Progress in Hodgkin's Disease PDF
Preview Progress in Hodgkin's Disease
Editorial Advisory Board Robert Kisilevsky Kingston, Ontario, Canada M. Mihatsch Basel, Switzerland Peter C. Nowell Philadelphia, Pennsylvania Steen Olsen Aarhus, Denmark U. Pfeifer Bonn, Germany Sibrand Poppema Edmonton, Alberta, Canada Stephen T. Reeders New Haven, Connecticut Andrew H. Wyllie Edinburgh, Scotland R. M. Zinkernagel Zürich, Switzerland International Review of EXPERIMENTAL ©PATHOLOGY Volume 33 PROGRESS IN HODGKIN'S DISEASE Edited by G. W.Richter Department of Pathology University of Rochester Medical Center Rochester, New York Kim Solez Department of Pathology Faculty of Medicine University of Alberta Edmonton, Alberta Canada Guest Editor Sibrand Poppema Department of Laboratory Medicine Cross Cancer Institute Edmonton, Alberta Canada ACADEMIC PRESS, INC. Harcourt Brace Jovanovich, Publishers San Diego New York Boston London Sydney Tokyo Toronto This book is printed on acid-free paper. © Copyright © 1992 by ACADEMIC PRESS, INC. All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Academic Press, Inc. San Diego, California 92101 United Kingdom Edition published by Academic Press Limited 24-28 Oval Road, London NW1 7DX Library of Congress Catalog Number: 62-21145 International Standard Book Number: 0-12-364933-1 PRINTED IN THE UNITED STATES OF AMERICA 92 93 94 95 9 8 7 6 5 4 3 2 1 Contributors Numbers in parentheses indicate the pages on which the authors' contributions begin. M. H. Bennett, Department of Pathology, Mount Vernon Hospital, Nort- wood, Middlesex, England (27) Volker Diehl, Klinik I für Innere Medizin, Universität zu Köln, D-5000 Köln 41, Germany (185) Nancy L. Harris, Department of Pathology, Massachusetts General Hospi- tal, Harvard Medical School, Boston, Massachusetts 02114 (1) B. Vaughan Hudson, U.C.M.S.M., London W 1, England (27) G. Vaughan Hudson, U.C.M.S.M., London W 1, England (27) Judith Hugh, Department of Laboratory Medicine, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada, and Department of Pathology, Uni- versity of Alberta, Edmonton, Alberta T6G 2R7, Canada (81) Christof v. Kalle, Klinik I für Innere Medizin, Universität zu Köln, D-5000 Köln 41, Germany (185) K. A. MacLennan, Department of Pathology, The Royal Marsden Hospital, London SW3 6S5, England (27) D. Macchia, Department of Clinical Immunology, University of Florence, 50134 Florence, Italy (141) E. Maggi, Department of Clinical Immunology, University of Florence, 50134 Florence, Italy (141) Elisabeth Paietta, Department of Oncology, Montefiore Medical Center and Albert Einstein Cancer Center, Bronx, New York 10467 (115) P. Parronchi, Department of Clinical Immunology, University of Florence, 50134 Florence, Italy (141) M.-P. Piccinni, Department of Clinical Immunology, University of Flor- ence, 50134 Florence, Italy (141) Sibrand Poppema, Department of Laborary Medicine, Cross Cancer Insti- tute, Edmonton, Alberta T6G 1Z2, Canada, and Department of Pathol- ogy, University of Alberta, Edmonton, Alberta T6G 2R7, Canada (53, 81) ix X Contributors S. Romagnani, Department of Clinical Immunology, University of Flor- ence, 50134 Florence, Italy (141) C. Simonelli, Department of Clinical Immunology, University of Florence, 50134, Italy (141) Lawrence M. Weiss, Department of Surgical Pathology, Division of Anatomical Pathology, City of Hope National Medical Center, Duarte, California 91010 (165) Preface Volume 33 of the International Review of Experimental Pathology summa- rizes the progress that has been made in the diagnosis and understanding of the pathogenesis of Hodgkin's disease in the past ten years. This volume provides data that go beyond those covered in current textbooks in pathol- ogy and hematology and should be of interest to all pathologists and clini- cians dealing with the diagnosis and management of Hodgkin's disease, as well as to lymphoma researchers. The first half of this volume deals with diagnostic aspects, whereas the second half focuses on recent developments in the understanding of the pathogenesis of Hodgkin's disease. The first chapter discusses the differen- tial diagnosis between Hodgkin's disease and non-Hodgkin's lymphomas, and provides needed guidelines on how to deal in a practical way with the grey areas between these two groups of diseases. In the second chapter, the criteria for a prognostically relevant histological grading of the most fre- quent subtype of Hodgkin's disease, the nodular sclerosis subtype, are de- scribed and supported with results from over 2000 patients. The third