Neoplastic Hematopathology CONTEMPORARY HEMATOLOGY Judith E

Neoplastic Hematopathology CONTEMPORARY HEMATOLOGY Judith E. Karp, MD, Series Editor

For other titles published in the series, go to www.springer.com/series/7681 Neoplastic Hematopathology

Experimental and Clinical Approaches

Edited by Dan Jones, MD, PhD Department of Hematopathology M. D. Anderson Cancer Center The University of Texas Houston, TX USA Editor Dan Jones Department of Hematopathology M. D. Anderson Cancer Center The University of Texas Houston, TX USA [email protected]

ISBN 978-1-60761-383-1 e-ISBN 978-1-60761-384-8 DOI 10.1007/978-1-60761-384-8 Springer New York Dordrecht Heidelberg London

Library of Congress Control Number: 2009932414

© Humana Press, a part of Springer Science + Business Media, LLC 2010 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not iden- tified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, nei- ther the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Printed on acid-free paper

Humana Press is part of Springer Science+Business Media (www.springer.com) Preface

My goal for this textbook is to provide an overview of the discipline of hematopathology that connects the field with recent advances in immunology research and with current clinical practice in the treatment of lymphomas and leukemias. With separate sections on laboratory techniques, diagnostic hematopathology, treatment, and stem cell transplantation, this book is designed to be useful for both trainees and specialists in pathology and hematology-oncology. We have also summarized the current directions in translational research that will be of most interest to experienced hematopathologists and scientists working in lymphoma and leukemia biology. The terminology and diagnostic categories used are those of the 4th World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues, which was released in late 2008. However, the chapter authors also provide a clinical and experimental context for this classification and point out areas where improvements are needed. A study guide is provided which highlights central concepts from each chapter to make the book suit- able for boards review in hematopathology and hematology-oncology. The concluding chapter attempts to connect broad swaths of cancer biology and immunology with the trend towards individualized risk prediction and therapeutics (i.e. personalized medicine). No area of pathology currently encompasses as many disparate disciplines as hematopathology, including laboratory medicine, molecular diagnostics, surgical pathology, clinical hematology and translational science. For this reason, I believe there is a need for a broader approach to the diagnostic endeavor that encompasses other approaches and concerns. My reasons for taking this more multidisciplinary approach arise out of my interactions over the last 10 years with my clinical colleagues at M. D. Anderson Cancer Center in the departments of Leukemia, Lymphoma, and Stem Cell Transplantation, all of whom have helped me focus on the elements of diagnosis that most impact clinical care. I am grateful to have some of those colleagues joining me as coauthors to provide their insights into treatment. My interest in linking diagnostics more closely with clinical management was also shaped by my train- ing at Brigham and Women’s Hospital in Boston where I had three terrific role models in this regard in Geraldine Pinkus, Chris Fletcher, and Ramzi Cotran. For their constant support of my work, I dedicate this book to my parents, Bernice Katz Jones and Professor Richard Victor Jones, whose boundless intellectual curiosity remains a continuing source of inspiration for me. I thank all the authors for their outstanding contributions and for their willingness to participate in this type of multi-disciplinary project. I also greatly appreciate the editorial assistance of Frances Louie at Humana Press and Sundardevadoss Dharmendra at SPi, as well as Brian Stewart, Jenna Boatright, Lakisha Rodgers, Orelia Kelly, and Steven Reyes at M.D. Anderson. Finally, I am greatly indebted to Roberto Miranda for his expert assistance with chapter review and editing. Houston, TX Dan Jones, MD, PhD

v Contents

Preface...... v Contributors...... xi How to Use This Book...... xv

Section 1 Introduction to Diagnosis and Laboratory Techniques

1 Approaches to Classification of Lymphoma and Leukemia...... 3 Dan Jones

2 Immunohistochemical Profiling of Lymphoma...... 21 Matthew W. Anderson and Yasodha Natkunam

3 Flow Cytometry in the Evaluation of Hematologic Malignancies...... 45 Jeffrey L. Jorgensen

4 Molecular Diagnostics and Cytogenetic Testing...... 61 Su Chen, Zhuang Zuo, and Dan Jones

Section 2 Neoplasms of the Bone Marrow

5 The Bone Marrow in Normal and Disease States...... 99 Dan Jones and Roberto N. Miranda

6 Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms...... 123 Sa A. Wang

7 Acute Myeloid Leukemia...... 145 Carlos E. Bueso-Ramos

8 Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes...... 165 Farhad Ravandi

