss syndrome, 613 hypersensitivity pneumonitis, 458 mediastinal mass, 883 plasma cell, 835, 836 pulmonary nodules multiple, 132, 133 solitary calcified, 121, 124 sarcoidosis, 548, 641, 643, 657 silicosis, 463 granulomatosis, drug-induced, 513–515, 513, 514 exogenous lipid pneumonia, 514–515, 516, 517 pneumonitis, 514 vasculitis, 514 granulomatous lung disorders, 642, 642 gray-scale processing, digital chest radiography, 4 great vessel injury, 1121 ground-glass opacities, 14, 90–91, 97, 140 acute eosinophilic pneumonia, 661–662, 662 acute interstitial pneumonia, 580 acute respiratory distress syndrome, 431, 432 aspergillosis, 324, 325, 326, 326, 327 bronchioloalveolar carcinoma, 814, 815, 816, 817 cryptogenic organizing pneumonia, 575, 577 desquamative interstitial pneumonia, 453, 584 diffuse alveolar (pulmonary) hemorrhage, 621, 621 fat embolism syndrome, 1159 Fleischner Society glossary definition, 160, 160

Index high-resolution CT, 177–179, 178, 179, 180, 195, 196 associated conditions, 178 hypersensitivity pneumonitis, 458, 460, 460, 461 leukemic infiltration of lungs, 848 lung cancer, 793–794 population screening, 820 lymphoid interstitial pneumonia, 581, 581 microscopic polyangiitis, 613, 613 mixed connective tissue disease, 604 nonspecific interstitial pneumonia, 574, 574, 582, 584 Pneumocystis jirovecii pneumonia, 304, 304, 305, 307, 319 polymyositis/dermatomyositis, 601 pulmonary alveolar microlithiasis, 680 pulmonary alveolar proteinosis, 678, 678, 679 pulmonary metastases, 858 pulmonary surfactant deficiencies, 582 radiation-induced lung injury, 544, 545, 546, 546, 549 respiratory bronchiolitis/respiratory bronchiolitis interstitial lung disease, 452, 452 rheumatoid arthritis, 587 sarcoidosis, 650, 651 scleroderma, 596, 597, 599 Sjögren syndrome, 603, 604 solitary pulmonary nodule, 126–127, 127 usual interstitial pneumonia, 565, 566, 568, 571, 572, 572 Wegener granulomatosis, 611, 613 gunshot wounds, 1153, 1155, 1156

H1N1 swine influenza, 272 Haemophilus influenzae pneumonia, 207, 214, 273 cystic fibrosis, 733 HIV/AIDS, 297 halo sign, 97, 131, 132 aspergillosis, 324, 326, 326 invasive, 267, 268 Candida infection, immunocompromised patients, 329 Fleischner Society glossary definition, 160, 160 mucormycosis, 330 posttransplant lymphoproliferative disorder, 369 hamartomas, 826–829, 828, 830 solitary pulmonary nodule, 121, 122, 124, 126, 127 Hamman–Rich syndrome see acute interstitial pneumonia Hamton hump, 387, 388 hantavirus cardiopulmonary syndrome, 434, 434 haptens, drug-induced hypersensitivity reactions, 509 hard metal pneumoconiosis, 483, 483 Hashimoto thyroiditis, 573, 947 head cheese sign, 180 heart disease, chylothorax, 1030 heart failure amyloidosis, 694 hypereosinophilic syndrome, 675 mediastinal lymphadenopathy, 426, 906

pleural effusion, 1015, 1020, 1020 loculated, 1011, 1012, 1013 pulmonary edema see cardiogenic pulmonary edema pulmonary sequestration with shunt, 1096 see also cor pulmonale heart transplantation, 340, 342–343, 342, 925 constrictive bronchiolitis complicating, 743 indications, 340 opportunistic pulmonary infections, 342–343, 343 orthotopic/heterotopic, 340 posttransplant malignancy, 343 lung cancer, 788 transplant graft vasculopathy, 343 heart trauma, 1148, 1150 heart–lung transplantation, 340, 342 posttransplant lymphoproliferative disorder, 368 HELLP syndrome, 1020 helminthic infection, 276–281 hemangioendothelioma, 829 mediastinum, 917 hemangioma, 829, 833, 886 mediastinum, 917, 919, 919, 920 sclerosing, 834, 834 hemangiopericytoma, 830 hematologic malignancy, pulmonary alveolar proteinosis association, 677 hematoma, lung parenchyma, 1134, 1135, 1137 hematopoietic stem cell transplantation, 336–340 engraftment syndrome, 337–338 graft-versus-host disease, 341 acute, 338, 339 chronic, 339, 340 idiopathic pneumonia syndrome, 338, 339, 340 indications, 336 posttransplant lymphoproliferative disorder, 369 pulmonary complications, 335, 336, 336, 337, 338 early phase, 338–339, 338, 339, 340 late phase, 339–340 neutropenic phase, 336–337 pulmonary cytolytic thrombi, 339 hemiazygos vein, 75 hemodialysis, pleural effusions, 1023 hemopericardium, 1148, 1150 hemopneumothorax, 1004 hemorrhage, diffuse alveolar see diffuse alveolar (pulmonary) hemorrhage hemosiderosis, 142, 145 hemothorax, 1015, 1031, 1032 aortic injury, 1125 catamenial, 1040 causes, 1031 gunshot wounds, 1153, 1155 lung transplantation patients, 365 pneumothorax complication, 1046, 1048 rib fracture, 1148, 1151 Henoch–Schönlein purpura (anaphylactoid purpura), 615–616 heparin-induced thrombocytopenia, 518 hepatic abscess, pleural effusions, 1020 hepatic cirrhosis, pleural effusion (hepatic hydrothorax), 1004, 1007, 1010, 1022

hepatic metastases, 813 hepatitis C, 616 hepatitis, pleural effusion, 1022 hepatopulmonary syndrome, 420–421, 421, 422 hereditary hemorrhagic telangiectasia (Rendu–Osler–Weber disease), 1081, 1084, 1085 hereditary spherocytosis, extramedullary hematopoiesis, 897 heritable connective tissue disorders, pneumothorax, 1041–1042, 1041 Hermansky–Pudlak syndrome, 691–692, 693 herniation, lung, 1156, 1158 heroin overdose, 532 herpes simplex pneumonia, 275, 332 hematopoietic stem cell transplantation patients, 337, 337, 338 HIV/AIDS patients, 312 lung transplantation patients, 357 hiatal hernia, 884, 886, 891, 892, 893, 1109 hibernoma, 896 high-resolution CT (HRCT), 153–196 airspace opacities, 91 airways disease, 187–192 large, 187–189 small, 22, 189–192 artifacts, 20–21 clinical aspects, 192–196 disease reversibility/prognosis assessment, 195–196, 196 indications, 192–193, 193 sensitivity (diffuse lung disease), 193 specificity (diffuse lung disease), 193–194 Fleischner Society glossary of terms, 155–171 ground-glass opacities, 177–179, 178, 179, 180 image noise (quantum mottle), 21 image reconstruction, 20 radiation dose, 20, 193 spatial resolution, 153, 154 window settings, 19 high-altitude pulmonary edema (mountain sickness), 434 high-kilovoltage radiographs, 1–2 highly active antiretroviral agents see antiviral therapy hilar haze, pulmonary edema, 426, 426 hilar lymph nodes, 45, 67, 68, 808 AJCC–UICC classification, 68, 69 mimicking pulmonary embolism, 394, 395 normal size, 808 tuberculosis, 229 hilar lymphadenopathy, 45 amyloidosis, 694, 696 beryllium-related disease, 485, 486, 486 causes, 904 chest radiography, 911, 915, 915 coccidioidomycosis, 258 CT, 915–916, 916 cryptococcosis, 255 cystic fibrosis, 733, 734, 738 diagnosis, 907–908 pitfalls, 917 diphenylhydantoin toxicity, 526 drug-induced eosinophilic lung disease, 673

1179

Index histoplasmosis, 253, 253 HIV/AIDS, 302 imaging features, 915–917 Kaposi sarcoma, 315, 315 lung cancer, 797, 808, 809 lymphangitis carcinomatosa, 863 lymphoma, 838–839 metastatic adenocarcinoma, 915 methotrexate hypersensitivity, 530, 531 MRI, 917 Mycoplasma pneumonia, 271 pulmonary surfactant deficiencies, 582 sarcoidosis, 644–646, 644, 645, 646, 904, 915 silicosis, 464 tuberculosis, primary, 229, 230, 231, 240 calcification, 230 hilar mass, 881 bronchial carcinoid, 823, 824 lung cancer, 796–797, 798 see also hilar lymphadenopathy hilum, Fleischner Society glossary definition, 160 histiocytoma (plasma cell granuloma), 835, 836 histiocytosis X see Langerhans cell histiocytosis Histoplasma capsulatum, 250, 251, 309, 310 Histoplasma gondii, 251 histoplasmoma, 123, 252, 254, 255, 256 histoplasmosis, 142, 143, 144, 211, 250–254, 250, 254, 255, 332, 740, 904 asymptomatic, 252, 252 chronic pulmonary, 252–253, 254 disseminated, 251, 252, 254 fibrosing mediastinitis, 922, 923, 924, 926, 927, 928 HIV/AIDS patients, 309, 310 immunocompromised patients, 330 intrathoracic lymph node calcification, 908, 909, 910 multiple pulmonary nodules, 133 pneumonia, 210 symptomatic, 252, 253 HIV/AIDS, 295–319 AIDS-related airway disease, 312, 312 AIDS-related lymphoma, 312–313, 314, 315, 319 antiretroviral therapy, 295, 312, 313, 313, 520 aspergillosis, 310–311, 311 chronic necrotizing, 310 obstructing bronchopulmonary, 311, 311 bacillary angiomatosis, 298 bacterial pneumonia, 319 bacterial (pyogenic) infections, 296–298 imaging findings, 297, 298 Blastomyces dermatitidis, 309–310 Castleman disease, 907 CD4 counts, 295–296, 314 antiretroviral therapy response, 312 influence on pulmonary manifestations, 296, 297, 298, 299, 304, 308, 309, 310, 311 coccidioidomycosis, 308–309 cryptococcosis, 255, 308, 309, 310, 311 diffuse alveolar (pulmonary) hemorrhage, 619 emphysema, 312, 756

1180

follicular bronchiolitis, 748 frank AIDS, 296 fungal infections, 302, 304–311 pneumonia, 308 histoplasmosis, 309, 310 human herpes virus infections, 312 immune reconstitution inflammatory syndrome, 295, 298, 305, 308, 309, 312, 313 sarcoid-like syndrome, 642 Kaposi sarcoma, 312, 313–315, 315, 316, 317, 319 lung cancer, 318–319, 319, 788 lung transplantation donor screening, 345 lymph node calcification, 908 lymphoid interstitial pneumonia, 315–317, 317, 318, 580, 581 lymphoproliferative disorders, 315–316 mediastinal lymphadenopathy, 904 mycobacterial infections, 298–302, 299 nonspecific interstitial pneumonia, 317–318 nontuberculous mycobacterial infections, 242, 299, 302, 302 pathophysiology, 295 persistent generalized lymphadenopathy, 318 Pneumocystis jirovecii pneumonia, 302–308, 303, 304, 305, 305, 306, 307, 308, 312, 319 primary effusion lymphoma, 845 protozoal infections, 311 pulmonary hypertension, 319, 416–417 pulmonary manifestations, 295, 296 antiretroviral agent-treated patients, 295, 296 imaging diagnosis, 319, 320 opacities evaluation/differential diagnosis, 334 septic pulmonary emboli, 298, 298, 319 thoracic malignancies, 312–315, 314 toxoplasmosis, 311 tuberculosis, 228, 231, 298–299, 299, 300, 301, 319 Hodgkin lymphoma classification, 836, 837 intrathoracic lymphadenopathy, 838–839, 838, 839, 840, 842, 909 lymph node calcification, 910 pleural disease, 844–845 posttreatment residual masses, 839, 839, 843 primary pulmonary, 841 pulmonary lesions, 841, 844, 845 role of imaging, 847 staging, 837, 837 thymic enlargement, 839 thymic lymphoma, 954 honeycombing, 139–147 acute interstitial pneumonia, 580 asbestosis, 477, 482, 482 cryptogenic organizing pneumonia, 577 familial lung fibrosis, 581 Fleischner Society glossary definition, 161, 161 high-resolution CT, 173, 173, 174, 174 hypersensitivity pneumonitis, 458, 460, 460 idiopathic pulmonary fibrosis, 174, 174 nonspecific interstitial pneumonia, 574, 583

sarcoidosis, 653, 655 scleroderma, 596, 599 usual interstitial pneumonia, 564, 565, 566, 566, 567, 568, 568, 582, 584 hookworm infection, 276–277 hormone replacement therapy, pulmonary thromboembolism, 518 horseshoe lung, scimitar syndrome association, 1079 hot tub lung, 457 Hounsfield Units, 19, 121 see also pixel density Hughes–Stovin syndrome, 420, 617, 618 human chorionic gonadotrophin, 884, 898, 900, 902 human herpes virus 8, 366, 907 HIV/AIDS patients, 312, 314, 319 human immunodeficiency virus infection see HIV/AIDS human metapneumovirus, 272 human T lymphotropic virus type 1, 272 hump sign, 1146, 1147 hyaline membrane disease, 85 hydatid disease (Echinococcus infection), 279–281, 280 mediastinal cysts, 281 pleural cysts, 281 pulmonary cyst rupture, 279, 280–281, 280 solitary pulmonary nodule, 130, 131 hydralazine, drug-induced lupus, 512 hydrocarbon aspiration, 493, 494 hydrocarbon waterproofing spray inhalation injury, 490, 491 hydrochlorothiazide toxicity, 527, 673 hydropneumothorax, 1006, 1013 hydrothorax hepatic, 1022 peritoneal dialysis-related, 1023 see also pleural effusion hypercalcemia, punctate calcification, 99 hypereosinophilic syndrome, 675–676, 676 clinical features, 675, 675 hyperimmunoglobulin E syndrome, 676–677 hyperinflation asthma, 752 bronchopulmonary dysplasia, 537 constrictive bronchiolitis, 743 cystic fibrosis, 733, 734, 735, 736 emphysema, 758, 758, 759 foreign body-related obstruction, 494 hyperparathyroidism, 143, 519, 884, 938, 939 calcification diffuse pulmonary, 681 punctate, 100, 101 hypersensitivity pneumonitis, 142, 144, 177, 177, 457–461, 457, 459, 460, 747, 747, 748 causes, 457–458, 457 chronic, 582, 583 clinical features, 458 CT, 458–461, 458, 459, 460 high-resolution CT, 193, 195, 196 diagnosis, 461, 461 differential diagnosis, 461, 582, 583 granulomas, 642 imaging features, 458–461 interstitial pneumonia, 563 nonspecific, 573 phases of disease, 461

