A.C. Feller . J. Diebold Histopathology of Nodal and Extranodal Non-Hodgkin's Lymphomas

Springer Berlin Heidelberg New York Hong Kong London Milan Paris Tokyo

Alfred C. Feller· Jacques Diebold in Collaboration with M. Paulli and A. Le Tourneau

Histopathology of Nodal and Extranodal Non-Hodgkin's Lymphomas (Based on the WHO Classification)

Third, Completely Revised and Updated Edition

With 307 Figures in 345 Parts

, Springer

Prof. Dr. med. Alfred Christian Feller Universitatsklinikum Schleswig-Holstein, Campus Lubeck Institut fUr Pathologie Ratzeburger Allee 160,23538 Lubeck

Professor emeritus Jacques Diebold Hotel-Dieu de Paris Service Central d' Anatomie et de Cytologie Pathologique 1, place du Parvis Notre Dame, 78181 Paris Cedex 04 Frankreich

Library of Congress Cataloguing-in-Publication Data Feller, Alfred C. Histopathology of nodal and extra-nodal non-Hodgkin's lymphomas/Alfred C. Feller, Jacques Diebold. - 3rd, completely rev. and updated ed. p.;cm. Rev. ed. of: Histopathology of non-Hodgkin lymphomas/Karl Lennert. 2nd ed. 1992. Includes bibliographical references and index. ISBN 978-3-642-62224-3 (alk. paper) l. Lymphomas - Histopathology. I. Title: Histopathology of non-Hodgkin lymphomas. II. Diebold, Jacques. III. Lennert, KarL Histopathology of non-Hodgkin lymphomas. IV. Title. [DNLM: l. Lymphoma, Non-Hodgkin-classification. 2. Lymphoma, Non-Hodgkin - patholo­gy. QZ 350 F318h 2003] RC280.L9L4613 2003 616.99'446-dc21 2002042885

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law.

http://www.springer.de

© Springer-Verlag Berlin Heidelberg 2004 Originally published by Springer-Verlag Berlin Heidelberg New York in 2004 Softcover reprint of the hardcover 3rd edition 2004

The use of general descriptive names, registered names, trademarks, 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. Product liability: The publishers cannot guarantee the accuracy of any information about the application of operative techniques and medications contained in this book. In every individ­ual case the user must check such information by consulting the relevant literature.

Cover design: E. Kirchner, D-69121 Heidelberg Typesetting: FotoSatz Pfeifer GmbH, D-82166 Grafelfing Printed on acid-free paper 21/3150 - 5 4 3210

Prof. Dr. med. Alfred Christian FeIler Universitätsklinikum Schleswig-Holstein, Campus Lübeck Institut für Pathologie Ratzeburger Allee 160,23538 Lübeck

Professor emeritus Jacques Diebold Hotel-Dieu de Paris Service Central d' Anatomie et de Cytologie Pathologique 1, place du Parvis Notre Dame, 78181 Paris Cedex 04 Frankreich

ISBN 978-3-642-62224-3 ISBN 978-3-642-18653-0 (eBook) DOI 10.1007/978-3-642-18653-0

Library of Congress Cataloguing-in-Publication Data Feiler, Alfred C. Histopathology of nodal and extra-no da! non-Hodgkin's lymphomas/Alfred C. Feiler, Jacques Diebold. - 3rd, completely rev. and updated ed. p.;cm. Rev. ed. of: Histopathology of non-Hodgkin lymphomas/Karl Lennert. 2nd ed. 1992. Includes bibliographical references and index. ISBN 978-3-642-62224-3 (alk. paper) l. Lymphomas - Histopathology. I. Title: Histopathology of non-Hodgkin lymphomas. H. Diebold, Jacques. III. Lennert, KarL Histopathology of non-Hodgkin lymphomas. IV. Title. [DNLM: l. Lymphoma, Non-Hodgkin-classification. 2. Lymphoma, Non-Hodgkin - patholo­gy. QZ 350 F318h 2003] RC280.L9L4613 2003 616.99'446-dc21 2002042885

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law.

http://www.springer.de

© Springer-Verlag Berlin Heidelberg 2004 Originally published by Springer-Verlag Berlin Heidelberg New York in 2004 Softcover reprint of the hardcover 3rd edition 2004

The use of general descriptive names, registered names, trademarks, 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 genera! use. Product liability: The publishers cannot guarantee the accuracy of any information about the application of operative techniques and medications contained in this book. In every individ­ual case the user must check such information by consulting the relevant literature.

