Diagnostic Pathology: Blood and Bone Marrow

SECTION 1: INTRODUCTION

4 Hematopoiesis and Bone Marrow Histology
Kathryn Foucar, MD

14 Bone Marrow Examination and Techniques
Kathryn Foucar, MD and Kaaren K. Reichard, MD

26 Synoptic/Integrated Bone Marrow Reporting and Algorithmic Testing
Amer Mahmoud, MD, FCAP and Cordelia Sever, MD, FCAP

30 Overview of Constitutional and Acquired Bone Marrow Disorders
Kathryn Foucar, MD

SECTION 2: ANEMIA

38 Overview of Anemia
Kathryn Foucar, MD
ACQUIRED ANEMIAS

44 Anemias of Inflammation, Chronic Kidney Disease, and Cancer
Qian-Yun Zhang, MD, PhD

48 Iron Deficiency Anemia
Qian-Yun Zhang, MD, PhD

52 Autoimmune Hemolytic Anemias
Qian-Yun Zhang, MD, PhD

58 Alloimmune Hemolytic Anemia and Hemolytic Disease of Newborn
Qian-Yun Zhang, MD, PhD

62 Microangiopathic Hemolytic Anemia
Qian-Yun Zhang, MD, PhD, Jay S. Raval, MD, and Marian Rollins-Raval, MD, MPH

68 Megaloblastic Anemia
Kristin Hunt Karner, MD and Daniel Babu, MD

76 Acquired Nonneoplastic Sideroblastic Anemia
Brittany Coffman, MD and Kaaren K. Reichard, MD

80 Alcoholism-Associated Anemia
Brittany Coffman, MD, Kathryn Foucar, MD, and Kaaren K. Reichard, MD

84 Anemia in Older Adults
Kathryn Foucar, MD

88 Copper Deficiency-Associated Anemia
Carla S. Wilson, MD, PhD

92 Acquired Red Cell Aplasia
Kristin Hunt Karner, MD

96 Transient Erythroblastopenia of Childhood
Kathryn Foucar, MD

98 Parvovirus-Induced Red Cell Aplasia
Kristin Hunt Karner, MD

102 Paroxysmal Nocturnal Hemoglobinuria
Kristin Hunt Karner, MD

108 Acquired Aplastic Anemia
Kathryn Foucar, MD and David R. Czuchlewski, MD
CONSTITUTIONAL ANEMIAS

112 Thalassemia
Kristin Hunt Karner, MD

118 Sickle Cell Anemia
Kristin Hunt Karner, MD

122 Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
Brittany Coffman, MD and Kathryn Foucar, MD

124 Pyruvate Kinase Deficiency
Kristin Hunt Karner, MD

126 Hereditary Spherocytosis
Carla S. Wilson, MD, PhD

132 Hereditary Elliptocytosis, Including Hereditary Pyropoikilocytosis
Brittany Coffman, MD, Kathryn Foucar, MD, and Kaaren K. Reichard, MD

