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English Pages XVII, 376 [378] Year 2020
Pulmonary Disease Pathology, Radiology, Bronchoscopy Carol Farver Subha Ghosh Thomas Gildea Charles D. Sturgis
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Pulmonary Disease
Carol Farver • Subha Ghosh Thomas Gildea • Charles D. Sturgis
Pulmonary Disease Pathology, Radiology, Bronchoscopy
Carol Farver, MD Department of Pathology Cleveland Clinic Cleveland, OH USA
Subha Ghosh, MD, MBA Department of Diagnostic Radiology Cleveland Clinic Cleveland, OH USA
Thomas Gildea, MD Department of Pulmonary, Allergy and Critical Care Medicine Cleveland Clinic Cleveland, OH USA
Charles D. Sturgis, MD Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, MN USA
ISBN 978-3-030-47597-0 ISBN 978-3-030-47598-7 (eBook) https://doi.org/10.1007/978-3-030-47598-7 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Preface
This book was born out of the case-based discussions of a team of pulmonologists, radiologists, and pathologists at the Cleveland Clinic over the past 5 years. Meeting weekly to seek solutions for our most perplexing patients, we found ourselves increasingly grappling with diagnostic and therapeutic puzzles that were best solved by the collective wisdom of our multidisciplinary group. In conference after conference, it became apparent that we did the best for our patients when we talked with, and learned from, each other. As our discussions became increasingly rich and sophisticated, we concluded that the world needed a book that brought together the essential clinical, radiologic, and pathologic insights for the major diseases of the lung. This is that book. Pulmonary Disease: Pathology, Radiology, Bronchoscopy is divided into 24 chapters. Chapter 1 briefly reviews the technologies employed by each discipline. Chapters 2–24 are organized around disease entities, presenting the essentials of the clinical, imaging, and pathologic features of each. The topics are presented in outline form, providing easy access to the essential facts with plentiful figures to beautifully illustrate those facts. Among these illustrations is a collection of state-of-the-art bronchoscopic images showing the airway manifestations of the diseases, as well as a set of unique images generated by cutting-edge radiologic technologies. The pathology sections present a spectrum of specimens ranging from large resections to small biopsies and cytologic preparations, spotlighting the architectural and cellular features of the pathology. The essential histochemical, immunohistochemical, and molecular technologies are discussed, the tools needed to facilitate the most specific diagnoses and thus the most appropriate therapies. This book is intended for clinicians who diagnose and treat lung diseases, whatever their discipline and level of training. It covers the essential information for the most common pulmonary diseases as well as many of the rarer ones. It should be a rich resource for those in need of a board review or a quick update. Pulmonologists will find the imaging and pathologic descriptions helpful to correlate to their clinical impressions. Pathologists and radiologists will find clinical pearls that put their diagnoses into context. Finally, although the information for the various entities
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cannot be exhaustive, each chapter provides a list of suggested references to guide further reading. We gratefully acknowledge everyone at Springer for their unwavering support even when deadlines came and went under the pressure of our busy clinical schedules. In particular, we would like to thank our team of editors, most notably the incomparable Stephanie Frost, whose optimistic attitude kept us going when we weren’t sure we could. Thanks to Lillie Mae Gaurano for her steadfast support throughout and to Richard Hruska for his enthusiastic commitment to seeing this project through to the end. We stand in debt to our colleagues at the Cleveland Clinic for inspiring us through their dedication to providing outstanding patient care every day. Finally, to our families we offer our gratitude and love for making all of this and more possible. Cleveland, OH, USA Cleveland, OH, USA Cleveland, OH, USA Rochester, MN, USA
Carol Farver, MD Subha Ghosh, MD, MBA Thomas Gildea, MD Charles D. Sturgis, MD
Contents
1 Introduction to Multidisciplinary Techniques�������������������������������������� 1 1.1 Bronchoscopy ���������������������������������������������������������������������������������� 1 1.2 Imaging �������������������������������������������������������������������������������������������� 3 1.2.1 Chest X-Ray�������������������������������������������������������������������������� 3 1.2.2 Chest Computerized Tomography Scans (Chest CT Scans) 4 1.2.3 CT Pulmonary Angiography ������������������������������������������������ 5 1.2.4 Positron Emission Tomography (PET) �������������������������������� 6 1.2.5 Magnetic Resonance Imaging (MRI) Scan�������������������������� 7 1.3 Pathology������������������������������������������������������������������������������������������ 8 1.3.1 Surgical Pathology���������������������������������������������������������������� 8 1.3.2 Cytopathology���������������������������������������������������������������������� 12 Suggested Readings ���������������������������������������������������������������������������������� 13 2 Benign Tumors ���������������������������������������������������������������������������������������� 15 2.1 Hamartoma���������������������������������������������������������������������������������������� 15 2.1.1 Clinical���������������������������������������������������������������������������������� 15 2.1.2 Imaging �������������������������������������������������������������������������������� 15 2.1.3 Bronchoscopy ���������������������������������������������������������������������� 16 2.1.4 Pathology������������������������������������������������������������������������������ 18 2.2 Sclerosing Pneumocytoma���������������������������������������������������������������� 20 2.2.1 Clinical���������������������������������������������������������������������������������� 20 2.2.2 Imaging �������������������������������������������������������������������������������� 20 2.2.3 Pathology������������������������������������������������������������������������������ 21 2.3 Alveolar Adenoma���������������������������������������������������������������������������� 23 2.3.1 Clinical���������������������������������������������������������������������������������� 23 2.3.2 Imaging �������������������������������������������������������������������������������� 24 2.3.3 Pathology������������������������������������������������������������������������������ 24 2.4 Papillary Adenoma���������������������������������������������������������������������������� 25 2.4.1 Clinical���������������������������������������������������������������������������������� 25 2.4.2 Imaging �������������������������������������������������������������������������������� 25 2.4.3 Pathology������������������������������������������������������������������������������ 26 vii
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2.5 Solitary Papilloma���������������������������������������������������������������������������� 26 2.5.1 Clinical���������������������������������������������������������������������������������� 26 2.5.2 Imaging �������������������������������������������������������������������������������� 27 2.5.3 Bronchoscopy ���������������������������������������������������������������������� 27 2.5.4 Pathology������������������������������������������������������������������������������ 27 Suggested Readings ���������������������������������������������������������������������������������� 29 3 Salivary Gland-Like Tumors������������������������������������������������������������������ 31 3.1 Mucoepidermoid Carcinoma (MEC)������������������������������������������������ 31 3.1.1 Clinical���������������������������������������������������������������������������������� 31 3.1.2 Imaging �������������������������������������������������������������������������������� 31 3.1.3 Bronchoscopy ���������������������������������������������������������������������� 32 3.1.4 Pathology������������������������������������������������������������������������������ 33 3.2 Adenoid Cystic Carcinoma �������������������������������������������������������������� 36 3.2.1 Clinical���������������������������������������������������������������������������������� 36 3.2.2 Imaging �������������������������������������������������������������������������������� 36 3.2.3 Bronchoscopy ���������������������������������������������������������������������� 37 3.2.4 Pathology������������������������������������������������������������������������������ 37 Suggested Readings ���������������������������������������������������������������������������������� 39 4 Common Non-Small Cell Carcinomas �������������������������������������������������� 41 4.1 Adenocarcinoma ������������������������������������������������������������������������������ 41 4.1.1 Clinical���������������������������������������������������������������������������������� 41 4.1.2 Imaging �������������������������������������������������������������������������������� 41 4.1.3 Bronchoscopy ���������������������������������������������������������������������� 44 4.1.4 Pathology������������������������������������������������������������������������������ 45 4.2 Squamous Cell Carcinoma���������������������������������������������������������������� 50 4.2.1 Clinical���������������������������������������������������������������������������������� 50 4.2.2 Imaging �������������������������������������������������������������������������������� 51 4.2.3 Bronchoscopy ���������������������������������������������������������������������� 52 4.2.4 Pathology������������������������������������������������������������������������������ 54 4.3 Adenosquamous Carcinoma ������������������������������������������������������������ 56 4.3.1 Clinical���������������������������������������������������������������������������������� 56 4.3.2 Imaging �������������������������������������������������������������������������������� 57 4.3.3 Bronchoscopy ���������������������������������������������������������������������� 57 4.3.4 Pathology������������������������������������������������������������������������������ 57 4.4 Large Cell Carcinoma ���������������������������������������������������������������������� 60 4.4.1 Clinical���������������������������������������������������������������������������������� 60 4.4.2 Imaging �������������������������������������������������������������������������������� 60 4.4.3 Bronchoscopy ���������������������������������������������������������������������� 61 4.4.4 Pathology������������������������������������������������������������������������������ 61 Suggested Readings ���������������������������������������������������������������������������������� 63 5 Small Cell Carcinoma and Large Cell Neuroendocrine Carcinoma�������������������������������������������������������������������� 65 5.1 Small Cell Carcinoma ���������������������������������������������������������������������� 65 5.1.1 Clinical���������������������������������������������������������������������������������� 65
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5.1.2 Bronchoscopy ���������������������������������������������������������������������� 65 5.1.3 Imaging �������������������������������������������������������������������������������� 66 5.1.4 Pathology������������������������������������������������������������������������������ 66 5.2 Large Cell Neuroendocrine Carcinoma�������������������������������������������� 72 5.2.1 Clinical���������������������������������������������������������������������������������� 72 5.2.2 Bronchoscopy ���������������������������������������������������������������������� 72 5.2.3 Imaging �������������������������������������������������������������������������������� 72 5.2.4 Pathology������������������������������������������������������������������������������ 73 Suggested Readings ���������������������������������������������������������������������������������� 75 6 Carcinoid Tumors and Diffuse Idiopathic Neuroendocrine Cell Hyperplasia���������������������������������������������������������������������������������������������� 77 6.1 Typical and Atypical Carcinoid Tumors ������������������������������������������ 77 6.1.1 Clinical���������������������������������������������������������������������������������� 77 6.1.2 Bronchoscopy ���������������������������������������������������������������������� 77 6.1.3 Imaging �������������������������������������������������������������������������������� 78 6.1.4 Pathology������������������������������������������������������������������������������ 79 6.2 DIPNECH ���������������������������������������������������������������������������������������� 86 6.2.1 Clinical���������������������������������������������������������������������������������� 86 6.2.2 Imaging �������������������������������������������������������������������������������� 86 6.2.3 Pathology������������������������������������������������������������������������������ 86 Suggested Readings ���������������������������������������������������������������������������������� 87 7 Sarcomatoid Carcinomas������������������������������������������������������������������������ 89 7.1 Pleomorphic, Spindle Cell, and Giant Cell Carcinoma�������������������� 89 7.1.1 Clinical���������������������������������������������������������������������������������� 89 7.1.2 Imaging �������������������������������������������������������������������������������� 89 7.1.3 Bronchoscopy ���������������������������������������������������������������������� 89 7.1.4 Pathology������������������������������������������������������������������������������ 89 7.2 Carcinosarcoma�������������������������������������������������������������������������������� 93 7.2.1 Imaging �������������������������������������������������������������������������������� 93 7.2.2 Bronchoscopy ���������������������������������������������������������������������� 93 7.2.3 Pathology������������������������������������������������������������������������������ 94 Suggested Readings ���������������������������������������������������������������������������������� 96 8 Mesenchymal Tumors of the Lung �������������������������������������������������������� 97 8.1 Epithelioid Hemangioendothelioma ������������������������������������������������ 97 8.1.1 Clinical���������������������������������������������������������������������������������� 97 8.1.2 Imaging �������������������������������������������������������������������������������� 97 8.1.3 Pathology������������������������������������������������������������������������������ 98 8.2 Angiosarcoma ���������������������������������������������������������������������������������� 101 8.2.1 Clinical���������������������������������������������������������������������������������� 101 8.2.2 Imaging �������������������������������������������������������������������������������� 101 8.2.3 Pathology������������������������������������������������������������������������������ 103 8.3 Kaposi Sarcoma�������������������������������������������������������������������������������� 104 8.3.1 Clinical���������������������������������������������������������������������������������� 104 8.3.2 Imaging �������������������������������������������������������������������������������� 104
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8.3.3 Bronchoscopy ���������������������������������������������������������������������� 105 8.3.4 Pathology������������������������������������������������������������������������������ 106 8.4 Pulmonary Artery Intimal Sarcoma�������������������������������������������������� 107 8.4.1 Clinical���������������������������������������������������������������������������������� 107 8.4.2 Imaging �������������������������������������������������������������������������������� 107 8.4.3 Pathology������������������������������������������������������������������������������ 108 8.5 Inflammatory Myofibroblastic Tumor���������������������������������������������� 110 8.5.1 Clinical���������������������������������������������������������������������������������� 110 8.5.2 Imaging �������������������������������������������������������������������������������� 110 8.5.3 Pathology������������������������������������������������������������������������������ 111 8.6 Lymphangioleiomyomatosis ������������������������������������������������������������ 112 8.6.1 Clinical���������������������������������������������������������������������������������� 112 8.6.2 Imaging �������������������������������������������������������������������������������� 113 8.6.3 Pathology������������������������������������������������������������������������������ 113 Suggested Readings ���������������������������������������������������������������������������������� 115 9 Lymphoproliferative Diseases���������������������������������������������������������������� 117 9.1 Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma) �������������������������������������������� 117 9.1.1 Clinical���������������������������������������������������������������������������������� 117 9.1.2 Bronchoscopy ���������������������������������������������������������������������� 117 9.1.3 Imaging �������������������������������������������������������������������������������� 119 9.1.4 Pathology������������������������������������������������������������������������������ 120 9.2 Lymphomatoid Granulomatosis�������������������������������������������������������� 123 9.2.1 Clinical���������������������������������������������������������������������������������� 123 9.2.2 Imaging �������������������������������������������������������������������������������� 124 9.2.3 Pathology������������������������������������������������������������������������������ 124 9.3 Diffuse Large B-Cell Lymphoma ���������������������������������������������������� 126 9.3.1 Clinical���������������������������������������������������������������������������������� 126 9.3.2 Bronchoscopy ���������������������������������������������������������������������� 126 9.3.3 Imaging �������������������������������������������������������������������������������� 126 9.3.4 Pathology������������������������������������������������������������������������������ 127 Suggested Readings ���������������������������������������������������������������������������������� 128 10 Tumors of the Pleura ������������������������������������������������������������������������������ 131 10.1 Diffuse Malignant Mesothelioma �������������������������������������������������� 131 10.1.1 Clinical������������������������������������������������������������������������������ 131 10.1.2 Imaging ���������������������������������������������������������������������������� 131 10.1.3 Bronchoscopy�������������������������������������������������������������������� 132 10.1.4 Pathology�������������������������������������������������������������������������� 133 10.2 Solitary Fibrous Tumor ������������������������������������������������������������������ 138 10.2.1 Clinical������������������������������������������������������������������������������ 138 10.2.2 Imaging ���������������������������������������������������������������������������� 138 10.2.3 Bronchoscopy�������������������������������������������������������������������� 141 10.2.4 Pathology�������������������������������������������������������������������������� 141 Suggested Readings ���������������������������������������������������������������������������������� 143
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11 Chronic Obstructive Pulmonary Diseases �������������������������������������������� 145 11.1 Emphysema������������������������������������������������������������������������������������ 145 11.1.1 Clinical������������������������������������������������������������������������������ 145 11.1.2 Imaging ���������������������������������������������������������������������������� 146 11.1.3 Bronchoscopy�������������������������������������������������������������������� 148 11.1.4 Pathology�������������������������������������������������������������������������� 149 11.2 Asthma/Chronic Bronchitis������������������������������������������������������������ 151 11.2.1 Clinical������������������������������������������������������������������������������ 151 11.2.2 Imaging ���������������������������������������������������������������������������� 151 11.2.3 Bronchoscopy�������������������������������������������������������������������� 154 11.2.4 Pathology�������������������������������������������������������������������������� 154 11.3 Bronchiectasis �������������������������������������������������������������������������������� 157 11.3.1 Clinical������������������������������������������������������������������������������ 157 11.3.2 Imaging ���������������������������������������������������������������������������� 157 11.3.3 Bronchoscopy�������������������������������������������������������������������� 158 11.3.4 Pathology�������������������������������������������������������������������������� 158 Suggested Readings ���������������������������������������������������������������������������������� 160 12 Small Airway Diseases ���������������������������������������������������������������������������� 161 12.1 Respiratory Bronchiolitis (RB) ������������������������������������������������������ 161 12.1.1 Clinical������������������������������������������������������������������������������ 161 12.1.2 Imaging ���������������������������������������������������������������������������� 161 12.1.3 Bronchoscopy�������������������������������������������������������������������� 162 12.1.4 Pathology�������������������������������������������������������������������������� 162 12.2 Follicular Bronchiolitis ������������������������������������������������������������������ 164 12.2.1 Clinical������������������������������������������������������������������������������ 164 12.2.2 Imaging ���������������������������������������������������������������������������� 165 12.2.3 Bronchoscopy�������������������������������������������������������������������� 165 12.2.4 Pathology�������������������������������������������������������������������������� 165 12.3 Constrictive Bronchiolitis �������������������������������������������������������������� 167 12.3.1 Clinical������������������������������������������������������������������������������ 167 12.3.2 Imaging ���������������������������������������������������������������������������� 168 12.3.3 Bronchoscopy�������������������������������������������������������������������� 169 12.3.4 Pathology�������������������������������������������������������������������������� 169 Suggested Readings ���������������������������������������������������������������������������������� 171 13 Acute Lung Injury ���������������������������������������������������������������������������������� 173 13.1 Diffuse Alveolar Damage���������������������������������������������������������������� 173 13.1.1 Clinical������������������������������������������������������������������������������ 173 13.1.2 Imaging ���������������������������������������������������������������������������� 173 13.1.3 Bronchoscopy�������������������������������������������������������������������� 174 13.1.4 Pathology�������������������������������������������������������������������������� 175 13.2 Organizing Pneumonia�������������������������������������������������������������������� 177 13.2.1 Clinical������������������������������������������������������������������������������ 177 13.2.2 Imaging ���������������������������������������������������������������������������� 177 13.2.3 Bronchoscopy�������������������������������������������������������������������� 179
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13.2.4 Pathology�������������������������������������������������������������������������� 179 13.3 Acute Fibrinous and Organizing Pneumonia���������������������������������� 181 13.3.1 Clinical������������������������������������������������������������������������������ 181 13.3.2 Imaging ���������������������������������������������������������������������������� 181 13.3.3 Bronchoscopy�������������������������������������������������������������������� 181 13.3.4 Pathology�������������������������������������������������������������������������� 182 Suggested Readings ���������������������������������������������������������������������������������� 183 14 Common Interstitial Pneumonias���������������������������������������������������������� 185 14.1 General Clinical������������������������������������������������������������������������������ 185 14.2 Usual Interstitial Pneumonia���������������������������������������������������������� 185 14.2.1 Clinical������������������������������������������������������������������������������ 185 14.2.2 Imaging ���������������������������������������������������������������������������� 186 14.2.3 Bronchoscopy�������������������������������������������������������������������� 187 14.2.4 Pathology�������������������������������������������������������������������������� 188 14.3 Nonspecific Interstitial Pneumonia (NSIP)������������������������������������ 190 14.3.1 Clinical������������������������������������������������������������������������������ 190 14.3.2 Imaging ���������������������������������������������������������������������������� 190 14.3.3 Bronchoscopy�������������������������������������������������������������������� 191 14.3.4 Pathology�������������������������������������������������������������������������� 191 14.4 Respiratory Bronchiolitis-Interstitial Lung Disease/Desquamative Interstitial Pneumonia�������������������������������� 192 14.4.1 Clinical������������������������������������������������������������������������������ 192 14.4.2 Imaging ���������������������������������������������������������������������������� 193 14.4.3 Bronchoscopy�������������������������������������������������������������������� 193 14.4.4 Pathology�������������������������������������������������������������������������� 194 Suggested Readings ���������������������������������������������������������������������������������� 195 15 Other Interstitial Lung Diseases������������������������������������������������������������ 189 15.1 Hypersensitivity Pneumonitis �������������������������������������������������������� 189 15.1.1 Clinical������������������������������������������������������������������������������ 189 15.1.2 Bronchoscopy�������������������������������������������������������������������� 189 15.1.3 Imaging ���������������������������������������������������������������������������� 190 15.1.4 Pathology�������������������������������������������������������������������������� 192 15.2 Sarcoidosis�������������������������������������������������������������������������������������� 193 15.2.1 Clinical������������������������������������������������������������������������������ 193 15.2.2 Bronchoscopy�������������������������������������������������������������������� 194 15.2.3 Imaging ���������������������������������������������������������������������������� 195 15.2.4 Pathology�������������������������������������������������������������������������� 197 15.3 Langerhans Cell Histiocytosis�������������������������������������������������������� 201 15.3.1 Clinical������������������������������������������������������������������������������ 201 15.3.2 Imaging ���������������������������������������������������������������������������� 201 15.3.3 Pathology�������������������������������������������������������������������������� 202 15.4 Pulmonary Alveolar Proteinosis ���������������������������������������������������� 205 15.4.1 Clinical������������������������������������������������������������������������������ 205 15.4.2 Bronchoscopy�������������������������������������������������������������������� 205 15.4.3 Imaging ���������������������������������������������������������������������������� 206
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15.4.4 Pathology�������������������������������������������������������������������������� 206 15.5 Eosinophilic Pneumonia ���������������������������������������������������������������� 208 15.5.1 Clinical������������������������������������������������������������������������������ 208 15.5.2 Imaging ���������������������������������������������������������������������������� 209 15.5.3 Pathology�������������������������������������������������������������������������� 210 Suggested Readings ���������������������������������������������������������������������������������� 212 16 Pneumoconioses���������������������������������������������������������������������������������������� 223 16.1 Silicosis ������������������������������������������������������������������������������������������ 223 16.1.1 Clinical������������������������������������������������������������������������������ 223 16.1.2 Imaging ���������������������������������������������������������������������������� 223 16.1.3 Pathology�������������������������������������������������������������������������� 225 16.2 Coal Workers’ Pneumoconiosis������������������������������������������������������ 227 16.2.1 Clinical������������������������������������������������������������������������������ 227 16.2.2 Imaging ���������������������������������������������������������������������������� 227 16.2.3 Pathology�������������������������������������������������������������������������� 228 16.3 Asbestosis �������������������������������������������������������������������������������������� 230 16.3.1 Clinical������������������������������������������������������������������������������ 230 16.3.2 Imaging ���������������������������������������������������������������������������� 230 16.3.3 Pathology�������������������������������������������������������������������������� 230 16.4 Hard-Metal Pneumoconiosis���������������������������������������������������������� 232 16.4.1 Clinical������������������������������������������������������������������������������ 232 16.4.2 Imaging ���������������������������������������������������������������������������� 232 16.4.3 Pathology�������������������������������������������������������������������������� 233 Suggested Readings ���������������������������������������������������������������������������������� 234 17 Vasculitis �������������������������������������������������������������������������������������������������� 235 17.1 Granulomatosis with Polyangiitis (GPA)���������������������������������������� 235 17.1.1 Clinical������������������������������������������������������������������������������ 235 17.1.2 Bronchoscopy�������������������������������������������������������������������� 235 17.1.3 Imaging ���������������������������������������������������������������������������� 236 17.1.4 Pathology�������������������������������������������������������������������������� 238 17.2 Microscopic Polyangiitis���������������������������������������������������������������� 240 17.2.1 Clinical������������������������������������������������������������������������������ 240 17.2.2 Imaging ���������������������������������������������������������������������������� 240 17.2.3 Pathology�������������������������������������������������������������������������� 241 17.3 Eosinophilic Granulomatosis with Polyangiitis (EGPA)���������������� 243 17.3.1 Clinical������������������������������������������������������������������������������ 243 17.3.2 Imaging ���������������������������������������������������������������������������� 243 17.3.3 Pathology�������������������������������������������������������������������������� 244 Suggested Readings ���������������������������������������������������������������������������������� 245 18 Hypertensive Vascular Diseases�������������������������������������������������������������� 247 18.1 Pulmonary Hypertension���������������������������������������������������������������� 247 18.1.1 Clinical������������������������������������������������������������������������������ 247 18.1.2 Imaging ���������������������������������������������������������������������������� 247 18.1.3 Pathology�������������������������������������������������������������������������� 249
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18.2 Chronic Thromboembolic Disease������������������������������������������������� 252 18.2.1 Clinical������������������������������������������������������������������������������ 252 18.2.2 Imaging ���������������������������������������������������������������������������� 253 18.2.3 Pathology�������������������������������������������������������������������������� 254 18.3 Pulmonary Veno-occlusive Disease������������������������������������������������ 255 18.3.1 Clinical������������������������������������������������������������������������������ 255 18.3.2 Imaging ���������������������������������������������������������������������������� 256 18.3.3 Pathology�������������������������������������������������������������������������� 256 18.4 Pulmonary Capillary Hemangiomatosis ���������������������������������������� 257 18.4.1 Clinical������������������������������������������������������������������������������ 257 18.4.2 Imaging ���������������������������������������������������������������������������� 257 18.4.3 Pathology�������������������������������������������������������������������������� 258 18.5 Talcosis������������������������������������������������������������������������������������������� 259 18.5.1 Clinical������������������������������������������������������������������������������ 259 18.5.2 Imaging ���������������������������������������������������������������������������� 259 18.5.3 Pathology�������������������������������������������������������������������������� 260 Suggested Readings ���������������������������������������������������������������������������������� 261 19 Bacterial Infections���������������������������������������������������������������������������������� 263 19.1 Actinomycosis�������������������������������������������������������������������������������� 263 19.1.1 Clinical������������������������������������������������������������������������������ 263 19.1.2 Imaging ���������������������������������������������������������������������������� 264 19.1.3 Pathology�������������������������������������������������������������������������� 266 19.2 Nocardiosis ������������������������������������������������������������������������������������ 267 19.2.1 Clinical������������������������������������������������������������������������������ 267 19.2.2 Imaging ���������������������������������������������������������������������������� 268 19.2.3 Pathology�������������������������������������������������������������������������� 269 19.3 Legionella Pneumonia�������������������������������������������������������������������� 271 19.3.1 Clinical������������������������������������������������������������������������������ 271 19.3.2 Imaging ���������������������������������������������������������������������������� 272 19.3.3 Pathology�������������������������������������������������������������������������� 272 19.4 Malakoplakia���������������������������������������������������������������������������������� 273 19.4.1 Clinical������������������������������������������������������������������������������ 273 19.4.2 Imaging ���������������������������������������������������������������������������� 273 19.4.3 Pathology�������������������������������������������������������������������������� 273 19.5 Aspiration Pneumonia�������������������������������������������������������������������� 274 19.5.1 Clinical������������������������������������������������������������������������������ 274 19.5.2 Bronchoscopy�������������������������������������������������������������������� 275 19.5.3 Imaging ���������������������������������������������������������������������������� 275 19.5.4 Pathology�������������������������������������������������������������������������� 278 Suggested Readings ���������������������������������������������������������������������������������� 280 20 Mycobacterial Infections ������������������������������������������������������������������������ 283 20.1 Tuberculous Mycobacterial Infections�������������������������������������������� 283 20.1.1 Clinical������������������������������������������������������������������������������ 283 20.1.2 Bronchoscopy�������������������������������������������������������������������� 284
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20.1.3 Imaging ���������������������������������������������������������������������������� 285 20.1.4 Pathology�������������������������������������������������������������������������� 288 20.2 Non-tuberculous Mycobacterial Infections������������������������������������ 290 20.2.1 Clinical������������������������������������������������������������������������������ 290 20.2.2 Imaging ���������������������������������������������������������������������������� 290 20.2.3 Pathology�������������������������������������������������������������������������� 292 Suggested Readings ���������������������������������������������������������������������������������� 294 21 Viral Infections���������������������������������������������������������������������������������������� 295 21.1 General Clinical������������������������������������������������������������������������������ 295 21.2 General Imaging������������������������������������������������������������������������������ 295 21.3 General Pathologic Patterns������������������������������������������������������������ 296 21.4 RNA Viruses ���������������������������������������������������������������������������������� 296 21.4.1 Clinical������������������������������������������������������������������������������ 296 21.4.2 Imaging ���������������������������������������������������������������������������� 297 21.4.3 Pathology�������������������������������������������������������������������������� 298 21.5 DNA Viruses ���������������������������������������������������������������������������������� 300 21.5.1 Clinical������������������������������������������������������������������������������ 300 21.5.2 Imaging ���������������������������������������������������������������������������� 300 21.5.3 Bronchoscopy�������������������������������������������������������������������� 301 21.5.4 Pathology�������������������������������������������������������������������������� 303 Suggested Readings ���������������������������������������������������������������������������������� 306 22 Common Fungal Infections�������������������������������������������������������������������� 307 22.1 Aspergillosis����������������������������������������������������������������������������������� 307 22.1.1 Clinical������������������������������������������������������������������������������ 307 22.1.2 Imaging ���������������������������������������������������������������������������� 308 22.1.3 Bronchoscopy�������������������������������������������������������������������� 311 22.1.4 Pathology�������������������������������������������������������������������������� 312 22.2 Histoplasmosis�������������������������������������������������������������������������������� 315 22.2.1 Clinical������������������������������������������������������������������������������ 315 22.2.2 Imaging ���������������������������������������������������������������������������� 316 22.2.3 Bronchoscopy�������������������������������������������������������������������� 318 22.2.4 Pathology�������������������������������������������������������������������������� 318 22.3 Pneumocystis Pneumonia���������������������������������������������������������������� 321 22.3.1 Clinical������������������������������������������������������������������������������ 321 22.3.2 Imaging ���������������������������������������������������������������������������� 321 22.3.3 Bronchoscopy�������������������������������������������������������������������� 323 22.3.4 Pathology�������������������������������������������������������������������������� 323 22.4 Cryptococcus���������������������������������������������������������������������������������� 325 22.4.1 Clinical������������������������������������������������������������������������������ 325 22.4.2 Imaging ���������������������������������������������������������������������������� 325 22.4.3 Bronchoscopy�������������������������������������������������������������������� 326 22.4.4 Pathology�������������������������������������������������������������������������� 326 22.5 Blastomycosis �������������������������������������������������������������������������������� 328 22.5.1 Clinical������������������������������������������������������������������������������ 328
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22.5.2 Imaging ���������������������������������������������������������������������������� 329 22.5.3 Bronchoscopy�������������������������������������������������������������������� 330 22.5.4 Pathology�������������������������������������������������������������������������� 330 22.6 Coccidioidomycosis������������������������������������������������������������������������ 332 22.6.1 Clinical������������������������������������������������������������������������������ 332 22.6.2 Imaging ���������������������������������������������������������������������������� 332 22.6.3 Bronchoscopy�������������������������������������������������������������������� 333 22.6.4 Pathology�������������������������������������������������������������������������� 333 Suggested Readings ���������������������������������������������������������������������������������� 334 23 Parasitic Infections���������������������������������������������������������������������������������� 335 23.1 Strongyloidiasis������������������������������������������������������������������������������ 335 23.1.1 Clinical������������������������������������������������������������������������������ 335 23.1.2 Imaging ���������������������������������������������������������������������������� 335 23.1.3 Bronchoscopy�������������������������������������������������������������������� 336 23.1.4 Pathology�������������������������������������������������������������������������� 337 23.2 Dirofilariasis������������������������������������������������������������������������������������ 338 23.2.1 Clinical������������������������������������������������������������������������������ 338 23.2.2 Imaging ���������������������������������������������������������������������������� 339 23.2.3 Bronchoscopy�������������������������������������������������������������������� 339 23.2.4 Pathology�������������������������������������������������������������������������� 339 23.3 Echinococcosis�������������������������������������������������������������������������������� 341 23.3.1 Clinical������������������������������������������������������������������������������ 341 23.3.2 Imaging ���������������������������������������������������������������������������� 342 23.3.3 Bronchoscopy�������������������������������������������������������������������� 343 23.3.4 Pathology�������������������������������������������������������������������������� 343 23.4 Toxoplasmosis�������������������������������������������������������������������������������� 345 23.4.1 Clinical������������������������������������������������������������������������������ 345 23.4.2 Imaging ���������������������������������������������������������������������������� 345 23.4.3 Bronchoscopy�������������������������������������������������������������������� 346 23.4.4 Pathology�������������������������������������������������������������������������� 347 Suggested Readings ���������������������������������������������������������������������������������� 348 24 Lung Involvement by Systemic Diseases������������������������������������������������ 349 24.1 Amyloidosis������������������������������������������������������������������������������������ 349 24.1.1 Clinical������������������������������������������������������������������������������ 349 24.1.2 Imaging ���������������������������������������������������������������������������� 350 24.1.3 Bronchoscopy�������������������������������������������������������������������� 352 24.1.4 Pathology�������������������������������������������������������������������������� 353 24.2 Light Chain Deposition Disease ���������������������������������������������������� 355 24.2.1 Clinical������������������������������������������������������������������������������ 355 24.2.2 Imaging ���������������������������������������������������������������������������� 355 24.2.3 Pathology�������������������������������������������������������������������������� 357 24.3 IgG4-Related Sclerosing Disease �������������������������������������������������� 359 24.3.1 Clinical������������������������������������������������������������������������������ 359 24.3.2 Imaging ���������������������������������������������������������������������������� 359
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24.3.3 Pathology�������������������������������������������������������������������������� 360 24.4 Relapsing Polychondritis���������������������������������������������������������������� 361 24.4.1 Clinical������������������������������������������������������������������������������ 361 24.4.2 Imaging ���������������������������������������������������������������������������� 361 24.4.3 Bronchoscopy�������������������������������������������������������������������� 362 24.4.4 Pathology�������������������������������������������������������������������������� 363 24.5 Rheumatoid Nodule������������������������������������������������������������������������ 364 24.5.1 Clinical������������������������������������������������������������������������������ 364 24.5.2 Imaging ���������������������������������������������������������������������������� 364 24.5.3 Pathology�������������������������������������������������������������������������� 365 24.6 Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) ������������������������������������������������������������������ 366 24.6.1 Clinical������������������������������������������������������������������������������ 366 24.6.2 Imaging ���������������������������������������������������������������������������� 367 24.6.3 Pathology�������������������������������������������������������������������������� 368 Suggested Readings ���������������������������������������������������������������������������������� 369 Index������������������������������������������������������������������������������������������������������������������ 371
Chapter 1
Introduction to Multidisciplinary Techniques
1.1 Bronchoscopy • Transbronchial biopsy –– An essential skill all pulmonologists master during their training. –– Instrument is most commonly a forceps biopsy, but brush, needle, needle- brush, and aspiration catheter may be included in this group. Usually transnasal or transoral approach. –– Three types of forceps: cup, toothed (most common), and needle. –– Accessible even for distal peripheral lesions via bronchial lumen. Fluoroscopy may be helpful to confirm location of instrument. –– Guideline recommendations for sample number: 4–6 samples for diffuse disease. 7–8 samples for local lung condition. –– Complications are rare. –– High diagnostic yield in focal lesions and many diffuse parenchymal lung diseases. Nodules have 30–70% sensitivity if ≥2 cm and 80% for nodules >4 cm. Diffuse diseases such as Langerhans cell histiocytosis, eosinophilic pneumonia, drug-induced pneumonitis, alveolar proteinosis, and sarcoidosis have 90% sensitivity if 4 or more tissue fragments are obtained. Infections have an 83% diagnostic yield with bronchoalveolar alveolar lavage (see below).
