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(BQ) Part 1 book “High-Resolution CT of the lung” has contents: Normal lung anatomy, technical aspects of high-resolution CT, diffuse pulmonary neoplasms and pulmonary lymphoproliferative diseases, pneumoconiosis, occupational, and environmental lung disease, miscellaneous infiltrative lung diseases, cystic lung diseases,… and other contents.
High-Resolution CT of the Lung #152201 Cust: LWW Au: Webb Pg No i DESIGN SERVICES OF #152201 Cust: LWW Au: Webb Pg No ii DESIGN SERVICES OF High-Resolution CT of the Lung FIFTH EDITION W Richard Webb, MD Professor Emeritus of Radiology and Biomedical Imaging Emeritus Member, Haile Debas Academy of Medical Educators University of California San Francisco San Francisco, California Nestor L Müller, MD, PhD Professor Emeritus of Radiology Department of Radiology, University of British Columbia Vancouver, British Columbia, Canada David P Naidich, MD, FACR, FAACP Professor of Radiology and Medicine New York University Langone Medical Center New York, New York #152201 Cust: LWW Au: Webb Pg No iii DESIGN SERVICES OF Senior Executive Editor: Jonathan W Pine, Jr Acquisitions Editor: Ryan Shaw Product Development Editor: Amy G Dinkel Production Project Manager: David Orzechowski Senior Manufacturing Coordinator: Beth Welsh Marketing Manager: Dan Dressler Senior Designer: Joan Wendt Production Service: S4Carlisle Publishing Services Copyright © 2015 Wolters Kluwer Health Two Commerce Square 2001 Market Street Philadelphia, PA 19103 USA LWW.com 4th edition © 2009 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business All rights reserved This book is protected by copyright No part of this book may be reproduced in any form by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright Printed in China Library of Congress Cataloging-in-Publication Data Webb, W Richard (Wayne Richard), 1945- author High-resolution CT of the lung / W Richard Webb, Nestor L Müller, David P Naidich — Fifth edition p ; cm Includes bibliographical references and index ISBN 978-1-4511-7601-8 (alk paper) I Müller, Nestor Luiz, 1948- , author II Naidich, David P., author III Title [DNLM: 1. Lung—radiography. 2. Tomography, X-Ray Computed. 3. Lung Diseases—pathology WF 600] RC734.T64 616.2’407572—dc23 2014003388 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of the information in a particular situation remains the professional responsibility of the practitioner The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new or infrequently employed drug Some drugs and medical devices presented in the publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings It is the responsibility of the health care providers to ascertain the FDA status of each drug or device planned for use in their clinical practice To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320 International customers should call (301) 223-2300 Visit Lippincott Williams & Wilkins on the Internet: at LWW.com Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to pm, EST 10 #152201 Cust: LWW Au: Webb Pg No iv DESIGN SERVICES OF DEDICATION To my father, who encouraged my curiosity and taught me to figure things out ––WRW To my wife, Isabela, and my children—Alison, Phillip, and Noah Müller ––NLM To Jocelyn, whose constant love and support has always been my greatest inspiration ––DPN #152201 Cust: LWW Au: Webb Pg No v DESIGN SERVICES OF #152201 Cust: LWW Au: Webb Pg No vi DESIGN SERVICES OF Contributing Authors Brett M Elicker, MD Associate Professor of Clinical Radiology and Biomedical Imaging Chief, Cardiac and Pulmonary Imaging University of California San Francisco San Francisco, California Myrna C B Godoy, MD, PhD Assistant Professor of Radiology University of Texas MD Anderson Cancer Center Houston, Texas C Isabela S Müller, MD, PhD Department of Radiology Delfin Clinic Salvador, Bahia, Brazil vii #152201 Cust: LWW Au: Webb Pg No vii DESIGN SERVICES OF #152201 Cust: LWW Au: Webb Pg No viii DESIGN SERVICES OF Preface During the past 25 years, high-resolution CT (HRCT) has become established as an indispensable tool in the evaluation of patients with diffuse lung disease HRCT is now commonly used in clinical practice to detect and characterize a variety of lung abnormalities In the approximately years since our fourth edition was published, considerable progress has taken place in the understanding of diffuse lung diseases and the recognition of new entities and their nature, causes, and characteristics Without doubt, HRCT has played a fundamental role in contributing to this progress and has become essential to the diagnosis of a number of diffuse diseases This fifth edition continues what the three of us, independently, in conjunction, and with each other’s encouragement and support, began some 30 years ago The photograph of the three of us below was taken by a local resident at the 1989 Diagnostic Course in Davos, on a walk we took on the promenade above the Sweitzerhof on the day of our arrival, when as junior faculty, we were more than a little anxious about teaching along with such important and impressive chest radiologists as Fraser, Felson, Greenspan, Milne, Flowers, Heitzman, and many others At this meeting, we each spoke about the use of HRCT, which, at the time, was a little-known technique that was regarded with skepticism by many radiologists We learned from each other as we spoke, compared slides in the speaker-ready room, and gained confidence from our shared opinions At this meeting, we began thinking about a collaboration that would combine our experience and thoughts about this new modality and its potential uses Our first edition of this book was published in late 1991, with a grand total of 159 pages It was a quarter of an inch thick, and, to our knowledge, referenced every known paper on HRCT From our perspective, it was the most important thing we had ever done That is how things start Maybe that is the best way things should start It was certainly fun and rewarding for each of us And we three have stuck together over the years, out of our combined respect, admiration, friendship, and good humor Each one of us believes that we learned more from our collaboration than we taught In this edition, we have incorporated an update and review