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MALIGNANT MESOTHELIOMA Edited by Douglas W. Henderson Flinders Medical Centre, Bedford Park, Adelaide, South Australia Keith B. Shilkin Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia Suzanne Le P. Langlois Royal Adelaide Hospital, Adelaide, South Australia Darrel Whitaker Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia With a Foreword by J. Christopher Wagner Formerly, MRC Pneumoconiosis Research Unit, Llandough Hospital, Penarth, South Glamorgan, Wales, United Kingdom HEMISPHERE PUBLISHING CORPORATION A member of the Taylor & Francis Group New York Washington Philadelphia London 1 DEFENDANT'S s EXHIBIT !2 HWBUI0007549 MALIGNANT MESOTHELIOMA Copyright 1992 by Hemisphere Publishing Corporation. All rights reserved. Printed in the United States of America. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher. 1234567890 EBEB 987654321 This book was set in Tunes Roman by Hemisphere Publishing Corporation. The editors were Andrew N. Bartlett and S. Michele Nix; the production supervisor was Peggy M. Rote; and the typesetters were Linda Andros, Cynthia L. Dalton, Lori Knoemschtid, and Sandra F. Watts. Cover design by Rend Winfield. Printing and binding by Edwards Brothers, Inc. A CIP catalog record for this book is available from the British Library. Library of Congress Catalogtag-in-PubUcation Data Malignant mesothelioma / edited by Douglas W. Henderson . . . [et al.] : with a foreword by J. Christopher Wagner, p. cm.--(The Cancer series) Includes bibliographical references and index. 1. Mesothelioma. 2. Asbestosis--Toxicology. I. Henderson, Douglas W. II. Series: Cancer series (New York, N.Y.) [DNLM: 1. Mesothelioma. QZ 340 M251) RC280.L8M25 1992 DNLM/DLC 616.99'42--dc20 for Library of Congress ISBN 0-89116-977-6 ISSN 1043-9439 91-7046 CIP HWBUI0007550 Contents Contributors xv Foreword xvii Preface xxvii ; Acknowledgments xxix Introduction and Historical Aspects--With Comments on Mesothelioma Registries Douglas W. Henderson, Keith B. Shilkin, and Darrel Whitaker 1 j*1 Section 1: Asbestos, Asbestosis, Lung Cancer, and Mesothelioma 1 11 Asbestos--Nature and History 1 Asbestos, Asbestosis, and Lung Cancer 3 Malignant Mesothelioma 7 t Section 2: Possible Mechanisms for Asbestos-Induced Oncogenesis 9 General Considerations and the Possible Capacity of Asbestos to Induce Genetic Injury in Cells 9 > Synergism of Asbestos with Other Carcinogenic Agents, and Its Role as an Initiator or 5 Promoter in Oncogenesis 12 f. Summary 13 vii 4 Section 3: Mesothelioma Registries 14 Panel Membership 14 Method of Operation 14 Categorization Systems: Probability Indices Panel Opinion and Reports 15 Observer Variation 16 Material 16 Effect and Ongoing Function of Panels 17 Acknowledgments 17 References 17 15 CONTENTS PATHOLOGY AND DIAGNOSIS OF MESOTHELIOMA The Pathobiology of the Mesothelium Darrel Whitaker, Linda S. Manning, Bruce W. S. Robinson, and Keith B. Shilkin 25 Section 1: The Normal Mesothelium 25 Introduction 25 Historical Aspects 25 Embryological Origin 26 Mesothelium: Structure and Function 26 The Mesothelium In Vitro 31 Intermediate Filaments (IF) and Their Proteins (IFP) in Mesothelial Cells 34 Section 2: The Healing Mesothelium 36 Reaction to Serosal Damage 36 The Healing Process and Theories of Healing 36 The "Stem Cell" Controversy--The Subserosal Cell Versus the Surface Mesothelial Cell 38 Multipotential Subserosal Cells (MSC)--Do They Exist? 