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Contents

Erythrocytes...................................................................................................................................................... 48Erythrocyte, Normal .....................................................................................................................................50Acanthocyte (Spur Cell) .............................................................................................................................52 Acanthocyte Formation ...............................................................................................................54Bite Cell ..................................................................................................................................................................56 Bite Cell Formation ...........................................................................................................................58Blister Cell/Prekeratocyte .........................................................................................................................60 Vacuolated Non-Nucleated Red Blood Cells ...............................................................62Echinocyte (Burr Cell, Crenated Cell) ..............................................................................................64 Spiculated Red Blood Cells ........................................................................................................66Fragmented Red Cell ..................................................................................................................................68 Microangiopathic Hemolytic Anemias ............................................................................72 Diagnostic Morphology in MAHA and Heinz Body Anemia ..........................74Macrocyte, Oval or Round .....................................................................................................................76 Megaloblastic Anemia ..................................................................................................................78Microcyte (with Central Pallor) ............................................................................................................80 Iron Deficiency Anemia ................................................................................................................82Ovalocyte (Elliptocyte) ...............................................................................................................................86 Hereditary Elliptocytosis .............................................................................................................88Polychromatophilic Red Cell (Non-Nucleated) ......................................................................96Red Cell Agglutinates ..................................................................................................................................98Rouleaux ............................................................................................................................................................ 100 Sticky Red Blood Cells ............................................................................................................... 102Sickle Cell (Drepanocyte) ..................................................................................................................... 104 Sickle Cell Anemia......................................................................................................................... 106Spherocyte ....................................................................................................................................................... 110 Red Cell Membrane Loss and Spherocytosis.......................................................... 112Stomatocyte ................................................................................................................................................... 114Target Cell (Codocyte) ............................................................................................................................ 116 How Target Cells Form .............................................................................................................. 118 Thalassemia........................................................................................................................................ 120Teardrop Cell (Dacrocyte) .................................................................................................................... 124 How Teardrop Cells Form ........................................................................................................ 126

Introduction ..........................................................................................................................................................2Bloodlines: Part 1 Hematology Becomes a Discipline ........................................................4 Part 2 The Evolution of the Microscope..........................................................12The Tools of Hematology: The Complete Blood Count ...................................................20Why Examine a Peripheral Blood Smear? ...................................................................................22Pediatric Hematology .................................................................................................................................25Results Reporting ...........................................................................................................................................29Flow Cytometry ................................................................................................................................................30Molecular Studies and Cytogenetics ..............................................................................................42 Automated Hematology ...........................................................................................................................44Digital Cell Morphology Instruments ............................................................................................46

A Closer Look At…Discussions ..........................................................................................................viiiHeme CAPsules Video ...................................................................................................................................ixForeword...................................................................................................................................................................xPreface to First Edition ................................................................................................................................ xiiPreface to Second Edition ......................................................................................................................xiiiContributors .......................................................................................................................................................xivCurrent and Past HCMRC Members.................................................................................................xvAcknowledgments .......................................................................................................................................xviHow to Interpret PT Data and Use the Interactive Features .................................... xvii

Section EditorsParul Bhargava, MDJoan Etzell, MD

Section EditorDavid Blomberg, MD

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Granulocytes and Monocytes ........................................................................................................168Promyelocyte ................................................................................................................................................. 170Myelocyte ......................................................................................................................................................... 172Metamyelocyte ............................................................................................................................................. 174 Life Cycle of Neutrophils ......................................................................................................... 176Neutrophil, Segmented or Band .................................................................................................... 178 The Band vs. Seg Controversy ............................................................................................. 182 Neutrophil Homeostasis .......................................................................................................... 184Monocyte, Immature (Promonocyte, Monoblast) ........................................................... 186Monocyte .......................................................................................................................................................... 188 Life Cycle of Monocytes ........................................................................................................... 190Eosinophil, Any Stage ............................................................................................................................. 192 Eosinophilia ........................................................................................................................................ 194Basophil, Any Stage .................................................................................................................................. 196Mast Cell ............................................................................................................................................................. 198 Mast Cells and Basophils ........................................................................................................ 200Neutrophil with Hypersegmented Nucleus ......................................................................... 202Neutrophil with Pelger-Hüet Nucleus ....................................................................................... 204 Acquired Neutrophil Abnormalities .............................................................................. 208Neutrophil, Toxic ........................................................................................................................................ 210Leukocyte with Alder (Alder-Reilly) Anomaly Inclusions ........................................... 214Leukocyte with Chédiak-Higashi Anomaly Inclusion(s) ............................................. 216 May-Hegglin Anomaly .............................................................................................................. 218 Cytoplasmic Inclusions in Neutrophils ........................................................................ 220Myeloblast with Auer Rod ................................................................................................................... 222 Auer Bodies ........................................................................................................................................ 224Promyelocyte, Abnormal ..................................................................................................................... 226 Acute Myeloid Leukemia and Related Neoplasms ............................................ 228Neutrophil with Dysplastic Nucleus/Hypogranular Cytoplasm ........................... 230 Myelodysplasia ................................................................................................................................ 232Neutrophil Necrobiosis (Degenerated Neutrophil) ...................................................... 234 Cell Death ............................................................................................................................................ 236

