Bone Marrow Pathology Third Edition (2 Vol set)

The new 2-volume edition of Bone Marrow Pathology is the best of both worlds a comprehensive atlas of diagnostic
imaging and illustrations of genetic results combined with practical advice from experts. A virtual roadmap to the
latest best practices, the new edition integrates the full scope of the 2008 WHO criteria with answers to your day-to-
day diagnostic questions.

Tables by Chapter
1: Hematopoiesis
t1.1 Cell Types Produced by Hematopoietic
and Mesenchymal Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
t1.2 Features of Mesenchymal Stem Cells (MSC) . . . . . . . . . . . . . . . . 5
t1.3 Bone Marrow Microenvironment . . . . . . . . . . . . . . . . . . . . . . . . . . 6
t1.4 Features of Hematopoietic Stem Cells (HSC) . . . . . . . . . . . . . . . . 6
t1.5 Future Directions and Current Controversies:
Regenerative Medicine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
t1.6 General Features of Hematolymphoid Growth Regulatory
Factors (Cytokines) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
t1.7 Selected Genes Involved in Hematopoiesis . . . . . . . . . . . . . . . . . . 8
t1.8 Granulopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
t1.9 B-Cell Maturation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
t1.10 T-Cell Maturation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2: Morphologic Review of Blood and Bone Marrow
t2.1 Age/Gender-Related Physiologic Variations in Normal Blood
Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
t2.2 Age-Related Normal Values in Bone Marrow . . . . . . . . . . . . . . . 32
t2.3 Normal Adult Values for Bone Marrow Diff erential Cell Counts 34
t2.4 Erythroid Lineage Checklist. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
t2.5 Granulocytic Lineage Checklist. . . . . . . . . . . . . . . . . . . . . . . . . . . 38
t2.6 Megakaryocytic Lineage Checklist . . . . . . . . . . . . . . . . . . . . . . . . 38
t2.7 Lymphoid Lineage Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
t2.8 Bone Marrow Stroma Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
t2.9 Causes of Bone Marrow Artifacts . . . . . . . . . . . . . . . . . . . . . . . . . 46
3: Procurement and Indications for
Bone Marrow Examination
t3.1 Indications for Bone Marrow Examination . . . . . . . . . . . . . . . . . 53
t3.2 Decision-Making Variables for Bone Marrow Examination in
the Evaluation of Patients with Peripheral Blood Abnormalities 54
t3.3 Complications of Bone Marrow Examination . . . . . . . . . . . . . . . 55
t3.4 Types of Routine Bone Marrow Preparations . . . . . . . . . . . . . . . 60
t3.5 Comparison of Bone Marrow Preparations . . . . . . . . . . . . . . . . . 61
t3.6 Specialized Techniques in Bone Marrow Evaluation . . . . . . . . . 63
t3.7 Cytochemical Stains Commonly Used
in Bone Marrow Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
4: Specialized Techniques
in Bone Marrow Evaluation
t4.1 Histologic Grading of Storage Iron . . . . . . . . . . . . . . . . . . . . . . . . 68
t4.2 Key Tips When Assessing BM Storage Iron . . . . . . . . . . . . . . . . . 68
t4.3 Bone Marrow Reticulin and Collagen Fiber Grading Systems . 69
t4.4 Key Tips When Evaluating and Reporting BM Fibrosis. . . . . . . 70
t4.5 Indications for Immunohistochemistry in BM Evaluation . . . . 70
t4.6 Common Antibodies in BM Immunohistochemistry. . . . . . . . . 70
t4.7 Selected Immunohistochemical Antibodies with Diagnostic/
Prognostic Signifi cance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
t4.8 Comparison of Immunophenotypic Testing Modalities . . . . . . 71
t4.9 Key Quality Control Issues in Decalcifi ed Bone Marrow
Immunohistochemistry (IHC). . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
t4.10 Indications for Flow Cytometry in Blood/Bone Marrow
Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
t4.11 Key Quality Control Issues for Flow Cytometry. . . . . . . . . . . . . 73
