Williams Hematology Malignant Lymphoid Diseases Oliver W. Press, MD, PhD John P. Leonard, MD Giuliani/Press Endowed Chair in Cancer Research Richard T. Silver Distinguished Professor of Hematology and Fred Hutchinson Cancer Research Center Medical Oncology Professor of Medicine and Bioengineering Joan and Sanford I. Weill Department of Medicine University of Washington Weill Cornell Medical College Seattle, Washington New York Presbyterian Hospital New York, New York Marshall A. Lichtman, MD Professor Emeritus of Medicine (Hematology-Oncology) and of Biochemistry and Biophysics Dean, Emeritus School of Medicine and Dentistry University of Rochester Medical Center Rochester, New York New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto 00_Lichtman_FM_i-xiv.indd 1 09/10/17 2:12 pm Copyright © 2018 by McGraw-Hill Education. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher. ISBN: 978-1-26-011707-3 MHID: 1-26-011707-3 The material in this eBook also appears in the print version of this title: ISBN: 978-1-26-011706-6, MHID: 1-26-011706-5. eBook conversion by codeMantra Version 1.0 All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps. McGraw-Hill Education eBooks are available at special quantity discounts to use as premiums and sales promotions or for use in corpo- rate training programs. To contact a representative, please visit the Contact Us page at www.mhprofessional.com. Notice Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or com- plete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. TERMS OF USE This is a copyrighted work and McGraw-Hill Education and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill Education’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms. THE WORK IS PROVIDED “AS IS.” McGRAW-HILL EDUCATION AND ITS LICENSORS MAKE NO GUARANTEES OR WAR- RANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill Education and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill Education has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise. William J. Williams, MD 1926 – 2016 Medical educator, investigator, physician, mentor, academic leader, colleague, and the founding editor of Williams Hematology 00_Lichtman_FM_i-xiv.indd 3 09/10/17 2:12 pm 1 2 3 4 5 6 1 . Transmission electron micrograph (TEM) of a normal blood lymphocyte. 2. Scanning electron micrograph (SEM) of a normal blood lymphocyte. 3. TEM of Sézary cell in a patient with the erythrodermic type of cutaneous T-cell lymphoma. Note the cell’s characteristic profoundly misshaped (cerebriform) nucleus. 4. TEM of a hairy cell. Arrow indicates a ribosome-lamella complex. This structure is not specific for hairy cell leukemia but is found in a variable proportion of hairy cells in about 50 percent of cases examined by TEM. Frequent cytoplasmic membrane, “hairy,” projections. 5. TEM of plasmablast (undifferentiated myeloma cell). Arrow points to a Russell body. 6. A lymphoblast from the marrow of a patient with acute lymphoblastic leukemia. Very high nuclear-to-cytoplasmic ratio. Prominent nucleolus. The nucleus is virtually all euchromatin (likely transcriptionally active). (Reproduced with permission from Lichtman’s Atlas of Hematology, www.accessmedicine.com.) 00_Lichtman_FM_i-xiv.indd 4 09/10/17 2:13 pm v CONTENTS Contributors .............................................. vii 12. Marginal Zone B-Cell Lymphomas .......................175 Preface.....................................................xi Pier Luigi Zinzani and Alessandro Broccoli 13. Burkitt Lymphoma.....................................183 1. Classification of Malignant Lymphoid Disorders .............1 Carla Casulo, Jonathan W. Friedberg, and Andrew G. Evans Robert A. Baiocchi 14. Cutaneous T-Cell Lymphoma (Mycosis Fungoides and 2. Acute Lymphoblastic Leukemia...........................13 Sézary Syndrome)......................................191 Richard A. Larson Larisa J. Geskin and Christina C. Patrone 3. Chronic Lymphocytic Leukemia ..........................37 15. Mature T-Cell and Natural Killer Cell Lymphomas .........207 Farrukh T. Awan and John C. Byrd Neha Mehta-Shah, Alison Moskowitz, and Steven Horwitz 