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 Hematopathology
THIRD EDITION
A Volume in the Series: Foundations in Diagnostic Pathology

Eric D. Hsi, MD
Professor of Pathology
Chair
Department of Laboratory Medicine
Cleveland Clinic;
Professor of Pathology
Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio

Series Editor
John R. Goldblum, MD
Chairman of Pathology
Cleveland Clinic,
Professor of Pathology
Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio

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1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899

HEMATOPATHOLOGY: A VOLUME IN THE SERIES: FOUNDATIONS IN

DIAGNOSTIC PATHOLOGY, THIRD EDITION ISBN: 978-0-323-47913-4
Copyright © 2018 by Elsevier, Inc. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).

Notices

Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical treatment may
become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating
and using any information, methods, compounds, or experiments described herein. In using such
information or methods they should be mindful of their own safety and the safety of others, including
parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most
current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be
administered, to verify the recommended dose or formula, the method and duration of administration, and
contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge
of their patients, to make diagnoses, to determine dosages and the best treatment for each individual
patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume
any liability for any injury and/or damage to persons or property as a matter of product liability,
negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas
contained in the material herein.

Previous editions copyrighted 2012 and 2007.

Library of Congress Cataloging-in-Publication Data

Names: Hsi, Eric D., editor.

Title: Hematopathology / [edited by] Eric D. Hsi.
Other titles: Hematopathology (Hsi) | Foundations in diagnostic pathology.
Description: Third edition. | Philadelphia, PA : Elsevier, [2018] | Series:
Foundations in diagnostic pathology | Includes bibliographical references
and index.
Identifiers: LCCN 2017034574 | ISBN 9780323479134 (hardcover : alk. paper)
Subjects: | MESH: Hematologic Diseases–pathology | Hematologic
Diseases–diagnosis | Lymphatic Diseases–pathology | Lymphatic
Diseases–diagnosis
Classification: LCC RB145 | NLM WH 120 | DDC 616.07/561–dc23 LC record available
at https://lccn.loc.gov/2017034574

Content Strategist: Michael Houston

Content Development Specialist: Meghan Andress
Publishing Services Manager: Catherine Jackson
Senior Project Manager: Rachel E. McMullen
Design Direction: Renee Duenow

Printed in China

Last digit is the print number: 9 8 7 6 5 4 3 2 1

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 To my teachers and mentors who inspired me,
our trainees who constantly challenge and question,
and my family who makes it all worthwhile.

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 ■ C O N T R I B U TO R S

John Anastasi, MD Judith A. Ferry, MD

Associate Professor Professor of Pathology
Department of Pathology Department of Pathology
University of Chicago, Pritzker School of Medicine; Harvard Medical School;
Director Director of Hematopathology
Section of Hematopathology, Clinical Hematology Laboratory Department of Pathology
University of Chicago Medical Center Massachusetts General Hospital
Chicago, Illinois Boston, Massachusetts
Daniel A. Arber, MD William G. Finn, MD
Professor Department of Pathology Medical Director
University of Chicago Warde Medical Laboratory
Chicago, Illinois Ann Arbor, Michigan
Dong Chen, MD, PhD Juehua Gao, MD, PhD
Consultant Assistant Professor of Pathology
Division of Hematopathology Department of Pathology
Mayo Clinic; Northwestern University
Associate Professor Chicago, Illinois
Laboratory Medicine and Pathology
Tracy I. George, MD
College of Medicine, Mayo Clinic
Professor
Rochester, Minnesota
Department of Pathology
Kudakwashe Chikwava, MB, ChB University of New Mexico School of Medicine;
Assistant Professor Vice Chair of Clinical Affairs
Department of Pathology and Cell Biology Hematopathology Division Chief
University of Pennsylvania School of Medicine; Department of Pathology
Sydney Kimmel Medical College–Thomas Jefferson University; University of New Mexico Health Sciences Center
Pediatric Pathologist Albuquerque, New Mexico
Department of Pathology
Robert Paul Hasserjian, MD
Nemours/Alfred L. duPont Hospital for Children
Associate Professor
Philadelphia, Pennsylvania
Department of Pathology
John Kim Choi, MD, PhD Massachusetts General Hospital and Harvard Medical School
Director of Hematopathology Boston, Massachusetts
Department of Pathology
Rong He, MD
St. Jude Children’s Research Hospital
Consultant,
Memphis, Tennessee
Assistant Professor
James R. Cook, MD, PhD Division of Hematopathology
Department of Laboratory Medicine Mayo Clinic
Cleveland Clinic; Rochester, Minnesota
Associate Professor of Pathology
James D. Hoyer, MD
Cleveland Clinic Lerner College of Medicine
Consultant,
Cleveland, Ohio
Professor
Yuri Fedoriw, MD Division of Hematopathology
Associate Professor, Director of Hematopathology Mayo Clinic
Department of Pathology and Laboratory Medicine Rochester, Michigan
University of North Carolina
Eric D. Hsi, MD
Chapel Hill, North Carolina
Professor of Pathology
Falko Fend, MD Chair
Professor Department of Laboratory Medicine Cleveland Clinic;
Institute of Pathology Professor of Pathology
University Hospital Tübingen Cleveland Clinic Lerner College of Medicine
Tübingen, Germany Cleveland, Ohio

