SECTION 1: INTRODUCTION<br>4 Hematopoiesis and Bone Marrow Histology<br>Kathryn Foucar, MD<br>14 Bone Marrow Examination and Techniques<br>Kathryn Foucar, MD and Kaaren K. Reichard, MD<br>26 Synoptic/Integrated Bone Marrow Reporting and Algorithmic Testing<br>Amer Mahmoud, MD, FCAP and Cordelia Sever, MD, FCAP<br>30 Overview of Constitutional and Acquired Bone Marrow Disorders<br>Kathryn Foucar, MD<br><br>SECTION 2: ANEMIA<br>38 Overview of Anemia<br>Kathryn Foucar, MD<br>ACQUIRED ANEMIAS<br>44 Anemias of Inflammation, Chronic Kidney Disease, and Cancer<br>Qian-Yun Zhang, MD, PhD<br>48 Iron Deficiency Anemia<br>Qian-Yun Zhang, MD, PhD<br>52 Autoimmune Hemolytic Anemias<br>Qian-Yun Zhang, MD, PhD<br>58 Alloimmune Hemolytic Anemia and Hemolytic Disease of Newborn<br>Qian-Yun Zhang, MD, PhD<br>62 Microangiopathic Hemolytic Anemia<br>Qian-Yun Zhang, MD, PhD, Jay S. Raval, MD, and Marian Rollins-Raval, MD, MPH<br>68 Megaloblastic Anemia<br>Kristin Hunt Karner, MD and Daniel Babu, MD<br>76 Acquired Nonneoplastic Sideroblastic Anemia<br>Brittany Coffman, MD and Kaaren K. Reichard, MD<br>80 Alcoholism-Associated Anemia<br>Brittany Coffman, MD, Kathryn Foucar, MD, and Kaaren K. Reichard, MD<br>84 Anemia in Older Adults<br>Kathryn Foucar, MD<br>88 Copper Deficiency-Associated Anemia<br>Carla S. Wilson, MD, PhD<br>92 Acquired Red Cell Aplasia<br>Kristin Hunt Karner, MD<br>96 Transient Erythroblastopenia of Childhood<br>Kathryn Foucar, MD<br>98 Parvovirus-Induced Red Cell Aplasia<br>Kristin Hunt Karner, MD<br>102 Paroxysmal Nocturnal Hemoglobinuria<br>Kristin Hunt Karner, MD<br>108 Acquired Aplastic Anemia<br>Kathryn Foucar, MD and David R. Czuchlewski, MD<br>CONSTITUTIONAL ANEMIAS<br>112 Thalassemia<br>Kristin Hunt Karner, MD<br>118 Sickle Cell Anemia<br>Kristin Hunt Karner, MD<br>122 Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency<br>Brittany Coffman, MD and Kathryn Foucar, MD<br>124 Pyruvate Kinase Deficiency<br>Kristin Hunt Karner, MD<br>126 Hereditary Spherocytosis<br>Carla S. Wilson, MD, PhD<br>132 Hereditary Elliptocytosis, Including Hereditary Pyropoikilocytosis<br>Brittany Coffman, MD, Kathryn Foucar, MD, and Kaaren K. Reichard, MD<br>136 Diamond-Blackfan Anemia<br>David R. Czuchlewski, MD<br>140 Fanconi Anemia<br>David R. Czuchlewski, MD<br>144 Congenital Dyserythropoietic Anemia<br>Kathryn Foucar, MD<br>150 Congenital Sideroblastic Anemia<br>David R. Czuchlewski, MD<br>154 Congenital Megaloblastic Anemia<br>David R. Czuchlewski, MD<br><br>SECTION 3: ERYTHROCYTOSIS<br>CONSTITUTIONAL<br>162 Congenital Erythrocytosis<br>David R. Czuchlewski, MD<br>ACQUIRED<br>166 Acquired Erythrocytosis<br>Kathryn Foucar, MD<br><br>SECTION 