© Springer Nature Switzerland AG 2020 C. Farver et al., Pulmonary Disease, https://doi.org/10.1007/978-3-030-47598-7_1
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1 Introduction to Multidisciplinary Techniques
• Transbronchial needle aspiration (TBNA) –– Developed to diagnose mediastinal pathology by mediastinal and/or hilar nodal samples. –– 19–25-gauge needle. –– Can be blind technique. –– Commonly used with endobronchial ultrasound-guided TBNA. –– Peripheral TBNA is used to obtain the cytology specimen from lung lesions often under fluoroscopic guidance. Increases yield in nodules inside the bronchus. –– Complications are less than 0.3%. –– Rapid onsite evaluation (ROSE) can be used during procedure to provide immediate preliminary results regarding diagnosis and quantity of material. • Endobronchial needle aspiration (EBNA) –– Used to obtain cytology specimens from endoscopically visible lesions. –– 19–22-gauge needle. Lack of crush artifact is the advantage of this technique over forceps. –– 2–3 passes usually have high diagnostic yield. –– In exophytic lesions, penetration to core of lesion increases yield of viable cells versus necrotic surface tissue. • Exfoliative respiratory cytology techniques –– Sputum cytology Easily obtained. Low diagnostic yield except for central airway lesions. –– Bronchial washings and brushings Usually done with biopsy. Must be done prior to biopsy to eliminate blood contamination. Advantage of direct visualization of lesion and sampling. But area sampled can be limited. Usually have diagnostic yield of 70–80%. –– Washings: 3–5 ml of sterile saline is installed and re-aspirated. Fresh material to laboratory for studies or put in fixative. –– Brushings Bristle brush used to scrape cells from the lesion. Direct smears made from brush material.
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• Bronchoalveolar lavage –– Used to evaluate distal airways and alveolar fluid. 100–300 ml warm saline instilled and re-aspirated at 20–100 ml aliquots. Commonly used to study diffuse disease. • Infectious workup is most commonly used especially in immunosuppressed patients. • Cell count and differential from bronchoalveolar fluid. • Commonly used to study diffuse diseases –– –– –– –– –– ––
Cultures and organismal stains can be performed. Nonneoplastic diffuse lung diseases best studied include: Interstitial lung disease Pulmonary hemorrhage Lymphoproliferative diseases Malignancy
• Transthoracic needle biopsy and aspiration –– Requires chest CT scan, ultrasound or fluoroscopic guidance (see below). –– Done for peripheral lung lesions. –– Complication rate is higher than bronchial cytology procedures. Pulmonary hemorrhage and pneumothorax. High gauge needles have fewer complications.
1.2 Imaging 1.2.1 Chest X-Ray • Equipment –– X-ray tube –– Imaging plate • Procedures –– Views Posterior-anterior (front) view Decubitus Lordotic • Common Uses –– Usually first imaging test performed for the following: Cough, fever, difficulty breathing, trauma
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1 Introduction to Multidisciplinary Techniques
• Benefits of Procedure –– –– –– ––
Painless Inexpensive Widely available Quick results
• Risks of Procedures –– Small risk of radiation exposure Harmful effects on embryo in pregnant women Minimal increased risk of cancer • Limitations –– Some parts of the chest may be hidden on standard views. –– Asthma, COPD, and pulmonary embolism cannot be seen. • Common Abnormalities on CXR –– Nodules –– Pleural abnormalities –– “Shadows” Reticular pattern Nodular pattern Cysts Honeycombing Ground glass Consolidations –– Mediastinal hilar and chest wall abnormalities
1.2.2 C hest Computerized Tomography Scans (Chest CT Scans) • Equipment –– Movable CT table –– X-ray tubes and detectors –– Computer and software to interpret multiple images to generate cross- sectional images • Procedures –– Data generated by CT scanner produces crisp images of “slices” of human body (cross-sectional images).
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–– Bone appears white, air appears black, and most soft tissues and fluid appear different shades of gray. –– Newer scanners can produce thinner slides with greater clarity in a shorter scan time. • Common Uses –– Primary comprehensive diagnostic imaging test Small airway disease • Air-trapping • Tree and bud pattern in acute, inflammatory bronchiolitis Diffuse lung diseases • Sarcoidosis –– Lung and hilar lymph node involvement • Pulmonary fibrosis –– Problem-solving tool for further evaluation of potentially abnormal findings on CXR –– Diagnosis and staging of primary lung cancer Spread of malignant disease throughout the lung and distant metastases. Planning radiation therapy and assessing treatment response. • Benefits –– –– –– ––
Painless, fast, and easy Accurate detection of disease. Can image bone and soft tissues with lung simultaneously. Can be fused with functional imaging in an attempt to differentiate benign from malignant. –– Can be used to guide needle biopsies.
• Risks –– Injected contrast material involved in allergic-like reaction to dye and kidney damage
1.2.3 CT Pulmonary Angiography • Equipment –– Iodine-containing dye (contrast media) –– CT scanner
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• Procedures –– Non-invasive imaging test for visualizing the pulmonary arteries using CT with intravenous injection of iodinated contrast. –– The contrast is injected through a small vein in the arm or leg. –– The scanning is optimally timed such that the contrast is within the pulmonary arteries at the time that the image is acquired. –– The scanning time is usually about 5 seconds, and the entire time within the scanner is approximately 5 minutes. –– Demonstrates: Normal pulmonary arteries as white (they are opacified by radio contrast dye). Blood clot (pulmonary embolism) as dark (filling defect) within the blood vessels. Size of the vessels can be accurately measured for dilatations. • Common Uses –– Aorta, pulmonary arteries, pulmonary veins –– Common diseases Pulmonary embolism Abnormalities of the aorta • Dissections • Aneurysms • Benefits –– Highly effective for diagnosing pulmonary embolism in even small pulmonary arteries. –– Painless, fast, and easy to perform. –– Can detect disease elsewhere within the lungs or adjacent structures.
1.2.4 Positron Emission Tomography (PET) • Equipment –– Non-invasive modality that focuses on biochemical changes that occur in diseased tissue. –– Performed in nuclear medicine laboratory. –– Rapid cell growth occurs in tumor and infections and leads to a higher metabolic activity. • Procedures –– Injection of radioactive glucose analog (5-fluorodeoxyglucose or FDG) into blood stream.
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–– Gamma rays emitted are detected by a special camera, converting that signal into computer-processed images. –– Can be combined with low-dose CT scan to form “fusion” images of anatomical structures (CT) and metabolic and biochemical activity in the affect region (PET). • Common Uses –– May be helpful in determining malignant and benign nodules. Not helpful in nodules less than 8 mm. –– Spread of tumor to lymph nodes and distant organs. Not useful in neurologic tissues (brain and spinal cord). –– Posttreatment follow-up PET scan may reveal residual or recurrent tumor. –– Active infection and inflammation may show false-positive metabolically active nodules. –– Slow-growing tumors may not demonstrate PET positivity.
1.2.5 Magnetic Resonance Imaging (MRI) Scan • Equipment –– Non-invasive imaging modality that uses powerful magnetic field and radio waves to generate signals from different body parts. –– Computer/software processes data to generate detailed images. • Procedures –– Chest MRI generates increased soft tissue contrast. Heart and great vessels are commonly viewed. Air in the lungs may limit MRI use. • Hyperpolarized inert gases may improve images. –– Helium –– Xenon • Common Uses –– Assessment of lung cancer to adjacent nerves, blood vessels, and the chest wall. –– Most valuable in question about metastatic spread to the vessels, heart, or chest wall. • Limitations –– Contraindicated in patients with cardiac pacemakers and defibrillators.
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–– Limited availability of technology –– Long scan time limits use in: Unstable patients Patients with claustrophobia • Ventilation/perfusion scintigraphy (VQ scanning) –– Non-invasive medical imaging test used to diagnose PE. –– Less widely used owing to wider availability of CT technology. –– Uses radioactive materials in relatively low doses, which are inhaled and injected into the human body. –– While passing through the human body, radioactive materials emit certain rays such as gamma rays. –– Gamma cameras detect rays, and data is used to create a computer-generated image of that part of the body. –– The test involves two phases: Ventilation and perfusion phases • Evaluate how well air and blood are able to circulate through the bronchial airways and the pulmonary circulation, respectively. Ventilation phase • Inhalation of a gaseous radionuclide such as xenon or technetium DTPA. • Inhaled radiotracers due to airway obstruction or pneumonia leads to image voids from the corresponding lung on the ventilation scan. Perfusion phase • Injection of a radionuclide tracer (usually radioactive technetium tagged to macroaggregated albumin) into one of the arm veins. • Tracer circulates through the lungs via the blood stream. • Blood clots within pulmonary arteries result in impaired circulation of the radionuclide in that lung or part of the lung. • Depicted as wedge-shaped area(s) of decreased uptake of radio tracer in that part of lung. • “Matched defect”
1.3 Pathology 1.3.1 Surgical Pathology • Morphologic analysis of surgical pathology specimens –– Formalin-fixed, paraffin-embedded sections. –– Usually cut on microtome at 4–5 microns. –– Hematoxylin and eosin stains are most commonly used for evaluation of tissue morphology.
1.3 Pathology
• Excisional specimens –– –– –– ––
Wedge Segmentectomy Lobectomy Pneumonectomy
• Biopsy specimens –– –– –– ––
Transbronchial Endobronchial Core needle biopsy Video-assisted thoracoscopic biopsy (VATS)
• Frozen section analysis –– Preliminary diagnosis to answer intraoperative questions Surgical margins of neoplastic resections Adequacy of tissue for postsurgical analysis Appropriate triage of fresh tissue specimen for ancillary studies • Flow cytometric analysis • Molecular and/or cytogenetic studies, if needed • Special tissue fixation procedures –– Electron microscopy –– Immunofluorescence • Ancillary studies –– Flow cytometric analysis Lymphoproliferative lesions –– Immunofluorescence Immunologically mediated diseases. Direct and indirect techniques. –– Electron microscopy Allows for ultrastructural analysis most commonly used in: • Mesothelioma • Immune complex diseases • Amyloid and light chain diseases • Histological stains –– Hematoxylin and eosin Standard stain for morphologic evaluation
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–– Connective tissue stains Elastic Trichrome Reticulin Movat pentachrome –– Mucin stains Periodic acid-Schiff Mucicarmine Alcian blue Colloidal iron Metachromatic stains –– Iron Perls Prussian blue –– Fat Oil Red O • Must be done on fresh smears or frozen tissue –– Tissue organismal stains Fungal • Silver stains • Grocott or Gomori methenamine silver • Periodic acid-Schiff Mycobacteria • Ziehl-Neelsen • Fite • Nocardia Bacteria • Gram-positive and Gram-negative organisms • Brown-Hopps • Brown and Brenn Giemsa • H. pylori • Steiner • Spirochetes • Immunohistochemical stains –– Malignancy Carcinoma
1.3 Pathology
• Epithelial antibodies –– Cytokeratin: AE1/AE3, CAM 5.2, CK7, CK20 –– Epithelial membrane antigen • Non-small cell carcinoma –– MOC-31, Ber-EP4 • Adenocarcinomas –– Carcinoembryonic antigen, MOC-31 –– TTF-1: Specific for pulmonary origin • Squamous cell carcinoma –– p40, p63, CK5/6 Mesothelioma • Calretinin, WT-1, CK5/6 • D2-40: More commonly seen in sarcomatoid variant Sarcoma • Smooth muscle tumors –– Desmin, smooth muscle actin • Skeletal muscle tumors –– Desmin • Vascular sarcomas –– CD31, CD34, ERG, factor VIII –– HHV-8: Kaposi sarcoma –– CAMTA-1: Epithelioid hemangioendothelioma Lymphoma –– CD20, CD45, CD43, CD45RB Melanoma –– S-100 protein, Melan A, SOX-10 • Infections –– Antibodies to: Cytomegalovirus Adenovirus Herpesvirus
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1.3.2 Cytopathology • Cytopreparatory techniques –– A sample (not the entire nodule) is removed and examined directly under a microscope to look for signs of cancer or other diseases. The goal is to reduce artificial cellular changes of the tissue sample while optimizing diagnostic cellular samples. Methods include: • Direct smears –– Simplest preparation –– Best for small volume cellular samples (i.e., fine needle aspiration (FNA)) –– 1–2 drops of material –– Two slides produced via smear One air-dried • Useful for rapid onsite evaluation (ROSE) for adequacy –– Bronchoscopy suite or interventional radiology –– Can be stained for Giemsa stains (e.g., Diff-Quick stain) • Excellent cytoplasmic details –– Mucin may also be visualized. • Valuable in the identification of microorganisms One fixed (95% alcohol) • Usually Papanicolaou stained –– Excellent nuclear detail Chromatin Nucleoli Orangeophilia in keratinizing squamous epithelium and neoplasia • Hematoxylin and eosin less commonly used Concentration of liquid samples by cytocentrifugation • Proprietary liquid-based systems (e.g., ThinPrep and SurePath) –– Centrifugation may: Enhance specimen quality by eliminating air-drying artifacts Diminish false-negative rates
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–– Some include filtration step to decrease background debris resulting in sharper cytomorphologic features. Cell blocks/pellets • Can be obtained with both needle aspiration samples and fluids with high enough cellularity. • Processed histologically for use in other testing. –– Histochemistry Mucin stains • Organism stains GMS, AFB –– Immunohistochemistry –– In situ hybridization –– Molecular tests • Can be fixed in either alcohol or formalin
Suggested Readings Dadhich H, Toi PC, Siddaraju N, et al. A comparative analysis of conventional cytopreparatory and liquid based cytological techniques (SurePath) in evaluation of serous effusion fluids. Diagn Cytopathol. 2016;44:874–9. Ghosh S, Haramati LB. Imaging modalities in respiratory diseases. Ch 4-2. In: Duffy R, Berman A, Prezant D, editors. Respiratory Disease and the Fire Service – IAFF. Washington DC; 2016. p. 293–312. Hogan PG, Donald KJ, McEvoy JD. Immunofluorescence of lung biopsy tissue. Am Rev Respir Dis. 1978;118:537–45. Keebler CM. In: Bibbo M, editor. Cytopreparatory Techniques in Comprehensive Cytopathology. 2nd ed. Philadelphia: WB Saunders; 1997. p. 889–917. Magaki S, Hojat SA, Wei B, So A, Yong WH. An introduction to the performance of immunohistochemistry. Methods Mol Biol. 1897;2019:289–98. Mazzone P, Jain P, Arroliga AC, Matthay RA. Bronchoscopy and needle biopsy techniques for diagnosis and staging of lung cancer. Clin Chest Med. 2002;23:137–58. Prasoon J, Hadique S, Mehta AC. Transbronchial lung biopsy. In: Mehta A, Prasoon J, editors. Interventional Multi-disciplinary Techniques: Bronchoscopy: A Clinical Guide. New York: Springer; 2013. Rajesh R, Patel J, Utz P. Bronchoscopic lung Biopsy. In: Ko-Pen Wang KP, Mehta AC, Turner JF, editors. Flexible Bronchoscopy. 3rd ed. Oxford, UK: Willey-Blackwell; 2012. Yarmus L, Van der Kloot T, Lechtzin N, et al. A randomized prospective trial of the utility of rapid on-site evaluation of transbronchial needle aspirate specimens. J Bronchology Interv Pulmonol. 2011;18:121–7. Webpath.med.utah.edu
Chapter 2
Benign Tumors
2.1 Hamartoma 2.1.1 Clinical • Contains varying amounts of at least two types of mesenchymal tissue including hyaline cartilage, adipose tissue, smooth muscle, and fibrovascular tissue. • The most common benign pulmonary neoplasm. • Most commonly peripheral, well-circumscribed nodules. –– Distributed randomly throughout the lungs. • 10% are found centrally as endobronchial lesions. –– These may cause obstructive symptoms when large.
2.1.2 Imaging • The most common presentation is a solitary pulmonary nodule (SPN), which is defined as smaller than 3 cm and surrounded by normal lung (Fig. 2.1a, b). • The imaging differential diagnosis of SPN. –– Granuloma (TB, Histoplasma), hamartoma, and malignancy such as bronchogenic carcinoma. • Usually smooth margins, which may be mildly lobulated. • Have benign pattern of calcification on CXR or CT (coarse, “popcorn” type, central) and presence of fat densities (MRI > CT) when present are pathognomonic.
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Fig. 2.1 Hamartoma. Unenhanced CT chest scan. (a). lung, (b). mediastinal windows) A right lower lobe smoothly marginated nodule with central fat and soft tissue attenuation suggestive of a hamartoma (arrow). Note pulmonary vasculature which may simulate nodular densities (arrowheads) can be differentiated from true lung nodules by the adjacent bronchi (red thin arrows)
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Fig. 2.2 Hamartoma. Bronchoscopic image. (a) The smooth, round obstructive lesion and (b) after biopsy and endobronchial ablation
2.1.3 Bronchoscopy • Bronchoscopic view notes the smooth round obstructive lesion (Figs. 2.2a, b, 2.3a–e). • When large can cause obstructive symptoms. • When the biopsy removes the surface epithelium, lipomas often have yellow fatty material that can be identified (Fig. 2.3d). • Endobronchial ablation can remove the lesion (Fig. 2.3e). • Additional therapy is typically not needed for these benign lesions. • Recurrence has been rarely reported.
2.1 Hamartoma
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Fig. 2.3 Hamartoma/lipoma. CT scan and bronchoscopic images. (a) CT scan revealing fatty tissue in hilum bulging into lumen of the lingular bronchus (arrow). (b) Bronchoscopic images reveal smooth lesion extruding from lumen. (c) Yellow tissue under the mucosa suggestive of lipoma (arrow). (d) Lipid droplets (arrow) are seen as the biopsy forceps close on the lesion. (e) Lingular bronchus after cautery ablation of the lesion
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Fig. 2.4 Hamartoma. Excisional biopsy. (a) Hamartoma with predominantly cartilaginous features extending into proximal airway lumen. (b) Entrapped respiratory epithelium is seen within cartilaginous tissue Fig. 2.5 Hamartoma. Excisional biopsy. Hamartoma with predominantly lipomatous elements excised from lumen of proximal airway
2.1.4 Pathology 2.1.4.1 Surgical Pathology • Microscopic evidence of at least two of the following: hyaline cartilage, adipose tissue, smooth muscle, and fibrovascular tissue (Fig. 2.4a, b). –– Usually chondroid or chondromyxoid tissue is present. • Entrapped benign respiratory epithelium is present (Fig. 2.4b). • Endobronchial variant can have a predominant lipoma type (Fig. 2.5). 2.1.4.2 Cytopathology • Fragments of cartilaginous or fibromyxoid tissue classically are present (Fig. 2.6). • Other elements such as adipose tissue and muscle fibers are possible.
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Fig. 2.6 Hamartoma. Cytopathology direct smear. Fragments of cartilage and fibromyxoid tissue present in cytology smear from hamartoma. (Papanicolaou stain)
Fig. 2.7 Hamartoma. Cytopathology direct smear. Particles of bland adipose tissue and traversing capillaries in direct smear of lipoma. (Papanicolaou stain)
• Alveolar parenchyma, ciliated and nonciliated epithelial cells such as reserve cells, and metaplastic cells typically seen. • When predominantly lipoma, particles of cytologically bland adipose tissue can be seen (Fig. 2.7). –– Occasional traversing capillaries are present. 2.1.4.3 Pathological Differential Diagnosis • Chondroma –– Rare lesion found in Carney’s triad (gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paragangliomas) containing only cartilage (hyaline or myxohyaline).
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–– These have only cartilage and do not have entrapped respiratory epithelium. • Metastatic lesions from leiomyosarcoma, chondrosarcomas, etc. –– Metastatic sarcomas have significant cellular atypia unlike hamartomas. 2.1.4.4 Ancillary Studies • Immunohistochemical studies can define mesenchymal elements present but are usually not needed for diagnosis.
2.2 Sclerosing Pneumocytoma 2.2.1 Clinical • • • •
80% found in females, usually middle-aged. Peripheral and solitary lesions. Asymptomatic. Regional lymph node metastases have been reported but are rare.
2.2.2 Imaging • Most present as solitary lung nodule or mass with similar imaging features as alveolar adenoma (Fig. 2.8a–d). • Additional CT signs described in the case of solitary lung nodule are as follows: –– Marginal pseudocapsule sign Compressed adjacent lung parenchyma –– Overlying vessel sign Engorged feeding vessel adjacent to lesion –– Air crescent sign Crescentic lucency without lung markings around the lesion. –– Halo sign Peripheral ground-glass opacity surrounding the lesion
2.2 Sclerosing Pneumocytoma
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Fig. 2.8 Sclerosing pneumocytoma. (a, b) Contrast-enhanced CT chest shows a 3 cm, well- circumscribed, soft tissue attenuation mass in the medial left lower lobe. (c, d) PET scan shows uniform and modest FDG uptake in the nodule
2.2.3 Pathology 2.2.3.1 Surgical Pathology • Two cell types present (Fig. 2.9a, b). • • • •
Cuboidal surface cells, pneumocyte-like appearance Stromal cells Both neoplastic Four growth patterns can be seen: • • • •
Papillary Sclerotic Solid Hemorrhagic
• Lesion can be diagnosed on transbronchial or needle biopsy (Fig. 2.10a, b). • Immunohistochemical studies may be helpful to distinguish it from a low- grade adenocarcinoma. (See Ancillary Studies.)
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Fig. 2.9 Sclerosing pneumocytoma. Wedge excision. (a) Hemorrhagic pattern of this lesion reveals large hemorrhagic spaces with areas of solid pattern. (b) High power reveals two cell populations with cuboidal surface cells with pneumocyte-like appearance (arrow) and stromal cells with solid nests (arrowhead)
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Fig. 2.10 Sclerosing pneumocytoma. Core biopsy. (a) Biopsy of lesion reveals predominantly solid nests of stromal cells with scattered nests of surface, pneumocyte-type cells (arrows). (b) Immunohistochemical studies for pancytokeratin highlight surface cells; note that stromal cells are negative for pancytokeratin
2.2.3.2 Cytopathology • Epithelial cells surrounding delicate vascular structures (Fig. 2.11). • Epithelial cells resemble hobnail nonneoplastic type 2 pneumocytes, sometimes with intranuclear cytoplasmic inclusions. • Singly dispersed epithelial cells and stromal cells present apart from papillae and acini. 2.2.3.3 Differential Diagnosis • Carcinoid tumor. • A single cell population versus two cell populations in sclerosing pneumocytoma.
2.3 Alveolar Adenoma
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Fig. 2.11 Sclerosing pneumocytoma. Cytopathology direct smear. Lesional epithelial cells surrounding a delicate vascular structure with a type 2 pneumocyte-type morphology. (Papanicolaou stain)
• Positive for neuroendocrine markers, which are negative in sclerosing pneumocytoma. • Papillary adenocarcinoma. • Single cell population. • Malignant cytologic atypia. 2.2.3.4 Ancillary Studies • Cuboidal surface cells • +: Pancytokeratin, epithelial membrane antigen (EMA), CAM 5.2, CK7, TTF-1, and Napsin A (Fig. 2.10b) • Stromal cells • +: CAM 5.2 (focal), CK7 (focal), EMA, TTF-1 • -: Pancytokeratin
2.3 Alveolar Adenoma 2.3.1 Clinical • • • • •
Exceedingly rare. Asymptomatic. Usually an incidental finding. More common in lower lobes but can be found in any lobe. Benign lesion with no malignant potential.
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Fig. 2.12 Alveolar adenoma. Contrast enhanced axial CT chest images (a-mediastinal and b-lung windows) show a subpleural, well-circumscribed, homogenously hypodense lung nodule (arrows) in the RML with minimal to no peripheral enhancement (dome of right hemi-diaphragm highlighted by star)
2.3.2 Imaging • Usually reported as solitary peripheral or subpleural, round or ovoid nodule with smooth margins and homogenous attenuation (Fig. 2.12a, b). • Imaging features shared by other benign lesions (sclerosing hemangioma, papillary adenoma, hamartoma, granuloma, and leiomyoma). • Spotty contrast enhancement has been shown, in a pattern similar to but less than sclerosing pneumocytoma.
2.3.3 Pathology 2.3.3.1 Surgical Pathology • • • • • •
Multicystic mass. Cystic spaces resembling alveolar spaces (Fig. 2.13a, b). May be larger toward the center of lesion. Cuboidal epithelial cells resembling pneumocytes line spaces. Stain like type II pneumocytes. Bland spindle stromal cells.
2.3.3.2 Differential Diagnosis • Lymphangioma. –– Cells lining spaces are D2-40 positive and not cytokeratin positive.
2.4 Papillary Adenoma
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Fig. 2.13 Alveolar adenoma. Wedge excision. (a) Multiple cystic spaces lined by thin walls resembling alveolar spaces. (b) Alveolar space-like areas have proteinaceous material and are lined by cuboidal cells. Bland spindle cells are present in underlying stroma
• Sclerosing pneumocytoma. • Metastatic sarcoma may have cystic spaces. –– Have marked cytologic atypia. 2.3.3.3 Ancillary Studies • Epithelial cells lining cystic spaces are +: TTF-1 and CEA. • Stromal cells may be positive for smooth muscle markers.
2.4 Papillary Adenoma 2.4.1 Clinical • • • • •
Very rare Somewhat male predominance Clinically asymptomatic Picked up as incidental findings on imaging studies Benign without metastatic potential
2.4.2 Imaging • Peripheral and solitary mass • Well-circumscribed
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Fig. 2.14 Papillary adenoma. Wedge excision. (a) Well-circumscribed intra-parenchymal nodule with papillary architecture. (b) A single layer of cuboidal and columnar cells over a fibrovascular stroma
2.4.3 Pathology 2.4.3.1 Surgical Pathology • Well-circumscribed (Fig. 2.14a, b) • Bland cuboidal to columnar epithelium lining stroma with fibrovascular stroma 2.4.3.2 Differential Diagnosis • Sclerosing pneumocytoma. • Varied patterns versus a uniform pattern for papillary adenoma. • Two cell populations in sclerosing pneumocytoma with stromal cells negative for pancytokeratin. • Papillary adenocarcinoma. –– More marked cellular atypia than in papillary adenoma. 2.4.3.3 Ancillary Studies • Surface cuboidal/columnar cells are +: TTF-1, CK-7, pancytokeratin, and EMA.
2.5 Solitary Papilloma 2.5.1 Clinical • Very rare as single lesions. • Most commonly endobronchial. • Men>women.
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• Obstructive symptoms. • Association with HPV 6/11 and 16/18 can be demonstrated in less than half of squamous papillomas. • All solitary papillomas have a benign clinical course with complete excision.
2.5.2 Imaging • Small endobronchial polyps or airway nodules
2.5.3 Bronchoscopy • Single polyp in wall of large proximal airways. • Multiple polyps usually indicate papillomatosis.
2.5.4 Pathology 2.5.4.1 Surgical Pathology • Bland stratified squamous, glandular, or a mix of squamous and glandular epithelium overlying a fibrovascular core. • Squamous papilloma is most common (Fig. 2.15a, b).
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Fig. 2.15 Squamous papilloma. Excisional biopsy. (a) Exophytic squamous papilloma in proximal airway extending into lumen. (b) Perinuclear clearing consistent with koilocytic changes and basal to surface maturation is seen
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• Koilocytic changes can be seen. • Maturation from basal layer to surface is seen. • Glandular polyps will have pseudostratified of columnar epithelium (Fig. 2.16a, b). • Can be ciliated or nonciliated. • Mixed glandular and squamous papillomas (Fig. 2.17a, b). • Squamous component will not show viral effects and may represent metaplastic change. • Glandular component can be columnar, pseudostratified columnar, and ciliated or nonciliated. 2.5.4.2 Differential Diagnosis • Inflammatory polyps • Squamous cell carcinoma a
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Fig. 2.16 Glandular papilloma. Excision biopsy. (a) Papilloma arising out of cartilaginous airway. (b) Epithelium is predominantly pseudostratified columnar without cilia
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Fig. 2.17 Mixed glandular and squamous papilloma. Excisional biopsy. (a) Lesion is arising out of proximal airway and has both glandular (right side) and squamous (left side) epithelium. (b) Glandular epithelium is intermixed with squamous (arrow) areas. The surrounding alveolar spaces contain mucin
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• Squamous papillomatosis • Multiple papillomas with malignant degeneration possible • More commonly in laryngeal and tracheal areas 2.5.4.3 Ancillary Studies • Demonstration of HPV 6/11 and/or 16/18 can be seen in some cases of squamous papillomas. • Glandular or mixed papillomas do not have HPV 6/11 or 16/18 association.
Suggested Readings Ahmed S, Arshad A, Mador MJ. Endobronchial hamartoma; a rare structural cause of chronic cough. Respir Med Case Rep. 2017;22:224–7. Cornejo KM, Shi M, Akalin A, et al. Pulmonary papillary adenoma: a case report and review of the literature. J Bronchology Interv Pulmonol. 2013;20:52–7. Dettrick A, Meikle A, Fong KM. Fine-needle aspiration diagnosis of sclerosing hemangioma (pneumocytoma): report of a case and review of the literature. Diagn Cytopathol. 2014; 42:242–6. Flieder DB. Benign neoplasms of the lung, Chapter 31, In: Pulmonary Pathology, Zander D, Farver CF, eds. a volume in the series Foundations in Diagnostic Pathology, J Goldblum ed., 2nd ed. Philadelphia, PA: Elsevier; 2017. Keylock JB, Galvin JR, Franks TJ. Sclerosing hemangioma of the lung. Arch Pathol Lab Med. 2009;133:820–5. Kozu Y, Maniwa T, Ohde Y, Nakajima T. A solitary mixed squamous cell and glandular papilloma of the lung. Ann Thorac Cardiovasc Surg. 2014;20(Suppl):625–8. Shin SY, Kim MY, Oh SY, Lee HJ, Hong SA, Jang SJ, Kim SS. Pulmonary sclerosing pneumocytoma of the lung: CT characteristics in a large series of a tertiary referral center. Medicine (Baltimore). 2015;94(4):e498. Suut S, Al-Ani Z, Allen C, Rajiah P, Sabih DE, Al-Harbi A, et al. Pictorial essay of radiological features of benign intrathoracic masses. Ann Thorac Med. 2015;10(4):231–42.
Chapter 3
Salivary Gland-Like Tumors
3.1 Mucoepidermoid Carcinoma (MEC) 3.1.1 Clinical • • • • • • • •
Approximately 1% of lung neoplasms. No gender predominance. No association with smoking. Smoothly marginated nodule or mass commonly arising from a distal bronchus (segmental > lobar/main bronchus or trachea). Wheezing, cough, and hemoptysis are usual symptoms. Some patients may be asymptomatic. Low-grade lesions have excellent prognosis. High-grade lesions can metastasize to bone, the liver, or the brain.
3.1.2 Imaging • Imaging finding of endoluminal mass in the tracheobronchial tree is fairly nonspecific. • Punctate calcifications are fairly common. • MEC is a large, well-circumscribed mass arising from/in close proximity to a segmental bronchus (Fig. 3.1a, b). • Mucoid impaction in distal obstructed bronchi or distal atelectasis is common.
