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SPEC - Hematopathology, 2nd Edition, 12-Month Access, eBook

SPEC - Hematopathology, 2nd Edition, 12-Month Access, eBook

Elaine Sarkin Jaffe | Daniel A. Arber | Elias Campo | Nancy Lee Harris | Leticia Quintanilla-Fend

(2016)

Additional Information

Book Details

Abstract

The world's leading reference in hematopathology returns with this completely updated second edition. Authored by international experts in the field, it covers a broad range of hematologic disorders -- both benign and malignant -- with information on the pathogenesis, clinical and pathologic diagnosis, and treatment for each. Comprehensive in scope, it's a must-have resource for both residents and practicing pathologists alike.

  • Authored by the chief architects of the WHO classification in neoplasms of hematopoietic and lymphoid tissue.
  • Covers the newest diagnostic techniques, including molecular, immunohistochemical, and genetic studies.
  • Confirm or challenge your diagnostic interpretations by comparing specimens to over 1,000 high-quality color images.
  • Boasts detailed, practical advice from world leaders in hematopathology.
  • Places an emphasis on pathologic diagnoses, including molecular and genetic testing.
  • Updated with the most current WHO classifications of hematologic disease, including lymphoma and leukemia and peripheral T-cell lymphomas.
  • Covers hot topics in hematopathology, such as the latest genetic insights into lymphoma and leukemia; the new nomenclature for myelodysplastic syndromes; new developments on the subject of Grey zone lymphoma; and much more.

Table of Contents

Section Title Page Action Price
Front Cover cover
Inside Front Cover ifc1
Hematopathology i
Copyright Page ii
Contributors iii
Preface xi
Table Of Contents xiii
I Technical Aspects 1
1 Processing of the Lymph Node Biopsy Specimen 3
Outline 3
Instructions for the Surgeon 3
Gross Processing of the Lymph Node Biopsy by the Pathologist 4
Gross Examination 4
Frozen Sections 4
Cytologic Preparations 4
Sectioning 6
Fixation 7
Contribution of the Histotechnologist 10
Routine Histologic, Histochemical, and Special Stains 10
Choice of Ancillary Studies 11
Reporting the Lymph Node Biopsy 12
Pearls and Pitfalls 13
Key References 13
References 13.e1
2 Fine Needle Aspiration of Lymph Nodes 15
Outline 15
Specimen Collection and Processing 15
Ancillary Studies 16
Immunocytochemistry 16
Flow Cytometry 16
Molecular Studies 17
Non-Neoplastic Aspirates 18
Aspirates of Lymphoid Neoplasms 18
Mature B-Cell Neoplasms 18
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified 18
Cytomorphology 18
Differential Diagnosis 19
Follicular Lymphoma 19
Cytomorphology 19
Grading 20
II Normal and Reactive Conditions of Hematopoietic Tissues 129
8 Normal Lymphoid Organs and Tissues 131
Outline 131
Normal Lymphoid Tissues 131
Primary (Central) Lymphoid Tissues 132
Bone Marrow 132
Thymus 132
Secondary (Peripheral) Lymphoid Tissues 134
Lymph Nodes 134
Cortical Area 134
Paracortex 138
Lymph Node Vasculature and Conduit System 139
Spleen 140
White Pulp 140
Red Pulp 140
Mucosa-Associated Lymphoid Tissue 140
B-Cell and T-Cell Differentiation 142
Differentiation of Cells of the Adaptive Immune Response 143
B-Cell Differentiation 143
Antigen-Independent B-Cell Differentiation 143
Precursor B Cells 143
Naïve B Cells 144
Antigen-Dependent B-Cell Differentiation 145
T-Cell–Independent B-Cell Reaction 145
T-Cell–Dependent Germinal-Center Reaction 145
Proliferation. 147
Somatic Hypermutation. 147
Selection. 147
Differentiation. 148
Memory B Cells. 148
Plasma Cells. 149
Mucosa-Associated Lymphoid Tissue. 149
T-Cell Differentiation 149
Antigen-Independent T-Cell Differentiation 149
Cortical Thymocytes 149
Naïve T Cells 149
Antigen-Dependent T-Cell Differentiation 150
T Immunoblasts 150
Effector T Cells 150
Differentiation of Cells of the Innate Immune Response 150
Gamma-Delta T Cells 150
Natural Killer Cells 152
Pearls and Pitfalls 152
Key References 152
References 152.e1
9 Reactive Lymphadenopathies 153
Outline 153
Follicular and Nodular Patterns 153
Follicular Hyperplasia 153
Differential Diagnosis 154
Monocytoid B-Cell Proliferation 154
Autoimmune Disorders (Rheumatoid Arthritis) 156
Luetic Lymphadenitis 158
Castleman’s Disease, Hyaline Vascular Type (Angiofollicular Lymphoid Hyperplasia, Giant Lymph Node Hyperplasia) 158
Histology 159
Immunophenotype 159
Differential Diagnosis 159
Progressive Transformation of Germinal Centers 159
Differential Diagnosis 160
Mantle-Zone Hyperplasia 161
Mycobacterial Spindle Cell Pseudotumor 161
Predominantly Sinus Pattern 162
Sinus Histiocytosis 162
Histiocytic Expansion Due to a Specific Cause (Storage Disease, Lymphangiogram, Prosthesis, Whipple’s Disease) 162
Whipple’s Disease 163
Vascular Transformation of Sinuses 164
Hemophagocytic Lymphohistiocytosis 164
Interfollicular or Mixed Patterns 165
Paracortical Hyperplasia and Dermatopathic Reaction 165
Granulomatous Lymphadenitis 165
Non-necrotizing Granulomas 165
Necrotizing Granulomas (Tuberculosis, Fungal Infections, Cat Scratch Disease) 166
Tuberculosis 166
Fungal Infection 166
Cat Scratch Disease 166
Immunoglobulin G4–Related Lymphadenopathy 167
Kimura’s Disease 168
Toxoplasmic Lymphadenitis 169
Systemic Lupus Erythematosus 169
Kikuchi’s Lymphadenitis (Kikuchi-Fujimoto Lymphadenitis, Histiocytic Necrotizing Lymphadenitis) 170
Kawasaki’s Disease (Mucocutaneous Lymph Node Syndrome) 170
Inflammatory Pseudotumor 172
Bacillary Angiomatosis 172
Diffuse Pattern 172
Infectious Mononucleosis 172
Cytomegalovirus Infection 173
Herpes Simplex Lymphadenitis 175
Dilantin-Associated Lymphadenopathy 176
Pearls and Pitfalls 176
Key References 176
References 177.e1
10 Normal Bone Marrow 179
Outline 179
Hematopoiesis 181
Erythropoiesis 181
Granulopoiesis 181
Megakaryocytes and Thrombopoiesis 185