Cover design: E. Kirchner, D-69121 Heidelberg Typesetting: FotoSatz Pfeifer GmbH, D-82166 Gräfelfing Printed on acid-free paper 21/3150 - 5 4 3210

Preface

Roughly 10 years ago, the second edition of "Histopathology of Non-Hodgkin's Lym­phomas" was published. The book gave an excellent overview of predominantly nodal non-Hodgkin's lymphomas. Since then, advances in the field of immunology and the development of new techniques, including new monoclonal antibodies, have allowed a more precise definition of several lymphoma entities as well as a better understanding of the lymphoid system.

Thus, in addition to the entities described in the updated Kiel Classification, reports of new, especially extranodal entities have appeared in the literature. Of these, the most important is MALT-lymphoma, which is one of the most frequently occurring extranodallymphomas. In addition, a large number of rare diseases have been identified, some of which seem to be well-defined clinicopathological entities. An increasing number of monoclonal antibodies that react with formalin fixed material, as well as PCR, sequencing techniques, and the detection of chromosomal abnormalities could aid in establishing the relevance of some of these newly described diseases.

Meetings of The European Association of Hematopathology (EAHP) have opened Europe to the United States and have led to closer contact between the EAHP and its American counterpart, the Society for Hematopathology (SH). Based on these joint discussions, a group of well-known hematopathologists from both sides of the Atlantic suggested the Revised European-American Lymphoma Classification (REAL classification), which in many respects was based on the earlier Kiel classifi­cation. In turn, this encouraged the WHO to formulate a consensus classification, which was eventually approved by both hematopathological societies and issued in 2001.

Around that time, Prof. Karl Lennert encouraged us to rewrite the second edition of the "Histopathology of Non-Hodgkin's Lymphomas". Thus, this new edition is completely based on the WHO classification. However, the reader who is familiar with the previous edition and with the Kiel Classification system will recognize that almost all of the nodal lymphoma entities described in the updated Kiel Classifica­tion appear in the WHO Classification. For this reason, we feel that the WHO Classi­fication is, in many aspects, based on the Kiel Classification.

In order to stress the importance of distinguishing between nodal and extranodal lymphomas and to clearly differentiate between them, we decided to organize dis­cussions of the lymphoma entities according to the organs in which they primarily occur. Thus, a large chapter is devoted to describing primary nodal lymphomas. Since these lymphomas occur in extranodal sites as well, they are then also discussed in the chapters on the various organs, with cross-references to their extensive

VI Preface

description in the chapter on nodal lymphomas, while the organ-specific lymphoma types are described in the respective organ chapters. We think that assigning the dis­tinct lymphoma types to individual chapters makes the book easier to use.

This new edition is intended chiefly for use by pathologists in every-day diagnos­tics, as was true for the previous edition. Although we have included the latest molecular genetic and cytogenetic results, the information provided is limited, as we feel that, even today, the most important diagnostic principle still lies in the mor­phology and the immunohistochemistry. Moreover, no attempt was made at provid­ing a complete citation of the literature since an online search quickly renders cita­tions in a printed book out of date.

For diagnostic purposes, we have included a separate chapter that describes in detail the distinct patterns of lymphoma infiltration in the bone marrow. The last chapter of the book provides technical advice, but the reader should be well aware that the information is very incomplete and in some way provisional as new tech­niques are constantly being developed. However, basic techniques, especially those which are prey to pitfalls arising from the use and interpretation of results of molec­ular genetics, are discussed.

We would not have been able to write this book without the tremendous work of Karl Lennert, who wrote the first and the second edition. We therefore are most grateful to Prof. Lennert for teaching us over many years and for giving us the possi­bility to write this third edition.