Index subacute, 186 cystic airspaces, 183, 184 mosaic attenuation pattern, 180, 181 usual interstitial pneumonia, 564 hypersensitivity reactions antiretroviral therapy, 295 drug-induced lung disease, 509, 510, 511 drug-induced vasculitis, 513 hypocomplementemic urticarial vasculitis syndrome, 616, 756 hypogammaglobulinemia, 884 bronchiectasis, 732 hypogenic lung syndrome see scimitar syndrome hypoplastic right heart syndrome, 1075

idiopathic acute respiratory distress syndrome see acute interstitial pneumonia idiopathic bronchiectasis, 732 idiopathic chylothorax, 1028, 1029–1039 idiopathic diffuse lung disease, 641–699 idiopathic giant bullous disease (vanishing lung syndrome), 767 idiopathic interstitial pneumonia, 561–622, 562 abbreviations, 562 classification, 561–563, 561, 562 clinical features, 563 CT quantitation of disease extent, 584 reversibility/survival prediction, 584 structure/function correlations, 583–584 diagnosis CT accuracy, 582–583 interdisciplinary approach, 583 distribution of disease, 186 lung biopsy, 563, 568 idiopathic mediastinal fibrosis, 923, 924 idiopathic pleuroparenchymal fibroelastosis, 584, 585, 1034 idiopathic pneumonia syndrome, 338, 339, 340 idiopathic (primary) pulmonary arterial hypertension, 410–412, 412 genetic factors, 410–411 idiopathic (primary) pulmonary siderosis, 620, 620, 621 diffuse pulmonary hemorrhage, 620 idiopathic pulmonary fibrosis see usual interstitial pneumonia IgG precipitins, hypersensitivity pneumonitis, 458 image noise (quantum mottle), highresolution CT, 21 image reconstruction, CT, 14–15, 15 high-resolution CT, 20 pulmonary angiography, 391 targeted, 11 volumetric, 763 imatinib toxicity, 541, 677 imipramine hypersensitivity, 673 immediate (type I) hypersensitivity reactions, drug-induced, 509 immobile cilia syndrome see ciliary dyskinesia syndrome immune complex disorders diffuse pulmonary hemorrhage, 620 drug-induced hypersensitivity reactions (type III), 509, 513 vasculitis, 513, 615–616

immune reconstitution inflammatory syndrome, 295, 309, 312, 313, 520 sarcoid-like syndrome, 642 immunocompromised patients, 295–370 aspergillosis, invasive, 264, 265, 266, 267 bacterial pneumonia, 321–322 cryptococcosis, 255, 256 fungal infections, 322–331 hematopoietic stem cell transplantation patients see hematopoietic stem cell transplantation histoplasmosis, 251, 252 mechanisms of immune compromise, 321 mucormycosis, 268 nocardiosis, 247 nonspecific interstitial pneumonia, 335–336 nontuberculous mycobacterial infection, 242, 243 organizing pneumonia, 335–336, 335 Pneumocystis jirovecii pneumonia, 331, 332 protozoal infection, 332–333 pulmonary alveolar proteinosis, 677 pulmonary infections, 319, 321–333, 321 airspace opacities, 98 imaging features, 321, 322 pulmonary opacities evaluation/ differential diagnosis, 333–335 tuberculosis, 322 viral infections, 331–332 immunosuppressive agents, 366, 520, 538 inert dust pneumoconiosis, 483–484 infectious mononucleosis, 274 inferior accessory fissure, 56, 58, 59 inferior pulmonary ligaments, 59–60 inferior vena cava, 75 infiltrate (pulmonary infiltrate) Fleischner Society glossary definition, 161 usual interstitial pneumonia, 564 inflammatory bowel disease, 532, 688–690 pulmonary complications, 689 inflammatory myofibroblastic tumor (plasma cell granuloma), 835, 836 inflammatory pseudotumor of lung (plasma cell granuloma), 835, 836 infliximab, 235, 249, 520, 532, 591, 690 influenza virus, 272–273, 455 pneumonia, 271, 273 bacterial superinfection, 273 hematopoietic stem cell transplantation patients, 337, 339 lung transplantation patients, 357 inhalational lung disease, 451–496, 562 intensity-modulated radiation therapy, 546–547 intercostal stripe, 53 interface sign, 176 interferons, lung toxicity, 527 sarcoid-like reaction, 514, 515 interleukin-2, lung toxicity, 527, 529, 529 pleural effusions/thickening, 1025 interlobular septa, 51 Fleischner Society glossary definition, 161, 161 high-resolution CT, 153, 154, 154 see also septal lines interlobular septal thickening acute eosinophilic pneumonia, 662, 662 amyloidosis, 694 asbestosis, 477, 481

associated diseases, 172 bronchiectasis, 731 fat embolism syndrome, 1159 Fleischner Society glossary definition, 161, 161 high-resolution CT, 171, 172, 174 idiopathic (primary) pulmonary siderosis, 620, 620, 621 interstitial lung disease, 171 Kaposi sarcoma, 314 lymphangitis carcinomatosa, 862, 862 nodular pattern, 176 Pneumocystis jirovecii pneumonia, 305 pulmonary alveolar microlithiasis, 680, 680 pulmonary alveolar proteinosis, 678 pulmonary metastases, 858 pulmonary surfactant deficiencies, 582 reticular pattern, 171 sarcoidosis, 171, 173 spurious, 174 International Labor Organization (ILO) classification of pneumoconiosis radiographs, 462, 462 International Staging System for nonsmall cell lung cancer, 797 interstitial emphysema acute respiratory distress syndrome, 432 bronchopulmonary dysplasia, 537 Fleischner Society glossary definition, 162, 162 interstitial fibrosis, 142, 143 air bronchograms, 85 polymyositis/dermatomyositis, 600–601 Wegener granulomatosis, 609 interstitial pneumonia, 142, 142, 143, 205–206 drug-induced, 508–509, 509, 521, 525, 538, 539 rheumatoid arthritis, 588, 588 silica exposure-related risk, 468 Sjögren syndrome, 603 see also acute interstitial pneumonia; idiopathic interstitial pneumonia; lymphoid interstitial pneumonia; nonspecific interstitial pneumonia; usual interstitial pneumonia interstitium, Fleischner Society glossary definition, 162 intralobular lines, Fleischner Society glossary definition, 162, 162 intravascular bronchioloalveolar tumor see epithelioid hemangioendothelioma intravascular papillary endothelial hyperplasia (intravascular endothelial perforation), 835 intravenous drug abuse, thoracic complications, 532–533, 532 iodine content, mediastinal lesions, 883 iodine contrast enhancement, CT pulmonary angiography, 389–390, 390 irinotecan, lung toxicity, 507, 539 isocyanate, hypersensitivity pneumonitis, 457 isoniazid, drug-induced lupus, 512 isoxsuprine toxicity, 511

juvenile dermato/polymyositis, 602 juxtaphrenic peak, 162, 162

1181

Index kaolinosis, 482 Kaposi sarcoma, 295, 296, 312, 313–315, 315, 316, 317, 319, 343, 344, 366, 833, 845, 907 Kartagener syndrome, 737 Kerley A (deep septal) lines, 136, 139 Kerley B (interlobular septal) lines, 51, 52, 98, 136, 138, 139, 153 see also interlobular septal thickening kerosene pneumonia, 494 Klebsiella pneumoniae pneumonia, 97, 131, 207, 208, 214, 216, 1048 krypton-81m ventilation scanning, 27, 28 kyphoplasty, pulmonary cement embolism, 518 L-tryptophan hypersensitivity, 673 laceration, lung parenchyma, 1121, 1135 Lady Windermere syndrome, 245, 245 Langerhans cell histiocytosis, 140, 142, 143, 453–455, 454 cystic airspaces/cysts, 183, 184, 185, 186, 454, 455, 455 distribution of disease, 186, 186 imaging features, 454, 454, 455, 456 nodules, 454, 455, 455 pneumothorax, 1039, 1048 pulmonary hypertension, 412, 413, 453, 455, 456 recurrence following lung transplantation, 364 vanishing lung syndrome, 767 Lanois–Bensaude syndrome (multiple symmetric lipomatosis), 896 large B cell lymphoma, 839 intravascular, 843 primary effusion lymphoma, 845 pyothorax-associated diffuse, 845 thymic enlargement, 839 large cell carcinoma, 787–788, 789 imaging features, 793 laryngeal papillomatosis, 829, 831, 834, 835 laryngospasm, pulmonary edema, 434, 435 lateral decubitus view, 2, 2 lateral radiograph, 1 normal chest, 40 lead poisoning, 537 lead-time bias, 818 leflunomide toxicity, 591, 677 left accessory minor fissure, 59, 60 left-to-right shunt congenital, pulmonary arterial hypertension, 414–416, 415 scimitar (venolobular) syndrome, 1079 Legionella, 595 Legionella micdadei pneumonia, 97, 208 immunocompromised patients, 322, 322 Legionella pneumophila constrictive bronchiolitis, 741 pneumonia, 97, 207, 208, 210, 214, 216, 217 HIV/AIDS, 296–297 immunocompromised patients, 322, 322 Legionnaires disease see Legionella pneumophila, pneumonia leiomyoma, 829, 833–834, 834, 886 esophagus, 886, 893, 894 multiple, 834 leiomyosarcoma, 829, 830 esophagus, 893 Lemierre syndrome, 222 lenalidomide toxicity, 518

1182

length bias, 818 lentil aspiration pneumonia, 493 Leptospira, 219 leptospirosis, 219–220 leukemia, 847–848 infiltration of lungs, 847, 848, 848 leukostasis, 847, 848, 849 mediastinal lymphadenopathy, 904, 912, 914 pleural thickening, 1034 leukostasis, 847, 848, 849 leukotriene antagonists, drug-induced pulmonary vasculitis, 513 Libman–Sachs endocarditis, 595 ligamentum arteriosum, 65 linear opacities, 135–137 acute interstitial pneumonia, 580 allergic bronchopulmonary aspergillosis, 667, 668, 669, 670 amyloidosis, 694 ankylosing spondylitis, 606 bronchiectasis, 725, 727 causes, 136 chronic bronchitis, 755 diffuse alveolar hemorrhage, 621 lung cancer (pleural tail sign), 789, 790 lymphangitis carcinomatosa, 862, 863 nonspecific interstitial pneumonia, 574 pneumothorax, 1038, 1043, 1044, 1045 pulmonary alveolar microlithiasis, 680 sarcoidosis, 653 usual interstitial pneumonia, 566, 567, 582 see also bandlike opacities lipoblastoma, 883 lipoid pneumonia, 126, 182 endogenous (golden pneumonia), lung cancer, 795 exogenous, 514–515, 516, 517 Wegener granulomatosis, 609 lipoma, 829, 833, 886 endobronchial, 833 mediastinum, 883, 884, 896 pleura, 857, 857 lipomatosis mediastinal, 893, 895, 895, 896 multiple symmetric (Madelung disease), 896 liposarcoma, 126, 829, 883, 884, 941 mediastinum, 896–897, 897 pleura, 857 liquid-crystal display, 4 lithoptysis broncholithiasis, 740 ciliary dyskinesia syndrome, 737 liver transplantation, diffuse pulmonary calcification, 681 lobar atelectasis see atelectasis lobar pneumonia, 205, 206, 207 tuberculosis, 233–235, 234 lobe, Fleischner Society glossary definition, 162 lobular core structures, Fleischner Society glossary definition, 162, 162 lobules, pulmonary, 51 Fleischner Society glossary definition, 163, 163 high-resolution CT, 153, 154 localized fibrous tumor of pleura, 833, 849–850 clinical features, 849 imaging findings, 849–850, 850, 851, 852

localized pleural mesothelioma see localized fibrous tumor of pleura Löffler syndrome see simple eosinophilic pneumonia Löfgren syndrome, 642, 643 lordotic view, 2–3, 3 luftsichel sign, 105 lung abscess actinomycosis, 249 acute respiratory distress syndrome, 430 amebic, 276, 277 anaerobic pneumonia, 219, 220 empyema differentiation, 225, 226, 227 nocardiosis, 248, 248 solitary pulmonary nodules, 130, 131 lung cancer, 787–822 ablation therapies, 552, 552 adrenal gland metastases, 813, 813 apical (Pancoast; superior sulcus) tumors, 805–807, 806, 807 asbestos-related, 471, 482 bone metastases, 813, 814 brain metastases, 813, 814 central tumor imaging, 795–797 hilar enlargement, 796–797 classification (TNM), 800 clinical features, 788–789 extrapulmonary manifestations, 789 CT see CT cytoxic agent toxicity, 539 extrathoracic metastases imaging, 812–814, 813 growth rate, 128–129, 129 HIV/AIDS patients, 318–319, 319 liver metastases, 813 mediastinal disease, 882 metastatic lymphadenopathy, 905 ‘missed’ on chest radiography, 822 organ transplantation-related, 366, 367 native lung of single lung transplant recipients, 364, 365 pathology, 787–788 peripheral tumor imaging, 789–795, 789 air bronchograms, 794 calcification, 791, 792, 793 cavitation, 793, 793 contrast enhancement, 794 corona radiata, 789, 790 cyst-like lucencies, 794 edge definition, 790, 791 ground-glass opacities, 793–794 mucoid impaction, 790, 792 rate of growth, 794–795 shape, 789–790 pneumothorax, 1039 polymyositis/dermatomyositis association, 602 population screening see lung cancer screening posttreatment recurrence, 551, 817, 818 radiotherapy radiation-induced lung injury, 543, 544, 547, 548, 551 recurrence following, 551 rheumatoid arthritis association, 591 risk factors, 788 sarcoid-like reaction, 642 scleroderma association, 597–598, 598 silica exposure association, 467–468

Index solitary pulmonary nodule, 119, 120, 126, 131, 132 adjacent bone destruction, 131 contrast enhancement, 127, 128, 128 corona radiata, 130 size, 129, 130 staging, 799 international staging system, 797 summary, 812, 812 treatment selection, 798, 800 usual interstitial pneumonia association, 569, 569, 571 WHO classification, 787, 788, 788 see also nonsmall cell lung cancer; small cell lung cancer lung cancer screening, 818–822 bias, 818–819 lead-time, 818 length, 818 overdiagnosis, 818–819 chest radiography, 819 CT, 14 algorithms for small pulmonary nodule follow-up, 820–821 evaluation, 821–822, 821 imaging appearances, 820 low-dose, 819, 820 radiation dose, 821 outcome measures, 818, 818 lung cysts see cystic airspaces; cysts lung fibrosis acute radiation pneumonitis, 542 asbestos-related see asbestosis bleomycin toxicity, 524 dendriform pulmonary ossification, 681 familial, 581–582 idiopathic see usual interstitial pneumonia lung cancer risk, 788 lung edema, 426 lung transplantation complications (upper lobe), 366, 366 mediastinal lymphadenopathy, 906, 906 methotrexate toxicity, 530 nitrosurea toxicity, 536 radiation-induced, 542–543, 543, 544, 544, 546, 547, 550 rheumatoid arthritis, 588 risk factors, 563 sarcoidosis, 641, 652–653, 653, 654 scleroderma (systemic sclerosis), 596, 597, 598 smoking-related risk, 456–457, 563 spontaneous pneumomediastinum, 939 systemic lupus erythematosus, 594, 594 tuberculosis, reactivation (postprimary), 229 see also interstitial fibrosis; interstitial lung disease lung herniation, 1156, 1158 lung hyperlucency, 147–148 emphysema, 758–759 radiation-induced lung injury, 547 see also lung decreased attenuation lung nodules see nodules lung, normal, 50–51 high-resolution CT, 153–155, 154 lung transplantation, 343–366 bilateral, 344, 345 communicating pleural spaces (‘buffalo chest’), 365, 365

