HANOBUCH OER SPEZIELLEN PA THOLOGISCHEN ANATOMIE UNO HISTOLOGIE

BEGRONDET VON

O. LUBARSCH UND F. HENKE

FORTGEFOHRT VON

R. ROSSLE

HERAUSGEGEBEN VON

E. UEHLINGER ZURICH

ERSTER BAND

BLUT· KNOCHENMARK· LYMPHKNOTEN· MILZ

DRITTER TElL

LYMPHKNOTEN/LYMPH NODES BANDTEIL B

MALIGNANT LYMPHOMAS

OTHER THAN HODGKIN'S DISEASE

SPRINGER-VERLAG

BERLIN· HEIDELBERG· NEW YORK

1978

MALIGNANT LYMPHOMAS OTHER THAN HODGKIN'S DISEASE

HISTOLOGY· CYTOLOGY· ULTRASTRUCTURE· IMMUNOLOGY

BY

KARL LENNERT

IN COLLABORATION WITH

NOBORU MOHRI· HARALD STEIN EDWIN KAISERLING • HANS KONRAD MOLLER-HERMELINK

TRANSLATED BY

FREDERICK D. DALLENBACH AND MARTHA SOEHRING

WITH 287 FIGURES, 47 IN COLOR

425 SEPARATE ILLUSTRATIONS

SPRINGER-VERLAG

BERLIN· HEIDELBERG· NEW YORK

1978

Prof. Dr. med. K. LENNERT

Dr. med. habil. H. STEIN

Dr. med. habil. E. KAISERLING

Dr. med. habil. HANS KONRAD MULLER-HERMELINK

Pathologisches Institut der Universitiit, HospitalstraBe 42, 0-2300 Kiel

Prof. Dr. med. N. MOHR!

Tokyo University Branch Hospital, Bunkyoku, Mejirodai 3-28-6, 112 Tokyo (Japan)

ISBN-13: 978-3-642-81094-7 e-ISBN-13: 978-3-642-81092-3 DOl: 10.1007/978-3-642-81092-3

Library of Congress Cataloging in Publication Data (Revised). Henke, Friedrich, 1868-1943, ed. Handbuch der speziellen pathologischen Anatomie und Histologie. Each vol. has also special t.p. Edited 1934- by O. Lubarsch, F. Henke, and R. ROssIe; 1969- by E. Uehlinger. Includes bibliographies. On t.p. ofvols. issued from 1969-- : Begriindet von O. Lubarsch und F. Henke. Fortgefiihrt von R. RossIe. Hrsg. von E. Uehlinger. Vol. 3, pt. 5 entirely in English. Contents: I. Bd. Blut. Knochenmark. Lymphknoten. Milz. 3. Bd. Atmungswege und Lungen. [etc.] Anatomy, Pathological. 2. Histology, Pathological. I. Lubarsch, Otto, 1860-1933, joint ed. II. RossIe, Robert, 1876-1956, ed. III. Uehlinger, Erwin A., ed. IV. Title.

RB25.H4 616.07 25-11247

The use of general descnptive names, trade names, trade marks, etc. in this publication, even if the former are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely by anyone. This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law whe!" copies are made for other than private use, a fee is payable to the publisher, the amount of the fee to be determined

by agreement with the publisher. © by Springer-Verlag, Berlin· Heidelberg 1978 Softcover reprint of the hardcover I st edition 1978

2122/3120-543210

To

my wife Amanda and

my daughters Monika and Claudia

Wc; "WIWVeVW erwye lv T0 :naeovn :neet aVTOV TOVTOV OV cptAo­C10CPWC; [xewalA.' wCJ:n;ee of :navv Ma{~eVTot cptAOVDtWC;. "at yae l"e'ivOt {hav :neet TOV ap,CPtC1{JrITWC1W, a:nn pi'll [xet :neet cD'll a'll 0 MyoC; fI ov cpeOV't'tCoVC1W, a:nwc; ~i a. aVTot WevTo TavTa ~o~et TO'iC; :naeoVcrw, TOVTO :neO{}vp,oVvTat .

... since that very issue is one that I may not be facing as a philosopher should, but rather as one bent on victory, like those quite devoid of education. They too, when they dispute about something, care nothing for the truth of the matter under discussion, but are eager only that those present shall accept their own thesis. SOCRATES in PLATO'S Phaedo (91 a).

