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 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

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 William J. Williams, MD
1926 – 2016
Medical educator, investigator, physician, mentor, academic leader,
colleague, and the founding editor of Williams Hematology

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 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.)

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 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

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 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

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 viii Contributors

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

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 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

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 xi

PREFACE
Bifurcation is an essential feature of biology. It underlies differentiation The lymphoid neoplasms are the subject of this text. Neoplasms
as one cell, through a process of mitosis accompanied by altered gene originating in the lymphoid progenitor cell hierarchy constitute the
expression, forms two distinct cell lineages. The hematopoietic system lymphomas and lymphocytic leukemias. These tumors afflicted over
is a dramatic example of this phenomenon. A single lymphohematopoi- 105,000 Americans and resulted in over 23,000 deaths in 2017. Their
etic stem cell, can over the course of several bifurcations, differentiate effects worldwide are dramatically larger. It is these compelling numbers
and then mature into at least 11 unique functional cells. In some cases, that prompted the editors to prepare a “breakaway” text on the malig-
these cells can mature further into different phenotypes influenced by nant lymphocytic neoplasms, based on the chapters that discussed these
the environment in which they reside. Consider, for example, the mono- diseases in the ninth edition of Williams Hematology. Approximately
cytes, Kupffer cells, osteoclasts, microglia, and alveolar macrophages. 3 years have passed since those chapters were written. The editors asked
One of the critical points of hematopoietic bifurcation is the dif- the authors of these 21 chapters to revise and update them in the light
ferentiation of the lymphohematopoietic stem cell into the common of three recent developments: an expanded classification of the lym-
myeloid and common lymphoid progenitor. It is at this point that phocytic neoplasms by the World Health Organization, advances in the
differentiation into these distinct lineages separates hematology into understanding of biology and genetics of these tumors, and advances in
two specialized areas of research and clinical practice: the myeloid and therapeutic approaches to the lymphomas and lymphocytic leukemias.
lymphoid neoplasms. Unlike most of the maturing myeloid cells, the The authors have graciously and expeditiously done so. With their help
lymphoid cells do not lose their mitotic capability. This requirement and expertise, we can now provide a timely text that covers the lymphomas
for continued replication and repair of DNA, along with the rearrange- and lymphocytic leukemias.
ments required of immunoglobulin and T-cell receptor genes dur- It is hoped the reader, from the accessibility of these new versions
ing maturation, provides the risk of neoplastic gene mutations; these of the chapters, will derive benefit in their research, clinical practice,
requirements result in a panoply of lymphocytic neoplasms, grossly and learning.
divided into B-lymphocyte, T-lymphocyte, and natural killer cell tumors.
The complexity of this array is extensive, with over 70 specific lympho- Marshall A. Lichtman
cytic tumors in the 2016 World Health Organization classification of Oliver W. Press
lymphocytic malignancies. John P. Leonard

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 - -- '
,, I

: ~

killer cell large granular lymphocytic leukemia (Chap. 5), 1 myeloma,

CHAPTER 1 and plasmacytoma ( Chap. 18). Hodgkin lymphoma also is derived from
a neoplastic B cell that has highly mutated immunoglobulin genes that are
CLASSIFICATION OF no longer expressed as protein (Chap. 8).
To provide a unified international basis for clinical and investiga-