vii
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viii Contributors

Rebecca L. King, MD Jennifer L. Oliveira, MD

Assistant Professor of Laboratory Medicine and Pathology Consultant,
Division of Hematopathology Assistant Professor
Mayo Clinic Division of Hematopathology
Rochester, Minnesota Mayo Clinic
Rochester, Minnesota
Kandice Kottke-Marchant, MD, PhD
Medical Director Hemostasis and Thrombosis Dennis P. O’Malley, MD
Department of Laboratory Medicine Hematopathologist
Cleveland Clinic Foundation; Neogenomics
Professor of Pathology Aliso Viejo, California
Cleveland Clinic Lerner College of Medicine
Jennifer Lee Picarsic, MD
Cleveland, Ohio
Assistant Professor
Paul J. Kurtin, MD Department of Pathology
Professor of Laboratory Medicine and Pathology University of Pittsburgh School of Medicine;
Division of Hematopathology Attending Pathologist
Mayo Clinic Division of Anatomic Pathology
Rochester, Minnesota Children’s Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania
Steven J. Kussick, MD, PhD
Director of Hematopathology and Flow Cytometry Leticia Quintanilla-Martinez, MD
PhenoPath Laboratories; Professor
Clinical Assistant Professor Institute of Pathology
Department of Laboratory Medicine University Hospital, Eberhard-Karls-University Tübingen
University of Washington Tübingen, Germany
Seattle, Washington
Heesun J. Rogers, MD, PhD
Pei Lin, MD Staff Hematopathologist
Professor Department of Laboratory Medicine
Department of Hematopathology Cleveland Clinic Foundation
University of Texas–MD Anderson Cancer Center Cleveland, Ohio
Houston, Texas
Jonathan W. Said, MD
William R. Macon, MD Professor of Pathology
Professor of Laboratory Medicine and Pathology Department of Pathology
Division of Hematopathology David Geffen School of Medicine;
Mayo Clinic Vice Chair Research, Chief of Hematopathology
Rochester, Minnesota Department of Pathology
David Geffen School of Medicine and UCLA Medical Center
Sara A. Monaghan, MD
Los Angeles, California
Associate Professor
Department of Pathology Graham W. Slack, MD
University of Pittsburgh School of Medicine Pathologist
Pittsburgh, Pennsylvania Department of Pathology and Laboratory Medicine
British Columbia Cancer Agency;
Megan O. Nakashima, MD
Clinical Associate Professor
Department of Laboratory Medicine
University of British Columbia
Cleveland Clinic
Vancouver, British Columbia, Canada
Cleveland, Ohio
Lauren Smith, MD
Phuong L. Nguyen, MD
Associate Professor of Pathology,
Associate Professor of Laboratory Medicine and Pathology
Section Head, Hematopathology,
Division of Hematopathology
Director, Hematopathology Fellowship,
Mayo Clinic
Director, Medical School Path of Excellence in Ethics
Rochester, Minnesota
University of Michigan
Robert S. Ohgami, MD, PhD Ann Arbor, Michigan
Assistant Professor,
Beenu Thakral, MD
Associate Program Director for Anatomic Pathology
Assistant Professor
Department of Pathology
Department of Hematopathology
Stanford University
MD Anderson Cancer Center
Stanford, California
Houston, Texas

