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Published in 2005 by Taylor & Francis Group 6000 Broken Sound Parkway NW Boca Raton, FL 33487–2742 # 2005 by Taylor & Francis Group, LLC No claim to original U.S. Government works Printed in the United States of America on acid-free paper 10987654321 International Standard Book Number-10: 0–8247–5812–9 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. 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Library of Congress Cataloging-in-Publication Data Catalog record is available from the Library of Congress Visit the Taylor & Francis Web site at http :==www.taylorandfrancis.com Contents Preface . xxi Contributors . xxiii Abbreviations . xxv INTRODUCTION 1. Cutaneous Lymphomas—Historical Aspects . ................... 1 Michael Geiges, Roman Specker, Werner Kempf, and Gu¨nter Burg 2. Unique Features of Cutaneous Lymphomas....................... 7 Gu¨nter Burg and Werner Kempf 3. Cutaneous Lymphoma: A Prototype Neoplasia for Cancer Research . 11 Gu¨nter Burg and Werner Kempf 4. Epidemiology . .......................................... 13 Gu¨nter Burg and Werner Kempf Cutaneous Lymphomas . 13 Cutaneous T-cell Lymphomas . 13 Epidemiologic Factors Influencing Incidence and Mortality Rates . 16 Cutaneous B-cell Lymphomas (CBCL) . 17 STRUCTURE AND FUNCTION OF THE LYMPHOID SYSTEM 5. The Lymphoid System . ............................... 21 Marshall E. Kadin 6. Structure and Function of Secondary Lymphoid Tissues . ........... 23 Marshall E. Kadin Spleen . 27 Mucosa-Associated Lymphoid Tissues. 27 Skin........................................................ 28 7. Ontogeny of Lymphoid Cells. ............................... 29 Marshall E. Kadin B-cell Ontogeny. 29 T-cell Ontogeny. 30 g=d T-cells . 30 iii iv Contents Natural Killer Cells . 31 Myeloid Cells . 31 Eosinophils . 32 Basophils and Mast Cells . 32 Monocytes and Macrophages . 33 8. Histo- and Cytomorphology . .............................. 37 Marshall E. Kadin 9. Growth Patterns of Lympho- and Myeloproliferative Infiltrates of the Skin . .......................................... 39 Gu¨nter Burg, Marshall E. Kadin, and Werner Kempf Principal Growth Pattern . 39 Growth Pattern in Cutaneous Lymphomas . 40 Growth Patterns of Myeloproliferative Infiltrates in the Skin . 43 DIAGNOSTIC APPROACH TO CUTANEOUS LYMPHOMAS 10. Stepwise Approach to the Diagnosis of Lymphoproliferative Skin Infiltrates and Related Disorders .............................. 45 Monika Hess Schmid, Gu¨nter Burg, and Werner Kempf History. 45 Clinical Features . 45 11. Clinical Staging of Cutaneous Lymphomas ....................... 49 Monika Hess Schmid, Gu¨nter Burg, Sonja Michaelis, and Werner Kempf Classical Alibert–Bazin Staging. 49 TNM Staging . 49 Tumor Burden Index . 50 12. Laboratory Investigations . .................................. 53 Monika Hess Schmid, Gu¨nter Burg, and Werner Kempf Skin Biopsies . 53 Lymph Node and Bone Marrow Biopsies . 53 Blood Tests. 53 Radiologic Tests . 54 13. Immunohistochemistry and Phenotypic Features ................... 57 Werner Kempf, Dmitry V. Kazakov, and Gu¨nter Burg Introduction . 57 Technical Aspects of Immunophenotyping in Cutaneous Lymphomas . 57 A Practical Stepwise Approach to Cutaneous Lymphomas . 58 CTCL and Cytotoxic Lymphomas . 58 CD30-Positive Lymphoproliferative Diseases . 59 CBCL and B-cell Pseudolymphoma . 61 Leukemic Infiltrates of the Skin . 63 Immunophenotypic Markers as Prognostic Parameters . 63 14. Genotyping . .......................................... 65 Udo Do¨ebbeling, Werner Kempf, Antonio Cozzio, Reinhard Dummer, and Gu¨nter Burg The Identification of a Malignant T-cell Clone by PCR-DGGE. 66 Advantages and Limitations of PCR-DGGE . 67 v 15. Cytogenetic Studies in Cutaneous Lymphomas . ................... 69 Werner Kempf, Antonio Cozzio, Dmitry V. Kazakov, and Gu¨nter Burg Introduction . 69 Genetic Abnormalities in Cutaneous T-cell Lymphomas . 69 Genetic Abnormalities in Cutaneous B-cell Lymphomas . 70 Conclusions . 71 16. Functional Profiling by Microarray Technology. ................... 73 Antonio Cozzio, Werner Kempf, Reinhard Dummer, and Gu¨nter Burg Types of Microarray Experiments . 74 DNA Microarray Experiments . 75 Protein-Based Gene Expression Analysis . 76 Cutaneous Lymphoma. 76 17. Classification of Nodal Lymphomas in Historical Perspective . ....... 79 Marshall E. Kadin Revised European–American (REAL) Classification . 82 World Health Organization (WHO) Classification of Hematologic Malignancies. 82 18. Classification of Cutaneous Lymphomas in Historical Perspective ....... 83 Christian A. Sander, Michael J. Flaig, Werner Kempf, and Gu¨nter Burg 19. WHO=EORTC Classification of Cutaneous Lymphomas . ........... 91 Gu¨nter Burg, Werner Kempf, Dmitry V. Kazakov, Sonja Michaelis, and Reinhard Dummer 20. Prognostic Categorization of Lymphoproliferative Disorders of the Skin: A New and Clinically Oriented Approach . ........................... 95 Gu¨nter Burg, Sonja Michaelis, Philippa Golling, and Werner Kempf Prognostic Categories . 95 CUTANEOUS T-CELL AND NK-CELL LYMPHOMAS 21. Mycosis Fungoides. ..................................... 101 Dmitry V. Kazakov, Gu¨nter Burg, and Werner Kempf Classification. 101 Definition . 101 Clinical Features . 101 Histology . 104 Immunohistochemistry. 105 Molecular Biology . 106 Cytogenetic Analysis . 107 Treatment. 107 Clinical Course and Prognosis . 107 Differential Diagnosis . 108 Comments . 109 Mycosis Fungoides in Childhood and Adolescence . 109 Clinical Features . 109 Histology . 109 Immunohistochemistry. 109 Molecular Biology . 109 Treatment. 109 Clinical Course and Prognosis . 110 Differential Diagnosis . ..