Preface The first review of malignant lymphomas, other than Hodgkin's disease,

in this Handbook series was given by C. STERNBERG in 1926. It comprised seven pages. The magnitude of this second presentation of the same subject reflects the enormous increase in knowledge gathered over the past 50 years. Experimental immunology and lymphocyte research of the past two decades are especially to blame. They forced us to reconsider lymphocytic reactions and neoplasms and to correlate these with new experimental data. In order to make such correlations, it was necessary to apply the tools of experimental immunology to the definition of the cells involved. In this way, it was possible not only to redefine the normal and reactive cells of lymphatic tissue, but also to come to a better understanding of the malignant neoplasms of these cells.

In collaboration with E. KAISERLING, N. MOHRI, H.K. MULLER-HERMELINK, and H. STEIN, I have endeavored since 1970 to study and to classify the malignant lymphomas in the light of modern lymphocyte research. Our investigations made use of both special morphologic methods (Giemsa staining in sections, imprints, cytochemistry, and electron microscopy) and immunologic techniques. The major morphologic groundwork for our lymphoma studies was laid by the experimental work of F.J. KEUNING and his school. With the help of the methods we applied, particularly the immunologic techniques, it was possible to confirm some of our earlier, morphologically defined concepts, e.g., the morphologic identity of germinal-center cells and the tumors of these cells. It was also possible, however, to eliminate certain errors made in the past. It was shown, for instance, that most cases of "reticulosarcoma" are actually immuno­blastic lymphomas. Furthermore, some new entities were discovered, e.g., lympho­plasmacytoid immunocytoma.

These and other data encouraged us to make an attempt to draft and pursue a new concept of the malignant lymphomas other than Hodgkin's disease, which are now generally known as "non-Hodgkin's lymphomas". We were honored to have our concept accepted in principle by the other members of the European Lymphoma Club, R. GERARD-MARCHANT, IRIS HAMLIN, F. RILKE,

VIII Preface

A.G. STANSFELD, and J.A.M. VAN UNNIK. In joint discussions in 1974, the Club worked out a new terminology that was acceptable to all members and will hopefully be acceptable to other pathologists. Since then, it has been called the Kiel Classification. We are also pleased that the clinicians belonging to the Kiel Lymphoma Study Group-foremost A. STACHER and G. BRITTINGER­have been able to present preliminary data on the clinical relevance of the new classification. Finally, our optimism was fortified by the findings of R.J. LUKES and R.D. COLLINS, which largely concur with ours in both concept and practical significance.

This book is divided into six main sections. First, there is a chapter on normal cytology that supplements and, in some respects, revises the presentation given in Part A of this Handbook (1961). H.K. MULLER-HERMELINK played a major role in the writing of the first chapter. The second chapter is a brief description of the light-microscopic techniques that are used in our laboratories and have proved to be suitable for a precise diagnosis of lymph-node diseases. In the third chapter, a number of basic considerations are presented in relation to malignant lymphomas and their classification. Part Four is the focus of this book. In separate chapters on each type of lymphoma, it describes the histologic, cytologic, and cytochemical features of each one. Furthermore, in conformity with Part A, it provides data on the occurrence, localization, diag­nosis, differential diagnosis, and prognosis of the various types of lymphomas. N. MOHRI of Tokyo had a major part in the 'preparation of the histologic and statistical data. In Part Five, E. KAISERLING presents the ultrastructure of the malignant lymphomas. Part Six was written by H. STEIN and describes immunologic techniques and the results of their application to lymphomas.

Hodgkin's disease and the malignant neoplasms of reticulum cells have been left out of this book on purpose. Although much is known about Hodgkin's disease, we are still looking for answers to fundamental questions, e.g., the origin of Sternberg-Reed cells. The whole concept of reticulosarcoma and malig­nant reticulosis (histiocytosis) was upset by the separation of immunoblastic lymphoma and will have to be reconsidered and studied with new methods.