136 Diamond-Blackfan Anemia
David R. Czuchlewski, MD

140 Fanconi Anemia
David R. Czuchlewski, MD

144 Congenital Dyserythropoietic Anemia
Kathryn Foucar, MD

150 Congenital Sideroblastic Anemia
David R. Czuchlewski, MD

154 Congenital Megaloblastic Anemia
David R. Czuchlewski, MD

SECTION 3: ERYTHROCYTOSIS
CONSTITUTIONAL

162 Congenital Erythrocytosis
David R. Czuchlewski, MD
ACQUIRED

166 Acquired Erythrocytosis
Kathryn Foucar, MD

SECTION 4: BENIGN LEUKOCYTE DISORDERS IN BLOOD AND BONE MARROW

172 Overview of Benign Leukocyte Disorders in Blood and Bone Marrow
Kathryn Foucar, MD

176 Pancytopenia
Kathryn Foucar, MD

184 Neutropenia
Kathryn Foucar, MD

190 Neutrophilia
Kathryn Foucar, MD

196 Monocytosis
Carla S. Wilson, MD, PhD

202 Eosinophilia
Carla S. Wilson, MD, PhD

210 Basophilia
Kathryn Foucar, MD

212 Lymphocytosis
Qian-Yun Zhang, MD, PhD

216 Lymphopenia, Constitutional and Acquired
Qian-Yun Zhang, MD, PhD

220 Plasmacytosis of Bone Marrow
Kathryn Foucar, MD

228 Hematogones in Bone Marrow
Devon Chabot-Richards, MD and Kaaren K. Reichard, MD

238 Lymphoid Aggregates in Bone Marrow
Kathryn Foucar, MD and Kaaren K. Reichard, MD

246 Granulomas in Bone Marrow
Kathryn Foucar, MD

SECTION 5: CONSTITUTIONAL GRANULOCYTIC DISORDERS
CONSTITUTIONAL NEUTROPENIAS

254 Severe Congenital Neutropenia and Cyclic Neutropenia
David R. Czuchlewski, MD

258 Shwachman-Diamond Syndrome
David R. Czuchlewski, MD

262 Chediak-Higashi Syndrome
David R. Czuchlewski, MD

266 Myelokathexis in WHIM Syndrome
Kathryn Foucar, MD
CONSTITUTIONAL NEUTROPHIL ANOMALIES

270 Pelger-Huët Anomaly
Kathryn Foucar, MD

274 MYH9-Related Disorders
David R. Czuchlewski, MD

278 Selected Lysosomal Storage Diseases With Abnormal Leukocyte Granulation
David R. Czuchlewski, MD

SECTION 6: MEGAKARYOCYTIC DISORDERS

286 Overview of Megakaryocytic Disorders
Kathryn Foucar, MD, Marian Rollins-Raval, MD, MPH, and Kaaren K. Reichard, MD
ACQUIRED PLATELET DISORDERS WITH THROMBOCYTOPENIA

296 Immune-Mediated Thrombocytopenia
Kristin Hunt Karner, MD

302 Hemolytic Uremic Syndrome
Kristin Hunt Karner, MD

308 Heparin-Induced Thrombocytopenia (HIT)
Marian Rollins-Raval, MD, MPH and Evelyn L. Lockhart, MD, MScBMC

312 Thrombotic Thrombocytopenic Purpura
Kristin Hunt Karner, MD, Jay S. Raval, MD, and Marian Rollins-Raval, MD, MPH

316 Pregnancy-Associated Thrombocytopenia
Kathryn Foucar, MD, Marian Rollins-Raval, MD, MPH, and Evelyn L. Lockhart, MD, MScBMC
CONSTITUTIONAL PLATELET DISORDERS WITH THROMBOCYTOPENIA

320 Thrombocytopenia Absent Radius Syndrome
David R. Czuchlewski, MD

324 Congenital Amegakaryocytic Thrombocytopenia
David R. Czuchlewski, MD

328 Gray Platelet Syndrome
David R. Czuchlewski, MD

332 Wiskott-Aldrich Syndrome-Related Disorders
David R. Czuchlewski, MD

336 Congenital Thrombotic Thrombocytopenic Purpura
David R. Czuchlewski, MD
THROMBOCYTOSIS

340 Thrombocytosis
Kristin Hunt Karner, MD

SECTION 7: INFECTIONS

346 Overview of Infections
Carla S. Wilson, MD, PhD and Karissa Culbreath, PhD, D(ABMM)

350 Hantavirus Pulmonary Syndrome
Carla S. Wilson, MD, PhD

354 Human Immunodeficiency Virus
Karissa Culbreath, PhD, D(ABMM) and Carla S. Wilson, MD, PhD

364 Infectious Mononucleosis Syndromes (Epstein-Barr Virus, Cytomegalovirus)
Karissa Culbreath, PhD, D(ABMM) and Carla S. Wilson, MD, PhD