of numerous recent advances in the classification and understanding of diffuse lung diseases and their HRCT features Recent technical modifications in obtaining HRCT have also been reviewed, most notably the use of helical HRCT and dose-reduction techniques We hope the reader will find these changes and updates helpful As is our wont, we have reorganized our discussions into new sections and chapters, which we feel best presents the most important topics in HRCT diagnosis for reference and learning A new section has been added at the end of the book to provide a general review of HRCT, including an illustrated glossary of HRCT terms and a chapter providing a compilation of the common and typical appearances of the most common diffuse lung diseases encountered in clinical practice These sections are intended to provide an illustrated index to the detailed descriptions of diseases found elsewhere in the book It is with a great deal of pride that we complete our fifth edition of this book, which has occupied so much of our thoughts, efforts, and time over the years This task is accomplished in the hope that this book will encourage future generations of thoracic imagers to develop mutually productive relationships with friends and colleagues, in order to explore important questions in our understanding of the role of imaging in the assessment of thoracic disease To this end, we acknowledge the contributions of three esteemed colleagues, our former fellows, who have authored parts of this book Their efforts have greatly inspired our own enthusiasm for the considerable task of bringing this edition to fruition W Richard Webb Nestor L Müller David P Naidich ix #152201 Cust: LWW Au: Webb Pg No ix DESIGN SERVICES OF C hapter 11 Diffuse Pulmonary Neoplasms and Pulmonary Lymphoproliferative Diseases FIGU RE 11-22 Focal lymphoid hyperplasia, biopsy proven CT in a patient with Sjögren syndrome shows multiple nodular opacities containing air bronchograms of a mixture of polyclonal lymphocytes, plasma cells, and histiocytes (74) The term focal lymphoid h yperplasia is used by some authors as synonymous with pseudolymphoma (72,74) It is likely, however, that many lesions previously called pseudolymphomas would currently be classified as MALTomas (73,79); therefore, the term pseudolymphoma is not currently recommended The most frequent radiologic manifestation of focal lymphoid hyperplasia consists of a solitary nodule or a focal area of consolidation (72,80) The nodules or nodular areas of consolidation usually measure to cm in diameter and contain air bronchograms (80) Multiple nodules or regions of consolidation may be seen (Fig 11-22) (81) There is no associated lymphadenopathy Follicular Bronchiolitis Follicular bronchiolitis, defined as hyperplasia of BALT, is characterized histologically by the presence of diffuse proliferation of lymphoid follicles with reactive germinal centers in the interstitial tissue adjacent to bronchioles and bronchi (73,76,82) Follicular bronchiolitis is commonly present in patients who have chronic bronchial inflammation (i.e., bronchiectasis), and is a common incidental finding on lung biopsy; this is termed secondary follicular bronchiolitis Primary follicular bronchiolitis is much less common and is usually seen in patients who have a history of an underlying immunodeficiency (including AIDS), connective tissue disease (particularly Sjögren syndrome or rheumatoid arthritis), hypersensitivity, or eosinophilia (73,76,82–84) Primary follicular bronchiolitis is commonly associated with dyspnea Prognosis is related to age, with younger patients often having progressive disease (82) Response to steroid treatment is variable (82) In patients who have follicular bronchiolitis, chest radiographs characteristically show a diffuse reticular or reticulonodular pattern (82) HRCT typically demonstrates 297 FIGU RE 11-23 Follicular bronchiolitis HRCT in a patient who has rheumatoid arthritis shows small nodules in a centrilobular (straight arrows) and peribronchovascular (curved arrow) distribution Also noted are subpleural nodules and nodules adjacent to the left interlobar fissure small nodular opacities in a centrilobular and peribronchovascular distribution or lung cysts (Figs 11-23 and 11-24) (76,83,85,86) In the majority of cases, nodules measure to mm in diameter, although occasionally they can measure as much as cm in diameter (83) Lungs cysts are the same as present in LIP Howling et al (83) reviewed the HRCT findings in 12 patients who had biopsy-proven follicular bronchiolitis The predominant abnormalities consisted of small nodules and areas of ground-glass opacity The nodules had a centrilobular distribution in all 12 patients, corresponding to the location of small bronchioles In some patients, the centrilobular opacities had a branching appearance, reflecting the morphology of the small airways involved Additional peribronchial nodules were present in (42%) and subpleural nodules in (25%) of the 12 patients The nodules were diffuse but mainly involved the lower lung zones Nine (75%) patients had patchy bilateral areas of ground-glass opacity Additional findings seen in a small number of patients included mild interlobular septal thickening, bronchial wall thickening, FIGU RE 11-24 Biopsy-proven follicular bronchiolitis in a patient with juvenile rheumatoid arthritis Extensive cystic abnormalities are visible, similar to those in patients with LIP 298 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease A B FIGU RE 11-25 Biopsy-proven follicular bronchiolitis in a patient with Sjögren syndrome A and B: Patchy areas of lucency representing mosaic perfusion are visible in the lower lobes These were associated with air trapping on expiratory views and peribronchial consolidation (76,83) Diffuse air trapping on expiratory HRCT has also been reported in association with follicular bronchiolitis (Fig 11-25) (87) Lymphoid Interstitial Pneumonia LIP is a benign lymphoproliferative disorder, characterized histologically by a diffuse interstitial infiltrate of mononuclear cells consisting predominantly of lymphocytes and plasma cells (73,76,88,89) It is distinguished from follicular bronchiolitis in that the abnormality is not limited to the airways LIP frequently