We are very grateful for the help of many colleagues. We would like to thank Prof. Marco Paulli for writing the chapters on anaplastic large-cell lymphomas and lym­phomatoid papulosis. Dr. Agnes Le Tourneau provided us with many photomicro­graphs. Prof. Philippe Gaulard supported us with the chapter on hepatosplenic NK/T-celllymphoma, first described by himself. We also want to thank Prof. Hart­mut Merz for interesting discussions on many of the topics of this book. Dagmar Schmoe organized the bibliography with great enthusiasm. We are grateful to the many technicians from the institutes in Lubeck and Paris. It would not have been possible to design and write this book without the tremendous help of our secretar­ies, Catherine Belorgey, Birgit Kalus, Jaqueline Geron and Silja Klein.

It was a great pleasure to co-operate with Springer-Verlag. First of all, we want to thank Dr. Julia Heidelmann for her continuous stimulation and support in finalizing this book. We also thank Wendy Ran for her excellent copy-editing, and Joachim W. Schmidt for his support during the production process as well as his careful atten­tion to the quality of the illustrations.

Lubeck and Paris, Summer 2003 Alfred C. Feller, Jaques Diebold

Contents

1 History of Lymphoma Classification 1.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1 1.2 The Kiel Classification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 2 1.3 The REAL Classification Proposal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 5 1.4 The WHO Classification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 5 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 6

2 Current Status of Lymphoma Classification 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8 2.2 Small- and Large-Cell Versus Low- and High-Grade ................ 10 2.3 Primary Versus Secondary Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . .. 11 2.4 Definition of Immunocytoma and Its Border with Marginal Zone

B-Cell Lymphoma ............................................ 11 2.5 Indistinct Border Between Nodal Marginal Zone B-Cell Lymphoma

and Follicular Lymphoma with Marginal Zone Differentiation. . . . . .. 12 2.6 Grading of Follicular Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 12 2.7 Distinction Between Diffuse Large B-Cell Lymphoma and Burkitt's

Lymphoma: Reproducibility and Value of Subclassification. . . . . . . . .. 12 2.8 Problems in Reproducibly Recognizing Anaplastic Large-Cell Lymphoma

and Lymphoblastic Lymphoma on Purely Morphological Grounds ... 12 2.9 Is Peripheral T-Cell Lymphoma, Unspecified a Distinct Clinico-

pathological Entity or a Catchall Term? .......................... 13 2.10 Neither the WHO nor the EORTC Classification of Cutaneous

Lymphoma Covers Today's Knowledge . . . . . . . . . . . . . . . . . . . . . . . . . .. 13 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 13

3 Epidemiology 3.1 Introduction ................................................. 14 3.2 Statistical Data of the Kiel Lymphoma Registry .................... 16 3.2.1 Age and Sex Distribution ...................................... 16 3.2.2 Malignant Lymphoma of Childhood ............................. 16 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 17

4 Nodal B-Cell Lymphoma 4.1 Precursor B-Cell Lymphoblastic Leukemia ........................ 19 4.2 Peripheral B-Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 22

VIII Contents

4.2.1 Small-B-Cell Lymphoma ....................................... 22 4.2.1.1 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. . . .. 23 4.2.l.2 Lymphoplasmacytic Lymphoma - Partially Corresponding to

Macroglobulinemia Waldenstrom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 34 4.2.1.3 Hairy Cell Leukemia .......................................... 39 4.2.1.4 Plasmacytoma ............................................... 42 4.2.1.5 Nodal Marginal Zone B-Cell Lymphoma ......................... 44 4.2.1.6 Follicular Lymphoma ......................................... 53 4.2.1.7 Mantle Cell Lymphoma ........................................ 66 4.2.2 Large-B-Cell Lymphoma ....................................... 75 4.2.2.1 Diffuse Large-B-Cell Lymphoma - Common Features. . . . . . . . . . . .. 75 4.2.2.2 Diffuse Large-B-Cell Lymphoma - Morphological Variants. . . . . . . .. 80 4.2.2.3 Diffuse Large-B-Cell Lymphoma - Clinical Variants. . . . . . . . . . . . . .. 99 4.2.3 Burkitt's Lymphoma ......................................... 99 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 107