complications, 347–366 acute rejection, 351–352, 351, 352, 353, 355 airway, 354–355, 354, 355, 356 bronchiolitis obliterans syndrome, 359–362, 360, 361, 362, 363 constrictive bronchiolitis, 743 early, 347, 347 hyperacute rejection, 347 infection, 352, 353, 354 late, 355, 357 lobar torsion, 351 native lung (single lung recipients), 362, 364, 364 obliterative bronchiolitis, 359–362, 360 opportunistic infection, 355, 357, 358, 359, 359 phrenic nerve paralysis, 366 pleural, 365–366, 365 primary graft dysfunction, 347–348, 348, 349 recurrent disease, 364–365, 365, 687 upper lobe fibrosis, 366, 366 vascular, 348, 350, 351 CT, 23, 24 differential diagnosis of new pulmonary opacities, 370, 370 donor selection, 345 historical aspects, 343 indications, 344, 344 living related donors, 345, 346 lung cancer risk, 788 lymphangioleiomyomatosis, 364, 687, 689 organizing pneumonia, 335, 578 posttransplant lymphoproliferative disorder, 368, 368 recipient evaluation, 345, 347, 347 sarcoidosis, 643 single lung, 344–345, 362, 364 surgical technique, 345 types, 344–345 lung volume reduction surgery, preoperative evaluation, 764–765, 765, 766 lung–chest wall interface, 53–54, 53, 54 lupus anticoagulant, 595 lymph nodes AJCC–UICC classification, 67, 68, 69 calcification, 647, 647, 908–909, 910 causes, 909 metastases, 908 hilar, 45, 67, 68, 68 intrapulmonary, 51, 51, 52 mediastinum, 65, 66, 67, 68, 68 normal size, 68–69 lymphadenopathy actinomycosis, 250 drug-induced, 519–520, 520 Fleischner Society glossary definition, 163, 163 HIV/AIDS patients, 299, 300, 302 leukemia, 847, 848, 848 lymphoma, 838–839, 842 Mycoplasma pneumonia, 270, 271 nontuberculous mycobacterial infections, 302 tuberculosis, primary, 229, 230, 230, 231, 231, 232, 240, 300 lymphangiectasia, 1027, 1087, 1088, 1088, 1089 lymphangiography, associated oil embolism, 518

lymphangioleiomyomatosis, 143, 146, 685–687 angiomyolipomas, 686, 687, 689 chylothorax, 1030 cystic airspaces, 183, 184, 185 genetic factors, 684, 685 high-resolution CT, 193 lung transplantation, 687, 689 recurrence in transplanted lung, 364, 687 pneumothorax, 686, 687, 1048 pulmonary manifestations, 685–686, 686, 688 tuberous sclerosis, 684–685, 684 lymphangioma (cystic hygroma), 883, 884, 1027, 1087, 1087, 1088 capillary, 1087 cavernous, 1087 chylothorax, 1030 cystic, 1087 lymphangiomatosis, 1087, 1088, 1089 chylothorax, 1030, 1088 lymphangiomyomatosis, pneumothorax, 1039 lymphangitic radiographic pattern, 1027 lymphangitis carcinomatosa, 50, 142, 143, 862, 863 bat’s wing/butterfly airspace opacities, 98, 99 high-resolution CT, 171, 171, 173 interface sign, 176 interlobular septal thickening, 171, 171, 173 lymphatic development, congenital disorders, 1087–1089, 1087 lymphatic dysplasia syndrome, 1087, 1088 lymphatic vessels dilated, 51 lung parenchyma, 51 thorax, 1027, 1028 lymphoangiography, thoracic duct injury, 1140 lymphocele, 890 thoracic duct rupture, 1140, 1142 lymphocytic bronchiolitis, 315 lymphocytosis, hypersensitivity pneumonitis, 458 lymphofollicular thymic hyperplasia, 947–948, 948 lymphography, chylothorax, 1030–1031 lymphoid aggregates, rheumatoid lung disease, 588, 590 lymphoid interstitial pneumonia, 561–562, 562, 580–581, 847 cystic airspaces, 183, 183 drug-induced, 508 Fleischner Society glossary definition, 163, 163 HIV/AIDS patients, 315–317, 317, 318 radiographic appearances, 581, 581 Sjögren syndrome, 603, 604 lymphoid non-neoplastic pulmonary lesions, 847, 847 lymphoma, 85, 522, 535, 545, 546, 836–847 AIDS-related, 296, 312–313, 314, 315, 319 airspace opacities, 91, 98 chest wall invasion, 845, 846 chylothorax, 1029, 1030 classification, 836, 836 CT angiogram sign, 91, 93 endobronchial disease, 844

1183

Index intrathoracic lymphadenopathy, 838–839, 904, 906, 909 lymph node calcification, 910 egg-shell, 909 mediastinal, 882, 883, 884, 886 pericardial, 844–845 pleural, 844–845 pleural thickening, 1034 apical, 1035 pneumothorax, 1039 posttreatment cystic degeneration of thymus, 839 posttreatment residual masses, 839, 839, 843 pulmonary, 840, 841 with extrapulmonary disease, 839 rheumatoid arthritis association, 591 role of imaging, 847 sarcoid-like reaction, 642 solitary pulmonary nodules, 130 staging, 837 thymic, 839, 942, 954, 954 trachea, 829 see also Hodgkin lymphoma; non-Hodgkin lymphoma lymphomatoid granulomatosis (angiocentric immunoproliferative lesion), 843–844, 846 lymphoproliferative disease HIV/AIDS patients, 315–316 lung transplantation patients, 355 Sjögren syndrome, 602

Mach band, 940, 1043 McLeod syndrome see Swyer–James syndrome macroaggregated human serum albumin, perfusion scanning, 26–27 Madelung disease (multiple symmetric lipomatosis), 896 magnetic resonance angiography, 29 lung cancer, mediastinal invasion, 803 pulmonary artery aneurysms Behçet disease, 616 Hughes–Stovin syndrome, 617 pulmonary embolism, 398–399, 398, 400 magnetic resonance pancreatography, pancreato-pleural fistula, 1023 major fissures, 54, 54, 55, 55, 56, 56 malignant fibrous histiocytoma, 829 malignant melanoma, 527, 535 MALT lymphoma, primary pulmonary, 95, 841–842, 845 Marfan syndrome, 756, 960, 967, 1042, 1042 bullae, 1042 clinical features, 1042 cystic medial necrosis, 966 cysts, 1042 emphysema, 1042 pneumothorax, 1042 marfanoid hypermobility syndrome, 1042 marijuana smoking, 767 spontaneous pneumomediastinum, 939 mass, Fleischner Society glossary definition, 163 massive aspiration of gastric contents, 492, 492, 493 Masson bodies, 509

1184

maximum intensity projections, 16–17, 17 pulmonary nodules detection, 175 measles virus infection, 274, 751 mechanical ventilation-related barotrauma acute respiratory distress syndrome complication, 432, 433 alveolar rupture with pneumomediastinum, 939–940 pneumothorax, 1043 smoke/fire injury, 488 mechanical ventilation-related pulmonary edema, 426 mediastinal abscess, 924 acute mediastinitis, 921 esophageal rupture, 1140 mediastinal cysts/cystlike lesions, 883, 884, 886–890, 887 mediastinal disease, 881–959 imaging techniques, 881–882 mediastinal hemorrhage/hematoma, 919, 921, 925, 1121, 1124, 1125, 1128, 1130 aortic branch vessel injury, 1133, 1134, 1135 mediastinal lipomatosis, 881, 882, 893, 895, 895, 896 mediastinal lymph nodes, 808 calcification, 908–909, 909 normal size, 808 mediastinal lymphadenopathy, 883, 904–915 amyloidosis, 694, 695 beryllium-related disease, 485, 486, 486 Castleman disease, 906–907, 909 causes, 904, 904, 906 coccidioidomycosis, 258 cryptococcosis, 255 diagnosis, 907–908 chest radiography, 911–912, 913 CT, 912–914, 913, 914 contrast enhancement, 909–910 low attenuation, 909 MRI, 914 pitfalls, 917 positron emission tomography, 914–915 diphenylhydantoin toxicity, 526 fungal infection, 904, 909 heart failure, 906 with hazy opacification of fat, 426 histoplasmosis, 252, 253, 253 HIV/AIDS, 302, 904 Hodgkin disease, 909 Kaposi sarcoma, 315, 317 leukemia, 904, 912, 914 lung cancer (nonsmall cell), 807, 808, 809, 810 staging, 808–809 lymph node calcification, 908–909, 909 lymphoma, 838–839, 838, 839, 904, 906, 909 posttreatment residual masses, 839, 839 methotrexate hypersensitivity, 530 nonspecific interstitial pneumonia, 574 nontuberculous mycobacterial infection, 909, 912 paratracheal, 884, 885 paravertebral, 886 prevascular masses, 884 pulmonary fibrosis, 906, 906 pulmonary surfactant deficiencies, 582 sarcoidosis, 644–646, 645, 647, 904, 905, 909, 911 scleroderma, 906

silicosis, 464 T cell leukemia, 848, 849 tuberculosis, 229, 904, 905, 909, 911 calcification, 230 primary, 229, 230, 231, 231, 240 usual interstitial pneumonia, 565–566, 567 mediastinal mass children, 882, 883 differential diagnosis, 882–883 esophageal lesions, 892–893, 892 frequency, 882, 883 imaging techniques, 881–882 neurofibromatosis type I, 683 paracardiac, 884, 885 paraesophageal, 884–886, 885 paratracheal, 884–886, 885 paravertebral, 886, 886 prevascular, 884, 884 subcarinal, 884–886, 885 mediastinal panniculitis, 924 mediastinal paraganglioma, 929, 936–938, 937, 938 mediastinal shift atelectasis of whole lung, 115 lobar atelectasis, 103 mediastinal tumors fatty, 896–897 invasive lung cancer, 801, 801, 802, 803, 803 lymphovascular, 917, 919 metastases, 883, 885, 904, 905, 909 neurogenic, 929–938, 929 mediastinal venous obstruction, 942, 946 mediastinal widening acute mediastinitis, 921 aortic dissection, 968 mediastinal hemorrhage, 1121, 1124 diagnostic criteria, 1124–1125 mediastinal panniculitis, 924 mediastinitis, 921–928 acute, 921–922 descending cervical, 921–922 esophageal rupture, 1140 fibrosing, 922–924, 923, 926, 927, 928 mediastinum anterior junction, 65, 67 blood vessels, 61, 63–64 venous anatomy, 63 compartments, 882 Fleischner Society glossary definition, 163 contours on plain chest radiographs (frontal view), 69–70 anterior junction, 70, 72 azygoesophageal recess, 71, 73, 73, 74 left mediastinal border, 69–70, 69, 70, 71 paraspinal lines, 73 posterior junction, 71–72, 72 right mediastinal border, 70 contours on plain radiographs, 74–75, 74 inferior vena cava, 75 retrosternal line, 75 trachea/retrotracheal area, 74–75, 75 divisions, 60 esophagus, 64 lymph nodes, 65, 66, 67 AJCC–UICC classification, 67, 68, 69 normal size, 68–69 normal, 60 paraspinal areas, 67

Index paraspinal lines, 65, 67, 67, 68 posterior junction, 65, 67 spaces, 65–67 aortopulmonary window, 65, 66–67 posterior tracheal, 67 pretracheal, 65–66 prevascular, 65, 67 retrocrural, 67, 68 right paratracheal, 65, 67 subcarinal, 65, 67 thymus, 64–65 Meigs syndrome, 1022, 1023 melanoptysis, coal worker’s pneumoconiosis, 469 melioidosis, 217–218, 218 melphalan, lung toxicity, 507 Mendelson syndrome, 492 meningioma, 833 meningocele, 883, 886, 890 mephenesin hypersensitivity, 673 mesenchymal cystic hamartoma, 183 mesenchymal tumors esophagus, 886 mediastinum, 884 paraspinal, 886 mesodermal cyst, 30 mesothelioma, 471, 472, 474, 851, 853–857 asbestos exposure association, 851 benign see localized fibrous tumor of pleura clinical features, 852 imaging findings, 852, 854, 855, 856, 856 latent period, 472, 851 pathology, 851 pleural effusions, 1019 pleural thickening, 1033, 1034 pneumothorax, 1039 staging, 851, 853 metastases, 858–864, 858, 859, 860, 861 detection chest radiograph, 860 CT, 860–861 MRI, 861–862 positron emission tomography, 862 radionuclide imaging, 862 hilar lymphadenopathy, 915 mediastinal lymphadenopathy, 904, 905, 909 multiple pulmonary nodules, 132, 133, 133 nodular pattern, 176 pneumothorax, 1039 pulmonary calcification, 519, 519, 680–681, 681 pulmonary lacunae (air cysts), 859 solitary pulmonary nodules, 120 methadone overdose, 532 methicillin-resistant Staphylococcus aureus pneumonia, 212, 213 lung transplantation patients, 352 methotrexate immunosuppression, 520 lung toxicity, 507, 509, 513, 514, 519, 520, 529–531, 530, 531, 591, 591, 673 hypersensitivity reactions, 509 pleural effusions/thickening, 1024–1025 methylmethacrylate cement, pulmonary embolism, 518, 518 methylphenidate abuse, 756 methysergide toxicity, 519, 531, 923 pleural effusions/thickening, 1025

microaerophilic Streptococcus, 219 microaspiration, 493 microliths (calcispherites), 679 micronodules, 176 Fleischner Society glossary definition, 163 microscopic polyangiitis, 608, 609, 613, 613 diffuse pulmonary hemorrhage, 620 microwave ablation therapy, 552 middle lobe syndrome, 101, 110, 111, 111 midsternal stripe sign, sternal dehiscence, 922 migraine, 531 migratory lung opacities, 575 cryptogenic organizing pneumonia, 576, 576 miliary nodulation, 176 blastomycosis, 262, 262 coccidioidomycosis, 259 Fleischner Society glossary definition, 163–164, 164 histoplasmosis, 252, 254 pneumonia, 210, 210 pulmonary metastases, 859, 861 miliary tuberculosis, 230, 232, 235–236, 237 milk-alkali syndrome, 519 mineral dust pneumoconiosis, 102, 142 minimal aortic injury, 1130, 1131, 1132, 1132 minimum intensity projections, 17, 17, 18 small airways disease, 190 minor (horizontal) fissure, 54, 55, 55, 56, 56, 57 mitomycin toxicity, 507, 515, 531 pleural effusions/thickening, 1025 radiation therapy potentiation (recall pneumonitis), 542 mitoxantrone, lung toxicity, 539 mitral regurgitation, 426 mitral stenosis diffuse alveolar hemorrhage, 619 pulmonary arterial hypertension, 416, 416 raised pulmonary venous pressure, 423 mitral valve disease, 143, 145, 146 pulmonary arterial hypertension, 416 pulmonary edema, 426 mixed connective tissue disease, 604, 605 mixed cryoglobulinemia, 616 mixed dust pneumoconiosis, 470 mixed germ cell tumors, 902 mixed lymphangioma/hemangioma, 919 monoclonal antibody therapy, lung toxicity, 532, 591–592 Morgagni (anterior) hernia, 884, 1107, 1111, 1112 mosaic attenuation pattern asthma, 754 chronic thromboembolic disease, 419, 419 constrictive bronchiolitis, 191, 192, 743, 744, 744, 745 CT, 23 high-resolution CT, 179–180, 180, 181 cystic fibrosis, 736, 739 diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, 750, 750 Fleischner Society glossary definition, 164 hypersensitivity pneumonitis, 460, 461 small airways disease, 22, 190, 740 motion artifact CT pulmonary angiography, 391 high-resolution CT, 20–21 MRI, 399

Mounier–Kuhn syndrome see tracheobronchomegaly mountain sickness (high-altitude pulmonary edema), 434 MRI, 1, 29–32, 824 applications, 30–32, 30, 31, 32 fast spin-echo (turbo-spin-echo) imaging, 29 field-of-view, 29 image contrast, 29 indications, 32 motion artifacts, 29 navigator echo for respiratory monitoring, 30 pleural fluid imaging, 1017, 1019, 1020 signal-to-noise ratio, 29, 30 slice misregistration artifact, 30 spatial resolution, 30 technical considerations, 29–30 ventilation imaging, 32 mucinous cystadenocarcinoma, 793 mucocele, 137, 138 esophagus, 892 segmental bronchial atresia, 1069, 1070, 1070, 1071 see also mucoid impaction mucoepidermoid carcinoma, 833, 833 mucoid impaction (bronchocele), 135–136, 137, 138 allergic bronchopulmonary aspergillosis, 667, 669, 670, 670 asthma, 753 bronchial carcinoid, 823, 825 cystic fibrosis, 735 Fleischner Society glossary definition, 158, 158 lung cancer, 790 Mucor, 250, 329 Mucorales, 268 mucormycosis (zygomycosis), 250, 268–269, 270, 329 hypersensitivity pneumonitis, 457 immunocompromised patients, 324, 329, 330, 331 angioinvasive, 324 imaging findings, 324 lung transplantation patients, 357, 358 airways infection, 354 pneumonia, 208 mucoviscidosis see cystic fibrosis multidetector CT (MDCT), 1, 7, 10, 11, 11 acquisition parameters, 11, 12 anomalous bronchi, 41 aortic aneurysm, 962 aortic disease, 960 aortic dissection, 970 bronchiectasis, 21 central airway disease, 24 CT angiography, 24 high-resolution CT, 20 image reconstruction, 14 intravenous contrast enhancement, 17, 18 lung cancer liver metastases, 813 mediastinal invasion, 801 mediastinal disease, 882 mediastinal lymphadenopathy, 912 protocols, 19 pulmonary embolism, 389, 390, 391, 395, 396