4: BENIGN LEUKOCYTE DISORDERS IN BLOOD AND BONE MARROW<br>172 Overview of Benign Leukocyte Disorders in Blood and Bone Marrow<br>Kathryn Foucar, MD<br>176 Pancytopenia<br>Kathryn Foucar, MD<br>184 Neutropenia<br>Kathryn Foucar, MD<br>190 Neutrophilia<br>Kathryn Foucar, MD<br>196 Monocytosis<br>Carla S. Wilson, MD, PhD<br>202 Eosinophilia<br>Carla S. Wilson, MD, PhD<br>210 Basophilia<br>Kathryn Foucar, MD<br>212 Lymphocytosis<br>Qian-Yun Zhang, MD, PhD<br>216 Lymphopenia, Constitutional and Acquired<br>Qian-Yun Zhang, MD, PhD<br>220 Plasmacytosis of Bone Marrow<br>Kathryn Foucar, MD<br>228 Hematogones in Bone Marrow<br>Devon Chabot-Richards, MD and Kaaren K. Reichard, MD<br>238 Lymphoid Aggregates in Bone Marrow<br>Kathryn Foucar, MD and Kaaren K. Reichard, MD<br>246 Granulomas in Bone Marrow<br>Kathryn Foucar, MD<br><br>SECTION 5: CONSTITUTIONAL GRANULOCYTIC DISORDERS <br>CONSTITUTIONAL NEUTROPENIAS<br>254 Severe Congenital Neutropenia and Cyclic Neutropenia<br>David R. Czuchlewski, MD<br>258 Shwachman-Diamond Syndrome<br>David R. Czuchlewski, MD<br>262 Chediak-Higashi Syndrome<br>David R. Czuchlewski, MD<br>266 Myelokathexis in WHIM Syndrome<br>Kathryn Foucar, MD<br>CONSTITUTIONAL NEUTROPHIL ANOMALIES<br>270 Pelger-Huët Anomaly<br>Kathryn Foucar, MD<br>274 MYH9-Related Disorders<br>David R. Czuchlewski, MD<br>278 Selected Lysosomal Storage Diseases With Abnormal Leukocyte Granulation<br>David R. Czuchlewski, MD<br><br>SECTION 6: MEGAKARYOCYTIC DISORDERS<br>286 Overview of Megakaryocytic Disorders<br>Kathryn Foucar, MD, Marian Rollins-Raval, MD, MPH, and Kaaren K. Reichard, MD<br>ACQUIRED PLATELET DISORDERS WITH THROMBOCYTOPENIA<br>296 Immune-Mediated Thrombocytopenia<br>Kristin Hunt Karner, MD<br>302 Hemolytic Uremic Syndrome<br>Kristin Hunt Karner, MD<br>308 Heparin-Induced Thrombocytopenia (HIT)<br>Marian Rollins-Raval, MD, MPH and Evelyn L. Lockhart, MD, MScBMC<br>312 Thrombotic Thrombocytopenic Purpura<br>Kristin Hunt Karner, MD, Jay S. Raval, MD, and Marian Rollins-Raval, MD, MPH<br>316 Pregnancy-Associated Thrombocytopenia<br>Kathryn Foucar, MD, Marian Rollins-Raval, MD, MPH, and Evelyn L. Lockhart, MD, MScBMC<br>CONSTITUTIONAL PLATELET DISORDERS WITH THROMBOCYTOPENIA<br>320 Thrombocytopenia Absent Radius Syndrome<br>David R. Czuchlewski, MD<br>324 Congenital Amegakaryocytic Thrombocytopenia<br>David R. Czuchlewski, MD<br>328 Gray Platelet Syndrome<br>David R. Czuchlewski, MD<br>332 Wiskott-Aldrich Syndrome-Related Disorders<br>David R. Czuchlewski, MD<br>336 Congenital Thrombotic Thrombocytopenic Purpura<br>David R. Czuchlewski, MD<br>THROMBOCYTOSIS<br>340 Thrombocytosis<br>Kristin Hunt Karner, MD<br><br>SECTION 7: INFECTIONS<br>346 Overview of Infections<br>Carla S. Wilson, MD, PhD and Karissa Culbreath, PhD, D(ABMM)<br>350 Hantavirus Pulmonary Syndrome<br>Carla S. Wilson, MD, PhD<br>354 Human Immunodeficiency Virus<br>Karissa Culbreath, PhD, D(ABMM) and Carla S. Wilson, MD, PhD<br>364 Infectious Mononucleosis Syndromes (Epstein-Barr Virus, Cytomegalovirus)<br>Karissa Culbreath, PhD, D(ABMM) and Carla S. Wilson, MD, PhD<br>374 Parvovirus B19 Infection<br>Carla S. Wilson, MD, PhD<br>378 Bacterial Infections, Blood and Bone Marrow Features<br>Karissa Culbreath, PhD, D(ABMM) and Carla S. Wilson, MD, PhD<br>388 Fungal Infections, Blood and Bone Marrow Features<br>Mohammad A. Vasef, MD<br>394 Helminthic Infections<br>Carla S. Wilson, MD, PhD and Karissa Culbreath, PhD, D(ABMM)<br>398 Malaria<br>Carla S. Wilson, MD, PhD<br>406 Other Protozoan Infections<br>Karissa Culbreath, PhD, D(ABMM), Kathryn Foucar, MD, and Carla S. Wilson, MD, PhD<br>412 COVID-19 Infection (SARS-CoV-2)<br>Daniel Babu, MD, Kathryn Foucar, MD, and Karissa Culbreath, PhD, D(ABMM)<br><br>SECTION 8: MISCELLANEOUS NONNEOPLASTIC DISORDERS AND CONDITIONS<br>418 Overview and Classification of Hemophagocytic Disorders in Bone Marrow<br>Mohammad A. Vasef, MD<br>426 Hematologic Manifestations of Collagen Vascular Disorders<br>Kristin Hunt Karner, MD<br>432 Hematologic Manifestations of Chronic Kidney Disease<br>Kathryn Foucar, MD<br>434 Lysosomal Storage Diseases With Predominantly Histiocytic Storage<br>David R. Czuchlewski, MD<br>440 Homeopathic Remedies and Medications Affecting Blood and Bone Marrow Morphology<br>Brittany Coffman, MD and Kathryn Foucar, MD<br>444 Other Pregnancy-Associated Hematologic Disorders<br>Kathryn Foucar, MD<br>448 VEXAS Syndrome<br>Brittany Coffman, MD and Kathryn Foucar, MD<br>452 Gelatinous Transformation and Other Bone Marrow<br>Stromal Disorders<br>Carla S. Wilson, MD, PhD<br>456 Bone Marrow Necrosis<br>Kathryn Foucar, MD<br>460 Crystals in Bone Marrow<br>Carla S. Wilson, MD, PhD<br>466 Bone Abnormalities in Bone Marrow Specimens<br>Kathryn Foucar, MD<br><br>SECTION 9: MYELOID NEOPLASMS<br>476 Overview and Classification of Myeloid Neoplasms<br>Kathryn Foucar, MD<br>482 Specialized Testing in Myeloid Neoplasms<br>David R. Czuchlewski, MD<br>MYELOPROLIFERATIVE NEOPLASMS<br>484 Overview of Myeloproliferative Neoplasms<br>Kathryn Foucar, MD<br>488 Chronic Myeloid Leukemia<br>Daniel Babu, MD, Kathryn Foucar, MD, and Kaaren K. Reichard, MD<br>498 Chronic Neutrophilic Leukemia<br>Kathryn Foucar, MD, Devon Chabot-Richards, MD, and Kaaren K. Reichard, MD<br>506 Polycythemia Vera<br>Mohammad A. Vasef, MD and M. Carmen Frias Kletecka, MD<br>512 Primary