LYMPH NODE AND SPLEEN CYTOHISTOLOGY
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1 LYMPH NODE AND SPLEEN CYTOHISTOLOGY
2 CYTOHISTOLOGY OF SMALL TISSUE SAMPLES Published in association with the Papanicolaou Society of Cytopathology Series editors: Kim R. Geisinger, M.D. Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA Martha B. Pitman, M.D. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Other titles in this series Cytohistology: Essential and Basic Concepts Edited by Prabodh Gupta and Zubair Baloch (ISBN ) Lung and Mediastinum Cytohistology Edited by Syed Z. Ali and Grace C. H. Yang (ISBN ) Musculoskeletal Cytohistology Lester J. Layfield, Carlos W. Bedrossian, Julia R. Crim, and Lucio Palombini (ISBN ) Cytohistology of the Serosal Surfaces Edited by Claire W. Michael, David C. Chhieng, and Carlos W. M. Bedrossian (ISBN ) Breast Cytohistology Edited by Joan Cangiarella, Aylin Simsir, and Sana O. Tabbara (ISBN )
3 LYMPH NODE AND SPLEEN CYTOHISTOLOGY Andrew S. Field, MB. BS. (Hons), F.R.C.P.A., F.I.A.C., Dip.Cytopath. (R.C.P.A.) Deputy Director and Senior Consultant, Department of Anatomical Pathology, St. Vincent s Hospital, Sydney; Senior Lecturer at the University of New South Wales, and Adjunct Associate Professor at Notre Dame Medical School, Sydney, Australia William R. Geddie, M.D., F.R.C.P.C., M.I.A.C., F.R.M.S. Cytopathologist, University Health Network, Toronto, and Assistant Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
4 The Edinburgh Building, Cambridge CB2 8RU, United Kingdom Published in the United States of America by Cambridge University Press, New York Cambridge University Press is part of the University of Cambridge. It furthers the University s mission by disseminating knowledge in the pursuit of education, learning, and research at the highest international levels of excellence. Information on this title: / This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published 2014 Printed and bound in Spain by Grofos SA, Arte sobre papel ISBN Hardback Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. All material contained within the CD-ROM is protected by copyright and other intellectual property laws. The customer acquires only the right to use the CD-ROM and does not acquire any other rights, express or implied, unless these are stated explicitly in a separate licence.... Every effort has been made in preparing this book to provide accurate and up-to-date information which is in accord with accepted standards and practice at the time of publication. Although case histories are drawn from actual cases, every effort has been made to disguise the identities of the individuals involved. Nevertheless, the authors, editors and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use.
5 CONTENTS Preface page vii 1. Introduction to fine needle and core biopsy: Techniques 1 2. Protocols for FNB, core biopsies, and ancillary techniques Diagnosis of lymph node FNB using pattern recognition and cell type assessment in an algorithmic approach Diagnosis of lymphoma on FNB lymph node material and the role of core biopsy Metastases to lymph nodes Suppurative and suppurative granulomatous patterns Granulomatous pattern Necrotizing pattern Follicle germinal center tissue fragments in dispersed, heterogeneous, predominantly small to intermediate lymphoid cell pattern with small lymphocytes predominating: Follicular hyperplasia Follicular center cell tissue fragments in a dispersed heterogeneous small to intermediate lymphoid cell pattern, with centrocytes and centroblasts predominating: Follicular and marginal zone lymphomas Dispersed heterogeneous small to intermediate lymphoid cell pattern with small lymphocytes predominating, plus prominent immunoblasts: Immunoblastic reactive lymph nodes Dispersed heterogeneous small to intermediate lymphoid cell pattern with small lymphocytes predominating, plus other inflammatory cells and large alien cells: Hodgkin lymphoma Dispersed heterogeneous small to intermediate lymphoid cell pattern with small lymphocytes predominating, plus prominent histiocytes: Sinus histiocytosis Dispersed monotonous predominantly small to intermediate lymphoid cell pattern, with no predominance of small lymphocytes, with or without vague nodularity: Small cell lymphomas 191 v
6 CONTENTS 15. Dispersed monotonous predominantly intermediate to large lymphoid cell pattern: Large cell lymphomas Pediatric lymphadenopathy Fine needle biopsy of spleen 237 Index 266 vi