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Fig. 3.1 Mucoepidermoid carcinoma, low grade. (a) Unenhanced CT chest axial images in mediastinal window demonstrate a large, well-circumscribed mass arising from/in close proximity to a segmental bronchus in the LLL with punctate eccentric calcification in the tumor (arrow) and mild distal linear atelectasis. (b) Lung windows highlight mass
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Fig. 3.2 Mucoepidermoid carcinoma, low grade, bronchoscopic image. (a) Tan-pink-gray intraluminal mass. (b) Hemorrhagic ulcer bed present after bronchoscopic excision of mass
3.1.3 Bronchoscopy • Commonly present as gray-white-pink polypoid lesions in proximal airways (Fig. 3.2a). • A combination of needle aspiration and endobronchial biopsy or excisional biopsy is useful to make a diagnosis. • Biopsy near the charred area of lesion surface after laser ablation can lead to a non-diagnostic result (Fig. 3.2b). • Bleeding risk is not elevated for this kind of tumor, but the lesion location and size make this a more difficult case. • Mucoepidermoid tumors are more amenable to surgical resection since they tend to be very localized.
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3.1.4 Pathology 3.1.4.1 Surgical Pathology • Three cell types can be present: mucin-secreting, squamoid, and intermediate cells (Fig. 3.3a–c). • All three cell types can be seen on small biopsies (Fig. 3.4a, b). • Solid and cystic patterns may be present. • Cystic component usually consists of mucin-secreting columnar cells (Fig. 3.3a). • Solid component usually consists of intermediate and/or squamoid cells (Fig 3.3b). • Can be subclassified into low and high grade. • Low grade: • Usually contains all three cell types. • Solid and cystic patterns can be present. • Stromal calcification and ossification are often seen. • High grade: • A rare diagnosis – histologically similar to adenosquamous carcinoma. • Atypical squamoid and intermediate cells usually comprise this neoplasm. • Cyst and glandular formation is rare. • Exophytic endobronchial growth is common. • May have transitional areas to low-grade MEC. 3.1.4.2 Cytopathology • Cohesive sheets and three-dimensional aggregates of mixed neoplastic squamoid and mucus-secreting glandular cells (Fig. 3.5). • Admixed “intermediate” and clear cells often present. • Extracellular mucus material common in lower-grade lesions. • Higher-grade lesions with overt features of malignancy, often resembling a nonkeratinizing squamous carcinoma and sometimes associated with necrosis.
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Fig. 3.3 Mucoepidermoid carcinoma, low grade, resection specimen. (a) Low-power view of intraluminal MEC. (b) Surface reveals solid cells and surface epithelial mucin-producing cells. (c) Mucicarmine stain highlights mucin-secreting cells
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Fig. 3.4 Mucoepidermoid carcinoma, low grade, biopsy specimen. (a) Low-power view of endobronchial biopsy specimen with bland epithelioid cells and sclerosis. (b) Solid cells with bland nuclei Fig. 3.5 Mucoepidermoid carcinoma, low grade, cytologic specimen. Modified Giemsa stain of cohesive sheet of squamoid and mucus-secreting glandular cells. Background reveals mucus material
3.1.4.3 Pathological Differential Diagnosis • Low-grade MEC. • Low-grade adenocarcinoma. • Solid cells may be confused with carcinoid neoplasm. • High-grade MEC. • Adenosquamous cell carcinoma. • Difficult to reliably distinguish this from high-grade MEC without MAML2 rearrangement evaluation.
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3.1.4.4 Ancillary Studies • Mucin stains are helpful in revealing mucin-secreting cells (Fig. 3.3c). • TTF-1 and Napsin A are negative and may help to differentiate from adenocarcinoma. • MAML2 rearrangement is diagnostic of MEC. • Fusion gene CRTC1-MAML2 present in both low- and high-grade MEC.
3.2 Adenoid Cystic Carcinoma 3.2.1 Clinical • May present with post-obstructive pneumonitis or wheezing. • May be clinically misdiagnosed as asthma. • Circumferential and/or longitudinal mural thickening and tracheal stenosis (rare presentation).
3.2.2 Imaging • Polypoidal or lobulated mass arising from the trachea or main bronchi with luminal encroachment and focal nodular wall thickening (common presentation) (Fig. 3.6a, b). • Intra-tumoral calcifications are rare.
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Fig. 3.6 Adenoid cystic carcinoma. (a) Contrast enhanced CT chest axial mediastinal window and (b) coronal lung window images demonstrate a smoothly marginated, polypoidal mass growing into the tracheal lumen with semi-circumferential, focal mural thickening along the left lateral tracheal wall (arrows)
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3.2.3 Bronchoscopy • Polypoid or annular mass in proximal airways. • Differential diagnoses include the following: • Squamous cell carcinoma • Carcinoid (young adult, vascular enhancement) • Metastasis (direct invasion from the lung, thyroid; distant metastasis from melanoma, renal, etc.) • Papilloma (HPV infection, nasopharyngeal involvement)
3.2.4 Pathology 3.2.4.1 Surgical Pathology • • • • • •
Epithelial and myoepithelial cells (Fig. 3.7a–c). Epithelial cells have bland nuclei. Architecture includes solid, tubular, and cribriform patterns. Two layers of cells with luminal (cuboidal) and peripheral/myoepithelial cells. PAS-positive basal lamina material. Perineural invasion is common.
3.2.4.2 Cytopathology • Cohesive sheets and three-dimensional aggregates of uniform basaloid cells with scant cytoplasm (Fig. 3.8). • Associated with hyaline globules of basement membrane material that appear as pale, transparent, blue-green rounded balls on Papanicolaou and are metachromatic on modified Giemsa stains. 3.2.4.3 Pathological Differential Diagnosis • Adenocarcinoma of the lung • Basaloid squamous carcinoma
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Fig. 3.7 Adenoid cystic carcinoma, resection specimen. (a) Tumor nodule arising within cartilaginous airway (arrow) with predominantly cribriform pattern of neoplastic cells. (b) Tumor cells with round, uniform, hyperchromatic nuclei line cystic spaces filled with pale-blue glycosaminoglycans. (c) Two cell populations with cuboidal cells and flat, myoepithelial cells (arrow)
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Fig. 3.8 Adenoid cystic carcinoma, cytopathology (Papanicolaou, direct smear). Three-dimensional aggregates of uniform basaloid cells with scant cytoplasm associated with hyaline globules of basement membrane material
3.2.4.4 Ancillary Studies • Tubules formed by two layers of cells with following immunophenotype are similar to other epithelial-myoepithelial neoplasms. • Luminal cells: (+) for cytokeratin and epithelial membrane antigen (EMA). • Peripheral/myoepithelial cells: (+) for p63, S-100, and smooth muscle actin.
Suggested Readings Cipriani NA, Lusardi JJ, McElherne J, Pearson AT, Olivas AD, Fitzpatrick C, Lingen MW, Blair EA. Mucoepidermoid carcinoma: a comparison of histologic grading systems and relationship to MAML2 rearrangement and prognosis. Am J Surg Pathol. 2019;43:885–97. Dacic S, Gilbert S, Ocak I, Lacomis J. Salivary gland neoplasm of the lung, chapter 30. In: Spencer’s pathology of the lung. sixth ed. New York: Cambridge University Press; 2013. p. 1127–50. Falk N, Weissferdt A, Kalhor N, Moran CA. Primary pulmonary salivary gland-type tumors: a review and update. Adv Anat Pathol. 2016;23:13–23. Kalhor N, Moran CA. Pulmonary mucoepidermoid carcinoma: diagnosis and treatment. Expert Rev. Respir Med. 2018;12:249–55.
Chapter 4
Common Non-Small Cell Carcinomas
4.1 Adenocarcinoma 4.1.1 Clinical • The most common type of non-small cell carcinoma. • Causes include cigarette smoking, radon, other environmental agents, and air pollution. • May occur in never smokers. • Clinical symptoms are variable from asymptomatic to chest pain, shortness of breath, and unresolving infiltrates/consolidations.
4.1.2 Imaging • Imaging findings depend on histologic growth pattern. • Single nodule or mass, consolidation or GGO, or multi-centric disease (nodules or masses) (Fig. 4.1a–c). • Nodules can be solid, part-solid (ground-glass with solid components) or ground- glass attenuation (Fig. 4.2a, b). • Spiculated margins, pleural tags, “bubble lucencies or pseudo-cavitations,” “cheerio sign,” air bronchograms and CT angiogram signs, as well as “crazy- paving pattern” may be observed (Figs. 4.3a, b and 4.4a, b). • Percentage of solid component increases with more aggressive adenocarcinoma subtypes, and GGO usually correlates with predominant or purely lepidic pattern of histologic growth.
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Fig. 4.1 Adenocarcinoma. Axial CT chest (lung windows). (a) Small GGO in the LUL which could represent AAH or AIS (arrow). (b) Follow-up CT after 5 years demonstrates a 4 mitoses per 10 High power fields (HPF). 10.2.4.2 Cytopathology • FNA samples have variably cellular (often low cellularity). • Lesional cells in loose aggregates, some singly dispersed and most tumor cells often cytologically bland, resembling fibroblasts (Fig. 10.17). • Small nuclei are oval to elongated, some with bipolar tapering.
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Fig. 10.17 Fine needle aspiration cytology demonstrates lesional cells in loose aggregates, some singly dispersed. Cells are most often cytologically bland, resembling fibroblasts, (Papanicolaou, direct smear)
• Delicate, poorly defined cytoplasm with a syncytial appearance and scattered naked nuclei. • Cytoplasm may appear myxoid. 10.2.4.3 Pathological Differential Diagnosis • Other mesenchymal tumors of the pleura, including sarcomas (synovial, leiomyosarcoma, and peripheral nerve sheath tumor). • Sarcomatoid mesotheliomas may be considered but are usually present as diffuse, pleura disease and not as a mass; imaging studies are useful in this differential. (See above.) • Type A thymoma. 10.2.4.4 Ancillary Studies • Immunohistochemical studies are most useful for a definitive diagnosis on small core needle biopsies and cytology. –– CD34 and STAT 6 are usually positive (Fig. 10.18a–c). –– SFT and other spindle cell lesion markers: Mesothelioma markers: Cytokeratins, calretinin, WT-1, and D2-10 are negative in SFT. Sarcoma markers: S-100 and smooth muscle actin (SMA) are usually negative in SFT. Type A thymoma markers: Cytokeratin is negative in SFT. Synovial sarcoma specific markers: TLE-1 and CD99 are negative in SFT. • The t(X;18)(p11.2q11.2) translocation is present only in synovial sarcomas.
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Fig. 10.18 Solitary fibrous tumor. (a) Core needle biopsy of solitary fibrous tumor reveals diagnostic pattern of spindle cells and small vessels. (b) Immunohistochemical study with STAT-6 reveals diffuse nuclear staining. (c) Immunohistochemical study with CD34 has more variable cytoplasmic staining
Suggested Readings Aluja Jaramillo F, Gutierrez F, Bhalla S. Pleural tumours and tumour-like lesions. Clin Radiol. 2018;73:1014–24. Attanoos RL, Pugh MR. The diagnosis of pleural tumors other than mesothelioma. Arch Pathol Lab Med. 2018;142:902–13. Chapel DB, Churg A, Santoni-Rugiu E, Tsujimura T, Hiroshima K, Husain AN. Molecular pathways and diagnosis in malignant mesothelioma: a review of the 14th international conference of the international mesothelioma interest group. Lung Cancer. 2019;127:69–75. Galateau-Salle F, Churg A, Roggli V. Travis WD; World Health Organization Committee for Tumors of the Pleura. The 2015 World Health Organization Classification of Tumors of the Pleura: advances since the 2004 classification. J Thorac Oncol. 2016;11:142–54. Tsao AS, Lindwasser OW, Adjei AA, Adusumilli PS, Beyers ML, Blumenthal GM, et al. Current and future management of malignant Mesothelioma: a consensus report from the National Cancer Institute, thoracic malignancy steering committee, International Association for the Study of Lung Cancer, and Mesothelioma Applied Research Foundation. J Thorac Oncol. 2018;13:1655–67. You X, Sun X, Yang C, Fang Y. CT diagnosis and differentiation of benign and malignant varieties of solitary fibrous tumor of the pleura. Medicine (Baltimore). 2017;96:e9058.
Chapter 11
Chronic Obstructive Pulmonary Diseases
11.1 Emphysema 11.1.1 Clinical • Defined as abnormal, permanent enlargement of the airspaces distal to the terminal bronchiole due to destruction of their walls. • Dyspnea is the main clinical findings; spirometry reveals decreased FEV1. • Three major clinically significant types: • Centrilobular –– Most common. –– Strongly associated with smoking. • Panacinar –– Associated with alpha-1 antitrypsin deficiency. –– Rare causes include familial, injection abuse of methylphenidate, hypocomplementemic urticarial vasculitis (HVUS). • Distal acinar –– May be associated with smoking. –– Most commonly found in young males with pneumothorax. • One clinical minor type without clinical significance. • Irregular emphysema. –– Usually secondary to scarring of adjacent lung.
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Fig. 11.1 Centrilobular emphysema. CT chest axial lung windows. (a) Mild, upper lobe predominant emphysema. A well-defined RUL lucency with “peripheral dot” suggestive of centrilobular artery (arrow) is surrounded by normal lung architecture. (b) Severe, diffuse emphysema with bilateral “holes” with no walls, surrounding small vessels and minimal preserved peripheral normal lung. Note “saber-sheath” morphology of the trachea (arrow), often associated with severe COPD. (c) Right upper lobe semi-solid mass (arrow) with centrilobular emphysema in surrounding lung
11.1.2 Imaging 11.1.2.1 Centrilobular • Upper lung zone predominant (Fig. 11.1a, b). • Multiple, round, lucencies (destroyed lung, dilated respiratory bronchiole) at the center of the secondary pulmonary lobule, surrounding a preserved centrilobular artery, which often presents as a “dot”; without any walls (Fig. 11.1a). • Can have normal peripheral and basilar lung parenchyma (in mild-moderate cases). • Found in the setting of a history of smoking and can be associated with lung carcinoma (Fig. 11.1c). 11.1.2.2 Panacinar • Usually basilar predominant (or diffuse), but most pronounced in lower lobes (Fig. 11.2a, b).
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• Uniform low attenuation of the entire secondary pulmonary lobule (destruction of the entire lobule distal to the respiratory bronchiole), without normal lung (Fig. 11.2a, b). 11.1.2.3 Distal Acinar • Usually peripheral, apical, or dorsal (Fig. 11.3a, b). • Sub-pleural and/or peri-fissural blebs (10 mm) due to destruction of the peripheral portions of the secondary pulmonary lobule; can cause pneumothorax in young adults (Fig. 11.3a, b). • Adjacent lung often normal. a
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Fig. 11.2 Panacinar emphysema. CT chest axial image in lung window (a) setting demonstrates panlobular emphysema. There is complete replacement of normal lung architecture in both lower lobes with lucent lung parenchyma. (b) Coronal reformatted minimum intensity projection image, which has high sensitivity for detection of subtle emphysematous changes (seen in the upper lobes), clearly reveals lower lobe predominance
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Fig. 11.3 Distal acinar emphysema. (a) HRCT axial images demonstrate multiple bullae (>1 cm) and small blebs ( peripheral (CF, ABPA) (Fig. 11.20a, b)
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Fig. 11.19 Bronchiectasis. HRCT image shows dilated airways (blue arrows), >1.5 times larger than accompanying pulmonary artery (yellow arrows) in cross-section (“signet ring” appearance), and uniform, non-tapered bronchi with wall thickening (“tram-track” sign) in long axis (white arrows)
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Fig. 11.20 Cystic bronchiectasis. (a) HRCT chest demonstrates thick-walled, cystic bronchiectasis in the RLL (star). (b) Infected, thick-walled, cystic bronchiectasis in the upper lobes. Note intracavitary debris in the large RUL cavity (mycetoma)
11.3.3 Bronchoscopy • The role of bronchoscopy is usually to define cause of obstruction in localized bronchiectasis and to rule out complications including infection (fungal). • Bronchoscopy is commonly used to obtain cultures and clear endobronchial lesions that may be associated with bronchiectasis (Fig. 11.21).
11.3.4 Pathology 11.3.4.1 Surgical Pathology • Inflamed airways with marked neutrophilic inflammation and reactive bronchus- associate lymphoid tissue (BALT) (Fig. 11.22). • Chronic sequelae of airways are common including epithelial erosions with squamous metaplasia and fibrosis of the airway wall.
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Fig. 11.21 Bronchiectasis. Direct bronchoscopic image. Purulent secretions associated with Pseudomonas infection. Therapeutic aspiration of secretions was performed and microbiological cultures were obtained
Fig. 11.22 Bronchiectasis. Explant pneumonectomy. Neutrophilic inflammation and increased bronchus- associated lymphoid tissue (BALT) in case of cystic fibrosis
11.3.4.2 Cytopathology • Marked neutrophilic and lymphocytic inflammation with degenerating epithelium, mucous, and metaplastic squamous epithelium are common. • Fungi (Aspergillus) may be seen as colonizers (aspergilloma) within mucoid impaction. 11.3.4.3 Ancillary Studies • Tissue organismal stains to highlight fungal hyphae or acid-fast organism may be helpful. • Movat pentachrome stains to evaluate amount of fibrosis and transmural bronchial/bronchiolar destruction can be used but are usually not needed.
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Suggested Readings Emphysema Churg A, Wright JL. Proteases and emphysema. Curr Opin Pulm Med. 2005;11:153–9. Greene R. Saber-sheath. Trachea: Relation to Chronic Obstructive Pulmonary Disease Am J Roentgenol March. 1978;130:441–5. Hogg JC. A pathologist’s view of airway obstruction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186: v-vii. Litzky LA, Green LK. Emphysema and diseases of large airways. Chap. 20. In: Pulmonary Pathology, Zander DS, Farver CF, eds., a volume in the series Foundations in Diagnostic Pathology , J. Goldblum, ed., 2nd ed, Philadelphia: Elsevier: 2018.
Asthma/Chronic Bronchitis Duprez A, Mampuys R. Cystic enlargement of the mucous glands of the bronchus associated with chronic bronchitis. Thorax. 1953;8(2):141–7. Kim V, Criner GJ. The chronic bronchitis phenotype in chronic obstructive pulmonary disease: features and implications. Curr Opin Pulm Med. 2015;21:133–41. Trejo Bittar HE, Yousem SA, Wenzel SE. Pathobiology of severe asthma. Annu Rev. Pathol. 2015;10:511–45.
Bronchiectasis Flume PA, Chalmers JD, Olivier KN. Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet. 2018;392:866–90. Moulton BC, Barker AF. Pathogenesis of bronchiectasis. Clin Chest Med. 2012;33:211–7. Novosad SA, Barker AF. Chronic obstructive pulmonary disease and bronchiectasis. Curr Opin Pulm Med. 2013;33:61–78.
Chapter 12
Small Airway Diseases
12.1 Respiratory Bronchiolitis (RB) 12.1.1 Clinical • Most commonly found in the setting of smoking where it is usually asymptomatic. • When found with clinical and pathologic evidence of interstitial lung disease, it is best categorized as respiratory bronchiolitis-interstitial lung disease (RB-ILD) (see Chap. 14). • Pigmented macrophages may be found in most smokers; therefore, RB must be diagnosed in smokers only when other small airway diseases have been excluded. • Rarely reported with occupation exposures of asbestos and other fumes.
12.1.2 Imaging • Ill-defined centrilobular nodules or GGO (3–10 mm) (Fig. 12.1a). • Seen in smokers, often associated with centrilobular emphysema and bronchial wall thickening. • Upper lobe predominant or may be diffuse (smoking-related spectrum of RB, RB-ILD/DIP). • RB-associated ILD (when patient is symptomatic) is similar to RB on imaging parameters. • Differential diagnosis: –– Hypersensitivity pneumonitis (usually not seen in smokers, associated with lobular air-trapping) (Fig. 12.1b). –– Infectious bronchiolitis (well-defined, “tree in bud”) (Fig. 12.1c).
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Fig. 12.1 Respiratory bronchiolitis. (a) Ill-defined upper lobe predominant, centrilobular ground- glass nodules. (b) Hypersensitivity pneumonitis, can mimic RB on CT. (c) Infectious bronchiolitis is in the differential diagnosis but typically shows branching and solid (“tree-in-bud”) nodules
12.1.3 Bronchoscopy • Bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsies may help provide enough information to make a diagnosis. • There are no specific endobronchial findings to support a diagnosis of small airway diseases. • In addition to clinical and radiographic assessment, surgical lung biopsy is considered the gold standard. (See Pathology.)
12.1.4 Pathology 12.1.4.1 Surgical Pathology • Pigmented macrophages are found within and immediately surround small airway lumens and are usually found in the setting of emphysema (Fig. 12.2a, b).
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Fig. 12.2 Respiratory bronchiolitis. (a) Pigmented macrophages are found in the airway and in the surrounding alveoli (arrow); emphysema is commonly found. (stars) (b) Pigmented macrophages within the lumen of an airway with RB Fig. 12.3 Respiratory bronchiolitis. Tissue from a bronchoscopic biopsy of a smoker revealing pigmented macrophages (arrows) in a small airway, consistent with RB
• Mucous can be seen within and surrounding the small airway. 12.1.4.2 Small Biopsy Specimens/Cytopathology • Pigmented macrophages seen in small biopsies and cytopathology can suggest RB (Figs. 12.3, 12.4a, b). 12.1.4.3 Pathological Differential Diagnosis • Respiratory bronchiolitis and interstitial lung disease (RB-ILD)
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Fig. 12.4 Respiratory bronchiolitis. (a) Pigmented macrophages in a bronchoalveolar lavage specimen from the lung of a patient with a significant smoking history (black arrows). Streaks of mucin from the airways can also be seen (white arrow). (b) Intracytoplasmic black and brown pigment in alveolar macrophages, consistent with a history of smoking
12.1.4.4 Ancillary Studies • No histochemical or immunohistochemical studies are helpful in the pathologic diagnosis. • Iron stains may be useful to distinguish hemosiderin pigment in pulmonary hemorrhage from the “smokers” pigment found in RB. –– Smokers’ macrophages always stain for some iron present in phagolysosomes of macrophages, so careful scrutiny is needed.
12.2 Follicular Bronchiolitis 12.2.1 Clinical • Uncommon disorder of small airways usually found in adults and children. • Associated with both congenital and acquired immunodeficiency, connective tissue diseases, and pulmonary infections and may be idiopathic. • Clinical symptoms are nonspecific but most commonly include fever, cough, and dyspnea. • Pulmonary function testing may reveal restrictive, obstructive, or mixed physiologic defects. • Therapy (corticosteroids) has variable success.
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Fig. 12.5 Follicular bronchiolitis. (a) Chest CT scan of shows ill-defined centrilobular nodules and peribronchial ground-glass opacities in follicular bronchiolitis. (b) Chest CT scan coronal reformatted image shows ill-defined centrilobular nodules and peribronchial groundglass opacities
12.2.2 Imaging • Ill-defined centrilobular or peribronchiolar lung nodules (usually 25% lung volume) is a more sensitive, earlier abnormality (Figs. 12.8 and 12.9). • Associated bronchial dilatation and bronchial wall thickening may develop at a later stage (Fig. 12.10) Fig. 12.8 Constrictive bronchiolitis. Chest CT scan shows alternating areas of normal lung and areas with decreased attenuation and vascularity (so-called mosaic pattern), consistent with the air-trapping seen in constrictive bronchiolitis
Fig. 12.9 Constrictive bronchiolitis. Chest CT scan shows air-trapping found in the setting of lung transplantation with chronic rejection (arrows in left lung). Note marked interstitial fibrosis in native right lung
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Fig. 12.10 Constrictive bronchiolitis. Bilateral bronchiectasis (arrow), bronchial wall thickening and subtle mosaic attenuation, a late stage of constrictive bronchiolitis in the setting of a patient with a history of rheumatoid arthritis
Fig. 12.11 Constrictive bronchiolitis. Early constrictive bronchiolitis with minimal collagen deposition in the subepithelial area of the airway (arrow). (Movat pentachrome stain)
12.3.3 Bronchoscopy • Bronchoscopic examination usually reveals unremarkable proximal airways. • Small biopsies can make the diagnosis on small pieces of tissue. (See Pathology.)
12.3.4 Pathology 12.3.4.1 Surgical Pathology • Usually arises out of chronic lymphocytic bronchiolitis. • Early fibrosing lesion: small airway walls have subepithelial fibrosis; surrounding lung may be unremarkable (Fig. 12.11).
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Fig. 12.12 Constrictive bronchiolitis. (a) Small airway partially narrowed by collagen deposited in the subepithelial area. (b) Movat pentachrome stain highlights the early collagen deposition with blue-green color
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Fig. 12.13 Constrictive bronchiolitis. (a) Small airway completely obliterated by intraluminal collagen. (b) Movat pentachrome stain highlights collagen obliterating the lumen of the small airway. The minimal residual smooth muscle (arrows) and the elastic (black line) encircle the periphery of the airway
• Obliterative lesions: small airway lumen is partially narrowed (Fig. 12.12a, b) and then replaced by fibrosis (Fig. 12.13a, b). • Small airway in bronchoscopic biopsies may reveal features of subepithelial fibrosis when evaluated with elastic or Movat pentachrome stains (Fig. 12.14). 12.3.4.2 Pathological Differential Diagnosis • Lymphocytic interstitial pneumonitis
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Fig. 12.14 Constrictive bronchiolitis. Disruption of the bronchial epithelium and early collagen deposition (arrow) can be seen in bronchoscopic biopsies in the setting of constrictive bronchiolitis
12.3.4.3 Ancillary Studies • Trichrome and/or elastic or Movat pentachrome stains highlight residual elastic fibers in obliterated bronchiole (Fig. 12.13b) and are helpful in diagnosing increased collagen in subepithelial area in biopsy specimens (Fig. 12.14).
Suggested Readings Barker AF, Bergeron A, Rom WN, Hertz MI. Obliterative bronchiolitis. N Engl J Med. 2014;370:1820–8. Beasley MG. Smoking-related small airway disease---a review and update. Adv Anat Pathol. 2010;17:270–6. Burgel PR, Bergeron A, de Blic J, Bonniaud P, Bourdin A, Chanez P, Chinet T, et al. Small airways diseases, excluding asthma and COPD: an overview. Eur Respir Rev. 2013;22:131–47. Fraig M, Shreesha U, Savici D, et al. Respiratory bronchiolitis: a clinical-pathologic study in current smokers, ex-smokers, and never-smokers. Am J Surg Pathol. 2002;26:647–53. Kang EY, Woo OH, Shin BK, Yong HS, Oh YW, Kim HK. Bronchiolitis: classification, computed tomographic and histopathologic features, and radiologic approach. J Comput Assist Tomogr. 2009 Jan-Feb;33(1):32–41. Lynch JP, Weight SS, DerHovanessian A, Fishbein MC, Gutierrez A, Belperio JA. Obliterative (constrictive) bronchiolitis. Semin Respir Crit Care Med. 2012;33:509–32. Pappas K. Bronchiolitis and bronchial disorders in interstitial lung disease. Curr Opin Pulm Med. 2011;17:316–24. Visscher DW, Myers JL. Bronchiolitis: the pathologist’s perspective. Proc Am Thorac Soc. 2006;3(1):41–7.
Chapter 13
Acute Lung Injury
13.1 Diffuse Alveolar Damage 13.1.1 Clinical • Diffuse alveolar damage is the imaging and pathologic equivalent of clinical syndromes of ALI/ARDS. • Three clinical phases: –– Acute, exudative phase: Sudden onset, rapidly progressing, non-cardiogenic pulmonary edema and capillary leak –– Proliferative/organizing phase: Steroid-responsive phase highlighted by “stiffening” of the lungs –– Chronic phase: Severe fibrosis, which will occur in some patients • Various etiologies include pulmonary (infection, aspiration, etc.) and extrapulmonary/systemic causes (sepsis, pancreatitis, toxicities, etc.). • Sometimes referred to as acute interstitial pneumonia (AIP) or Hamman-Rich syndrome when no etiology is found.
13.1.2 Imaging • Diffuse or patchy bilateral ground-glass opacities (GGO) and/or early consolidations (initially often basilar predominant) that may spare some regions (heterogeneous involvement) (Fig. 13.1a). • Areas of GGO may be interspersed with smooth interlobular septal thickening and intralobular lines (“crazy-paving pattern”). • Progression to adjacent lung may lead to diffuse, homogenous consolidations with air bronchograms and small pleural effusions (Fig. 13.1b). • The lung vascular pedicles remain relatively narrow. © Springer Nature Switzerland AG 2020 C. Farver et al., Pulmonary Disease, https://doi.org/10.1007/978-3-030-47598-7_13
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Fig. 13.1 Diffuse alveolar damage/acute interstitial pneumonia. CXR portable (a) followed by CT chest (b) 2 days later in ARDS. Rapid progression of bilateral lower lobe-predominant heterogeneous opacities (CXR) to diffuse consolidations, architectural distortion, and traction bronchiectasis throughout both lungs. Note cystic changes and loculated fissural pneumothorax (arrowhead) due to barotrauma
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Fig. 13.2 Diffuse alveolar damage/acute interstitial pneumonia. CT chest axial (a, b) and coronal reformatted (c) images show peripheral GGO with basilar predominant consolidations and traction bronchiectasis in chronic organizing DAD
• Abnormalities may resolve or progress to lower lobe predominant fibrotic lung disease with architectural distortion, coarse reticulation, and traction bronchiectasis (Fig. 13.2a–c).
13.1.3 Bronchoscopy • Bronchoscopic transbronchial biopsies may yield diagnostic specimens when interpreted with the imaging studies. (See Pathology.)
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Fig. 13.3 Diffuse alveolar damage. Diffuse hyaline membranes lining the alveolar spaces in this acute diffuse alveolar damage
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Fig. 13.4 Diffuse alveolar damage. (a) Type II pneumocytes that are re-epithelializing the alveolar surface. (b) Pneumocytes may have foamy cytoplasm (arrow) as they secrete surfactant to lower surface tension in this proliferative phase of diffuse alveolar damage
• Gross airway findings during these procedures are usually nonspecific and/or unremarkable.
13.1.4 Pathology 13.1.4.1 Surgical Pathology • The exudative or acute phase of DAD is highlighted by breakdown of the epithelial- endothelial barrier resulting in hyaline membrane formation (Fig. 13.3). • The proliferative phase of DAD reveals type II pneumocytes that are re- epithelializing the alveolar surface and secreting surfactant to lower surface tension (Fig. 13.4a, b). • Chronic DAD has both proliferating pneumocytes and collagen deposition in the alveolar walls (Figs. 13.5a, b).
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Fig. 13.5 Diffuse alveolar damage. (a) Chronic diffuse alveolar damage revealing the expansion of the collagen within the alveolar walls (Movat pentachrome stain). (b) Chronic diffuse alveolar damage has both proliferating pneumocytes and collagen deposition in the alveolar walls (Movat pentachrome stain)
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Fig. 13.6 Diffuse alveolar damage. (a) Bronchoscopic biopsy with acute and early proliferative phases. (b) Movat pentachrome stains are helpful in highlighting evidence of organizing and chronic (collagenous) phase of the DAD. (c) Clusters of reactive pneumocytes that mimic adenocarcinoma can be seen
• Bronchoscopic biopsies must be interpreted within the context of the clinical findings. • Can show evidence of all three phases of diffuse alveolar damage: –– Acute/exudative and early proliferative phases: Intra-alveolar fibrin and type II pneumocytes (Fig. 13.6a). –– Movat stains are helpful in highlighting evidence of organizing and chronic (collagenous) phase of the DAD (Fig. 13.6b).
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13.1.4.2 Cytopathology • Cytopathology specimens usually yield little if any diagnostic tissue, except when evidence of diagnostic infectious agents are present (e.g., granulomas or viral inclusions; see Chapters 20–22). • Reactive pneumocytes that mimic adenocarcinoma can be seen (Fig. 13.6c). 13.1.4.3 Pathological Differential Diagnosis • Acute and/or organizing pneumonia • Acute fibrinous organizing pneumonia • Other pathologic processes that be a secondary causes of acute lung injury (i.e., vasculitis/capillaritis, acute pneumonia) 13.1.4.4 Ancillary Studies • Connective tissue stains such as Movat pentachrome, elastic, reticulin, and trichrome stains to evaluate for the presence of organizing fibrosis or collagen deposition
13.2 Organizing Pneumonia 13.2.1 Clinical • Common histologic reaction to different causes including: –– Infection, connective tissue disease, and drug reaction • Cryptogenic organizing pneumonia (OP) if no cause found • Commonly a sequelae of acute, infectious pneumonia • May present as nonresolving (possible worsening) airspace disease in spite of adequate antibiotic coverage –– Other diseases should be considered in this differential diagnosis including lymphoma and adenocarcinoma.