The magnitude of this book may be appalling at first. Nevertheless, it is incomplete in many respects. For instance, the historical review of some of the lymphomas is unjustly confined to the literature written in English, French, and German. Readers who are familiar with other languages are asked to forgive this selection. I recommend the reader who is in a hurry, i.e., the pathologist who is looking for quick information under the pressure of daily routine, to concentrate on the sections Definition and Diagnosis in each chapter of Part Four and on the illustrations. The most important diagnostic criteria are summarized in tabular form.

Since the publishers gave us no other choice but to publish this book in English, we were at a loss for a good translation. So we were all the more thankful thatF.D. DALLENBAcH, Deutsches Krebsforschungszentrum, Heidelberg, spontaneously offered to translate the manuscript - truly a great sacrifice for an active scientist. He translated about half of the book. The other half was translated with help of Mrs. M. SOEHRING, our secretary from Boston. A.G. STANSFELD, Department of Pathology, St. Bartholomew's Hospital, Lon-

Preface IX

don, was then kind enough to read most of the English manuscript from the viewpoint of a lymphoma expert and to make helpful suggestions.

The original manuscript of Parts Two, Three, and Four was delivered to the translator in May 1975. Later, we were able to include references that appeared up to July 1, 1976. More recent references could merely be mentioned here and there or added to the footnotes. Parts One and Five were completed in June 1976; again, more recent literature could not be taken into full consider­ation. Part Six was not ready until January 1977; the literature cited in that chapter is, understandably, the most up-to-date. It is evident from the text of the chapters written in 1975, however, that the investigations of the past two years have not necessitated any significant changes.

We are aware that our concept will not be the last word. The future will have to show how far it fulfills the ultimate criterion of scientific truth, viz.: the ability to forecast events. Nevertheless, we believe that it is time to abandon all the old lymphoma concepts that pathologists have become so fond of, and to embark on a new one that takes account of both the structure and the function of the tumor cells. One should no longer cling to old, scientifically incorrect classifications, even if they have so far been clinically useful-there are no arguments indicating that our new classification is not just as clinically useful.

In London in 1973, H. RAPPAPORT quoted an old saying, which is symboli­cally inscribed on a bridge: "Alles ist nur ein Vbergang" -everything is merely a transition. Our classification may be seen as such a transition. Its purpose is to help the sufferers from lymphoma without hindering scientific progress.

Kiel, February 1978 KARL LENNERT

Acknowledgements

This book is not the work of just one or five persons-it is the fruit of manifold cooperation, friendship, and criticism. We are therefore indebted to many people for their assistance and guidance.

A decisive role in the genesis of this book was played by our clinical partners, particularly those who belong to the Kiel Lymphoma Study Group, which was originally initiated by Professor Dr. A. STACHER, Vienna, and is thriving under the leadership of Professor Dr. G. BRITTINGER, Essen. The groups working in the fields of leukemia and oncology in childhood led by Professor Dr. G. LANDBECK, Hamburg, and Professor Dr. B. KORNHUBER, Frankfurt, made a similar contribu­tion to the lymphomas of childhood. Finally, there were surgeons and otolaryngologists at the University of Kie\ (under the leadership of Professor Dr. B. LOHR and Professor Dr. E. MULLER, respectively) and at several other German hospitals who were willing to cooperate with us. All the mentioned clinicians cooperated by sending us fresh tissue, imprints, and tumor tissue specially fixed for electron microscopy. This was the crucial reason why we were able to work out a classifica­tion based on morphologic (histologic, cytologic, and ultrastructural), cytochemical, and immuno­logic studies.

The hours invested by our clinical colleagues were innumerable. The time spent per case often amounted to several hours. This book is a commemorative to such unique, selfless cooperation. Not to be forgotten are the pathologists who normally work with the cooperating clinicians-they willingly agreed to our receiving material from the clinicians and were contented with a copy of our diagnosis. Especially helpful colleagues from the very first were Professor Dr. ALEXANDRA PIRINGER-KuCHINKA, Vienna; Professor Dr. H.-W. ALTMANN, Wiirzburg; Professor Dr. H. BREDT, Mainz; Professor Dr. E. LANGER, Munich; and Professor Dr. W. MULLER, Essen.