Other Myeloid Cells 187
Cytologic Abnormalities in Myeloid Cells in Hematologically Normal Subjects 188
Bone Marrow Lymphoid Cells 188
Other Cells Present in Normal Bone Marrow 190
Normal Bone Marrow Components 190
Extraneous Cells and Tissues 190
Cytochemistry and Histochemistry 191
Cytochemistry 191
Histochemistry 192
Immunophenotyping Including Immunohistochemistry 192
Conclusion 192
Pearls and Pitfalls 194
Key References 194
References 194.e1
11 Evaluation of Anemia, Leukopenia, and Thrombocytopenia 195
Outline 195
Evaluation of Anemia 195
Microcytic Anemia 196
Iron Deficiency 197
Thalassemias 198
Normochromic Normocytic Anemia or Hypochromic Microcytic Anemia 201
Anemia of Chronic Disease 201
Sideroblastic Anemias 202
Normochromic Normocytic Anemia, Underproduction 205
Pure Red Cell Aplasia 205
Aplastic Anemia 207
Myelophthisic Anemias 207
Anemia of Chronic Renal Failure 207
Normochromic Normocytic Anemia, High Output 207
Posthemorrhagic Anemia 207
Hemolytic Anemias 207
Hemolysis Due to Intrinsic Red Cell Disorders 208
Red Blood Cell Membrane Disorders 208
Hereditary Spherocytosis 208
Hereditary Elliptocytosis and Hereditary Pyropoikilocytosis 210
Hereditary Stomatocytosis Syndromes. 210
Red Blood Cell Enzyme Defects. 210
Hemoglobinopathies. 211
Immune-Mediated Hemolytic Anemia 213
Autoimmune Hemolytic Anemias. 213
Drug-Induced Immune Hemolysis. 214
Hemolysis Due to Physicomechanical Disruption. 214
Infection-Associated Hemolytic Anemia. 214
Macrocytic Anemia 215
Megaloblastic Anemias 215
Constitutional Causes 217
Congenital Dyserythropoietic Anemias 218
Evaluation of Leukopenia 219
Neutropenia 219
Acquired Neutropenia in Infancy and Childhood 219
Neonatal Alloimmune Neutropenia 219
Primary Autoimmune Neutropenia 219
Acquired Neutropenia in Adults 220
Drug-Induced Neutropenia 220
Secondary Autoimmune Neutropenia 221
Chronic Idiopathic Neutropenia 221
Infection-Related Neutropenia 221
Nutritional Deficiency–Related Neutropenia 221
Congenital Neutropenia 221
Severe Congenital Neutropenia 221
Cyclic Neutropenia 223
Shwachman-Diamond Syndrome 223
Chédiak-Higashi Syndrome 223
Myelokathexis 223
Additional Disorders 223
Lymphopenia 223
Therapeutic Agents 223
Congenital Disorders 224
Reactive Disorders 224
Autoimmune Disorders 224
Evaluation of Thrombocytopenia 224
Immune-Mediated Thrombocytopenia 225
Primary Immune Thrombocytopenia 225
Secondary Immune Thrombocytopenia 228
Heparin-Induced Thrombocytopenia 228
Infection-Associated Thrombocytopenia 228
Microangiopathic Processes 229
Splenic Sequestration 230
Constitutional Thrombocytopenia 230
Evaluation of Specific Bone Marrow Failure Syndromes 231
Paroxysmal Nocturnal Hemoglobinuria 231
Aplastic Anemia 232
Fanconi Anemia 233
Dyskeratosis Congenita 233
Key References 234
References 234.e1
12 Bone Marrow Findings in Inflammatory, Infectious, and Metabolic Disorders 235
Outline 235
Reactive Neutrophilia 235
Reactive Lymphocytosis 236
Reactive Eosinophilia 237
Reactive Basophilia 238
Reactive Monocytosis 238
Bone Marrow in Infectious Disorders 238
Bacterial Infection 238
Rickettsial Infection 239
Parasitic Infection 240
Viral Infection 240
Cytomegalovirus 240
Epstein-Barr Virus 241
Human Immunodeficiency Virus 242
Hepatitis 242
Hantavirus 242
Parvovirus B19 242
Fungal Infection 243
Bone Marrow Necrosis 243
Fever of Unknown Origin 244
Bone Marrow in Non-infectious Systemic and Inflammatory Disorders 244
Non-infectious Granuloma 244
Autoimmune Disease 244
Sarcoidosis 247
Alcohol Abuse 247
Hepatic Disease 247
Renal Disease 248
Hypothyroidism 248
Hyperthyroidism 248
Conclusion 248
Key References 248
References 249.e1
III Lymphoid Neoplasms 251
13 Principles of Classification of Lymphoid Neoplasms 253
Outline 253
Historical Background 253
Early Events in Lymphoid Neoplasia: Borderlands of Malignancy 256
Small B-Cell Neoplasms 258
Aggressive B-Cell Lymphomas and Borderline Malignancies 258
Peripheral T-Cell Lymphomas 259
Histiocytic and Dendritic Cell Neoplasms 259
Conclusion 259
Pearls and Pitfalls 260
Key References 260
References 260.e1
1 Mature B-Cell Neoplasms 261
14 B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Monoclonal B-Cell Lymphocytosis, and B-Cell Prolymphocytic Leukemia 261
Outline 261
B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (B-CLL/SLL) 261
Definition of Disease 261
Epidemiology and Incidence 262
Clinical Features 262
Morphology 263
Lymph Node 263
Spleen 264
Blood 264
Bone Marrow 265
Other Organs 266
Morphologic Variants 267
Atypical/Mixed CLL 267
CLL/SLL with Plasmacytoid Differentiation 267
CLL/SLL with Reed-Sternberg Cells 268
Mu Heavy Chain Disease 268
Immunophenotype 269
Genetic and Molecular Features 269
Cytogenetic Abnormalities 270
13q14 Deletion 270
Trisomy 12 274
11q22-23 Deletion 275
17p13 Deletion 275
Other Cytogenetic Abnormalities 275
Comparative Genomic Hybridization 275
Somatic Mutations and Next-Generation Sequencing 275
Postulated Cell of Origin and Normal Counterpart Cell 276
CLL Immunoglobulin Structure and Stereotyped Receptors 276
Clinical Course and Prognosis 276
Transformation 277
Differential Diagnosis 278
Monoclonal B-Cell Lymphocytosis (MBL) 279
Definition of Disease 279
Epidemiology and Incidence 281
Clinical Features 281
Morphology 281
Peripheral Blood 281
Bone Marrow 281
Lymph Node 281
Immunophenotype 282
Genetic and Molecular Features 282
Clinical Course 283
B-Prolymphocytic Leukemia 283
Pearls and Pitfalls 283
Key References 284
References 284.e1
15 Lymphoplasmacytic Lymphoma and Waldenström Macroglobulinemia 285
Outline 285
Definition of Disease 285
Epidemiology and Incidence 285
Clinical Features 286
Morphology 286
Peripheral Blood and Bone Marrow 286
Lymph Nodes 288
Spleen and Other Tissues 288
Immunophenotype 291
Genetic Features 291
MYD88 L265P Mutation 291
Other Somatic Mutations 291
Cytogenetic Abnormalities 293
