Malignant Lymphomas Other than Hodgkin’s Disease: Histology · Cytology · Ultrastructure · Immunology

848 Pages·1978·33.805 MB·English

by  Prof. Dr. med. Karl Lennert (auth.)

HANOBUCH OER
SPEZIELLEN PA THOLOGISCHEN
ANATOMIE UNO HISTOLOGIE
BEGRONDET VON
O. LUBARSCH F. HENKE
UND
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
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C10CPWC; [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
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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 immuno
blastic lymphomas. Furthermore, some new entities were discovered, e.g., lympho
plasmacytoid 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. BRITTINGER
have 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, diag
nosis, 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 malig
nant 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 consider
ation. 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 symboli
cally 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 contribu
tion 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 classifica
tion based on morphologic (histologic, cytologic, and ultrastructural), cytochemical, and immuno
logic 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, stimula
tion, 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 Forschungsgemein
schaft (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