A second group of colleagues who played a crucial role in the genesis of this book was the so-called European Lymphoma Club, which is made up of Professor Dr. N. CHELLOUL t, Paris; Dr. R. GERARD-MARCHANT, Villejuif; Dr. IRIS M.E. HAMLIN, London; Professor Dr. F. RILKE, Milan; Dr. A.G. STANSFELD, London; Professor Dr. J.A.M. VAN UNNIK, Utrecht; and the author (K.L.). All members of the Club have advocated the jointly created Kiel Classification in their own countries and elsewhere. This scientific and amicable solidarity among lymphoma experts from five different European countries also set an example for cooperation in Europe, i.e., irrespective of national borders. The many suggestions, corrections, and comments made by our Club colleagues are reflected in this book. Their constant support as friends encouraged us to stay on the path and to present this publication.

The writer is also indebted to all the people who work at our Institute for the loyalty they showed, either directly or indirectly, during the whole project-directly by being actively involved in the project; indirectly by doing more than their normal share of work to give us time to prepare this book. The indirect helpers are too numerous to mention by name; but they are represented by my head assistants Professor Dr. L.-D. LEDER and Professor Dr. H.-J. STUTTE; Professor Dr. D. HARMS, Head of the Department of Paidopathology; Professor Dr. M.R. PARWARESCH, who introduced us to polyacrylamide-gel electrophoresis; and Dr. E.-W. SCHWARZE, who offered me constant assistance in the work of the Lymph Node Registry.

XII Acknowledgments

Directly involved in the preparation of this book were: Mrs. M. SOEHRING, who not only helped to translate, but also prepared the English manuscript

for publication with a critical eye and good judgment. She also read and corrected all of the proofs with perfection.

Miss K. SOHRWEIDE, who typed the German manuscript, and Mrs. S. SOOTER, who typed parts of the English manuscript.

Professor Dr. H. UHLIG, who helped us prepare the color photomicrographs with a Zeiss Ultraphot II (photomicroscope).

Mrs. H. BLESSMANN, who developed and enlarged the photomicrographs. Mrs. R. KOPKE, who was responsible for enlarging the electron micrographs. Mr. W. VATER, who did all of the graphic work with utmost precision and competence. Mrs. A. ROHDE and Mrs. D. SCHMIDT, who were responsible for the precise preparation of

the references. Mrs. SCHMIDT also read and corrected the proofs of the references and footnotes. Mrs. A. LURZ and Mr. W. GLUCK, who prepared the histologic sections of excellent technical

quality. Mrs. B. PETERSEN, who assisted with the cytochemical reactions. Mrs. I. HORN, Mrs. K. KONIG, Miss C. MADER, Miss P. MICHEELS, and Mr. E. GROSSKOPF,

who assisted with the immunologic investigations. Miss D. AECKERLE, Miss O. BRACKER, Miss F. KHUEN, Miss F. MARTEN, Miss M. NEUBERT,

and Miss A. VOGLER, who provided excellent technical assistance in our electron-microscopic laboratory.

The preparation of the statistical data was possible only through the effort of the secretarial and technical assistants at our Lymph Node Registry, Mrs. C. BANNER and Mrs. I. KIEKBUSCH. Professor Dr. G. GRIESSER and his assistant Mr. J.D. Voss from the Department of Medical Statistics and Documentation helped us in every way with the computerization and storage of our data.

Dr. R. SATODATE, Dr. R. SUGIYAMA, Dr. E.-W. SCHWARZE, Mrs. D. HELBRON, and Mrs. U. MULLER-HERMELINK made contributions to certain chapters and the application of certain special techniques. These are mentioned in the text.

The loyal support of those who work at our Institute never faltered, from the time we started to write this book in 1974 until its completion. In addition, however, I received much help, stimula­tion, and criticism from colleagues both in and outside Germany. I can name only a few of the many colleagues who gave us substantial support:

Professor Dr. Dr. E. UEHLINGER, the Editor of this Handbook, has not only encouraged me with constant sympathy for two decades, but also read this book with a critical eye and made valuable suggestions.