occurs in association with other conditions, most commonly Sjögren syndrome (90–92) and other collagen-vascular diseases (93), congenital or acquired immunodeficiency syndromes (e.g., AIDS) (94), primary biliary cirrhosis, or multicentric Castleman disease (88,95,96) Except for AIDS, in which those affected are most often children, the majority of patients who have LIP are adults, with the mean age at presentation being approximately 50 years The main clinical symptoms are cough and dyspnea LIP is illustrated in greater detail in Chapter A The radiographic findings of LIP consist of a reticular or reticulonodular pattern involving mainly the lower lung zones (88,97,98) Less common abnormalities include a nodular pattern, ground-glass opacities, and airspace consolidation The HRCT findings of LIP depend at least in part on the underlying disease present HRCT abnormalities may consist of diffuse bilateral areas of ground-glass opacity and poorly defined centrilobular nodules, subpleural nodules, thickening of the bronchovascular bundles, lung cysts, and patchy ground-glass opacity (Figs 11-26 to 11-28, Table 11-6) (76,86,96,99,100) In some patients, the appearance of LIP may closely mimic that of lymphangitic spread of carcinoma In Sjögren syndrome, LIP is typically associated with lung cysts that are thin walled, round in shape, and limited in number (Fig 11-26) (90,91) In congenital immunodeficiency syndromes, LIP most often appears as patchy ground-glass opacity (Fig. 11-27) In patients with AIDS, LIP most often appears as centrilobular or perilymphatic nodules (Fig 11-28) (94) Johkoh et al (96) reviewed the HRCT findings in 22 patients who had LIP All patients had areas of B FIGU RE 11-26 Lymphoid interstitial pneumonia in a patient with Sjögren syndrome A and B: Multiple thin-walled cysts are visible bilaterally This appearance is most typical of LIP in Sjögren syndrome C hapter 11 Diffuse Pulmonary Neoplasms and Pulmonary Lymphoproliferative Diseases 299 TABLE 11-6 HRCT Findings in Lymphoid Interstitial Pneumonia Ground-glass opacitya Poorly defined centrilobular nodulesa Subpleural nodulesa Interlobular septal thickening or nodulesa Thickening of peribronchovascular interstitiuma Cystic airspacesa,b Lymph node enlargementa a b FIGU RE 11-27 Lymphoid interstitial pneumonia in a patient with common variable immunodeficiency Patchy areas of ground-glass opacity are visible bilaterally ground-glass opacity and poorly defined centrilobular nodules Small subpleural nodules were seen in 19 (86%) patients, thickening of the peribronchovascular interstitium in 19 (86%), mild interlobular septal thickening in 18 (82%), and cystic airspaces in 15 (68%) (90) Lung cysts were usually thin walled, were less than 30 mm in diameter, and involved less than 10% of the lung parenchyma (Fig 11-26) Less common manifestations included small nodules, airspace consolidation, bronchiectasis, and, occasionally, honeycombing (96,101) Lymph node enlargement may be seen on CT (96) Centrilobular nodules visible on HRCT correlate with the presence of peribronchiolar infiltration with Most common findings Findings most helpful in differential diagnosis lymphocytes and plasma cells, whereas the ground-glass opacities reflect a diffuse interstitial infiltration Cystic airspaces occurring in LIP are likely due to airway obstruction by the peribronchiolar cellular infiltrates, resulting in air trapping (99) Supporting this contention is a report of severe air trapping in a patient with follicular hyperplasia of BALT (87) In a study by Honda et al (102), HRCT findings of LIP were compared to those in patients who had malignant lymphoma Several significant differences in the appearances of these diseases were found Cysts were more common in patients who had LIP (82%) than in patients who had malignant lymphoma (2%), whereas airspace consolidation and large nodules (11–30 mm in diameter) were more common in patients who had malignant lymphoma (66% and 41%, respectively) than in patients who had LIP (18% and 6%) (p < 0.001) Pleural effusions (25%) were seen only in patients who had malignant lymphoma Nonetheless, MALT lymphoma may coexist with and be associated with typical HRCT findings of LIP (77,103) Angioimmunoblastic Lymphadenopathy FIGU RE 11-28 Lymphoid interstitial pneumonia in a patient with AIDS Small sharply marginated nodules are visible in relation to the right major fissure Some septal nodules and centrilobular nodules are also visible AILD is an uncommon systemic disease that commonly results in intrathoracic lymph node enlargement (72,73,75) In some cases, the lung and pleura are also involved Histologically, abnormal lymph nodes show a proliferation of vessels and infiltration by a heterogeneous population of lymphocytes, plasma cells, and immunoblasts T-cell proliferation is most common, and the EBV genome has been detected in most cases An association with drug treatment suggests that a hypersensitivity reaction may also be involved in the development of AILD Progression to malignant lymphoma may occur, a condition termed AILD-like T-cell lymphoma AILD patients are usually older than 50 years Constitutional symptoms are typical with fever and weight loss; other findings include hepatomegaly, splenomegaly, rash, generalized lymph node enlargement, polyclonal hypergammopathy, and Coombs-positive anemia (75) The clinical course is variable, with three distinct patterns being identified: 50% of patients have rapid progression to death, 25% have prolonged survival with steroid and 300 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease cell lymphoma, peripheral T-cell lymphoma, and other cell types (112,114) Primary pulmonary Hodgkin lymphoma (HL) is rare Low-Grade MALT Lymphoma (Extranodal Marginal Zone B-Cell Lymphoma of MALT) FIGU RE 11-29 Angioimmunoblastic lymphadenopathy-like lymphoma HRCT shows extensive interlobular septal thickening The appearance mimics that of lymphangitic spread of carcinoma antineoplastic treatment, and 25% have prolonged survival without treatment The radiographic appearance of AILD is similar to that of lymphoma (72,73,104) Approximately 55% of cases show extensive mediastinal and hilar lymph node enlargement One-third of cases show lung involvement Interstitial