374 Parvovirus B19 Infection
Carla S. Wilson, MD, PhD

378 Bacterial Infections, Blood and Bone Marrow Features
Karissa Culbreath, PhD, D(ABMM) and Carla S. Wilson, MD, PhD

388 Fungal Infections, Blood and Bone Marrow Features
Mohammad A. Vasef, MD

394 Helminthic Infections
Carla S. Wilson, MD, PhD and Karissa Culbreath, PhD, D(ABMM)

398 Malaria
Carla S. Wilson, MD, PhD

406 Other Protozoan Infections
Karissa Culbreath, PhD, D(ABMM), Kathryn Foucar, MD, and Carla S. Wilson, MD, PhD

412 COVID-19 Infection (SARS-CoV-2)
Daniel Babu, MD, Kathryn Foucar, MD, and Karissa Culbreath, PhD, D(ABMM)

SECTION 8: MISCELLANEOUS NONNEOPLASTIC DISORDERS AND CONDITIONS

418 Overview and Classification of Hemophagocytic Disorders in Bone Marrow
Mohammad A. Vasef, MD

426 Hematologic Manifestations of Collagen Vascular Disorders
Kristin Hunt Karner, MD

432 Hematologic Manifestations of Chronic Kidney Disease
Kathryn Foucar, MD

434 Lysosomal Storage Diseases With Predominantly Histiocytic Storage
David R. Czuchlewski, MD

440 Homeopathic Remedies and Medications Affecting Blood and Bone Marrow Morphology
Brittany Coffman, MD and Kathryn Foucar, MD

444 Other Pregnancy-Associated Hematologic Disorders
Kathryn Foucar, MD

448 VEXAS Syndrome
Brittany Coffman, MD and Kathryn Foucar, MD

452 Gelatinous Transformation and Other Bone Marrow
Stromal Disorders
Carla S. Wilson, MD, PhD

456 Bone Marrow Necrosis
Kathryn Foucar, MD

460 Crystals in Bone Marrow
Carla S. Wilson, MD, PhD

466 Bone Abnormalities in Bone Marrow Specimens
Kathryn Foucar, MD

SECTION 9: MYELOID NEOPLASMS

476 Overview and Classification of Myeloid Neoplasms
Kathryn Foucar, MD

482 Specialized Testing in Myeloid Neoplasms
David R. Czuchlewski, MD
MYELOPROLIFERATIVE NEOPLASMS

484 Overview of Myeloproliferative Neoplasms
Kathryn Foucar, MD

488 Chronic Myeloid Leukemia
Daniel Babu, MD, Kathryn Foucar, MD, and Kaaren K. Reichard, MD

498 Chronic Neutrophilic Leukemia
Kathryn Foucar, MD, Devon Chabot-Richards, MD, and Kaaren K. Reichard, MD

506 Polycythemia Vera
Mohammad A. Vasef, MD and M. Carmen Frias Kletecka, MD

512 Primary Myelofibrosis
Kathryn Foucar, MD, Daniel Babu, MD, and Kaaren K. Reichard, MD

522 Essential Thrombocythemia
Kathryn Foucar, MD, Daniel Babu, MD, and Kaaren K. Reichard, MD

530 Chronic Eosinophilic Leukemia, Not Otherwise Specified
Kathryn Foucar, MD and Kaaren K. Reichard, MD

538 Myeloproliferative Neoplasm, Unclassifiable
Kathryn Foucar, MD and Kaaren K. Reichard, MD
MASTOCYTOSIS

544 Systemic Mastocytosis
Marian Rollins-Raval, MD, MPH and Kaaren K. Reichard, MD

554 Mast Cell Leukemia
Marian Rollins-Raval, MD, MPH, Kathryn Foucar, MD, and Kaaren K. Reichard, MD
MYELOID/LYMPHOID NEOPLASMS WITH EOSINOPHILIA AND TYROSINE KINASE GENE FUSIONS

562 Myeloid/Lymphoid Neoplasms With Eosinophilia and PDGFRA
David R. Czuchlewski, MD

564 Myeloid/Lymphoid Neoplasms With Eosinophilia and PDGFRB
David R. Czuchlewski, MD

566 Myeloid/Lymphoid Neoplasms With Eosinophilia and FGFR1
David R. Czuchlewski, MD

568 Myeloid/Lymphoid Neoplasms With Eosinophilia and FLT3 and Other Uncommon Fusion Genes
Kathryn Foucar, MD and Brittany Coffman, MD
MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASMS

570 Overview of Myelodysplastic/Myeloproliferative Neoplasms
Kathryn Foucar, MD

574 Chronic Myelomonocytic Leukemia and Precursor Lesions
David R. Czuchlewski, MD

578 Atypical Chronic Myeloid Leukemia
Qian-Yun Zhang, MD, PhD

582 Myelodysplastic/Myeloproliferative Neoplasm With and Without SF3B1 Mutation and Thrombocytosis
Devon Chabot-Richards, MD