4. Hairy Cell Leukemia ....................................63 16. Plasma Cell Neoplasms: General Considerations ...........223 Michael R. Grever and Gerard Lozanski Guido Tricot, Siegfried Janz, Kalyan Nadiminti, Erik Wendlandt, 5. Large Granular Lymphocytic Leukemia ....................73 and Fenghuang Zhan Pierluigi Porcu and Aharon G. Freud 17. Essential Monoclonal Gammopathy ......................237 6. General Considerations of Lymphomas: Epidemiology, Marshall A. Lichtman Etiology, Heterogeneity, and Primary Extranodal Disease.....81 18. Myeloma .............................................249 Oliver W. Press and Marshall A. Lichtman Elizabeth O’Donnell, Francesca Cottini, Noopur Raje, and Kenneth Anderson 7. Pathology of Lymphomas ................................99 Randy D. Gascoyne and Brian F. Skinnider 19. Immunoglobulin Light-Chain Amyloidosis................291 Morie A. Gertz, Taimur Sher, Angela Dispenzieri, and 8. Hodgkin Lymphoma ...................................115 Francis K. Buadi Oliver W. Press and John P. Leonard 20. Macroglobulinemia ....................................303 9. Diffuse Large B-Cell Lymphoma and Related Neoplasms ....137 Steven P. Treon, Jorge J. Castillo, Zachary R. Hunter, and Stephen D. Smith and Oliver W. Press Giampaolo Merlini 10. Follicular Lymphoma...................................153 21. Heavy-Chain Disease...................................321 Oliver W. Press and John P. Leonard Dietlind L. Wahner-Roedler and Robert A. Kyle 11. Mantle Cell Lymphoma.................................165 Index .................................................... 331 Martin Dreyling 00_Lichtman_FM_i-xiv.indd 5 09/10/17 2:13 pm This page intentionally left blank 00_Lichtman_FM_i-xiv.indd 6 09/10/17 2:13 pm vii CONTRIBUTORS Kenneth Anderson, MD Angela Dispenzieri, MD Dana-Farber Cancer Institute Division of Hematology Boston, Massachusetts Mayo Clinic Rochester, Minnesota Farrukh T. Awan, MD Associate Professor of Internal Medicine Martin Dreyling, MD Division of Hematology Department of Internal Medicine III Department of Internal Medicine Medical Center of the University of Munich The Ohio State University Comprehensive Cancer Center Munich, Germany Columbus, Ohio Andrew G. Evans, MD, PhD Robert A. Baiocchi, MD, PhD Assistant Professor Associate Professor of Medicine Department of Pathology and Laboratory Medicine Division of Hematology University of Rochester Medical Center Department of Internal Medicine Rochester, New York The Ohio State University Columbus, Ohio Aharon G. Freud, MD, PhD Assistant Professor Alessandro Broccoli, MD Department of Pathology Institute of Hematology “L. e A. Seràgnoli” The Ohio State University University of Bologna Columbus, Ohio Bologna, Italy Jonathan W. Friedberg, MD Francis K. Buadi, MD Samuel Durand Professor of Medicine Division of Hematology Director, Wilmot Cancer Institute Mayo Clinic University of Rochester Medical Center Rochester, Minnesota Rochester, New York John C. Byrd, MD Randy D. Gascoyne, MD, FRCPC D. Warren Brown Chair of Leukemia Research Clinical Professor of Pathology Professor of Medicine, Medicinal Chemistry, and Veterinary Research Director, Centre for Lymphoid Cancers Biosciences Departments of Pathology and Advanced Therapeutics Director, Division of Hematology British Columbia Cancer Agency, the BC Cancer Research Center, and Department of Medicine University of British Columbia The Ohio State University Vancouver, British Columbia, Canada Columbus, Ohio Morie A. Gertz, MD, MACP Jorge J. Castillo, MD Division of Hematology Assistant Professor of Medicine Mayo Clinic Dana-Farber Cancer Institute Rochester, Minnesota Harvard Medical School Boston, Massachusetts Larisa J. Geskin, MD, FAAD Associate Professor of Dermatology and Medicine Carla Casulo, MD Director, Division of Cutaneous Oncology and Comprehensive Skin Assistant Professor of Medicine Cancer Center James P. Wilmot Cancer Institute Department of Dermatology University of Rochester Medical Center Columbia University Rochester, New York New York, New York Francesca Cottini, MD Dana-Farber Cancer Institute Boston, Massachusetts 00_Lichtman_FM_i-xiv.indd 