5 Nodal and Leukemic NK/T -Cell Lymphoma 5.1 Precursor T-Lymphoblastic Leukemia/Lymphoma ................ 121 5.2 Peripheral NK/T-Cell Lymphoma .............................. 125 5.2.1 Peripheral NK/T-Cell Lymphoma - Predominately Leukemic ....... 125 5.2.1.1 T-Cell Chronic Lymphocytic/Prolymphocytic Leukemia ........... 125 5.2.l.2 Adult T-Cell Leukemia/Lymphoma ............................. 128 5.2.2 Peripheral NK/T-Cell Lymphoma Predominately Nodal ............ 132 5.2.2.1 Angioimmunoblastic T-Cell Lymphoma ......................... 132 5.2.2.2 Peripheral T-Cell Lymphoma, Unspecified ....................... 144 5.2.2.3 Mycosis Fungoides/Sezary's Syndrome Secondary to the

Lymph Node ................................................ 163 5.2.2.4 Anaplastic Large-Cell Lymphoma (T and Null Types) ............. 166 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177

6 6.1 6.2 6.2.1 6.2.1.1 6.2.1.2 6.2.1.3 6.2.1.4 6.2.1.5 6.2.2 6.2.2.1 6.2.2.2 6.2.2.3 6.3 6.3.1 6.3.2 6.3.3 6.3.3.1 6.3.3.2

Extranodal Lymphoma Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 186 Gastrointestinal Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 187 B-Cell Lymphoma ........................................... 187 Extranodal Marginal Zone B-Cell Lymphoma of MALT. . . . . . . . . . .. 187 Intestinal Follicular Lymphoma ................................ 197 Multiple Lymphomatous Polyposis - Intestinal Mantle Cell Lymphoma 198 Diffuse-Large-B-Cell Lymphoma of Gastrointestinal Tract ......... 200 Burkitt's Lymphoma of the Gastrointestinal Tract. . . . . . . . . . . . . . . .. 204 Primary Gastrointestinal T-Cell Lymphoma ..................... 205 Enteropathy-Type T-Cell Lymphoma ........................... 205 NK/T-Cell Lymphoma, Nasal Type ............................. 212 Anaplastic Large-Cell Lymphoma .............................. 213 Lymphoma of the Upper Aerodigestive Tract ..................... 213 Lymphoma of the Oral Cavity ................................. 213 Lymphoma ofWaldeyer's Ring and the Pharynx .................. 214 Lymphoma of the Nasal Cavity and Paranasal Sinuses . . . . . . . . . . . .. 217 B-Cell Lymphoma ........................................... 217 Extranodal NK/T-Cell Lymphoma - Nasal Type .................. 218

6.3.4 6.4 6.5 6.5.1 6.5.2 6.5.3 6.6 6.6.1 6.6.2 6.6.3

6.6.4 6.6.5

6.6.6 6.7 6.7.1 6.7.1.1 6.7.1.2 6.7.1.3 6.7.1.4

6.7.1.5 6.7.1.6 6.8 6.8.1 6.8.1.1 6.8.1.2 6.8.2 6.9 6.9.1 6.10 6.10.1

6.10.1.1 6.10.1.2 6.10.1.3 6.10.1.4 6.10.1.5 6.10.1.6 6.10.1.7 6.10.1.8 6.10.1.9 6.10.2 6.10.2.1 6.10.2.2 6.10.2.3 6.10.2.4