1185

Index section thickness, 11 superior vena cava syndrome, 942 multifocal pulmonary ossification, 143 multifrequency processing, digital chest radiography, 4 multiplanar reconstructions, 14 multiple endocrine neoplasia syndrome type 1, 955 multiple organ failure, acute respiratory distress syndrome, 432 multiple pulmonary nodules, 132–135, 133, 134 differential diagnosis, 132 growth rate, 133 management, 133–135, 135 multiple symmetric lipomatosis (Madelung disease; Lanois–Bensaude syndrome), 896 muscle relaxants, pleural effusions/ thickening, 1025 mushroom worker’s lung, 457 mustard gas exposure, 742 myasthenia gravis, 882, 884 lymphofollicular thymic hyperplasia, 947, 950 thymoma, 950, 954 mycetoma, 606 Fleischner Society glossary definition, 164, 164 pleural thickening, 1034, 1035 solitary pulmonary nodules, 131 see also aspergilloma mycobacterial infection, 177 exogenous lipid pneumonia superinfection, 515 lung transplantation recipients, 359 pretransplantation, 345 progressive massive fibrosis (silicosis) superinfection, 464, 468 silica exposure-related risk, 468 Mycobacterium abscessus, 241, 247, 733 Mycobacterium avium–intracellulare, 228, 241, 243, 243, 244, 247, 733, 912 complicating usual interstitial pneumonia, 569, 571 high-resolution CT, 245–246, 245, 246 HIV/AIDS patients, 302, 302, 303 hypersensitivity pneumonitis, 457 lung transplantation patients, 359 radiographic features of infection, 244–246, 245 silica exposure-related risk, 468 Mycobacterium chelonae see Mycobacterium fortuitum–chelonae Mycobacterium fortuitum–chelonae, 241, 244, 247, 302, 515, 733 Mycobacterium genavense, 241 Mycobacterium gordonae, 241, 247, 302 Mycobacterium kansasii, 228, 241, 242, 246, 247, 733 HIV/AIDS patients, 302 silica exposure-related risk, 468 Mycobacterium malmoense, 241, 247, 302, 303 Mycobacterium scrofulaceum, 241 Mycobacterium simae, 241 Mycobacterium szulgai, 241 Mycobacterium terrae, 468 Mycobacterium tuberculosis, 228, 229 fibrosing mediastinitis, 922 HIV/AIDS patients, 296

1186

lung transplantation patients, 359 pneumonia, 97, 207 pulmonary alveolar proteinosis, 679 pulmonary gangrene, 208 silica exposure-related risk, 468 see also tuberculosis Mycobacterium xenopi, 241, 247, 247, 302 Mycoplasma pneumonia, 142, 143, 206, 207, 210, 210, 269–270, 269, 271, 751 sickle cell disease, acute chest syndrome, 421 Mycoplasma pneumoniae, 206, 207, 210, 210, 269 constrictive bronchiolitis, 741, 742 mycotic aneurysm, 420, 421, 965–966 intravenous drug users, 532, 533 mycotic pseudoaneurysm, 533 myelolipoma, 896 myeloma, 694, 913 myocardial contusion, 1148 myocarditis, systemic lupus erythematosus, 595 myxedema, pleural effusions, 1026 myxoid liposarcoma, 897, 897 myxosarcoma, 830

naproxen hypersensitivity, 673 National Lung Screening Trial (NLST), 822 near-drowning, 491–492, 492 Necator americanus, 276, 674 necrotizing sarcoid angiitis, 618, 618 necrotizing tracheobronchitis, aspergillosis, 323 NELSON trial, 822 nematode infestations eosinophilic lung disease, 674, 674 tropical pulmonary eosinophilia, 673 neonatal respiratory distress, ciliary dyskinesia syndrome, 737 neostigmine, drug-induced asthma, 511 nephrotic syndrome, pleural effusions, 1023 nerve sheath tumors, 935, 935 malignant, 935, 936 mediastinum, 883, 929, 935 neurenteric cysts, 889, 889 antenatal detection, 1098 neurilemmoma, 829, 833 neuroblastoma, 935, 935, 936 mediastinum, 929 neurocutaneous syndromes, 682–685 neuroendocrine tumors lung, 822 thymus, 942, 955, 955 neurofibroma, 829, 833, 935, 936, 936, 1012 mediastinum, 929, 931 trachea, 829 neurofibromatosis, 767, 890, 929, 930, 935 neurofibromatosis type I, 682–683 chest wall involvement, 682 diagnostic criteria, 682 lung involvement, 683–683, 683 mediastinal masses, 683 thoracic lesions, 682 neurofibrosarcoma, 830 neurogenic pulmonary edema, 433, 434 neurogenic tumors imaging, 929, 929, 935–936 mediastinum, 882, 883, 884, 929–938, 929

neutropenia aspergillosis, 322, 323 angioinvasive, 324, 327, 328, 329 mucormycosis, 330 pulmonary complications, 321, 322 hematopoietic stem cell transplantation patients, 336–337 pulmonary opacities evaluation/ differential diagnosis, 334 Niemann–Pick disease, 691, 692 nitrofurantoin toxicity, 195, 195, 509, 509, 513, 514, 519, 534–535, 534, 535, 621, 673 hypersensitivity reactions, 509 pleural effusions/thickening, 1025 nitrogen oxides toxicity, 489, 490, 756 constrictive bronchiolitis (silo-filler disease), 742 nitrosurea toxicity, 535–536 nitrous oxide inhalation, spontaneous pneumomediastinum, 939 Nocardia asteroides, 247, 298, 298, 322, 323, 741 Nocardia brasiliensis, 247 nocardiosis, 247–248, 248, 520, 595 constrictive bronchiolitis, 741 heart transplantation patients, 342 HIV/AIDS patients, 297, 298, 298 immunocompromised patients, 322, 323 lung transplantation patients, 359 pulmonary alveolar proteinosis, 679 nodular lymphoid hyperplasia, 847 nodular opacities, 90, 139–147, 139 centrilobular, associated conditions, 178 differential diagnosis, 141–142, 141 diffuse (Japanese) panbronchiolitis, 746, 746, 747 Fleischner Society glossary definition, 164, 164 high-resolution CT, 175–177 hypersensitivity pneumonitis, 458, 459, 461 idiopathic (primary) pulmonary arterial hypertension, 412, 412 mucormycosis, 330 pulmonary alveolar microlithiasis, 680 silicoproteinosis, 467 silicosis, 463, 463, 465 see also nodules nodules amyloidosis, 694, 697, 699 aspergillosis, 311, 324, 325, 327 Behçet disease, 616 chest radiography, anatomic noise, 3 Churg–Strauss syndrome, 615, 615 CT, 12 maximum intensity projections, 16 positron emission tomography combined examination, 26, 26, 28 computer-aided detection, 6, 8, 9 cryptococcal pneumonia, 308 detection, 175 diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, 750 digital tomosynthesis, 8 dual-energy subtraction imaging, 5, 6 Fleischner Society glossary definition, 164, 164 HIV/AIDS patients, 311, 313 bacterial pneumonia, 297 Kaposi sarcoma, 314, 316

Index Langerhans cell histiocytosis, 454, 455, 455 lung cancer, population screening, 820–821 lymphoma, 841 AIDS-related, 313, 315 posttransplant lymphoproliferative disorder, 368–369, 369 pulmonary metastases, 858 rheumatoid arthritis, 587, 588–590, 589 Caplan syndrome, 590 sarcoidosis, 648, 648, 649, 650–651, 651 Sjögren syndrome, 603 tuberous sclerosis, 684, 685 vasculitis, 608 Wegener granulomatosis, 610, 610, 611, 613 see also multiple pulmonary nodules; solitary pulmonary nodule non-Hodgkin lymphoma chest wall invasion, 846 classification, 836 intrathoracic lymphadenopathy, 838–839, 841 pleural disease, 844–845 posttreatment residual masses, 839, 839 primary pulmonary, 841–842 pulmonary lesions, 841, 844, 845 role of imaging, 847 staging, 837 childhood disease, 837, 837 nonseminomatous germ cell malignancies, 902, 903, 903 residual mass following treatment (growing teratoma syndrome), 903–904, 904 nonsmall cell lung cancer, 526, 532, 541 apical (Pancoast/superior sulcus) tumors, 805–807, 806, 807 chest wall invasion, 803–805, 804, 805 mediastinal invasion, 801, 801, 802, 803, 803 mediastinal lymph node involvement, 807–808, 808 positron emission tomography–CT combined examination, 26 staging, 797, 798, 799, 800–812 distant spread, 811 imaging, 800–805 intrathoracic lymph nodes, 807–811 pleural involvement, 811–812 primary tumor, 801–805 prognosis, 800 summary, 812, 812 treatment decision-making, 798, 800, 801, 803, 807 TNM classification, 799, 800 nonspecific interstitial pneumonia, 179, 221, 562, 562, 563, 572–574 causes, 573, 573 cellular subtype, 572, 573 clinical features, 573 diagnosis, 582–583 drug-induced, 508 epidemiology, 573 familial lung fibrosis, 581 fibrotic subtype, 572, 573 Fleischner Society glossary definition, 164–165, 165 histologic features, 572, 573, 573 HIV/AIDS patients, 317–318

imaging appearances, 573, 573, 584 CT, 582–583 immunocompromised patients, 335–336 irreversible fibrosis, 195, 195 polymyositis/dermatomyositis, 601 prognosis, 584 rheumatoid arthritis, 588 systemic lupus erythematosus, 594, 594 nonsteroidal anti-inflammatory drugs, hypersensitivity reactions, 509 nontuberculous mycobacterial infection, 228, 241–247, 242, 606 bronchiectasis, 732 cystic fibrosis, 733 HIV/AIDS patients, 296, 299, 302, 302 hypersensitivity pneumonitis, 457 lung transplantation patients, 359 mediastinal lymphadenopathy, 909, 912 pulmonary alveolar proteinosis, 679 radiographic features, 242–243, 242, 243, 244 Noonan syndrome, 1088, 1089 normal chest, 39–78, 40, 41 lung, high-resolution CT, 153–155, 154 nucleoside-induced lactic acidosis, 295

obesity, morbid, 417 oblique view, 3 obliterative bronchiolitis (bronchiolitis obliterans), 741 bronchiectasis, 731 drug-induced, 518–519 graft-versus-host disease, 339, 340 lung transplantation, 359–362, 360 see also bronchiolitis obliterans syndrome lung transplantation patients, 355 pathology, 741, 741 rheumatoid arthritis, 590, 590 toxic fume inhalation, 489, 490 see also constrictive bronchiolitis obliterative small airways disease, high-resolution CT, 184, 185 occlusive thromboarteriopathy see Takayasu arteritis (Takayasu disease) occlusive vascular disease decreased attenuation lung, 185 mosaic attenuation pattern, 180 octreotide scintigraphy see somatostatin receptor scintigraphy OKT3 toxicity, 532 oligemia, Fleischner Society glossary definition, 165, 165 opacity Fleischner Society glossary definition, 165 see also airspace opacities; pulmonary opacities opiates, lung toxicity, 532 neurogenic pulmonary edema, 511 opportunistic infection heart transplantation patients, 342–343 HIV/AIDS patients, 295 lung transplantation patients, 352, 355, 357, 358, 359, 359 systemic lupus erythematosus, 595 usual interstitial pneumonia, 569 see also specific infections oral contraceptives, pulmonary thromboembolism association, 518

organ transplantation patients malignant disease, 366–367, 367 posttransplant lymphoproliferative disorder, 367–369 organizing pneumonia, 562, 574–579, 575 associated conditions, 575 diagnosis, 583 drug-induced, 508–509, 521, 525, 534, 535, 538 Fleischner Society glossary definition, 165, 165 graft-versus-host disease, 339, 340 HIV/AIDS patients, 312 immunocompromised patients, 335–336 inflammatory bowel disease, 690 intraluminal fibrosis, 574 perilobular distribution, 174, 174 polymyositis/dermatomyositis, 601 rheumatoid arthritis, 588, 589 sytemic lupus erythematosus, 595 Wegener granulomatosis, 609 see also cryptogenic organizing pneumonia Osler–Weber–Rendu syndrome, 133 ossification bronchial carcinoid, 823, 824 pulmonary see diffuse pulmonary ossification osteogenesis imperfecta, 756 osteogenic sarcoma, 529, 1039 osteosarcoma, 829, 941 pleura, 857 radiation-induced, 550 ovarian carcinoma, 539 ovarian hyperstimulation syndrome, pleural effusions, 1022, 1025, 1026 overdiagnosis bias, 818–819 oxygen, pulmonary toxicity, 536–537 bronchopulmonary dysplasia, 537, 538, 539

paclitaxel toxicity, 509, 526, 539 panacinar emphysema, 757, 759, 761, 761, 762, 765 alpha1-antitrypsin deficiency, 746, 763, 763, 764 decreased attenuation lung, 184, 185 Fleischner Society glossary definition, 165, 165 Pancoast tumor, 789, 805–807, 806, 807 apical pleural thickening, 1035, 1035 pancreatic cancer, 526 pancreatic disease, pleural effusions, 1022–1023 pancreatic pseudocyst, 886, 1023 mediastinum, 889–890, 890 pancreatitis, chronic chylothorax, 1030 pleural effusions, 1023, 1024 pancreatopleural fistula, 1023 papillary adenoma, 833 papillomatosis, 834–835 laryngeal, 829, 831, 834, 835 tracheobronchial, 834 para-aminosalicylic acid, hypersensitivity reactions, 509, 673 Paracoccidioides brasiliensis, 259 paracoccidioidomycosis, 259, 261 paraganglioma, 829, 884 intracardiac, 936, 938 mediastinum, 929, 936–938, 937, 938

1187

Index paragonimiasis, 278–279, 279 Paragonimus westermani, 278 parainfluenza pneumonia, 271, 273 hematopoietic stem cell transplantation patients, 337, 339 lung transplantation patients, 357 paraseptal emphysema, 757, 761, 761, 1038 Fleischner Society glossary definition, 165, 165 paraspinal abscess, 886 paraspinal hematoma, 1125, 1126, 1127 paraspinal lines, 65, 67, 67, 68, 73 paraspinal mass, 884 parathyroid adenoma, 884, 938 parathyroid cyst, mediastinum, 939 parathyroid glands, ectopic mediastinal, 938 parathyroid lesions, mediastinum, 938–939, 938, 939, 940 paratracheal cysts, 724 paratracheal lymph nodes, 68 paratracheal space, right, 65, 67 paratracheal stripe, right, 70 Fleischner Society glossary definition, 169, 169 paravertebral stripes, 73 parenchyma, lung density increase, pulmonary edema, 426 Fleischner Society glossary definition, 165–166 high-resolution CT, 153–154, 154 axial connective tissue fibers (peribronchovascular interstitium), 153 peripheral (subpleural) interstitium, 153 pulmonary lobules (paraseptal interstitium), 153 septal connective tissue fibers (interlobular interstitium), 153 injury, 1134–1137, 1134 normal, 50–51 parenchymal band, Fleischner Society glossary definition, 166, 166 parenchymal disease, high-resolution CT, 20–21 parenchymal opacification Fleischner Society glossary definition, 166 high-resolution CT, 177–182 parenchymal scars, 135 Parkinson disease, 524 partial volume effects, 11, 175 Pasteurella multocida, 218 patent ductus arteriosus, 415 pathologic rib fracture, 1151 pectus excavatum, 40, 70 silhouette sign, 85, 87 penetrating atherosclerotic ulcer, aorta, 966, 967 imaging, 968, 968 penicillamine toxicity, 509, 515, 518, 537, 590, 591, 621, 743 hypersensitivity reactions, 509, 673 penicillin hypersensitivity, 673 Penicillium, hypersensitivity pneumonitis, 457 Peptococcus, 218 Peptostreptococcus, 218 perceptual errors, chest radiograph interpretation, 3 perfusion, MRI, 32