7 09/10/17 2:13 pm viii Contributors Contributors ix Michael G. Grever, MD Neha Mehta, MD Chair and Professor Department of Medicine Department of Internal Medicine Memorial Sloan Kettering Cancer Center Bertha Bouroncle MD and Andrew Pereny Chair in Medicine New York, New York The Ohio State University Columbus, Ohio Giampaolo Merlini, MD Director, Center for Research and Treatment of Systematic Steven Horwitz, MD Amyloidosis Department of Medicine University Hospital Policlinico San Meteo Memorial Sloan Kettering Cancer Center Professor, Department of Medicine New York, New York University of Pavia Pavia, Italy Zachary R. Hunter, PhD Bing Center for Waldenstrom’s Macroglobulinemia Alison Moskowitz, MD Dana-Farber Cancer Institute Department of Medicine Instructor of Medicine, Harvard Medical School Memorial Sloan Kettering Cancer Center Boston, Massachusetts New York, New York Siegfried Janz, MD, DSc Kalyan Nadiminti, MD Division of Hematology/Oncology and Blood and Division of Hematology/Oncology and Blood and Marrow Transplantation Marrow Transplantation Department of Pathology, Carver College of Medicine Department of Pathology, Carver College of Medicine University of Iowa Health Care University of Iowa Health Care Iowa City, Iowa Iowa City, Iowa Robert A. Kyle, MD Elizabeth O’Donnell, MD Professor of Medicine Massachusetts General Hospital Laboratory Medicine and Pathology Boston, Massachusetts Mayo Clinic Rochester, Minnesota Christina C. Patrone, BA Columbia University College of Physicians and Surgeons Richard A. Larson, MD New York, New York Section of Hematology/Oncology Department of Medicine and the Comprehensive Cancer Center Pierluigi Porcu, MD University of Chicago Professor of Internal Medicine Chicago, Illinois Division of Hematology and Comprehensive Cancer Center The Ohio State University John P. Leonard, MD Columbus, Ohio Richard T. Silver Distinguished Professor of Hematology and Medical Oncology Oliver W. Press, MD, PhD Joan and Sanford I. Weill Department of Medicine Giuliani/Press Endowed Chair in Cancer Research Weill Cornell Medical College Fred Hutchinson Cancer Research Center New York Presbyterian Hospital Professor of Medicine and Bioengineering New York, New York University of Washington Seattle, Washington Marshall A. Lichtman, MD Professor Emeritus of Medicine and of Biochemistry and Biophysics Noopur Raje, MD Dean Emeritus, School of Medicine and Dentistry Massachusetts General Hospital University of Rochester Medical Center Boston, Massachusetts Rochester, New York Taimur Sher, MD Gerard Lozanski, MD Division of Hematology/Oncology Director, Hematopathology Mayo Clinic Medical Director Jacksonville, Florida Flow Cytometry Laboratory Associate Professor—Clinical Department of Pathology The Ohio State University Columbus, Ohio 00_Lichtman_FM_i-xiv.indd 8 09/10/17 2:13 pm viii Contributors Contributors ix Brian F. Skinnider, MD Dietlind L. Wahner-Roedler, MD Clinical Associate Professor Professor of Medicine Department of Pathology Mayo Clinic Vancouver General Hospital, British Columbia Cancer Agency, and Rochester, Minnesota University of British Columbia Vancouver, British Columbia, Canada Erik Wendlandt, PhD Division of Hematology/Oncology and Blood and Stephen D. Smith, MD Marrow Transplantation Seattle Cancer Care Alliance Department of Pathology, Carver College of Medicine Seattle, Washington University of Iowa Health Care Iowa City, Iowa Steven P. Treon Director, Bing Center for Waldenstrom’s Macroglobulinemia Fenghuang Zhan, MD, PhD Dana-Farber Cancer Institute Division of Hematology/Oncology and Blood and Associate Professor, Harvard Medical School Marrow Transplantation Boston, Massachusetts Department of Pathology, Carver College of Medicine University of Iowa Health Care Guido Tricot, MD, PhD Iowa City, Iowa Division of Hematology/Oncology and Blood and Marrow Transplantation Pier Luigi Zinzani, MD, PhD Department of Pathology, Carver College of Medicine Professor University of Iowa Health Care Institute of Hematology “L. e A. Seràgnoli” Iowa City, Iowa University of Bologna Bologna, Italy 00_Lichtman_FM_i-xiv.indd 9 09/10/17 2:13 pm