t4.12 Flow Cytometric Clues to Help Identify an Abnormal Population 73
t4.14 Basic Components of Chromosomal Analysis . . . . . . . . . . . . . . . 74
t4.13 Indications for Conventional Cytogenetic Studies
in Bone Marrow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
t4.15 Key Quality Control Issues in Cytogenetic Analysis . . . . . . . . . 75
t4.16 Advantages of Conventional Cytogenetic Testing . . . . . . . . . . . 75
t4.17 Comparison of FISH with Conventional Karyotyping . . . . . . . 76
t4.18 Basic Components of FISH Analysis . . . . . . . . . . . . . . . . . . . . . . . 77
t4.19 Key Quality Control Issues in FISH Testing . . . . . . . . . . . . . . . . 77
t4.20 Indications for Molecular Testing . . . . . . . . . . . . . . . . . . . . . . . . . 78
t4.21 Comparison of Polymerase Chain Reaction (PCR)
and Southern Blot Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
t4.22 Key Quality Control Issues in Polymerase Chain Reaction
(PCR)-Based Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
t4.23 Comparison of 4 Specialized Techniques . . . . . . . . . . . . . . . . . . . 79
t4.24 Basic Components of Gene Expression Profi ling . . . . . . . . . . . . 80
t4.25 Key Quality Assurance Issues in Gene Expression Profi ling. . . 80
t4.26 Selected Gene Expression Profi ling Findings
in Hematolymphoid Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
t4.27 microRNAs in Selected Hematolymphoid Tumors. . . . . . . . . . . 81
5: Bone Marrow Reporting
and Quality Assurance
t5.1 Desired Clinical Information for Complete BM Interpretation 85
t5.2 Ideal Components for BM Examination . . . . . . . . . . . . . . . . . . . . 85
t5.3 Obtainable Data from Diff erent Components
of Bone Marrow Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
t5.4 Suggested Checklist for Evaluation of BM Specimens . . . . . . . . 87
t5.5 Key Components of a Bone Marrow Writt en Report . . . . . . . . . 88
t5.6 Components of a Final Integrated Report . . . . . . . . . . . . . . . . . . 88
t5.7 Key Technical Quality Control Issues in BM Examination. . . . 89
t5.8 Key Interpretative Quality Control Issues in BM Examination 89
t5.9 Key Components of a Quality Assurance Program
for BM Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
6: Anemias
t6.1 Age- and Sex-Related Variations in Erythrocyte Normal Ranges 93
t6.3 Overview of Classifi cation of Anemias: Prototypic Features . . 94
t6.2 Systematic Approach to Anemia Evaluation . . . . . . . . . . . . . . . . 94
t6.4 Classifi cation of Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
t6.5 Peripheral Blood and Bone Marrow Findings in Patients
with Congenital Dyserythropoietic Anemias (CDAs) . . . . . . . 101
t6.6 Tests Useful in the Diagnosis and Distinction
of Cobalamin and Folate Defi ciencies . . . . . . . . . . . . . . . . . . . . . 109
t6.7 Blood and Bone Marrow Findings in Megaloblastic Anemias 109
t6.8 Causes of Bone Marrow Megaloblastosis . . . . . . . . . . . . . . . . . . 113
t6.9 Causes of Ring Sideroblastosis in Bone Marrow . . . . . . . . . . . . 114
t6.10 Erythrocyte Survival Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
t6.11 Paroxysmal Nocturnal Hemoglobinuria (PNH). . . . . . . . . . . . 120
t6.12 Components of Diagnostic Interpretation of Anemias. . . . . . . 124
7: Aplastic Anemia and Multilineage Bone Marrow
Failure Disorders
t7.1 Proposed Criteria for Diagnosis of Aplastic Anemia . . . . . . . . 131
t7.2 Severity of Aplastic Anemia by Absolute Neutrophil Count. . 131
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t7.3 Multiparametric Assessment of BM Failure. . . . . . . . . . . . . . . . 131
t7.4 Molecular Pathogenesis of
Constitutional Bone Marrow Failure Disorders . . . . . . . . . . . . 140
t7.5 Recognized Genetic Mutations
in Inherited Bone Marrow Failure Syndromes . . . . . . . . . . . . . 141
t7.6 Components for Diagnostic Interpretation in Aplastic Anemia 147
8: Erythroblastopenia
t8.1 Erythroblastopenic Disorders (Red Cell Aplasia). . . . . . . . . . . 151