Section EditorsParul Bhargava, MDJoan Etzell, MD

Section EditorsTracy George, MDCarla S. Wilson, MD, PhD

Erythrocyte Inclusions ..........................................................................................................................128Nucleated Red Cell, Normal or Abnormal .............................................................................. 130Reticulocyte (Supra-Vital Stain) ...................................................................................................... 134Basophilic Stippling (Coarse) ............................................................................................................ 136 How Basophilic Stippling Forms ....................................................................................... 138 Red Cell Inclusions........................................................................................................................ 140Heinz Body ....................................................................................................................................................... 144 Heinz Body Anemia ..................................................................................................................... 146Hemoglobin C and SC Crystals ........................................................................................................ 148Hemoglobin H Inclusions (Supravital Stain) ........................................................................ 152 Different Types of Precipitated Hemoglobin .......................................................... 154Howell-Jolly Body (Wright-Giemsa Stain) .............................................................................. 156Howell-Jolly Body (Iron Stain) .......................................................................................................... 158 How Howell-Jolly Bodies Form .......................................................................................... 160Pappenheimer Bodies (Wright-Giemsa Stain) .................................................................... 162Pappenheimer Bodies (Iron Stain) ................................................................................................ 164 How Pappenheimer Bodies Form .................................................................................... 166

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Lymphocytes and Plasma Cells ....................................................................................................238Lymphoblast ................................................................................................................................................... 242

How to Differentiate Blasts .................................................................................................... 246Lymphocyte .................................................................................................................................................... 252Lymphocyte, Reactive ........................................................................................................................... 256

Normal vs. Reactive Lymphocytes .................................................................................. 260The Reactive Lymphocyte Project ................................................................................... 262

Lymphocyte, Large Granular ........................................................................................................... 274Lymphoma Cell ............................................................................................................................................ 278

Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia ............ 292Prolymphocytes ............................................................................................................................. 296Hairy Cells and Hairy Cell Leukemia .............................................................................. 300Sézary Cells and Sézary Syndrome ................................................................................. 306

Plasma Cell, Morphologically Mature or Abnormal ....................................................... 310Plasma Cell Leukemia ................................................................................................................ 314

Miscellaneous Identifications .......................................................................................................340Cryoglobulin ................................................................................................................................................... 342

Cryoglobulinemia ......................................................................................................................... 344Endothelial Cell ............................................................................................................................................ 346Epithelial Cell .................................................................................................................................................. 348Metastatic Tumor Cell or Tumor Cell Clump ......................................................................... 350

Circulating Tumor Cells ............................................................................................................. 352Mitotic Figure ................................................................................................................................................. 354

Megakaryocytes and Platelets......................................................................................................316Megakaryocytes (Normal, Abnormal, or Naked Nucleus) ......................................... 318

Circulating Megakaryocytes ................................................................................................ 322Platelet, Normal ........................................................................................................................................... 324

Origin of Platelets .......................................................................................................................... 326Platelet, Giant ................................................................................................................................................. 328Platelet, Hypogranular ........................................................................................................................... 332Platelet Satellitism ..................................................................................................................................... 334

Platelet Satellitism ........................................................................................................................ 336Erythrocyte with Overlying Platelet ............................................................................................ 338

Section EditorsSherrie L. Perkins, MD, PhD Kyle T. Bradley, MD

Section EditorsJoan Etzell, MDPatrick C.J. Ward, MB, BCh

Section EditorDavid R. Czuchlewski, MD

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Microorganisms..........................................................................................................................................356Leukocyte with Anaplasma/Ehrlichia ......................................................................................... 358

Ehrlichia and Anaplasma Organisms and Diseases ........................................... 360Babesia .............................................................................................................................................................. 362

The Life Cycle of Babesia ......................................................................................................... 365Bacteria, Extracellular (Cocci or Rod) .......................................................................................... 366Bacteria, Extracellular (Spirochete) .............................................................................................. 368Fungi, Extracellular .................................................................................................................................... 370Leukocyte with Phagocytized Fungi .......................................................................................... 372Leukocyte with Phagocytized Bacteria .................................................................................... 374Malaria (Plasmodium Species) .......................................................................................................... 376

Species Differences Among Malarial Parasites ..................................................... 380Babesia vs. Malaria ........................................................................................................................ 382