1188

perfusion scintigraphy, 26–27 lung cancer treatment decision-making, 800 lung transplantation, 348 see also ventilation/perfusion (V/Q) scan pergolide toxicity, 519 peribronchovascular interstitium, Fleischner Society glossary definition, 166 pericardial cysts, 882, 883, 884, 887–888, 888, 889 pericardial disease, pleural effusions, 1021–1022 pericardial effusion lymphoma, 845 pulmonary arterial hypertension, 409, 410, 410 radiation-induced, 546, 552 pericardial fibrosis, asbestos-related, 472 pericardial injury, 1148 pericardial recesses, 883 high-riding, 917, 917 pericardial tumor, 884 pericarditis pleural effusions, 1021 systemic lupus erythematosus, 595 perilobular distribution, 174, 174 Fleischner Society glossary definition, 166, 166 perilymphatic distribution, Fleischner Society glossary definition, 166, 166 peritoneal dialysis, 1022, 1023 persistent generalized lymphadenopathy, 318 persistent left superior vena cava, 61, 64, 918 persistent pulmonary hypertension of newborn, 411 pertussis (whooping cough), 216–217, 217, 751 phenytoin toxicity, 512, 519, 673 phleboliths, mediastinal hemangiomas, 919 phosgene, 756 phrenic nerve, 76, 76 lung cancer involvement, 801 phrenic nerve tumor, 929 PIOPED, 403, 407 PIOPED II, 392, 397 pixel density emphysema extent quantification (CT densitometry), 762, 762 interstitial fibrosis/functional impairment correlations, 584 plague, 218, 904 plasma cell–histiocytoma complex (plasma cell granuloma), 835, 836 plasmacytoma, 831–832 pleura, 857 pleura, 53–54 asbestos exposure-related changes, 471 fissures see fissures inferior pulmonary ligaments, 59–60 lung cancer invasion, 804, 804, 811–812 parietal, 53, 53, 1003, 1004 physiology, 1003–1004 visceral, 53, 53, 1003, 1004 pleural biopsy, 1015 pleural effusion, 1004 pleural calcification, 1036–1037, 1036 pleural disorders, 1003–1051 pleural effusion, 85, 1003–1027, 1004 abdominal surgery-related, 1024 actinomycosis, 250 acute eosinophilic pneumonia, 662

acute mediastinitis, 921 acute respiratory distress syndrome, 432 amyloidosis, 694 anaphylactoid purpura (Henoch–Schönlein purpura), 615 anthrax, 214 asbestos exposure, 1004 benign effusions, 471–472, 471 ascites differentiation, 1015 ascites fluid, 1022 bacterial parapneumonic, 222–227 complicated/uncomplicated, 222 cardiac surgery association, 1021 causes, 1004–1005, 1004, 1005, 1017 Churg–Strauss syndrome, 615 cryptococcosis, 258 drainage, reexpansion pulmonary edema, 435 drug-induced, 519, 521, 530, 531, 534, 1024–1025, 1025 drug-induced eosinophilic lung disease, 673 drug-induced lupus, 512 eosinophilic, 1004–1005 esophageal rupture, 1140 exudates, 1004, 1004, 1015 causes, 1005 familial Mediterranean fever, 1026 heart failure, 1004, 1020, 1020 heart transplantation patients, 342 hepatic cirrhosis (hepatic hydrothorax), 1004, 1022 hepatitis, 1022 hypereosinophilic syndrome, 675 Kaposi sarcoma, 315 leukemia, 848 loculated, 1011–1012, 1011, 1012, 1013, 1014, 1016 lower lobe collapse differentiation from pleural fluid, 115, 117, 117 lung cancer, 788, 811 lung transplantation patients, 365–366 lymphoma, 844, 1004 AIDS-related, 313 non-Hodgkin, 842 malignant, 864, 1004, 1005, 1008, 1015, 1016 mechanism of development, 1004 Meigs syndrome, 1022, 1023 mesothelioma, 856, 1019 microscopic polyangiitis, 613 myxedema, 1026 ovarian hyperstimulation syndrome, 1022, 1025, 1026 pancreatic disease, 1022–1023 pancreatitis, chronic, 1023, 1024 pericardial disease, 1021–1022, 1021 pneumonia, 205, 210, 211, 213, 223, 297 pneumothorax complication, 1046 pneumothorax ex vacuo (negative pressure pneumothorax), 1026, 1027 pregnancy-related, 1020 pulmonary embolism, 387, 387, 1004, 1022 pulmonary infarction, 1004 radiation-induced, 546, 1024 renal disease, 1023 rheumatoid arthritis, 587, 587, 588, 1004 sarcoidosis, 658 sickle cell disease, acute chest syndrome, 421

Index silicosis, 468 splenic disease, 1023 subpulmonic, 1007–1008, 1008, 1009 superior vena cava syndrome, 1021–1022 systemic lupus erythematosus, 592, 593, 1004 transudates, 1004, 1004, 1007, 1015 causes, 1004 traumatic, lung parenchymal injury, 1135, 1137 tuberculosis, 1004, 1005, 1006 primary, 230 upper abdominal infections, 1020 Wegener granulomatosis, 612 yellow nail syndrome, 1026, 1026 see also hydrothorax pleural fibroma see localized fibrous tumor of pleura pleural fibrosis, drug-induced, 519 pleural fluid, 1003–1004 milky appearance, 1028 protein concentration, 1004 pleural line, pneumothorax detection, 1038, 1043, 1044, 1045 pleural lipoma, 857, 857 pleural metastases, 864, 864 pleural mouse (fibrin body), 1048 pleural peel, 223, 223 pleural plaques asbestos-related, 472–473, 473, 474, 475, 476 differential diagnosis, 472–473 Fleischner Society glossary definition, 166, 167 nonasbestos materials-related, 472 pleural space, 1003, 1004 lymphatic drainage, 1004 pleural tail sign, lung cancer, 789 pleural thickening, 1031–1035, 1032 causes, 1031–1032, 1032 mimics, 1034–1035 apical pleural cap, 1034–1035, 1034 extrapleural fat, 1034, 1034 pleurodesis-related, 1035 pneumothorax/hemothorax complication, 1048 pleural tumors, 857 see also mesothelioma pleurisy, sarcoidosis, 658 pleuritis Sjögren syndrome, 603 systemic lupus erythematosus, 592 tuberculosis, 236–237, 238, 238 pleurodesis indications, 1035 radiographic appearance following, 1035–1036, 1036 pleuroesophageal line/stripe, 71, 73 pleuroparenchymal scars, 135 pneumatocele, 135, 136 acute respiratory distress syndrome, 432, 433 Fleischner Society glossary definition, 167, 167 pneumonia, 207–208, 209 Pneumocystis jirovecii, 306–308, 307, 308 posttraumatic lung cysts, 1135 transient postinfective, 183 see also cysts pneumococcal pneumonia see Streptococcus pneumoniae, pneumonia

pneumococcal vaccination, 210 pneumoconiosis, 142, 143, 462–484 classification, 462, 462 International Labor Organization (ILO) standardized scoring system, 462, 462 lung transplantation, 362 nodular pattern, 176 severity determinants, 462 Pneumocystis carinii pneumonia see Pneumocystis jirovecii pneumonia Pneumocystis jirovecii pneumonia, 208, 520, 595 bat’s wing airspace opacities, 98 complicating usual interstitial pneumonia, 569, 570 cystic airspaces, 183 high-resolution CT, 196 HIV/AIDS patients, 295, 296, 297, 302–308, 303, 304, 305, 305, 306, 307, 308, 312, 319 immunocompromised patients, 331, 332 intrathoracic lymph node calcification, 908 pneumomediastinum, 939–941, 942, 943 acute mediastinitis, 921 acute respiratory distress syndrome, 432, 433 asthma, 753, 753 causes, 940 esophageal rupture, 924, 1140 Fleischner Society glossary definition, 167, 167 imaging features, 940–941, 941 pneumothorax complication, 1048 spontaneous, 939, 940 spontaneous alveolar rupture, 939 traumatic, 1121 central airways injury, 1138, 1139 usual interstitial pneumonia, 565, 566 pneumonia, 84, 85, 90, 142 acute respiratory distress syndrome, 432 air bronchograms, 87, 88 airspace opacities, 91, 91, 92, 93, 97, 98, 100 bat’s wing, 98, 99 immunocompromised host, 98 aspiration see aspiration pneumonia bacterial see bacterial pneumonia bronchopulmonary dysplasia, 537 CT angiogram sign, 91 consolidation, 97 cryptogenic organizing see cryptogenic organizing pneumonia decision-making in management, 207 diagnosing cause, 206–207 eosinophilic see eosinophilic pneumonia Fleischner Society glossary definition, 167 foreign body inhalation complication, 493, 494 hospital-acquired, 214 infection, 205–206 community-acquired, 207 hospital-acquired, 207, 214 lung transplantation patients, 352, 353, 354 radiographic patterns, 205 interstitial see interstitial pneumonia lobar, 205, 206, 207 tuberculosis, 233–235, 234 lung cancer, 788

obstructive, 97 neoplastic, 795–796, 796 organizing see organizing pneumonia pleural effusions, 205, 210, 211, 213, 223, 297 pleural thickening, 1032, 1032 predisposing conditions, 207 resolution, 210 reticulonodular pattern, 210 scleroderma, 598 smoke/fire inhalational injury, 488 smoking-related risk, 456 solitary pulmonary nodules cavitation, 131 focal, 130, 130 round, 130 spherical (round/nodular), 205, 206, 208, 208, 210 systemic lupus erythematosus, 595 ventilator-associated, 210 see also bronchopneumonia; specific infective agents pneumonitis, granulomatous drug-induced, 514 pneumopericardium, 940, 1148, 1149 Fleischner Society glossary definition, 167, 167 pneumothorax, 85, 1037–1050 ablation therapy complication, 552 acute respiratory distress syndrome, 432, 1045, 1046 asthma, 753, 1039 bilateral, 1048 Birt–Hogg–Dubé syndrome, 687 causes, 1038 chronic obstructive pulmonary disease, 1039 complications, 1046, 1050 computer-aided diagnosis, 6 cystic fibrosis, 733, 736, 739, 1039, 1041, 1047 drug toxicity, 1048 Ehlers–Danlos syndrome, 1042 emphysema, 1038 endometriosis (catamenial pneumothorax), 1040, 1040, 1041 esophageal rupture, 1140 Fleischner Society glossary definition, 167, 167 heritable disorders, 1041–1042, 1041 idiopathic upper lobe fibrosis/ fibroelastosis, 584 interstitial lung disease, 1039 Langerhans cell histiocytosis, 453, 454, 1039, 1048 localized, 1046, 1048 loculated, 1046, 1047 lymphangioleiomyomatosis, 686, 687, 1048 lymphangiomyomatosis, 1039 management, 1049–1050 Marfan syndrome, 1042 mechanical ventilation-related, 1043 mesothelioma, 1039 neoplastic disease, 1039, 1048 passive atelectasis, 101 persistent air leak, 1050 pleural effusion, 1004, 1046 pneumomediastinum, 939, 940, 1048 pulmonary hypoplasia, 1074, 1075 pulmonary infarction, 1039–1040

1189

Index radiographic signs, 2, 1043–1044 free pneumothorax, 1043–1044 supine patient, 1045–1046, 1045, 1046 ultrasonographic detection, 1046 radiotherapy complication, 1039–1040 recurrence, 1048 reexpansion pulmonary edema, 435, 1049, 1049, 1050 sarcoidosis, 1048 spontaneous primary, 1037–1039, 1038 secondary, 1039–1040, 1039 subpulmonic, 1046 tension, 1048–1049, 1049 torsion of lung/lobe, 1153–1154, 1156 traumatic, 1121 central airways injury, 1138, 1139 gunshot wounds, 1153 lung parenchymal injury, 1135, 1137, 1137 rib fracture, 1148 tuberculosis, 1044, 1046 usual interstitial pneumonia, 565 pneumothorax ex vacuo (negative pressure pneumothorax), 1026, 1027 Pneumotox online, 1024 Poland syndrome, 147 polyangiitis overlap syndrome, 618 polyarteritis nodosa, 608, 947 polymyositis/dermatomyositis, 573, 578, 599–602, 599, 600 classification, 599 interstitial lung disease, 600–601 juvenile form, 602 malignancy, 602 mixed connective tissue disease, 604 overlap syndrome, 602 secondary manifestations, 602 thoracic manifestations, 600, 601 popcorn calcification, 124 hamartomas, 827, 828 solitary pulmonary nodule, 121 portable chest radiography, 3 positive bronchus sign, 130 positive end-expiratory pressure (PEEP), acute respiratory distress syndrome, 432 positron emission tomography (PET), 1 cryptogenic organizing pneumonia, 577 CT combined examination see positron emission tomography–CT (PET-CT) indications, 26 lung cancer, 790, 794, 794, 798 screening follow-up, 820, 821 mediastinal lymphadenopathy, 914–915 pulmonary alveolar microlithiasis, 680 pulmonary metastases, 862 techincal aspects, 24, 26 see also 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) positron emission tomography–CT (PET-CT), 24, 26, 26, 27, 28 asbestos-related rounded atelectasis, 476 bronchioloalveolar carcinoma, 815 brown fat, 896, 896 hibernomas, 896 diffuse malignant mesothelioma, 854 lung cancer pleural invasion, 811, 811 staging, 812

