HISTORY OF THE EUROPEAN ASSOCIATION FOR HAEMATOPATHOLOGY

(1)

HISTORY OF

THE EUROPEAN ASSOCIATION FOR HAEMATOPATHOLOGY

(2)

KARL LENNERT HISTORY OF

THE EUROPEAN ASSOCIATION FOR HAEMATOPATHOLOGY

TRANSLATED BY MARTHA SOEHRING

123

(3)

Prof. em. Dr. med. Dr. h.c. mult. Karl Lennert Niemannsweg 26

24105 Kiel, Germany Formerly:

Director, Institute of Pathology University of Kiel

24105 Kiel, Germany

ISBN-10 3-540-34886-7 Springer Berlin Heidelberg New York ISBN-13 978-3-540-34886-3 Springer Berlin Heidelberg New York Library of Congress Control Number: 2006926722

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 illustra- tions, recitation, broadcasting, reproductiononmicrofilmor inanyotherway, andstorage indata 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 permissions for use must always be obtained from Springer. Violations are liable for pros- ecution under the German Copyright Law.

Springer is a part of Springer Science+Business Media springer.com

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 ex- empt 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 dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature.

Editor: Gabriele Schröder, Heidelberg Desk Editor: Ellen Blasig, Heidelberg

Cover design: Frido Steinen-Broo, EStudio Calamar, Spain

Typesetting and production: LE-TEX Jelonek, Schmidt&Vöckler GbR, Leipzig, Germany Printed on acid-free paper 27/3100/YL 5 4 3 2 1 0

(4)

V

#.# HEADLINE-2

PREFACE

During the last quarter of the 20^th century a paradigmatic change occurred in the understanding and classification of malignant lymphomas. This was primarily a result of the discovery of the two lymphocyte systems (the B-cell and T-cell systems with numerous variants), which was made possible mainly through the use of many antibodies, most of which were monoclonal. In order to distinguish the various types of lymphoma it is necessary to use an optimum technique that allows recognition of the same cell types in both imprints and sections. The pioneer work of A. A. Maximow more than 100 years ago laid the basis for developing such a technique for preparing sections and imprints of high quality, which are a prerequisite for both exact morphological diagnoses and the application of antibodies. This led to the development of new classifications that also proved to be largely valid when tested with recent molecular genetic techniques.

The development began in Europe in 1972 and soon led to the systematic application of a new lymphoma classification, which was proposed by the members of the European Lymphoma Club at a meeting in Kiel, Germany (thus the name “Kiel classification”) in 1974. The classification quickly came into widespread use in Europe. In the USA (and institutions dependent on the USA), however, the classification met with great resistance and opposi- tion. Finally, a breakthrough occurred after an international study suggested by Dr. J.O. Armitage and performed by a group of true lymphoma experts (pathologists); the overwhelming results of this study were presented by Dr. S.A. Rosenberg in Omaha, NE, USA in 1997.

Since the USA-dominated Society for Hematopathology was not inter- ested in establishing a separate section for the large group of European haematopathologists, the European Association for Haematopathology was founded in 1988. The Association has developed into an effective organiza- tion with a steadily growing number of members (from 246 in 1988 to more than 500 registered participants at the last congress in Thessaloniki, Greece).

The author has been asked many times to write a chronicle of these devel- opments. On the one hand, it was a pleasure to accept – for the sake of a good cause. On the other hand, there were several difficulties. First, I had to rely mostly on notes taken in my own diary; I was well aware of the risk that the report would be too personal. Second, it was difficult to give due honour to the many colleagues involved and to mention them all in the report. It felt

(5)

VI PREFACE

awkward to write “I” so many times, knowing that none of the studies would have been possible without the participation of colleagues, especially co- workers at the Institute of Pathology in Kiel. I thank them all for their pa- tience, cooperation, and loyalty. Of my many co-workers there are four who deserve special mention, namely, Professor E. Kaiserling, Profes- sor H. K. Müller-Hermelink, Professor E. W. Schwarze, and Profes- sor H. Stein. I am also grateful to my loyal clinical colleague Profes- sor G. Brittinger and his large group of clinicians, who readily provided biopsy material and clinical data even under difficult conditions. In order to obtain the material the local pathologists had to give their consent, and they did so generously. The concepts underlying the Kiel classification were scru- tinized in immunological studies done by members of a “special research area” (sponsored by the German Research Foundation), of which Profes- sor W. Müller-Ruchholtz was co-chairman; he was a crucial critical partner. The harmonious cooperation within the European Lymphoma Club was of great value, and I could always rely on the members’ support. My thanks are also due to the medical technicians at the Institute in Kiel; when I examined the slides they had prepared I was often spurred on by their excel- lent skills (e.g. Giemsa staining).

