Skin Lymphoma The Illustrated Guide
To Helmut Kerl, a teacher, mentor, and friend, who welcomed me in Graz as a son, and provided me with a second home
Skin Lymphoma The Illustrated Guide Lorenzo Cerroni MD Director, Cutaneous Lymphoma Unit Director, Dermatopathology Research Center Department of Dermatology Medical University of Graz Graz, Austria Fourth Edition
This edition first published 2014, 1998, 2004, 2009, 2014 by John Wiley & Sons, Ltd Registered office: Editorial offices: John Wiley & Sons, Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 9600 Garsington Road, Oxford, OX4 2DQ, UK The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 111 River Street, Hoboken, NJ 07030-5774, USA For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell The right of the author to be identified as the author of this work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by health science practitioners for any particular patient. The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. Library of Congress Cataloging-in-Publication Data Cerroni, Lorenzo, author. Skin lymphoma : the illustrated guide / Lorenzo Cerroni. Fourth edition. p. ; cm. Includes bibliographical references and index. ISBN 978-1-118-49249-9 (cloth) I. Title. [DNLM: 1. Skin Neoplasms diagnosis. 2. Skin Neoplasms therapy. 3. Lymphoma pathology. WR 500] RC280.S5 616.99'477 dc23 2013049539 A catalogue record for this book is available from the British Library. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Cover image: Lorenzo Cerroni Set in 9.5/12 pt MinionPro-Regular by Toppan Best-set Premedia Limited 1 2014
Contents List of teaching cases, vii Preface, ix Acknowledgments, xi 1 Introduction, 1 Section 1: Cutaneous NK/T-cell lymphomas 2 Mycosis fungoides, 11 3 Sézary syndrome, 74 4 Primary cutaneous CD30 + lymphoproliferative disorders, 85 Lymphomatoid Papulosis, 86 Cutaneous Anaplastic Large Cell Lymphoma, 99 Borderline Cases, 109 5 Subcutaneous panniculitis-like T-cell lymphoma, 120 6 Aggressive cutaneous cytotoxic lymphomas, 133 Primary Cutaneous Aggressive Epidermotropic CD8 + Cytotoxic T-cell Lymphoma, 134 Primary Cutaneous γ/δ T-cell Lymphoma, 137 Cutaneous Extranodal NK/T-cell Lymphoma, Nasal Type, 143 7 Cutaneous peripheral T-cell lymphoma, not otherwise specified (NOS), 155 8 Cutaneous CD4 + small medium T-cell lymphoma, 163 Indolent CD8 + Lymphoid Proliferation of the Ear (Face), 166 Primary Cutaneous T-follicular helper (T FH )-cell Lymphoma, 167 9 Cutaneous adult T-cell leukemia/lymphoma, 172 10 Other cutaneous NK/T-cell lymphomas, 176 Angioimmunoblastic T-cell Lymphoma, 176 Hydroa Vacciniforme-Like Lymphoma, 179 Section 2: Cutaneous B-cell lymphomas 11 Cutaneous follicle center lymphoma, 185 12 Cutaneous marginal zone lymphoma (cutaneous MALT-lymphoma) and variants, 201 Cutaneous Marginal Zone Lymphoma, Conventional Variant, 202 Cutaneous Marginal Zone Lymphoma, Lymphoplasmacytic Variant, 208 Cutaneous Marginal Zone Lymphoma, Plasmacytic Variant, 212 Cutaneous Marginal Zone Lymphoma, Blastoid Variant, 213 13 Cutaneous diffuse large B-cell lymphoma, leg type, 220 14 Intravascular large cell lymphomas, 232 Intravascular Large B-cell Lymphoma, 232 Intravascular Large NK/T-cell Lymphoma, 237 Intralymphatic CD30 + Large T-cell Lymphoma, 239 15 Other cutaneous B-cell lymphomas, 245 Cutaneous EBV + Diffuse Large B-cell Lymphoma of the Elderly, 245 Specific Cutaneous Manifestations in Mantle Cell Lymphoma, 247 Specific Cutaneous Manifestations in Extracavitary Primary Effusion Lymphoma, 248 Specific Cutaneous Manifestations in Multiple Myeloma, 250 Specific Cutaneous Manifestations in Burkitt Lymphoma, 252 Cutaneous Lymphomatoid Granulomatosis, 253 Cutaneous Plasmablastic Lymphoma, 256 Cutaneous T-cell/Histiocyte-rich B-cell Lymphoma, 258 v
vi Contents Section 3: Cutaneous lymphomas in immunosuppressed individuals 16 Cutaneous post-transplant lymphoproliferative disorders, 265 17 Cutaneous lymphomas in HIV-infected individuals, 275 18 Cutaneous lymphoproliferative disorders in other iatrogenic and non-iatrogenic immune deficiencies, 281 Section 4: Specific cutaneous manifestations of leukemias and of precursor hematologic neoplasms 19 Cutaneous manifestations of B-cell chronic lymphocytic leukemia, 287 20 Cutaneous manifestations of myelogenous leukemia, 296 21 Blastic plasmacytoid dendritic cell neoplasm, 306 22 Cutaneous manifestations of other leukemias, 317 T-cell Prolymphocytic Leukemia, 317 Aggressive Natural Killer Cell Leukemia, 318 Specific Skin Manifestations of other Types of Leukemia, 319 23 Cutaneous lymphoblastic lymphomas, 320 Cutaneous B-lymphoblastic Lymphoma, 320 Cutaneous T-lymphoblastic