Postulated Normal Counterpart and Pathogenesis 293
Clinical Course, Treatment, and Prognosis 293
Differential Diagnosis 294
Neoplastic Conditions 294
IgM-Secreting Disorders 295
Other Conditions 296
Pearls and Pitfalls 296
Key References 296
References 297.e1
16 Hairy Cell Leukemia 299
Outline 299
Definition of Disease and Nomenclature 299
Epidemiology 299
Etiology 299
Clinical Features 299
Symptoms and Signs 299
Imaging Studies 300
Diagnostic Procedures 300
Morphology 300
Cell Morphology on Smear Preparations 300
Cell Morphology in Bone Marrow Sections 302
Spleen and Other Organs 302
Phenotype 302
Flow Cytometry 302
Immunohistochemistry and Cytochemistry 303
Genetics and Molecular Findings 305
Postulated Cell of Origin and Normal Counterpart 305
Variants 306
Differential Diagnosis 306
Clinical Course and Treatment 307
Prognostic and Predictive Factors 307
Pearls and Pitfalls 308
Key References 308
References 308.e1
17 Splenic Marginal-Zone Lymphoma and Other Small B-Cell Neoplasms in the Spleen 309
Outline 309
Definition 309
Epidemiology 309
Etiology 309
Clinical Features 310
Morphology 310
Immunophenotype 310
Genetics 310
Genetic Abnormalities 310
Antigen Receptor Genes 315
Gene-Expression Profiling 315
Cell of Origin 316
Clinical Course 316
Differential Diagnosis 316
Other Splenic B-Cell Lymphomas 316
Splenic Diffuse Red Pulp Small B-Cell Lymphoma 316
Hairy Cell Leukemia Variant 319
Pearls and Pitfalls 319
Key References 319
References 319.e1
18 Follicular Lymphoma 321
Outline 321
Definition 321
Epidemiology 321
Clinical Features 322
Sites of Involvement 322
Clinical Evaluation and Staging 322
Morphologic Features 323
Cellular Composition 323
Grading 323
Pattern 327
Diffuse Areas in Follicular Lymphoma 330
Diffuse Follicular Lymphoma 330
Partial Nodal Involvement 330
Morphology in Sites Other Than Lymph Nodes 330
Spleen 330
Bone Marrow 332
Peripheral Blood 332
Histologic Transformation 332
Immunophenotype 332
Cytogenetic and Genetic Features 335
Antigen Receptor Genes 335
Cytogenetic Abnormalities 335
Recurrent Gene Rearrangements 339
BCL2 339
BCL6 339
MYC 339
Other Genetic Alterations 339
Gene-Expression Profiles 340
Postulated Normal Counterpart and Pathogenesis 340
Etiology 340
Clinical Course 340
Natural History 340
Treatment 340
Prognosis and Predictive Factors 341
Clinical Factors 341
Histologic Grade 341
Diffuse Areas 341
Histologic Transformation 341
Variants 342
“In Situ” Follicular Neoplasia (In Situ Follicular Lymphoma) 342
Duodenal-Type Follicular Lymphoma 343
Extranodal Follicular Lymphoma 343
Follicular Lymphoma with Predominantly Diffuse Growth Pattern and 1p36 Deletion 343
Follicular Lymphoma with Mutations of NOTCH1 or NOTCH2 343
Other Lymphomas with Follicular Pattern 346
Pediatric-Type Follicular Lymphoma 346
Large B-Cell Lymphoma with IRF4 Translocation 346
Differential Diagnosis 347
Follicular Hyperplasia 347
Morphologic Criteria 349
Pattern 349
Cytology 349
Immunophenotyping 349
Molecular Genetic Analysis 350
Other Small B-Cell Lymphomas 350
Morphologic Features 350
Immunophenotype 350
Genetic Analysis 351
Conclusion 351
Pearls and Pitfalls 352
Key References 352
References 352.e1
19 Extranodal Marginal Zone Lymphoma 353
Outline 353
Histology of the Mucosal Immune System 353
Peyer’s Patches 353
Definition of Malt Lymphoma 354
Epidemiology 355
Etiology 355
Infectious Agents 355
Helicobacter pylori and Gastric MALT Lymphoma 355
Campylobacter jejuni and Immunoproliferative Small Intestinal Disease 356
Borrelia burgdorferi and Cutaneous MALT Lymphoma 357
Chlamydia psittaci and Ocular Adnexal MALT Lymphoma 357
Establishing an Etiologic Link 357
Histopathology of Acquired Malt 357
Salivary Gland Acquired MALT (Lymphoepithelial Sialadenitis) 357
Helicobacter pylori Gastritis 359
Pathology of Malt Lymphoma 359
Macroscopic Appearance 359
Histopathology 359
Morphology of Gastric MALT Lymphoma Following Eradication of Helicobacter pylori 360
Dissemination 360
Immunohistochemistry 364
Genetic Features of Malt Lymphoma 364
Antigen Receptor Genes 364
Genetic Abnormalities 365
Postulated Cell of Origin 366
Clinical Course 366
Differential Diagnosis 366
Reactive Versus Neoplastic MALT 366
MALT Versus Other Small B-Cell Lymphomas 368
Pearls and Pitfalls 368
Key References 368
References 368.e1
20 Primary Cutaneous B-Cell Lymphomas 369
Outline 369
Classification 369
Concept of Primary Cutaneous Lymphomas 369
WHO-EORTC, WHO 2008, and Revised WHO 2016 Classification 370
Primary Cutaneous Marginal-Zone Lymphoma 370
Definition 370
Epidemiology 371
Etiology 371
Clinical Features 371
Histopathology 371
Immunophenotype 371
Genetic Features 371
Differential Diagnosis 371
Prognosis and Predictive Factors 373
Therapy 373
Primary Cutaneous Follicle-Center Lymphoma 373
Definition 373
Epidemiology 374
Clinical Features 374
Histopathology 374
Immunophenotype 374
Genetic Features 374
Differential Diagnosis 376
Prognosis and Predictive Factors 376
Therapy 376
Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type 378
Definition 378
Epidemiology 378
Clinical Features 378
Histopathology 379
Immunophenotype 379
Genetic Features 379
Differential Diagnosis 379
Prognosis, Predictive Factors, and Treatment 379
Intravascular Large B-Cell Lymphoma 379
B-Lymphoblastic Lymphoma 380
Cutaneous Immunodeficiency-Associated Lymphproliferative Disorders 380
Pearls and Pitfalls 381
Key References 381
References 381.e1
21 Nodal Marginal Zone Lymphoma 383
Outline 383
Definition 383
Epidemiology, Etiology, and Cofactors 383
Clinical Features 384
Morphology 384
Cytologic Features 384
Architectural Features 384
Other Anatomic Sites 388
Grading 388
Immunophenotype 388
Genetics and Molecular Findings 390
Postulated Cell of Origin 390
Clinical Course and Prognostic Factors 390
Pediatric Nodal Marginal Zone Lymphoma 390
Morphology and Immunophenotype 390
Genetic Features 391
Clinical Features 391