13.2.2 Imaging • Peripheral and peribronchial consolidations (unilateral or bilateral) (Fig. 13.7).
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Fig. 13.7 Organizing pneumonia. CT chest shows peripheral consolidation and GGO in the upper lobes (arrows). Differential – chronic eosinophilic pneumonia
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Fig. 13.8 Organizing pneumonia. CT chest shows “reverse halo” or “atoll” sign with multiple bilateral ring-like consolidations (arrows) which surround central GGO (a, b). Differential – Wegener’s granulomatosis, mucormycosis Fig. 13.9 Organizing pneumonia. CT chest shows perilobular pattern in the LLL (arrow)
• Reverse halo (Atoll sign) – Round or crescentic consolidations surrounding central GGO (Fig. 13.8a, b). • Perilobular opacities (arc-like) along margins of secondary pulmonary lobule (Fig. 13.9). • GGO and nodules (rarely GGO with interlobular septal thickening as “crazy- paving” pattern)
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Fig. 13.10 Organizing pneumonia. (a) Organizing fibroblasts involving the majority of the alveoli. (b) Fibroblasts admixed with alveolar macrophages are commonly seen. (c) Movat pentachrome stain is useful in highlighting (blue) the organizing (immature) fibrosis
13.2.3 Bronchoscopy • Bronchoscopic transbronchial biopsies may yield diagnostic specimens when interpreted with the imaging studies. (See Pathology.) • Gross findings during these procedures are usually nonspecific and/or unremarkable.
13.2.4 Pathology 13.2.4.1 Surgical Pathology • Intra-alveolar organizing fibrosis (Fig. 13.10a–c). 13.2.4.2 Small Biopsies/Cytopathology • Patches of organizing fibrosis can be seen in small biopsies (Fig. 13.11a, b). • Foamy macrophages are commonly seen adjacent to organizing fibrosis (Fig. 13.11c).
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Fig. 13.11 Organizing pneumonia. (a) Bronchoscopic biopsy reveals the organizing plugs of fibroblasts in organizing pneumonia. (b) The organizing fibrosis is centered within the alveolar space. (c) Foamy macrophages can be seen adjacent to these fibromyxoid plugs. (d) Reactive pneumocytes can be seen in the surrounding lung. (e) Organizing fibroblasts from a cytologic specimen in a patient with organizing pneumonia
• May have adjacent reactive pneumocytes (proliferative DAD-like pattern) (Fig. 13.11d). • Intra-alveolar plugs of organizing fibrosis can be seen in cytopathologic specimens (Fig. 13.11e).
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13.2.4.3 Pathological Differential Diagnosis • Organizing diffuse alveolar damage (DAD) • Partially sampled acute fibrinous and organizing pneumonia 13.2.4.4 Ancillary Studies • Movat pentachrome studies to highlight organizing fibrosis help in small biopsies (Fig. 13.6c)
13.3 Acute Fibrinous and Organizing Pneumonia 13.3.1 Clinical • Found in similar clinical scenarios as DAD, acute eosinophilic pneumonia (AEP), and acute and organizing pneumonia • Usually acute or subacute presentation with cough and shortness of breath • Can be severe and result in respiratory failure, but usually less severe than DAD
13.3.2 Imaging • Similar to OP on imaging parameters with peripheral and peribronchial foci of GGO and consolidations (see Figs. 13.7, 13.8, and 13.9.) • Greater extent than OP and with basilar predominance, simulating AIP/DAD
13.3.3 Bronchoscopy • Bronchoscopic transbronchial biopsies may yield diagnostic specimens when interpreted with the imaging studies. (See Pathology.) • Gross findings during these procedures are usually nonspecific and/or unremarkable.
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13.3.4 Pathology 13.3.4.1 Surgical Pathology • Intra-alveolar “fibrin balls,” no hyaline membranes, and no eosinophilia (Fig. 13.12). • Patches of organizing fibrosis may be scattered/scant (Fig. 13.12 – upper left corner). 13.3.4.2 Small Biopsy/Cytopathology • Can be diagnosed on small biopsies if both fibrinous and organizing patterns are seen (Fig. 13.13a, b). • Usually requires correlation with clinical and imaging studies to confirm this diagnosis Fig. 13.12 Acute fibrinous and organizing pneumonia. Intra-alveolar “fibrin balls” are present throughout this thoracoscopic biopsy. Note patches of organizing fibrosis can be seen in left upper corner
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Fig. 13.13 Acute fibrinous and organizing pneumonia. (a) Bronchoscopic biopsy reveals intraalveolar eosinophilic exudate (arrow). (b) Small patch of organizing pneumonia is seen beginning to form adjacent to intra-alveolar exudate (arrow)
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13.3.4.3 Pathological Differential Diagnosis • Acute eosinophilic pneumonia (AEP): –– Intra-alveolar fibrin balls with eosinophils. –– Treatment may eliminate eosinophils and pathology may be very similar to AFOP. • Poorly sampled acute diffuse alveolar damage (DAD) 13.3.4.4 Ancillary Studies • Movat pentachrome stains may help to highlight organizing inflammation/ fibrosis.
Suggested Readings Aublanc M, Perinel S, Guérin C. Acute respiratory distress syndrome mimics: the role of lung biopsy. Curr Opin Crit Care. 2017;23:24–9. Beasley MB. The pathologist's approach to acute lung injury. Arch Pathol Lab Med. 2010;134:719–27. Beasley MB, Franks TJ, Galvin JR, Gochuico B, Travis WD. Acute fibrinous and organizing pneumonia: a histological pattern of lung injury and possible variant of diffuse alveolar damage. Arch Pathol Lab Med. 2002;126:1064–70. Cardinal-Fernández P, Lorente JA, Ballén-Barragán A, Matute-Bello G. Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage. New Insights on a Complex Relationship. Ann Am Thorac Soc. 2017;14:844–50. Elicker BM, Jones KT, Naeger DM, Frank JA. Imaging of Acute Lung Injury. Radiol Clin N Am. 2016;54:1119–32. Hughes KT, Beasley MB. Pulmonary Manifestations of Acute Lung Injury: More Than Just Diffuse Alveolar Damage. Arch Pathol Lab Med. 2017;141:916–22. Johkoh T, Fukuoka J, Tanaka T. Rare idiopathic intestinal pneumonias (IIPs) and histologic patterns in new ATS/ERS multidisciplinary classification of the IIPs. Eur J Radiol. 2015 Mar;84:542–6. Kligerman SJ, Franks TJ, Galvin JR. From the radiologic pathology archives: organization and fibrosis as a response to lung injury in diffuse alveolar damage, organizing pneumonia, and acute fibrinous and organizing pneumonia. Radiographics. 2013;33:1951–75. Mukhopadhyay S, Parambil JG. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS). Semin Respir Crit Care Med. 2012;33:476–85. Roberton BJ, Hansell DM. Organizing pneumonia: a kaleidoscope of concepts and morphologies. Eur Radiol. 2011;21:2244–54. Torrealba JR, Fisher S, Kanne JP, Butt YM, Glazer C, Kershaw C, et al. Pathology-radiology correlation of common and uncommon computed tomographic patterns of organizing pneumonia. Hum Pathol. 2018;71:30–40.
Chapter 14
Common Interstitial Pneumonias
14.1 General Clinical • A group of idiopathic interstitial pneumonias (IIP) that cause lung fibrosis. • The American Thoracic Society/European Respiratory Society (ATS/ERS) recognizes six major types. –– –– –– –– –– ––
Idiopathic pulmonary fibrosis (IPF/UIP) Idiopathic nonspecific interstitial pneumonia (NSIP) Respiratory bronchiolitis-interstitial lung disease (RB-ILD) Desquamative interstitial pneumonia (DIP) Cryptogenic organizing pneumonia (see Chap. 13) Acute interstitial pneumonia (see Chap. 13)
• The diagnosis of each of the entities emphasizes the need for a multidisciplinary team approach comprising clinicians, radiologist, and pathologists. • Interstitial pneumonia with autoimmune features (IPAF) is pathology found in IIP patients with signs/symptoms of an underlying autoimmune process or positive serologic biomarkers for connective tissue disease, but not meeting defined criteria for specific connective tissue disease.
14.2 Usual Interstitial Pneumonia 14.2.1 Clinical • A specific histopathological pattern associated with idiopathic pulmonary fibrosis (IPF). • It may be idiopathic or associated with diseases, drugs, and exposures that include: © Springer Nature Switzerland AG 2020 C. Farver et al., Pulmonary Disease, https://doi.org/10.1007/978-3-030-47598-7_14
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Connective tissue disease (CTD) Hermansky-Pudlak syndrome Asbestosis Familial Genetic mutations to TERC, TERT, SPC genes.
• Idiopathic disease usually occurs in the following clinical setting: –– –– –– –– ––
Elder adults >65 years Caucasian Male History of gastroesophageal reflux History of smoking
• IPF has the worst prognosis of all IIP. • Recent anti-fibrotic medications have been shown to be effective in stabilizing disease.
14.2.2 Imaging • Definitive diagnosis of UIP on HRCT is “honeycombing.” –– Bilateral subpleural, basilar predominant, reticular abnormalities, honeycombing with or without traction bronchiectasis in the absence of other inconsistent signs (upper or mid-lung predominance, peribronchovascular distribution, extensive ground glass abnormality, multiple nodules, discrete cysts, mosaicism/air-trapping and consolidations) is definite UIP (Fig. 14.1a). a
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Fig. 14.1 Usual interstitial pneumonia. Chest CT scan (a) UIP pattern with classic multilayered honeycomb cysts in subpleural, basilar portions of both lungs with reticular opacities and traction bronchiectasis. (b) Probable UIP pattern with subpleural, basilar predominant reticular opacities with minimal or no honeycombing and/or traction bronchiectasis. Note absence of features inconsistent with UIP in both figures
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Fig. 14.2 Combined pulmonary fibrosis and emphysema. Emphysematous changes are upper lobe predominant; reticular opacities and honeycombing are along the subpleural regions (and bases)
Fig. 14.3 Status-post unilateral left lung transplant for UIP. Basilar predominant coarse reticular opacities with traction bronchiectasis in the native right lung. Note 2 left chest tubes
–– Bilateral subpleural and basilar reticulations in the absence of other inconsistent signs suggest probable UIP (Fig. 14.1b). • “Honeycomb” cysts are usually 2–10 mm, with thick walls, and clustered in the subpleural regions. • Honeycombing in characteristic distribution has positive predictive value (PPV) of 90–100% for histologic pattern of UIP. • Combined pulmonary fibrosis and emphysema (CPFE) is UIP found in the setting of emphysema (Fig. 14.2). • Patients with UIP may undergo a single lung transplantation (Fig. 14.3).
14.2.3 Bronchoscopy • Bronchoscopic biopsy for UIP is usually done in the setting of atypical clinical behavior to rule out other infiltrative lung diseases that may clinically mimic UIP.
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–– Malignancies: adenocarcinoma and lymphomas –– Infections: bacterial • Bronchoscopy for UIP reveals nonspecific airway findings. • If bronchoscopic biopsy is done, a multidisciplinary discussion regarding the location (lobes, segments) to biopsy may be helpful to optimize the diagnostic yield. –– Cryobiopsy is a bronchoscopic technology that procures larger tissue fragments and may be useful in certain clinical settings where thoracoscopic biopsies are contraindicated. (See Pathology.)
14.2.4 Pathology 14.2.4.1 Surgical Pathology • Three features are needed for a pathologic diagnosis. –– Patchy fibrosis with peripheral lobular distribution (Fig. 14.4a) a
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Fig. 14.4 Usual interstitial pneumonia. Explant pneumonectomy (a) Patchy fibrosis. (b) Focus of fibroblastic proliferation reveals fibroblasts with overlying re-epithelized alveolar surface. (c) Movat pentachrome stains may be useful to highlight immature fibroblastic proliferations in UIP. (d) Honeycomb changes reveal fibrotic lobule (right side) with remodeled airspaces and non- fibrotic lung (left side) with intervening area containing fibroblastic foci (arrow)
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–– Fibroblastic foci (Fig. 14.4b, c) –– Honeycomb changes (Fig. 14.4d) 14.2.4.2 Small Biopsies/Cytopathology • Bronchoscopic biopsies are predominantly used to rule out other causes of infiltrative lung diseases as they usually do not provide enough tissue for a definitive UIP diagnosis. • Cryobiopsies in the appropriate clinical context (multidisciplinary discussion) may be helpful (Fig. 14.5a, b). • Cytopathologic features are nonspecific, usually consisting of alveolar macrophages and/or lymphocytes. • Evidence of other diagnoses (malignancies, granulomas/giant cells) can help to rule out UIP. 14.2.4.3 Pathological Differential Diagnosis • Chronic hypersensitivity pneumonitis • Fibrosing NSIP • Organizing diffuse alveolar damage with honeycomb changes 14.2.4.4 Ancillary Studies • Movat pentachrome stains may be helpful in highlighting fibroblastic foci (Fig. 14.4c).
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Fig. 14.5 Usual interstitial pneumonia. Cryobiopsy. (a) Patchy fibrosis and early evidence of honeycomb change (arrow). (b) Fibroblastic foci (arrows) are present adjacent to early honeycomb changes to help for definitive diagnosis of UIP
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14.3 Nonspecific Interstitial Pneumonia (NSIP) 14.3.1 Clinical • Form of IIP usually seen in younger individuals (40–60) • Found in the following clinical settings: –– Connective tissue disease (CTD) – most common –– Idiopathic –– Drug reaction • Two distinct subtypes on histopathology: cellular and fibrotic –– Fibrotic NSIP Most common and worse prognosis –– Cellular NSIP Better prognosis and less common
14.3.2 Imaging • Bilateral, symmetrical lower lobe predominant ground-glass opacities (most common pattern) (Fig. 14.6a). • Lower lobe predominant irregular reticular opacities with traction bronchiectasis (75% cases) (Fig. 14.6b). • Subpleural sparing, considered characteristic, may distinguish NSIP from UIP (Fig. 14.6a, b). a
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Fig. 14.6 Nonspecific interstitial pneumonia. Chest CT scan (a) Lower lobe predominant patchy, peribronchial GGO in cellular-type NSIP. (b) Lower lobe predominant peribronchial reticular opacities, GGO, and traction bronchiectasis in fibrotic NSIP. Note subpleural sparing is evident in both patterns of NSIP
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• Peribronchial consolidation if present may represent OP pattern and suggests possible connective tissue disease. • Honeycombing is minimal or absent initially but may develop with fibrotic disease progression.
14.3.3 Bronchoscopy • The role of bronchoscopy is limited in IIP (see above UIP).
14.3.4 Pathology 14.3.4.1 Surgical Pathology • Categorized as cellular or fibrosing subtypes: –– Cellular (30% of cases): diffuse infiltration of alveolar septa (Fig. 14.7a). Foci of organizing pneumonia can be seen (Fig. 14.7b). • Lymphoid aggregates and/or germinal centers may suggest CTD clinical setting (Fig. 14.7b). –– Fibrosing (70% of cases): Diffuse collagenous-type fibrosis gradually replaces inflammatory infiltrates (Fig. 14.8). Any amount of fibrosis qualifies NSIP as fibrosing type: • Honeycomb changes are unusual but can be seen.
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Fig. 14.7 Nonspecific interstitial pneumonia, cellular type. Thoracoscopic biopsy (a) Diffuse, cellular infiltrates without evidence of fibrosis. (b) Diffuse lymphocytic infiltration of the alveolar septa and scattered lymphoid aggregates are present
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Fig. 14.8 Nonspecific interstitial pneumonia, fibrosing type. Explant pneumonectomy. Diffuse thickening of the alveolar septa by fibrosis. Lymphoid aggregates are seen scattered throughout
14.3.4.2 Small Biopsies/Cytopathology • Bronchoscopic biopsies may have either chronic interstitial pneumonitis or minimal interstitial fibrosis, but findings are nonspecific. • Cytopathologic specimens are nonspecific (see above UIP). 14.3.4.3 Pathological Differential Diagnosis • Chronic hypersensitivity pneumonitis • Poorly sample UIP 14.3.4.4 Ancillary Studies • Movat stains may be helpful in early stages of fibrosis to identify collagen deposition (Fig. 14.4c).
14.4 R espiratory Bronchiolitis-Interstitial Lung Disease/ Desquamative Interstitial Pneumonia 14.4.1 Clinical • On the spectrum of lung diseases caused by smoking. –– Respiratory bronchiolitis (see Chap. 12) –– Desquamative interstitial lung disease
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• Seen in smokers and known to be caused by cigarette smoking (not truly idiopathic). • Considered a diagnosis of exclusion in a smoker with clinical and imaging evidence of interstitial lung disease but no other causes. • Desquamative interstitial pneumonia can be seen in the setting of smoking, but also seen in other settings of environmental insults to the lung. –– More lower lobe and inflammatory symptoms than RB-ILD. –– Some may consider it steroid responsive.
14.4.2 Imaging • RB and RB-ILD are indistinguishable on imaging. –– Ill-defined centrilobular ground-glass nodules in both upper lobes (see Chap. 12). –– DIP has diffuse mild GGO mostly in the peripheral basilar portions of both lungs (Fig. 14.9).
14.4.3 Bronchoscopy • Bronchoscopy is similar to RB where no specific features are seen and biopsy and bronchoalveolar lavage are done to rule out other causes of ILD.
Fig. 14.9 Desquamative interstitial pneumonia. Chest CT scan. Diffuse ground-glass opacities are present through the basilar areas of chest CT
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14.4.4 Pathology 14.4.4.1 Surgical Pathology • Abundant pigmented alveolar macrophages centered around small airways with spread into the alveoli (Fig. 14.10). • Can be accompanied by smoking-related interstitial fibrosis (SRIF), a hyalinizing fibrosis in the alveolar septa of uncertain clinical significance (Fig. 14.11). • DIP has abundant pigmented macrophages involving all of the alveolar spaces (Fig. 14.12a). –– Also has more acute inflammatory changes including eosinophils and neutrophils and may have lymphoid aggregates in the surrounding interstitium (Fig. 14.12b) Fig. 14.10 Respiratory bronchiolitis-interstitial lung disease. Respiratory bronchiolitis-interstitial lung disease is histologic similar to RB, but is found in setting of clinical disease, and alveolar macrophage infiltrate may be more pronounced extending from the small airways into the surrounded alveolar spaces
Fig. 14.11 Smoking- related interstitial fibrosis. Lobectomy. Hyalinizing fibrosis that is seen accompanying RB-ILD. (Movat pentachrome stain)
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Fig. 14.12 Desquamative interstitial pneumonia. Explant pneumonectomy. (a) Pronounced macrophages infiltrate throughout all alveolar spaces. (b) Acute inflammatory infiltrate can be seen including eosinophils (arrow)
14.4.4.2 Cytopathology • Abundant alveolar macrophages with pigment are seen in both RB-ILD and DIP. • Eosinophils and/or neutrophils are usually seen in DIP. 14.4.4.3 Pathological Differential Diagnosis • RB • Pulmonary congestions with pigmented macrophages 14.4.4.4 Ancillary Studies • Movat pentachrome stain to highlight areas of hyalinizing fibrosis may be helpful (Fig. 14.11).
Suggested Readings Hodnett PA, Naidich DP. Fibrosing interstitial lung disease: a practical high-resolution computed tomography-based approach to diagnosis and management and a review of the literature. Am J Respir Crit Care Med. 2013;188:141–9. Kumar A, Cherian SV, Vassaillo, et al. Current concepts in pathogenesis, diagnosis and management of smoking-related interstitial lung diseases. Chest. 2018;154:394–408. Lederer DJ, Martinez JF. Idiopathic pulmonary fibrosis. N Engl J Med. 2018;378:1811–23. Mira-Avendan I, Abril A, Burger CD, et al. Interstitial lung disease and other pulmonary manifestations in connective tissue diseases. Mayo Clin Proc. 2019;94:309–25. Smith ML. Update on pulmonary fibrosis: not all fibrosis is created equally. Arch Pathol Lab Med. 2016;140:221–9.
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Travis WD, Hunninghake G, King TE Jr, et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Respir Crit Care Med. 2008;77:1338–47. Travis WD, Costabel U, Hansell DM, Valeyre D, et al. An Official American Thoracic Society/ European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care. 2013;188:733–48.
Chapter 15
Other Interstitial Lung Diseases
15.1 Hypersensitivity Pneumonitis 15.1.1 Clinical • Interstitial lung disease with lung inflammation and/or fibrosis caused by inhalation of environmental antigens (organic or inorganic) in susceptible individuals • Three clinical types of hypersensitivity pneumonitis (HP): –– Acute HP: Short-term High-level exposure Symptoms onset within hours –– Subacute HP: Intermittent High-level exposure Symptom onset days/weeks after exposure –– Chronic HP: Continuous Low-level exposure Symptom insidious over weeks/months of exposure
15.1.2 Bronchoscopy • Nonspecific bronchoscopic images.
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Fig. 15.1 Subacute hypersensitivity pneumonitis. Chest CT scan. Ill-defined centrilobular nodules and patchy GGO alternating with normal/lucent lung parenchyma (mosaic pattern). Differential diagnosis based on this imaging is respiratory bronchiolitis
• Bronchoscopic transbronchial biopsies are used to rule out other infiltrative lung diseases that may mimic HP (e.g., infiltrative neoplasms such as adenocarcinoma/lymphoma).
15.1.3 Imaging • Acute HP: –– Mimics pulmonary edema pattern • Subacute HP (Figs. 15.1 and 15.2a–e): –– –– –– ––
Ground-glass opacities Centrilobular nodules Mosaic attenuation (inspiration) Air-trapping (expiration)
• Chronic HP (Fig. 15.3): –– Reticular opacities –– Traction bronchiectasis superimposed on findings of acute HP • HP versus UIP and NSIP: –– Combination of obstructive (mosaic/air-trapping) with restrictive (reticulation) pattern –– Juxtaposition of low, normal, and high attenuation (“headcheese sign”) –– Distribution (craniocaudal): Upper and mid zones; may spare lung bases –– Distribution (axial): Peripheral and/or peribronchovascular; subpleural sparing not a feature
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Fig. 15.2 Subacute hypersensitivity pneumonitis. Chest CT scan. (a–c) Inspiratory HRCT through the upper (a), mid (b), and lower (c) lung zones demonstrate patchy mild reticulations superimposed over GGO, tiny centrilobular nodules, and lobular areas of decreased attenuation and vascularity in both lungs. (d, e) Expiratory HRCT images through the upper (d) and mid (e) lung zones demonstrate areas of air-trapping (arrows)
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Fig. 15.3 Chronic hypersensitivity pneumonitis. Chest CT scan. Coarse reticular opacities with traction bronchiectasis predominantly in the upper-mid lung zones (bases are spared) in chronic HP. The differential diagnosis for this may include sarcoidosis. These features are not typical UIP/NSIP
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Fig. 15.4 Hypersensitivity pneumonitis. Thoracoscopic biopsy. (a) Chronic lymphocytic bronchiolitis (arrow) with a patchy lymphocytic interstitial infiltrate and scattered giant cells or granulomas are the characteristic triad of features seen in this pathology. (b, c) Giant cells (arrows) and/or granulomas (arrowhead) are present in varying amounts; the latter are ill-formed consisting of histiocytic aggregates
15.1.4 Pathology 15.1.4.1 Surgical Pathology • Pathology is characterized by (Fig. 15.4a–c): –– Chronic lymphocytic bronchiolitis –– Patchy chronic interstitial pneumonitis with lymphocytes and plasma cells –– Giant cells or granulomas, predominantly in the peribronchiolar and interstitial distribution
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Fig. 15.5 Hypersensitivity pneumonitis. Transthoracic needle biopsy. (a) Pathologic features can be seen in biopsy specimens; (a) low power reveals patchy interstitial infiltrates (arrow), and (b) higher power reveals interstitial giant cell (arrow)
• Diagnosis can be made on bronchoscopic or needle biopsy specimens (Fig. 15.5a, b). 15.1.4.2 Pathologic Differential Diagnosis • Aspiration pneumonia: –– Airway-centered giant cells usually with foreign/food material. –– Neutrophils are a more common feature. • Infections: fungal and mycobacterial. –– Giant cells/granulomas are more airway-centered and may have necrosis. • Drug reactions: –– Can have more eosinophils than HP 15.1.4.3 Ancillary Studies • Tissue organismal stains should be performed to rule out infection. • Polarization may reveal birefringent material as a possible etiology.
15.2 Sarcoidosis 15.2.1 Clinical • Chronic multisystem disease with formation of non-necrotizing granulomas. • 90% of patients have lung and/or thoracic lymph node involvement. • Skin involvement is common.
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• More common in: –– 50 years ago) still used; has prognostic value. –– Stage 0: No radiographic abnormality (5% of patients at presentation) –– Stage 1: Thoracic lymphadenopathy (50% of patients at presentation) (Fig. 15.7a–d) –– Stage 2: Lymphadenopathy with lung infiltrates (25–30% of patients at presentation) (Fig. 15.8a–c)
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Fig. 15.8 Sarcoidosis. Imaging Stage 2. (a) CXR PA. Symmetrical bilateral hilar lymphadenopathy with perihilar reticular opacities in both lungs. (b) CT chest, mediastinal window image confirms bilateral hilar and subcarinal lymphadenopathy; (c) CT chest, lung window image. Tiny peribronchovascular nodular densities in both lungs
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Fig. 15.9 Sarcoidosis. Imaging Stage 3: (a, b) CT chest axial (a) and coronal reformatted (b) images demonstrate multiple upper lobe predominant 2–4 mm nodules along the bronchial and vascular walls of both lungs
–– Stage 3: Lung infiltrates (shrinking nodes) (10–12% of patients at presentation) (Fig. 15.9a, b) –– Stage 4: Advanced lung fibrosis (5% of patients at presentation) (Fig. 15.10a, b) • HRCT lungs are very sensitive to distinguish active inflammation (reversible) from fibrosis (irreversible).
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Fig. 15.10 Sarcoidosis. (a) Coronal reformatted images demonstrate architectural distortion with fibrotic changes and traction bronchiectasis in bilateral upper lobes. Note bilateral hilar fullness and superior retraction of the hila due to scarring in the upper lung lobes. Emphysematous and cystic changes are noted in both lungs. (b) Axial mediastinal window image demonstrates evidence of pulmonary hypertension with dilatation of main and central pulmonary arteries (which account for hilar fullness)
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Fig. 15.11 Sarcoidosis. Patterns of thoracic lymph node calcification. CT chest images. (a) Soft or cloud-like calcifications are often called “icing sugar” type. (b) Dense rim of peripheral calcifications referred to as “egg shell” type
• Symmetrical bilateral hilar +/− mediastinal (usually right paratracheal) lymphadenopathy in 95%. –– Calcification is common (Fig. 15.11a, b). • Fibrotic changes and coalescence of nodules are imaging evidence of end-stage sarcoidosis (Figs. 15.12 and 15.13).
15.2.4 Pathology 15.2.4.1 Surgical Pathology • Well-formed granulomas in a lymphatic distribution (Fig. 15.14). • Granulomas in bronchovascular area can form mucosal nodules (Fig. 15.15). –– See also bronchoscopic image (Fig. 15.6b).
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Fig. 15.12 Sarcoidosis. End-stage. Fibrocystic changes of sarcoidosis in bilateral upper lobes with fungal ball (arrow) in the LUL
Fig. 15.13 Sarcoidosis. Sarcoid “galaxy” of larger nodules formed as a result of coalescence of multiple tiny nodules in bilateral upper lobes (arrows)
Fig. 15.14 Sarcoidosis. Thoracoscopic biopsy. Well-formed granulomas involving the lung in a lymphatic distribution, including pleura (arrowhead), interlobular septa, and bronchovascular area (arrows)
• Lymphatic distribution can be seen in biopsy specimens (Fig. 15.16). • Granulomas can coalesce and undergo fibrosis and form nodules (Fig. 15.17). • Chronic, end-stage sarcoidosis has hyalinizing fibrosis with only scattered, small residual granulomas (Fig. 15.18).
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Fig. 15.15 Sarcoidosis. Thoracoscopic biopsy. Well-formed granulomas involving the bronchovascular airway can cause submucosal nodules (arrow) seen on bronchoscopy. (See Fig. 15.6)
Fig. 15.16 Sarcoidosis. Transbronchial biopsy. Lymphatic distribution of well-formed granulomas may be seen on transbronchial biopsy and suggest sarcoidosis
15.2.4.2 Cytopathology • Non-necrotizing microgranulomata comprised of cohesive spindled and epithelioid macrophages (Fig. 15.19). • Accompanying mononuclear chronic inflammatory cells.
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Fig. 15.17 Sarcoidosis. Thoracoscopic biopsy. Granulomas and fibrosis may coalesce into nodules; sometimes referred to as “nodular sarcoidosis”
Fig. 15.18 Sarcoidosis. Explant pneumonectomy. End-stage sarcoidosis has prominent hyalinizing fibrosis and may have very scant number of small granulomas and/or giant cells (arrow)
15.2.4.3 Pathologic Differential Diagnosis • Fungal and mycobacterial infections. –– Infectious granulomas are airway-centered; sarcoidosis is in a lymphatic distribution. –– Berylliosis: Very similar pathology to sarcoidosis with a lymphatic distribution of granulomas • Clinical history of occupational exposure is essential. –– Granulomatous-lymphocytic interstitial lung disease (GLILD): GLILD has more infiltrating chronic lymphoplasmacytic infiltrate. Immunologic workup is needed to document immune deficiencies in GLILD.
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Fig. 15.19 Sarcoidosis. Cytology direct smear, (Papanicolaou). Cohesive spindled and epithelioid macrophages needed for diagnosis of granulomata; scattered lymphocytes are seen in the background
15.2.4.4 Ancillary Studies • Tissue organismal stains are important to rule out fungal or mycobacterial infections. • Lymphocyte proliferation testing is positive in berylliosis and negative in sarcoidosis.
15.3 Langerhans Cell Histiocytosis 15.3.1 Clinical • • • •
A smoking-related interstitial lung disease. More common in younger adults (20–40 years). Cough with dyspnea are common clinical symptoms. Therapy is smoking cessation.
15.3.2 Imaging • Combination of nodules (early) and cysts (later) in the upper and mid lung zones (Figs. 15.20a, b and 15.21): –– Nodules – centrilobular/peribronchial, irregular margins, can cavitate or undergo cystic change. –– Cysts – initially thick-walled 1 cm
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Fig. 16.7 Coal workers’ simple pneumoconiosis. Thoracoscopic biopsy. Irregular pattern of fibrosis obliterates small airways
Fig. 16.8 Coal workers’ pneumoconiosis. Cytocentrifuge preparation (modified Giemsa). Numerous macrophages with cytoplasmic distension by coarsely granular black-gray anthracotic pigment
–– Caplan lesions: Nodular/necrobiotic lesions in the setting of coal workers with rheumatoid arthritis 16.2.3.2 Cytopathology • Numerous macrophages with cytoplasmic distension by coarsely granular black- gray anthracotic pigment (Fig. 16.8). 16.2.3.3 Pathologic Differential Diagnosis • Other exposures, including silica • Hyalinizing granulomas from infection and sarcoidosis
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16.2.3.4 Ancillary Studies • Mineralogical analysis of the lung can help to confirm pathologic diagnosis.
16.3 Asbestosis 16.3.1 Clinical • Asbestosis: –– –– –– ––
Construction, mining, shipping/automotive industries. Develops at least 10–15 years after exposure and is dose-related. Diffuse interstitial fibrosis. Asbestos-related pleural disease. Effusion, pleural plaque, diffuse pleural thickening, and rounded atelectasis
–– Latency for pleuropulmonary malignancy at least 20 years after exposure. –– Incidence is decreasing in industrial countries. –– Shortness of breath, cough and fine crackles, finger clubbing. Slowly progressive Increased risk of lung cancer
16.3.2 Imaging • Early –– Dorsal lung parenchyma affected with fine reticulation, pleural-based tiny nodules, subpleural curvilinear lines, and increased attenuation (Fig. 16.9a) –– May mimic dependent atelectasis • Advanced –– Peripheral and posterior lung honeycomb-like changes, coarse reticulations, traction bronchiectasis, and parenchymal bands (Fig. 16.9b) –– Mimic idiopathic pulmonary fibrosis (UIP pattern) (Fig. 16.9c)
16.3.3 Pathology 16.3.3.1 Surgical Pathology • Nonspecific interstitial and fibrotic changes: –– Accentuated in subpleural and peribronchiolar areas (Fig. 16.10) –– Asbestos bodies at elevated levels by mineral analysis
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Fig. 16.9 Asbestosis. Early. Supine HRCT image. (a) Changes in the lung bases mimic gravity- dependent atelectasis. Late. (b) Prone image confirms subpleural reticulations associated with mild traction bronchiectasis in the dorsal lower lungs. (c) Coronal reformatted image demonstrates apical-to-basilar gradient. CT findings are similar to that seen in UIP/IPF Fig. 16.10 Asbestosis. Explant pneumonectomy specimen. Diffuse fibrosis with more accentuated changes in the subpleural and peribronchiolar areas
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16.3.3.2 Cytopathology • May see ferruginous bodies in lavage specimens 16.3.3.3 Pathologic Differential Diagnosis • Chronic fibrosing interstitial pneumonias including usual interstitial pneumonia, nonspecific interstitial pneumonia, hypersensitivity pneumonitis, etc. 16.3.3.4 Ancillary Studies • Mineral analysis of bronchoalveolar fluid or lung tissue. • Transmission and scanning electron microscopy can be used.
