BOOK
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 |