This report would not have been possible without the energetic support of the President of the European Association for Haematopathology, Dr. M. A. Piris, and the Treasurer, Professor J. H. J. M. van Krieken. They spontaneously agreed to have the Association cover the costs of publication.

As with earlier books, I am also very grateful to Mrs. M. Soehring for her prudent and constructive support while translating the text.

It was a pleasure to work with Ms. G. Schröder und Ms. E. Blasig of Springer-Verlag, whose competent and untiring efforts made it possible to publish this report in time for the next congress of the European Association for Haematopathology in Vienna, Austria.

Kiel, May 2006 Karl Lennert

(6)

VII

#.# HEADLINE-2

FOREWORD

The European Association for Haematopathology (EAHP) was created with the aim of integrating lymphoma basic and clinical research, stemming from the deeply held conviction that only by pursuing research into clinical translation will we eventually be able to refine lymphoma diagnostic categories.

This will make it possible for us to develop new diagnostic and therapeutic tools, using more efficiently the therapies that are currently available. The work of the EAHP and the Society of Hematopathology created the basis for the REAL Classification that finally, under the sponsorship of the WHO, led to the publication of the unique WHO Lymphoma Classification that is now recognized throughout the world. The efforts to promote a lymphoma classification with a solid biological foundation is described in this extraordi- nary book, in which Professor K. Lennert narrates his memories of those years and of the work that was so infused with his strength of purpose and dedication.

Many of today’s young clinicians and researchers will find it difficult to appreciate the damage that the confusion concerning lymphoma classification wrought on patients suffering from lymphoproliferative conditions during the period related here. Professor Lennert’s personal recollections de- scribe the formula by which this crisis was overcome – the integration of basic and clinical research in enthusiastically conducted work directed to- wards well-chosen ends. This formula has been adopted by leading pathologists in Europe and the USA, so ensuring that the Lymphoma Classification will continue to be kept up to date. Indeed, this synthesis of fundamental and applied research has become the model of choice, replicated by other scientific societies throughout the clinical world.

The fruits of Professor Lennert’s scientific career and objectives are now embodied within the WHO Lymphoma Classification. This fully embraces the main proposals of the Kiel Classification, the establishment of tumoral categories that integrate cell lineage, stage of differentiation, molecular mark- ers and diagnostic morphological features. As such, it provides haematopathologists and clinicians with a reliable tool for the accurate identification of the different lymphoma types.

While the European Association for Haematopathology was created during the era described in this book, it remains an exemplary pathology society, open to basic and clinical researchers, and currently has around 500 members worldwide. Today it represents the natural continuation of the

(7)

VIII FOREWORD

spirit that in the 1970s and 1980s pervaded the Institute of Pathology in Kiel.

It was there that Professor Lennert was host to dozens of haematopathologists from all over the world, and where he provided them with an opportu- nity to share projects, exchange ideas and compare results. This contributed greatly to establishing the community as we know it today, with its freedom from international boundaries.

In recognition of all this, we take great pleasure in writing this foreword to Professor Lennert’s memoirs and welcome the publication of this book to mark the occasion of his 85^th birthday.

Dr. Miguel A Piris Prof. Stefano Pileri President EAHP President Elect EAHP

(8)