MALIGNANT LYMPHOID tive work in this field, the International Lymphoma Study Group pro-
posed a classification termed the revised European-American Lymphoma
(REAL) classification (Chap. 6), 2 which was modified in 2001 and again
DISORDERS in 2008 by the World Health Organization (WHO). 3.4 The REAL/WHO
classification scheme makes use of the pathologic, immunophenotypic,
genetic, and clinical features of given lymphocyte tumors to delineate
Robert A. Baiocchi them into separate disease entities (Table 1-1 and Chap. 7). 5 For some of
these entities, the neoplastic lymphocytes have distinctive cytogenetic
abnormalities, which can be identified using molecular techniques that
are increasingly being used in clinical pathology laboratories. 6 •7
SUMMARY The REAL/WHO classification recognizes a basic distinction
between nodular lymphocyte-predominant Hodgkin lymphoma and
This chapter outlines the category of preneoplastic and neoplastic lymphocyte classic Hodgkin lymphoma, reflecting the differences in clinical presen-
and plasma cell disorders. It introduces a framework for evaluating neoplastic tation and behavior, morphology, phenotype, and molecular features
(Chap. 8). 3 Studies have identified features that can be used to distin-
lymphocyte and plasma cell disorders, outlines clinical syndromes associated
guish classical Hodgkin lymphoma from anaplastic large cell lymphoma
with such disorders, and guides the reader to the chapters in the text that
and, to a lesser extent, between nodular lymphocyte-predominant
discuss each of these disorders in greater detail. Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma.
The updated WHO classification (summarized in Ref. 4) provided
several revised guidelines for defining diseases such as chronic lym-
phocytic leukemia (CLL), 8 Waldenstrom macroglobulinemia, 9 plasma
e CLASSIFICATION cell neoplasms, 10 and diffuse large B-cell lymphoma (DLBCL). 11 - 14 The
classifications of several T-cell lymphomas were also refined, including
Lymphocyte and plasma cell malignancies present a broad spectrum enteropathy-associated T-cell lymphoma, anaplastic large cell lymphoma
of different morphologic features and clinical syndromes (Table 1-1). (ALK positive and ALK negative), and subcutaneous panniculitis-like
Lymphocyte neoplasms can originate from cells that are at a stage prior T-cell lymphoma.4 In 2014, a Clinical Advisory Committee meeting was
to T- and B-lymphocyte differentiation from a primitive stem cell or held to review literature and provide an update prior to the preparation
from cells at stages of maturation after stem cell differentiation. For of the next WHO tumor monograph series. The update reviews major
example, acute lymphoblastic leukemias arise from an early lymphoid areas from the WHO 2018 edition that changed significantly14" and are
progenitor cell that may give rise to cells with either B- or T-cell phe- summarized in Table 1-1.
notypes (Chap. 2), whereas chronic lymphocytic leukemia arises from
a more mature B-lymphocyte progenitor (Chap. 3) and myeloma from
progenitors at even later stages ofB-lymphocyte maturation (Chap. 18).
Disorders oflymphoid progenitors may result in a broad spectrum oflym-
. CLINICAL BEHAVIOR
phocytic diseases, such as B- orT-celllymphomas (Chaps. 9 and 15), hairy Lymphomas of similar histology can have widely different spectra of
cell leukemia (Chap. 4), prolymphocytic leukemia (Chap. 3), natural associated clinical symptoms and clinical aggressiveness, making the
categorization of lymphoid tumors impossible using a generic grad-
ing system based on morphology alone. For example, the neoplastic
cells in mantle cell lymphoma appear smaller and more differentiated
Acronyms and Abbreviations: a/PTCR, T-cell-receptor genes encoding the a and p than those of anaplastic large cell lymphomas. However, the validation
chains of the T-cell receptor; ALK, gene encoding anaplastic lymphoma kinase; BCL2, studies for the REAL classification revealed that patients with mantle
gene encoding B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2; BCL6, gene cell lymphoma and anaplastic large cell lymphomas have 5-year sur-
encoding B-cell chronic lymphocytic leukemia (CLL)/lymphoma 6; clg, cytoplasmic vival rates of approximately 30 percent and approximately 80 percent,
immunoglobulin; EBER, Epstein-Barr-virus-encoded RNA; EBV, Epstein-Barr virus; respectively. 15• 16 Generally, T-cell lymphomas/leukemias have a more
y/oTCR, T-cell-receptor genes encoding they and ochains of the T-cell receptor; HL, aggressive clinical behavior than B-cell lymphomas of comparable his-
Hodgkin lymphoma; HLA, human leukocyte antigen; HTLV-1, human T-cell leukemia tology. The tendency for more aggressive disease also applies to lym-
virus type 1; HHV8, human herpes virus 8; lg, immunoglobulin; lgR, immunoglobulin phoid tumors derived from natural killer cells. A helpful distinction
gene rearrangement; IL, interleukin; MALT, mucosa-associated lymphoid tissue; is to divide the lymphoid tumors into one of two categories, namely,
MUM/, gene encoding multiple myeloma oncogene 1; neg., negative; NK cell, natural indolent lymphomas versus aggressive lymphomas, based upon on the
killer cell; NOS, not otherwise specified; NPM, gene encoding nucleophosmin; PAXS, characteristics of the disease at the time of presentation and patients'
paired box gene S; POEMS, polyneuropathy, organomegaly, endocrinopathy, mono- life expectancy if the disease is left untreated. 17 •18 Clinical studies have
clonal gammopathy, and skin changes; REAL, revised European-American lymphoma; verified that the different disease categories defined in the REAL/WHO
R-S, Reed-Sternberg; slg, surface immunoglobulin; slgD, surface immunoglobulin D; classification each can be segregated into one or the other of these two
slgM, surface immunoglobulin M; TAL 1, gene encoding T-cell acute leukemia-1; major categories (Tables 1- 2 and 1- 3, respectively). 15 Analyses of gene-
TCR, T-cell receptor; TdT, terminal deoxynucleotidyl transferase; Th 2, T-helper type 2; expression patterns using microarray technology have enabled identi-
WHO, World Health Organization. fication of subcategories within some of the disease categories defined
by the REAL/WHO classification that have different tendencies for
 2 Williams Hematology Malignant Lymphoid Diseases