Contents IX

Lymphoma of the Larynx and Trachea . . . . . . . . . . . . . . . . . . . . . . . . .. 222 Malignant Lymphoma of the Major Salivary Glands ............... 223 Lymphoma of the Eye, Lachrymal Glands, and Orbit .............. 227 Lymphoma of the Conjunctiva, Eyelids, Lachrymal Glands, and Orbit 227 Lymphoma of the Uvea and Retina (Similar to CNS Lymphoma) .... 227 Primary Lymphoma of the Eye, Lachrymal Glands, and Orbit ...... 228 Lymphoma of the Mediastinum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 231 Mediastinal (Thymic) Large-B-Cell Lymphoma .................. 231 Extranodal Marginal Zone B-Cell Lymphoma of the Thymus . . . . . .. 235 Mediastinal Involvement in Precursor T- or B-Cell Lymphoblastic Lymphoma ................................................. 235 Mediastinal Involvement in Small-B-Cell Lymphoma .............. 236 Mediastinal Involvement in Large-B-Cell Lymphoma Other Than Primary Mediastinal Large-B-Cell Lymphoma and Burkitt's Lymphoma ................................................. 236 Mediastinal Involvement in NK/T -Cell Lymphoma. . . . . . . . . . . . . . .. 236 Lymphoma of the Lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 236 Primary Lymphoma of the Lung ............................... 236 Extranodal Marginal Zone B-Cell Lymphoma of MALT . . . . . . . . . . .. 236 Primary Diffuse Large-B-Cell Lymphoma of the Lung ............. 239 Primary Lung Intravascular Large-B-Cell Lymphoma ............. 239 Large B-Cell Lymphoma Secondary to Liebow's Lymphomatoid Granulomatosis ............................................. 240 Primary Lung Plasmacytoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 242 Primary NK/T-Cell Lymphoma of the Lung ...................... 243 Lymphoma of the Pleura. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 243 Primary Lymphoma of the Pleura . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 243 Primary Effusion Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 243 Pyothorax-Associated Primary Lymphoma ...................... 245 Secondary Pleural Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 247 Lymphoma of the Heart ...................................... 247 Primary Cardiac Lymphoma .................................. 247 Splenic Lymphoma .......................................... 248 Primary Splenic Lymphoma or Lymphoma with a Splenic Predominance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 248 Hairy Cell Leukemia ......................................... 251 Splenic Marginal Zone Lymphoma ............................. 254 Primary Splenic Lymphoplasmacytic Lymphoma. . . . . . . . . . . . . . . .. 259 Plasmacytoma .............................................. 261 B-Prolymphocytic Leukemia .................................. 261 Large B-Cell Lymphoma of the Spleen .......................... 262 Hepatosplenic T-Cell Lymphoma ............................... 263 T-Cell Large Granular Lymphocytic Leukemia ................... 267 Other Types of Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 269 Secondary Splenic Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 269 Small-B-Cell Lymphoma ...................................... 269 Other Types of B-Cell Lymphoma .............................. 273 Peripheral NK/T-Cell Lymphoma .............................. 273 Precursor Cell Neoplasias: B- and T-Lymphoblastic Lymphoma ..... 274

X Contents

6.11 Lymphoma of the Liver ....................................... 274 6.11.1 Primary Lymphoma of the Liver ............................... 274 6.11.1.1 Primary Lymphoma Presenting as a Tumorous Infiltrate of the Liver 274 6.11.1.2 Primary Hepatic Lymphoma Presenting as Severe Hepatic Disease .. 277 6.1l.2 Secondary Lymphoma of the Liver ............................. 277 6.12 Lymphoma of the Breast, Reproductive, and Urinary Systems ...... 278 6.12.1 Malignant Lymphoma of the Breast. ............................ 278 6.12.1.1 Primary Lymphoma of the Breast .............................. 278 6.12.l.2 Secondary Lymphoma of the Breast ............................ 281 6.12.2 Malignant Lymphoma of the Uterus ............................ 281 6.12.2.1 Primary Uterine Lymphoma ................................... 281 6.12.2.2 Addendum: Primary Lymphoma of the Vagina ................... 282 6.12.2.3 Secondary Uterine and Vaginal Lymphoma ...................... 282 6.12.3 MalignantLymphoma of the Ovary ............................. 282 6.12.3.1 Primary Lymphoma of the Ovary .............................. 282 6.12.3.2 Secondary Lymphoma of the Ovary ............................ 284 6.12.4 Lymphoma of Testis .......................................... 285 6.12.5 Malignant Lymphoma of the Prostate ........................... 286 6.12.6 Lymphoma of the Kidney ..................................... 287 6.12.6.1 Primary Lymphoma of the Kidney ............................. 287 6.12.6.2 Secondary Kidney Lymphoma ................................ 288 6.12.7 Malignant Lymphoma of the Urinary Bladder . . . . . . . . . . . . . . . . . . .. 288 6.13 Endocrine Gland Lymphoma .................................. 289 6.13.1 Malignant Lymphoma of the Thyroid Gland ..................... 289 6.13.2 Malignant Lymphoma of the Adrenal Gland ..................... 292 6.14 Cutaneous Lymphoma ........................................ 294 6.14.1 Primary Cutaneous B-Cell Lymphoma .......................... 295 6.14.1.1 Cutaneous Marginal Zone B-Cell Lymphoma/SALT ............... 295 6.14.1.2 Follicular Lymphoma ........................................ 299 6.14.1.3 Plasmacytoma .............................................. 302 6.14.1.4 Diffuse Large-B-Cell Lymphoma ............................... 302 6.14.2 Cutaneous T-Cell Lymphoma .................................. 305 6.14.2.1 Mycosis Fungoides - Classical Type ............................ 305 6.14.2.2 Sezary's Syndrome ........................................... 311 6.14.2.3 Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders ... 311 6.14.2.4 Primary Cutaneous NK/T-Cell Lymphoma ....................... 322 6.15 Lymphoma of Soft Tissues .................................... 327 6.16 Lymphoma of the Bone ....................................... 328 6.16.1 Primary Lymphoma of Bone .................................. 328 6.16.2 Secondary Bone Lymphoma ................................... 330 6.17 Lymphoma of the Central Nervous System ....................... 330 6.18 Intravascular Large-B-Cell Malignant Lymphoma. . . . . . . . . . . . . . . .. 335 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 338