Microfilaria ....................................................................................................................................................... 384Onchocerciasis (River Blindness) ...................................................................................... 387Species Differences Among Microfilariae ................................................................. 388

Trypanosomes (Protozoan, Nonmalarial) ............................................................................... 390African Trypanosomiasis ......................................................................................................... 392

Artifacts .............................................................................................................................................................394Basket Cell / Smudge Cell .................................................................................................................... 396Stain Precipitate ........................................................................................................................................... 398

Appendix ..........................................................................................................................................................400How to Perform Proficiency Testing ............................................................................................ 402Proficiency Testing in Hematology .............................................................................................. 403Master List of Identifications ............................................................................................................. 409 Virtual Peripheral Blood Smears ..................................................................................................... 410 QR Code Apps .................................................................................................................................. 412 Virtual Peripheral Blood PT Program ............................................................................. 413References ........................................................................................................................................................ 438Index ..................................................................................................................................................................... 446

Section EditorKatherine A. Galagan, MD

Section EditorLuke R. Shier, MD

Section EditorsDavid Blomberg, MDEric F. Glassy, MD

Miscellaneous Identifications .......................................................................................................340Cryoglobulin ................................................................................................................................................... 342

Cryoglobulinemia ......................................................................................................................... 344Endothelial Cell ............................................................................................................................................ 346Epithelial Cell .................................................................................................................................................. 348Metastatic Tumor Cell or Tumor Cell Clump ......................................................................... 350

Circulating Tumor Cells ............................................................................................................. 352Mitotic Figure ................................................................................................................................................. 354

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A Closer Look At… Discussions

Erythrocytes Acanthocyte Formation .............................................................. 54 Bite Cell Formation .......................................................................... 58 Vacuolated Non-Nucleated Red Blood Cells .............. 62 Spiculated Red Blood Cells ....................................................... 66 Microangiopathic Hemolytic Anemias ........................... 72 Diagnostic Morphology in MAHA and Heinz Body

Anemia ............................................................................................... 74 Megaloblastic Anemia ................................................................. 78 Iron Deficiency Anemia ............................................................... 82 Hereditary Elliptocytosis ............................................................ 88 Sticky Red Blood Cells ............................................................... 102 Sickle Cell Anemia......................................................................... 106 Red Cell Membrane Loss and Spherocytosis.......... 112 How Target Cells Form .............................................................. 118 Thalassemia........................................................................................ 120 How Teardrop Cells Form ........................................................ 126

Erythrocyte Inclusions How Basophilic Stippling Forms ....................................... 138 Red Cell Inclusions........................................................................ 140 Heinz Body Anemia ..................................................................... 146 Different Types of Precipitated Hemoglobin .......... 154 How Howell-Jolly Bodies Form .......................................... 160 How Pappenheimer Bodies Form .................................... 166

Granulocytes and Monocytes Life Cycle of Neutrophils ......................................................... 176 The Band vs. Seg Controversy ............................................. 182 Neutrophil Homeostasis .......................................................... 184 Life Cycle of Monocytes ........................................................... 190 Eosinophilia ........................................................................................ 194 Mast Cells and Basophils ........................................................ 200 Acquired Neutrophil Abnormalities .............................. 208 May-Hegglin Anomaly .............................................................. 218 Cytoplasmic Inclusions in Neutrophils ........................ 220 Auer Bodies ........................................................................................ 224 Acute Myeloid Leukemia and

Related Neoplasms ............................................................... 228 Myelodysplasia ................................................................................ 232 Cell Death ............................................................................................ 236

Lymphocytes and Plasma Cells How to Differentiate Blasts .................................................... 246 Normal vs. Reactive Lymphocytes .................................. 260 The Reactive Lymphocyte Project ................................... 262 Chronic Lymphocytic Leukemia/

Small Lymphocytic Leukemia (CLL/SLL) ............. 292 Prolymphocytes ............................................................................. 296 Hairy Cells and Hairy Cell Leukemia .............................. 300 Sézary Cells and Sézary Syndrome ................................. 306 Plasma Cell Leukemia ................................................................ 314

Megakaryocytes and Platelets Circulating Megakaryocytes ................................................ 322 Origin of Platelets .......................................................................... 326 Platelet Satellitism ........................................................................ 336

Miscellaneous Identifications Cryoglobulinemia ......................................................................... 344 Circulating Tumor Cells ............................................................. 352

Microorganisms Ehrlichia and Anaplasma Organisms ............................. 360 The Life Cycle of Babesia ......................................................... 365 Species Differences Among Malarial Parasites ..... 380 Babesia vs. Malaria ........................................................................ 382 Onchocerciasis (River Blindness) ...................................... 387 Species Differences Among Microfilariae ................. 388 African Trypanosomiasis ......................................................... 392

A Closer Look At…