Professor W.ST.e. SYMMERS, London, pointed out important matters of style and terminology. Professor Dr. H. ZUR HAUSEN, Erlangen, made a significant contribution to the serology of

EBV infection in Burkitt's tumor and Iymphoepithelial carcinoma. Dr. W. HIJMANS, Rijswijk, and Dr. P. LOPES CARDOZO, Leiden, an inimitable pioneer in cytol­

ogy, were a source of stimulation in fruitful discussions. Dr. F.e. COLLIER, Rutherford, Professor 1. FIORE-DoNATI, Verona, and Dr. RENATE REIF,

Zrifin, read various parts of this book. We are grateful for their comments and suggestions. Finally, we wish to thank all skeptics for often questioning us and forcing us to exercise self­

scrutiny. Many of the studies behind this book, especially those of our immunologic laboratory, would

not have been possible without the generous financial support of the Deutsche Forschungsgemein­schaft (Sonderforschungsbereich Ill) and the Kind-Philipp-Stiftung.

The publishers also contributed all they could to the success of this book. Dr. H. GOTZE accepted and encouraged its publication even before it was written-an expression of unearned trust and his own optimism. Mr. W. BERGSTEDT and Mr. K. TEICHMANN were always willing to help, even when adverse circumstances might have earned their resentment. The color illustrations are worthy of praise, and we thank the Graph. Kunstanstalt Gustav Dreher GmbH, Stuttgart, for their effort.

We are much indebted to all the many people who contributed to the success of this book. They all have given more than the actual writers, whose main task was to interpret and verbalize the results of much hard work.

Contents

Part One The Cytologic, Histologic, and Functional Bases for a Modern Classification of Lymphomas By H.K. MULLER-HERMELINK and K. LENNERT.

I. Lymphocytes 2

A. A New Understanding of Lymphocyte Physiology 2 1. Lymphocytes Are Not Obligate End Cells. . . 3 2. Lymphocytes Are a Heterogeneous Group of Cells with Different

Origins and Functions . 4 3. Lymphocytes Are Destined to Migrate 6

B. Identification of B- and T-Lymphocytes . 9 1. Functional Identification of Human T-Lymphocytes 12 2. Functional Identification of Human B-Lymphocytes 14 3. Lymphocytes of Cell-Mediated, Antibody-Dependent Cytotoxicity (K-cells) 17

C. Cooperation of B- and T-Lymphocytes ....... 19 D. Derivation of Lymphocytes from the Hemopoietic Stem Cell. 20

II. Immunoblasts (Basophilic Stem Cells) . 24

III. Plasma Cells 26 Addendum: The So-Called T-Associated Plasma Cell 31

IV. Histomorphology of the B-Cell Region. 33

A. Cytology of Germinal Centers. 33 B. Phases of Germinal-Center Development 38 C. Kinetics of Germinal-Center Cells 40 D. The Function of Germinal Centers 43

V. Histomorphology of the T-Cell Region. 45

VI. Histochemistry of B- and T-Cell Regions. 48

VII. Stationary Elements of the Lymph Node. 51

A. Reticulum Cells . . . . . . . 51 1. Histiocytic Reticulum Cell . 53

Addendum: Epithelioid Cell. 55 2. Fibroblastic Reticulum Cell (" Dictyocyte") . 58 3. Dendritic Reticulum Cell (Long-Branching Nonphagocytosing Reticulum Cell) 59 4. Interdigitating Reticulum Cell. . . . . . . . . . . . . . . . . . . . .. 65

XIV Contents

B. Sinus Endothelial Cells . . . . . . . . . . . . . . . . . . I. Endothelial Cells of the Marginal Sinus. . . . . . . . . . 2. Endothelial Cells of the Intermediate and Medullary Sinuses

C. Mast Cells . . . . . . . . . . . . . . . . . . . . . . .

69 69 70 70

Part Two Methodologic Prerequisites for a Differential Diagnosis of Lymphomas By K. LENNERT ............................. .

Appendix: Some Stainings and Cytochemical Reactions Used in Our Laboratories.

Part Three Classification of Non-Hodgkin's Lymphomas By K. LENNERT . . . . . . . . . . . . . . . . .