infiltration in the lower lobes associated with septal thickening or patchy consolidation is typical (Fig.11-29) (104,105) Pleural effusion may be present (72) Enlarged lymph nodes may be enhanced if contrast infusion is used (106) Primary Pulmonary Lymphoma Lymphoma involving the lung can be considered primary pulmonary lymphoma if there is no history of lymphoma, mediastinal lymph node enlargement is invisible on chest radiographs, it is unassociated with extrathoracic disease, and there is no evidence of extrathoracic dissemination for at least months after the initial diagnosis (75,107) Primary pulmonary lymphoma is an uncommon neoplasm; in one study of 1,269 cases of lymphoma, less than 1% was deemed to have a pulmonary origin (108) Indolent B-cell lymphomas are most common as a cause of primary pulmonary lymphoma, accounting for more than 80% of cases, and most are low-grade MALT, termed extranodal marginal zone B-cell lymphoma of MALT according to the Revised European-American Lymphoma (REAL) and WHO classifications of lymphoid diseases (74,109–113) Diffuse large B-cell lymphoma is another common cause of primary pulmonary lymphoma, with some tumors occurring in relation to MALT (112,114) Non-MALT lymphomas are generally considered to be intermediate or high grade Primary T-cell lymphomas are occasionally seen but are less common than B-cell tumors; these include anaplastic large The most frequent cause of primary pulmonary lymphoma is extranodal marginal zone B-cell lymphoma of MALT, also known as MALT lymphoma or MALToma (74,109–111,113) In two recent reviews, low-grade MALT lymphomas accounted for 54% to 58% of primary pulmonary lymphomas (112,114) In the lung, these tumors are believed to arise from cells present in BALT and have also been termed BALT lymphoma or BALToma (111) This tumor tends to remain localized to the lung for long periods of time, follows an indolent course, and is associated with a good prognosis (111) For example, in one study of 43 cases, the overall 5-year survival rate was 84% (115) They are believed to arise because of chronic antigenic stimulation, associated with smoking, local chronic inflammatory disease, or autoimmune diseases (110,111,116) At least some of these tumors were previously classified as pseudolymphomas, but they are now regarded as true neoplasms (73,79,80) MALT lymphoma may be asymptomatic when localized More diffuse lung involvement may be associated with cough, dyspnea, and chest pain (116) Systemic symptoms of fever, night sweats, and weight loss are relatively uncommon with low-grade MALT lymphoma (110,112) The most common radiologic manifestation of primary low-grade B-cell lymphoma consists of a solitary nodule or a focal area of consolidation measuring from to 8 cm in diameter (Fig 11-30) (117–120) Air bronchograms are visible in approximately 50% of cases (107) Other patterns of lung involvement include a localized area of consolidation, which may range from a small subsegmental area to an entire lobe, or, less commonly, multiple nodules or multifocal areas of consolidation (121,122) FIGU RE 11-30 MALToma in a 69-year-old woman HRCT shows focal area of consolidation in the right middle lobe Follow-up months later showed no interval change The diagnosis was proven at surgical resection C hapter 11 Diffuse Pulmonary Neoplasms and Pulmonary Lymphoproliferative Diseases The parenchymal abnormalities typically show an indolent course, with slow growth over months or years (107,123) On CT and HRCT, multiple or solitary nodules or masses or areas of consolidation are most typical (76,111,116,124,125) (Table 11-7) They may be seen as primarily peribronchial in location, and air bronchograms are frequently visible Bronchi within the affected lung parenchyma may appear dilated or stretched and slightly narrowed (116,118,122,126) Pulmonary nodules or masses may be associated with the halo sign (108) Enhanced vessels visible within the nodules or masses (i.e., the CT angiogram sign) may be seen (116) A perilymphatic distribution of abnormalities is typical, with tumor involving the peribronchovascular interstitium and interlobular septa (76,116) Rarely, airway involvement is manifested by bronchial wall thickening and marked narrowing of the bronchial lumen (127) Other findings seen on HRCT include centrilobular nodules, interlobular septal thickening, ground-glass opacities, or cystic or bubblelike lesions (119,126) Mosaic attenuation due to small airway obstruction has also been reported with BALT lymphoma (128) Abnormalities are bilateral in one-half to two-thirds of cases (111,116) In one study (111) of CT findings in 22 patients with MALT lymphoma, pulmonary abnormalities included a solitary nodule (23%), multiple nodules (32%), lung mass or consolidation (45%), consolidation with air bronchograms (18%), and patchy airspace or interstitial infiltrates (23%) (111) In a similar CT and HRCT study of 24 patients with MALT lymphoma (116), one or more pulmonary masses or masslike areas of consolidation larger than cm in diameter were found in 87%, while nodules cm in diameter or smaller were seen in 75% Multiple masses, nodules, or areas of consolidation were present in 79%, while 17% had a solitary lesion In 88%, air bronchograms were visible in relation to nodules or masses, and in 58% of patients, the bronchi appeared dilated Pleural effusion is present in 10% to 33% of cases, usually in association with evidence of parenchymal TABLE 11-7 HRCT Findings in Low-Grade B-cell ymphoma (MALToma or BALToma) L Multiple or solitary nodulesa,b Halo sign Multiple or localized areas of consolidationa Air bronchogramsa Peribronchial distributiona,b Interlobular septal thickening Slow growtha,b Pleural effusion a b Most common findings Findings most helpful in differential diagnosis 301 FIGU RE 11-31 High-grade non-Hodgkin lymphoma HRCT demonstrates bilateral nodules with irregular margins and focal areas of subpleural thickening involvement (107,111,117) Lymphadenopathy is evident in up to 30% of cases (111,126) High-Grade Lymphoma Most cases of high-grade primary pulmonary lymphoma are of B-cell type, and some originate from MALT (110) These may arise from the transformation of an indolent MALT lymphoma or occur in patients with an underlying