Myelofibrosis<br>Kathryn Foucar, MD, Daniel Babu, MD, and Kaaren K. Reichard, MD<br>522 Essential Thrombocythemia<br>Kathryn Foucar, MD, Daniel Babu, MD, and Kaaren K. Reichard, MD<br>530 Chronic Eosinophilic Leukemia, Not Otherwise Specified<br>Kathryn Foucar, MD and Kaaren K. Reichard, MD<br>538 Myeloproliferative Neoplasm, Unclassifiable<br>Kathryn Foucar, MD and Kaaren K. Reichard, MD<br>MASTOCYTOSIS<br>544 Systemic Mastocytosis<br>Marian Rollins-Raval, MD, MPH and Kaaren K. Reichard, MD<br>554 Mast Cell Leukemia<br>Marian Rollins-Raval, MD, MPH, Kathryn Foucar, MD, and Kaaren K. Reichard, MD<br>MYELOID/LYMPHOID NEOPLASMS WITH EOSINOPHILIA AND TYROSINE KINASE GENE FUSIONS<br>562 Myeloid/Lymphoid Neoplasms With Eosinophilia and PDGFRA<br>David R. Czuchlewski, MD<br>564 Myeloid/Lymphoid Neoplasms With Eosinophilia and PDGFRB<br>David R. Czuchlewski, MD<br>566 Myeloid/Lymphoid Neoplasms With Eosinophilia and FGFR1<br>David R. Czuchlewski, MD<br>568 Myeloid/Lymphoid Neoplasms With Eosinophilia and FLT3 and Other Uncommon Fusion Genes<br>Kathryn Foucar, MD and Brittany Coffman, MD<br>MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASMS<br>570 Overview of Myelodysplastic/Myeloproliferative Neoplasms<br>Kathryn Foucar, MD<br>574 Chronic Myelomonocytic Leukemia and Precursor Lesions<br>David R. Czuchlewski, MD<br>578 Atypical Chronic Myeloid Leukemia<br>Qian-Yun Zhang, MD, PhD<br>582 Myelodysplastic/Myeloproliferative Neoplasm With and Without SF3B1 Mutation and Thrombocytosis<br>Devon Chabot-Richards, MD<br>586 Myelodysplastic/Myeloproliferative Neoplasms, Not Otherwise Specified, and Provisional Entity<br>Kathryn Foucar, MD<br>MYELODYSPLASTIC SYNDROMES<br>588 Overview and Classification of Myelodysplastic Syndromes<br>Kathryn Foucar, MD<br>598 Myelodysplastic Syndrome Precursor Lesions<br>Devon Chabot-Richards, MD<br>600 Myelodysplastic Syndromes With Mutated SF3B1<br>Carla S. Wilson, MD, PhD<br>604 Myelodysplastic Syndrome With del(5q)<br>Marian Rollins-Raval, MD, MPH and Kaaren K. Reichard, MD<br>612 Myelodysplastic Syndrome With Multihit TP53 Mutation<br>Devon Chabot-Richards, MD<br>614 Myelodysplastic Syndromes, Not Otherwise Specified<br>Carla S. Wilson, MD, PhD<br>620 Myelodysplastic Syndromes With Excess Blasts<br>Carla S. Wilson, MD, PhD<br>624 Myelodysplastic Syndrome/Acute Myeloid Leukemia<br>Kathryn Foucar, MD<br>628 Mimics of Myelodysplasia<br>Qian-Yun Zhang, MD, PhD and Brittany Coffman, MD<br>HEMATOLOGIC NEOPLASMS WITH GERMLINE PREDISPOSITION, PEDIATRIC MYELODYSPLASTIC SYNDROME, AND JUVENILE MYELOMONOCYTIC LEUKEMIA<br>632 Juvenile Myelomonocytic Leukemia and Similar Neoplasms<br>Devon Chabot-Richards, MD and Qian-Yun