7 Plasma Cell Proliferations 7.1 Plasma Cell Myeloma/Bone Marrow Plasmacytoma ............... 364 7.1.1 Clinical Variants ............................................. 370 7.1.1.1 Diffuse Decalcifying Myelomatosis ............................. 370 7.1.1.2 Osteosclerotic Myeloma ...................................... 370

Contents XI

7.1.1.3 Nonsecretory Myeloma ....................................... 371 7.1.1.4 Solitary Myeloma ............................................ 371 7.1.1.5 Plasma Cell Leukemia ........................................ 371 7.1.1.6 Variants with Peculiar Clinical Behavior ......................... 371 7.2 Extraosseous (Extramedullary) Plasmacytoma ................... 371 7.3 Associated Diseases .......................................... 372 7.3.1 Castleman's Disease .......................................... 372 7.3.2 POEMS Syndrome ........................................... 372 7.3.3 Primary Amyloidosis ......................................... 372 7.3.4 Light- and/or Heavy-Chain Deposition Diseases .................. 373 7.4 Heavy-Chain Diseases ........................................ 374 References .......................................................... 376

8 8.1

8.1.1 8.1.2 8.1.3 8.1.4 8.1.5 8.1.6 8.1.7 8.1.8 8.2

Lymphoma Occurring in a Setting of Immunodeficiency Lymphoproliferative Disorders Associated with Congenital Immunodeficiencies ......................................... 379 Ataxia-Telangiectasia ......................................... 380 Wiskott-Aldrich Syndrome .................................... 381 Common Variable Immunodeficiency Disorder .................. 381 Severe Combined Immunodeficiency . . . . . . . . . . . . . . . . . . . . . . . . . .. 382 X-linked Lymphoproliferative Disorder ......................... 383 Hyper-IgM Syndrome ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 383 JOB Syndrome .............................................. 384 Nijmegen Breakage Syndrome ................................. 384 Lymphoma and Lymphoproliferative Disorders Associated with Acquired Immunodeficiency .................................. 385

8.2.1 HIV -Related Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 385 8.2.2 Post-transplant Lymphoproliferative Disorders ................... 389 8.2.2.1 Plasmacytic Hyperplasia and Infectious-Mononucleosis-like PTLD .. 390 8.2.2.2 Polymorphic PTLD .......................................... 390 8.2.2.3 Monomorphic B-Cell PTLD ................................... 391 8.2.2.4 Monomorphic T-Cell PTLD ................................... 392 8.2.2.5 Hodgkin's-Like PTLD ........................................ 392 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 392

9 9.1 9.1.1 9.1.2 9.1.2.1 9.1.2.2 9.1.2.3 9.1.2.4 9.1.3 9.2 9.2.1 9.2.2 9.2.3 9.2.3.1