16.4 Hard-Metal Pneumoconiosis 16.4.1 Clinical • Hard-metal lung disease due to exposure to synthetic tungsten: –– Found in occupations that use machine tools made by blending tungsten and cobalt • Criteria needed to establish diagnosis include: –– Occupational exposure history (cobalt and tungsten carbide or a mixture) Usually greater than 10 years –– Clinical features and imaging signs suggestive of interstitial lung disease –– Characteristic histology and presence of metal in lung tissue on histopathology
16.4.2 Imaging • HRCT features are similar to other idiopathic interstitial pneumonias. –– GGO +/− consolidations, subpleural cysts, reticulations, traction bronchiectasis, architectural distortion, and honeycombing (late) (Fig. 16.11a–c)
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Fig. 16.11 Hard-metal pneumoconiosis. CT chest. Progressive fibrotic changes in bilateral upper (a), mid (b), and lower (c) lung zones with coarse reticulations, traction bronchiectasis, and subpleural cystic changes
16.4.3 Pathology 16.4.3.1 Surgical Pathology • Can progress through three stages: –– Bronchiolitis (earliest stage) –– Subacute fibrosing alveolitis: Variable amounts Syncytial giant cells: may have lymphocytes and neutrophils in their cytoplasm (Fig. 16.12a, b) –– Interstitial fibrosis with honeycombing (advanced, can be rapidly progressive) 16.4.3.2 Pathologic Differential Diagnosis • Hypersensitivity pneumonitis with prominent giant cells • Viral pneumonitis with giant cells including measles and parainfluenza • Marked desquamative interstitial pneumonitis pattern
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Fig. 16.12 Hard-metal pneumoconiosis. Explanted pneumonectomy. (a) Airway-centered alveolitis with early fibrosis. (b) Scattered macrophages, syncytial giant cells
16.4.3.3 Ancillary Studies • Cobalt and tungsten found in mineralogical analysis
Suggested Readings Ahuja J, Kanne JP, Meyer CA, Pipavath SN, Schmidt RA, Swanson JO, Godwin JD. Histiocytic disorders of the chest: imaging findings. Radiographics. 2015;35(2):357–70. Beer C, Kolstad HA, Søndergaard K, Bendstrup E, Heederik D, Olsen KE, et al. A systematic review of occupational exposure to coal dust and the risk of interstitial lung diseases. Eur Clin Respir J. 2017;4(1):1264711. Gaffney A, Christiani DC. Gene-environment interaction from international cohorts: impact on development and evolution of occupational and environmental lung and airway disease. Semin Respir Crit Care Med. 2015;36(3):347–57. Hall NB, Blackley DJ, Halldin CN, Laney AS. Current review of pneumoconiosis among US coal miners. Curr Environ Health Rep. 2019;6(3):137–47. Honma K, Abraham JL, Chiyotani K, De Vuyst P, Dumortier P, Gibbs AR, et al. Proposed criteria for mixed-dust pneumoconiosis: definition, descriptions, and guidelines for pathologic diagnosis and clinical correlation. Hum Pathol. 2004;35(12):1515–23. Long J, Stansbury RC, Petsonk EL. Small airways involvement in coal mine dust lung disease. Semin Respir Crit Care Med. 2015;36(3):358–65. Ohori NP, Sciurba FC, Owens GR, Hodgson MJ, Yousem SA. Giant-cell interstitial pneumonia and hard-metal pneumoconiosis. A clinicopathologic study of four cases and review of the literature. Am J Surg Pathol. 1989;13(7):581–7. Roggli VL. Fiber analysis vignettes: Electron microscopy to the rescue! Ultrastruct Pathol. 2016;40(3):126–33. Seaman DM, Meyer CA, Kanne JP. Occupational and environmental lung disease. Clin Chest Med. 2015;36(2):249–68.
Chapter 17
Vasculitis
17.1 Granulomatosis with Polyangiitis (GPA) 17.1.1 Clinical • Granulomatous vasculitis that primarily involves the upper and lower respiratory tract and the kidney. • May affect the skin, eye, and central nervous system. • Peak incidence 40–60 years of age; M = F incidence. • Clinical symptoms: sinusitis, lung disease, and glomerulonephritis. –– Epistaxis –– Hemoptysis –– Dyspnea • Antibodies in the serum are helpful in diagnosis (anti-neutrophil cytoplasmic antibodies (ANCAs). –– c-ANCA: cytoplasmic staining Proteinase 3 is the target antigen. –– p-ANCA: perinuclear staining Myeloperoxidase is the target antigen.
17.1.2 Bronchoscopy • Varying degrees of erosion, ulceration, and scarring (Fig. 17.1a, b). • Endobronchial biopsies of ulcer edge may provide diagnostic features (see Surgical Pathology). © Springer Nature Switzerland AG 2020 C. Farver et al., Pulmonary Disease, https://doi.org/10.1007/978-3-030-47598-7_17
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Fig. 17.1 Granulomatosis with polyangiitis. Bronchoscopic image. (a) Punctate hemorrhage on bronchial mucosa in patient with recent onset GPA. (b) Mucosal scarring from patient with chronic GPA and multiple episodes of therapy
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Fig. 17.2 Granulomatosis with polyangiitis. Chest CT scan. RUL and LLL cavitary lung nodules. Lung window image (a) shows subtle ground-glass halo surrounding the larger nodule (arrow). (b) Mediastinal window images with show irregular and nodular mural thickening of both right and left lung nodules
17.1.3 Imaging • Lower respiratory tract: –– Nodules or masses – multiple, with cavitation (50%), irregular margins, often peribronchovascular (Fig. 17.2a, b) –– Airspace consolidations – peribronchial or wedge-shaped peripheral (may mimic lung infarcts) –– GGO – may be associated with nodules or masses (CT “halo sign”), as opposed to diffuse GGO in diffuse alveolar hemorrhage (Fig. 17.3) –– Bronchiectasis and tracheobronchial wall thickening (Fig. 17.4a, b)
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Fig. 17.3 Patient with hemoptysis and cANCA+. Chest radiograph. Diffuse alveolar hemorrhage presenting as dense consolidations in both mid and lower lung zones
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Fig. 17.4 Granulomatosis with polyangiitis: Chest CT scan, mediastinal images. (a) Diffuse wall thickening of the distal trachea and right main bronchus (arrows); (b) Thickening of right bronchus intermedius (arrow) requiring endobronchial stent placement
• Upper airways: –– Subglottic tracheal and bronchial stenosis, sinusitis, and nasal septal perforation • Mediastinum and hilar compartments: –– Lymph node enlargement • Pleura: –– Effusions (10–25%)
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17.1.4 Pathology 17.1.4.1 Surgical Pathology • Granulomatous vasculitis with inflammation and necrosis (Fig. 17.5a–d): –– Giant cells: Giant cells and histiocytic border of necrosis No well-formed granulomas –– Neutrophils, eosinophils, and lymphocytes –– Basophilic necrosis • Biopsies specimens can reveal all three features (Figs. 17.5 and 17.6). 17.1.4.2 Cytopathology • Features of hemosiderosis due to pulmonary hemorrhage (Fig. 17.7):
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Fig. 17.5 Granulomatosis with polyangiitis: Needle biopsy. (a) Large areas of basophilic necrosis (arrow). (b) Giant cells (arrow) adjacent to early neutrophilic abscess (left side of image). (c) Scattered giant cells throughout biopsy (arrows) (d) Movat pentachrome stain highlights area of fibrinous necrosis in vessel (arrow)
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Fig. 17.6 Granulomatosis with polyangiitis: Bronchoscopic biopsy. Multiple areas of granulomatous inflammation with neutrophilic abscess (arrows) and giant cells (arrowhead)
Fig. 17.7 Granulomatosis with polyangiitis: Cytopathology (Papanicolaou, cytocentrifuge preparation). Numerous macrophages with coarse golden-brown cytoplasmic hemosiderin pigment
–– Numerous macrophages with coarse golden-brown cytoplasmic hemosiderin pigment –– No significant accompanying inflammation 17.1.4.3 Pathological Differential Diagnosis • Infections: Mycobacterial or fungal –– The absence of granulomas in GPA –– Presence of granulomas in infections • Necrotizing sarcoid granulomatosis (NSG): –– Well-formed granulomas in NGS in lymphatic distribution
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• Rheumatoid nodule: –– Clinical history of rheumatoid arthritis 17.1.4.4 Ancillary Studies • Movat pentachrome stain highlights the destruction of elastica in vessels.
17.2 Microscopic Polyangiitis 17.2.1 Clinical • Necrotizing small vessel vasculitis without granulomatous inflammation, characterized by rapidly progressive glomerulonephritis and DAH: –– Perinuclear ANCA+ • Most common cause of pulmonary-renal syndrome • Rapid onset of symptoms
17.2.2 Imaging • Initial phase of active bleeding (Fig. 17.8): –– Diffuse, bilateral, perihilar airspace consolidations and ground-glass opacities (stage of active hemorrhage with alveolar filling) Fig. 17.8 Microscopic polyangiitis: Chest CT scan. Diffuse alveolar hemorrhage secondary to MPA. Lungs demonstrate diffuse, bilateral, perihilar airspace consolidations and ground-glass opacities (stage of active hemorrhage with alveolar filling)
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• Cessation of alveolar hemorrhage: –– Consolidations/GGO resolve over days-weeks (slower than edema yet faster than infection). –– Smooth interlobular septal thickening often superimposed over GGO (crazy- paving pattern). • Chronic recurrence of bleeding: –– Ill-defined, 1–3 mm, diffuse centrilobular nodules –– Alveolar macrophages with hemosiderin –– Different phases of DAH: GGO/consolidations/crazy-paving +/− underlying cause of DAH • Severe repeat hemorrhage: –– May progress to interstitial fibrosis
17.2.3 Pathology 17.2.3.1 Surgical Pathology • Predominantly small vessel pattern (arterioles, venules, and capillaries) with neutrophilic infiltrate (Fig. 17.9a–e). • Fibrinoid necrosis of alveolar wall • Evidence of hemosiderin deposition: –– Hemosiderin-laden macrophages –– Iron encrustation of elastic fibers around vasculature 17.2.3.2 Cytopathology • Hemosiderin-laden macrophages (Figs. 17.7 and 17.9) 17.2.3.3 Pathological Differential Diagnosis • Acute pneumonia in the setting of hemosiderosis: –– Neutrophilic infiltrate should be predominantly within the alveolar space and not in septal capillaries. –– Hemosiderin deposition should be minimal. • Pulmonary congestion: –– No neutrophils
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Fig. 17.9 Microscopic polyangiitis: Thoracoscopic biopsy. (a) Alveolar hemorrhage with hemosiderin-laden macrophages and neutrophilia present predominantly in septal capillaries. (b) Focus of alveolar septal destruction (arrow). (c) Movat pentachrome stain highlights destruction of elastic fibers (arrow); note alveolar macrophages with marked hemosiderin pigment in adjacent alveolar space. (d) Iron encrusting elastic fibers around vessels consistent with a history of pulmonary hemorrhage. (e) Prussian blue iron stain highlights hemosiderin-laden macrophages
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17.2.3.4 Ancillary Studies • Movat pentachrome may highlight destruction of capillary wall (Fig. 17.9). • Iron stains highlight presence of hemosiderin deposition (Fig. 17.9).
17.3 Eosinophilic Granulomatosis with Polyangiitis (EGPA) 17.3.1 Clinical • Small vessel vasculitis associated with asthma and eosinophilia • Cardiac and peripheral neuropathy much more common than pulmonary hemorrhage and glomerulonephritis • Perinuclear ANCA+
17.3.2 Imaging • Transient, patchy, nonsegmental, and often peripheral opacities without zonal predilection (Fig. 17.10): –– Differential diagnosis is eosinophilic pneumonia and organizing pneumonia. • Small centrilobular nodules +/− reticular opacities. • DAH-type imaging findings are rare. • Cardiac manifestations: –– Endocardial thickening, thrombus formation, and myocardial dysfunction Fig. 17.10 EGPA: Chest CT scan. A 59-year-old with asthma, eosinophilia, and + ANCA with bilateral, peripheral, patchy opacities consistent with EGPA
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17.3.3 Pathology 17.3.3.1 Surgical Pathology • • • •
Eosinophilic pneumonia (Fig. 17.11a–d) Vasculitis with fibrinoid necrosis and abundant eosinophils Hemosiderin deposition Evidence of asthma (see Chap. 11): –– Curschmann spirals –– Charcot-Leyden crystals –– Thickened basement membranes with goblet cell hyperplasia of large airways
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Fig. 17.11 EGPA: Thoracoscopic biopsy. (a) Patchy areas of basophilic geographic necrosis. (b) Eosinophilic microabscess (arrow) surrounded by giant cells. (c) Degenerating eosinophils within microscopic abscess. (d) Congo red stain highlights granules in degenerating eosinophils
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17.3.3.2 Cytopathology • Evidence of hemosiderin deposition (see Fig. 17.7). • Lavage may have evidence of asthma with eosinophils, Charcot-Leyden crystals, and Curschmann spirals (see Chap. 11). 17.3.3.3 Pathological Differential Diagnosis • Granulomatosis with polyangiitis • Eosinophilic pneumonia • Capillaritis 17.3.3.4 Ancillary Studies • Movat pentachrome stain may highlight destruction of elastic fibers in vessels. • Congo red stain highlights eosinophil granules (Fig. 17.11d). • Silver stains may be helpful to highlight fungal hyphae fragments that can be seen in asthmatic lungs.
Suggested Readings Alba MA, Jennette JC, Falk RJ. Pathogenesis of ANCA-associated pulmonary vasculitis. Semin Respir Crit Care Med. 2018;39:413–24. Scapa JV, Fishbein GA, Wallace WD, Fishbein MC. Diffuse alveolar hemorrhage and pulmonary vasculitides: histopathologic findings. Semin Respir Crit Care Med. 2018;39:425–33. Wick MR. Pulmonary disorders that are potentially associated with anti- neutrophilic cytoplasmic antibodies: a brief review. Semin Diagn Pathol. 2018;35:304–14. Wu EY, Hernandez ML, Jennette JC, Falk RJ. Eosinophilic granulomatosis with polyangiitis: clinical pathology conference and review. J Allergy Clin Immunol Pract. 2018;6:1496–504.
Chapter 18
Hypertensive Vascular Diseases
18.1 Pulmonary Hypertension 18.1.1 Clinical 18.1.1.1 Pulmonary Arterial Hypertension (PAH) • Mean PA pressure >20 mm Hg at rest or >35 mm Hg with exercise; high pulmonary vascular resistance • Updated WHO Classification of Pulmonary Hypertension –– Group 1: Pulmonary arterial hypertension 1’ Pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH) –– –– –– ––
Group 2: Pulmonary hypertension due to left heart disease Group 3: Pulmonary hypertension due to lung disease and/or hypoxia Group 4: Chronic thromboembolic pulmonary hypertension Group 5: Pulmonary hypertension with unclear multifactorial mechanisms
18.1.2 Imaging • Dilated main and central pulmonary arteries (MPA >=30 mm and larger than the thoracic aorta) (Fig. 18.1a–e) • Abrupt tapering tortuous peripheral pulmonary vessels • RV hypertrophy (>4 mm) and enlargement (RV-to-LV diameter >1:1): –– Septal bowing toward LV
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Fig. 18.1 Pulmonary hypertension. A 23-year-old female with primary pulmonary hypertension. (a) PA chest radiograph shows dilated main and central pulmonary arteries (arrows) with a normal- sized heart. Contrast-enhanced CT chest images. (b) Lung window images show mosaic perfusion abnormality with lobular and perihilar distribution in the upper and (c) lower lobes. (d) Mediastinal window setting shows markedly dilated 4 cm main pulmonary artery (MPA) > ascending aorta and (e) enlarged right heart chambers (RV > LV) with straightening of the interventricular septum
• Tricuspid regurgitation, dilated RA, IVC and hepatic veins, ascites, pericardial effusion • Mosaic perfusion pattern in the lungs (alternating normal and lucent lung parenchyma) • Small, tortuous peripheral arteries without connection to pulmonary veins (seen with arteriovenous shunt) (Figs. 18.2a–c and 18.3a–c)
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Fig. 18.2 Plexiform pulmonary hypertension. CT features of plexiform arteriopathy in three different patients. A 22-year-old female with idiopathic pulmonary hypertension. CT angiogram (CTA) images in (a) mediastinal, (b) lung, and (c) bone window settings reveal dilated MPA with abnormal tortuous, peripheral arteries (a–c arrows). Note dilated RA and RV with reverse bowing of the interventricular septum
• GGO closely associated with abnormal tortuous peripheral pulmonary arteries (Fig. 18.3)
18.1.3 Pathology 18.1.3.1 Surgical Pathology • Vascular changes in low-grade pulmonary arterial hypertension (PAH): –– Medial hypertrophy (Fig. 18.4): Can be seen in hypoxic settings –– Intimal fibroplasia (Fig. 18.5): Cellular (Fig. 18.5a) Concentric (Fig. 18.5b) • Vascular changes present in high-grade PAH:
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Fig. 18.3 Plexiform pulmonary hypertension. (a, b) Multiple coronal reformatted images in lung window settings highlight abnormal tortuous small peripheral pulmonary arteries without any connection to veins. (c) Axial lung window image shows abnormal lobular ground-glass opacities (GGO) closely associated with tiny tortuous small peripheral arteries
–– Plexiform lesion (Fig. 18.6) –– Vasodilatation lesion (Fig. 18.7) –– Arteritis with fibrinoid necrosis Rarely seen lesion 18.1.3.2 Differential Diagnosis • Chronic thromboembolic pulmonary hypertension (CTEPH): –– The intimal fibrosis seen in low-grade pulmonary arterial hypertension is concentric.
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Fig. 18.4 Pulmonary arterial hypertension. Explanted lung. Small artery with smooth muscle hypertrophy (arrow), of predominantly inner longitudinal smooth muscle layers
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Fig. 18.5 Pulmonary arterial hypertension. Explanted lung. Movat pentachrome stain highlights (a) intimal fibrosis (arrow) of small artery and (b) concentric intimal fibrosis with “onionskin”type pattern in small arteriole
Intimal fibrosis in CTEPH is eccentric. –– Plexiform lesions may be misdiagnosed as chronic thromboembolic arteriopathy with recanalized vessels. Chronic organizing thrombi in vessels have intact elastic lamina, unlike plexiform lesions where internal and external elastic lamina have been destroyed and remodeled. 18.1.3.3 Ancillary Studies • Elastic or Movat pentachrome stains can help to define the extent of injury in artery/arterial wall (Figs. 18.6 and 18.7).
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Fig. 18.6 Pulmonary arterial hypertension. Explanted lung. Plexiform lesion usually seen in severe pulmonary hypertension, including idiopathic and heritable types. Slit-like spaces represent remodeled vessel with abnormal proliferating endothelial cells
Fig. 18.7 Pulmonary arterial hypertension. Explanted lung. Vasodilation lesion with blood-filled dilated small vessels adjacent to residual plexiform areas (arrow)
18.2 Chronic Thromboembolic Disease 18.2.1 Clinical 18.2.1.1 Chronic Thromboembolic Pulmonary Hypertension • • • •
Can be seen in any age Most common in hospitalized, immobile patients 10% mortality reported in post-operative patients with risk factors Usually minimal clinical symptoms: –– Pleuritic pain secondary to peripheral infarction due to thromboembolism
• Can cause right-sided heart enlargement and cor pulmonale
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Fig. 18.8 Chronic thromboembolic pulmonary hypertension. CT angiogram. (a) Mediastinal window image shows mural thrombus with thickening of the wall of the LPA. Intra-luminal contrast and a linear band is noted along the anterior wall of the LPA (arrow), anterior segmental artery LUL and RUL branches. Note dilated distal MPA and LPA and bronchial arterial collaterals. (b) Corresponding lung window image shows segmental and subsegmental pattern of mosaic perfusion abnormality in both lungs with attenuation of pulmonary vessels in the lucent lung regions. Note peripheral opacities in the dorsal regions of both lungs likely sequelae of prior infarcts
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Fig. 18.9 Chronic thromboembolic pulmonary hypertension. CT angiogram chest in two different patients highlight the different imaging appearances of chronic and acute PE. (a) Partly endothelialized wall thrombus with eccentric mural thickening of the LPA represents chronic PE. (b) Acute PE appears as central filling defects in the left and right PA branches
18.2.2 Imaging • Direct visualization of occluded vessels, eccentric mural thrombi, and thickening: –– +/− calcifications of the vessel wall • Irregularity of the intimal lining adjacent to luminal contrast and intraluminal bands/webs (Figs. 18.8a, b and 18.9a, b). • Combination of marked variation in size of small vessels and mosaic lung attenuation. • Segmental and subsegmental vessels are abnormally narrowed in the lucent lung in comparison to accompanying bronchi, or abruptly cut-off in the hypo-perfused regions.
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Fig. 18.10 Chronic thromboembolic pulmonary hypertension. Wedge excision. Eccentric intimal fibrosis with early recanalized blood-filled channel in small artery
• VQ scan good screening test (high sensitivity, low specificity): –– 1 or more mismatched defect(s) • Catheter pulmonary angiography: –– Less used due to CT pulmonary angiography (CTA) • Mosaic attenuation in segmental and subsegmental distributions (as opposed to perihilar or lobular mosaic in idiopathic PAH): –– Due to poor perfusion in the affected vessels with increased shunting of flow to adjacent unaffected regions • Presence of systemic artery collaterals, usually bronchial. • Peripheral lung opacities caused by remote infarction and bronchial dilatation in under-perfused regions.
18.2.3 Pathology 18.2.3.1 Surgical Pathology • Blood clot incorporated into vessel wall over stages causes eccentric intimal fibrosis: –– Fibrin with blood –– Endothelial cells and fibroblasts organize thrombus into vessel wall (Fig. 18.10) • Endothelial cells develop new recanalized channels within vessel lumen resulting in “punched-out” lumina (Fig. 18.11).
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Fig. 18.11 Chronic thromboembolic pulmonary hypertension. Wedge excision. Recanalized small artery with round, organized vascular channels within the lumen of small artery
18.2.3.2 Ancillary Studies • Elastic or Movat pentachrome stains can help to definite extent of injury and elastic destruction in artery/arterial wall.
18.3 Pulmonary Veno-occlusive Disease 18.3.1 Clinical • Idiopathic. • Familial form with genetic mutation has been defined; EIF2AK4. • Can be associated with viral infections, drug toxicity (chemotherapy, OCP), pregnancy, and bone marrow transplantation. • Age range from 8 weeks -70 years; (M = F). • Rapidly progressive. • Combination of usual manifestations of pulmonary arterial hypertension with radiographic evidence of pulmonary edema and normal pulmonary artery occlusion pressure is considered virtually diagnostic. • Distinction from PAH is important for clinicians as administration of vasodilator drugs for presumed PAH may precipitate life-threatening pulmonary edema in PVOD patients.
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Fig. 18.12 Pulmonary veno-occlusive disease. Lung window images show widespread smooth interlobular septal thickening with mild bilateral symmetrical peripheral ground-glass opacities
Fig. 18.13 Pulmonary veno-occlusive disease. Explant pneumonectomy. Intimal scarring with “colander-like” area (arrow) of vein within interlobular septum
18.3.2 Imaging • Extensive smooth interlobular septal thickening (Fig. 18.12): –– Can have diffuse or centrilobular and somewhat nodular GGO (Fig. 18.12) • Normal size or small left atrium, normal caliber central pulmonary veins. • Pleural effusions may be present.
18.3.3 Pathology 18.3.3.1 Surgical Pathology • Intimal fibrosis of veins within interlobular septum (Fig. 18.13). • Veins may become arterialized with elastic lamina.
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• Pulmonary arterial hypertensive changes with medial hypertrophy usually present. • Hemosiderosis may be present. • Pulmonary capillary hemangiomatosis can be present. 18.3.3.2 Differential Diagnosis • Diseases that may produce interseptal scarring can mimic PVOD. –– Chronic sarcoidosis with hyalinizing granulomas in interlobular septae Granulomas are usually found elsewhere and are not a component of PVOD. –– Chronic atelectasis can cause septal thickening and fibrosis. Usually lobule is collapsing and overlying pleuritis is seen. 18.3.3.3 Ancillary Studies • Elastic stains or Movat pentachrome stains can help to define the extent of injury in veins and define colander lesions.
18.4 Pulmonary Capillary Hemangiomatosis 18.4.1 Clinical • • • • •
Very similar to PVOD in clinical manifestations. Familial, congenital, and sporadic forms. Typically presents between 20 and 40 yrs. Hemoptysis and pleural effusions are usually presenting signs. May be present in connective tissue disease.
18.4.2 Imaging • Most often indistinguishable from PVOD on imaging. • PCH reportedly may show more circumscribed nodular GGO and relatively scarce smooth septal thickening in comparison to PVOD, which shows widespread interlobular septal lines and diffuse GGO (Fig. 18.14).
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Fig. 18.14 Pulmonary capillary hemangiomatosis. CT angiogram. Lung windows show diffuse bilateral centrilobular and vaguely nodular GGO with smooth interlobular septal thickening
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Fig. 18.15 Pulmonary capillary hemangiomatosis. Explant pneumonectomy. (a) Alveolar walls expanded by capillary proliferations surrounded bronchovascular area. (b) Thickened alveolar walls contain multiple nuclei of endothelial cells. (c) Immunohistochemical study for CD31 highlights multiple endothelial cells of capillaries within the lesion
18.4.3 Pathology 18.4.3.1 Surgical Pathology • Multiple capillary proliferations expanding alveolar wall (Fig. 18.15a–c). • Bronchocentric distribution. • Hemosiderin-laden macrophages are present.
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18.4.3.2 Differential Diagnosis • Cardiac congestion with dilatation of capillaries can mimic PCH. –– Immunohistochemical studies to define increased/aberrant growth of capillaries within alveolar wall are essential to diagnose PCH. 18.4.3.3 Ancillary Studies • Immunohistochemical studies for cytokeratin staining pneumocytes in alveolar wall will help to highlight alveolar wall thickening. • Vascular immunohistochemical studies such as CD31 or ERG will highlight the proliferation of capillaries within the alveolar wall (Fig. 18.15).
18.5 Talcosis 18.5.1 Clinical • Associated with intravenous abuse of medications meant for oral consumption. • Insoluble fillers used in oral tablets become trapped in small vessels and cause vascular occlusion. • Lower lobe predominant panacinar emphysema in intravenous methylphenidate (Ritalin) abuse can be seen.
18.5.2 Imaging • Diffuse micronodular pattern throughout both lungs (Fig. 18.16). • Perihilar conglomerate masses with intrinsic high attenuation, fibrosis, and honeycombing can be seen. Fig. 18.16 Pulmonary talcosis. HRCT. A 32-year-old intravenous drug abuser shows diffuse bilateral small nodules of injection talc granulomatosis
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Fig. 18.17 Pulmonary talcosis. CT chest in Ritalin abuse with lower lobe predominant panlobular emphysema
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Fig. 18.18 Pulmonary talcosis. Wedge excision. (a) Giant cell reaction to birefringent material within alveolar wall (arrows). (b) Polarized light highlights birefringent material within giant cells
• Enlarged main pulmonary artery. • Lower lobe predominant panlobular emphysema may be seen on imaging studies (simulates alpha-1 antitrypsin deficiency) (Fig. 18.17).
18.5.3 Pathology 18.5.3.1 Surgical Pathology • Insoluble material, usually intended for oral use, injected in veins: –– Includes talc, microcrystalline cellulose, and crospovidone. –– Pale-yellow particles within walls of blood vessels with giant cells (Fig. 18.18a, b). –– Plate-like particles may be present with larger injected material (crushed pills) (Fig. 18.19).
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Fig. 18.19 Pulmonary talcosis. Wedge excision. Foreign material consisting of insoluble injected oral material within lumen of small artery
• Foreign material is highlighted under polarized light (Fig. 18.18). • Panacinar emphysema can be seen secondary to chronic intravenous drug infection (Fig. 18.17). 18.5.3.2 Ancillary Studies • Foreign material can be highlighted by: –– Periodic acid-Schiff (PAS)+ –– Movat pentachrome
Suggested Readings Cool CD. Vascular diseases in pulmonary pathology, Chapter 7. In: Zander D, Farver CF, editors. A volume in the series Foundations in Diagnostic Pathology. 2nd ed. Philadelphia: Elsevier; 2018. p. 98–126. Lang IM, Dorfmüller P, Vonk Noordegraaf A. The pathobiology of chronic thromboembolic pulmonary hypertension. Ann Am Thorac Soc. 2016;13(Suppl 3):S215–21. O'Keefe MC, Post MD. Pulmonary capillary hemangiomatosis: a rare cause of pulmonary hypertension. Arch Pathol Lab Med. 2015;139(2):274–7. Olschewski A, Berghausen EM, Eichstaedt CA, Fleischmann BK, Grünig E, Grünig G, et al. Pathobiology, pathology and genetics of pulmonary hypertension: update from the Cologne consensus conference 2018. Int J Cardiol. 2018;272S:4–10. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41. Szturmowicz M, Kacprzak A, Szołkowska M, Burakowska B, Szczepulska E, Kuś J. Pulmonary veno-occlusive disease: pathogenesis, risk factors, clinical features and diagnostic algorithm state of the art. Adv Respir Med. 2018;86(3) Tuder RM. Pathology of pulmonary arterial hypertension. Semin Respir Crit Care Med. 2009;30(4):376–85.
Chapter 19
Bacterial Infections
19.1 Actinomycosis 19.1.1 Clinical • Chronic suppurative infection caused by Actinomycosis israelii. –– Gram-positive, filamentous anaerobic bacteria. –– An oropharyngeal saprophyte. –– 20% of infections by Actinomyces occur in the lung. • Common forms of thoracic actinomycosis: –– Parenchymal/nodular form: Aspiration of oropharyngeal contents in patients with poor oral hygiene or spread from cervicofacial infection May begin as nodule and progress to dense consolidations that may mimic a neoplasm Upper lobe predominant Progresses to chronic segmental airspace consolidation Associated pleural reaction (thickening and/or effusion) and thoracic lymphadenopathy Left untreated, can cross fissures and erode into the pleura/chest wall –– Endobronchial form: Aspiration with infection of preexisting broncholith or aspiration of contaminated foreign body such as fish/chicken bone, leading to post-obstructive pneumonia
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Fig. 19.1 Actinomycosis. Unenhanced CT chest. Extensive areas of low attenuation and cavitation within the RLL consistent with necrotizing pneumonia and lung abscess formation. Note empyema necessitans with extension of inflammation, necrotic material, and an air-fluid level within the right lateral chest wall (arrow), which required surgical drainage/resection
–– Bronchiectasis: Secondary colonization of bronchiectatic airways from prior TB, chronic inflammatory process, and others
19.1.2 Imaging • Parenchymal form (Fig. 19.1): –– Central necrotic low-attenuation centers, which often cavitate with wall enhancement • Endobronchial form (Fig. 19.2a–d): –– Associated with broncholithiasis – proximal endobronchial calcified broncholith and distal segmental or lobar post-obstructive pneumonia with central necrosis –– Associated with foreign body aspiration – proximal impacted endobronchial foreign body with distal post-obstructive pneumonia showing central necrosis • Bronchiectatic form (Fig. 19.3a, b): –– Bronchiectasis with worsening dilatation, wall thickening, and peribronchial consolidation
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Fig. 19.2 Actinomycosis. Chest CT scan. A 73-year-old female with recurrent right-sided pneumonia due to impacted foreign body. (a) (lung windows) Right lower lobe consolidation, (b) (lung windows), (c) (mediastinal windows), and (d) (bone windows). Foreign body detected within the bronchus intermedius was a fish bone (arrows) and was subsequently extracted on bronchoscopy
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Fig. 19.3 Actinomycosis. Chest CT scan. A 74-year-old female. (a) Chronic volume loss and RLL bronchiectasis. (lung windows). (b) Calcified broncholiths seen, which may represent sequelae of prior TB. Actinomyces and nocardia may colonize lungs with preexisting bronchiectasis
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19.1.3 Pathology 19.1.3.1 Surgical Pathology • Usually airway-centered suppurative infection with foci of “sulfur granules” (Fig. 19.4): –– Aggregates of filamentous, beaded bacteria with radial orientation (Fig. 19.5) –– Splendore-Hoeppli effect Eosinophilic material on the filaments –– Seen on Gomori methenamine silver and bacterial stains (Tworts and Gram) as Gram-positive filamentous organisms (Fig. 19.6a, b) • Areas of chronic pneumonia commonly present surrounding abscess. 19.1.3.2 Pathologic Differential Diagnosis • Necrotizing bacterial infections with Splendore-Hoeppli effect: –– Botryomycosis: Mixture of Gram-positive and Gram-negative organisms within abscess Fig. 19.4 Actinomycosis. Lobectomy. Bronchiectasis with marked chronic inflammation and sulfur granule (arrow) within dilated airway
Fig. 19.5 Actinomycosis. Wedge excision. Sulfur granule in the middle of abscess with eosinophilic rods on the edge of granule (Splendore-Hoeppli effect)
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–– Nocardiosis: Non-branching filamentous organisms (see below) Positive on Fite stain –– Fungal hyphae: Thicker hyphae forms 19.1.3.3 Ancillary Studies • Silver-positive and Gram-positive tissue staining of organisms (Fig. 19.6)
19.2 Nocardiosis 19.2.1 Clinical • Nocardia asteroides most common organism. • Opportunistic infection caused by filamentous, Gram-positive, weakly acid-fast aerobic bacteria. • Lung most common site of infection. • Disseminated disease with hematogenous spread from lungs to the CNS, skin and joints can develop in the immunosuppressed. • Associated with impaired cell immunity (AIDS, post-transplant, steroids). • Risk factors include: –– Pulmonary alveolar proteinosis –– Impaired cell immunity (AIDS, post-transplant, steroids)
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Fig. 19.6 Actinomycosis. Wedge excision. (a) Gram stain highlights the filamentous branching rods with in the sulfur granule. (b) Organisms are highlighted in black silver on Gomori methenamine silver stain
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19.2.2 Imaging • Imaging patterns similar to actinomycosis and MTB infections: –– May colonize lungs with preexisting bronchiectasis • Airspace consolidation(s) with central low attenuation and cavitation (Fig. 19.7a, b) • Nodules and masses, which may also show central low-attenuation and/or ground-glass halo (Figs. 19.8, 19.9, and 19.10) • Pleural and chest wall involvement (empyema necessitans) –– Sinus tracts common a
b
Fig. 19.7 Nocardiosis. Chest CT scan. A 74-year-old female with unilateral left lung transplant and fibrotic interstitial disease in the native right lung. (a) (Lung windows) and (b) (mediastinal windows). A peripheral, cavitary mass in the RLL abuts the pleura. Transbronchial biopsy demonstrated nocardiosis Fig. 19.8 Nocardiosis. Chest CT scan. Solitary LUL solid nodule in a 59-year-old with COPD on long-term steroids
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Fig. 19.9 Nocardiosis. Chest CT scan. RUL cavitary mass with surrounding ground-glass halo in a 45-year-old male
Fig. 19.10 Nocardiosis. Chest CT scan. A cavitary nodule (arrow) and multiple solid lung nodules (mostly in the LLL), in a 54-year-old male with alpha-1 antitrypsin deficiency
19.2.3 Pathology 19.2.3.1 Surgical Pathology (Fig. 19.11) • Neutrophilic and histiocytic abscesses. • Multinucleated giant cells may be seen. • Organisms mostly found in necrosis: –– Long, filamentous, Gram-negative bacilli with branching at right angles. –– Fite and silver-positive stains will highlight. • Endobronchial biopsies will have predominantly acute, necrotizing inflammation and may have abundant organisms present (Fig. 19.12a, b).