1190

mediastinal liposarcoma, 897, 898 radiation-induced lung injury, 548 sarcoidosis, 905 Takayasu arteritis, 420 thymic epithelial neoplasia, pathologic correlations, 954 post-cardiac injury syndrome, 1021 posterior (Bochdalek) hernia, 1107, 1110, 1111 posterior junction, 65, 67, 71–72 posterior tracheal space, 67 posterior tracheal stripe/band, 74, 75, 75 esophageal dilatation, 893, 894 posteroanterior (PA) view, 1 inspiratory/expiratory film, 1, 2 normal chest, 40 postpericardiotomy syndrome, 1021 postprocessing, digital chest radiography, 4 postsurgical bronchopleural fistula, 1051, 1051 posttransplant lymphoproliferative disorder, 367–369, 367, 368, 369 classification, 368 clinical features, 368 imaging features, 369 Potter syndrome, 1075, 1078 practolol toxicity, 1025 preeclampsia, 1020 pregnancy aspiration of gastric contents, 492 pleural effusion, 1020 pulmonary embolism diagnosis, 397, 405 ventilation/perfusion (V/Q) scanning, 29 premature infants, bronchopulmonary dysplasia, 537 pretracheal space, 65–66 primary biliary cirrhosis, 573 primary graft dysfunction, lung transplant, 347–348, 348 procainamide-induced lupus, 512, 513 procarbazine toxicity, 519 pleural effusions/thickening, 1025 progressive massive fibrosis, 100, 102 coal worker’s pneumoconiosis, 464, 466, 469 Fleischner Society glossary definition, 167, 168 multiple pulmonary nodules, 133, 134 silicosis, 464–466, 464 Propionibacterium, 219 propoxyphene overdose, 532 propranolol, drug-induced asthma, 511 propylthiouracil toxicity, 621 Proteus pneumonia, 97, 207, 214 protozoal infections, 276 HIV/AIDS patients, 311 immunocompromised patients, 332–333 pseudocavity, Fleischner Society glossary definition, 168, 168 pseudochylothorax, 1031 pseudocoarctation of aorta, 981, 984 Pseudomonas aeruginosa pneumonia, 97, 207, 214, 297, 298, 321, 352, 354 Pseudomonas infection, 593 cystic fibrosis patients, 733 hyperimmunoglobulin E syndrome, 676 lung transplantation recipients, 345, 352, 354 pyopneumothorax, 1048 pseudonodule, 120 pseudoplaque, Fleischner Society glossary definition, 168, 168

pulmonary agenesis, 1073, 1074 pulmonary alveolar microlithiasis, 679–680, 680 pulmonary alveolar proteinosis, 677–679, 678 bat’s wing airspace opacities, 98, 99 imaging findings, 678 infection complicating, 678–679 interlobular septum thickening, 171, 172 recurrence following lung transplantation, 364 pulmonary angiography, 46 arteriovenous malformations, 1081, 1083, 1084, 1085, 1086, 1086 complications, 405 fibrosing mediastinitis, 924, 926 pulmonary embolism, 405–407, 406 pulmonary hypertension, chronic thromboembolism, 419 pulmonary sequestration, 1095 Takayasu arteritis, 420 pulmonary aplasia, 1073, 1074, 1075 pulmonary arterial stenosis, 147 pulmonary arteries, 45, 46, 47, 64 diameter, 45 enlargement acute respiratory distress syndrome, 429 chronic thromboembolism, 418, 419 collagen vascular disease, 585 congenital systemic-to-pulmonary shunts, 415 mixed connective tissue disease, 604 polymyositis/dermatomyositis, 600 pulmonary arterial hypertension, 408, 408, 409, 409, 411, 412, 418, 419 scleroderma, 597 fat tissue at bifurcation (anatomic variant), 45, 50 high-resolution CT, 153 injury, 1134 pulmonary embolism, 392–393, 392, 393 sites, 385 unilateral absence, 1079, 1081, 1082, 1083 within lung parenchyma, 50, 51 measurements, 50–51 pulmonary artery aneurysm, 420, 420, 421 Behçet disease, 616 Hughes–Stovin syndrome, 617, 618 pulmonary aspiration syndromes, 491–496, 491 pulmonary blood flow redistribution Fleischner Society glossary definition, 168, 168 upper zone, pulmonary edema, 423, 424 pulmonary capillary hemangiomatosis, 413 pulmonary hypertension, 412 pulmonary collapse therapy, 238, 239 pulmonary contusion see contusion, lung parenchyma pulmonary dysmorphic abnormalities, classification, 1074 pulmonary edema, 85, 142, 423–427 acute inhalational injury smoke/fire injury, 488, 489 toxic fume inhalation, 489 acute respiratory distress syndrome see acute respiratory distress syndrome airspace opacities, 90, 91, 99 bat’s wing/butterfly pattern, 98, 99

Index alveolar, 426–427, 428 bronchial wall thickening, 424 cardiogenic, 423, 424, 425 differentiation from noncardiogenic, 432 resolution, 426, 427 causes, 423 hydrostatic, 423, 424 permeability, 423 CT angiogram sign, 91 drug-induced, 511, 512, 521, 530, 534, 538 heart transplantation patients, 342 hematopoietic stem cell transplantation patients, 336, 337–338 high-altitude, 434 hilar haze, 426, 426 hypereosinophilic syndrome, 675 interlobular septal thickening/septal lines, 138, 171, 172, 424, 425 lung parenchyma density increase, 426 microscopic polyangiitis, 613 neurogenic, 433, 434 pulmonary embolism, 386 radiographic signs, 424–426 raised pulmonary venous pressure, 423–424, 423 upper zone redistribution of blood flow, 423, 424 reexpansion, 435–436 pneumothorax treatment-related, 1049, 1049, 1050 subpleural edema, 424, 425, 426, 426 upper airway obstruction, 434–435 pulmonary embolism, 15, 147, 385–407 antiphospholipid syndrome, 595 chest radiography, 386–387, 387, 403 acute embolism with infarction, 387, 388 acute embolism without infarction, 386, 386, 387 Hampton hump, 387, 388 chronic/recurrent, secondary pulmonary hypertension, 417–419, 418, 419 CT pulmonary angiography, 24, 25, 387, 389–398, 389, 390, 391 acute embolism, 392–393, 392, 393 chronic/recurrent embolism, 393–394, 393, 394 technical aspects, 389–392 diagnosis, 386, 396–397, 399, 403 pregnant women, 397, 405 drug-induced, 518, 541 epidemiology, 385 magnetic resonance angiography, 30, 398–399, 398, 400 pathophysiologic consequences, 385–386, 386 pleural effusions, 387, 387, 1022 pulmonary angiography, 405–407, 406 pulmonary infarction, 385–386, 403 saddle emboli, 385 scintigraphy, 26, 399, 401–405, 402, 403 infarction-related ventilation defect, 399, 401 mismatched perfusion defect, 399, 401, 403 reversed V/Q mismatch, 399, 399 V/Q scan interpretation, 399, 403, 405 septic emboli, 222, 222 intravenous drug users, 532, 533

pulmonary eosinophilia see eosinophilia; eosinophilic lung disease pulmonary fibrosis see lung fibrosis pulmonary gangrene, 208, 209, 216 mucormycosis, 330 pulmonary hemorrhage airspace opacities, 91, 94, 98, 99, 99 CT halo sign, 97 aspergillosis, 326 drug-induced pulmonary vasculitis, 513 hematopoietic stem cell transplantation patients, 336, 338, 338 leukemia, 335, 848 systemic lupus erythematosus, 593, 593, 595 see also diffuse alveolar (pulmonary) hemorrhage pulmonary hila, 47, 48, 50 normal, 41, 45 pulmonary hypertension, 407–420, 916 chronic bronchitis, 755 chronic lung disease/hypoxemia, 416–417, 417 chronic thromboembolism, 417–419, 418, 419 classification, 407, 408 congenital systemic-to-pulmonary shunts, 414, 415, 416 CREST syndrome, 599 cystic fibrosis, 733, 738 drug-induced, 516 fenfluramine toxicity, 526 hematopoietic stem cell transplantation patients, 338 HIV/AIDS patients, 295, 319 idiopathic (primary), 410–411, 412 CT features, 412, 412 lung transplantation, 344 plexiform lesions, 411, 412 Langerhans cell histiocytosis, 453, 455, 456 left heart disease, 416 mixed connective tissue disease, 604 pulmonary artery atheroma, 410, 411 pulmonary capillary hemangiomatosis, 413 pulmonary embolism, 386 pulmonary microvasculopathy, 413 pulmonary vasculitides, 419 pulmonary venoocclusive disease, 414, 414 radiographic features, 408–410, 408, 409, 410 vessel dilatation, 411, 412 rheumatoid arthritis, 590–591 risk factors, 408 sarcoidosis, 657, 657 scleroderma, 596, 597, 598 sickle cell disease, 422, 423 systemic lupus erythematosus, 595 tumor embolism, 407 pulmonary hypoplasia, 1065, 1074–1078, 1076, 1077, 1078 accessory diaphragm association, 1107 associated conditions, 1076 bilateral, primary, 1074 congenital diaphragmatic hernia association, 1105 pneumothorax, 1074, 1075 secondary, 1075, 1078 unilateral, primary, 1074

pulmonary infarction airspace opacities, 91, 94 drug-induced pulmonary vasculitis, 513 Fleischner Society glossary definition, 161, 161 pleural effusion, 1004 pneumothorax, 1039–1040 pulmonary embolism, 385, 393, 394, 403 chest radiography, 387, 389 scintigraphic ventilation defect, 399, 401 round (target) infarction, angioinvasive fungal infection, 324, 326, 326 sickle cell disease, acute chest syndrome, 421, 422, 423 solitary pulmonary nodule, 122 pulmonary infiltration with eosinophilia, 659 see also eosinophilic lung disease pulmonary laceration, 1121, 1135 pulmonary ligament lymph nodes, 68 pulmonary ligaments, 59–60 pneumatocele, 1046 pulmonary light chain deposition disease, 699 pulmonary metastases see metastases pulmonary microvasculopathy, 413 pulmonary ossification see diffuse pulmonary ossification pulmonary renal syndromes, vasculitis, 608 pulmonary sequestration, 1065, 1093–1096, 1094 antenatal detection, 1096, 1097, 1100 arterial supply demonstration, 1096, 1098, 1099 bronchogenic cyst association, 1089, 1098 congenital cystic adenomatoid malformation association, 1098, 1099, 1100 differential diagnosis, 1098–1099 extralobular, 1093, 1095, 1096, 1097, 1098, 1099 imaging features, 1098 intralobular, 1093, 1095, 1096, 1096, 1097, 1098, 1098, 1099 intralobular/extralobular comparison, 1093, 1093 pulmonary stenosis, 1075 pulmonary varix, 1086–1087 pulmonary veins, 45, 46, 47 impedance of drainage, pulmonary hypertension, 416 within lung parenchyma, 50 measurements, 50–51 pulmonary venoocclusive disease, 413, 414 pulmonary arterial hypertension, 416 systemic lupus erythematosus, 595 pulmonary venous pressure elevation pulmonary edema, 423–424, 423 upper zone redistribution of blood flow, 423, 424 pulseless disease see Takayasu arteritis (Takayasu disease) punctate calcification, 100, 101 solitary pulmonary nodule, 121 pyopneumothorax, 1048 pyothorax-associated diffuse large B cell lymphoma, 845

Q fever, 208, 220, 221

1191

Index radiation dose CT, 12–14, 13, 19 high-resolution CT, 20, 193 digital subtraction angiography, 406 lung cancer screening, 821 measurement, 13, 13 technetium-99m perfusion scintigraphy, 27 radiation pleuritis, 1024 apical pleural thickening, 1035 radiation pneumonitis, 1024 radiation therapy, 541 ablation therapies, 552 related lesions, 552, 552, 553 bony thorax injury, 552 cardiac/mediastinal injury, 552 chylothorax, 1030 3D conformational/intensity-modulated techniques, 546–547, 549 determinants of injury to normal tissue, 542 esophageal injury, 552, 552 hematopoietic stem cell transplantation regimens, 336 lung injury, 338 hyperfractionated regimens, 541 lung cancer risk, 788 pleural effusion, 1024 pneumothorax complicating, 1039–1040 secondary organizing pneumonia, 578, 579 stereotactic body radiation, 541, 547, 549 total-body/half-body, 541 radiation-induced fibrosis, 88, 91, 92, 542–543 radiation-induced lung injury, 541–553 differential diagnosis, 550 imaging manifestations, 543–550, 543, 544, 545, 546, 547, 548 pneumonitis, 1024 acute, 542 pulmonary fibrosis (radiation-induced fibrosis), 88, 91, 92, 542–543 radiation-induced opacitis, 543–544, 543 syndromes, 542–543 radiation-induced malignancy (secondary primary tumors), 547, 550, 550 radiofrequency ablation therapy-related lesions, 552, 552, 553 radionuclide imaging, 26–27 bronchial atresia, 1070, 1071 bronchial carcinoid, 824, 826 bronchopleural fistula, 1051 emphysema, 763 evaluation for lung volume reduction surgery, 764 hepatopulmonary syndrome, 420 lung cancer, nodal metastases staging, 810–811, 810 neuroendocrine thymic tumors, 955 neurogenic tumors (mediastinum), 936 paraganglioma (mediastinum), 936 parathyroid glands, ectopic mediastinal, 938, 939 perfusion scanning see perfusion scintigraphy pulmonary alveolar microlithiasis, 680 pulmonary embolism, 399, 401–405 pulmonary metastases, 862 solitary pulmonary nodules, 128 splenosis, thoracic, 1037 sternal osteomyelitis, 922

1192

thymic epithelial neoplasia, pathologic correlations, 954 thymus, normal, 65 thyroid goiter, intrathoracic, 958–959, 960 ventilation scanning see ventilation scintigraphy rapamycin see sirolimus toxicity Rasmussen aneurysms, 420 Raynaud syndrome, 563 reactive lymph node hyperplasia, 904, 906 rebound thymic hyperplasia, 948–949, 949 recall pneumonitis, 542 recurrent laryngeal nerve palsy, 788 red cell aplasia, 884 reexpansion pulmonary edema, 435–436, 1049, 1049, 1050 rejection heart transplantation, 342 lung transplantation acute, 351–352, 351, 352, 353, 355 hyperacute, 347 relapsing polychondritis, 605–606, 606 renal cell carcinoma, 527 renal disease metastatic pulmonary calcification, 680–681, 681 pleural effusion, 1023 systemic lupus erythematosus, 595 Rendu–Osler–Weber disease (hereditary hemorrhagic telangiectasia), 1081, 1084, 1085 respiratory bronchiolitis, 451, 452, 452, 748–749, 749 respiratory bronchiolitis–interstitial lung disease (RB-ILD), 451–453, 452, 562, 562, 563, 749, 749, 750 Fleischner Society glossary definition, 168, 168 respiratory failure acute eosinophilic pneumonia, 661, 662 acute interstitial pneumonia, 579 tension pneumothorax, 1048 usual interstitial pneumonia, 564, 570 respiratory syncytial virus constrictive bronchiolitis, 741 pneumonia, 271, 273 hematopoietic stem cell transplantation patients, 337, 338, 339 lung transplantation patients, 357 reticular pattern, 139, 140 asbestosis, 477, 481 bronchopulmonary dysplasia, 537 cryptogenic organizing pneumonia, 577 Fleischner Society glossary definition, 168, 168 high-resolution CT, 171–175 lymphoid interstitial pneumonia, 581 mixed connective tissue disease, 604 morphologic subtypes, 171 nonspecific interstitial pneumonia, 574, 582 organizing pneumonia, 583 Pneumocystis jirovecii pneumonia, 304, 319 polymyositis/dermatomyositis, 601 pulmonary alveolar microlithiasis, 680, 680 pulmonary alveolar proteinosis, 678 silicosis, 463 usual interstitial pneumonia, 564, 565, 565, 566, 568, 571

reticulonodular pattern, 139–147 bleomycin toxicity, 524 cryptococcal pneumonia, 308 differential diagnosis, 141–142, 141 diffuse alveolar (pulmonary) hemorrhage, 621 drug-induced eosinophilic lung disease, 673 Fleischner Society glossary definition, 169, 169 hypersensitivity pneumonitis, 458 lymphangitis carcinomatosa, 862, 863 lymphoid interstitial pneumonia, 581 lymphoma, 841 polymyositis/dermatomyositis, 601 sarcoidosis, 648–650, 648, 649 scleroderma, 596 Sjögren syndrome, 603 usual interstitial pneumonia, 565 retinoic acid syndrome, 520 retrocrural space, 67, 68 retrosternal line, 75, 76 retrotracheal area, mediastinal contours on plain radiographs, 74–75, 75 reversed-halo sign cryptogenic organizing pneumonia, 575 Fleischner Society glossary definition, 169, 169 paracoccidioidomycosis, 259 rhabdomyosarcoma, 829, 832, 941 rheumatoid arthritis, 527, 529, 532, 537, 573, 578, 585–592, 602 AA amyloidosis, 694 airways disease, 590, 590 associated conditions, 591–592 Caplan syndrome, 590, 591 complications, 585 constrictive bronchiolitis, 742, 743, 744, 745 drug-induced lung injury, 591–592, 591 follicular bronchiolitis, 748 interstitial pneumonia/fibrosis, 588, 588, 589 lung disease, 142, 587 CT findings, 585, 586, 587 mixed connective tissue disease, 604 necrobiotic pulmonary nodules, 588–589, 589 pleural disease, 587, 587, 588 pleural effusion, 1004 pseudochylothorax, 1031 pulmonary arterial hypertension, 590–591 pulmonary drug toxicity, 591 pulmonary vasculopathy, 590–591 solitary pulmonary nodules, 131 rheumatoid factor, 563, 588 Rhizopus, 329 Rhodococcus equi infection HIV/AIDS patients, 297, 297 immunocompromised patients, 322 rib fracture, 1121, 1125, 1135, 1135, 1148, 1150–1151, 1151 child abuse, 1151 healing, dual-energy subtraction imaging, 5 multiple in alcoholic patients, 1151 pathologic, 1151 rib pseudoarthroses, 1151 Rickettsia pneumonia, 207, 220–221 Rickettsia rickettsii, 220