40 The Case for the Surface Cell 44 Summary and Conclusions 47 Section 3: Malignant Mesothelioma--Animal Models and Cell Lines 47 Malignant Mesothelioma in Animals 47 Mesothelial and Mesothelioma Cell Lines Acknowledgments 56 References 56 53 The Pathology of Malignant Mesothelioma, Including Immunohistology and (Jltrastructure Douglas W. Henderson, Keith B. Shilkin, Darrel Whitaker, Harold D. Attwood, Theo J. Constance, Richard H. Steele, and Peter J. Leppard 69 CONTI 3. HWBUI0007552 CONTENTS ix Introduction 69 Cell Populations Identifiable in Serosal Membranes and Their Possible Relationship to Phenotypic Expression in Mesothelioma 71 Classification of Mesothelium-Related Neoplasms 74 Section 1: Gross Pathology and Conventional Light Microscopy of Epithelial Mesothelioma 75 Distribution and Gross Morphology of Malignant Mesothelioma Relative Proportions of Mesothelioma Subtypes 77 Epithelial Mesothelioma: Conventional Light Microscopy 77 75 Section 2: Mucin Histochemistry of Epithelial Mesothelioma 84 Section 3: Immunohistochemistry of Epithelial Mesothelioma 89 Carcinoembryonic Antigen (CEA) 89 Epithelial Membrane Antigen (EMA) and Human Milk Fat Globule Protein (HMFG) 92 Miscellaneous Antibodies 94 Intermediate Filament Protein Analysis: Cytokeratins and Vimentin 94 Section 4: Ultrastructural Pathology of Epithelial Mesothelioma 97 Microvilli 102 Intermediate Filaments 104 Intercellular Junctions 106 Secretions and Crystalloidal Structures 107 Other Cytoplasmic and Nuclear Features 108 Electron Microscopy of Exfoliated Cells 109 Fine Structure of Poorly Differentiated Epithelial Mesotheliomas 110 Section 5: Bimorphic, Sarcomatoid, and Transitional Mesotheliomas 113 Mixed (Bimorphic) Mesothelioma 113 Sarcomatoid Mesothelioma and Malignant Fibrous Tumors of the Pleura Transitional Mesothelioma 125 115 Section 6: Spread of Malignant Mesothelioma 127 Acknowledgments References 129 128 Unusual Histological Types and Anatomic Sites of Mesothelioma Douglas W. Henderson, Keith B. Shilkin, Darrel Whitaker, Harold D. Attwood, Theo J. Constance, Richard H. Steele, and Peter J. Leppard 140 Desmoplastic Mesothelioma 140 Lymphohistiocytoid Mesothelioma and Lymphocyte Subpopulations in Mesotheliomas 144 Cystic Mesothelioma of the Peritoneum 148 X CONTENTS Well-Differentiated Papillary Mesothelioma and Serous Papillary Tumors of Serosal Surfaces 159 Mesothelioma of the Tunica Vaginalis Testis 161 Pericardial Mesothelioma 163 Acknowledgments 163 References 163 4. Cytological Appearances of Malignant Mesothelioma Darrei Whitaker, Keith B. Shilkin, and Gregory F. Sterrett 167 Introduction 167 The Value of Cytodiagnosis 167 Cytological Samples, Techniques, and Tests Descriptive Cytodiagnosis: Effusions 171 Ancillary Tests on Effusions 174 Fine-Needle Aspiration (FNA) Cytodiagnosis Conclusion 178 Acknowledgments 178 References 178 170 177 5. The Differential Diagnosis of Malignant Mesothelioma: A Practical Approach to Diagnosis During Life Douglas W. Henderson, Darrel Whitaker, and Keith B. Shilkin 183 Section 1: A General Approach to the Pathological Diagnosis of Mesothelioma 183 An Approach Based on Limited Sampling Essential Requirements 185 Ancillary Techniques 185 Correlation 186 183 Section 2: Differential Diagnosis 186 Reactive Mesothelial Hyperplasia and Fibrosis 187 Secondary Adenocarcinoma, Renal-Cell Carcinoma, Malignant Melanoma, and Carcinosarcoma 190 Primary Sarcomas of Chest and Abdominal Walls; Secondary Sarcoma in Serosal Tissue; So-Called Synovial Sarcoma and Epithelioid Sarcoma 192 References 194 II. MINERALOGY AND EPIDEMIOLOGY OF MESOTHELIOMA 6. Mineral Fiber Content of Lung Tissue in Patients with Malignant Mesothelioma Victor L. Roggli 201 CONTENT Int 7- T 3 I 1 I 8. 