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Contributors ix

David S. Viswanatha, MD James M. Ziai, MD

Consultant, Research Pathologist
Professor Genentech, Inc.
Division of Hematopathology San Francisco, California
Mayo Clinic
Rochester, Minnesota
Sa A. Wang, MD
Associate Professor
Department of Hematopathology
MD Anderson Cancer Center
Houston, Texas

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As any practicing pathologist knows, it is not possible for
any single individual to master all of the skills and knowledge
required to perform all areas of surgical pathology at the
highest level. Providing a correct diagnosis is challenging
enough, but the standard of care has now far surpassed simply
providing an accurate pathologic diagnosis. We are now asked
to provide an enormous amount of ancillary information,
both diagnostic and prognostic, often on minute tissue frag-
ments, a task that can be daunting even for the most skilled
and experienced pathologists.
Although general surgical pathology textbooks remain
useful resources, they cannot possibly cover many of the
detailed aspects that pathologists need to know and include
in their diagnostic reports. For this reason, Foundations in
Diagnostic Pathology was initiated. This series of books is
designed to cover the major areas of surgical pathology, with
each volume focusing on one major topic. The goal of every
book in this series, which is now in its third edition, is to
provide the essential information that any pathologist—whether
general or subspecialized, in training or in practice—would
find useful in the evaluation of virtually any type of specimen
encountered.
My colleague of many years at Cleveland Clinic, Dr. Eric
Hsi, has edited this outstanding book on hematopathology
that fulfills the goals and philosophy behind Foundations in
Diagnostic Pathology. This third edition cuts to the essentials
of what all practicing pathologists want and need to know about
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■ FOREWORD
this rapidly evolving group of neoplastic and non-neoplastic
disorders. As always, the list of contributors is impressive and
includes a who’s who of hematopathologists, all of whom were
extremely generous in providing their time and expertise to
this book. By design, there is uniformity in the organization
of these chapters, each of which includes practical informa-
tion and numerous photographs that emphasize the essential
diagnostic points. Importantly, there is seamless integration
of ancillary diagnostic techniques including immunohisto-
chemistry, cytogenetics, and molecular techniques, which are
essential to the modern practice of hematopathology.
The book is organized into four major sections: Non-
Neoplastic Disorders; Lymphomas; Leukemias, Chronic
Myeloproliferative Neoplasms, and Myelodysplasia; and finally
Disorders of Histiocytes, Mast Cells, Plasma Cells, Spleen,
and Ancillary Techniques. This edition features 24 chapters
written by leaders in the field, and each chapter cuts to the
heart of what practicing pathologists need to know.
I would like to extend my deepest appreciation to Dr. Eric
Hsi and all of the authors who have contributed to this
outstanding third edition of the Foundations in Diagnostic
Pathology series. I strongly believe this edition improves on
what was already an exceptional volume in this series, and
I am confident you will enjoy this edition of the Foundations
in Diagnostic Pathology series.
John R. Goldblum, MD
xi
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Since the first edition of this text in 2007, classifications have
evolved to incorporate much more information that has an
impact on the diagnosis and therapy of hematologic diseases.
I am honored to have been asked to embark on a third edition
of this book. New authors have been added and chapters
updated and revised. I am pleased to have incorporated a
more complete treatment of coagulation that serves to dif-
ferentiate this book as one that now covers the spectrum of
non-neoplastic hematopathology, neoplastic hematopathology,
and coagulation. I believe this text will give the reader a solid
foundation for learning and practicing hematopathology.
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■ P R E FA C E
Importantly, it incorporates information and classifications
relevant to the long-awaited 2016 WHO update. As in previous
editions, I am indebted to the numerous expert contributors
who have given of themselves to produce excellent and concise
chapters (with a minimal amount of nagging from me …).
They are the true resource and talent for this book, and it
has been an honor to work with this group of outstanding
pathologists and educators.
Eric D. Hsi, MD
xiii
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 ■ CONTE NTS