Zhang, MD, PhD<br>636 Pediatric Myelodysplastic Syndrome (Refractory Cytopenia of Childhood)<br>Carla S. Wilson, MD, PhD<br>642 Hematologic Neoplasms With Germline Predisposition<br>David R. Czuchlewski, MD<br>644 Myeloid Proliferations Related to Down Syndrome<br>David R. Czuchlewski, MD<br>ACUTE MYELOID LEUKEMIA<br>648 Overview of Acute Myeloid Leukemia<br>Kathryn Foucar, MD and Kaaren K. Reichard, MD<br>656 Acute Promyelocytic Leukemia With t(15;17)(q24.1;q21.2)/PML::RARA<br>Mohammad A. Vasef, MD and Kathryn Foucar, MD<br>662 Acute Promyelocytic Leukemia With Other RARA Rearrangements<br>Devon Chabot-Richards, MD and Kathryn Foucar, MD<br>664 Acute Myeloid Leukemia With t(8;21)(q22;q22.1)/RUNX1::RUNX1T1<br>Daniel Babu, MD, Devon Chabot-Richards, MD, and Kaaren K. Reichard, MD<br>674 Acute Myeloid Leukemia With inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/CBFB::MYH11<br>Daniel Babu, MD, Devon Chabot-Richards, MD, and Kaaren K. Reichard, MD<br>682 Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3)/MLLT3::KMT2A and Other<br>KMT2A Rearrangements<br>Devon Chabot-Richards, MD, Daniel Babu, MD, and Kaaren K. Reichard, MD<br>690 Acute Myeloid Leukemia With Mutated TP53<br>Kristin Hunt Karner, MD and Kathryn Foucar, MD<br>694 Acute Myeloid Leukemia With Uncommon Cytogenetic Abnormalities<br>David R. Czuchlewski, MD<br>698 Acute Myeloid Leukemia With Myelodysplasia-Related Gene Mutations or Cytogenetic Abnormalities<br>Kathryn Foucar, MD<br>704 Acute Myeloid Leukemia, Not Otherwise Specified<br>Qian-Yun Zhang, MD, PhD and Kathryn Foucar, MD<br>708 Acute Leukemia of Ambiguous Lineage<br>Marian Rollins-Raval, MD, MPH, Kathryn Foucar, MD, and Kaaren K. Reichard, MD<br>714 Measurable Residual Disease Testing Strategies in<br>Acute Myeloid Leukemia<br>Brittany Coffman, MD and Kathryn Foucar, MD<br>BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM<br>718 Blastic Plasmacytoid Dendritic Cell Neoplasm<br>Devon Chabot-Richards, MD and Kaaren K. Reichard, MD<br><br>SECTION 10: LYMPHOID NEOPLASMS<br>728 Overview of Lymphoid Neoplasms<br>Kathryn Foucar, MD<br>734 Specialized Testing in Lymphoid Neoplasms<br>Brittany Coffman, MD and Devon Chabot-Richards, MD<br>B-PRECURSOR NEOPLASMS<br>738 B-Acute Lymphoblastic Leukemias: Cytogenetic Subtypes and Not Otherwise Specified (ICC)<br>Qian-Yun Zhang, MD, PhD<br>746 B-Acute Lymphoblastic Leukemia, BCR::ABL1-Like<br>Joanna L. Conant, MD, Devon Chabot-Richards, MD, and Mohammad A. Vasef, MD<br>750 Novel Genetic Subtypes of B-Acute Lymphoblastic Leukemia<br>Devon Chabot-Richards, MD<br>754 Measurable Residual Disease Testing Strategies in Acute Lymphoblastic Leukemia<br>David