9 Myeloproliferative Neoplasms...... 177 C. Cameron Yin and Dan Jones

vii viii Contents

10 Chronic Myelogenous Leukemia...... 193 Robert P. Hasserjian

11 Treatment of Myeloproliferative Neoplasms...... 213 Starla Sweany and Elias Jabbour

Section 3 Tumors of the Lymph Node and Extranodal Tissues

12 Lymph Node Biology and Lymphadenitis...... 223 Roberto N. Miranda

13 Lymphoblastic Leukemia and Lymphoma...... 239 Andrea M. Sheehan

14 Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma...... 251 Ellen Schlette

15 Marginal Zone Lymphomas...... 263 Rachel L. Sargent

16 Follicular Lymphoma and Mantle Cell Lymphoma...... 279 Dan Jones

17 Aggressive B-cell Lymphomas: Diffuse Large B-cell Lymphoma and Burkitt Lymphoma...... 303 Henry Y. Dong

18 Therapy of B-cell Lymphoproliferative Disorders...... 323 Nathan Fowler, Sandra Horowitz, and Peter McLaughlin

19 Plasma Cell Myeloma and Other Plasma Cell Dyscrasias...... 333 Marwan A. Yared

20 Hodgkin Lymphoma...... 349 Robert Lin, Dan Jones, and Sherif Ibrahim

21 Treatment of Hodgkin Lymphoma...... 367 Samer A. Srour and Luis E. Fayad

22 Classification of T-cell and NK-cell Malignancies...... 391 Dan Jones

23 Clinical Management of Non-cutaneous T-cell and NK-cell Malignancies...... 413 Marco Herling

24 Cutaneous T-cell Lymphomas...... 427 Pranil Chandra, Mauricio P. Oyarzo, and Dan Jones

25 Treatment of Cutaneous T-cell Lymphomas...... 449 Katherine M. Cox and Madeleine Duvic

26 Histiocytic and Dendritic Cell Neoplasms...... 459 Kedar V. Inamdar and Dan Jones Contents ix

27 Extranodal Lymphomas and Tumors of the Thymus...... 477 Brian D. Stewart, John T. Manning, and Dan Jones

Section 4 Stem Cell Transplantation

28 Clinical Aspects of Hematopoietic Stem Cell Transplantation...... 505 Elizabeth J. Shpall and Marcos de Lima

29 Post-transplant Molecular Monitoring...... 513 Dan Jones

30 Post-transplant Immune Function and the Development of Lymphoma...... 521 Deqin Ma and Dan Jones

Section 5 Experimental Hematopathology

31 Hematopoiesis and Stem Cell Biology...... 531 Claudiu Cotta

32 Role of Host Genetics in Lymphoma...... 545 Ahmet Dogan

33 Developing Prognostic Models for Diffuse Large B-cell Lymphoma...... 553 Izidore S. Lossos

34 Growth Signaling and Survival Pathways in Aggressive B-cell Lymphoma...... 563 Lan V. Pham and Richard J. Ford

35 Proteomic Profiling and Target Identification in Lymphoma...... 573 Megan S. Lim

36 Mouse Models of Lymphoma and Lymphoid Leukemia...... 583 M. James You

37 Mouse Models of Myeloid Leukemia...... 597 Robert B. Lorsbach

38 Designing Targeted Therapies for Lymphomas and Leukemias...... 611 Dan Jones

Study Guide...... 627

Index...... 635 Contributors

Matthew W. Anderson, MD, PhD Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

Carlos E. Bueso-Ramos, MD, PhD Department of Hematopahology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Pranil Chandra, DO ACL Laboratories, Great Lakes Pathology, Milwaukee, WI

Su Chen, MD, PhD Department of Hematopahology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Claudiu Cotta, MD, PhD Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA

Katherine M. Cox, MD Department of Dermatology, University of Texas Medical School at Houston, Houston, TX, USA

Marcos de Lima, MD Department of Stem Cell Transplantation and Cell Therapy, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Ahmet Dogan, MD, PhD Departments of Anatomic Pathology and Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