IX CONTENTS

CONTENTS

1 Introduction . . . . 1

2 Classification of Malignant Lymphomas . . . . 5

2.1 1958−1971 . . . . 5

2.2 The WHO Classification I (1968–1976) . . . . 6

2.3 Lymphocyte Transformation and the B-Cell and T-Cell Systems. Initial Immunochemical Studies, 1971–1972 . . . . 8

2.4 The Kiel Lymphoma Study Group . . . . 11

2.5 1972–1973 . . . . 14

2.6 Prelude to European Cooperation, 1973 . . . . 14

2.7 The European Lymphoma Club (ELC) . . . . 17

2.8 The Kiel Classification, 1974 . . . . 18

2.9 Presentation of the Kiel Classification, 1974–1980 . . . . 25

2.9.1 Vienna, Austria, 29–31 August 1974 . . . . 26

2.9.2 London, UK, 24–28 August 1975 . . . . 26

2.9.3 Bad Nauheim, Germany, 29 September – 1 October 1975 . . . . . 27

2.9.4 Vienna, 6–11 October and 14 November 1975 . . . . 27

2.9.5 Damp, Germany, 3–8 November 1975 . . . . 28

2.9.6 Jerusalem, Israel, 17–31 March 1976 . . . . 28

2.9.7 Spain, 23–25 September 1976 and 21–22 October 1978 . . . . 29

2.9.8 Boston, MA, USA, 15 October 1976 . . . . 29

2.9.9 Washington, DC, USA, 17–21 October 1976 . . . . 30

2.9.10 Brazil, 25–29 October 1976 . . . . 31

2.9.11 Japan, 2–8 April 1977 . . . . 32

2.9.12 Brussels, Belgium, 14 May 1977 . . . . 33

2.9.13 Bucharest, Rumania, 25–27 May 1977 . . . . 34

2.9.14 Cold Spring Harbor, NY, USA, 7–12 September 1977 . . . . 35

2.9.15 Chicago, IL and Winston-Salem, NC, USA, 18–22 September 1977 . . . . 36

2.9.16 Rochester, MN, USA, 1–3 October 1977 . . . . 36

2.9.17 Munich, Germany, 16–18 June 1978 . . . . 37

2.9.18 Poland, 9–12 October 1978 . . . . 37

2.9.19 Thessaloniki, Greece, 16–17 October 1978 . . . . 39

2.9.20 Lisbon, Portugal, 27–30 January 1980 . . . . 39

2.9.21 New York, NY, USA, 2–8 March 1980 . . . . 39

2.9.22 Paris, France, 15–19 September 1980 . . . . 40

2.10 Other Means of Dissemination of the Kiel Classification . . . . . 41

(9)

X CONTENTS

2.10.1 Establishment of Research Centres and Study Groups . . . . 41

2.10.2 Major Publications . . . . 41

2.11 Clinical Relevance of the Kiel Classification . . . . 42

2.12 Genetic and Molecular Genetic Studies . . . . 43

2.13 A Sideline: Gastrointestinal Lymphomas in Tunisia, 11–15 December 1978 . . . . 44

2.14 Attempts to Agree on a Universal Classification of Malignant Lymphoma, 1974–1982 . . . . 46

2.14.1 Florence, Italy, 20–26 October 1974 . . . . 47

2.14.2 Warrenton, VA, USA, 4–5 September 1975 . . . . 47

2.14.3 Villejuif, France, 20–25 June 1977 . . . . 50

2.14.4 Geneva, 1–5 May 1978 . . . . 50

2.14.5 The NCI Study, 1975–1980 . . . . 52

2.14.5.1 Tour of the Institutions Involved in the NCI Study . . . . 54

2.14.5.2 Evaluation of the Results of the NCI Study . . . . 55

2.14.6 Presentation of the Working Formulation, 1982 . . . . 56

2.15 Comparison of the Lukes-Collins Classification and the Kiel Classification . . . . 61

2.15.1 Washington, DC, 20 October 1976 . . . . 63

2.15.2 Stockholm, Sweden, 29–31 March 1979 . . . . 63

2.15.3 Noordwijkerhout, The Netherlands, 3–6 April 1979 . . . . 63

2.15.4 Athens, Greece, 6–10 April 1981 . . . . 65

2.15.5 Kiel, Germany, 16–21 April 1981 . . . . 67

2.16 Acceptance of the Kiel Classification, 1981–1987 . . . . 68

2.16.1 Vienna, 15–18 February 1981 . . . . 68

2.16.2 Ljubljana, Yugoslavia, 14–15 April 1981 . . . . 69

2.16.3 Erice, Sicily, 3–9 May 1981 . . . . 70

2.16.4 Erfurt, Germany, 13 May 1981 . . . . 70

2.16.5 Montreal, Canada, 17–21 September 1981 . . . . 70

2.16.6 Jerusalem, 22–25 September 1981 . . . . 71

2.16.7 Kiel, 7–9 October 1981 . . . . 72

2.16.8 Oxford, UK, 25–30 January 1982 . . . . 72

2.16.9 USA, 25 February – 5 March 1982 . . . . 75

2.16.10 Copenhagen, Denmark, 28–30 June 1982 . . . . 77

2.16.11 Freiburg, Germany, 6 July 1982 . . . . 78

2.16.12 Kiel, 2–6 August 1982 . . . . 78

2.16.13 Seattle, WA, USA, 6–7 September 1982 . . . . 79

2.16.14 Birmingham, UK, 20 September 1982 . . . . 80

2.16.15 Brazil, 22–26 September 1982 . . . . 81

2.16.16 Rome, Italy, 3–6 October 1982 . . . . 84

2.16.17 1983 . . . . 84

2.16.17.1 Wiesbaden, Germany, 14 April 1983 . . . . 84

(10)