Differential Diagnosis 392
Extranodal Marginal Zone Lymphoma 392
Lymphoplasmacytic Lymphoma 392
Marginal Zone Hyperplasia and Related Reactive Conditions 392
Monocytoid B-Cell Hyperplasia 392
Follicular Lymphoma With Marginal Zone Differentiation 393
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With a Parafollicular Pattern 394
Splenic Marginal Zone Lymphoma 394
Pearls and Pitfalls 394
Key References 396
References 396.e1
22 Mantle Cell Lymphoma 397
Outline 397
Definition 397
Epidemiology and Clinical Manifestations 397
Postulated Cell of Origin 398
Morphology 399
Architectural Patterns 399
Cytologic Variants 399
Bone Marrow and Peripheral Blood 400
Spleen 401
Gastrointestinal Tract 401
Histologic Progression 403
Composite Mantle Cell Lymphoma 403
Immunophenotype 403
Cytogenetic Findings 405
Molecular Characteristics 406
Translocation (11;14) and Cyclin D1 Expression 406
Cyclin D1 Oncogenic Mechanisms 407
SOX11 Oncogenic Mechanisms 407
Altered Molecular Pathways 407
Cell Cycle Deregulation 407
DNA Damage Response Pathway 408
Cell Survival and Other Pathways 409
Multistep Development and in Situ Mantle Cell Neoplasia 409
Mantle Cell Lymphoma Variants 410
Leukemic Non-nodal Mantle Cell Lymphoma 410
Cyclin D1–Negative Mantle Cell Lymphoma 410
Clinical Course 411
Indolent Mantle Cell Lymphoma 411
Prognostic Parameters 411
Therapy 412
Differential Diagnosis 412
Benign Disorders 412
Cyclin D1–Negative Mantle Cell Lymphoma 412
Atypical Leukemic Lymphoid Neoplasms 413
Chronic Lymphocytic Leukemia–Small Lymphocytic Lymphoma 413
Follicular Lymphoma 413
Marginal-Zone Lymphoma 413
Diffuse Large B-Cell Lymphoma 413
Acute Leukemias 414
Pearls and Pitfalls 414
Key References 414
References 414.e1
23 Diffuse Large B-Cell Lymphoma 415
Outline 415
Definition 415
Epidemiology 415
Etiology 416
Clinical Features 416
Morphology 417
Immunophenotype 423
Genetics 425
Molecular Subtypes: Germinal-Center B-Cell Type and Activated B-Cell Type 425
Postulated Cell of Origin 427
Clinical Course 427
Prognostic Factors 428
Clinical 428
Morphologic 428
Immunohistochemical 428
Molecular 429
Differential Diagnosis 429
Other Lymphomas of Large B-Cells 433
T-Cell/Histiocyte–Rich Large B-Cell Lymphoma 433
Definition 433
Epidemiology 433
Etiology 434
Clinical Features 434
Morphology 434
Immunophenotype 434
Genetics 434
Postulated Cell of Origin 436
Clinical Course 436
Differential Diagnosis 436
Primary Mediastinal (Thymic) Large B-Cell Lymphoma 437
Definition 437
Epidemiology 437
Etiology 437
Clinical Features 437
Morphology 437
Immunophenotype 437
Genetics 438
Postulated Cell of Origin 440
Clinical Course 440
Differential Diagnosis 440
Intravascular Large B-Cell Lymphoma 442
Definition 442
Epidemiology 442
Etiology 442
Clinical Features 442
Morphology 442
Immunophenotype 443
Genetics 444
Postulated Cell of Origin 444
Clinical Course 444
Differential Diagnosis 444
Pearls and Pitfalls 444
Key References 444
References 445.e1
24 Burkitt’s Lymphoma and Its Mimics 447
Outline 447
Burkitt’s Lymphoma 447
Definition 448
Epidemiology 448
Endemic Burkitt’s Lymphoma 448
Sporadic Burkitt’s Lymphoma 449
Immunodeficiency-Associated Burkitt’s Lymphoma 449
Etiology and Pathogenesis 449
Clinical Features 450
Endemic Burkitt’s Lymphoma 450
Sporadic Burkitt’s Lymphoma 450
Immunodeficiency-Associated Burkitt’s Lymphoma 451
Staging 451
Morphology 451
Classic Burkitt’s Lymphoma 451
Variant Burkitt’s Lymphoma with Plasmacytoid Appearance 452
Other Morphologic Variations 453
Immunophenotype 453
Gene Expression Profiling 454
Genetics 455
IG/MYC Translocations 455
Other Molecular Genetic Changes in Burkitt’s Lymphoma 457
Is MYC Translocation Specific to Burkitt’s Lymphoma? 458
Burkitt-Like Lymphoma with 11q Aberrations: Do MYC Breakpoint–Negative Burkitt’s Lymphomas Exist? 458
Clinical Course 459
High-Grade B-Cell Lymphomas Other Than Burkitt’s Lymphoma and Diffuse Large B-Cell Lymphoma 460
High-Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements (Double Hit) 460
High-Grade B-Cell Lymphoma, Not Otherwise Specified 462
Other Differential Diagnoses of Burkitt’s Lymphoma 462
Diffuse Large B-Cell Lymphoma 462
Lymphoblastic Lymphoma 463
Mantle Cell Lymphoma 463
Peripheral T-Cell Lymphoma, Not Otherwise Specified 463
Myeloid Sarcoma 463
A Practical Approach to the Diagnosis of Burkitt’s Lymphoma 463
Pearls and Pitfalls 464
Key References 464
References 464.e1
25 Plasmablastic Neoplasms Other Than Plasma Cell Myeloma 465
Outline 465
Plasmablastic Lymphoma 465
Definition 465
Epidemiology 465
Clinical Features 465
Pathology 466
Genetic Features 467
Differential Diagnosis 467
ALK-Positive Large B-Cell Lymphoma 468
Definition 468
Epidemiology 469
Clinical Features 469
Pathology 469
Genetic Features 470
Differential Diagnosis 470
Pearls and Pitfalls 470
Key References 471
References 472.e1
26 Plasma Cell Neoplasms 473
Outline 473
Plasma Cell Neoplasms 473
Definition 473
Classification 474
Plasma Cell Myeloma (Multiple Myeloma) 474
Definition 474
Diagnostic Criteria 474
Epidemiology 474
Etiology and Pathogenesis 474
Clinical Features 475
Laboratory Findings 475
Radiographic Studies 476
Blood Smear and Bone Marrow Findings 477
Histopathology 479
Plasma Cell Myeloma Clinical Variants 481
Non-Secretory Plasma Cell Myeloma 481
Smoldering Plasma Cell Myeloma (Asymptomatic Myeloma) 482
Plasma Cell Leukemia 483
Immunophenotype (Flow Cytometry) 483
Immunophenotypic Features of Normal and Neoplastic Plasma Cells 483
Normal Plasma Cells 483
Neoplastic Plasma Cells 485
Technical Issues 486
General Technical Issues 486
Technical Issues Related to Minimal Residual Disease Analysis 486
Diagnostic Issues 487
Unusual Morphologic Variants of Myeloma 487
Florid Reactive Plasmacytosis 487
Non-Hodgkin’s Lymphomas With Extreme Plasma Cell Differentiation 487
Prediction of Genetic Abnormalities 488
Prognostic Issues 488