chap- ter summarizes data indicating that the nodular lymphocyte predominance subtype of Hodgkin's disease is a separate entity, different in morphology, immunophenotype, and clinical behavior from the other subtypes of Hodgkin's disease. The fourth chapter provides a thorough inventory of the various reagents that have been used to try to define the immunopheno- type of Reed-Sternberg cells. Also, an attempt is made, for the first time, to correlate the expression of surface markers on Reed-Sternberg cells with clinical behavior. In the fifth chapter, the focus is on potential mediators of lymphocyte ag- glutination to Reed-Sternberg cells. Special emphasis is given to a lectin on Reed-Sternberg cells that functions as an ectosialyltransferase and perhaps is a lymphocyte mitogenic factor. The sixth chapter deals with the immuno- logical alterations in Hodgkin's disease. The findings support a hypothesis that the T cell reaction in Hodgkin's disease may reflect an autologous mixed leukocyte reaction in vivo. This reaction might be a consequence of an abnormal recognition by T cells of autologous major histocompatibility complex class II determinants. In the seventh chapter, an overview of molecular genetic studies into the pathogenesis of Hodgkin's disease is pre- sented. Immunoglobulin gene analysis has shown that cases of Hodgkin's disease with a high percentage of Reed-Sternberg cells frequently have XI XÜ Preface clonal rearrangements. Also, in up to half of the patients with Hodgkin's disease, Epstein-Barr virus genomes can be demonstrated in the Reed- Sternberg cells by in situ hybridization. These findings suggest that at least in a subgroup of patients, Epstein-Barr virus transformation of B cells may play some role in the pathogenesis of Hodgkin's disease. The final chapter deals with the results of studies on Hodgkin cell lines. Cell lines have played an important part in Hodgkin's disease research, mostly because of the scarcity of Reed-Sternberg cells in the involved lymph nodes. Most no- tably, Hodgkin cell lines have been used as an immunogen to produce an- tibodies with Reed-Sternberg cell reactivity. Also, Hodgkin cell lines are good models to study the production of cytokines, which may play a role in the complex interactions between Reed-Sternberg cells and the sur- rounding reactive cells. I greatly appreciate the effort by all of my collaborators on this volume to provide such a thorough review of their respective fields of interest. I be- lieve that the content of this volume is an appropriate reflection of what has been achieved in the past ten years as a result of experimental pathologic studies into Hodgkin's disease. Sibrand Poppema Differential Diagnosis between Hodgkin's Disease and Non-Hodgkin's Lymphoma Nancy L. Harris Department of Pathology Massachusetts General Hospital Harvard Medical School Boston, Massachusetts 02114 I. Introduction II. Low-Grade B Cell Lymphoma A. Definitions B. Morphology C. Immunophenotype D. Genotype III. Pleomorphic ("Peripheral") T Cell Lymphomas A. Definitions B. Morphology C. Immunophenotype D. Molecular Genetics IV. Large Cell Lymphoma and Anaplastic Large Cell Lymphoma . A. Definitions B. Morphology C. Immunophenotype D. Molecular Genetics V. Conclusions References I. INTRODUCTION Despite all the advances in immunology and molecular genetics of the last two decades, the diagnosis of Hodgkin's disease (HD) remains primarily morphologic, based on the appearance of the complex infiltrate on routine, paraffin-embedded, hematoxylin- and eosin-stained sections. Although frustrating to researchers, who regularly offer new diagnostic immunologie or molecular genetic tests for the disease, this is good news for the practic- International Review of Experimental Pathology, Volume 33 Copyright © 1992 by Academic Press, Inc. All rights of reproduction in any form reserved. 1 2 Nancy L. Harris ing pathologist, who can usually both diagnose and subclassify this com- mon type of lymphoma with confidence, based on relatively simple and straightforward histologie criteria. This review will focus on specific criteria, most of which are covered in greater detail elsewhere in this volume, that are useful in distinguishing HD from other lymphomas. In most cases, as in- dicated, morphologic criteria will suffice. Immunophenotypic and, less often, molecular genetic analysis may play a role in confirming the impres- sion based on morphologic examination, and the utility of these techniques in specific situations will be addressed. No discussion of this differential