Lymphoma, 323 Section 5: Cutaneous manifestations of Hodgkin lymphoma 24 Cutaneous manifestations of Hodgkin lymphoma, 331 Section 6: Cutaneous lymphomas in children and adolescents 25 Cutaneous lymphomas in children and adolescents, 341 Section 7: Pseudolymphomas of the skin 26 Pseudolymphomas of the skin, 351 Actinic reticuloid, 353 Lymphomatoid contact dermatitis, 354 Solitary idiopathic B/T-cell pseudolymphoma, 355 Lichenoid (lymphomatoid) keratosis, 357 Lichen aureus/lichenoid pigmented purpuric dermatitis, 357 Lichen sclerosus, 359 Vitiligo, 360 Annular lichenoid dermatitis of youth, 361 Pseudolymphomatous acrodermatitis chronica atrophicans, 361 Pseudolymphomatous atopic dermatitis, 362 Non-neoplastic erythroderma in adult patients, 363 Pseudolymphomatous cutaneous infiltrates in human immunodeficiency virus (HIV)-infected patients and in other immune deficiencies, 367 CD30 + T-cell pseudolymphomas, 367 Persistent nodular arthropod bite reactions and nodular scabies, 369 Pseudolymphomas in herpes simplex and herpes zoster infections, 371 Epstein Barr virus (EBV)-associated mucocutaneous ulcers, 372 Hydroa vacciniforme, 373 Pityriasis lichenoides, 374 Pseudolymphomas associated with lupus erythematosus, 376 Lymphomatoid drug reactions, 379 Lymphocytoma cutis, 380 Pseudolymphomas at sites of vaccination, 384 Pseudolymphomas in tattoos, 385 Localized scleroderma/morphea, 386 Cutaneous IgG4-related disease, 386 Pseudolymphomas in syphilis, 386 Cutaneous plasma cell granuloma, 388 Cutaneous and systemic plasmacytosis, 389 Cutaneous manifestations of Castleman disease, 392 Pre-tibial lymphoplasmacytic plaque in children, 393 Cutaneous extramedullary hematopoiesis, 394 Histiocytoid Sweet syndrome, 395 Intralymphatic histiocytosis, 396 Benign intralymphatic proliferation of T-cell lymphoid blasts, 397 Other accidental pseudolymphomas, 398 Malignant pseudolymphomas, 399 Section 8: The cutaneous atypical lymphoid proliferation 27 The cutaneous atypical lymphoid proliferation, 413 Index, 415
List of teaching cases Diagnosis 2.1 Bullous (erosive) mycosis fungoides, 62 2.2 Solitary mycosis fungoides with large cell transformation, 63 2.3 Mycosis fungoides without epidermotropism and with dermal edema, 64 3.1 Sézary syndrome with palmar purpura, 81 4.1 Angiocentric ( angiomatoid ) lymphomatoid papulosis, type E, 110 4.2 PLEVA-like lymphomatoid papulosis, 112 4.3 Anaplastic large cell lymphoma with intralymphatic spread, 114 5.1 Subcutaneous panniculitis-like T-cell lymphoma with loss of ßF1 expression, 128 6.1 Extranodal NK/T-cell lymphoma, nasal-type with early ( inflammatory-like ) lesions, 150 7.1 Peripheral T-cell lymphoma, NOS with early lesions, 160 8.1 CD4+ small-medium T-cell lymphoma arising on the leg and showing aberrant CD20 expression (mimicking diffuse large B-cell lymphoma,leg-type), 169 11.1 Follicle center lymphoma with histopathologic features of large cell lymphocytoma, 198 12.1 Marginal zone lymphoma arising at the site of acrodermatitis chronica atrophicans, 216 13.1 Diffuse large B-cell lymphoma, leg-type simulating mycosis fungoides, 228 14.1 Intravascular large B-cell lymphoma, early lesion, 242 15.1 Diffuse large B-cell lymphoma, angiocentric / angiodestructive, 259 16.1 Post-transplant plasmablastic lymphoma, 272 17.1 HIV-associated peripheral T-cell lymphoma, NOS, 278 19.1 Composite lymphoma (B-CLL and mycosis fungoides), 293 20.1 Myelogenous leukemia mimicking lymphoblastic lymphoma, 303 21.1 Blastic plasmacytoid dendritic cell neoplasm with fast relapse after chemotherapy, 314 23.1 Unclassifiable, epidermotropic (pagetoid reticulosis-like) precursor T-cell lymphoma, 326 24.1 Regional lymphomatoid papulosis misdiagnosed as primary cutaneous Hodgkin lymphoma, 335 25.1 PLEVA-like mycosis fungoides in adolescent, 345 26.1 Lichenoid ( lymphomatoid ) keratosis with intraepidermal collections of lymphocytes (Darier s nests), 401 26.2 Lymphomatoid contact dermatitis, 403 26.3 Lupus erythematosus with angiocentric infiltrates, 405 vii