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Fig. 19.11 Nocardiosis. Wedge excision. Neutrophilic and histiocytes intra- alveolar exudate
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Fig. 19.12 Nocardiosis. Endobronchial biopsy. (a) Acute, exudative infiltrate in patient with Nocardia-positive culture. (b) Infiltrate is predominantly neutrophilic with necrosis on surface
19.2.3.2 Cytopathology • Findings are nonspecific, showing abundant neutrophilic debris (Fig. 19.13). 19.2.3.3 Pathologic Differential Diagnosis • Other necrotizing pneumonias with filamentous organisms, e.g., Actinomyces 19.2.3.4 Ancillary Studies • Silver and modified acid-fast (Fite) stains highlight organisms (Figs. 19.14 and 19.15).
19.3 Legionella Pneumonia Fig. 19.13 Nocardiosis. Cytopathology. (Modified Giemsa, EBUS FNA lung, direct smear). High cellularity samples with innumerable neutrophils, a few histiocytes, and scattered reactive epithelial cells
Fig. 19.14 Nocardiosis. Wedge excision. Gomori methenamine silver stain highlights filamentous bacilli
19.3 Legionella Pneumonia 19.3.1 Clinical • • • • • •
L. pneumophila is a causal organism. Most common in adults. Chills and rigors with hypoxia and pleuritic chest pain. Diagnosis usually made by sputum or bronchoalveolar lavage cultures. Urine antigens for L. pneumophila are sensitive marker for clinical disease. 5–25% mortality.
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Fig. 19.15 Nocardiosis. Organisms are partially acid-fast and are highlighted in red-pink in tissue with Fite stain
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Fig. 19.16 Legionella pneumonia. Wedge excision. (a) Neutrophilic and histiocytic exudate fill alveolar space. (b) Organisms appear as pleomorphic rods on Dieterle stain
19.3.2 Imaging • Usually starts as lower lobe infiltrates. • Multilobar spread is rapid. • Pleural effusions are common.
19.3.3 Pathology 19.3.3.1 Surgical Pathology (Fig. 19.16a, b) • Characteristic fibrinopurulent exudates fill alveolar spaces with predominantly necrotic inflammatory cells (histiocytes and neutrophils predominate). • Peripheral edges of lesions have edema and hyaline membranes. • Organisms are seen best on silver stains such as Warthin-Starry, Steiner, and Dieterle (Fig. 19.16b).
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19.3.3.2 Pathologic Differential Diagnosis • Hemorrhagic pneumonias such as S. pneumoniae • Some viral pneumonias including influenza 19.3.3.3 Ancillary Studies • Do not stain on Gram stains. • Silver stains will highlight organisms. –– Warthin-Starry –– Steiner –– Dieterle (Fig. 19.16b)
19.4 Malakoplakia 19.4.1 Clinical • Found in immunocompromised patients. • Upper lobe predominant. • R. equi is a Gram-positive pleomorphic coccobacillus. –– Weakly acid-fast positive –– Found in soil and barnyard animals • Good prognosis with antimicrobial therapy.
19.4.2 Imaging • Mass-like consolidations or lung nodules, often with central cavitation. • Mimic infections such as TB, pulmonary vasculitis such as GPA, or malignancy.
19.4.3 Pathology 19.4.3.1 Surgical Pathology • Histiocytic predominant pneumonia with Michaelis-Gutmann bodies (Fig. 19.17)
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Fig. 19.17 Malakoplakia. Wedge excision. Marked histiocytic pneumonia with scattered neutrophils
19.4.3.2 Pathologic Differential Diagnosis • Histiocytic-rich lesions of the lung including: –– M. avium complex –– Disseminated fungal infections –– Storage diseases 19.4.3.3 Ancillary Studies • Gram stains positive. • May be weakly acid-fast positive on Ziehl-Neelsen staining. • Michaelis-Gutmann bodies are seen on PAS, von Kossa (calcium), or iron stains.
19.5 Aspiration Pneumonia 19.5.1 Clinical • Aspiration of foreign material in the lungs may cause: –– Aspiration pneumonia – polymicrobial flora from the aerodigestive tract –– Bacteria may include: Bacteroides sp., Fusobacterium sp., and Actinomyces –– Chemical pneumonitis – acute onset bilateral, multifocal perihilar, or basilar airspace disease –– Lipoid pneumonia – consolidation with fat density or GGO with smooth septal lines (crazy paving) • Material can enter via upper airways or fistula.
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• Aspiration of gastric contents can range from an easily cleared particle to fatal event from airway occlusion and asphyxiation. • Chronic aspiration can lead to chronic infections, aspiration pneumonitis, or scarring.
19.5.2 Bronchoscopy • Bronchoscopy early after event can remove material. –– Foreign body (Fig. 19.18) –– Suction of liquid contents including gastric/bile fluid and purulent secretions associated with infection (Figs. 19.19 and 19.20)
19.5.3 Imaging • Unilateral or bilateral patchy areas of consolidation, GGO, centrilobular nodules with fluid in airways (Figs. 19.21, 19.22a–c and 19.23). • Aspirated foreign material can be seen in more proximal airways (Fig. 19.24a, b). Fig. 19.18 Aspiration pneumonia. Direct bronchoscopic image. Capsule endoscope aspirated while trying to look for the source of a GI bleed
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Fig. 19.19 Aspiration pneumonia. Direct bronchoscopic image. Large bile contamination from a tracheoesophageal fistula. Note the green/ yellow color of the foamy secretions
Fig. 19.20 Aspiration pneumonia. Direct bronchoscopic image. Purulent secretions associated with Pseudomonas infection. Therapeutic aspiration of secretions was performed and microbiological cultures were obtained
• Dependent distribution in the lungs: –– Posterior segment RUL and superior segment both LL in recumbent posture –– Basilar segments of bilateral LL, RML, and lingular segments LUL in erect position • Complications – abscess (common cause), necrotizing pneumonia, pleural effusion, and empyema.
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Fig. 19.21 Aspiration pneumonia. Chest CT scan. LLL pneumonia in an elderly patient with cerebrovascular accident and preferred left decubitus sleeping posture
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Fig. 19.22 Aspiration pneumonia. Chest CT scan. (a) A 46 year-old female with tracheoesophageal fistula (arrow). Note dilated esophagus (star). (b, c) Lung window images demonstrate patchy GGO and lucent areas (mosaic attenuation) in the RML, and RLL > LLL, associated with bronchial wall thickening (RML) and focal bronchiectasis in the RLL (arrow)
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Fig. 19.23 Aspiration pneumonia. Chest CT scan, lung window images. Tree-in-bud and patchy peribronchial ground-glass opacities in multiple lung lobes. RLL bronchial secretions noted (arrow)
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Fig. 19.24 Aspiration pneumonia. Chest CT scan. (a) (Lung windows), (b) (mediastinal windows). Aspiration of tooth (arrow) in the bronchus intermedius retrieved by bronchoscopy
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Fig. 19.25 Aspiration pneumonia. Wedge excision. (a) Small airway with marked neutrophilic inflammation and giant cells within mucin. (b) Giant cell reaction surrounding periphery of microabscess
19.5.4 Pathology 19.5.4.1 Surgical Pathology • Bronchopneumonia with marked neutrophils and giant cell reaction to foreign/ particulate material (Fig. 19.25a, b).
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Fig. 19.26 Aspiration pneumonia. Endobronchial biopsy. (a) Iron encrustation of endobronchial wall in patient who aspirated iron pill. (b) Iron stain highlights iron deposition
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Fig. 19.27 Aspiration pneumonia. Core biopsy. (a) Lipid vacuoles from nodular infiltrate of patient with mineral oil aspiration. (b) Varying-sized lipid vacuoles with a few surrounding histiocytes
• Gram stains may reveal polymicrobial infections with both Gram-positive and Gram-negative cocci and bacilli. • Aspiration of large particles (e.g., pills, etc.) may cause local pathologic changes due to contents (Fig. 19.26a, b). • Aspiration of lipid forms giant cell reaction to fat vacuoles in tissue (Fig. 19.27a, b). • Old aspirated particles become hyalinized and may have calcium, features consistent with chronic aspiration (Fig. 19.28). 19.5.4.2 Pathologic Differential Diagnosis • Granulomatous infections with giant cells including fungus and mycobacteria • Other necrotizing pneumonias including Pseudomonas, Staphylococcus, etc. 19.5.4.3 Ancillary Studies • Gram stain may confirm polymicrobial organisms.
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Fig. 19.28 Aspiration pneumonia. Hyalinized nodule with focal calcium deposition in lung transplant patient with history of chronic aspiration
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Fig. 19.29 Aspiration pneumonia. Postmortem lung. (a) Large foreign particles present in abscess of patient with acute and chronic aspiration from tracheoesophageal fistula. (b) Under polarized light, foreign material is birefringent. Vegetable particle (arrow) reveals no birefringence
• Immunohistochemical studies may be helpful in highlighting cytokeratinaceous squamous debris from oral contents. • Some foreign material (food stuff, contents of pills, etc.) may contain birefringent material and can been seen under polarized light (Fig. 19.29a, b).
Suggested Readings Cunha BA, Cunha CB. Legionnaire’s disease: a clinical diagnostic approach. Infect Dis Clin N Am. 2017;31(1):81–93. Farver CF. Bacterial diseases, Chapter 10. In: Zander D, Farver CF, eds., Pulmonary Pathology, a volume in the series Foundations in Diagnostic Pathology. J. Goldblum ed., 2nd ed. Philadelphia: Elsevier; 2017.
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Herwaldt LA, Marra AR. Legionella: a reemerging pathogen. Curr Opin Infect Dis. 2018;31(4):325–33. Kanne JP, Yandow DR, Mohammed TL, Meyer CA. CT findings of pulmonary nocardiosis. AJR Am J Roentgenol. 2011;197(2):W266–72. Kwon KY, Colby TV. Rhodococcus equi pneumonia and pulmonary malakoplakia in acquired immunodeficiency syndrome. Pathologic features. Arch Pathol Lab Med. 1994;118:744–8. Mandell LA, Niederman MS. Aspiration Pneumonia. N Engl J Med. 2019;380:651–66. McHugh KE, Sturgis CD, Procop GW, Rhoads DD. The cytopathology of Actinomyces, Nocardia, and their mimickers. Diagn Cytopathol. 2017;45(12):1105–15. Mittal S, Singh AP, Gold M, Leung AN, Haramati LB, Katz DS. Thoracic imaging features of Legionnaire’s disease. Infect Dis Clin N Am. 2017;31:43–54. Sehgal IS, Dhooria S, Ram B, Singh N, Aggarwal AN, Gupta D, Behera D, Agarwal R. Foreign body inhalation in the adult population: experience of 25,998 bronchoscopies and systematic review of the literature. Respir Care. 2015;60(10):1438–48. Yildiz O, Doganay M. Actinomycoses and Nocardia pulmonary infections. Curr Opin Pulm Med. 2006;12(3):228–34.
Chapter 20
Mycobacterial Infections
20.1 Tuberculous Mycobacterial Infections 20.1.1 Clinical • Infections due to Mycobacterium tuberculosis (MTB) remain a leading cause of morbidity and mortality in the world with 1.5 million deaths per year reported. • Common person-to-person spread is by droplet inhalation: –– One (1) active MTB organism can infect 10–15 people. • Relatively rapid progression and more severe symptoms. • Poor cell-mediated immunity, such as in HIV, is the strongest risk factor. • Primary tuberculosis (TB) depends on host immunity: –– Intact cell-mediated immunity: Initial infection gets localized in the form of necrotizing granuloma formation. –– Tuberculoma – lung mass with central necrosis. –– Ghon focus: Healing granuloma undergoes dense or central calcification. –– Ranke complex: Corresponding lymph nodes also calcify (Ranke = Ghon + calcified nodes). –– Progressive primary infection: Poor cell-mediated immunity, such as HIV • Post-primary tuberculosis: –– Reactivation of previous dormant/latent infection or reinfection © Springer Nature Switzerland AG 2020 C. Farver et al., Pulmonary Disease, https://doi.org/10.1007/978-3-030-47598-7_20
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a
b
Fig. 20.1 (a) Endobronchial image of a pseudomembrane (arrow: fibrinous exudate) in the distal left main bronchus. (b) These can collapse causing airway occlusion and airway casts (arrow)
• Miliary tuberculosis: –– Innumerable granulomatous nodules (1–3 mm) throughout the lungs and throughout the body –– Usually present in primary progressive tuberculosis or in post-primary tuberculosis where disease spreads hematogenously throughout the body
20.1.2 Bronchoscopy • Endobronchial forceps biopsies of evident lesions can be done, but most diagnoses are made from bronchial washing or bronchoalveolar lavage (BAL) when sputum is negative. • Lesions can be ulcerative airway mucosa and necrosis (Fig. 20.1a). –– Often biopsy the crust and the edge of the ulcer to obtain the active process for microbiological cultures. –– These lesions collapse causing airway occlusion and airway casts (Fig. 20.1b). –– Inflammation and ulceration when healed may lead to airway strictures. –– TB-related airway strictures are the most common form of airway strictures around the world. Can be associated with other inhalational exposures and produce airway lesions known as anthracofibrosis (Fig. 20.2)
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Fig. 20.2 Endobronchial image of patient with a history of treated TB. This entity is known as anthracofibrosis. Worldwide it may be associated with TB and inhalational exposures
Fig. 20.3 Primary TB manifesting as left upper lobe consolidation in a young adult
20.1.3 Imaging 20.1.3.1 Primary Tuberculosis • Initial focus in the lungs may be too small to be recognized or develop patchy or lobar consolidation – predominantly seen in adults (Fig. 20.3). • Unilateral hilar or mediastinal lymphadenopathy is the hallmark of primary TB. (Fig. 20.4a, b). • Lymph nodes with involvement by TB have a characteristic sign of low-density centers within the node with peripheral contrast enhancement.
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a
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Fig. 20.4 Primary TB in a 23-year-old male with unilateral lymphadenopathy. (a) R paratracheal, (b) subcarinal and hilar lymphadenopathy
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Fig. 20.5 Re-infection post-primary TB. (a) Lingular consolidation with multiple centrilobular nodules (tree-in-bud) and cavitations in the left upper lobe and (b) left lower lobe
• Pleural effusions: –– More common in adults 20.1.3.2 Post-Primary Tuberculosis • Distribution of disease is apical, posterior segments of upper lobes; superior segment lower lobes. • Consolidation with cavity formation is seen. • The cavity typically is thick walled (without treatment). • Nodules with a centrilobular distribution and tree-in-bud opacities (sign of endobronchial spread) (Fig. 20.5a, b). • Interlobular septal thickening and linear opacities. • Lymphadenopathy is rare in post-primary tuberculosis.
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Fig. 20.6 A 48-year-old male with AIDS. Innumerable 1–3 mm nodules disseminated throughout both lungs consistent with miliary TB
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Fig. 20.7 Imaging of complications of TB. (a) Chronic empyema with pleural thickening, calcifications, and fibrothorax. (b) Broncholithiasis with calcified left hilar lymph nodes eroding into the LUL bronchus
20.1.3.3 Miliary Tuberculosis • Hematogenous spread of TB in the lungs that can occur as a feature of primary or post-primary TB with diffuse 1–5 mm nodules throughout both lungs (Fig. 20.6) 20.1.3.4 Complications of Pulmonary Tuberculosis (Fig. 20.7a, b) • Lung parenchymal architectural distortion with fibrosis and cyst/cavity formation • +/−secondary mycetoma may be seen. • Bronchiectasis with or without tracheobronchial stenosis and broncholith formation (calcified node eroding bronchus). • Chronic pleural effusions, thickening, and calcifications (fibrothorax) with empyema can be seen.
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• Constrictive pericarditis with or without pericardial calcifications can occur. • Rasmussen aneurysm is the presence of a tuberculosis cavity that erodes into a pulmonary artery branch (can be fatal).
20.1.4 Pathology 20.1.4.1 Surgical Pathology • Circumscribed nodule is seen consisting of a mass or masses composed of a granuloma (epithelioid macrophages with/without Langerhans giant cells) surrounded by lymphocytes (Fig. 20.8a, b). • The granulomas are necrotizing or non-necrotizing; necrosis in tuberculosis is usually “dirty,” with abundant neutrophilic debris, giving it a basophilic appearance (Fig. 20.8). • Granulomas usually are located in or around the bronchioles and may be multiple, especially in miliary tuberculosis (Fig. 20.9a, b). a
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Fig. 20.8 (a) Area of necrotizing granulomas in lung with TB (arrows). (b) Prominent basophilic necrosis is present (arrow) as well as a smaller non-necrotizing granuloma (arrowhead)
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Fig. 20.9 Miliary tuberculosis with (a) multiple necrotizing granulomas and (b) focal area of basophilic central necrosis (arrow)
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20.1.5 Cytopathology • Findings on cytologic specimens are similar in tuberculous and non-tuberculous specimens. • Loosely cohesive aggregates of epithelioid histiocytes and chronic inflammatory cells are seen (Fig. 20.10). • The background may or may not show necrosis (Fig. 20.11a, b). • Diagnosis rests with identification of acid-fast organisms. • Microorganism stains may be performed on cell blocks or direct smears (Fig. 20.12a, b). –– When abundant, acid-fast bacilli may appear as negative images in Romanowsky-type stains. Fig. 20.10 Aggregates of epithelioid histiocytes in a background of necrosis and acute and chronic inflammation; modified Romanowsky stain, intermediate magnification
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Fig. 20.11 (a) Necrosis and acute and chronic inflammation; modified Romanowsky stain, high magnification. (b) Loosely formed granuloma; modified Romanowsky stain; high magnification
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Fig. 20.12 (a) Acid-fast organism on cytology smear (Ziehl-Neelsen stain; high magnification). (b) In FNA sample, scattered tubercular acid-fast bacilli staining pink-red with focal beaded appearance
20.2 Non-tuberculous Mycobacterial Infections 20.2.1 Clinical • Unlike TB, it is extremely rare to have person-to-person spread of non-tuberculous mycobacteria (NTM). • Main patterns of involvement of the lungs in immunocompetent patients include: –– Fibrocavitary form – infection in middle-aged, elderly males who are heavy smokers or alcoholics –– Nodular bronchiectasis – infection in elderly females with no prior structural lung disease –– Hypersensitivity pneumonitis/hot tub lung – granulomatous hypersensitivity reaction (rather than true infection) to aerosolized NTM in healthy users of hot tubs • These infections are more protracted and have an indolent course with less severe symptomatology. • Lymphadenopathy is not a common feature. • Extrapulmonary manifestations are uncommon or absent.
20.2.2 Imaging • Fibrocavitary form – key imaging features on CT: –– Thin, smooth-walled cavity formation in the upper lobes (less commonly associated with consolidations), with fibrosis and associated pleural reaction or thickening (pleural effusions are rare) (Fig. 20.13a, b)
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Fig. 20.13 NTM in a 56-year-old smoker with emphysema. (a) Note thin-walled cavity, architectural distortion, and pleural thickening in the right upper lobe and (b) a nodule in the left lung
Fig. 20.14 NTM infection in a 66-year-old female with bronchiectasis and peribronchial consolidations in the middle lobe and lingula as well as scattered, bilateral tiny centrilobular nodules (Lady Windermere syndrome)
• Nodular bronchiectatic form – key imaging features on CT: –– Cylindrical bronchiectasis and scattered small nodules (20 nuclei/cell
Fig. 21.4 Parainfluenza. Thoracoscopic biopsy. Interstitial pneumonitis with scattered multinucleated giant cells (arrow)
Fig. 21.5 Measles. Bronchoscopic biopsy. Multinucleated giant cells floating in alveolar space
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21.5 DNA Viruses 21.5.1 Clinical • DNA viruses: Adenoviridae –– Adenovirus. Upper respiratory symptoms Conjunctivitis –– –– –– –– ––
Herpes simplex virus (HSV) Varicella-zoster virus Cytomegalovirus Epstein-Barr virus (EBV) Human papillomavirus (HPV)
• These viruses are found predominantly in immunocompromised setting. –– –– –– ––
Adenovirus HSV CMV EBV Patients s/p transplantation
–– HPV
21.5.2 Imaging • Adenovirus (Fig. 21.6a, b) –– Airway-based inflammation that may produce mosaic attenuation from air- trapping and bronchial wall thickening. –– Small airway-based nodules may occur. a
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Fig. 21.6 Adenovirus. Chest CT. (a) Mosaic lung attenuation from air-trapping and bronchial wall thickening (arrows). (b) Small branching lung nodules can be seen (arrows)
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Fig. 21.7 CMV. Chest CT. (a) Diffuse ground-glass opacities with smooth interlobular septal thickening. (b) Bilateral small lung nodules (arrows) Fig. 21.8 EBV. Chest CT. EBV infection with pleural-based consolidation and small nodules (arrows) in the left lower lobe
• CMV (Fig. 21.7a, b) –– Diffuse ground-glass opacities are commonly seen. –– Nodules may occur. • EBV (Fig. 21.8) –– Consolidation and/or nodules are common.
21.5.3 Bronchoscopy • CMV (Fig. 21.9) –– Endobronchial manifestations of CMV are nonspecific and can be simple tracheitis with many systemic manifestations of pneumonitis, colitis, etc. –– There have been cases of severe obstructing lesions related to severe mucosa necrosis or more subtle white plaques.
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Fig. 21.9 CMV. Endobronchoscopic image. Subtle white plaques on medial wall below anastomotic line in lung transplant patient
Fig. 21.10 HPV papilloma. Endobronchoscopic image. Image demonstrates clusters of polypoid lesions in the trachea
–– Endobronchial biopsies may reveal viral inclusions and BAL may also have virus isolated independent of any endobronchial disease. • HPV (Fig. 21.10) –– May cause polypoid lesions in the trachea. Transformation into squamous cell cancer may occur. Endobronchial biopsy specimens can be tested for histologic assessment and for HPV virus.
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21.5.4 Pathology 21.5.4.1 Surgical Pathology • Adenovirus (Fig. 21.11a, b) –– Bronchocentric necrotizing pneumonia: Early inclusions are amphophilic structures with peripheral chromatin. Mature inclusions have more basophilic nuclei, “smudge cell” morphology. Airspaces are congested and filled with exudative debris. • CMV (Fig. 21.12a–e) –– Interstitial pneumonitis is common. –– Focal areas of necrotizing pneumonia can be seen. –– Inclusions usually have a single nuclear inclusion with multiple basophilic cytoplasmic inclusions that stain for Gomori methenamine silver stains. • Herpes Simplex Virus (Fig. 21.13a–d) –– Necrotizing tracheobronchitis with inclusions present at margins. –– Necrotizing pneumonia has hemorrhagic necrosis and karyorrhectic debris. –– Multinucleation and nuclear molding ground-glass nuclear chromatin and ballooning degeneration of the cytoplasm. • Varicella Virus (Fig. 21.14a, b) –– Hemorrhagic foci with necrosis in a military pattern. –– Multinucleated syncytial cells may be seen at the edges of the lesions.
21.5.5 Cytopathology • Herpes Simplex Virus (Fig. 21.13d) –– Enlarged epithelial cells with multinucleation, open glassy chromatin, and nuclear molding. a
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Fig. 21.11 Adenovirus pneumonia. Postmortem lung. (a) Necrotizing pneumonia with early inclusions (arrow) surrounding by necrotizing pneumonia. (b) Basophilic inclusion (arrows) or so-called smudge cells represent more mature inclusions
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Fig. 21.12 CMV pneumonia. Bronchoscopic biopsy. (a) Nuclear (arrowhead) and cytoplasmic (arrow) inclusions are present in this large, CMV-infected macrophage. (b) Immunohistochemical study stains early nuclear antigens (brown stain). (c) Chromogenic in situ hybridization for CMV viral RNA highlights multiple CMV-infected cells. (d) Bronchoalveolar lavage specimen with large, CMV-infected cells with prominent nuclear inclusion. (e) Gomori methenamine silver stain highlights cytoplasmic inclusions (arrow) in CMV-infected cell
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Fig. 21.13 Herpes simplex viral pneumonia. Postmortem lung. (a) Necrotizing tracheobronchitis with multinucleated herpetic inclusions throughout the ulcer. (b) Herpes pneumonia in elderly patient with severe chronic obstructive lung disease. (c) Enlarged epithelial cells with multinucleation. (d) Herpetic inclusion from cytologic preparation with open glassy chromatin and nuclear mold and an enlarged squamous epithelial cell for size comparison; (Bronchoalveolar lavage cytocentrifuge preparation; Papanicolaou stain)
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Fig. 21.14 Varicella viral pneumonia. (a) Foci of hemorrhagic necrosis with some early acute lung injury in periphery. (b) Edge of hemorrhagic focus reveals multiple viral-infected syncytial cells in alveolar spaces
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21.5.5.1 Ancillary Studies • Direct detection in blood and/or respiratory secretions is most common way to detect most respiratory viral antigens. • Polymerase chain reaction (PCR) assays are widely used for secretions (bronchoalveolar lavage). • Tissue detection includes: –– Histochemical studies including Gomori methenamine silver (GMS) stains can detect intracytoplasmic includes of CMV (Fig. 21.12e). –– Immunohistochemical testing available that improves diagnostic yield in tissue (Fig. 21.12b). –– In situ hybridization. CMV (Fig. 21.12c)
Suggested Readings Cavallazzi R, Ramierez JA. Influenza and viral pneumonia. Clin Chest Med. 2018;39:703–21. Cunha BA. Cytomegalovirus pneumonia: community-acquired pneumonia in immunocompetent hosts. Infect Dis Clin N Am. 2010;24:147–58. Fortes HR, von Ranke FM, Escuissato DL, Araujo Neto CA, Zanetti G, Hochhegger B, Marchiori E. Recurrent respiratory papillomatosis: a state-of-the-art review. Respir Med. 2017;126:116–21. Keshishyan S, DeLorenzo L, Hammoud K, Avagyan A, Assallum JH, Harris K. Infections causing central airway obstruction: role of bronchoscopy in diagnosis and management. J Thorac Dis. 2017;9:1707–24. Murdoch DR. How recent advances in molecular tests could impact the diagnosis of pneumonia. Exp Rev Mole Diagn. 2016;16:533–40. Pritt BS, Aubry MC. Histopathology of viral infections of the lung. Semin Diagn Pathol. 2017;34:510–7.
Chapter 22
Common Fungal Infections
This chapter reviews six of the eight most common lung fungal infections seen in North America (Table 22.1).
22.1 Aspergillosis 22.1.1 Clinical • Saprophytic aspergillosis (aspergilloma) –– Aspergilloma – hyphae mixed with mucous and debris colonizing a preexisting cavity –– Most commonly due to scarring from former tuberculosis infection or sarcoidosis with no tissue invasion –– Can lead to hemoptysis • Allergic bronchopulmonary aspergillosis –– Hypersensitivity reaction to Aspergillus in asthmatics resulting in mucous plugging of dilated bronchi with fungal hyphae and eosinophils Table 22.1 Most common fungal infections in North America Endemic Histoplasmosis – Ohio and Mississippi valleys Coccidioidomycosis – Southwestern USA and Mexico Blastomycosis – endemic to North America
Opportunistic Aspergillosis Cryptococcosis Candidiasis Mucormycosis Pneumocystis pneumonia
© Springer Nature Switzerland AG 2020 C. Farver et al., Pulmonary Disease, https://doi.org/10.1007/978-3-030-47598-7_22
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• Semi-invasive (chronic necrotizing) aspergillosis –– Chronic steroid therapy, diabetics, alcoholics, debilitated and COPD patients • Airway invasive aspergillosis (acute tracheobronchitis, bronchitis, bronchopneumonia) –– Found in neutropenia, AIDS, and post lung transplant patients • Angio-invasive aspergillosis –– Severe neutropenic and post-transplant patients on immunosuppression
22.1.2 Imaging • Aspergilloma (Fig. 22.1a, b) –– Rounded mass within a cavity (typically upper lobes) with crescent of air separating dependent mass from the nondependent cavity walls Mass typically mobile with change in patient position • Allergic bronchopulmonary aspergillosis (Fig. 22.2a, b) –– Tubular, “finger-in-glove” opacities in a bronchial distribution on radiographs. –– Bronchiectasis (usually upper lobes, segmental or subsegmental) with mucoid impaction on CT. –– Endobronchial material may show increased attenuation or calcification in approximately 30% of cases. • Semi-invasive aspergillosis (Fig. 22.3a, b) –– Consolidations +/− cavitation, or a nodular opacity, which develops over months to years • Airway invasive aspergillosis (Fig. 22.4a–c)
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Fig. 22.1 Aspergillosis. RUL Aspergilloma in two different patients. (a) CT chest scan. Rounded mass in the dependent portion of a thin-walled cavity with crescent of air surrounding the mass. (b) Fungal ball almost fills the cavity with only a thin rim of air
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Fig. 22.2 Aspergillosis. ABPA in patient with history of asthma and eosinophilia and (a) Contrast- enhanced CT chest sagittal reformatted images in lung and (b) Mediastinal window settings. Both images reveal tubular, branching opacities with soft tissue attenuation, in a bronchial distribution in the LLL superior segment (“finger-in-glove”), suggestive of bronchiectasis with mucoid impaction. Note that the dilated bronchi, unlike the adjacent vessels, show no enhancement
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Fig. 22.3 Aspergillosis. (a) Semi-invasive aspergillosis associated with severe bullous emphysema (CXR) and (b) CT chest scan shows ill-defined left apical lung nodule (arrows), which developed over months, simulating malignancy
–– Centrilobular nodules and tree-in-bud opacities (bronchiolitis), bronchial wall thickening (bronchitis), and peribronchial consolidation (bronchopneumonia) • Angio-invasive aspergillosis (Figs. 22.5a, b and 22.6a, b) –– Nodules with surrounding ground glass (due to surrounding hemorrhage) in neutropenic patients with fever are considered highly suggestive. Differential diagnosis for this is mucormycosis and candida.
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Fig. 22.4 Aspergillosis. Airway invasive aspergillosis in AIDS. (a-c) CT chest shows upper lobe predominant multiple centrilobular nodules with ground-glass opacities and bronchial wall thickening in both lungs
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Fig. 22.5 Aspergillosis. Angio-invasive aspergillosis. AML with severe neutropenia; (a) initial CT chest shows a peripheral RUL mass with mild surrounding ground-glass halo. (b) CT chest obtained 2 weeks later shows development of a crescent of air within mass
–– Pleural-based, wedge-shaped consolidation (hemorrhagic infarcts). –– Over 2–3 weeks, with recovery from neutropenia, an air crescent may develop (due to sloughing off of necrotic lung or “pulmonary sequestra” from adjacent healthy lung parenchyma).