Qualitative Immunophenotypic Features 488
Quantitative Issues at Diagnosis 488
Minimal Residual Disease 488
Circulating Plasma Cells 488
Immunophenotype (Immunohistochemistry) 488
Genetics 489
Genetic Testing for Plasma Cell Myeloma 490
Differential Diagnosis 490
Treatment and Prognosis 492
Treatment 492
Prognosis 492
Monoclonal Gammopathy of Undetermined Significance 493
Definition 493
Epidemiology and Etiology 493
Clinical and Laboratory Features 494
Blood and Bone Marrow Findings 494
Immunophenotype 494
Flow Cytometry 494
Immunohistochemistry 495
Genetics 495
Differential Diagnosis 495
Clinical Course, Treatment, and Prognostic Factors 495
Clinical Course 495
Treatment 495
Prognostic Factors 495
Plasmacytoma 496
Solitary Plasmacytoma of Bone 496
Definition and Diagnostic Criteria 496
Epidemiology 496
Clinical Features 496
Morphology, Immunophenotype, and Genetics 497
Differential Diagnosis 497
Treatment, Clinical Course, and Prognosis 497
Extraosseous Plasmacytoma 497
Definition 497
Epidemiology 497
Clinical Features 497
Morphology 497
Immunophenotype and Genetics 497
Differential Diagnosis 498
Treatment, Clinical Course, and Prognosis 498
Immunoglobulin Deposition Diseases 498
Primary Amyloidosis 498
Definition 498
Epidemiology 498
Clinical Features 499
Laboratory Findings 499
Diagnosis 499
Blood and Bone Marrow Findings 499
Immunophenotype 500
Cytogenetics 501
Differential Diagnosis 501
Treatment and Prognosis 501
Treatment 501
Prognosis 501
Systemic Light Chain and Heavy Chain Deposition Diseases 501
Definition 501
Epidemiology 501
Pathophysiology 502
Clinical and Laboratory Findings 502
Morphology 502
Immunophenotype and Genetics 502
Differential Diagnosis 502
Treatment and Prognosis 502
Plasma Cell Neoplasms With Associated Paraneoplastic Syndrome 502
POEMS Syndrome (Osteosclerotic Myeloma) 502
Definition 502
Epidemiology, Etiology, and Pathogenesis 503
Clinical Features 503
Morphology 503
Immunophenotype 504
Cytogenetics 504
Differential Diagnosis 504
Treatment and Prognosis 504
TEMPI Syndrome 505
Definition 505
Etiology and Epidemiology 505
Clinical and Laboratory Features 505
Morphology 505
Immunophenotypic Features and Genetics 505
Differential Diagnosis 505
Treatment and Prognosis 505
Pearls and Pitfalls 506
References 506.e1
27 Nodular Lymphocyte–Predominant Hodgkin’s Lymphoma 507
Outline 507
Definition 507
Historical Background 507
Epidemiology 508
Clinical Features 508
Morphology 509
IV Myeloid Neoplasms 783
44 Principles of Classification of Myeloid Neoplasms 785
Outline 785
Evaluation of Myeloid Neoplasms 786
World Health Organization Classification 788
Myeloproliferative Neoplasms 788
Myeloid/Lymphoid Neoplasms With Eosinophilia and Rearrangement of PDGFRA, PDGFRB, or FGFR1 or With PCM1-JAK2 788
Myelodysplastic/Myeloproliferative Neoplasms 791
Myelodysplastic Syndromes 791
Acute Myeloid Leukemia 791
Acute Leukemias of Ambiguous Lineage 792
Myeloid Neoplasms With Germline Predisposition 792
Conclusion 792
Acknowledgment 792
Key References 792
References 792.e1
45 Myelodysplastic Syndromes 793
Outline 793
Incidence 794
Clinical Features 794
Laboratory Features 794
Peripheral Blood Parameters 794
Microscopic Features in Peripheral Blood and Bone Marrow 794
Extramedullary Manifestations 797
Flow Cytometry Abnormalities 797
Genetic Abnormalities 798
Role of Genetic Abnormalities in the Diagnosis of Myelodysplastic Syndromes 799
Role of Genetic Abnormalities in the Classification of Myelodysplastic Syndromes 800
Role of Genetic Abnormalities in the Prognostication of Myelodysplastic Syndromes 800
Other Biologic Abnormalities and Assessments 800
Loss of Function in Hematopoietic Cells 800
Apoptosis and Cell Cycle Analysis 800
Diagnosis 801
Classification 801
Myelodysplastic Syndrome–Related Disease versus De Novo Acute Myeloid Leukemia 801
General Biologic Subtypes of Myelodysplastic Syndrome 802
Low-Grade Myelodysplastic Syndromes 802
High-Grade Myelodysplastic Syndromes 802
World Health Organization Classification 802
Myelodysplastic Syndrome with Single Lineage Dysplasia (Previously: Refractory Cytopenia with Unilineage Dysplasia) 803
Myelodysplastic Syndrome with Ring Sideroblasts (Previously: Refractory Anemia with Ring Sideroblasts and Refractory Cytopenia with Multilineage Dysplasia and Ring Sideroblasts) 803
Myelodysplastic Syndrome with Multilineage Dysplasia (Previously: Refractory Cytopenia with Multilineage Dysplasia) 804
Myelodysplastic Syndrome with Excess Blasts (Previously: Refractory Anemia with Excess Blasts) 805
Myelodysplastic Syndrome with Isolated del(5q) 805
Myelodysplastic Syndrome, Unclassifiable (MDS-U) 805
Myelodysplastic Syndrome in Children, Including Refractory Cytopenia of Childhood and Familial Myeloid Neoplasms 806
Therapy-Related Myelodysplastic Syndromes 806
Prognostic Scoring Systems 806
Additional Considerations 807
Hypoplastic Myelodysplastic Syndrome 807
Erythroid-Predominant Myelodysplastic Syndromes 807
Myelodysplastic Syndromes with 3q26 Abnormalities 808
Myelodysplastic Syndromes with 17p Abnormalities 808
Myelodysplastic Syndromes with Fibrosis 808
Differential Diagnosis 808
Megaloblastic Anemia 808
Chemotherapy-Induced Dysplasia and Cytopenias 809
Marrow Recovery after Chemotherapy in Myelodysplastic Syndrome–Related Acute Myeloid Leukemia 809
Marrow Recovery after Acute Marrow Injury or Stem Cell Transplantation 809
Acute Myeloid Leukemia with Recurrent Genetic Abnormalities and Low Blast Count 809
Non–Myelodysplastic Syndrome Abnormal Hematopoiesis 810
Idiopathic Cytopenia of Undetermined Significance (ICUS) 810
Idiopathic Dysplasia of Undetermined Significance 810
Clonal Hematopoiesis of Indeterminate Potential (CHIP) 810
Marrow Dysplasia in HIV Infection 811
Large Granular Lymphocytic Leukemia 811
Congenital Dyserythropoietic Anemias 811
Non–Myelodysplastic Syndrome Sideroblastic Anemias 811