disorder or immunodeficiency such as AIDS or organ transplantation (posttransplant lymphoproliferative disorder); these are described later in this chapter Occasional cases of anaplastic large cell lymphoma or peripheral T-cell lymphoma have also been reported (110,129) Generally, the radiographic and CT features of highgrade lymphomas are similar to those of low-grade MALT lymphoma (116) The most common radiographic presentation consists of solitary or multiple nodules, masses, or regions of consolidation containing air bronchograms (Figs 11-31 and 11-32) (118,123) Lymph node enlargement may be present Secondary Pulmonary Lymphoma Pulmonary involvement in association with extrathoracic or diffuse lymphoma is more common than primary pulmonary lymphoma In one review of 651 patients who had lymphoma, 54 (8%) had histologically documented pulmonary involvement (130) Of these 54, the lung was the primary site of involvement in 21 (39%), whereas the lung was secondarily involved by tumor originating in a variety of distant sites in 33 (61%) (130) Intrathoracic abnormalities are common in patients who have lymphoma, being seen at presentation in 67% to 87% of patients who have HL, and 43% to 45% of patients who have non-Hodgkin lymphoma (NHL) (131– 133) In the majority of patients, intrathoracic disease is limited to lymph nodes Pulmonary involvement is apparent radiographically at presentation in approximately 5% to 10% of patients who have NHL and 10% to 15% of patients who have HL (131–135) In patients 302 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease A C who have HL, lung involvement at presentation is almost always associated with hilar or mediastinal lymph node enlargement (135); this is not the case with NHL However, radiographic and CT appearances of lung disease in HL and NHL are quite similar (123,130,136) The most frequent CT and HRCT finding in secondary pulmonary lymphoma consists of solitary or FIGU RE 11-33 Recurrent lymphoma HRCT shows nodules in the lingula Also noted is interlobular septal thickening in the lingula and right lower lobe The patient was a 38-year-old woman who had recurrent NHL B FIGU RE 11-32 A–C: High-grade T-cell lymphoma in a 33-yearold man HRCT demonstrates well-defined nodules surrounding bronchi or containing air bronchograms (arrows) multiple nodules, masses, or masslike consolidation, usually ranging from 0.5 to cm in diameter, often shaggy or ill-defined, and sometimes cavitary (Fig 11-33) (130,132–134,136–138) In one study, air bronchograms were visible within 47% of masses in NHL and 32% of masses in HL (136) A diffuse reticular pattern with thickening of the interlobular septa may also be seen, closely mimicking the appearance of lymphangitic carcinomatosis (Fig 11-34) (118,123) This pattern may reflect interstitial tumor infiltration or lymphatic or venous obstruction by mediastinal or hilar tumor Thickening of the peribronchovascular interstitium is seen in as many as 55% of cases (128) and is often associated with other findings Patchy airspace consolidation with air bronchograms may also be seen (118,123,130) and is associated with a poor prognosis (130) Lewis et al (136) reviewed the conventional CT findings in 31 patients who had secondary pulmonary lymphoma, including 15 with HL and 16 with NHL (Table 11-8); in most patients, pulmonary involvement occurred with relapse The most common pulmonary parenchymal manifestations were nodules or masses larger than cm in diameter or masslike areas of consolidation (68% of patients) and nodules smaller than cm in diameter (61% of patients) (136) Nodules or masses C hapter 11 Diffuse Pulmonary Neoplasms and Pulmonary Lymphoproliferative Diseases 303 A B FIGU RE 11-34 A–C: Lymphoma with secondary lung involvement in a 79-year-old man HRCT demonstrates extensive interlobular septal thickening, thickening of interlobar fissures, and peribronchovascular interstitial thickening identical in appearance to that of lymphangitic spread of carcinoma C larger than cm often contained air bronchograms, but those smaller than cm did not Both nodules and masses often had shaggy borders Although the findings seen in patients with HL and NHL were similar, the most common finding with HL was mass or masslike consolidation (80% of cases), whereas the most common finding with NHL was peribronchovascular interstitial thickening (69%) Pleural effusion was visible in 42% of cases TABLE 11-8 CT Findings (%) in Pulmonary Hodgkin Lymphoma and Non-Hodgkin Lymphoma Finding HL NHL Nodules (1 cm) 80 56 Pleural-based masses 33 33 Peribronchovascular interstitial thickening 40 69 Interstitial or alveolar infiltrates 40 31 Pleural effusion 40 44 Adenopathy 53 19 From Lewis ER, Caskey CI, Fishman EK Lymphoma of the lung: CT findings in 31 patients AJR Am J Roentgenol 1991;156:711–714 Lymph node enlargement was more common with HL (53%) than with NHL (19%) (136) Diederich et al (138) reviewed the CT findings in 33 examples of secondary pulmonary HL Pulmonary nodules were recorded in 88% of studies Nodules were multiple in 86% and bilateral in 66% of cases, respectively Nodule size ranged from mm to 10 cm In 83% of cases, nodules were 30 mm or smaller, and in 21%, they were cm or smaller In 83%, nodules were irregularly marginated Cavitation was visible in less than 1% of nodules Regions of diffuse lung infiltration were visible in 27% of cases, and more than half of these also showed nodules Infiltration was peribronchovascular in 56% of patients with infiltration, nodular in 33%, and alveolar in 11% It usually involved 25% or less of the lung parenchyma Hilar or mediastinal lymph node enlargement was always present at the time of initial diagnosis Not surprisingly, CT showed more abnormalities than plain radiographs (138) An example of diffuse pulmonary involvement by mycosis fungoides with clinical and radiographic manifestations simulating pneumonia has been reported (139) HRCT showed multiple, dense, peribronchovascular nodules with surrounding ground-glass opacity and wedge-shaped peripheral opacities The autopsy specimen revealed angiocentric and peribronchovascular involvement by mycosis fungoides and pulmonary infarctions distal to angiocentric infiltration of the tumor cells 304 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease AIDS-Related Lymphoma Prior to the use of HAART, lymphoma was reported to have an incidence of approximately 5% in patients with AIDS (140,141) HAART has reduced the incidence of ARL and improved patient survival following chemotherapy (61), but the incidence of ARL has not dropped to the same degree as it has for KS (142) Most frequently, ARL is a high-grade B-cell NHL (141,143,144) Ioachim et al (143) reviewed 111 cases of ARL; 100 represented NHL, whereas 11 were HL EBV has been implicated in at least some cases of both AIDSrelated NHL and HL (143,144) ARL is typically characterized by advanced clinical stage and high histologic grades (141) NHL in AIDS patients originates predominantly in extranodal locations and frequently involves multiple sites, including bone marrow, central nervous system, lung, liver, and bowel (143) ARL is associated with advanced AIDS and low CD4+ counts (145) Prior to the use of HAART, it was characterized by high aggressiveness, frequent posttreatment relapse, and short periods of survival (143,144) In one study, the median survival time was months, with progressive pulmonary lymphoma being the main cause of death (144) Thoracic involvement is common in patients who have ARL and is present in up to 70% of cases at autopsy (145) In a study of 116 consecutive cases of ARL, 20 (17%) patients were considered to have thoracic involvement, and in 15 cases, the thorax was the major site of disease (146) In another study, 11 of 35 (31%) patients who had ARL had biopsy-proven thoracic involvement (147) Primary pulmonary ARL is less frequent, and accounts for only 8% to 15% of cases (118,144) Pulmonary nodules or masses are the most common radiographic and CT finding in ARL, typically ranging in size from 0.5 to cm in diameter, although most nodules are larger than cm (Fig 11-35) (65,71,118,141,144,146,147) The nodules are usually A multiple and well defined, but may appear spiculated, and cavitation may be present (144) Localized consolidation or reticular opacities may also be seen Pleural effusion is common, usually in combination with multiple nodules; this appearance is considered typical of ARL (147) Mediastinal lymph node enlargement is more common in patients who have lung involvement occurring in association with disseminated ARL than it is in patients who have primary or localized pulmonary ARL Node enlargement in association with thoracic ARL was seen in of 11 patients studied by Sider et al (147) and in 54% of patients studied by Eisner et al (145), but it was not seen in two recent studies of primary ARL of the lung (141,144) The clinical, radiographic, and autopsy features of 38 patients who had AIDS-related NHL associated with pulmonary involvement were reviewed by Eisner et al (145) Most patients had respiratory symptoms (87%) and signs (84%), and systemic symptoms are common (144) The majority of patients had advanced HIV infection, with a mean CD4+ count of 67 (±65) Thoracic CT revealed pulmonary nodules (50%), lobular consolidation (27%), and lung mass (19%) as the most common parenchymal abnormalities Pleural effusion was visible in 68% of cases Posttransplantation Lymphoproliferative Disorder Several histologic patterns of lymphocyte proliferation, known collectively as posttransplantation lymphoproliferative disorder, can occur after bone marrow or solid organ transplantation (148–150) The histologic patterns range from benign hyperplastic proliferation of lymphocytes to malignant lymphoma (150) Most cases of PTLD have been associated with EBV infection, and it is likely that such infection is an essential step in the development of the majority of cases (148,150–152) PTLD affects approximately 2% of B FIGU RE 11-35 A and B: Non-Hodgkin lymphoma CT in a patient with AIDS who has NHL shows ill-defined nodules, many of which are perihilar and peribronchovascular, or contain air bronchograms This appearance mimics that of KS C hapter 11 Diffuse Pulmonary Neoplasms and Pulmonary Lymphoproliferative Diseases transplant recipients (153) The incidence is highest after lung transplantation, with PTLD being seen in approximately 6% to 9% of lung transplant recipients (78,154) The majority of patients present in the first year after transplantation PTLD can manifest as localized or disseminated disease and has a predilection for extranodal involvement (78) Lung involvement may occur as part of multiorgan disease or in isolation Thoracic PTLD can occur in any transplant recipient and should be regarded as a potentially fatal complication Heart and lung allograft recipients have the poorest prognosis because significant mortality accompanies transplant rejection with reduced immunosuppression necessary for treatment (150) Eleven cases of primary thoracic PTLD were identified among 3,085 solid-organ transplant patients and 1,662 bone marrow transplant patients (lung transplant, 3; kidney transplant, 3; kidney/pancreas transplant, 2; allogenic bone marrow transplant, 2; and heart transplant, 1) (150) The median time from transplantation to presentation was months (range, 1–97 months) CT evaluation revealed mediastinal lymph node enlargement or mass and pulmonary masses or nodules in 55% of cases, and 55% of patients also had extrathoracic disease Pathologic analysis revealed diffuse large B-cell lymphoma in patients, polymorphic PTLD in patients, anaplastic large cell lymphoma in patient, and HL in patient EBV infection was determined to be present in 84% of patients tested All patients were initially treated with a reduction in immunosuppression therapy, and patients (55%) received adjuvant chemotherapy The overall mortality rate was 64% Four patients died from complications of PTLD (kidney, 2; heart, 1; bone marrow, 1), and patients (all lung transplant recipients) died from rejection or infectious complications The median interval from diagnosis to death was 13 months (range, 1–42 months) (150) The most common CT findings in PTLD include (a) single or multiple, small or large pulmonary nodules, 305 TABLE 11-9 HRCT Findings in Posttransplantation Lymphoproliferative Disorder Single or multiple nodules, well-defined or ill-defineda Halo sign Patchy or focal consolidation or ground-glass opacityb Peribronchial, subpleural, or