TABLE 1–1. Classification of Lymphoma and Lymphoid Leukemia by the World Health Organization
Neoplasm Morphology Phenotype* Genotype†
B-CELL NEOPLASMS
Immature B-Cell Neoplasms
 Lymphoblastic leukemia/ Medium-to-large cells with TdT+, sIg–, CD10+, CD13+/–, CD19+, Clonal DJ rearrangement of IGH gene
lymphoma not otherwise finely stippled chromatin CD20–, CD22+, CD24+, CD34+/–, T(17;19), E2A-HLF, AML1 iAMP21 asso-
specified (NOS) (Chap. 2) and scant cytoplasm CD33+/–, CD45+/–, CD79a+, PAX5+ ciated with poor prognosis
 Lymphoblastic leukemia/ See above See above. B-ALL with t(9;22) with See individual genetic features in
lymphoma with recurrent CD25 and more frequent myeloid B-ALL subtypes below
genetic abnormalities antigens CD13, CD33
(Chap. 2)
B
    -ALL with t(v;11q23); See above CD19+, CD10–, CD24–, CD15+ Multiple MLL (11q23) fusion partners,
MLL rearranged including AF4 (4q21), AF9 (9p22),
and ENL (19p13). B-ALL with MLL
translocations overexpress FLT-3.
Poor prognosis
B
    -ALL with t(12;21) See above CD19+, CD10+, CD34+. Characteris- t(12;21)(p13;q22) ETV6-RUNX
(p13;q22); TEL-AML1 tically negative for CD9, CD20, and translocation
(ETV6-RUNX1) CD66c
B
    -ALL with See above CD19+, CD10+, CD45–, CD34+ Numerical increase in chromosomes
hyperdiploidy without structural abnormalities.
Most frequent chromosomes +21,
X, 14, and 4. +1, 2, 3 rarely seen.
Favorable prognosis
B
    -ALL with See above See above Loss of at least one or more chromo-
hypodiploidy somes (range from 45 chromosomes
to near haploid). Rare chromosome
abnormalities. Poor prognosis
B
    -ALL with t(5;14) See above with increase in See above. Even rare blasts with B-ALL t(5;14)(q31;q32); IL3-IGH leading
(q31;q32); IL3-IGH reactive eosinophilia immunophenotype with eosinophilia to overexpression of IL3. Unclear
strongly suggestive of this subtype of prognosis
B-ALL
B
    -ALL with t(1;19) See above CD10+, CD19+, cytoplasmic μ heavy t(1;19)(q23;p13.3); leads to overex-
(q23;p13.3); E2A-PBX1 chain. CD9+, CD34– pression of E2A-PBX1 fusion gene
product interfering with normal
transcription factor activity of E2A
and PBX1
Mature B-Cell Neoplasms
Leukemias
  