586 Myelodysplastic/Myeloproliferative Neoplasms, Not Otherwise Specified, and Provisional Entity
Kathryn Foucar, MD
MYELODYSPLASTIC SYNDROMES

588 Overview and Classification of Myelodysplastic Syndromes
Kathryn Foucar, MD

598 Myelodysplastic Syndrome Precursor Lesions
Devon Chabot-Richards, MD

600 Myelodysplastic Syndromes With Mutated SF3B1
Carla S. Wilson, MD, PhD

604 Myelodysplastic Syndrome With del(5q)
Marian Rollins-Raval, MD, MPH and Kaaren K. Reichard, MD

612 Myelodysplastic Syndrome With Multihit TP53 Mutation
Devon Chabot-Richards, MD

614 Myelodysplastic Syndromes, Not Otherwise Specified
Carla S. Wilson, MD, PhD

620 Myelodysplastic Syndromes With Excess Blasts
Carla S. Wilson, MD, PhD

624 Myelodysplastic Syndrome/Acute Myeloid Leukemia
Kathryn Foucar, MD

628 Mimics of Myelodysplasia
Qian-Yun Zhang, MD, PhD and Brittany Coffman, MD
HEMATOLOGIC NEOPLASMS WITH GERMLINE PREDISPOSITION, PEDIATRIC MYELODYSPLASTIC SYNDROME, AND JUVENILE MYELOMONOCYTIC LEUKEMIA

632 Juvenile Myelomonocytic Leukemia and Similar Neoplasms
Devon Chabot-Richards, MD and Qian-Yun Zhang, MD, PhD

636 Pediatric Myelodysplastic Syndrome (Refractory Cytopenia of Childhood)
Carla S. Wilson, MD, PhD

642 Hematologic Neoplasms With Germline Predisposition
David R. Czuchlewski, MD

644 Myeloid Proliferations Related to Down Syndrome
David R. Czuchlewski, MD
ACUTE MYELOID LEUKEMIA

648 Overview of Acute Myeloid Leukemia
Kathryn Foucar, MD and Kaaren K. Reichard, MD

656 Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2)/PML::RARA
Mohammad A. Vasef, MD and Kathryn Foucar, MD

662 Acute Promyelocytic Leukemia With Other RARA Rearrangements
Devon Chabot-Richards, MD and Kathryn Foucar, MD

664 Acute Myeloid Leukemia With t(8;21)(q22;q22.1)/RUNX1::RUNX1T1
Daniel Babu, MD, Devon Chabot-Richards, MD, and Kaaren K. Reichard, MD

674 Acute Myeloid Leukemia With inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11
Daniel Babu, MD, Devon Chabot-Richards, MD, and Kaaren K. Reichard, MD

682 Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3)/MLLT3::KMT2A and Other
KMT2A Rearrangements
Devon Chabot-Richards, MD, Daniel Babu, MD, and Kaaren K. Reichard, MD

690 Acute Myeloid Leukemia With Mutated TP53
Kristin Hunt Karner, MD and Kathryn Foucar, MD

694 Acute Myeloid Leukemia With Uncommon Cytogenetic Abnormalities
David R. Czuchlewski, MD

698 Acute Myeloid Leukemia With Myelodysplasia-Related Gene Mutations or Cytogenetic Abnormalities
Kathryn Foucar, MD

704 Acute Myeloid Leukemia, Not Otherwise Specified
Qian-Yun Zhang, MD, PhD and Kathryn Foucar, MD

708 Acute Leukemia of Ambiguous Lineage
Marian Rollins-Raval, MD, MPH, Kathryn Foucar, MD, and Kaaren K. Reichard, MD

714 Measurable Residual Disease Testing Strategies in
Acute Myeloid Leukemia
Brittany Coffman, MD and Kathryn Foucar, MD
BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM

718 Blastic Plasmacytoid Dendritic Cell Neoplasm
Devon Chabot-Richards, MD and Kaaren K. Reichard, MD

SECTION 10: LYMPHOID NEOPLASMS

728 Overview of Lymphoid Neoplasms
Kathryn Foucar, MD

734 Specialized Testing in Lymphoid Neoplasms
Brittany Coffman, MD and Devon Chabot-Richards, MD
B-PRECURSOR NEOPLASMS

738 B-Acute Lymphoblastic Leukemias: Cytogenetic Subtypes and Not Otherwise Specified (ICC)
Qian-Yun Zhang, MD, PhD

746 B-Acute Lymphoblastic Leukemia, BCR::ABL1-Like
Joanna L. Conant, MD, Devon Chabot-Richards, MD, and Mohammad A. Vasef, MD