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Fig. 22.6 Aspergillosis. Angio-invasive aspergillosis. Unilateral left lung transplant on chronic immunosuppressant. (a) CT chest. Severe emphysema in the native right lung. Note 5 mm solid nodule in the LLL (arrow). (b) CT chest scan 4 days later shows ground-glass halo around the nodule (arrow) Fig. 22.7 Aspergillosis. Bronchoscopic image. Endobronchial aspergillosis. Note black lesion (arrow)
22.1.3 Bronchoscopy • Wide range of endobronchial appearance of fungal disease related to the specific organism, host factors, and location. • Appearance ranges from topical plaques (Fig. 22.7) and aspergilloma (Fig. 22.8) to fully invasive and necrosis of invasive aspergillus. • Washing and endobronchial biopsy for pathology and tissue cultures are helpful in making a diagnosis.
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Fig. 22.8 Aspergillosis. Bronchoscopic image. Endobronchial aspergillosis. Endobronchial image of aspergilloma with black necrotic mass outside of the airway (arrow)
Fig. 22.9 Aspergilloma. Wedge resection. Fungal hyphae with acute angle branching and septated hyphae consistent with Aspergillus (Gomori methenamine silver stain)
22.1.4 Pathology 22.1.4.1 Surgical Pathology • Fungal hyphae with acute angle branching and septa (Fig. 22.9). • Aspergillus fumigatus is the most common fungus found in lung disease. • Aspergillus niger has a characteristic black pigment in tissue, which contains oxalate crystals that are visible upon polarization (Fig. 22.10a, b). • Aspergilloma: Fungal hyphae present with fibrotic cavity without tissue invasion (Fig. 22.11). • Chronic pulmonary aspergilloma: Fungal hyphae with superficial invasion into airway (Figs. 22.12a, b and 22.13a, b). • Invasive aspergillosis: Invasion of fungal hyphae into vessels with ischemic infarction (Fig. 22.14a, b).
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Fig. 22.10 Aspergilloma. Postmortem specimen. (a) Aspergillus niger fungal hyphae invading airways with brown/black pigment on hematoxylin and eosin section. (b) Oxalate crystals, produced by fungus, are commonly seen with polarized light Fig. 22.11 Aspergilloma. Wedge resection specimen. Aspergilloma with fungal hyphae present within a dilated airway
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Fig. 22.12 Chronic pulmonary aspergillosis. Wedge resection specimen. (a) Bronchial wall with superficial ulceration of airway. (b) Granulomatous inflammation is present on surface of airway
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Fig. 22.13 Chronic pulmonary aspergillosis. Biopsy specimen. (a) Bronchial wall with ulceration and fungal hyphae consistent with chronic pulmonary aspergillosis. Arrow denotes areas of ulceration and fungal invasion. (b) GMS stain highlights depth of invasion in airway (arrow)
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Fig. 22.14 Invasive aspergillosis. Postmortem specimen. (a) Invasive aspergillosis and pulmonary artery surrounded by ischemic infarction. (b) GMS stain highlights presence of fungal hyphae invading into the vessel wall
22.1.4.2 Cytopathology • Slender uniform septate hyphae with acute angle branching (Fig. 22.15). • Slide backgrounds vary from clear (in airway-derived samples) to necrotic/granulomatous (in aspirations of mass lesions). • Accompanying inflammation may include eosinophils. 22.1.4.3 Pathological Differential Diagnosis • Other fungal hyphae forms including Mucor 22.1.4.4 Ancillary Studies • Gomori methenamine silver (GMS) histochemical stain is needed to see all fungal hyphae.
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Fig. 22.15 Aspergillosis. Cytopathology (Papanicolaou, BAL ThinPrep). Uniform septate hyphae with acute angle branching
• Periodic acid-Schiff (PAS) may also be used. –– Mucor may be better visualized with this stain as it is weakly GMS positive.
22.2 Histoplasmosis 22.2.1 Clinical • Infection caused by Histoplasma capsulatum. –– Noncontagious. –– Most common endemic fungal infection in the USA. –– Most common in the Ohio and Mississippi river valleys. • Pathogenesis and imaging features mirror pulmonary tuberculosis and are broadly grouped into three stages: –– Primary histoplasmosis or acute pulmonary histoplasmosis Initial exposure to inhaled fungal forms may be completely asymptomatic or lead to flu-like illness. –– Chronic pulmonary histoplasmosis Usually seen in COPD patients or underlying structural lung disease –– Progressive disseminated histoplasmosis Hematogenous spread into multiple organs. Most common in immunocompromised patients. • AIDS • Immunosuppression drugs, i.e., steroids, chemotherapy
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–– Fibrosing mediastinitis Chronic complication of histoplasmosis
22.2.2 Imaging • Primary histoplasmosis or acute pulmonary histoplasmosis (Figs. 22.16a, b and 22.17) –– Unilateral consolidation or nodule(s) and hilar or mediastinal lymphadenopathy (if symptomatic) –– Granuloma formation with central “target” calcification (if asymptomatic or with signs of healing) a
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Fig. 22.16 Histoplasmosis. CT chest scan. (a) Acute histoplasma infection demonstrates a peripheral 12 mm RUL lung nodule with adjacent 5 mm satellite nodule (arrow). (b) Right hilar lymphadenopathy (arrow)
Fig. 22.17 Sequelae of remote Histoplasma infection. CT chest scan. RUL calcified granuloma (arrow head) and calcified right paratracheal node (arrow)
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• Chronic pulmonary histoplasmosis (Fig. 22.18) –– Upper lobe fibro-cavitary disease (resembles post-primary or reactivation TB). –– Bronchopneumonia pattern with nodules/consolidations, lymphadenopathy, +/− broncholithiasis. • Progressive disseminated histoplasmosis (Fig. 22.19a, b) –– Miliary pattern with 1–3 mm nodules disseminated throughout all lung lobes –– Consolidation, +/− cavitation, +/− lymphadenopathy –– Hepatosplenomegaly • Fibrosing mediastinitis (Fig. 22.20a–c) –– Hilar or mediastinal mass or infiltrating mediastinal soft tissues with calcification –– Narrowing or obstruction of bronchi, pulmonary artery, or superior vena cava Fig. 22.18 Chronic histoplasmosis. CT chest scan. LUL cavitary 7 mm lung nodule. Note signs of bronchogenic spread in the RUL
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Fig. 22.19 Progressive disseminated histoplasmosis. CT chest scan. (a) Diffuse histoplasma infection with multiple, bilateral 2–4 mm discrete lung nodules. (b) Miliary histoplasmosis with innumerable micro nodules disseminated throughout both lungs
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Fig. 22.20 Fibrosing mediastinitis. (a) CT chest lung window image shows volume loss of the right lung with marked narrowing of the right main and RUL bronchus (arrow). (b) Mediastinal window images demonstrate right hilar soft tissues with calcifications causing obstruction of the right pulmonary artery and right bronchus (arrow). (c) Note right hilar soft tissues with calcifications (arrowhead), and tortuous left pulmonary artery branches (arrow)
22.2.3 Bronchoscopy • Washing and endobronchial biopsy for pathology and tissue cultures are helpful in making a diagnosis. • Post-infectious states related to histoplasmosis are most common endobronchial manifestation. –– Broncholithiasis (Fig. 22.21) –– Fibrosing mediastinitis (Fig. 22.22)
22.2.4 Pathology 22.2.4.1 Surgical Pathology • Airway-based necrotizing and non-necrotizing granulomas (Fig. 22.23a, b). • Histoplasma capsulatum is most common organism (Fig. 22.24).
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Fig. 22.21 Histo plasmosis. Bronchoscopic image. Broncholith protruding into main bronchus in patient with calcified lymph nodes secondary to histoplasma infection
Fig. 22.22 Bronchoscopic image. Fibrosing mediastinitis related to histoplasmosis with severe hypervascularity of bronchial wall related to occluded pulmonary veins resulting in back pressure
• Inactive infection characterized by hyalinized fibrosis of granuloma that may calcify. • Disseminated histoplasmosis can have abundant organisms in histiocytes in tissue and in cytopathology preparations (Fig. 22.25a, b). 22.2.4.2 Cytopathology • Granulomas are seen in fine needle aspirations of lymph nodes and/or lung nodules. • Macrophages with numerous intracellular yeast forms are seen in disseminated disease (Fig. 22.25a, b).
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Fig. 22.23 Histoplasma granulomas. Lung, wedge excision. (a) Airway-based necrotizing granuloma with histiocytic border and central eosinophilic necrosis. (b) Histoplasma yeast forms seen in center of necrosis; arrow points to budding yeast form Fig. 22.24 Disseminated histoplasmosis. Bronchoscopic biopsy. Organizing pneumonia with foamy histiocytes with intracellular organisms (dot-like), apparent on hematoxylin and eosin stain
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Fig. 22.25 Lung nodule. Bronchoalveolar lavage, ThinPrep. (a) Papanicolaou stain of macrophages with numerous 1 to 2 micron intracellular yeast forms. (b) GMS stain of macrophages with numerous intracellular yeast forms, cell walls staining black on silver stain preparation
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22.2.4.3 Pathological Differential Diagnosis • Other granulomatous fungal infections –– –– –– ––
Cryptococcus Blastomyces Candida Pneumocystis
• Granulomas from mycobacterial infections 22.2.4.4 Ancillary Studies • Histochemical studies for fungal forms –– Silver stains (GMS) –– Periodic acid-Shiff (PAS)
22.3 Pneumocystis Pneumonia 22.3.1 Clinical • Pneumocystis jirovecii is an organism in human infections. • Opportunistic infection. –– AIDS patients: (CD4+ solitary), mass, or consolidation – peripheral/subpleural Fig. 22.31 Cryptococcal pneumonia in HIV+ patient. CT chest image reveals multiple small lung nodules (arrows) suggestive of cryptococcosis
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Fig. 22.32 Bronchoscopic image. Mucoid lesion in main bronchus in patient with cryptococcosis
22.4.3 Bronchoscopy • Endobronchial cryptococcus can reveal mucoid-type lesion (Fig. 22.32). • Washing and endobronchial biopsy for pathology and tissue cultures are helpful in making a diagnosis.
22.4.4 Pathology 22.4.4.1 Surgical Pathology • Organizing pneumonia with granulomas is the most common form in immunocompetent patient (Fig. 22.33). • Immunocompromised patients may have abundant yeast forms infiltrating alveolar and adjacent interstitial tissue (Fig. 22.34). 22.4.4.2 Cytopathology • Variable intermediate-sized extracellular yeast forms with narrow budding, often showing encapsulation, surrounded by acute inflammatory cells (Fig. 22.35)
22.4 Cryptococcus Fig. 22.33 Cryptococcal pneumonia in patient on chronic steroid use. Wedge excision. Organizing pneumonia with scattered loosely formed granulomas and giant cells
Fig. 22.34 Cryptococcal pneumonia in immunocompromised patient. Bronchoscopic biopsy. Yeast forms present throughout tissue seen on GMS stain
Fig. 22.35 Cryptococcal nodule. Fine needle aspiration (FNA), ThinPrep. Papanicolaou stain of variable intermediate-sized extracellular yeast forms with narrow budding, often showing encapsulation, surrounded by acute inflammatory cells
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22.4.4.3 Pathological Differential Diagnosis • Other fungal yeast forms –– –– –– ––
Histoplasma Cryptococcus Coccidioides Candida
22.4.4.4 Ancillary Studies • Silver stains (GMS) to highlight organisms (Fig. 22.34). • Mucin stains highlight mucin capsule (Fig. 22.36). • Melanin stain highlights the cell wall.
22.5 Blastomycosis 22.5.1 Clinical • • • •
Blastomyces dermatitidis is an organism that causes lung disease. Endemic to N. America. Acute and chronic presentation. Clinical presentation of blastomycosis is highly variable. –– “The great masquerader” –– Can mimic pyogenic bacterial pneumonia, other fungal infections, tuberculosis, or bronchogenic carcinoma
Fig. 22.36 Cryptococcal nodule. Wedge excision. Yeast forms staining a faint pink positive in this mucicarmine stain, highlighting mucoid capsule
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• Pulmonary manifestations are the most common presenting features. • Isolated lung involvement is seen in 70–75% of cases. • Disseminated disease is seen in 25–30%.
22.5.2 Imaging • Mass-like consolidation with or without cavitation; nodule(s) (Figs. 22.37 and 22.38). • Thoracic lymphadenopathy and pleural effusions are uncommon (unlike other granulomatous infections). • Disseminated blastomycosis can have miliary picture (Fig. 22.39). Fig. 22.37 Blastomycosis simulating primary TB with LUL mass-like consolidation
Fig. 22.38 Blastomycosis simulating re-activation TB with a large thick-walled LUL cavity
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Fig. 22.39 Blastomycosis with mass-like LUL consolidation and innumerable, bilateral, 2–4 mm centrilobular lung nodules suggestive of bronchogenic spread
22.5.3 Bronchoscopy • Blastomycosis is a fungal infection that can present as endobronchial disease. • Washing and endobronchial biopsy for pathology and tissue cultures are helpful in making a diagnosis.
22.5.4 Pathology 22.5.4.1 Surgical Pathology • Granulomatous nodules with necrosis with neutrophilic infiltrate (Fig. 22.40a). • 10–20 micron yeast with broad-based budding (Fig. 22.40b). • Double contour wall is apparent on PAS stain (Fig. 22.40b). 22.5.4.2 Cytopathology • Granulomas and neutrophilic infiltrate with yeast forms • Large rounded extracellular yeast forms (size of nucleated cells) with discernible cell walls (Figs. 22.41a, b) 22.5.4.3 Pathological Differential Diagnosis • Cryptococcus • Coccidioides
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Fig. 22.40 Blastomycosis. (a) Blastomyces dermatitidis with double contour wall and internal structure, see on H and E and (b) PAS staining. (c) Broad-based budding highlighted by silver stain
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Fig. 22.41 Blastomyces. Bronchoalveolar lavage; Centrifuge. (a) Modified Giemsa stain highlights large yeast forms with discernible cell walls. (b) GMS silver stain highlights broad-based budding organism
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22.5.4.4 Ancillary Studies • Silver stains –– GMS stains yeast wall. • Periodic-acid Schiff (PAS) –– Highlights double contour wall
22.6 Coccidioidomycosis 22.6.1 Clinical • Acute coccidioidomycosis • Chronic coccidioidomycosis • Disseminated coccidioidomycosis
22.6.2 Imaging • Consolidation and/or nodules and/or septal thickening; lymphadenopathy, +/− pleural effusions (Fig. 22.42) • Fibrocavitary disease similar to other granulomatous disease (“grape skin” thin walled cavity) (Fig. 22.43a, b) • Miliary pattern of tiny nodules throughout both lungs
Fig. 22.42 Coccidioidomycosis. CT chest scan revealed a solitary, circumscribed 10 mm RUL lung nodule with soft tissue attenuation and no calcification (arrow). PET-CT demonstrated mild FDG uptake by the lung nodule and a small right hilar lymph node which was strongly FDG-avid. Tissue sampling of the lung nodule and hilar node confirmed the diagnosis
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Fig. 22.43 Coccidioidomycosis. (a) Thin-walled (“grape skin”) cavities in the RUL posterior segment with a solid nodule in LUL (arrow). (b) Thin-walled cavity or cyst in the apical segment RUL in same patient Fig. 22.44 Coccidio idomycosis. Wedge resection. Spherules with spores highlighted with GMS stain
22.6.3 Bronchoscopy • Washing and endobronchial biopsy for pathology and tissue cultures are helpful in making a diagnosis.
22.6.4 Pathology 22.6.4.1 Surgical Pathology • Spherules measure 40–90 microns and contain abundant endospores (Fig. 22.44). • Needle biopsy with necrotizing granulomatous inflammation with Coccidiodes endospores (Fig. 22.45a).
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Fig. 22.45 Coccidioidomycosis. (a) Needle biopsy of upper lobe nodule with granulomatous inflammation and areas of necrosis (arrow). (b) Endospores “sprouting” pseudohyphae highlighted on PAS stain
22.6.4.2 Cytopathology • Granulomas, giant cells, and neutrophils are present. • Spherules and endospores may be seen on fine needle biopsy and cytopathology aspiration (Fig. 22.45b). 22.6.4.3 Pathological Differential Diagnosis • • • •
Blastomyces Histoplasma Myospherulosis Rhinosporidium
22.6.4.4 Ancillary Studies • Silver stains –– GMS stains
Suggested Readings Haque AK. Fungal diseases. Chapter 12. In: Zander DS, Farver CF, eds. Pulmonary Pathology, a volume in the series Foundations in Diagnostic Pathology. J. Goldblum, ed., 2nd ed. New York: Elsevier; 2018. Huerre MR, Dannaoui E, Develoux M. Mycetoma: Eumycetoma and Actinomycetoma. Chapter 14. In: Procop GW, Pritt BS, eds. Pathology of Infectious Diseases, a volume in the series Foundations in Diagnostic Pathology. J. Goldblum, ed., New York: Elsevier; 2015. Khayyata S, Moore CB, Richardson MD, Hasleton P, Farver C. Pulmonary mycotic infections. Chapter 7. In: Hasleton P, Flieder DB, eds. Spencer’s pathology of the lung, vol. 2. New York: Cambridge University Press; 2013. Wojewoda C, Procop GW. Infections with yeast and yeastlike fungi. Chapter 26. In: Procop GW, Pritt BS, eds. Pathology of Infectious Diseases, a volume in the series Foundations in Diagnostic Pathology, J. Goldblum, ed., New York: Elsevier; 2015.
Chapter 23
Parasitic Infections
23.1 Strongyloidiasis 23.1.1 Clinical • Strongyloidiasis is the infection by Strongyloides stercoralis, a microscopic nematode endemic in the tropics but is found worldwide. • Infective filariform larvae invade the lungs and small intestine through the skin from the soil. • Humans are primary hosts. • Eosinophilic pneumonia with wheezing, dyspnea, hoarseness, and hemoptysis is a common pulmonary symptom. • Acute and chronic disease is usually not fatal. • Hyperinfection is sepsis from enteric flora resulting from continuous autoinfection in patients with AIDS, chronic steroids, and other scenarios of a compromised immune system. –– Can result in massive and life-threatening infestation. –– Larva can be present in stool and sputum. –– Has a mortality of 50–90%, depending upon the host.
23.1.2 Imaging • Eosinophilia – patchy fleeting airspace opacities, which usually resolve in 1–2 weeks (Fig. 23.1a, b). • Hyperinfection syndrome – pneumonia, alveolar hemorrhage, ARDS, or rarely miliary pattern (Fig. 23.2). • Superimposed bacterial infection may have cavitation and abscess formation, +/− pleural effusions. © Springer Nature Switzerland AG 2020 C. Farver et al., Pulmonary Disease, https://doi.org/10.1007/978-3-030-47598-7_23
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Fig. 23.1 Strongyloidiasis. Chest CT scan. Strongyloides presenting as migratory, subtle ground- glass opacities (arrows) in the (a) LUL, (b) RML and dependent portions of both lower lobes with only minimal reticulations
Fig. 23.2 Strongyloidiasis. Chest CT scan. Hyperinfection in a 70-year-old lung transplant recipient (unilateral left lung transplant and native right lung UIP). Note extensive bilateral consolidations and pleural effusions
23.1.3 Bronchoscopy • Diagnosis can be made by pleural fluid, bronchoalveolar lavage fluid (BALF), or lung biopsy. –– BALF is commonly bloody in the setting of hyperinfection. –– The organism, seen in this aspirate fluid, is 300–700 microns in length with nonbulbous esophagus and a notched tail (Fig. 23.3). –– Rarely, organisms are visualized during bronchoscopy, usually when hyperinfection is present.
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Fig. 23.3 Strongyloidiasis. Bronchoscopic aspiration fluid. Bloody fluid with filariform larva (300–700 microns in length). Nonbulbous esophagus is present at one end (arrow) and notched tail at the opposite end of organism
Fig. 23.4 Strongyloidiasis. Postmortem lung. Hyperinfection. Lung with acute diffuse alveolar damage and early hyaline membrane formation with filariform larva in alveolar space
23.1.4 Pathology 23.1.4.1 Surgical Pathology • Filariform larvae can be seen in the lung most commonly in the setting of diffuse alveolar damage; neutrophils and abscesses may occur (Fig. 23.4). 23.1.4.2 Cytopathology • Detection of larvae in the sputum and/or bronchoalveolar lavage (BAL) is most common diagnostic tool (Fig. 23.5).
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Fig. 23.5 Strongyloidiasis. Bronchoalveolar lavage fluid. Multiple filariform larvae present in BAL fluid
23.1.4.3 Pathological Differential Diagnosis • Larvae must be differentiated from other parasites including Ascaris. 23.1.4.4 Ancillary Studies • Serologic assays measuring parasite-specific IgG are commonly employed diagnostic tools. –– More sensitive than examination of BAL or stool
23.2 Dirofilariasis 23.2.1 Clinical • Dirofilaria immitis is a filarial nematode transmitted by mosquitoes from dogs to humans (accidental hosts). • Immature adult worm is transported via the peripheral veins into the right ventricle where it develops into an immature adult worm. • Immature adult worm travels into the pulmonary arteries and lung. • Infarction and granulomatous response to the dead worm develop. • Incidence of clinical disease in humans parallels animal disease. • Most patients are asymptomatic. • Less than 10% will develop cough, hemoptysis, chest pain, fever dyspnea, and mild eosinophilia. • Usually self-limiting and requires no treatment.
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Fig. 23.6 Dirofilariasis. Chest CT scan. Dirofilariasis presenting as a solitary, peripheral, RLL subcentimeter lung nodule (arrow)
23.2.2 Imaging • Solitary lung nodule (usually left lung. Lower lobes > upper lobes. Males > female incidence; increased incidence in rural areas.
• E. granulosus cysts much more common than E. multilocularis. • Nonspecific pulmonary symptoms: hemoptysis (hydatid vomica), chest pain, fever, and allergic reactions. • Complications include bronchial fistulization, secondary bacterial infections, anaphylactic shock, and secondary hydatid spread. –– Hydatid vomica: rupture of cyst into bronchus and expectoration cyst fluid and hydatic vesicles
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Fig. 23.9 Echinococcosis. Echinococcosis cysts in a 30-year-old man from the Middle East. Two simple, round or ovoid, cystic masses in the left lung with central fluid attenuation and thin enhancing walls. (a) Coronal reconstruction of CT chest. The LUL cyst measures 10 cm and the LLL cyst measures 9 cm in maximum diameter. (b) Contrast-enhanced Chest CT axial images (mediastinal window). Left upper lobe cyst and (c) left lower lobe cyst. Both with central fluid attenuation. Note mild surrounding atelectasis with no signs of cyst rupture
23.3.2 Imaging • Smooth, rounded cystic lesions, 1–20 cm, with central fluid attenuation and thin enhancing walls (Fig. 23.9a–c). • Unilateral or bilateral (20–50%), single (60%) or multiple, usually lower lobe predominant (60%). • Coexistent liver lesions (6%), signs of transdiaphragmatic spread may be present (pleural effusions or pleural cysts, basilar atelectasis or consolidations, right hemidiaphragmatic elevation). • Signs of cyst rupture or complications include the following: –– Meniscus or crescent sign: Cyst erodes into a bronchus with air between pericyst and ectocyst. –– Cumbo or onion peel sign: Meniscus sign + air-fluid level within endocyst (sign of cyst rupture).
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–– Water lily sign: Endocyst floats within a partially fluid-filled cyst (sign of cyst rupture). –– Mass within the cavity sign: Endocyst floats within a completely fluid- filled cyst.
23.3.3 Bronchoscopy • Aspiration of cyst is not recommended as there is some risk for anaphylactic shock. • Surgical excision is best for diagnosis/therapy.
23.3.4 Pathology 23.3.4.1 Surgical Pathology • Cyst wall has outer acellular laminated layer (Fig. 23.10a–c). • Germinal membrane on internal aspect of cyst wall may be present. a
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Fig. 23.10 Echinococcosis: Thoracoscopic biopsy. (a) Low power of granulomatous inflammation to eosinophilic material from echinococcal cyst rupture (arrows). (b) Eosinophilic material with marked giant cell reaction from lung with ruptured echinococcal cyst. (c) Laminated cyst walls from hydatid cyst; residual germinal membrane (arrow) is present
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Fig. 23.11 Echinococcosis: Cyst fluid cell block. (a) Sediment from a thoracic hydatid cyst fluid prepared as a cell block; (b) Single parasitic organism with hooklets lining scolex
Fig. 23.12 Echino coccosis: Cyst fluid ThinPrep-Papanicolaou stain. Hydatid cyst fluid showing a single parasite with globular body containing organelles and an area near scolex with numerous intact hooklets (left side of organism)
23.3.4.2 Cytopathology • Fine needle aspiration of cyst contents can reveal sediment from a thoracic hydatid cyst fluid and prepared as a cell block. –– Needle aspiration is not recommended (see above). –– Cyst contents (“hydatid sand”) include protoscolices, hooklets, and inflammatory debris (Fig. 23.11a). –– Parasitic organism with scolex and shark tooth-shaped hooklets (Fig 23.11b). –– Globular body with hooklets and organelles can be seen (Fig. 23.12).
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23.3.4.3 Pathological Differential Diagnosis • Gross differential diagnosis includes infectious cysts and cavitary carcinoma. • Cyst wall and contents are pathognomonic. • Aspiration with granulomatous response to food particles. 23.3.4.4 Ancillary Studies • Hooklets from parasite may be positive for acid-fast histochemical stains. • Indirect immunofluorescence assay is sensitive in hepatic disease but insensitive in lung disease. –– May be helpful in the setting of appropriate clinical findings, i.e., cysts in the lung. –– False-positive findings can occur in patients with malignancies.
23.4 Toxoplasmosis 23.4.1 Clinical • Disease caused by Toxoplasma gondii. –– Obligate intracellular protozoan • • • •
Infection is highly prevalent worldwide. Common human zoonosis (typically from cats), usually benign. Infection is via consumption of oocysts in feces of host (cats). Pulmonary involvement is rare except in the immunocompromised. –– Seventy percent of disease occurs in setting of immunocompromised hosts.
• Clinical symptoms include cough, dyspnea, and fever. • Disseminated disease is fatal in 90% of cases. • Oocytes contain the tachyzoites, which infect and circulate in the infected host (human).
23.4.2 Imaging • Key imaging features: –– Simulates pulmonary edema, lymphangitis, and atypical or pneumocystis pneumonia
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Fig. 23.13 Toxoplasmosis. (a) Brain MRI demonstrates multiple white matter mass lesions (arrows) in AIDS patient with CNS toxoplasmosis. (b) Frontal chest radiograph and (c) CT chest scan (lung window) show diffuse ground-glass opacities associated with interlobular septal thickening and pleural effusions
–– Interstitial (reticular or reticulo-nodular) opacities on chest radiography (Fig. 23.13a–c) –– Ground-glass opacities with smooth interlobular septal or peribronchovascular thickening • Pleural effusion and nodules may be present.
23.4.3 Bronchoscopy • No specific bronchoscopic appearance. • Cyst can be found in transbronchial biopsies and needle aspiration (see below).
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Fig. 23.14 Toxoplasmosis. Postmortem examination, lung. (a) Acute necrotizing pneumonia with areas of fibrinous exudates and scattered dark cells containing “pseudo-cysts.” (b) Bradyzoites are present in alveolar macrophage in lung with toxoplasmosis
23.4.4 Pathology 23.4.4.1 Surgical Pathology • Acute necrotizing pneumonia with fibrinous exudate and coagulative necrosis is seen in disseminated disease (Fig. 23.14a, b). • Bradyzoites, the progeny of dividing tachyzoites, are present in “pseudo-cysts,” found predominantly in phagocytes such as the alveolar macrophages. 23.4.4.2 Cytopathology • Tachyzoites can be seen in sputum or bronchoalveolar lavage (BAL). • Can be seen on hematoxylin and eosin, Giemsa, and eosin-methylene blue stains. 23.4.4.3 Pathological Differential Diagnosis • Other causes of pneumonia in an immunocompromised host including Pneumocystis pneumonia, Aspergillus, Nocardia, and other viruses such as cytomegalovirus and herpetic pneumonias. • Bradyzoites in alveolar macrophages may simulate other cytoplasmic inclusions, i.e., CMV. –– Immunohistochemical studies for toxoplasmosis and CMV are helpful.
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23.4.4.4 Ancillary Studies • PAS and Giemsa stains highlight true cysts; bradyzoites in pseudo-cysts are PAS-positive. • Serologic studies are useful in the diagnosis of acute infection. –– IgM for acute disease –– IgG for chronic disease • Immunohistochemistry is superior to H and E, especially in the setting of rare organisms. • PCR assays may be a more sensitive assay for detection, though not currently approved for clinical use.
Suggested Readings Campagna AC. Pulmonary toxoplasmosis. Semin Respir Infect. 1997;12:98–105. Khemasuwan D, Farver CF, Mehta AC. Parasites of the air passages. Chest. 2014;145:883–95. Krolewiecki A, Nutman TB. Strongyloidiasis: a neglected tropical disease. Infect Dis Clin N Am. 2019;33:135–51. Lewin-Smith Michael R., Neafie RC. Helminth infections, Chapter 27. In: Pathology of Infectious Diseases, Procop GW and Pritt BS, eds., a volume in the series Foundations in Diagnostic Pathology, JR Goldblum, ed. Elsevier, Philadelphia, 2015. Rodrigues-Silva R, Moura H, Dreyer G, Rey L. Human pulmonary dirofilariasis: a review. Rev Inst Med Trop Sao Paulo. 1995;37:523–30. Santivanez S, Garcia HH. Pulmonary cystic echinococcosis. Curr Opin Pulm Med. 2010;16:257–61. Skalski JH, Limper AH. Fungal, viral, and parasitic pneumonias associated with human immunodeficiency virus. Semin Respir Crit Care Med. 2016;37:257–66. Turgut AT, Altinok T, Topçu S, Koşar U. Local complications of hydatid disease involving thoracic cavity: imaging findings. Eur J Radiol. 2009;70:49–56. Woodring JH, Halfhill H 2nd, Reed JC. Pulmonary strongyloidiasis: clinical and imaging features. AJR Am J Roentgenol. 1994;162:537–42.
Chapter 24
Lung Involvement by Systemic Diseases
24.1 Amyloidosis 24.1.1 Clinical • Represents many diseases where non-branching linear fibrils are deposited in tissues throughout the body, either as local disease or systemic disease. • Types of fibrils are: –– –– –– ––
Serum protein A (SAA) Amyloid light chain (AL) Amyloid-associated transthyretin (AATR) Beta-microglobulin
• Lung amyloidosis has four clinical settings. –– Systemic Fibrils deposited include: • AL: light-chain producing plasma cell dyscrasias • AA: long-standing inflammation, such as connective tissue disease • ATTR –– Wild type and associated with old age –– Hereditary with transthyretin mutation –– Localized Rare Tracheobronchial amyloidosis • Wheezing and cough
© Springer Nature Switzerland AG 2020 C. Farver et al., Pulmonary Disease, https://doi.org/10.1007/978-3-030-47598-7_24
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Fig. 24.1 Amyloidosis. CT chest mediastinal window images (a) Smoothly marginated, 4 cm solid nodule with calcification in the RML; (b) 3 cm nodule with calcification in the LLL. (c) Right paratracheal and (d) right hilar lymphadenopathy associated with calcifications
Nodules • Pleuritic pain and hemoptysis can present when multiple nodules. –– Diffuse alveolar septal AL • Dyspnea and cough –– Pleural AL
24.1.2 Imaging • Nodular (Fig. 24.1a–d) –– Solitary or multiple lung nodules Mimic granulomatous infection or malignancy Usually lower lobe predominant and peripheral, subpleural
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Fig. 24.2 Amyloidosis. Patient with Sjogren’s syndrome and lymphocytic interstitial pneumonia. CT chest images. (a–c) Multiple thin-walled cysts and solid lung nodules in both lungs with lower lobe predominance. Several lung nodules are partly calcified
–– Variable shapes and sizes with smooth, lobulated, or spiculated margins –– Calcification frequent (50%), cavitation rare, and rarely associated with cysts (Sjogren’s syndrome) • Diffuse (Figs. 24.2a–c, and 24.3) –– 2–4 mm nodules associated with reticular opacities, interlobular septal thickening, and confluent consolidations with basal, peripheral predominance. –– May mimic lymphangitic spread of cancer. –– Punctate lung calcifications and pleural effusions or thickening can occur. –– Lung cysts may be associated with Sjogren’s syndrome in setting of amyloidosis with lymphocytic interstitial pneumonia-LIP. • Tracheobronchial (Fig. 24.4a–c) –– Long-segment tracheal narrowing with high attenuation of tracheal wall due to calcifications or ossification –– Unlike cartilage disorders, does not spare the posterior membranous portions
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Fig. 24.3 Amyloidosis. CT chest scan. A 60-year-old male with plasma cell dyscrasia and alveolar septal amyloidosis with bilateral, diffuse, smooth interlobular septal thickening
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b
c
Fig. 24.4 Amyloidosis. CT chest scan. (a, b) Lung windows reveal a smooth tracheal wall thickening extending into the proximal carinal bifurcation. (c) Mediastinal windows reveal calcifications of the tracheal cartilages (usually involves cartilaginous and posterior membranous walls)
24.1.3 Bronchoscopy • Endobronchial disease characterized by yellowish waxy lesions on the airways that are friable (Fig. 24.5a, b). • Endobronchial biopsy can easily obtain sufficient tissue for diagnosis. • Moderate hemorrhage can occur when manipulated. • Endobronchial therapy may include laser or other ablative therapies. • Low-dose radiation can produce sustained benefit.