Chronic lymphocytic Small cells with round, sIg+(dim), CD5+, CD10–, CD19+, IgR+, trisomy 12 (~30%), del at 13q14
leukemia/small lym- dense nuclei CD20+(dim), CD22+(dim), CD23+, (~50%), 11q22–23, 17p13, and IGHV
phocytic lymphoma CD38+/–, CD45+, FMC-7– mutated status associated with
(Chap. 3) poor prognosis. Mutations in TP53,
NOTCH1, SF3B1, ATM, and BIRC3
  
Prolymphocytic leuke- ≥55% prolymphocytes sIg+(bright), CD5+/–, CD10–, CD19+, del13q.14(~30%); del17p (50%), IgR+
mia (Chap. 3) CD22+, CD23+/–, CD45+, CD79a+,
FMC7+
  
Hairy cell leukemia Small cells with cytoplas- sIg+(bright), CD5–, CD10–, BRAF mutations (~100%), IgR+ MAP2K
(Chap. 4) mic projections CD11c+(bright), CD19+, CD20+, mutations in BRAF wt
CD25+, CD45+, CD103+, Annexin A+
Lymphomas
  
Lymphoplasmacytic Small cells with plasmacy- cIg+, CD5–, CD10–, CD19+, CD20+/– IgR, 6q- in 50% of marrow-based
lymphoma (Chap. 20) toid differentiation Plasma cell population: CD38+, cases [the t(9;14) was proved to be
CD138+, cIgM+ wrong], +4 (20%)

(Continued )

01_Lichtman_CH01_001-012.indd 2 05/10/17 10:11 am

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 Science - Book Review
Third 2024 - College

Prepared by: Associate Prof. Garcia

Date: July 28, 2025

Review 1: Statistical analysis and interpretation

Learning Objective 1: Best practices and recommendations
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 1: Diagram/Chart/Graph]
Learning Objective 2: Theoretical framework and methodology
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Learning Objective 3: Historical development and evolution
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Learning Objective 4: Key terms and definitions
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Learning Objective 5: Research findings and conclusions
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Experimental procedures and results
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Interdisciplinary approaches
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Ethical considerations and implications
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Key terms and definitions
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Historical development and evolution
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Test 2: Literature review and discussion
Note: Key terms and definitions
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Problem-solving strategies and techniques
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 12: Current trends and future directions
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Experimental procedures and results
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Literature review and discussion
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Literature review and discussion
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Literature review and discussion
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Practical applications and examples
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Practical applications and examples
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Current trends and future directions
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Test 3: Study tips and learning strategies
Remember: Comparative analysis and synthesis
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Study tips and learning strategies
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Assessment criteria and rubrics
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Best practices and recommendations
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Ethical considerations and implications
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Remember: Fundamental concepts and principles
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Statistical analysis and interpretation
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 27: Diagram/Chart/Graph]
Remember: Historical development and evolution
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 28: Research findings and conclusions
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Current trends and future directions
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Conclusion 4: Statistical analysis and interpretation
Remember: Best practices and recommendations
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Research findings and conclusions
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 32: Diagram/Chart/Graph]
Definition: Statistical analysis and interpretation
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Practice Problem 33: Statistical analysis and interpretation
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Important: Fundamental concepts and principles
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Statistical analysis and interpretation
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Case studies and real-world applications
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Case studies and real-world applications
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Problem-solving strategies and techniques
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 39: Diagram/Chart/Graph]
Key Concept: Ethical considerations and implications
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Quiz 5: Comparative analysis and synthesis
Important: Best practices and recommendations
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Problem-solving strategies and techniques
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Comparative analysis and synthesis
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 43: Critical analysis and evaluation
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 44: Diagram/Chart/Graph]
Key Concept: Key terms and definitions
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Problem-solving strategies and techniques
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Comparative analysis and synthesis
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Historical development and evolution
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Critical analysis and evaluation
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Practical applications and examples
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Abstract 6: Historical development and evolution
Definition: Best practices and recommendations
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 51: Diagram/Chart/Graph]
Remember: Fundamental concepts and principles
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 52: Diagram/Chart/Graph]
Example 52: Research findings and conclusions
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Study tips and learning strategies
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Comparative analysis and synthesis
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Research findings and conclusions
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
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