XI CONTENTS

2.16.17.2 Lucerne, Switzerland, 24–28 May 1983 . . . . 85

2.16.17.3 Kiel, 5–11 September 1983 . . . . 85

2.16.17.4 Cold Spring Harbor, NY, USA, 14–15 September 1983 . . . . 86

2.16.17.5 Hamburg, Germany, 19–24 September 1983 . . . . 87

2.16.17.6 London, 29–30 September 1983 . . . . 87

2.16.17.7 Kiel, 1–7 October 1983 . . . . 87

2.16.17.8 Bologna, Italy, 17–18 October 1983 . . . . 87

2.16.17.9 Morocco, 23–26 October 1983 . . . . 88

2.16.18 1984 . . . . 88

2.16.18.1 France, 26–28 April 1984 . . . . 88

2.16.18.2 China, 29 April – 12 May 1984 . . . . 89

2.16.18.3 Japan, 12–19 May 1984 . . . . 94

2.16.18.4 Siena, Italy, 24–26 May 1984 . . . . 96

2.16.18.5 Kiel, 24–27 June 1984 . . . . 96

2.16.18.6 Buenos Aires, Argentina, 2–4 September 1984 . . . . 96

2.16.18.7 USA, 5–22 September 1984 . . . . 97

2.16.18.8 UK, 18–21 November 1984 . . . . 99

2.16.19 1985 . . . . 100

2.16.19.1 Puerto de la Cruz, Tenerife, 8–10 March 1985 . . . . 100

2.16.19.2 Kiel, 24–30 April 1985 . . . . 101

2.16.19.3 Stockholm, Sweden, 6 June 1985 . . . . 101

2.16.19.4 Kiel, 10–11 June 1985 . . . . 101

2.16.19.5 Prague, Czechoslovakia, 3–6 September 1985 . . . . 101

2.16.19.6 Kiel, 13–15 September 1985 . . . . 102

2.16.19.7 Athens, 4–5 October 1985 . . . . 102

2.16.19.8 Vienna, 6–9 October 1985 . . . . 103

2.16.20 Attempts to Form a European-American Alliance, 1986 . . . . 103

2.16.20.1 Kiel, 26–28 January 1986 . . . . 103

2.16.20.2 New Orleans, LA, USA, 8–12 March 1986 . . . . 103

2.16.20.3 After-Effects, April 1986 . . . . 106

2.16.20.4 Founding of the Society for Hematopathology in Retrospect . . . . 108

2.16.21 Further Events, 1986–1987 . . . . 109

2.16.21.1 April–July 1986 . . . . 109

2.16.21.2 Vienna, 27 August – 5 September 1986 . . . . 109

2.16.21.3 Far East, 22 September – 7 October 1986 . . . . 110

2.16.21.4 Chicago, 7–12 March 1987 . . . . 110

2.16.21.5 Garden City, Long Island, NY, USA, 13–14 March 1987 . . . . 111

2.16.21.6 Boston, MA, 15–17 March 1987 . . . . 111

2.16.21.7 Oberhausen, Germany, 23 March – 7 April 1987 . . . . 111

2.17 Founding of the European Lymphoma Study Group . . . . 112

2.17.1 Kiel, 7–8 November 1980 . . . . 112

(11)

XII CONTENTS

2.17.2 Kiel, 20–24 October 1981 . . . . 113

2.17.3 Southampton, UK, 25–28 September 1983 . . . . 115

2.17.4 Toulouse, France, 1–3 April 1985 . . . . 116

2.17.5 Brussels, 27–29 October 1986 . . . . 116

2.17.6 Geneva, 14–15 March 1988 . . . . 116

3 Founding of the European Association for Haematopathology . . . . 117

3.1 Prelude, 1986–1988 . . . . 117

3.1.1 Kiel, 9–11 December 1987 . . . . 117

3.1.2 Kiel, 17–19 February 1988 . . . . 118

3.1.3 21 March 1988 . . . . 118

3.2 Geneva, 11–15 April 1988 . . . . 119

3.3 Porto, Portugal, 6–7 September 1989 . . . . 122

4 Epilogue, 1989–2004 . . . . 123

References . . . . 125