Copper Deficiency and Zinc Toxicity 811
Arsenic Exposure 812
Chronic Viral Infections 812
Primary Myelofibrosis 812
Acute Megakaryoblastic Leukemia 812
Myelodysplastic/Myeloproliferative Neoplasms 812
Aplastic Anemia 812
Paroxysmal Nocturnal Hemoglobinuria 813
Causative Agents 813
Pathogenesis 813
Conclusion 814
Pearls and Pitfalls 814
Key References 814
References 815.e1
46 Acute Myeloid Leukemia 817
Outline 817
Epidemiology 818
Etiology 818
Clinical Features 818
Morphology 818
Cytochemistry 818
Immunophenotype 819
Genetics 819
Prognosis 819
Acute Myeloid Leukemia With Recurrent Genetic Abnormalities 819
Acute Myeloid Leukemia With t(8;21)(q22;q22.1) (RUNX1-RUNX1T1) 819
Acute Myeloid Leukemia With inv(16)(p13.1q22) or t(16;16)(p13.1;q22) (CBFB-MYH11) 820
Acute Promyelocytic Leukemia With PML-RARA 822
Acute Promyelocytic Leukemia With Variant RARA Translocations 823
Acute Myeloid Leukemia With t(9;11)(p21.3;q23.3) (KMT2A-MLLT3) 824
Acute Myeloid Leukemia With t(6;9)(p23;q34.1) (DEK-NUP214) 825
Acute Myeloid Leukemia With inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) (GATA2, MECOM/EVI1) 826
Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13.3;q13.1) (RBM15-MKL1) 827
Acute Myeloid Leukemia With BCR-ABL1 828
Other Acute Myeloid Leukemias With Recurrent Genetic Abnormalities 829
Acute Myeloid Leukemia With Gene Mutations 829
Acute Myeloid Leukemia With Mutated NPM1 830
Acute Myeloid Leukemia With Biallelic Mutations of CEBPA 832
Acute Myeloid Leukemia With Mutated RUNX1 832
Acute Myeloid Leukemia With Myelodysplasia-Related Changes 833
Therapy-Related Myeloid Neoplasms 835
Acute Myeloid Leukemia, Not Otherwise Specified 836
Acute Myeloid Leukemia With Minimal Differentiation 837
Acute Myeloid Leukemia Without Maturation 837
Acute Myeloid Leukemia With Maturation 837
Acute Myelomonocytic Leukemia 837
Acute Monoblastic and Monocytic Leukemias 837
Acute Erythroid Leukemia 838
Acute Megakaryoblastic Leukemia 839
Acute Basophilic Leukemia 839
Acute Panmyelosis With Myelofibrosis 840
Myeloid Proliferations of Down’s Syndrome 840
Transient Abnormal Myelopoiesis 840
Myeloid Leukemia Associated With Down’s Syndrome 841
Myeloid Sarcoma 842
Integrated Approach to the Diagnosis of Acute Myeloid Leukemia 844
Pearls and Pitfalls 845
Key References 845
References 845.e1
47 Myeloproliferative Neoplasms 847
Outline 847
Definition 847
Etiology and Pathogenesis 848
“Driver” Genetic Abnormalities in Myeloproliferative Neoplasms 848
Associated Mutations, Cytogenetic Abnormalities, and Pathogenetic Mechanisms in Myeloproliferative Neoplasms 852
Chronic Myeloid Leukemia, BCR-ABL1 Positive 852
Diagnosis 852
Clinical Findings 853
Laboratory Findings 853
Peripheral Blood, Chronic Phase 853
Bone Marrow, Chronic Phase 853
Extramedullary Tissues 855
Genetics 855
Disease Progression 856
Accelerated Phase 857
Blast Phase 857
Therapy, Disease Monitoring, and Prognosis 860
Differential Diagnosis 861
Chronic Phase 861
Myeloid or Lymphoid Blast Phase 862
Chronic Neutrophilic Leukemia 863
Diagnosis 863
Clinical Findings 863
Laboratory Findings 863
Peripheral Blood 863
Bone Marrow 864
Extramedullary Tissues 864
Genetics 864
Disease Progression and Prognosis 864
Differential Diagnosis 865
Polycythemia Vera 865
Diagnosis 866
Clinical Findings, Polycythemic Phase 866
Laboratory Findings, Polycythemic Phase 866
Peripheral Blood 866
Bone Marrow 866
Extramedullary Tissues 867
Genetics 867
Other Laboratory Findings 867
Disease Progression and Prognosis 868
Post-Polycythemic Myelofibrosis 868
Acute Leukemia/Myelodysplastic Phase 868
Differential Diagnosis 869
Primary Polycythemia, Acquired and Congenital 869
Secondary Polycythemia, Acquired and Congenital 869
Primary Myelofibrosis 869
Diagnosis 870
Clinical Findings 870
Laboratory Findings 871
Peripheral Blood 871
Bone Marrow 871
Extramedullary Tissues 873
Genetics 873
Disease Progression and Prognosis 875
Differential Diagnosis 875
Essential Thrombocythemia 876
Diagnosis 877
Clinical Findings 877
Laboratory Findings 877
Peripheral Blood 877
Bone Marrow 878
Extramedullary Tissues 878
Genetics 878
Disease Progression and Prognosis 878
Differential Diagnosis 879
Myeloproliferative Neoplasms, Unclassifiable 880
Pearls and Pitfalls 880
Key References 881
References 881.e1
48 Myelodysplastic/Myeloproliferative Neoplasms 883
Outline 883
Etiology and Pathogenesis 883
Chronic Myelomonocytic Leukemia 886
Clinical Findings 887
Laboratory Findings 888
Blood 888
Bone Marrow 888
Extramedullary Tissues 894
Immunophenotype 895
Cytogenetics and Genetics 895
Other Laboratory Findings 895
Differential Diagnosis 896
Reactive Monocytosis 896
Acute Myelomonocytic and Acute Monocytic Leukemia 897
Chronic Myeloid Leukemia, BCR-ABL1 Positive 897
Myeloid Neoplasms Associated With Eosinophilia and Rearrangements of PDGFRB 897
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative 897
BCR-ABL1–Negative Myeloproliferative Neoplasms Associated With Monocytosis 897
Myelodysplastic Syndrome 897
Prognosis, Prognostic Factors, and Progression 897
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative 898
Clinical Findings 898
Laboratory Findings 899
Blood 899
Bone Marrow 899
Extramedullary Tissues 900
Immunophenotype 900
Cytogenetics and Genetics 901
Differential Diagnosis 901
Chronic Myelomonocytic Leukemia 901
Chronic Myeloid Leukemia, BCR-ABL1 Positive 901
Myeloproliferative Neoplasms, BCR-ABL1 Negative (Chronic Neutrophilic Leukemia, Polycythemia Vera, Primary Myelofibrosis, Essential Thrombocythemia) 901
Myelodysplastic Syndrome 901
Prognosis and Prognostic Factors 902
Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis 902
Clinical Findings 902
Laboratory Findings 902
Blood 902
Bone Marrow 902
Immunophenotype 902
Cytogenetics and Genetics 902
Differential Diagnosis 903
Myelodysplastic Syndrome With Ring Sideroblasts 903