Preface In 1996, when Helmut Kerl, Kevin Gatter, and I discussed the project of a book on cutaneous lymphomas, little did I dream that one day I would be writing the fourth edition of it. Since Helmut Kerl retired in 2008 and Kevin Gatter is focusing on his excellent books on bone marrow diagnosis and diagnosis of lymphoproliferative diseases, we decided that I would continue this project alone. This was both a great responsibility and a Herculean task. I am grateful to the many friends who shared valuable information and provided useful suggestions for the completion of the book. I am well aware that in an era of computer learning, PubMed checking, and Google searching, any comprehensive medical book, no matter what the subject is, may seem antiquated and passé. On the other hand, dermatology and dermatopathology are visual disciplines, and pictures are paramount. In addition, a comprehensive text offers much information that cannot be found in any web search. Although I do not consider myself as a lymphomaniac, during the last 30 years cutaneous lymphomas have been the subject of my main academic interest, and of many of my scientific publications. Along with many other important things in my life, I did not choose this field on purpose, but rather happened to be involved in it as a young doctor, and subsequently got more and more attracted to it. The main responsibility for my engagement in cutaneous lymphomas lies with Sergio Chimenti, who introduced me to the subject and opened for me the door to Graz, and especially with Helmut Kerl, who taught me the essentials in the field and helped me constantly over the years. Together we scrutinized thousands of cases, in so doing also forging a friendship that endured for almost three decades. It is an invaluable benefit to have somebody with whom one can share difficult cases and problematic diagnoses. In addition to the feeling of protection that Helmut gave me as a mentor, he also helped me to refine my diagnostic skills during almost every encounter. On the other hand, maturation is inevitably bounded to the making of mistakes: I was fortunate to have a knowledgeable person near me, who showed me my many errors and who corrected them before they could bear any consequence. After so many years working together, I realize that in many ways the relationship between a mentor and a student is similar to the one that exists between a father and a son, and now that Helmut Kerl is retired I miss his guidance and continuous support. Most of the material in this book comes from the files of the Department of Dermatology of the Medical University of Graz. During many years we built a Register that now provides the necessary base for academic work in the field of cutaneous lymphomas. In 1987, when I came to Graz for the first time, I had the opportunity to go through all registers of the department. Helmut Kerl provided me with a small room under the roof where I lived for more than six years, checking daily histopathological slides, photographs, clinical records, and archives all of this at a time when the records were large, dusty books, and the pictures were kodachromes that had to be duplicated by a professional photographer. Many records dated from a time when I was in primary school, or not even born. On the other hand, we now have a documentation that includes initial biopsies and pictures of most of the patients seen in the Department, many of whom returned for regular follow-up over years or even decades. Even those who succumbed to their disease some of them long before I came to Graz, can still teach a lesson, as we are continuously re-evaluating old cases with new methods that did not exist at the time when the patients were observed, thereby learning how to better treat those who are coming today. In all previous editions of the book, particular emphasis was put on illustrations, as figures describe much better than words clinical lesions and histopathologic features. In this fourth edition the number of illustrations has been again considerably expanded, and the majority of the old figures have been replaced by new ones. In addition to updating diagnostic criteria and management options for all diseases, new chapters and many new entities have been included, both among the cutaneous lymphomas and the pseudolymphomas. Readers will now find data on primary cutaneous T-follicular helper (T FH )-cell lymphoma, intralymphatic CD30 + anaplastic large cell lymphoma, specific cutaneous manifestations in extracavitary primary effusion lymphoma, specific cutaneous manifestations in Burkitt lymphoma, cutaneous plasmablastic lymphoma, pseudolymphomatous acrodermatitis chronica atrophicans, pseudolymphomatous atopic dermatitis, non-neoplastic erythroderma in adult patients, Epstein Barr virus (EBV)-associated mucocutaneous ulcers, cutaneous IgG4-related disease, cutaneous and systemic plasmacytosis, benign intralymphatic proliferation of T-cell lymphoid blasts, and other conditions and disease variants that were not included in the previous editions. A new section on cutaneous lymphomas in children and adolescents offers an overview of these disorders in the pediatric population. The number of teaching cases has been greatly expanded, too. All of the old teaching cases have been replaced and new ones have been added to most chapters. These brief case reports offer the opportunity to look at rare presentations that deviate from ix