9. HWBUI0007554 CONTENTS Introduction 201 Techniques for Analysis of Pulmonary Fiber Content 202 Asbestos Bodies and Malignant Mesothelioma 206 Quantitative Assessment of Fiber Content in Mesothelioma 209 Malignant Mesothelioma Relative to Type of Exposure 212 Malignant Mesothelioma Relative to Asbestos Fiber Type 215 Summary 218 References 219 7. The Epidemiology of Asbestos and Mesothelioma Nicholas H. de Klerk and Bruce K. Armstrong 223 Introduction 223 Patterns of Worldwide Incidence in Relation to Asbestos Exposure 224 Mesothelioma and Fiber Dimensions 228 Mesothelioma and Asbestos Type 229 Quantitative Relationship of Mesothelioma Incidence to Exposure to Asbestos Risk of Mesothelioma from Environmental and Nonoccupational Exposure to Asbestos 236 Unresolved Issues 241 References 243 231 HI. CLINICAL INVESTIGATION AND MANAGEMENT OF MESOTHELIOMA 8. The Clinical Diagnosis of Malignant Mesothelioma Timothy I. Christmas 253 Introduction 253 Patient Profile 253 Presenting Clinical Features 254 Physical Signs 255 Radiographic Changes 255 Biochemical and Hematological Findings Bronchoscopy and Bronchoalveolar Lavage Gallium Lung Scanning 256 Clinical Staging 256 Pleural and Ascitic Fluid 256 References 258 256 256 A. William Musk and Radiological Investigation of Mesothelioma Douglas W. Henderson 259 Suzanne Le P. Langlois and Introduction 259 Radiological Features of Malignant Pleural Mesothelioma 260 The Radiological Investigation of Pleural Mesothelioma 261 xii Primary Peritoneal Mesothelioma 267 Mesothelioma of the Thnica Vaginalis Testis 269 Other Radiological Manifestations of Asbestos-Related Disease Radiological Investigation of Asbestos-Related Disease 274 Conclusion 276 Acknowledgments 276 References 276 269 CONTENTS 10. Immune Function Related to Asbestos Exposure and Mesothelioma, and Immunotherapy of Mesothelioma Linda S. Manning, Alison H. Rose, Rayleen V. Bowman, Timothy I. Christmas, Michael J, Garlepp, and Bruce W. S. Robinson 278 Introduction 278 Effects of Asbestos Fibers on Immune Cell Function In Vitro Asbestos Exposure and Immune Responses In Vivo 280 immune Function in Patients with Malignant Mesothelioma Mesothelioma Cells as Immune Targets 282 Effects of Mesothelioma Cells on Immune Function 283 Immunotherapy of Malignant Mesothelioma 284 Summary 286 References 286 279 282 11. Management of Malignant Mesothelioma A. William Musk, Rayleen V. Bowman, Timothy I. Christmas, and Bruce W. S. Robinson 292 Introduction 292 Early Diagnosis 293 Clinical Diagnosis 293 Clinical Staging 293 Disease Progression 293 Treatment 294 Palliative Therapy 297 Prognosis 298 Conclusions 299 References 299 IV. SOCIAL-HISTORICAL, MEDICOLEGAL, AND ETHICAL ASPECTS OF MESOTHELIOMA 12. The Blue Asbestos Industry at Wittenoom in Western Australia: A Short History Lenore Layman 305 The Industry 305 Workers' Experience 310 CO!1 13. 14. Name < Subject HWBUI0007556 CONTENTS Occupational Health in the Industry References and Notes 324 Medicolegal Issues in Mesothelioma and Asbestos Disease Litigation John R. C. Gordon 328 Introduction 328 No-Fault Statutory Compensation Issues 329 Claims for Damages in Negligence or Strict Liability Diagnosis 332 Historical Medical Knowledge 334 Medicolegal Similarities and Differences Between Asbestos-Caused Diseases Asbestosis and Lung Cancer/Mesothelioma--Different Forms of Damage? Causation 338 Impairment and Disability 342 Defenses 343 Acknowledgments 344 References 344 Appendix: Landmark Medicolegal References on Asbestos-Related Diseases The Asbestos Industry: A Perspective on the Bioethics of Industrial Activity and Disasters Joseph W. Smith 351 Introduction 351 The Ontology and Ethics of Corporate Moral Responsibility Does Life Have a Price? 353 The Epistemology of Asbestos Risk 355 What Can We Learn from Wittenoom? 357 Principles of Fair and Just Industry 358 References and Notes 360 Name and Place Index Subject Index 369 HWBUI0007557