Index right-sided aortic arch, 16, 979, 980, 980, 981, 982 right-to-left shunt, pulmonary arteriovenous malformations, 1081, 1086 Rocky Mountain spotted fever, 220–221 round (target) infarction, angioinvasive fungal infection, 324, 326, 326 round/rounded atelectasis see atelectasis roundworm infestation, 276–277 rubeola (measles) virus, 274, 751

saber-sheath trachea, 715, 717, 717, 718 saddle emboli, 385 salicylate toxicity, 537–538, 591 salivary gland tumors, 833 sarcoid-like reaction, drug-induced, 514 sarcoidosis, 88, 89, 98, 142, 144, 145, 641–659 air bronchograms, 100 airspace opacities, 98, 100, 102 airways involvement, 653, 653 obstruction, 656–657, 748, 748 biochemical changes, 643 chylous pleural effusions, 1030 clinical features, 641–643 CT, 658–659 diagnosis, 643–644 differential diagnosis, 582 epidemiology, 457, 642 extrathoracic disease, 642, 644 18 F-fluorodeoxyglucose-positron emission tomography, 659, 660 gallium-67 scintigraphy, 659 granulomas, 643, 657, 658 small airways, 748, 748 high-resolution CT, 193 disease reversibility assessment, 196 imaging patterns, 644–648, 649 immunologic disorders, 643 interferon-induced, 514, 515 interlobular septal thickening, 171, 173 intrathoracic lymph node calcification, 647, 647 egg-shell pattern, 908, 909, 911 lung biopsy, 643 lung transplantation, 643 recurrence in transplanted lung, 364, 365, 643 mediastinal mass, 883 mediastinal/hilar lymphadenopathy, 644–646, 644, 645, 646, 904, 905, 909, 911, 915 mosaic attenuation pattern, 180 MRI, 659 multiple pulmonary nodules, 133, 134 mycetoma complicating, 658, 658 nodular pattern, 175, 176, 176 normal chest radiograph (stage 0), 644 parenchymal, 648–649 alveolar, 650–652, 652 cavitation, 653, 655 cystic change, 653, 655 ground-glass opacities, 650, 651 irreversible fibrotic changes, 652–653, 653, 654 reticulonodular opacities/nodules, 648, 648, 649, 650–651, 650, 651 reversible changes, 648–652 pathology, 641–643 peribronchial fibrosis, 187, 187

pleural disease, 658 pleural thickening, 1034 pneumothorax, 1048 prognosis, 196, 644 pulmonary hypertension, 412, 657, 657 pulmonary vascular involvement, 657 staging, 644 systemic vein involvement, 657–658 tracheal dilatation, 719 tuberculosis association, 642 vanishing lung syndrome, 767 sarcoma mediastinum, 941, 944 pleura, 857 pneumothorax, 1039 primary pulmonary, 829–830 trachea, 829 Sauropus androgynus, 518 scapulothoracic dissociation, 1153, 1153 Scedosporium angioinvasive, 324 lung transplantation patients, 357 Schistosoma, 278, 674 schistosomiasis, 278, 278, 674 schwannoma, 935, 936 mediastinum, 929, 931, 932, 933 scimitar syndrome (hypogenic lung/ venolobular syndrome), 1073, 1074, 1078–1079, 1078, 1079, 1080 associated accessory diaphragm, 1107 scleroderma (systemic sclerosis), 142, 143, 585, 596–599, 602 associated malignant disease, 597–598 autoantibodies, 596 clinical features, 596 high-resolution CT, 193 imaging findings, 596–597, 597, 598 interstitial pneumonia, 563 lung disease progression, 599 mediastinal lymphadenopathy, 906 mixed connective tissue disease, 604 nonspecific interstitial pneumonia, 573 overlap syndrome, 599 pulmonary fibrosis, 596, 597, 598 silica exposure-related risk, 468 thoracic findings, 596, 596 see also CREST syndrome scleroma, tracheal narrowing, 717–718 sclerosing hemangioma, 834, 834 sclerosing mediastinitis see fibrosing mediastinitis secondary organizing pneumonia, 577–578, 579 causes, 578, 578 segment, Fleischner Society glossary definition, 169 seminoma, 898 mediastinum, 902–903, 902 sepiolite, 472 septal lines, 136–137, 142 causes, 137 deep (Kerley A), 136, 139 interlobular (Kerley B), 51, 52, 98, 136, 138, 139, 153 pulmonary edema, 424, 425 septic complications, intravenous drug users, 532 septic pulmonary emboli, 222, 222 HIV/AIDS patients, 298, 298, 319 intravenous drug users, 532, 533

Serratia marcescens pneumonia, 214 severe acute respiratory syndrome coronavirus, 274, 274, 275, 276 severe combined immune deficiency, pulmonary alveolar proteinosis, 677 Shaver disease, 483 sicca syndrome see Sjögren syndrome sickle cell disease, 180, 207, 421–423, 423, 927, 1158 acute chest syndrome, 421, 422 cardiomegaly, 422 extramedullary hematopoiesis, 897, 899 pulmonary hypertension, 422, 423 siderosilicosis, 484, 485 siderosis/arc-welder’s lung, 482–483, 483 signet ring sign bronchiectasis, 728, 729 cystic fibrosis, 728 Fleischner Society glossary definition, 169–170, 170 silhouette sign, 83–85, 86 Fleischner Society glossary definition, 169–170, 170 localization of radiographic density, 83, 84, 85 low opacity lesions detection, 83, 84 silica exposure, 462, 462 chronic bronchitis, 468 chronic interstitial pneumonia, 468 lung cancer, 467–468 mycobacterial infection, 468 scleroderma, 468 silicoproteinosis, 463, 466, 467 imaging features, 466–467 silicosis, 142, 143, 462–468, 484, 740, 883 accelerated, 463, 466 acute (silicoproteinosis), 463, 466 granulomatous response, 463 intrathoracic lymph node calcification (egg-shell calcification), 908, 909 miliary tuberculosis complicating, 236, 237 multiple pulmonary nodules, 133 nodular pattern, 176, 176 nodules, 463, 463 occupational risk, 462–463 sandblasters, 466 pathogenesis/pathology, 463 physiologic impairment, 463–464 pleural abnormalities, 468 progressive massive fibrosis, 464–466, 464, 465, 467, 468 lung cancer differential diagnosis, 465 scleroderma (Erasmus syndrome), 596 simple, 463–464, 463, 465 silo-filler’s lung, 489, 491, 742 simple eosinophilic pneumonia (Löffler syndrome), 614, 615, 660, 662–663 worm infestations, 674 single photon emission CT (SPECT) emphysema, 763 parathyroid glands, ectopic mediastinal, 938 radiation-induced lung injury, 544 solitary pulmonary nodules, 128 sirolimus toxicity, 514, 538, 539, 540, 677 situs ambiguous, 41 situs inversus, 41

1193

Index Sjögren syndrome, 183, 602–603, 603, 743, 842 amyloidosis, 694, 696, 698 collagen vascular disease, 602 European classification criteria, 602, 602 follicular bronchiolitis, 748 lymphoid interstitial pneumonia, 580, 581 lymphoproliferative disease, 602 pleuropulmonary manifestations, 602–603, 603 skinfold, simulating pneumothorax, 1043, 1043 SLC34A2 gene mutations, 679 sleep apnea alveolar hypoventilation, 417 pulmonary edema, 434 slot-scan technology, 4 small airways disease, 740–752 classification, 740, 741 CT, 22 high-resolution CT, 189–192 Fleischner Society glossary definition, 170 radiographic patterns, 740 mosaic attenuation, 180, 190 tree-in-bud, 190 rheumatoid arthritis, 590 sarcoidosis, 656 small cell carcinoma of thymus, 955 small cell lung cancer, 539, 569, 787–788, 789 calcification, 791 imaging features, 793 staging, 797 treatment, 800 smoke, acute inhalational injury, 488, 488 smoking acute eosinophilic pneumonia, 660 associated lung diseases, 451–457, 452, 456 in nonsmokers exposed to second-hand smoke, 451 asthma, 752, 754 chronic bronchitis, 754–755 emphysema, 756, 757, 763 lung cancer, 788 lung fibrosis, 563 respiratory bronchiolitis, 451–453, 748 respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), 451–453, 749 squamous cell carcinoma of trachea, 829 smoothing algorithms, CT, 11 soap-bubble destruction pattern, 183 solitary pulmonary nodule, 119–132, 122, 123 adjacent bone destruction, 131 air bronchograms, 130 air crescent sign, 130–131 bronchial carcinoid, 823 bronchioloalveolar carcinoma, 814, 815 bubblelike lucencies, 130 calcification, 121, 126, 132 cloudlike, 121 concentric (laminated), 121, 123 popcorn, 121, 124 punctate, 121 uniform, 121, 124 cavities, 130–131 contrast enhancement, 127–128, 128 CT halo sign, 131 differential diagnosis, 119–120, 121 fat density, 126, 127 ground-glass opacity, 126–127, 127

1194

growth rate, 128–129 lung cancer, 789 management, 131–132 shape, 130 size, 129–130 ‘tail’ sign, 130 somatostatin receptor scintigraphy antineutrophilic cytoplasmic antibodyassociated vasculitis, 613 bronchial carcinoid, 824, 826 neuroendocrine thymic tumors, 955 paraganglioma (mediastinum), 938 thymic epithelial neoplasia, pathologic correlations, 954 Spanish toxic oil syndrome, 516 spherical (round/nodular) pneumonia, 205, 206, 208, 208, 210 spinocerebellar ataxia, 1042 splenic disease, pleural effusion, 1023 splenosis, thoracic, 1037, 1037 Sporothrix schenckii, 269 sporotrichosis, 269, 270 squamous cell carcinoma, 522, 569, 787, 788, 790 imaging features, 793, 793, 794, 795 trachea, 829, 831 squamous papilloma, 829, 834, 835 stab wounds, 1153 stannosis, 143, 483, 484 Staphylococcus aureus cystic fibrosis infections, 733 empyema, 223 pneumonia, 87, 91, 97, 207, 208, 210, 212–213, 273, 274 hyperimmunoglobulin E syndrome, 676 imaging features, 213 immunocompromised patients, 321 lung transplantation patients, 352, 353 pyopneumothorax, 1048 statins, pulmonary toxicity, 538–539 Stenotrophomonas maltophila, 733 stereotactic body radiation, lung injury, 547, 549 sternal dehiscence, acute mediastinitis, 922, 925 sternal fracture, 1151–1152, 1152 sternal osteomyelitis, 922 sternoclavicular joint dislocation, 1152, 1152 storage diseases, 691–692, 692 strangulation, pulmonary edema, 434 Streptococcus pneumoniae empyema, 223 pneumonia, 97, 207, 208, 208, 210–211, 211, 212, 273, 274 HIV/AIDS patients, 296, 297 imaging features, 211 immunocompromised patients, 321 sickle cell disease, acute chest syndrome, 421 Streptococcus pyogenes pneumonia, 207, 210, 211–212, 274 stress fracture of rib, 1151 stripe sign, pulmonary embolism, 403 Strongyloides stercoralis, 276, 277, 332, 674, 674 hyperinfection syndrome, 333, 334 subaortic (aortopulmonary window) lymph nodes, 68 subarachnoid hemorrhage, 433, 434 subcarinal lymph nodes, 68 subcarinal space, 65, 67

subclavian artery, 61 aberrant, 61, 980, 981 subclavian artery injury, 1132 subglottis edema, smoke/fire injury, 488 subphrenic abscess, 1020 subpleural curvilinear line, Fleischner Society glossary definition, 170, 170 subpleural edema, 424, 425, 426, 426 subpleural lines curvilinear, 174–175, 175 usual interstitial pneumonia, 565 subpleural lymphatic vessels, 51 subpulmonic pneumothorax, 1046 sulfasalazine toxicity, 509, 690 hypersensitivity reactions, 509 sulfonamide hypersensitivity, 673 sulfur mustard gas inhalation injury, 490 summer-type hypersensitivity pneumonitis, 457 superior accessory fissure, 58–59, 59 superior intercostal vein, 70, 70, 71 superior pericardial recess, 66, 66 superior sulcus tumors see Pancoast tumors superior vena cava, 61 persistent left, 61, 64, 918 superior vena cava syndrome, 941–942, 944, 945 causes, 941 chylothorax, 1027, 1030, 1031 pleural effusion, 1021–1022 supernumerary bronchi, 41 surface shaded display, CT, 14, 15, 16 surfactant deficiency, 581–582 pulmonary alveolar proteinosis, 677 surfactant protein B (SFTPB) deficiency, 581, 582 surfactant protein C (SFTPC) deficiency, 581, 582, 582 Swyer–James (McLeod) syndrome, 147, 147, 274, 426, 742, 750–752, 750, 1065, 1079 bronchiectasis, 732 imaging features, 751–752, 751 synovial sarcoma, 941, 944 syphilis, 219, 979 systemic lupus erythematosus, 573, 592–596, 602 acute lupus pneumonia, 592–593, 593 antiphospholipid syndrome, 595, 595 autoantibodies, 592 clinical features, 592, 592 diaphragm dysfunction (‘shrinking lungs’), 594–595 drug-induced, 512–513, 513, 519 lung fibrosis, 594, 594 lupus anticoagulant, 595 mixed connective tissue disease, 604 pleuritis/pleural effusion, 519, 592, 593 pulmonary artery hypertension/vasculitis, 595 pulmonary hemorrhage, 593, 593, 595 thoracic manifestations, 592–596, 592 systemic sclerosis see scleroderma systemic urticarial vasculitis, 616

T cell leukemia, 848, 849 T cell lymphoma, 843 thymic enlargement, 839 Taenia saginata, 674