x Preface the conventional aspects of cutaneous lymphoproliferative disorders. During the last 20 years or so, many friends and colleagues from every corner of the world have visited me in Graz for the purpose of studying dermatopathology and cutaneous lymphomas. This mixture of genders, races, idioms, and ages has been great fun, as well as an invaluable source of cultural growth. Those who have been in Graz know that on the wall in front of my microscope there is a big poster of Bruce Springsteen. It is hanging there not only because I like his music, but especially because he has been a continuous source of inspiration since 1975, the year when as a teenager I came across his record Born to run. Even though I don t know him personally, I learned from him that there is a huge work behind any successful performance, and that talent, joy, and passion must be conjugated to professionalism, care, and commitment in order to produce outstanding results. If I had a wish for this book, it would be to transmit through it to the readers the enthusiasm that I feel for the field of cutaneous lymphomas, in the same way as Bruce Springsteen conveyed me the love and passion for his music for so many years. Lorenzo Cerroni Graz, May 2014
Acknowledgments The first words of thanks goes to Helmut Kerl and Kevin Gatter, who started this project with me many years ago. Without them the first three editions would have never been published. They have been, and still are, a continuous source of inspiration, and their friendship is a rare gift. I have a particular debt of gratitude to Sergio Chimenti, who followed and corrected my uncertain steps when I was a medical student and then a dermatology resident, and who gave me the opportunity to come to Graz. A teacher opens a door, a student enters alone : he has opened a door that changed my life. I would like to thank the many clinicians who provided the essential material and information necessary to prepare the book. A particular thanks goes to those who sent me unusual, interesting, and challenging cases in consultation, and especially to Elvira Bartolo, Giovanni Borroni, Fritz Breier, Sergio Chimenti, Maria Cristina Coccia, Carlo Cota, Fabio Facchetti, Gerardo Ferrara, Irene Hopfel-Kreiner, Akira Ishiko, Martin Laimer, Mario Magana, Robert Müllegger, Conny Müller, Luca Muscardin, Simonetta Piana, Luis Requena, Omar Sangueza, Hiroshi Shimizu, Tatsushi Shiomi, Wolfram Sterry, Pablo Umbert, Esmeralda Vale, Isabel Viana, Annika Volke, and Ferdinand Wutzelhofer, who allowed me to use clinical pictures of their patients. Special thanks are due to all technicians in the dermatopathology laboratory of the Department of Dermatology at the Medical University of Graz, and particularly to Uli Schmidbauer, who prepared superb histopathologic and immunohistochemical sections for all of the photomicrographs included in the book. A warm thanks also to Werner Stieber, Almuth Kunrath, and Silke Schweighart, the three photographers of our Department, who are responsible for the excellent quality of our clinical pictures. I would also like to thank all colleagues at the Department of Dermatology of the Medical University of Graz, and particularly the Chairman, Werner Aberer, the team of engaged and competent physicians that is participating in the management of patients with cutaneous lymphoma, Regina Fink-Puches, Ingrid Wolf, Erika Richtig, and Rainer Hofmann-Wellenhof, my excellent co-workers in the Dermatopathology Unit, Laila El Shabrawi-Caelen and Steven Kaddu, and those who are helping me with great passion and engagement in the academic work on cutaneous lymphomas, Cesare Massone, Isabella Fried, and Thomas Wiesner. I am greatly indebted to Patricia Bateson, Rob Blundell, Aileen Castell, Rebecca Huxley, Jan Ross, Martin Sudgen, Oliver Walter, and Hayley Wood, and all other persons involved at Wiley-Blackwell for the help and support provided in the preparation of this fourth edition. I wish also to express my deep gratitude to all of my patients. I hope that the lessons learned by studying their diseases will help to improve the lives of all individuals affected by cutaneous lymphomas. Finally, most of all I am grateful to my family, much more than I could put in words. My wife Ricarda, my daughter Livia, and my son Luca supported me daily, tolerating with infinite patience the long hours that I typed on a keyboard or clicked on a mouse while staring at the computer screen. They are my joy and my pride. xi