I. Historical Review of the Classifications of Lymphomas

II. Some Ideas for a Modern Lymphoma Classification. .

III. A Simplified Cellular Scheme as a Basis for a Modern Classification of Lymphomas . . . . . . . . . . . . . . . .

IV. The Kiel Classification and Its Clinical Relevance .

V. Incidence of the Different Types of Lymphoma in our Material .

Part Four Histopathology and Diagnosis of Non-Hodgkin's Lymphomas

73

77

83

83

93

98

101

106

By K. LENNERT and N. MOHR!. . . . . . . . . . . . III

I. Malignant Lymphomas of Low-Grade Malignancy III

A. Malignant Lymphoma, Lymphocytic . . . . . III I. Chronic Lymphocytic Leukemia, B-Cell Type (B-CLL) 111

Addenda: a) The Prolymphocytic Variant of B-CLL. 134 b) Is There a Nonleukemic Lymphoma of the CLL Type? 136

2. Chronic Lymphocytic Leukemia, T-Cell Type (T-CLL) . . . . . . 137 3. Hairy-Cell Leukemia (HCL). . . . . . . . . . . . . . . . . . 152

Addendum: Is There a Nonleukemic Lymphoma of the HCL Type? 165 4. Mycosis Fungoides (M.F.) . . . . . . . . . . . . . . . . . . 165

Addendum: Sezary's Syndrome, a Leukemic Variant of Mycosis Fungoides 186 5. Malignant Lymphoma, Lymphocytic, T-Zone Type (T-Zone Lymphoma) . 196

B. Lymphomas of Immunoglobulin-Secreting Cells . . . . . . . . . . . . . 209 I. Malignant Lymphoma, Lymphoplasmacytic/Lymphoplasmacytoid (LP Immunocy-

toma) . . . . . . . . . . . . . . . . . . . . . . . . 209 Addenda: a) The Leukemic Variants of LP Immunocytoma 249

b) The Heavy-Chain Diseases. . . . . . . 251 2. Malignant Lymphoma, Plasmacytic (Plasmacytoma) . . . . 263

Addenda: a) Metastases of Myeloma in Lymph Nodes . . 278 b) The Leukemic Variant of Plasmacytoma: Plasma-Cell Leukemia 279

C. Lymphomas of Germinal-Center Cells . . . . . . . 281 The Morphology of Centro blasts and Centrocytes . . . . 282 I. Malignant Lymphoma, Centrocytic (Centrocytoma) . . 284

Addendum: The Leukemic Variant of M.L. Centrocytic 301

Contents XV

2. Malignant Lymphoma, Centroblastic/Centrocytic . . . . . . . . . 302 Addendum: The Leukemic Variant of M.L. Centroblastic/Centrocytic 343

II. Malignant Lymphomas of High-Grade Malignancy 346

A. Malignant Lymphoma, Centro blastic 346 I. Primary Centroblastic Lymphoma . . . . . 347 2. Secondary Centro blastic Lymphoma . . . . 354 Addendum: The Leukemic Variant of M.L. Centroblastic . 359

B. Malignant Lymphoma, Lymphoblastic (Lymphoblastic Sarcoma, Including Acute Lymphoblastic Leukemia) 360 I. B-Lymphoblastic Lymphoma . . .. ........ 361

a) M.L. Lymphoblastic, Burkitt Type . . . . . . . . . 361 b) B-Lymphoblastic Lymphomas Other than Burkitt Type 381

2. T-Lymphoblastic Lymphoma . 381 a) M.L. Lymphoblastic, Convoluted-Cell Type . 381 b) T-Lymphoblastic Lymphomas without Convoluted Nuclei 399

3. M.L. Lymphoblastic, Unclassified, Including Null-Lymphoblastic Lymphomas 402 Addendum (to I ~ 3): The Leukemic Variants of Malignant Lymphoma, Lympho-blastic: Lymphoblastic Leukemias (ALL) . . . . . . . . . . . 410

C. Malignant Lymphoma, Immunoblastic (lmmunoblastic Sarcoma). 421 Addenda: a) The Leukemic Variant of M.L. Immunoblastic:

Immunoblastic Leukemia . . . . . . . . 448 b) Reticulosarcoma . . . . . . . . . . . . 451

I. Sarcomas of Histiocytic Reticulum Cells. 456 2. Sarcomas of Fibroblastic Reticulum Cells 463 3. Sarcomas of Dendritic Reticulum Cells . 464 4. Sarcomas of Interdigitating Reticulum Cells 465 5. Sarcomas of Sinus Endothelial Cells. . . . 465 6. Malignant Neoplasms of Monocytes and Their Derivatives. 467 Conclusions .. .................. 469