R. Czuchlewski, MD<br>T-PRECURSOR NEOPLASMS<br>756 T- and NK-Cell Acute Lymphoblastic Leukemia (ICC)<br>Mohammad A. Vasef, MD<br>762 Early T-Cell Precursor Acute Lymphoblastic Leukemia<br>David R. Czuchlewski, MD<br>MATURE B-CELL NEOPLASMS<br>764 Overview and Classification of Mature B-Cell Leukemias, Immunosecretory Neoplasms<br>Kathryn Foucar, MD and Kaaren K. Reichard, MD<br>772 Monoclonal B-Cell Lymphocytosis<br>Devon Chabot-Richards, MD<br>776 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma<br>Kathryn Foucar, MD<br>786 B-Cell Prolymphocytic Leukemia<br>Kathryn Foucar, MD<br>788 Splenic Marginal Zone Lymphoma<br>Qian-Yun Zhang, MD, PhD<br>794 Hairy Cell Leukemia<br>Kathryn Foucar, MD<br>804 Splenic B-Cell Leukemia, Hairy Cell Leukemia Variant<br>Kathryn Foucar, MD<br>806 Lymphoplasmacytic Lymphoma<br>Qian-Yun Zhang, MD, PhD<br>812 γ-Heavy Chain Disease<br>Kathryn Foucar, MD<br>816 Monoclonal Gammopathy<br>Carla S. Wilson, MD, PhD<br>822 Multiple Myeloma<br>Carla S. Wilson, MD, PhD<br>834 Burkitt Lymphoma<br>Qian-Yun Zhang, MD, PhD<br>842 Mantle Cell Lymphoma in Blood and Bone Marrow<br>Devon Chabot-Richards, MD<br>846 Follicular Lymphoma in Blood and Bone Marrow<br>Qian-Yun Zhang, MD, PhD<br>850 Marginal Zone Lymphoma in Blood and Bone Marrow<br>Devon Chabot-Richards, MD<br>854 Intravascular Large B-Cell Lymphoma<br>Mohammad A. Vasef, MD<br>858 Other Large B-Cell Lymphomas in Blood and Bone Marrow<br>Mohammad A. Vasef, MD<br>MATURE T-/NK-CELL NEOPLASMS<br>860 Overview and Classification of Mature T-/NK-Cell Neoplasms in Blood and Bone Marrow<br>Kathryn Foucar, MD<br>864 T-Cell Prolymphocytic Leukemia<br>Kathryn Foucar, MD<br>870 T-Cell Large Granular Lymphocytic Leukemia<br>Kathryn Foucar, MD<br>876 Chronic Lymphoproliferative Disorder of NK Cells<br>Kathryn Foucar, MD<br>878 Aggressive NK-Cell Leukemia<br>Kathryn Foucar, MD<br>882 Adult T-Cell Leukemia<br>Kathryn Foucar, MD<br>884 Sézary Syndrome<br>Kathryn Foucar, MD<br>890 Anaplastic Large Cell Lymphoma in Blood and Bone Marrow<br>Mohammad A. Vasef, MD<br>896 Angioimmunoblastic T-Cell Lymphoma in Blood and Bone Marrow<br>Mohammad A. Vasef, MD<br>898 Other Mature T-Cell Lymphomas Involving Blood and Bone Marrow<br>Mohammad A. Vasef, MD<br>HODGKIN LYMPHOMA IN BONE MARROW<br>902 Classic Hodgkin and Nodular Lymphocyte-Predominant B-Cell Lymphomas in Bone Marrow<br>Mohammad A. Vasef, MD<br><br>SECTION 11: OTHER NEOPLASMS INVOLVING BONE MARROW<br>910 Langerhans Cell Histiocytosis in Bone Marrow<br>Mohammad A. Vasef, MD<br>914 Posttransplant Lymphoproliferative Disorders in Bone Marrow<br>Mohammad A. Vasef, MD<br>920 Metastatic Carcinoma and Sarcoma<br>Mohammad A. Vasef, MD