Index tail sign, 130 Takayasu arteritis (Takayasu disease), 419–420, 420, 608, 979 pulmonary arterial hypertension, 420 talc, 756 granulomatosis, 514, 642 pneumoconiosis, 482 talc pleurodesis, 1035, 1036 taxanes, lung toxicity, 509, 539 Technegas aerosol ventilation scanning, 29 technetium-99m diethylenetriaminepentaacetic acid aerosol ventilation scan, 28, 29 excretion in breast milk, 29 perfusion scanning, 26–27, 28 radiation dose, 27 telomerase deficiency, 581 temporal subtraction imaging, 4, 5–6, 7 temsirolimus, 538 tension hydrothorax intrauterine, 1096 torsion of extralobular pulmonary sequestration, 1096 tension pneumomediastinum, 939 tension pneumothorax, 1048–1049, 1049 teratoma, 883, 884, 898, 899–902 benign intrapulmonary, 834, 834 immature, 899, 902 with additional malignant components, 899, 900, 902, 902 malignant, 831, 899–900 mature, 883, 884, 898, 899, 900, 901 rupture, 900–901 terbutaline, drug-induced pulmonary edema, 511 testicular malignancy, 522 thalassemia, extramedullary hematopoiesis, 897, 899 thalidomide bleomycin toxicity attenuation, 524 toxicity, 509, 518 thermal injury, acute inhalational injury, 488, 489 thin-film transistors, 4 thoracic cage injuries, 1148, 1150–1153 thoracic duct, 75, 1027 obstruction, 1027 thoracic duct atresia, 1030 thoracic duct cyst, 886, 890, 891 thoracic duct injury, 1140, 1140, 1141, 1142 thoracic goiter, 882, 883 thoracic splenosis, 1037, 1037 thorn sign, pleural effusions, 1006 thymic carcinoid, 955 thymic carcinoma, 942, 949, 950, 953, 953, 954 thymic cysts, 886, 950, 955–956, 956, 957 acquired, 956 congenital, 955–956, 956 thymic enlargement benign, 883 causes, 944 thymic epithelial neoplasia, 942, 949 classification, 949–950, 949, 950 imaging features, 949 pathologic correlation, 953–954, 953 thymic hyperplasia, 947–949 lymphofollicular, 947–948, 948 rebound, 839, 948–949, 949 thymic lesions, 884, 942, 947–956 thymic lymphoma, 839, 954, 954

thymic neoplasms, 882 thymic neuroendocrine tumors, 955, 955 thymolipoma, 883, 942, 955, 955 thymoma, 833, 883, 884, 942, 949, 950, 951, 952, 953, 954, 954 invasive, 950, 952, 953, 954 paraneoplastic syndromes, 949 staging classification, 949 thymus, 64–65, 65 children, 64, 65 normal, 942, 946, 947, 947 post-lymphoma treatment cystic degeneration, 839 ‘rebound’ response to chemotherapy, 64 thyroid adenoma, 958 thyroid carcinoma, 958, 959 thyroid gland (normal), 956–957, 957 thyroid lesions, intrathoracic, 956–959 imaging features, 957 thyroid mass, 884, 885–886 thyroid tumors, 882 thyrotoxicosis, thymic hyperplasia, 947, 948 TNM classification, lung cancer, 799, 800 topoisomerase inhibitors, lung toxicity, 539 topotecan, lung toxicity, 509, 539 torsion of lung/lobe, 1153–1154, 1154, 1157 radiographic findings, 1154, 1156 Torula histolytica, 254 torulosis see cryptococcosis toxic fumes inhalation, 756 acute inhalational injury, 489, 490 constrictive bronchiolitis, 742 toxic oil syndrome, 411 Toxocara canis (visceral larva migrans), 277, 277, 674 Toxocara cati, 277, 674 toxoplasmosis (Toxoplasma gondii), HIV/AIDS patients, 296, 311 trachea, 42 cartilage rings, 39 diameter, 39 mediastinal contours on plain radiographs (lateral view), 74–75, 75 normal, 39 tracheal adenoid cystic tumor, 716 tracheal bronchus (bronchus suis), 41, 45, 1067 tracheal cryptogenic stenosis, 717, 717, 719 tracheal disorders, 715–719 tracheal displacement, aortic injury, 1125 tracheal diverticula, 1079 tracheal filling defects, 723–724 causes, 724 tracheal narrowing, 715–719, 1065 causes, 716 sarcoidosis, 656, 656 Wegener granulomatosis, 611–612, 612 tracheal neoplasms, 829 tracheal papilloma, 724 tracheal rupture, 1121, 1137, 1138, 1140 tracheal widening, 719, 719 tracheobronchial amyloidosis, 696, 696, 697 tracheobronchial papillomatosis, 834 cystic airspaces, 183 tracheobronchitis, beryllium-related, 485 tracheobronchomalacia (dynamic airway collapse), relapsing polychondritis, 605 tracheobronchomegaly (Mounier–Kuhn syndrome), 183, 184, 720–721, 720, 721, 722

tracheocele, 721 tracheoesophageal fistula, 724, 725, 1065, 1069, 1073 causes, 724 tracheomalacia, 722–723, 722, 723 causes, 722 primary/secondary, 723 tracheopathia osteoplastica, 718–719, 719, 720 traction bronchiectasis, 173, 174, 187 asbestosis, 477, 481, 482 Fleischner Society glossary definition, 170, 170 nonspecific interstitial pneumonia, 573, 574, 582 organizing pneumonia, 583 polymyositis/dermatomyositis, 601 sarcoidosis, 653 scleroderma, 596, 597 usual interstitial pneumonia, 565, 568 tramline opacities, chronic bronchitis, 755 transfusion reactions, 335, 335 transfusion-related acute lung injury, 511 transplant graft vasculopathy, 343 trapped lung, pleural effusions, 1026–1027 trastuzumab toxicity, 532, 532 trauma, 1121–1160 aorta see aortic injury, blunt aortic pseudoaneurysm, 962, 963, 965 central airways, 1137–1139, 1138 chest radiography, 1121 chylothorax, 1027, 1029 CT, 1121 diaphragm see diaphragmatic injury/ rupture esophagus, 921, 922, 923, 1121, 1140, 1141 heart, 1148, 1150 indirect effects on lungs, 1156 lung parenchyma, 1134–1137, 1134 pericardium, 1148 pneumomediastinum, 940 thoracic cage, 1148, 1150–1153 thoracic duct, 1140, 1140, 1141, 1142 tree-in-bud pattern, 91, 153, 154 allergic bronchopulmonary aspergillosis, 670 bronchiectasis, 730, 730 cystic fibrosis, 736 diffuse (Japanese) panbronchiolitis, 22, 746, 747 exudative bronchiolitis, 192, 192 Fleischner Society glossary definition, 170, 170 small airways disease, 190, 740 tumor microemboli, 407, 407 tremolite, 471 see also asbestos-related disease Treponema pallidum, 219 Trichosporon asahii (cutaneum), 457 Trichosporon, hypersensitivity pneumonitis, 457 Trichuris trichiura, 674 tricyclic antidepressants, lung toxicity, 541 trimellitic anhydride toxicity, 621 trimethadione hypersensitivity, 673 trimipramine hypersensitivity, 673 trophoblastic tumors, 529 tropical pulmonary eosinophilia, 673 TSC1/2 gene mutations, 684, 685 tuberculin reaction, 229

1195

Index tuberculomas, 235, 236, 240 primary tuberculosis, 230 reactivation (postprimary) tuberculosis, 229 tuberculosis, 103, 228–241, 228, 740 airspace opacities, 90, 91, 92 assessment of activity, 238, 241 bronchiectasis, 732 broncholithiasis, 235, 236, 240 calcified solitary pulmonary nodule, 123, 124 CT, 230, 235, 237, 238–241, 240, 241 empyema, 223, 226, 237, 238 endobronchial, 235, 235 epidemiology, 228 extrathoracic, 229 focal scar carcinomas, 788 HIV/AIDS patients, 295, 296, 298–299, 299, 300, 301, 319 immunocompromised patients, 322 inflammatory response to infection, 228–229 intrathoracic complications, 240, 241 intrathoracic lymph node calcification, 908 lung transplantation patients, 359 mediastinal lymphadenopathy, 904, 905, 909, 911 miliary, 210, 210, 230, 232, 235–236, 237 multidrug-resistant, 298 multiple pulmonary nodules, 133 nodular opacities, 139, 142, 143, 144, 176 pleural calcification, 1036, 1037 pleural effusion, 1004, 1005, 1006 chylous, 1030 pleural thickening, 1032 apical, 1035 pleuritis, 236–237, 238, 238 pneumonia, 92, 97 pneumothorax, 1044, 1046 primary, 229–231, 230, 231, 232 Ghon focus, 229 progressive, 229 pseudochylothorax, 1031 pulmonary collapse therapy, 238, 239 radiographic appearances, 229–237 Rasmussen aneurysms, 420 reactivation (postprimary), 229, 231–233, 232, 233, 520 fibrous contraction, 233, 234 focal pulmonary disease, 231–233 lobar pneumonia/bronchopneumonia, 233–235 morphologic features, 229 sarcoidosis association, 642 silicosis-related risk, 468 smoking-related risk, 455 solitary pulmonary nodule, 131 calcification, 121 tracheal, 717, 717, 719 tracheal dilatation, 719, 720 tubercles, 229 caseous necrosis, 229, 231 tuberculoma formation, 235, 236, 240 tuberous sclerosis, 420, 684–685, 684, 1030 angiomyolipomas, 686 genetic factors, 684 lymphangioleiomyomatosis, 684 pulmonary involvement, 684, 685 tularemia, 218, 904 tumor embolism, 407, 407

1196

Turner syndrome, 967 tyrosine kinase inhibitors, lung toxicity, 541

ulcerative colitis, pulmonary complications, 688, 689, 690, 690 ultrasonography, 1 antenatal see antenatal diagnosis anterior (Morgagni) hernia, 1107 aortic injury, 1131–1132, 1132 bronchogenic cyst, 1092, 1093 congenital cystic adenomatoid malformation, 1097, 1100, 1103 congenital diaphragmatic hernia, 1106 diaphragmatic injury/rupture, 1147 empyema, 1017 fetal chest masses, 1097, 1098 hepatic abscess, 1020 intravascular, transplant graft vasculopathy, 343 lung cancer, 801 liver metastases, 813 nodal metastases staging, 811 lymphangioma (cystic hygroma), 1087 malignant pleural effusion, 864 mediastinal disease, 882 neurenteric cysts, 889 pericardial cysts, 888, 888 pleural effusions, 1007, 1010 hemidiaphragm inversion, 1008, 1010 pulmonary embolism, 387 subpulmonic, 1008 pleural fluid imaging, 1017, 1018, 1019 pleural thickening, 1032 pneumothorax, 1046 pulmonary hypoplasia, 1078 pulmonary sequestration, 1095, 1097, 1098 reverberation artifacts, 1046 round/rounded atelectasis, 119 asbestos-related, 476 subphrenic abscess, 1020 thymus, 65 uniform calcification, solitary pulmonary nodule, 121, 124 unilateral absence of pulmonary artery, 1079, 1081, 1082, 1083 unilateral increased transradiancy of lung, 147 Swyer–James syndrome, 750, 751, 751 upper airway surgery, pulmonary edema, 434 upper triangle sign, 111, 115 uremic pleurisy, 1023 urinary tract infection, 534 urinothorax, 1023 usual interstitial pneumonia, 174, 562, 562, 563, 564–572 acute exacerbation, 570–572, 571, 572 causes, 564, 564 clinical features, 564 complications, 569, 569, 570, 571 cystic airspaces (end-stage disease), 183, 184, 186 diagnosis, 566, 568 ATS criteria, 566 CT, 563, 582 lung biopsy, 568 drug-induced, 508 epidemiology, 564

familial lung fibrosis, 581 Fleischner Society glossary definition, 161, 161, 171, 171 high-resolution CT, 193, 195 histology, 564, 564 imaging appearances, 564–569, 566, 567, 568, 569, 584 lung transplantation, 344 morphologic pattern, 563, 564 pathogenesis, 564 prognosis, 584 pulmonary hypertension, 417, 417 reticular pattern, 172, 173, 174 rheumatoid arthritis, 588, 589 sequential changes, 568–569 silica exposure-related, 468, 468 smoking-related risk, 456 systemic lupus erythematosus, 594, 594 upper lobe, 584 V/Q scan mismatched perfusion defect, 403, 405

VACTEL complex, 1065, 1073 vagus nerve, 75 vagus nerve tumor, 929 valley fever, 258 vanishing lung syndrome (idiopathic giant bullous disease), 767 varicella-zoster virus, 90, 143, 145, 615 HIV/AIDS patients, 312 disseminated herpes zoster, 296 pneumonia, 275–276, 276, 332, 333 smoking-related risk, 455 vascular endothelial growth factor, lung cancer expression, 794 vasculitis, 608–618 antineutrophilic cytoplasmic antibodyassociated, 608, 608, 609–615 classification, 608, 608 drug-induced, 513, 513 granulomatosis, 514 immune-complex, 615–616 malignant disease association, 616 medium vessel, 608 pulmonary arterial hypertension, 419 rheumatoid arthritis, 590 small vessel, 608 systemic lupus erythematosus, 595 systemic urticarial, 616 VATER complex, 1065 venography fibrosing mediastinitis, 924 superior vena cava syndrome, 942 venolobular syndrome see scimitar syndrome venoocclusive disease, diffuse alveolar hemorrhage, 619 venous thrombosis, antiphospholipid syndrome, 595 ventilation scintigraphy, 27–28 aerosol ventilation imaging, 28, 29 MRI, 32 radionuclide imaging, 27–28 ventilation–perfusion mismatch causes, 403, 405 central airways injury, 1138 ventilation/perfusion (V/Q) scan bronchial atresia, 1070, 1071 chronic thromboembolism, secondary pulmonary hypertension, 419

Index emphysema, 763 fat embolism, 1160, 1160 fibrosing mediastinitis, 924, 928 lung transplantation recipient screening, 347 perfusion scan see perfusion scintigraphy in pregnancy, 29 pulmonary embolism, 26, 397, 399, 401–405, 402, 403 interpretation, 399, 403, 405 reversed mismatch, 399, 399 tumor embolism, 407 ventilation scan, 27–29, 32 ventricular septal defect, Eisenmenger reaction, 415 vertebral body anomalies, neurenteric cyst association, 889 vertebral fracture, 1153, 1154 vertebroplasty, pulmonary cement embolism, 518 vinblastine, mitomycin toxicity potentiation, 531 vincristine toxicity, radiation therapy K-potentiation (recall pneumonitis), 542 vindesine, mitomycin toxicity potentiation, 531 vinorelbine toxicity, 526 viral infection chronic bronchitis acute exacerbations, 755 constrictive bronchiolitis, 741, 742, 742 immunocompromised patients, 331–332

pneumonia, 142, 143, 206, 207, 209, 210, 270–276, 272 hematopoietic stem cell transplantation patients, 337, 338–339 HIV/AIDS patients, 312 lung transplantation patients, 357 sickle cell disease, acute chest syndrome, 421 Swyer–James (McLeod) syndrome, 751 virtual bronchoscopy, 14–15 visceral larva migrans (Toxocara canis), 277, 277, 674 volumetric image reconstruction, 763 volume rendering, 14, 15 von Recklinghausen disease see neurofibromatosis type I

Waardenburg anophthalmia syndrome, 679 wandering wire sign, sternal dehiscence, 922, 925 water lily sign, 280 Weber–Christian disease, 924 Wegener granulomatosis, 98, 525, 608, 609–613, 717 antineutrophilic cytoplasmic antibodies, 609 clinicopathologic features, 609 diffuse pulmonary hemorrhage, 620 imaging findings, 609–613, 610, 611, 612 lung biopsy, 609 multiple pulmonary nodules, 133 pleural thickening, 1034

solitary pulmonary nodules, 130, 131 tracheal stenosis, 611–612, 612 Weil disease see leptospirosis Westermark sign, 386, 386 Whipple disease, 909 white blood imaging, aortic dissection, 974 whooping cough see pertussis Williams–Campbell syndrome (congenital bronchiectasis), 1068, 1069 Wilms tumor, 1039 Wilson disease, 537 window settings, CT pulmonary angiography, 391 worm infestations eosinophilic lung disease, 674, 674 tropical pulmonary eosinophilia, 673 Wuchereria bancrofti, 278, 673

xanthogranuloma, 835, 836 xanthoma, 835, 836 xenon-133 (Xe-133) ventilation scanning, 27, 28

yellow nail syndrome, 1088, 1090 pleural effusion, 1026, 1026 Yersinia, 615 Yersinia (Pasteurella) pestis, 218 Young syndrome, 740

zygomycosis see mucormycosis

1197