750 Novel Genetic Subtypes of B-Acute Lymphoblastic Leukemia
Devon Chabot-Richards, MD

754 Measurable Residual Disease Testing Strategies in Acute Lymphoblastic Leukemia
David R. Czuchlewski, MD
T-PRECURSOR NEOPLASMS

756 T- and NK-Cell Acute Lymphoblastic Leukemia (ICC)
Mohammad A. Vasef, MD

762 Early T-Cell Precursor Acute Lymphoblastic Leukemia
David R. Czuchlewski, MD
MATURE B-CELL NEOPLASMS

764 Overview and Classification of Mature B-Cell Leukemias, Immunosecretory Neoplasms
Kathryn Foucar, MD and Kaaren K. Reichard, MD

772 Monoclonal B-Cell Lymphocytosis
Devon Chabot-Richards, MD

776 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Kathryn Foucar, MD

786 B-Cell Prolymphocytic Leukemia
Kathryn Foucar, MD

788 Splenic Marginal Zone Lymphoma
Qian-Yun Zhang, MD, PhD

794 Hairy Cell Leukemia
Kathryn Foucar, MD

804 Splenic B-Cell Leukemia, Hairy Cell Leukemia Variant
Kathryn Foucar, MD

806 Lymphoplasmacytic Lymphoma
Qian-Yun Zhang, MD, PhD

812 γ-Heavy Chain Disease
Kathryn Foucar, MD

816 Monoclonal Gammopathy
Carla S. Wilson, MD, PhD

822 Multiple Myeloma
Carla S. Wilson, MD, PhD

834 Burkitt Lymphoma
Qian-Yun Zhang, MD, PhD

842 Mantle Cell Lymphoma in Blood and Bone Marrow
Devon Chabot-Richards, MD

846 Follicular Lymphoma in Blood and Bone Marrow
Qian-Yun Zhang, MD, PhD

850 Marginal Zone Lymphoma in Blood and Bone Marrow
Devon Chabot-Richards, MD

854 Intravascular Large B-Cell Lymphoma
Mohammad A. Vasef, MD

858 Other Large B-Cell Lymphomas in Blood and Bone Marrow
Mohammad A. Vasef, MD
MATURE T-/NK-CELL NEOPLASMS

860 Overview and Classification of Mature T-/NK-Cell Neoplasms in Blood and Bone Marrow
Kathryn Foucar, MD

864 T-Cell Prolymphocytic Leukemia
Kathryn Foucar, MD

870 T-Cell Large Granular Lymphocytic Leukemia
Kathryn Foucar, MD

876 Chronic Lymphoproliferative Disorder of NK Cells
Kathryn Foucar, MD

878 Aggressive NK-Cell Leukemia
Kathryn Foucar, MD

882 Adult T-Cell Leukemia
Kathryn Foucar, MD

884 Sézary Syndrome
Kathryn Foucar, MD

890 Anaplastic Large Cell Lymphoma in Blood and Bone Marrow
Mohammad A. Vasef, MD

896 Angioimmunoblastic T-Cell Lymphoma in Blood and Bone Marrow
Mohammad A. Vasef, MD

898 Other Mature T-Cell Lymphomas Involving Blood and Bone Marrow
Mohammad A. Vasef, MD
HODGKIN LYMPHOMA IN BONE MARROW

902 Classic Hodgkin and Nodular Lymphocyte-Predominant B-Cell Lymphomas in Bone Marrow
Mohammad A. Vasef, MD

SECTION 11: OTHER NEOPLASMS INVOLVING BONE MARROW

910 Langerhans Cell Histiocytosis in Bone Marrow
Mohammad A. Vasef, MD

914 Posttransplant Lymphoproliferative Disorders in Bone Marrow
Mohammad A. Vasef, MD

920 Metastatic Carcinoma and Sarcoma
Mohammad A. Vasef, MD