7 PREFACE This book is our approach to diagnosing lymph node and splenic lesions by fine needle biopsy (FNB) and core biopsy with ancillary testing. It is the distillation of our training in cytopathology, plus our more than 50 years combined experience in routine diagnostic work and in teaching our trainee pathologists, cytotechnologists, and colleagues this approach. Lymphadenopathy is one of the commonest clinical problems presenting to clinicians in primary care and university teaching hospital practice, and this is particularly so in many resource-limited medical settings. Fine needle biopsy cytology offers a rapid, inexpensive, minimally invasive test, well tolerated by patients and capable of diagnosing most lymph node lesions, including specific infections such as tuberculosis, reactive lymphadenopathies, metastatic malignancies, and many lymphomas. Concurrent use of core biopsy and ancillary testing enhances utility by providing even greater degrees of diagnostic accuracy, and in many ways the addition of these techniques has answered the contentious arguments regarding the use of FNB material as a means of establishing the primary diagnosis and classification of lymphomas. At the very least, use of FNB in investigation of lymphadenopathy excludes common diseases and quickly identifies or triages the patients who need excision biopsy and ancillary testing. The same reasoning applies to splenic lesions, although they are less commonly encountered specimens. The key to FNB cytology providing this diagnostic service is the availability of cytopathologists trained in a sound approach to performing the FNB, making direct smears, and accurately interpreting the slides. The training challenge is greatest in resource-limited medical settings, exactly where the greatest potential benefits can be realized because of the high prevalence of diseases, such as tuberculosis, which are completely diagnosable by FNB. The next step is to utilize ancillary testing and core biopsies efficiently and costeffectively, when these are available, to refine or enhance the FNB diagnosis and quickly identify those patients who require an excisional biopsy. We hope this text will assist this teaching process with its algorithmic approach. Our working careers in cytology have bridged the period between the age of the founders of cytopathology many of whom we met as senior colleagues or teachers and the current era, when the explosion of immunophenotyping and molecular pathology have impacted greatly on FNB of lymph nodes and spleen. We have learned from many people over the years, but among them two in particular stand out. Torsten Löwhagen at the Karolinska Hospital, Stockholm, had a great impact on both of us when we attended a course there in His teaching was inspirational but also very systematic, placing great emphasis on the fundamental requirement for excellent technique in performing the FNB and in making direct smears, and on a logical process at the microscope that aimed at diagnosis through the recognition of key cytological features for each entity. When Svante Orell, a peer of Torsten Löwhagen at the Karolinska, immigrated to Australia in the 1960s, he preached a similar approach through his teaching and his textbook, the Manual and Atlas of Fine Needle Aspiration Cytology. This book is our development of the themes of these teachers, honed through the last 30 years of diagnostic work, teaching, and research and reflects our current practice. We have emphasized the crucial technical aspects of FNB cytology, and a diagnostic approach based on a new integration of pattern recognition and cell type assessment that we use and teach for lymph nodes and spleen cytology. And we have combined this with a presentation of the full range of ancillary testing currently available and the core biopsy findings, which should always be correlated with the cytology, to produce a practical guide to the handling of these small specimens. We recommend that readers faced with a FNB biopsy should first read Chapter 3 on pattern and cell type assessment and the algorithmic approach we have developed, and then if their case is lymphoid, Chapter 4, which details the diagnosis of reactive lymphoid vii
8 PREFACE processes and lymphoma. The reader should then refer to the chapter that details the various infectious, reactive,lymphomatousormetastaticgroupsoflesionsthat can produce that pattern and cell type. The key cytologic diagnostic criteria, differential diagnosis, histological features, and ancillary technique findings of each disease entity within a particular pattern are presented in each chapter. We realize that there is repetition in this discussion between patterns and cell types and specific disease entities. We think this is appropriate because it begins with the algorithmic approach to diagnosis based on low-power pattern and high-power cell type assessment and then provides, in logical organization, the detailed information and differential diagnoses of each specific disease. We have tried to use accurately descriptive terminology at all times for follicle germinal center tissue fragments ( lymphohistiocytic fragments ), follicular center cell tissue fragments ( nodules of follicular lymphoma ) and fragments of lymphoid cell cytoplasm ( lymphoglandular bodies ). We have used abbreviations for lymphomas, starting afresh in each chapter. We hope that readers will find this useful. We would like to thank all of the teachers and colleagues who have assisted us in our careers, and hope that this text will be a practical, bench top, step-by-step guide to pathologists and cytotechnologists in the diagnosis of lymph node and splenic lesions by FNB, core biopsy and ancillary testing. Finally, we would like to thank our wives Alison Field and Naomi Miller for their support during the writing of this text. Andrew S. Field William R. Geddie viii
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