diagnosis would be complete, however, without recognition of the fact that we still do not know exactly what Hodgkin's disease is, and what its relationship is with the disorders known as "non-Hodgkin's" lymphomas (NHLs). If, as the variety of suggested lin- eages implies, the neoplastic cell of HD may in some cases be a T lympho- cyte, in others a B lymphocyte, and in still others a monocyte/macrophage derivative, then there may be a true borderline between HD and NHL. In some patients, neoplastic transformation of a particular B or T cell might lead to a B or T NHL, but in others, because of a different immunologie makeup of the host, the same neoplastic B or T cell may give rise to the ex- traordinary, tumorous immunologie reaction that we recognize histologi- cally and clinically as HD. In general, we expect that most "difficult" cases result from problems in fixation, sectioning, sampling, or lack of experi- ence, but in fact the difficulty in some cases may result from a true overlap between HD and NHL—real borderline cases. Thus we may have to accept the fact that in occasional cases the differential diagnosis cannot be re- solved because the disease itself has not "decided" whether to be HD or NHL in this patient. There are three major categories of lymphoma that may be confused with various subtypes of Hodgkin's disease: low-grade B cell lymphomas, so- called peripheral T cell lymphomas, and large cell lymphomas, including the recently described anaplastic type. Each of these entities will be dis- cussed, reviewing morphologic, immunologie, and molecular genetic fea- tures that may be useful in the differential diagnosis. II. LOW GRADE B CELL LYMPHOMA A. Definitions Lymphocyte-predominance Hodgkin's disease (LPHD), by definition, con- tains a predominance of small, reactive-appearing lymphocytes, with only rare diagnostic Reed-Sternberg (RS) cells, although the characteristic mononuclear variants (L&H cells or the lymphocytic and/or histiocytic cells Hodgkin's vs. Non-Hodgkin's: Diagnosis 3 of Lukes and Butler) may be numerous (Lukes etal, 1966 a,b). The pattern may be either nodular (NLPHD) or diffuse (Fig. 1A and B). These fea- tures-predominance of small lymphocytes, rarity of malignant-appearing cells, and occasional follicular pattern-may give rise to a differential diag- nosis of non-Hodgkin's lymphoma (see Tables I and II). B. Morphology 1. LPHD versus Small Lymphocytic Lymphoma The lymphocytic background of LPHD is usually less monotonous than the nodal infiltrate produced by chronic lymphocytic leukemia/small lympho- cytic lymphoma (CLL/SLL) (Fig. 2A and B). The lymphocytes range from small, hyperchromatic cells with clumped chromatin and no nucleoli to slightly irregular, larger cells with indented or cleaved nuclei, resembling follicular center cells (centrocytes). Scattered immunoblasts may be present, but most large mononuclear cells either resemble centroblasts (large non- cleaved follicular center cells) or are examples of the so-called L&H cells, with popcorn-shaped, vesicular nuclei and small nucleoli apposed to the nuclear membrane (Burns etal, 1984). In contrast, the lymphocytes of CLL are usually round, have slightly more open chromatin than normal lympho- cytes, often with visible nucleoli, and have an extremely monotonous ap- pearance. Even when larger cells are admixed, the entire population looks as though it belongs to a single clone; like islands of maturing erythroid cells in the bone marrow, there is a continuum of morphology between the largest and the smallest cells, in contrast to the heterogeneity of a reactive population. When large cells are present, they resemble immunoblasts, with prominent central nucleoli, rather than the centroblasts and L&H cells of LPHD. In many cases, when large cells are present, they are concen- trated in pseudofollicular proliferation centers, visible at low magnification as regularly distributed, pale areas in the darker infiltrate of small lympho- cytes (Lennert, 1978). Other cell types are more numerous in LPHD than in CLL. The presence of large numbers of epithelioid histiocytes should increase suspicion for LPHD; these cells are relatively uncommon in CLL. Finally, a nodular pat- tern, if present, should suggest HD. 2. NLPHD versus Follicular Lymphoma The nodular pattern seen in many cases of LPHD may give rise to a differ- ential diagnosis of follicular lymphoma (CB/CC or centroblastic/centro- cytic lymphoma). The problem is compounded by the fact that the nodules
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