t8.2 Diamond-Blackfan Anemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
t8.3 Comparison of Erythroblastopenic Disorders . . . . . . . . . . . . . . 153
t8.5 Hematologic Manifestations of Parvovirus B19 Infection. . . . 157
t8.4 Features of Parvovirus B19 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
t8.6 Classifi cation of Acquired Sustained Red Cell Aplasia
(Pure Red Cell Aplasia) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
t8.7 Components of Diagnostic Interpretation in Red Cell Aplasia . 165
9: Erythrocytosis
t9.1 General Approach to Erythrocytosis. . . . . . . . . . . . . . . . . . . . . . 169
t9.2 General Defi nitions and Categories of Erythrocytoses . . . . . . 170
t9.3 2008 World Health Organization
Diagnostic Criteria for Polycythemia Vera. . . . . . . . . . . . . . . . . 170
t9.4 Comparison of Laboratory Tests Useful in Classifying
Acquired Polycythemic (Erythrocytotic) Disorders . . . . . . . . 171
t9.5 Peripheral Blood and Bone Marrow Findings
in Polycythemia Vera . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
t9.6 Causes of Neonatal Polycythemia . . . . . . . . . . . . . . . . . . . . . . . . 175
10: Non-Neoplastic Granulocytic and Monocytic
Disorders, Excluding Neutropenia
t10.1 Absolute Cell Counts by Patient Age. . . . . . . . . . . . . . . . . . . . . . 181
t10.2 Causes of Non-Neoplastic Neutrophilia . . . . . . . . . . . . . . . . . . . 182
t10.3 Granulocytic Morphologic Abnormalities . . . . . . . . . . . . . . . . . 183
t10.4 Morphologic Features of Reactive Neutrophilia
in Blood and Bone Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184
t10.5 Morphologic Features of Blood and Bone Marrow
in Patients Receiving Recombinant Growth Factor Th erapy . 185
t10.6 Peripheral Blood Findings in Hantavirus Pulmonary Syndrome 187
t10.7 Peripheral Blood Clues in Neutrophilia
to Suggest Bone Marrow Examination . . . . . . . . . . . . . . . . . . . . 188
t10.8 Neutrophilic Disorders in Children
that Mimic Overt Neoplastic Processes . . . . . . . . . . . . . . . . . . . 188
t10.9 Non-Neoplastic Constitutional Disorders
with Abnormal Granulocyte Morphology . . . . . . . . . . . . . . . . . 189
t10.10 Non-Neoplastic Acquired Disorders
with Abnormal Granulocyte Morphology . . . . . . . . . . . . . . . . . 190
t10.11 Causes of Secondary/Reactive Eosinophilia . . . . . . . . . . . . . . . 195
t10.12 Primary (Neoplastic) Eosinophilias . . . . . . . . . . . . . . . . . . . . . . 195
t10.13 Peripheral Blood Clues in Unexplained Eosinophilia
to Suggest Bone Marrow Examination . . . . . . . . . . . . . . . . . . . . 196
t10.14 Causes of Reactive Basophilia in Blood and Bone Marrow . . . 197
t10.15 Neoplastic Diff erential Diagnostic Considerations of Basophilia 197
t10.16 Peripheral Blood Clues in Unexplained Basophilia
to Suggest Bone Marrow Examination . . . . . . . . . . . . . . . . . . . . . . . . . 198
t10.17 Causes of Non-Neoplastic Monocytosis . . . . . . . . . . . . . . . . . . . 199
t10.18 Peripheral Blood Clues in Unexplained/Prolonged
Monocytosis to Suggest Bone Marrow Examination . . . . . . . . 200
11: Neutropenia and Agranulocytosis
t11.1 Selected Diagnostic Considerations When
Neutropenia Occurs with Other Cytopenia(s) . . . . . . . . . . . . . 207
t11.2 Eff ects of Demographic Characteristics
on Absolute Neutrophil Count (ANC) . . . . . . . . . . . . . . . . . . . . 207
t11.3 Mutations in Isolated Constitutional Neutropenia Syndromes 208
t11.4 Syndromes Associated with Constitutional Neutropenia
and Key Diagnostic Clues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
t11.5 Morphologic Clues to Suspected Constitutional Neutropenia 209
t11.6 Interplay between Initiating Causes and Direct Mechanisms
of Neutropenia and Agranulocytosis of Secondary Etiology. . 216
t11.7 Morphologic Approach to Isolated Neutropenia in Adults . . . 217
t11.8 Human Neutrophil Antigens (HNA),
with Standardized Nomenclature . . . . . . . . . . . . . . . . . . . . . . . . 220