Part Five Ultrastructure of Non-Hodgkin's Lymphomas By E. KAISERLING 471

Introduction 471

Remarks on Methods 473

I. Low-Grade Malignant Lymphomas 473

A. Malignant Lymphoma, Lymphocytic 473 I. Chronic Lymphocytic Leukemia. 473

a) B-Type 473 b) T-Type 480

2. Hairy-Cell Leukemia . 482 3. Mycosis Fungoides and Sezary's Syndrome 486

a) Mycosis Fungoides 486 b) Sezary's Syndrome 490

4. T-Zone Lymphoma 495 B. Malignant Lymphoma Lymphoplasmacytic/Lymphoplasmacytoid

(LP immunocytoma) 495 C. Malignant Lymphomas of Germinal-Center Cells. 502

I. Malignant Lymphoma, Centrocytic 502 2. Malignant Lymphoma, Centroblastic/Centrocytic 504

II. High-Grade Malignant Lymphomas . 509

XVI Contents

A. Malignant Lymphoma, Centro blastic . B. Malignant Lymphoma, Lymphoblastic

1. Burkitt Type . . . . . . . . . . 2. Convoluted-Cell Type (Acid Phosphatase Type) 3. T-Lymphoblastic Lymphoma without Convoluted Nuclei

(Malignant Lymphoma of T-Associated Plasma Cells) . . 4. Unclassified. . . . . . . . . . . . . . . . . . . . .

C. Malignant Lymphoma, Immunoblastic (Immunoblastic Sarcoma) . Addendum: Reticulosarcoma

509 511 511 515

517 519 519 523

Conclusions. . . . . . . . . . . . 526

Part Six The Immunologic and Immunochemical Basis for the Kiel Classification By H. STEIN. 529

Introduction ~ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 529

I. Immunochemical and Immunologic Methods and Markers and Their Significance for the Characterization of Lymphoid-Cell Populations . 530

A. Immunoglobulin Content of Tissue Extracts . 530 B. Demonstration of Monoclonality. . 536 C. Surface Immunoglubulin (Slg). . . . . . . 540 D. Cytoplasmic Immunoglobulin (Clg). . . . . 544 E. IgG-Fc-Fragment Receptor (lgG-Fc Receptor) 546 F. Complement Receptor . . . . . 549 G. Mouse-Erythrocyte (E) Receptor. . 556 H. Sheep-Erythrocyte (E) Receptor . . 556 Addendum: Evaluation of Rosette Tests 559 I. Human T-Associated Antigens 560

I. Human T-Lymphocyte Antigen (HTLA) 560 2. Thymocyte-Specific Antigen (THYSA) . 561 3. Human Thymus/Leukemia-Associated Antigen (HTHY-L) 561 4. CLL/Thymus Antigen (CLL-THY A). . . . . 561

J. Common-ALL Antigen. . . . . . . . . . . . 563 K. Human B-Associated Antigens: la-Like Antigens. 563 L. Terminal Deoxynucleotidyl Transferase (Tdt) . . 564 M. Receptor for Hemagglutinin A from the Snail Helix Pomatia (HP) . 565

II. Immunologic Findings and Their Relevance to the Classification of Non-Hodgkin's Lymphomas . . . . . . 565

A. Chronic Lymphocytic Leukemia (CLL) 565 B. Prolymphocytic Leukemia. . 579 C. Hairy-Cell Leukemia (HCL) . 580 D. Mycosis Fungoides. . . . . 587 E. Sezary's Syndrome . . . . . 588 F. Malignant Lymphoma, Lymphocytic, T-Zone Type (T-Zone Lymphoma). 590 G. Malignant Lymphoma, Lymphoplasmacytic/Lymphoplasmacytoid

(LP Immunocytoma) . . . . . . . . . . . . . . 591 H. Malignant Lymphoma, Plasmacytic (Plasmacytoma) 605 I. Malignant Lymphoma, Centrocytic. . . . . . . 609 J. Malignant Lymphoma, Centroblastic/Centrocytic. 614 K. Malignant Lymphoma, Centro blastic . . . . . . 622 L. Lymphoblastic Lymphoma, Burkitt Type . . . . 624 M. Lymphoblastic Lymphoma Other than the Burkitt Type. 632

Contents

N. Malignant Lymphoma, Immunoblastic Addendum: Reticulosarcoma

Summary and Final Remarks.