24.1 Amyloidosis
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Fig. 24.5 Amyloidosis. Bronchoscopic image. (a, b) Yellow plaque-like lesions present on mucosal surface in patient with tracheobronchial amyloid (arrows)
24.1.4 Pathology 24.1.4.1 Surgical Pathology • Amorphous eosinophilic material presents as: –– –– –– –– –– –– ––
Nodules (Figs. 24.6a–c and 24.7a, b). Diffuse alveolar septal involvement (Fig. 24.8a, b). Tracheobronchial thickening (Fig. 24.9a, b). Congo red and crystal violet stains highlight amyloid (Figs. 24.8b and 24.9b). Giant cell reaction is common around edges (Fig. 24.6c). Plasma cell infiltrate can be seen. Osseous metaplasia and calcium are often present (Fig. 24.10).
24.1.4.2 Cytopathology • Amorphous flocculent material (Fig. 24.11) 24.1.4.3 Pathological Differential Diagnosis • Light chain deposition disease (LCDD) –– Congo red is negative in LCDD. • Hyalinizing pulmonary granuloma (HPG) –– Congo red negative in HPG –– History of infection and/or sclerosing mediastinitis • IgG4-related sclerosing disease –– Usually has prominent sclerosing phlebitis in the lung
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Fig. 24.6 Amyloidosis. Thoracoscopic biopsy. (a) Nodule with eosinophilic waxy material. (b) Islands of fibro-inflammatory tissue and histiocytic border within a background of eosinophilic material. (c) Giant cells are commonly seen along edges
–– Elevated IgG4 serum levels –– Negative for light chain and amyloid studies • Hyalinizing granuloma due to infection –– Negative for light chain and amyloid studies –– History of infection and/or sclerosing mediastinitis 24.1.4.4 Ancillary Studies • +: Congo red stain. • +: Crystal violet. • Antibody stains to AA, A-kappa, A-lambda, ATTR, and beta-microglobulin are available. • Mass spectroscopy can be used to diagnose type of fibril present.
24.2 Light Chain Deposition Disease
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Fig. 24.7 Amyloidosis. Transbronchial biopsy. (a) Bronchoscopic biopsy can reveal intra-alveolar amyloid material. (b) Crystal violet stain highlights amyloid
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Fig. 24.8 Amyloidosis. Transbronchial biopsy. (a) Amyloid, present in bronchoscopic biopsy, is highlighted by Congo red staining within alveolar septae and around vessels (arrows). (b) Apple- green birefringence of Congo red stain is seen under polarized light
24.2 Light Chain Deposition Disease 24.2.1 Clinical • Deposition of non-amyloid forms of immunoglobulin light chains in alveolar walls, small airways, and blood vessels • Associated with underlying B cell malignancies –– These dictate overall prognosis.
24.2.2 Imaging • Multiple thin-walled lung cysts (corresponds to small airway dilatation) +/− small lung nodules. (Figs. 24.12a, b and 24.13a, b). • Thoracic lymphadenopathy may be present.
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Fig. 24.9 Amyloidosis. Endobronchial biopsy. (a) Dense, eosinophilic amyloid material in subepithelial area of small airway. (b) Congo red highlights amyloid
Fig. 24.10 Amyloidosis. Thoracoscopic biopsy. Multiple foci of osseous metaplasia (arrows) are present throughout this focus of nodular amyloidosis. Calcium and bone were highlighted in imaging studies
Fig. 24.11 Amyloidosis. Fine needle aspiration. Papanicolaou stain. Homogenous flocculant material is seen on cytologic preparations, diagnostic of nodular amyloid
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Fig. 24.12 Light chain deposition disease. A 48-year-old male with history of monoclonal gammopathy. Chest CT scan. (a, b) Innumerable, thin-walled cysts in both lungs with lower lobe predominance suggestive of LCDD
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Fig. 24.13 Light chain deposition disease. A 62-year-old female with multiple myeloma. Chest CT scan, lung window images. (a) Small, thin-walled cysts (arrow) and (b) nodules (arrow), mostly in the lung bases, suggestive of LCDD
24.2.3 Pathology 24.2.3.1 Surgical Pathology • Bland, acellular deposits of eosinophilic material (Fig. 24.14a–e). –– Negative for amyloid stains • Chronic inflammatory infiltrate containing plasma cells is usually present.
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Fig. 24.14 Light chain deposition disease. Wedge excision. (a) Lung nodule with eosinophilic acellular material. (b) Chronic lymphocytic infiltrate is present in intervening areas. (c) Plasma cells are usually part of infiltrate. (d) Chromogenic in situ hybridization (CISH) reveals increased kappa light chains, compared to (e) CISH for lambda light chain, consistent with monotypic kappa light chain restriction
24.3 IgG4-Related Sclerosing Disease
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24.2.3.2 Pathological Differential Diagnosis • Nodular bland eosinophilic material due to: –– Amyloid: +Congo red –– Hyalinizing pulmonary granuloma (HPG). Negative for light chain and amyloid studies History of infection and/or sclerosing mediastinitis –– Hyalinizing granuloma due to infection Negative for light chain and amyloid studies History of infection or positive tissue organismal stains (GMS or AFB) –– IgG4-related sclerosing disease Usually has prominent sclerosing phlebitis Negative for light chain and amyloid studies 24.2.3.3 Ancillary Studies • In situ hybridization for light chain restriction (Fig. 24.14d, e)
24.3 IgG4-Related Sclerosing Disease 24.3.1 Clinical • Increased circulating levels of IgG4 • Sclerosing inflammation in a variety of organs; can affect any organ –– Pancreas is most common. –– Lung, pleura, and lymph nodes may be involved. Typically responds to corticosteroids
24.3.2 Imaging • Four patterns on imaging studies. –– Round-shaped ground-glass opacity (Fig. 24.15a, b) –– Solid nodular pattern or mass (Fig. 24.15b) –– Alveolar-interstitial type with honeycombing, bronchiectasis, and diffuse ground-glass opacities
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a
b
Fig. 24.15 IgG4-related sclerosing disease. Chest CT scan. (a) Multiple round solid nodules with associated GGO in the RLL (arrows). (b) Solid nodule in right lower lobe (arrow)
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b
Fig. 24.16 IgG4-related sclerosing disease. Wedge excision. (a) Fibroinflammatory nodule with mixed lymphohistiocytic infiltrate. (b) Movat pentachrome reveals vein with sclerosis (arrow), characteristic feature of this disease
–– Bronchovascular type with thickening of bronchovascular bundles and interlobular septae • Extrapulmonary: Mediastinal lymphadenopathy and/or pleural thickening may be seen.
24.3.3 Pathology 24.3.3.1 Surgical Pathology • Variable patterns of lung pathology include: –– Discrete fibro-inflammatory nodules (Fig. 24.16a, b) Intimal fibrosis of veins and arteries is a common finding.
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–– Infiltrates Lymphohistiocytic infiltrate • Increased IgG4/IgG ratio in plasma cells –– > 40% is highly suggestive of disease. 24.3.3.2 Pathological Differential Diagnosis • Marginal-zone lymphoma of bronchus-associated lymphoid tissue –– Clonality if B cells present • Inflammatory myofibroblastic tumor –– ALK+ • Nodular lymphoid hyperplasia –– No increase in circulating IgG4 serum levels 24.3.3.3 Ancillary Studies • Immunohistochemical studies for IgG4-positive plasma cells
24.4 Relapsing Polychondritis 24.4.1 Clinical • Systemic autoimmune disease with classic manifestations in the airway with loss of cartilaginous airway support in 20–50% of patients. • Focal or diffuse throughout the airways. • Skip lesions can be seen. • Airway obstruction can result in accumulation of secretions and increased risk of pulmonary infections.
24.4.2 Imaging • Thickening of cartilaginous trachea and sparing of the posterior/membranous airway (Fig. 24.17)
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Fig. 24.17 Relapsing polychondritis. Chest CT scan. Mediastinal windows. Asymmetric thickening of tracheal wall (arrow)
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b
Fig. 24.18 Relapsing polychondritis. Bronchoscopic image. (a) Thickening of trachea (arrow) with sparing of the membranous surface (star). (b) Collapsed lumen secondary to loss of cartilaginous ring of trachea in patient with relapsing polychondritis
24.4.3 Bronchoscopy • Thickening of the cartilaginous trachea (Fig. 24.18a, b). –– Sparing of the posterior/membranous airway • Cartilage biopsies from endobronchial procedures are difficult. –– Sampling the pina or other cartilage is preferable. • Relapsing polychondritis can be exacerbated by manipulation. –– Airway is very weak and prone to complications, so bronchoscopy is seldom done.
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–– Usually biopsy is used to assess complications or infections. –– Airway stenting and tracheostomy are major challenges. May be used to palliate and secure unstable airways
24.4.4 Pathology 24.4.4.1 Surgical Pathology • Acute inflammation infiltrating cartilage and soft tissue of proximal airways (Fig. 24.19a, b). • Giant cell reaction may be seen (Fig. 24.19c). • Bronchial epithelium commonly has reparative changes and squamous metaplasia.
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b
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Fig. 24.19 Relapsing polychondritis. Wedge excision. (a) Cross section of trachea excision that reveals destroyed cartilage (arrow) and scarring and distortion of adjacent wall due to contraction (arrowhead). (b) Marked acute inflammatory infiltrate destroying hyaline cartilage. (c) Giant cells can be part of the reaction
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24.5 Rheumatoid Nodule 24.5.1 Clinical • Develops in patients with rheumatoid arthritis. –– Most patients have subcutaneous nodules prior to lung involvement. –– Nodules measure up to 5 cm. –– Necrobiotic nodules may or may not mirror the course of arthritis and may regress spontaneously.
24.5.2 Imaging • Multiple, rounded, peripheral/subpleural and usually upper/mid zone predominant (Fig. 24.20a–d) • May mimic metastases, GPA, and septic emboli on imaging • Frequently cavitate with thick walls and smooth margins, rarely calcify
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Fig. 24.20 Rheumatoid nodule. Chest CT scan. A 56-year-old male with rheumatoid arthritis and multiple, bilateral upper and lower lobe nodules with central cavitation and thick walls (a, c, lung windows; b, d, mediastinal windows)
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Fig. 24.21 Rheumatoid nodule. Wedge excision. (a) Granulomatous subpleural nodule with basophilic necrosis. (b) Border of palisading histiocytes and giant cells
24.5.3 Pathology 24.5.3.1 Surgical Pathology • Basophilic necrosis with irregular histiocytic border (Fig. 24.21a, b) • Usually present in subpleura, adjacent to or extending into visceral pleura 24.5.3.2 Cytopathology • Granular proteinaceous debris, histiocytes, and multinucleated giant cells (Fig. 24.22) • Challenging to specifically diagnose in cytology • Requires additional history, laboratory testing, and clinical workup to exclude infection is needed 24.5.3.3 Pathological Differential Diagnosis • Granulomatous inflammation from the following is difficult to distinguish on pathology unless clinical history of rheumatoid arthritis is known. –– Granulomatosis with polyangiitis –– Necrotizing sarcoid granulomatosis –– Necrotizing infectious granuloma
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Fig. 24.22 Rheumatoid nodule. Cytologic ThinPrep. Papanicolaou stain. Granular proteinaceous debris, histiocytes, and multinucleated giant cells
24.5.3.4 Ancillary Studies • Tissue organismal stains for fungus and mycobacteria are needed to exclude an infection.
24.6 G ranulomatous Lymphocytic Interstitial Lung Disease (GLILD) 24.6.1 Clinical • Found in the setting of immunoglobulin deficiencies including: –– Common variable immune deficiency (CVID) –– Primary immune deficiency characterized by hypogammaglobinemia (IgG, IgA, and/or IgM) and impaired antibody response • Ten percent of CVID patients have GLILD. • Non-infectious. –– Likely due to autoimmunity and lymphoproliferation
24.6 Granulomatous Lymphocytic Interstitial Lung Disease (GLILD)
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Fig. 24.23 Granulomatous lymphocytic interstitial lung disease. A 21-year-old male with CVID. Chest CT scan. (a, b) Bilateral bronchiectasis with bronchial dilatation and wall thickening
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Fig. 24.24 Granulomatous lymphocytic interstitial lung disease. Non-infectious manifestation of GLILD in a 44-year-old male with CVID. Chest CT scan. (a, b) Multiple bilateral solid lung nodules and ground-glass opacities
24.6.2 Imaging • Multiple lung nodules (mid and LL > UL), airspace consolidations, and ground- glass opacities (Fig. 24.23a, b). • Lymphadenopathy (thoracic or abdominal) and splenomegaly (extrapulmonary features). • Bronchiectasis with interstitial lung disease can be seen (Fig. 24.24a, b). –– May be seen secondary to repeated infection.
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24.6.3 Pathology 24.6.3.1 Surgical Pathology • Pathology may be nodular or infiltrative (Figs. 24.25a, b and 24.26a, b), • Pathology defined by the presence of non-necrotizing granulomatous inflammation and lymphoplasmacytic inflammation with multiple patterns: –– Organizing pneumonia –– Interstitial pneumonitis –– Follicular bronchiolitis • Granulomatous inflammation is usually non-necrotizing loosely formed granulomas or giant cells. a
b
Fig. 24.25 Granulomatous lymphocytic interstitial lung disease. Wedge excision. (a) Granulomatous and lymphocytic nodule. (b) Predominant lymphoplasmacytic infiltrate with histiocytic clusters (arrows)
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Fig. 24.26 Granulomatous lymphocytic interstitial lung disease. Wedge excision. (a) Infiltrative lung disease with predominantly organizing pneumonia. (b) Loosely formed granulomas (arrow) adjacent to organizing pneumonia
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24.6.3.2 Pathological Differential Diagnosis • Hypersensitivity pneumonitis –– No history of immune deficiencies • Infection –– Granulomatous infections such as mycobacterial and fungal infections 24.6.3.3 Ancillary Studies • Rule out infection with tissue organismal stains –– Gomori methenamine silver (GMS): fungal –– Acid fast: mycobacteria
Suggested Readings Cumbo-Nacheli G, Doyle AD, Gildea TR. Diseases of the central airways: a clinical guide. In: Mehta AC, Jain P, Gildea TR, editors. Respiratory Medicine series editor Sharon I.S. Rounds. Cham: Springer International Publishing; 2016. Farver CF. Other nonneoplastic focal lesions, inclusions, and depositions. Chapter 25, In: Zander D, Farver CF, eds., Pulmonary Pathology, a volume in the series Foundations in Diagnostic Pathology. Goldblum J, ed., 2nd ed. Philadelphia: Elsevier; 2017. Hurst JR, Verma N, Lowe D, Baxendale HE, Jolles S, Kelleher P, et al. British Lung Foundation/ United Kingdom primary immunodeficiency network consensus statement on the definition, diagnosis, and management of granulomatous-lymphocytic interstitial lung disease in common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2017;5:938–45. 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;12:405–13. Obusez EC, Jamjoom L, Kirsch J, Gildea T, Mohammed TL. Computed tomography correlation of airway disease with bronchoscopy: part I--nonneoplastic large airway diseases. Curr Probl Diagn Radiol. 2014;43(5):268–77. Picken MM. Modern approaches to the treatment of amyloidosis: the critical importance of early detection in surgical pathology. Adv Anat Pathol. 2013;20:424–39. Rho L, Qiu L, Strauchen JA, Gordon RE, Teirstein AS. Pulmonary manifestations of light chain deposition disease. Respirology. 2009;14:767–70. Richards JC, Lynch DA, Chung JH. Cystic and nodular lung disease. Clin Chest Med. 2015;36(2):299–312. Schneider F, Gruden J, Tazelaar HD, Leslie KO. Pleuropulmonary pathology in patients with rheumatic disease. Arch Pathol Lab Med. 2012;136:1242–52. Smyrk TC. Pathological features of IgG4-related sclerosing disease. Curr Opin Rheumatol. 2011;23:74–9. Tillie-Leblond I, Wallaert B, Leblond D, Salez F, Perez T, Remy-Jardin M, Tonnel AB. Respiratory involvement in relapsing polychondritis: clinical, functional, endoscopic, and radiographic evaluations. Medicine. 1988;77:168–76.
Index
A Acid fast bacilli, 289, 290 Actinomycosis bronchiectasis, 264, 265 chronic infections, 263 differential diagnosis, 266, 267 endobronchial form, 263–265 lobectomy, 266 parenchymal form/nodular form, 263, 264 silver-positive and gram-positive tissue staining, 267 surgical pathology, 266 wedge excision, 266, 267 Actinomycosis israelii, 263 Acute eosinophilic pneumonia (AEP), 183, 217 Acute lung injury acute fibrinous, 181–183 diffuse alveolar damage, 173–177 organizing pneumonia, 177–183 Acute pulmonary histoplasmosis, see Primary histoplasmosis Adenocarcinoma bronchoscopy, 44, 45 clinical features, 41 cytopathology, 49 differential diagnosis, 49 histochemical stains, 49, 50 imaging, 41–44 immunohistochemical studies, 50 molecular testing, 50 programmed death-ligand 1, 50 surgical pathology, 45–48 Adenocarcinoma in-situ (AIS), 45, 46 Adenoid cystic carcinoma, 36, 37, 39
Adenosquamous carcinoma, 56–60 Adenoviridae, 300 Airway invasive aspergillosis, 308, 310 Allergic bronchopulmonary aspergillosis, 308, 309 Alveolar adenoma, 23–25 American Thoracic Society/European Respiratory Society (ATS/ ERS), 185 Amyloidosis antibody stains, 354 bronchoscopy, 352, 353 clinical settings, 349 cytopathology, 353, 356 differential diagnosis, 353, 354 diffuse alveolar septal involvement, 351, 353, 355, 356 fibrils type, 349 imaging, 350–352 nodules, 350, 353–355 tracheobronchial amyloidosis, 351 Angio-invasive aspergillosis, 308–311 Angiosarcoma, 101, 103, 104, 102 Anthracofibrosis, 284, 285 Anti-neutrophil cytoplasmic antibodies (ANCAs), 235 Asbestosis, 230–232 Aspergilloma, 307, 308, 312, 313 Aspergillosis airway invasive aspergillosis, 308–310 allergic bronchopulmonary aspergillosis, 308, 309 angio-invasive aspergillosis, 308–311 aspergilloma, 307, 308, 312, 313 bronchoscopy, 311, 312
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Index
372 Aspergillosis (cont.) chronic pulmonary aspergillosis, 312–314 cytopathology, 314, 315 differential diagnosis, 314 GMS histochemical stain, 314 hypersensitive aspergillos, 307 invasive aspergillosis, 312, 314 periodic acid Schiff's, 315 semi-invasive aspergillosis, 308, 309 Aspergillus fumigatus, 312 Aspergillus niger, 312, 313 Aspiration pneumonia, 201 bronchoscopy, 275, 276 clinical indications, 274, 275 core biopsy, 279 differential diagnosis, 279 endobronchial biopsy, 279 hyalinized nodule with early calcium deposition, 280 imaging, 275–278 immunohistochemical studies, 280 under polarized light, 280 surgical pathology, 278, 279 wedge excision, 278 Asthma/chronic bronchitis, 151, 155, 157 Atypical adenomatous hyperplasia (AAH), 45 Atypical pneumonias, 295 B Bacterial infections actinomycosis (see Actinomycosis) aspiration pneumonia (see Aspiration pneumonia) L. pneumophila (see Legionella pneumonia) malakoplakia (see Malakoplakia) nocardiosis (see Nocardiosis) Basophilic necrosis, 238, 365 Benign tumors alveolar adenoma, 23–25 hamartoma, 15–20 papillary adenoma, 25, 26 sclerosing pneumocytoma, 20–23 solitary papilloma, 26–29 Berylliosis, 208 Blastomyces dermatitidis, 328 Blastomycosis, 328–332 Botryomycosis, 266 Bronchiectasis, 157–159, 264, 287 Bronchoalveolar lavage (BAL), 284 Bronchoalveolar lavage fluid (BALF), 336 Broncholithiasis, 287, 318 Bronchopneumonia, 278 Bronchoscopic biopsy, 299
Bronchus-associated lymphoid tissue (BALT), 165 Bunyaviridae, 297 C Capillaritis, 245 Carcinoid tumors ancillary studies, 85 bronchoscopy, 77 cytopathology, 81 DIPNECH, 86 typical and atypical, 77–79 Carcinosarcoma, 93, 95 Chemical pneumonitis, 274 Chronic bronchiolitis, 292, 293 Chronic eosinophilic pneumonia, 217, 218 Chronic hypersensitivity pneumonitis, 200 Chronic obstructive pulmonary disease asthma/chronic bronchitis, 151, 154, 156, 157 bronchiectasis, 157–159 emphysema, 145–150, 154, 156 Chronic pulmonary aspergilloma, 312–314 Chronic pulmonary histoplasmosis, 315, 317 Chronic thromboembolic pulmonary hypertension (CTEPH), 250, 252–255 Coal workers pneumoconiosis, 227, 229 Coccidioidomycosiss, 332–334 Combined pulmonary fibrosis and emphysema (CPFE), 187 Connective tissue disease (CTD), 186 Constrictive bronchiolitis, 167–171 Constrictive pericarditis, 288 Coronavirus, 297 Cryptococcal nodule, 327, 328 Cryptococcus, 325–328 Cumbo/onion peel sign, 342 Cylindrical bronchiectasis, 291 D Desquamative interstitial pneumonia, see Respiratory bronchiolitis-interstitial lung disease (RB-ILD) Dieterle stain, 272 Diffuse alveolar damage (DAD), 173–176 Diffuse alveolar hemorrhage (DAH), 241, 243 Diffuse large B-cell lymphoma, 126–128 Diffuse malignant mesothelioma ancillary studies, 136 bronchoscopy, 132 clinical, 131 cytopathology, 135, 136
Index imaging, 131, 132 pathological differential diagnosis, 136 surgical pathology, 133 Dirofilaria immitis, 338 Dirofilariasis, 338–341 DNA virus adenovirus, 300, 303 classification, 300 CMV, 301–304, 306 EBV, 301 HSV, 303, 305 HPV, 302 varicella virus, 303 E Echinococcosis, 342–345 Echinococcus granulosus, 341 Emphysema, 145, 147, 149, 150, 291 Empyema necessitans, 268 Endobronchial aspergillosis, 311, 312 Endobronchial forceps biopsies, 284 Endobronchial needle aspiration (EBNA), 2 Enterovirus, 296 Eosinophilic pneumonia (EP), 216–220, 244 Eosinophillic granulomatosis with polyangiitis, 243–245 Epithelioid hemangioendothelioma, 97–99, 101, 100 Epithelioid histiocytes, 289 Exfoliative respiratory cytology techniques, 2, 3 Explant pneumonectomy, 195 F Fibrils, 349 Fibrinoid necrosis, 241, 244 Fibrosing mediastinitis, 316, 318, 319 Follicular bronchiolitis, 164–167 Fungal hyphae, 267 Fungal infections aspergillosis (see Aspergillosis) blastomycosis (see Blastomycosis) coccidioidomycosis (see Coccidioidomycosis) cryptococcus (see Cryptococcus) histoplasmosis (see Histoplasmosis) pneumocystis pneumonia (see Pneumocystis pneumonia) G Ghon focus, 283 Giant cell carcinomas, 93
373 Gomori methenamine silver (GMS) stains, 266, 306 Granulomatosis with polyangiitis (GPA), 235–240 Granulomatous lymphocytic interstitial lung disease (GLILD), 208, 366–369 Ground glass opacities (GGO), 223 H Hamartoma, 15–20 Hantavirus, 297 Hard-metal pneumoconiosis, 232–234 Hemorrhagic pneumonia, 273 Hemosiderin-laden macrophages, 241 Hemosiderosis, 238, 241 Hermansky-Pudlak syndrome, 186 Herpes simplex virus, 303, 305 Hilar lymphadenopathy, 66 Histoplasma capsulatum, 315, 318 Histoplasmosis, 319 bronchoscopy, 318, 319 chronic pulmonary histoplasmosis, 315, 317 clinical features, 315 cytopathology, 319 differential diagnosis, 321 fibrosing mediastinitis, 316–318 histochemical studies, 321 primary histoplasmosis, 315, 316 progressive disseminated histoplasmosis, 315, 317 surgical pathology, 319 Human metapneumonvirus (HMPV), 296 Human T-cell lymphotropic virus type 1 (HTLV-1), 297 Hyalinizing pulmonary granuloma (HPG), 226, 353, 354, 359 Hydatid disease/hydatidosis, 341 Hyperinfection syndrome, 335 Hypersensitivity pneumonitis (HP), 197–201, 290, 293 Hypertensive vascular disease chronic thromboembolic disease (see Chronic thromboembolic pulmonary hypertension) pulmonary capillary hemangiomatosis (see Pulmonary capillary hemangiomatosis) pulmonary hypertension (see Pulmonary hypertension) pulmonary veno-occlusive disease (see Pulmonary veno-occlusive disease) talcosis (see Talcosis)
Index
374 I Idiopathic interstitial pneumonias (IIP), 185 IgG4-related sclerosing disease, 353, 359–361 Inflammatory myofibroblastic tumor, 110, 111 Interstitial lung diseases EP (see Eosinophilic pneumonia (EP)) HP (see Hypersensitivity pneumonitis (HP)) langerhans cell histiocytosis (see Langerhans cell histiocytosis) PAP (see Pulmonary alveolar proteinosis (PAP)) sarcoidosis (see Sarcoidosis) Interstitial pneumonia clinical features, 185 NSIP (see Nonspecific interstitial pneumonia (NSIP)) RB-ILD (see Respiratory bronchiolitis- interstitial lung disease (RB-ILD)) UIP (see Usual interstitial pneumonia (UIP)) Interstitial pneumonia with autoimmune features (IPAF), 185 Intimal fibroplasia, 249 Invasive aspergilloma, 312 Invasive aspergillosis, 314 K Kaposi Sarcoma, 104–107 Karyorrhectic debris, 70 L Lady Windermere syndrome, 291 Langerhans cell histiocytosis, 209–212 Large cell carcinoma, 60, 62 Large cell neuroendocrine carcinomas (LCNC), 72, 73, 75 Legionella pneumonia, 271–273 Lepidic predominant, 45 Light chain deposition disease, 353, 355, 357–359 Lipoid pneumonia, 274 Loeffler syndrome, 217 Lymphadenopathy, 286, 290 Lymphangioleiomyomatosis, 112, 113, 115 Lymphomatoid granulomatosis, 123, 124, 126 Lymphoproliferative diseases diffuse large B-cell lymphoma, 126, 128 lymphomatoid granulomatosis, 124, 126 MALT Lymphoma, 117–120, 123
M Malakoplakia, 273, 274 MALT Lymphoma, 117, 118, 120, 123 Measles, 296, 299 Mediastinal lymphadenopathy, 360 Mediastinal mass, 66 Meniscus/crescent sign, 342 Michaelis-Gutmann bodies, 273, 274 Microscopic polyangiitis, 240–243 Miliary tuberculosis, 284, 287, 288 Minimally invasive adenocarcinoma (MIA), 45, 46 Modified Romanowsky stain, 289 Movat pentachrome stains, 183 Mucoepidermoid carcinoma (MEC), 31–33, 35 Multi-disciplinary techniques, 1–10, 12, 13 Mycobacterial infections non-tuberuclous mycobacterial infections (see Non-tuberuclous mycobacterial infections) tuberuclous mycobacterial infections (see Tuberuclous mycobacterial infections) Mycobacterium tuberculosis, 283 N Necrotizing granulomas, 288 Necrotizing sarcoid granulomatosis (NSG), 239 Nocardia astereoides, 267 Nocardiosis, 267–272 Nodular bronchiectasis, 290 Non-small cell carcinomas adenocarcinoma, 41–50 adenosquamous carcinoma, 56–58, 60 large cell carcinoma, 60, 62 squamous cell carcinoma, 51–57 Nonspecific interstitial pneumonia (NSIP), 190–192 Non-tuberculous mycobacterial infections, 290–294 O Organizing pneumonia (OP), 177–182 Orthomyxovirida, 296 P Papillary adenoma, 25, 26 Parainfluenza, 296, 299 Paramyxoviridae, 296
Index Paramyxovirus, 299 Paraneoplastic syndromes, 65 Parasitic infections dirofilariasis (see Dirofilariasis) echinococcosis (see Echinococcosis) strongyloidiasis (see Strongyloidiasis) toxoplasmosis (see Toxoplasmosis) Picornaviridae, 296 Pleomorphic Carcinoma, 89, 92 Plexiform pulmonary hypertension, 249, 250 Pneumoconioses asbestosis (see Asbestosis) coal workers pneumoconiosis (see Coal workers pneumoconiosis) hard metal lung disease (see Hard-metal pneumoconiosis) silicosis (see Silicosis) Pneumocystis jiroveci, 321 Pneumocystis pneumonia, 321–325 Post-primary tuberculosis, 283 Primary histoplasma, 315, 316 Primary tuberculosis, 283, 285–286 Progressive disseminated histoplasmosis, 315, 317 Progressive massive fibrosis (PMF), 223–227 Pulmonary alveolar proteinosis (PAP), 213–216 Pulmonary arterial hypertension (PAH), 247 Pulmonary artery intimal sarcoma, 107–110 Pulmonary capillary hemangiomatosis (PCH), 247, 257–259 Pulmonary congestion, 241 Pulmonary hypertension, 247, 250–252 Pulmonary veno-occlusive disease (PVOD), 247, 255–257 R Ranke complex, 283 Rasmussen aneurysm, 288 Relapsing polychondritis, 361–363 Respiratory bronchiolitis-interstitial lung disease (RB-ILD), 192–195 Respiratory bronchiolitis (RB), 161–164 Respiratory syncytial virus (RSV), 296 Retroviridae, 297 Rheumatoid nodule, 240, 364–366 RNA viruses, 296–299 Romanowsky stain, 289 S Salivary gland-like tumors, 31, 32, 34–37, 39 Sarcoidosis, 202–209
375 Sclerosing pneumocytoma, 20–23 Semi-invasive aspergillosis, 308, 309 Silicoproteinosis, 223 Silicosis, 223–226 Simple pulmonary eosinophilia, 217 Small airway diseases constrictive bronchiolitis, 167–171 follicular bronchiolitis, 164–167 respiratory bronchiolitis, 161–164 Small cell carcinoma, 65–72 Smoking-related interstitial fibrosis (SRIF), 194 Solitary fibrous tumor, 138, 139, 141, 142, 140, 143 Solitary papilloma, 26–29 Solitary pulmonary nodule (SPN), 15 Spendore-Hoeppli effect, 266 Spindle cell carcinoma, 92 Splendore-Hoeppli effect, 266 Squamous cell carcinoma, 50–57 Steiner stain, 273 Strongyloides stercoralis, 335 Strongyloidiasis, 335–338 Subacute hypersensitivity pneumonitis, 198, 199 Sudden acute respiratory syndrome (SARS), 297 Sulfur granules, 266 Superior venocaval (SVC) syndrome, 65 Systemic diseases amyloidosis (see Amyloidosis) GLILD (see Granulomatous lymphocytic interstitial lung disease (GLILD)) IgG4 (see IgG4-related sclerosing disease) light chain deposition disease (see Light chain deposition disease) relapsing polychondritis (see Relapsing polychondritis) rheumatoid nodule (see Rheumatoid nodule) T Talcosis, 259–261 Toxoplasma gondii, 345 Toxoplasmosis, 345–348 Transbronchial biopsy, 1 Transbronchial needle aspiration (TBNA), 2, 3 Tuberuclous mycobacterial infections, 283–290 bronchoscopy, 284 clinical features, 283, 284 complications of pulmonary tuberculosis, 287, 288
Index
376 Tuberuclous mycobacterial infections (cont.) cytopathology, 289, 290 miliary tuberculosis, 287 post-primary tuberculosis, 286 primary tuberculosis, 285, 286 surgical pathology, 288 Tumorlet, 80, 86 U Usual interstitial pneumonia (UIP), 185–189 V Varicella virus, 303, 305 Vasculitis eosinophillic granulomatosis with polyangiitis (see Eosinophillic granulomatosis with polyangiitis)
granulomatous vasculitis (see Granulomatosis with polyangiitis (GPA)) microscopic polyangiitis (see Microscopic polyangiitis) Viral infections DNA (see DNA virus) imaging, 295, 296 pathologic patterns, 296 RNA (see RNA virus) viral pneumonia, 295 Viral pneumonia, 295 W Warthin-Starry stain, 273 Water-lily sign, 343 Z Ziehl-Neelsen staining, 274