Henry Y. Dong, MD, PhD Molecular Pathology, Genzyme Genetics, New York, NY, USA

Madeleine Duvic, MD Department of Dermatology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

xi xii Contributors

Luis E. Fayad, MD Department of Lymphoma & Myeloma, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Richard J. Ford, MD, PhD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Nathan Fowler, MD Department of Lymphoma & Myeloma, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Robert P. Hasserjian, MD Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Marco Herling, MD Department of Medicine I, Cologne University, Cologne, Germany

Sandra Horowitz, PharmD Pharmacy Clinical Programs, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Sherif Ibrahim, MD, PhD Department of Pathology, New York University Medical Center, New York, NY, USA

Kedar V. Inamdar, MD, PhD Department of Pathology, Henry Ford Hospital, Detroit, MI, USA

Elias Jabbour, MD Department of Leukemia, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Dan Jones, MD, PhD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Jeffrey L. Jorgensen, MD, PhD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Megan S. Lim, MD, PhD Department of Pathology, University of Michigan, Ann Arbor, MI, USA

Robert Lin, MD Department of Pathology, New York University Medical Center, New York, NY, USA

Robert B. Lorsbach, MD, PhD Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Izidore S. Lossos, MD Department of Lymphoma, Miller School of Medicine, University of Miami, Miami, FL, USA Contributors xiii

Deqin Ma, MD, PhD Department of Anatomic Pathology, National Institutes of Health, Bethesda, MD, USA

John T. Manning, MD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Peter McLaughlin, MD Department of Lymphoma & Myeloma, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Roberto N. Miranda, MD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Yasodha Natkunam, MD, PhD Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

Mauricio P. Oyarzo, MD Department of Pathology, Clinica Alemana, Santiago, Chile

Lan V. Pham, PhD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Farhad Ravandi, MD Department of Leukemia, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Rachel L. Sargent, MD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Ellen Schlette, MD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Andrea M. Sheehan, MD Department of Pathology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA

Elizabeth J. Shpall, MD Department of Stem Cell Transplantation and Cell Therapy, M. D. Anderson Cancer Center, The University of Texas, Houston, TX

Samer A. Srour, MB, ChB Department of Internal Medicine, The University of Oklahoma College of Medicine, Oklahoma City, OK

Brian D. Stewart, MD Department of Pathology, The University of Texas Health Sciences Center at Houston, Houston, TX, USA xiv Contributors

Starla Sweany, PharmD, BCOP Division of Pharmacy, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Sa A.Wang, MD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Marwan A. Yared, MD Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Cameron C. Yin, MD, PhD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

M. James You, MD, PhD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA

Zhuang Zuo, MD, PhD Department of Hematopathology, M. D. Anderson Cancer Center, The University of Texas, Houston, TX, USA How to Use This Book

As an overview of diagnostic hematopathology for hematologist-oncologists: • The pathologic overview of each group of tumors is followed by chapters written by experienced clinicians summarizing the current state of diagnosis, staging and treatment for lymphoma, leukemias and related neoplasms. • The active areas of research that will lead to new therapeutic agents and biomarkers development are summarized in the last section of the text (Chaps. 31–38). As a reference text for practicing pathologists: • Chapter 1 lists the current terminology derived from the 2008 WHO Classification of Haematopoietic and Lymphoid Tissues, which should be used for diagnosis whenever possible. • Diagnostic pitfalls and differential diagnoses that should be considered are highlighted in each of the pathology chapters. • The treatment overviews (Chaps. 8, 11, 18, 21, 23, 25 and 28) are primarily intended for those pathologists wanting a more in-depth understanding of current treatment issues. For boards review for pathology and hematopathology trainees: • Chapters 1 (all lymphoma/leukemia types), 2 (lymph node-based tumors), and 28 (extranodal lymphomas) list the core diagnostic entities and what markers are used for differential diagnosis. • In addition, the central concepts of each chapter are highlighted in the study guide. Trainees should concentrate their review on those chapters which have the most number of unfamiliar concepts. • The photomicrographs in each pathology chapter provide the classical appearances of tumor entities. As a reference for experimental scientists and graduate students working on lymphomas and leukemias: • The methodology sections (Chaps. 2–4) give helpful hints on the use of immunohisto- chemistry, flow cytometry and molecular techniques. • The last section (Chaps. 31–38) gives an overview of the main directions of research in stem cell biology, targeted therapy, lymphocyte signaling, and perspective on host genetics and immune function in lymphoma and leukemias. • The section on prognostic markers in each diagnostic chapter may be particular useful in highlighting outstanding questions in biomarker development which would benefit from additional experimental work.