Myeloproliferative Neoplasm With Ring Sideroblasts 903
Prognosis and Prognostic Factors 903
Juvenile Myelomonocytic Leukemia 904
Clinical Findings 904
Laboratory Findings 904
Blood 904
Bone Marrow 906
Extramedullary Tissues 906
Immunophenotype 906
Cytogenetics and Genetics 906
Genetic Susceptibility 906
Other Laboratory Findings 908
Differential Diagnosis 908
Infection 908
Other Myeloid Diseases 909
Prognosis and Prognostic Factors 909
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable 909
Pearls and Pitfalls 909
Key References 909
References 910.e1
49 Mastocytosis 911
Outline 911
Definition 911
General Aspects 912
Epidemiology and Etiology 912
Postulated Cell of Origin and Normal Counterpart 912
Genetics and Molecular Findings 912
Cytologic and Histologic Diagnosis 914
Histology 915
Immunophenotype 916
Histopathologic Findings 917
Bone Marrow 918
Spleen 918
Liver 918
Lymph Nodes 918
Gastrointestinal Tract 919
Skin 921
Differential Diagnosis 921
Classification 922
Cutaneous Mastocytosis 922
Definition 922
Epidemiology 923
Clinical Features 923
Morphology 924
Immunophenotype 924
Postulated Cell of Origin 924
Clinical Course 924
Differential Diagnosis 924
Indolent Systemic Mastocytosis 925
Definition 925
Epidemiology 925
Clinical Features 925
Morphology 925
Immunophenotype 925
Postulated Cell of Origin 926
Clinical Course 926
Subvariants and Differential Diagnosis 926
Systemic Mastocytosis with an Associated Hematologic Neoplasm 926
Definition 926
Epidemiology 926
Clinical Features 926
Morphology 926
Immunophenotype 927
Postulated Cell of Origin 927
Clinical Course 927
Differential Diagnosis 927
Aggressive Systemic Mastocytosis 927
Definition 927
Epidemiology 927
Clinical Features 927
Morphology 927
V Histiocytic Proliferations 955
52 Non-neoplastic Histiocytic Proliferations of Lymph Nodes and Bone Marrow 957
Outline 957
Sinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease) 957
Definition 957
Epidemiology 958
Etiology 958
Clinical Features 958
Morphology 958
Immunophenotype 959
Clinical Course 959
Differential Diagnosis 959
Hemophagocytic Syndromes 959
Familial (Primary) Hemophagocytic Lymphohistiocytosis 960
Definition 960
Epidemiology 960
Etiology 960
Clinical Features 961
Morphology 961
Immunophenotype 962
Clinical Course 962
Secondary Hemophagocytic Syndromes 962
Definition 962
Epidemiology 962
Etiology 963
Clinical Features 963
Morphology 963
Immunophenotype 963
Genetics 964
Clinical Course 964
Differential Diagnosis 964
Niemann-Pick Disease 964
Definition 964
VI Immunodeficiency Disorders 997
54 The Pathology of Primary Immunodeficiencies 999
Outline 999
Classification 1000
Epidemiology 1000
Severe Combined Immunodeficiency 1000
The Thymus in SCID, CID, and Leaky SCID 1000
Omenn’s Syndrome 1001
Combined ID Generally Less Profound Than SCID 1001
CD40L Deficiency or Hyper IgM Type 1 Syndrome 1002
AID Deficiency or Hyper IgM Type 3 Syndrome 1002
Common Variable Immunodeficiency 1002
PI3K-Related Immunodeficiencies 1004
Agammaglobulinemia 1006
X-Linked Agammaglobulinemia 1006
X-Linked Lymphoproliferative Disease 1006
X-Linked Inhibitor of Apoptosis 1007
Defects That Affect Homeostasis of the Immune System 1007
Autosomal Dominant Immune Dysregulation Syndrome with Heterozygous Germline Mutations of Cytotoxic T-Cell Antigen-4 1007
Autoimmune Lymphoproliferative Syndrome 1008
Defects in Synapse Formation and Crosstalk between Antigen-Presenting Cells and T-Cells 1009
Wiskott-Aldrich Syndrome 1009
Warts, Hypogammaglobulinemia, Infections, and Myelokathexis 1010
Ataxia Telangiectasia 1011
Pearls and Pitfalls 1011
Key References 1011
References 1011.e1
55 Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders 1013
Outline 1013
Definition 1013
Post-Transplant Lymphoproliferative Disorders 1013
Epidemiology 1013
Etiology 1015
Clinical Features 1015
Morphology 1017
Non-destructive Post-transplant Lymphoproliferative Disorders 1017
Polymorphic Post-transplant Lymphoproliferative Disorder 1017
Monomorphic Post-transplant Lymphoproliferative Disorder 1020
Monomorphic B-Cell Post-transplant Lymphoproliferative Disorder 1020
Monomorphic T/NK-Cell Post-transplant Lymphoproliferative Disorder 1022
Classical Hodgkin’s Lymphoma Post-transplant Lymphoproliferative Disorder 1023
Immunophenotype 1023
Genetics 1024
Clonality Studies 1024
Epstein-Barr Virus Studies 1024
Cytogenetic and Additional Molecular Studies 1024
Postulated Normal Counterparts 1025
Clinical Course 1025
Differential Diagnosis 1026
Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders in Non-transplant Settings 1027
Pearls and Pitfalls 1028
Key References 1028
References 1029.e1
VII Site-Specific Issues in the Diagnosis of Lymphoma and Leukemia 1031
56 Bone Marrow Evaluation for Lymphoma 1033
Outline 1033
Distinction between Benign Lymphoid Aggregates and Lymphoma 1034
Morphology 1034
Immunohistochemistry 1034
Flow Cytometric Immunophenotyping 1037
Molecular Diagnostic Studies 1038
Unusual Reactive Lymphoid Infiltrates 1039
Systemic Polyclonal Immunoblastic Proliferation 1039
Reactive Polymorphous Lymphohistiocytic Proliferation 1040
Non-Hodgkin’s Lymphoma Involving Bone Marrow 1041
Incidence of Bone Marrow Involvement 1041
Histologic Patterns of Bone Marrow Involvement 1041
Characteristic Features of B-Cell Lymphomas Involving Bone Marrow 1041
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 1043
Lymphoplasmacytic Lymphoma and Waldenström’s Macroglobulinemia 1044
Marginal Zone Lymphoma 1045
Splenic Marginal Zone Lymphoma 1045
Nodal Marginal Zone Lymphoma 1046
Extranodal Marginal Zone Lymphoma 1046
Follicular Lymphoma 1046
Mantle Cell Lymphoma 1047
Diffuse Large B-Cell Lymphoma 1050
Intravascular Large B-Cell Lymphoma 1052
Primary Effusion Lymphoma 1052
Burkitt’s Lymphoma 1052
High-Grade B-Cell Lymphoma 1053
B-Lymphoblastic Leukemia/Lymphoma 1053
Characteristic Features of T-Cell Lymphomas Involving Bone Marrow 1053