References, Part One . . . . . . Parts Two, Three and Four. Part Five Part Six

Author Index

Subject Index

XVII

644 653 656

659 676 717 725

743

797

AET ALL AML ATPase B-ALL BCG B-CLL C3 C3b

C3d

Clg CLL CLL-THYA CML common ALL

Con A DOC E EA EAC EAC3b

EAC3d EAChuman EACmouse EA test EBNA EBV EBV-DNA ESR Fab Fc FCC HCL hexosaminidase I

Abbreviations

2-amino-ethylisothiouronium-bromide acute lymphoblastic leukemia acute myeloid leukemia adenosine triphosphatase acute lymphoblastic leukemia of the B-cell type bacillus Calmette-Guerin chronic lymphocytic leukemia of the B-cell type third component of complement large fragment of C 3 that generates from C 3 through cleavage and liberation of the small fragment, C 3 a, by C 3 convertase, nonspecific proteases, or activation via the alternative pathway fragment of C 3 that generates from C 3 b through cleavage and liberation of the C 3 c fragment by C 3 b inactivator (intra)cytoplasmic immunoglobulin chronic lymphocytic leukemia CLL/thymus antigen chronic myeloid leukemia acute lymphoblastic leukemia devoid of T - and B-cell markers, but expressing common-ALL antigen (Greaves antigen) concanavalin A sodium desoxycholate erythrocyte erythrocyte-antibody complex crythrocyte-antibody-complement complex EAC composed of erythrocytes coated with IgM antibodies and purified human C3b EAC 3 b cleaved by C 3 inactivator and after liberation of C 3 c EAC prepared with human complement EAC prepared with mouse complement early-antigen test Epstein-Barr nuclear antigen Epstein-Barr virus Epstein-Barr-virus deoxyribonucleic acid erythrocyte sedimentation rate antigen-binding fraction of antibody constant region of antibody follicular-center cell hairy-cell leukemia isoenzyme I of o:-N-acetyl-hexosaminidase

xx

HP H rosette HTHY-L HTLA la-like antigen Ig IgGEA

I gG-F c receptor IgG-humanEA IgG-oxEA IgG-sheepEA IgMEA

IgMEAC IgM-EAC3b IgM-EAC3d IgM-Fc receptor Lit.

LP immunocytoma LPS MA test M.F. MIF MGP M.L. MPS null ALL PAP PAS PHA RES RHS Slg T-ALL T-CLL Tdt THY SA YCA

Abbreviations

hemagglutinin A from the snail Helix pomatia rosette with homologous (human) group-O Rh-negative erythrocytes human thymus/leukemia-associated antigen human T-lymphocyte antigen human glycoprotein complex resembling murine la-antigen immunoglobulin antigen-antibody complex composed of erythrocytes coated with anti-erythrocyte antibodies of the IgG type receptor for the Fc fragment (constant region) of the IgG molecule IgGEA prepared with human erythrocytes IgGEA prepared with ox erythrocytes IgGEA prepared with sheep erythrocytes antigen-antibody complex composed of erythrocytes coated with anti-erythro­cyte antibodies of the IgM type EAC composed of erythrocytes coated with IgM antibodies and complement =EAC3b =EAC3d receptor for the Fc fragment (constant region) of the IgM molecule literature (used in footnotes to indicate where a more complete list of references may be found) malignant lymphoma, lymphoplasmacytic/lymphoplasmacytoid lipopolysaccharides from Escherichia coli membrane-antigen test

. mycosis fungoides migration-inhibitory factor methyl-green pyronine malignant lymphoma mononuclear phagocyte system acute lymphoblastic leukemia devoid of T- and B-cell markers peroxidase-antiperoxidase periodic-acid Schiff phytohemagglutinin reticuloendothelial system reticulohistiocytic system surface immunoglobulin acute lymphoblastic leukemia of the T-cell type chronic lymphocytic leukemia of the T-cell type terminal deoxynucleotidyl transferase thymocyte-specific antigen viral-capsid antigen