Practical Guidelines for Lymphoma Diagnosis in Bone Marrow Patterns of Involvement ...................................... 396 Paratrabecular Infiltrates ..................................... 396 Intertrabecular Infiltrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 397 Interstitial Infiltrate .......................................... 397 Nodular Infiltrate ............................................ 397 Massive Infiltrate .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 398 Monocellular Dispersion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 399 Intrasinusoidal Infiltrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 400 Associated Lesions or Modifications ............................ 402 Reticulum Fibers Framework .................................. 402 Vascular Modifications ....................................... 402 Reactive Changes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 402 Interstitial Edema ........................................... 402

XII Contents

9.2.3.2 9.2.3.3 9.2.3.4 9.2.3.5 9.2.3.6 9.3

9.3.1 9.3.1.1 9.3.1.2 9.3.1.3 9.3.1.4 9.3.1.5 9.3.1.6

9.3.1.7 9.3.1.8 9.3.1.9 9.3.2 9.3.2.1 9.3.2.2 9.3.3 9.3.4

9.3.5 9.3.5.1 9.3.5.2 9.3.5.3 9.3.5.4 9.3.5.5 9.3.5.6 9.3.5.7 9.4 9.4.1 9.4.2 9.4.3 9.4.4 9.4.5 9.4.6

Polyclonal Plasmacytosis ..................................... 402 Reactive Lymphoid Nodules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 402 Chronic Inflammation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 402 Eosinophilic Necrosis ........................................ 403 Modifications of the Normal Hematopoietic Cell Lines ............ 403 Diagnosis of Bone Marrow Involvement According to the Different Types of Lymphoma ......................................... 403 Small B-Cell Lymphoma (Kroft et aI. 1995) ...................... 403 B-Cell Chronic Lymphocytic Leukemia ......................... 403 B-Prolymphocytic Leukemia .................................. 403 Lymphoplasmacytic Lymphoma ............................... 403 Follicular Lymphoma ........................................ 403 Mantle Cell Lymphoma . . . . . . . . . . . . . . . . .. . . . .. . . . . .. . . . . . . .... 404 Primary Splenic and Nodal and Extranodal Marginal Zone Lymphoma ................................................. 404 Hairy Cell Leukemia ......................................... 404 Myeloma ............................ . . . . . . . . . . . . . . . . . . . . . .. 404 Differential Diagnosis ........................................ 404 Large B-Cell Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 405 T-Cell-RichlHistiocyte-Rich Large-B-Cell Lymphoma ............. 405 Intravascular Large B-Cell Lymphoma .................. . . . . . . .. 405 Burkitt's Lymphoma ......................................... 405 Precursor Cell Lymphoma (B- and T-Cell Lymphoblastic Lymphoma or Acute Leukemia) .......................................... 405 NK/T-Cell Lymphoma ........................................ 405 T-Prolymphocytic Leukemia .................................. 405 T-Cell Large Granular Lymphocytic Leukemia ................... 405 Peripheral T-Cell Leukemia Lymphoma, Unspecified .............. 406 Peripheral T-Cell-Lymphoma, Angioimmunoblastic .............. 406 Anaplastic Large-Cell Lymphoma ...................... . . . . . . .. 406 Hepatosplenic T-Cell Lymphoma ............................... 406 General Comments .......................................... 406 Differential Diagnosis ........................................ 406 Reactive Lymphoid Nodules .................................. , 406 Reactive Intravascular Lymphocytosis .......................... 407 Hodgkin's Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 407 Non-lymphoid Acute Leukemia ................................ 407 Systemic Mastocytosis ....................................... , 407 Undifferentiated Carcinoma .................................. , 407

References ......................................................... , 407

10 Practical Advice: Methods for the Diagnosis of Malignant Lymphoma 10.1 The Diagnosis of Malignant Lymphoma ......................... 409 10.1.1 Practical Tips ............................................... 409 10.2 Immunohistochemistry and Molecular Clonality Analysis in the

Diagnosis ofLymphoma ..................................... , 414 References ......................................................... , 420

Subject Index ....................................................... 421