random distributionb Lymph node enlargement a b Findings most helpful in differential diagnosis Most common findings which may be well-defined, ill-defined, or associated with the halo sign (Fig 11-36); (b) patchy or focal consolidation or ground-glass opacity; (c) a predominantly peribronchial and subpleural or diffuse distribution of parenchymal abnormalities; and (d) hilar or mediastinal lymphadenopathy (Table 11-9) (118,149,150,155,156) In a review of the radiologic manifestations in 28 patients by Dodd et al., nodules were identified on the chest radiograph or CT in 16 patients (57%) (155) The nodules were well circumscribed, measured between 0.3 and cm in diameter, and were usually multiple and distributed randomly throughout the lungs Patchy, predominantly peribronchial airspace consolidation associated with air bronchograms was seen in patients, of whom also had lung nodules Mediastinal and hilar lymphadenopathy was seen in 17 of 28 (60%) patients, thymic involvement in 2, pericardial thickening or effusion in 2, and pleural effusion in Carignan et al (156) reviewed the HRCT findings in four patients who had PTLD All four patients had nodules on HRCT, two had hilar and mediastinal lymphadenopathy, and one had pleural effusion In three of the four patients, a halo of ground-glass opacity was seen surrounding the lung nodules; this finding has been reported in other studies, and pathologic correlation showed the halo to be related to infiltration of the adjacent lung by a less dense infiltrate of lymphoid cells (Fig 11-36) (149) In another investigation of 17 patients who had PTLD, 15 (88%) had multiple nodules on CT, (35%) had interlobular septal thickening, (29%) had areas of ground-glass opacity, (23%) had areas of airspace consolidation, and had hilar or mediastinal lymphadenopathy (78) The nodules had a predominantly peribronchovascular or subpleural distribution Lymphomatoid Granulomatosis (Angioimmune Proliferative Lesion) FIGU RE 11-36 Posttransplantation lymphocytic disorder after double lung transplant HRCT demonstrates left lower lobe nodule with irregular margins and halo of ground-glass attenuation (arrow) Also noted is a small left pleural effusion The term lymphomatoid granulomatosis (also known as angioimmune proliferative lesion or angiocentric immunoproliferative lesion) is used to refer to a group of angiocentric, angiodestructive abnormalities characterized by a lymphoid infiltrate and a variable degree of cellular atypia (72,74–76) Three grades are considered to exist based on the degree of cytologic abnormalities and 306 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease A B FIGU RE 11-37 Lymphomatoid granulomatosis A and B: HRCT demonstrates nonspecific small sharply defined lower lobe nodules necrosis, and their response to treatment (72) Progression to histologically overt lymphoma occurs in as many as 47% of cases (157) B cells appear to constitute the primary neoplastic proliferation in patients who have lymphomatoid granulomatosis, although an exuberant Tcell reaction is present (74,158) EBV has been detected in most cases investigated (72,158) The lung is the primary site of disease, although other organs, including skin, brain, kidneys, and heart, may be involved Radiographic and CT findings consist primarily of bilateral, well- or poorly defined nodular lesions, ranging from 0.5 to cm in diameter, with a basal predominance (Fig 11-37) (72,98,157,159) Nodules have a perilymphatic distribution and tend to be located in relation to the peribronchovascular interstitium or interlobular septa (157) In a review of five cases, the number of nodules ranged from to more than 60 (157) Lesions may progress rapidly and cavitate, mimicking Wegener granulomatosis Thin-walled cystic lesions may be seen, resulting from necrosis pleural effusion, and mediastinal lymph node enlargement may be present (157) Leukemia Pleuropulmonary infiltration is evident at autopsy in 20% to 66% of patients who have leukemia (1,160,161) However, the radiographic abnormalities in these patients are seldom due to pleuropulmonary leukemic infiltration alone In the majority of patients, parenchymal abnormalities seen on the radiograph are due to pneumonias, hemorrhage, drug-induced lung damage, or pulmonary edema (1,162,163) In an autopsy review of 60 patients who died from acute or chronic myelogenous or lymphocytic leukemia, radiographically demonstrable disease was related to hemorrhage in 74%, infection in 67%, edema or congestion in 57%, and leukemic infiltration in 26%; only 5% were radiographically normal (162) In a review of HRCT findings in 80 consecutive patients with chest complications of leukemia, 29 of whom had undergone bone marrow transplantation (BMT), the most common causes of pulmonary disease included bacterial pneumonia (31.3%), leukemic infiltration (16.3%), cytomegalovirus (CMV) infection (12.5%), pneumocystic pneumonia (10%), fungal pneumonia (7.5%), bronchiolitis obliterans (5%), and organizing pneumonia (3.8%) (1) Bronchiolitis obliterans and organizing pneumonia were seen only in patients having BMT CMV pneumonia was more frequent in patients having BMT, whereas leukemic infiltration was more frequent in patients not having BMT (1) The radiographic findings of pulmonary leukemic infiltration in the absence of other pulmonary complications consist of bilateral reticulation that resembles lymphangitic carcinomatosis Common manifestations include thickening of the peribronchovascular interstitium, interlobular septal thickening, and nodules with a perilymphatic distribution (1,164,165) Heyneman et al reviewed the HRCT findings of pulmonary leukemic infiltration in 10 patients who had histopathologically proven disease and no other concomitant pulmonary complications (164) The predominant abnormalities consisted of interlobular septal thickening, seen in all patients, and thickening of the bronchovascular bundles, seen in patients The septal thickening was smooth in patients and nodular in 4 patients Nodules measuring to 10 mm in diameter were present in 8 patients (Fig 11-38) Less common findings included focal areas of ground-glass opacity or consolidation (164) Tanaka et al (165) compared the CT and HRCT findings of 11 leukemic patients who had leukemic