S E C T I O N 1 Chapter 10
Immunodeficiency-Related Lymphoproliferative
Non-Neoplastic Disorders Disorders, 340
Jonathan W. Said, MD
Chapter 1
Red Blood Cell/Hemoglobin Disorders, 3 Chapter 11
Juehua Gao, MD, PhD, and Sara A. Monaghan, MD Hodgkin Lymphoma, 363
Falko Fend, MD, and Leticia Quintanilla-Martinez, MD
Chapter 2
Hemostasis and Thrombosis, 57

3
Heesun J. Rogers, MD, PhD, Megan O. Nakashima, MD,
and Kandice Kottke-Marchant, MD, PhD S E C T I O N
Chapter 3 Leukemias, Chronic
Non-Neoplastic Morphologic Abnormalities of White
Blood Cells and Macrophages, 106 Myeloproliferative Neoplasms,
Dennis P. O’Malley, MD, Eric D. Hsi, MD,
Lauren Smith, MD, and Yuri Fedoriw, MD
and Myelodysplasia
Chapter 12
Chapter 4 B-Cell Leukemias of Mature Lymphocytes, 397
Reactive Lymph Nodes and Castleman Disease, 118 Eric D. Hsi, MD
Judith A. Ferry, MD

Chapter 5 Chapter 13
Bone Marrow Failure Syndromes, 167 Mature T-Cell and Natural Killer–Cell
James R. Cook, MD, PhD Leukemias, 414
William G. Finn, MD, and William R. Macon, MD
Chapter 6
Benign Causes of Bone Marrow Abnormalities Including Chapter 14
Infections, Storage Diseases, Systemic Disorders, and Acute Myeloid Leukemia, 429
Stromal Changes, 184 Daniel A. Arber, MD
Dennis P. O’Malley, MD, Lauren Smith, MD, and
Yuri Fedoriw, MD Chapter 15
Precursor Lymphoid Neoplasms, 467
John Kim Choi, MD, PhD

S E C T I O N 2 Chapter 16
Lymphomas Acute Undifferentiated Leukemia and Mixed-Phenotype
Acute Leukemias, 481
John Kim Choi, MD, PhD
Chapter 7
Small B-Cell Lymphomas, 213
Rebecca L. King, MD, and Paul J. Kurtin, MD Chapter 17
Myeloproliferative and “Overlap” Myelodysplastic/
Chapter 8 Myeloproliferative Neoplasms, 488
Diffuse Aggressive B-Cell Lymphomas, 271 Beenu Thakral, MD, John Anastasi, MD, and
Graham W. Slack, MD, and Eric D. Hsi, MD Sa A. Wang, MD

Chapter 9 Chapter 18
Peripheral T-Cell Lymphomas, 306 Myelodysplastic Syndromes, 539
William R. Macon, MD Phuong L. Nguyen, MD, and Robert Paul Hasserjian, MD
xv
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xvi Contents

S E C T I O N 4 Chapter 22
Disorders of Histiocytes, Mast
Cells, Plasma Cells, Spleen,
and Ancillary Techniques
Chapter 19
Disorders of Histiocytes, 567
Jennifer Lee Picarsic, MD, and
Kudakwashe Chikwava, MB, ChB
Chapter 20
Mastocytosis, 617
Dong Chen, MD, PhD, and Tracy I. George, MD
Disorders of the Spleen, 664
Robert S. Ohgami, MD, PhD, James M. Ziai, MD, and
Daniel A. Arber, MD
Chapter 23
Flow Cytometric Principles in Hematopathology, 686
Steven J. Kussick, MD, PhD
Chapter 24
Molecular Hematopathology, 712
Rong He, MD, Jennifer L. Oliveira, MD,
James D. Hoyer, MD, and David S. Viswanatha, MD

Chapter 21
Multiple Myeloma and Other Plasma Cell
Neoplasms, 642
Pei Lin, MD

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 S E C T I O N
1
Non-Neoplastic
Disorders

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