T-Lymphoblastic Leukemia/Lymphoma 1053
Extranodal NK/T-Cell Lymphoma 1054
Enteropathy-Associated T-Cell Lymphoma 1054
Hepatosplenic T-Cell Lymphoma 1054
Subcutaneous Panniculitis-Like T-Cell Lymphoma 1056
Mycosis Fungoides and Sézary Syndrome 1056
Angioimmunoblastic T-Cell Lymphoma 1058
Peripheral T-Cell Lymphoma, Not Otherwise Specified 1058
Anaplastic Large Cell Lymphoma 1060
Characteristic Features of Hodgkin’s Lymphoma Involving Bone Marrow 1060
Non-lymphoid Malignant Neoplasms That Mimic Lymphomas 1061
Metastatic Tumors 1061
Systemic Mastocytosis 1062
Pearls and Pitfalls 1063
Key References 1064
References 1064.e1
57 Evaluation of the Bone Marrow After Therapy 1065
Outline 1065
General Approach 1065
Acute Leukemia or Myelodysplastic Syndrome 1068
Acute Myeloid Leukemia and Myelodysplastic Syndrome 1068
Morphologic Features 1068
Immunophenotyping 1069
Cytogenetics and Molecular Studies 1070
Acute Lymphoblastic Leukemia 1072
Morphologic Features 1072
Immunophenotyping 1072
Cytogenetics and Molecular Studies 1073
Distinguishing Hematogones from Leukemic Blasts 1074
BCR-ABL1–Positive Chronic Myeloid Leukemia 1074
Morphologic Features 1075
Immunophenotyping 1076
Cytogenetics and Molecular Studies 1076
BCR-ABL1–Negative Myeloproliferative Neoplasms 1077
Morphologic Features 1077
Immunophenotyping 1077
Cytogenetics and Molecular Studies 1077
Chronic Lymphoproliferative and Plasma Cell Disorders 1078
Morphologic Features 1078
Immunophenotyping 1078
Cytogenetics and Molecular Studies 1080
Other Bone Marrow Changes After Therapy 1082
Necrosis 1082
Fibrosis 1082
Serous Atrophy 1082
Solid Tumors 1082
Growth Factor Changes 1083
Late Effects of Therapy, Including Secondary Malignancies 1084
Key References 1087
References 1087.e1
58 Non-hematopoietic Neoplasms of the Bone Marrow 1089
Outline 1089
Definition 1089
Invasive Breast Carcinoma 1089
Carcinoma of the Lung 1092
Squamous Cell Carcinoma 1092
Adenocarcinomas 1092
Metastatic Prostate Cancer 1092
Carcinomas of the Stomach 1092
Colorectal Carcinomas 1093
Renal Cell Carcinoma 1093
Malignant Melanoma 1093
Pediatric Cancers 1093
Rhabdomyosarcoma 1093
Neuroblastoma 1093
Retinoblastoma 1094
Medulloblastoma 1095
Ewing’s Sarcoma 1095
Neuroectodermal Tumor of Bone 1095
Cartilage-Forming Tumors 1095
Hemangiomas 1095
Epithelioid Hemangioendotheliomas 1096
Other Soft Tissue Tumors 1096
Malignant Lymphomas 1096
Benign Tumor-Like Lesions of the Bone 1096
Metaphyseal Fibrous Defect (Non-Ossifying Fibroma) 1096
Paget’s Disease 1096
Chronic Osteomyelitis 1096
Conclusion 1097
Pearls and Pitfalls 1097
Key References 1097
References 1097.e1
59 Non-lymphoid Lesions of the Lymph Nodes 1099
Outline 1099
Metastatic Tumors in Lymph Nodes 1099
Histologic Features of Metastatic Tumors 1099
Characteristic Biologic Patterns of Metastasis 1101
Role of Immunohistochemistry in the Diagnosis of Metastatic Tumors 1102
Non-lymphoid Tumors With Prominent Reactive Lymphoid Components 1104
Benign Lymph Node Inclusions 1105
Epithelial and Mesothelial Inclusions in Lymph Nodes Adjacent to Solid Organs 1105
Keratin-Positive Fibroblastic Reticular Cells 1106
Nevus Cell Aggregates 1106
Mesenchymal Proliferations in Lymph Nodes 1107
Vascular Transformation of Lymph Node Sinuses and Lymphatic Proliferations 1107
Mixed Smooth Muscle–Vascular Proliferations 1107
Inflammatory Pseudotumor of Lymph Nodes 1108
Kaposi’s Sarcoma 1109
Vascular Tumors 1110
Metastatic Sarcomas of Other Types 1110
Bone Marrow Hematopoietic Elements and Tumors Involving Lymph Nodes 1111
Pearls and Pitfalls 1112
Key References 1112
References 1112.e1
60 Spleen 1113
Outline 1113
The Normal Spleen 1114
Gross Examination 1114
Diffuse Splenic Enlargement 1114
White Pulp Involvement 1114
Red Pulp Involvement 1116
Focal Splenic Pathology 1116
Splenic Rupture 1116
Lymphoid Hyperplasia 1116
Castleman’s Disease 1117
Autoimmune Lymphoproliferative Syndrome 1117
Hodgkin’s Lymphoma 1118
Non-Hodgkin’s Lymphomas 1118
Primary Splenic Lymphoma 1118
Secondary Splenic Involvement by Lymphoma 1119
Precursor Lymphoid Neoplasms 1119
Systemic or Secondary Mature B-Cell Lymphomas and Leukemias 1119
Primary B-Cell Lymphoid Neoplasms Presenting with Prominent Splenomegaly 1120
Mature T-Cell and NK-Cell Neoplasms 1120
T-Cell Lymphoid Neoplasms Presenting with Prominent Splenomegaly 1121
Myeloid Neoplasms 1121
Myeloproliferative Neoplasms 1121
Chronic Myeloid Leukemia 1121
Polycythemia Vera 1122
Primary Myelofibrosis 1122
Essential Thrombocythemia 1123
Other Chronic Myeloid Neoplasms 1123
Systemic Mastocytosis 1124
Proliferations of the Monocyte-Macrophage System 1124
Hemophagocytic Syndromes 1124
Mesenchymal Tumors and Non-Neoplastic Disorders That Mimic Neoplasms 1125
Splenic Hemangioma 1125
Littoral Cell Angioma 1125
Splenic Angiosarcoma 1125
Splenic Lymphangioma 1127
Sclerosing Angiomatoid Nodular Transformation of the Spleen 1127
Peliosis 1127
Splenic Hamartoma 1128
Inflammatory Pseudotumor-Like Dendritic Cell Sarcoma and Reactive Pseudotumoral Lesions of the Spleen 1129
Inflammatory Pseudotumor-like Dendritic Cell Sarcoma 1129
Other Proliferations 1129
Splenic Cysts 1129
Other Tumors 1130
Storage Diseases 1130
Pearls and Pitfalls 1131
Key References 1131
References 1131.e1
61 Diagnosis of Lymphoma in Extranodal Sites Other Than Skin 1133
Outline 1133
Nervous System and Meninges 1133
Central Nervous System 1133
Epidemiology and Etiology 1136
Clinical Features 1136
Morphologic Features 1136
Immunophenotype 1137
Genetic Features 1137
Postulated Normal Counterpart 1137
Staging, Treatment, and Outcome 1137
Differential Diagnosis 1137
Eye 1137
Clinical Features 1137
Index 1167
A 1167
B 1169
C 1172
D 1175
E 1176
F 1177
G 1178
H 1179
I 1181
J 1182
K 1183
L 1183
M 1186
N 1189
O 1190
P 1190
Q 1194
R 1194
S 1194
T 1196
U 1198
V 1198
W 1198
X 1199
Z 1199
Inside Back Cover ibc1