pulmonary infiltration with those of 22 leukemic patients with various other lung diseases, including pneumonias, hemorrhage, infarction, edema, and drug toxicity HRCT findings in patients with leukemic infiltration included thickening of the bronchovascular bundles (81.8%), prominence of peripheral pulmonary arteries (81.8%), interlobular septal thickening (54.5%), nonlobular and nonsegmental ground-glass opacities (90.9%), airspace consolidation (45.5%), and nodules with a random (27.3%) or peribronchovascular (18.2%) distribution Nodules smaller and larger than cm occurred in equal numbers Those findings significantly more frequent with leukemic infiltration were thickening of the bronchovascular C hapter 11 Diffuse Pulmonary Neoplasms and Pulmonary Lymphoproliferative Diseases FIGU RE 11-38 Leukemia HRCT targeted to the right lung demonstrates nodules (straight arrows) and nodular thickening of the interlobular septa (curved arrows) (Case courtesy of Dr Takeshi Johkoh, Osaka University Medical School, Osaka, Japan.) bundles (p < 0.001) and prominence of peripheral pulmonary arteries (p = 0.004) These latter two findings corresponded pathologically to leukemic cell infiltration around the pulmonary arteries, bronchi, or bronchioles Centrilobular nodules were significantly more frequent in patients with pulmonary complications other than leukemic infiltration (54.5%; p = 0.01) than in patients with leukemic infiltration (9%) This finding generally suggests infection in patients with leukemia (1) Nonspecific HRCT findings included interlobular septal thickening, ground-glass opacities, consolidation, and nodules At pathologic examination in the patients with leukemic infiltration, these abnormalities represented leukemic infiltration in some patients, and fibrosis, hemorrhage, DAD, edema, or infarction in others Adult T-Cell Leukemia/Lymphoma Adult T-cell leukemia/lymphoma (ATLL), according to the REAL and WHO classifications, is defined as a mature or peripheral T-cell neoplasm associated with infection by the human T-lymphotropic virus, type (HTLV-1) (166) HTLV-1 infection is rare in the United States, except in intravenous drug abusers However, the virus is endemic in southern Japan, the Caribbean, South America, and Africa ATLL is relatively uncommon among those infected with HTLV-1 The overall incidence of ATLL is estimated at about per 2,000 adult HTLV-1 carriers per year For example, antibodies against HTLV-1 have been found in more than million people in Japan, and approximately 307 500 patients develop ATLL annually (167,168) The cumulative risk of ATLL in an infected individual ranges from 0.5% to 5% (167) Virus transmission often occurs with breast feeding or blood transfusion There appears to be a latency period of 10 to 30 years between HTLV-1 infection and the development of ATLL (167) ATLL is characterized by circulating malignant T lymphocytes, skin lesions, lung infiltration, lymphadenopathy, hepatosplenomegaly, hypercalcemia, lytic bone lesions, central nervous system involvement, and a tendency to infection, often by CMV, P carinii, Aspergillus, Candida, and bacteria (168,169) ATLL is associated with a poor prognosis, partially depending on the clinical subtype of disease The acute subtype accounts for 55% of cases and has a median survival of about months (170) Patients with ATLL have a high frequency of pulmonary complications, including lung infiltration by leukemia cells, pulmonary hemorrhage, and pneumonia In one study, 93% of 29 ATLL patients presented with pulmonary abnormalities, most frequently tumor infiltration or infection Tumor infiltration was present in 45% (169) Okada et al (168) reviewed CT and HRCT in 87 patients with ATLL Abnormal findings were seen in 60 patients (69%), and 45 had lung parenchymal abnormalities detected HRCT findings included ground-glass opacity (n = 37; 61.7% of patients with lung abnormalities), centrilobular nodules (n = 25; 41.7%), thickening of bronchovascular bundles (n = 22; 36.7%), interlobular septal thickening (n = 17; 28.3%), consolidation (n = 13; 21.7%), and bronchiectasis (n = 13; 21.7%) Nodules were smaller than mm in diameter in 28 patients (46.7%), between and 10 mm in diameter in (11.7%), and larger than 10 mm in 13 (21.7%) These abnormalities were predominant in the peripheral lung (n = 26; 57.8%) Pleural effusions were present in 22 Mediastinal and hilar lymph node enlargement (11–82 mm) was found in 27 patients (45%) In 46 patients who underwent surgical biopsy or autopsy, the HRCT abnormalities corresponded to atypical interstitial or alveolar lymphocytic infiltrates Specifically, centrilobular nodules reflected infiltrates along respiratory bronchioles, ground-glass opacity reflected interstitial infiltration, and interlobular septal thickening reflected the presence of atypical lymphocytic infiltrates within the septa HRCT findings showed significant improvement with chemotherapy (168) Lung abnormalities, including lymphocytic alveolitis or bronchiolitis, may also be present in patients infected with HTLV-1, without respiratory symptoms being present These abnormalities are similar in appearance to those seen in patients with ATLL, but are less frequent In one study, HRCT was performed in 320 HTLV-1 carriers without evidence of ATLL (167) Abnormal findings were seen in 98 (30.1%) of patients These included centrilobular nodules, usually smaller than mm in diameter (n = 95; 97% of patients with abnormal scans), thickening of the bronchovascular interstitium (n = 55; 56%), ground-glass 308 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease opacity (n = 51; 52%), bronchiectasis (n = 50; 51%), interlobular septal thickening (n = 28; 29%), and consolidation (n = 5; 5%) These abnormalities predominated in the peripheral lung (n = 70; 71%) In 58 patients who had a biopsy, these findings corresponded to lymphocytic 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16 0 12 0 kV(p) 14 0 kV(p) 18 0 FIGU RE 1- 5 Effect of algorithm, kV(p), and mA on image noise Graph of HRCT image noise (SD of. .. (Figs 1- 2 to 1- 4) (6 ,10 ,12 ,16 ) Using a high-resolution algorithm is a critical element in performing HRCT (Table 1- 1) (11 ,15 ) In one study of HRCT techniques (10 ), the use of a high spatial frequency