t11.9 Selected Drugs Frequently Implicated
in Agranulocytosis (Excluding Chemotherapeutic Agents) . . 222
12: Megakaryocytic/Platelet Disorders
t12.1 Atypical Megakaryocytic Morphology
in Myeloid Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
t12.2 Approach to Blood Smears with Abnormal Platelet
Morphology and/or Size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
t12.3 Congenital Megakaryocytic Disorders
with Th rombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
t12.4 Acquired Megakaryocytic Disorders
with Th rombocytopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
t12.5 Constitutional Megakaryocytic Disorders
with Th rombocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
t12.6 Acquired Megakaryocytic Disorders with Th rombocytosis. . 240
t12.7 Causes of Neonatal Th rombocytopenia . . . . . . . . . . . . . . . . . . . 245
t12.8 Comparison of Blood and Bone Marrow Findings
in Reactive and Neoplastic Th rombocytotic Disorders . . . . . . 247
t12.9 Diff erential Diagnosis of Multinucleated
and/or Giant Cells in Bone Marrow. . . . . . . . . . . . . . . . . . . . . . . 247
13: Conceptual Overview of Myeloid Neoplasms
t13.1 Key Clinical Data Relevant to Myeloid Neoplasms . . . . . . . . . 253
t13.2 Integrative Diagnostic Approach to Myeloid Neoplasms. . . . . 253
t13.3 Hemogram Data in Myeloid Neoplasms . . . . . . . . . . . . . . . . . . . 254
t13.4 Blood Smear Features of Myeloid Neoplasms . . . . . . . . . . . . . . 254
t13.5 Bone Marrow Aspirate Features in Myeloid Neoplasms . . . . . 256
t13.6 Bone Marrow Core Biopsy Findings in Myeloid Neoplasms. . 256
t13.7 Blasts and Blast Equivalents in Myeloid Neoplasms. . . . . . . . . 257
t13.8 Myeloid Neoplasms Defi ned
by Cytogenetic Molecular Features . . . . . . . . . . . . . . . . . . . . . . 257
t13.9 Testing Recommendations for Myeloid Disorders . . . . . . . . . . 258
t13.10 Additional Suggestions/Considerations
for Specialized Testing Strategies . . . . . . . . . . . . . . . . . . . . . . . . 259
14: Myeloproliferative Neoplasms
t14.1 Recent Signifi cant Advances in the Classifi cation of MPNs . . 261
t14.2 Approach to the Diagnosis of an MPN . . . . . . . . . . . . . . . . . . . . 261
t14.3 Prototypic Blood and Bone Marrow Features of MPNs. . . . . . 264
t14.4 Lineage Assessment in MPNs . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
t14.5 Minimal Diagnostic Criteria in the Classic MPNs
(CML, PV, ET, PMF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
t14.6 Genetic Findings in MPNs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
t14.7 Comparative Blood/Bone Marrow Morphologic and Genetic
Features of Selected Myeloproliferative Neoplasms. . . . . . . . . 272
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t14.8 WHO 2008 Diagnostic Criteria for Polycythemia Vera,
Essential Th rombocythemia, and Primary Myelofi brosis . . . . 274
t14.9 Historical, Clinical, Epidemologic, and Prognostic Features
in Chronic Myelogenous Leukemia, BCR-ABL1+. . . . . . . . . . . 275
t14.10 Disease Phases of Chronic Myelogenous Leukemia,
BCR-ABL1+ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
t14.11 Hematologic and Morphologic Features of Chronic
Myelogenous Leukemia, BCR-ABL1+, in Chronic Phase . . . . 276
t14.12 Chronic Myelogenous Leukemia, BCR-ABL1+, Blast Phase . . 281
t14.13 Selected Key Tips Regarding Genetics in CML, BCR-ABL1+ 282
t14.14 Unique Disease Manifestations of CML, BCR-ABL1+ . . . . . . 283
t14.15 Key Features of PV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284
t14.16 Blood and Bone Marrow Features in PV. . . . . . . . . . . . . . . . . . . 284
t14.17 Key Features of ET . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
t14.18 Blood and Bone Marrow Features in ET. . . . . . . . . . . . . . . . . . . 288
t14.19 Clues to Aid in the Distinction of ET
from Prefi brotic PMF and/or Early Phase PV . . . . . . . . . . . . . . 290
t14.20 Key Clinical Features of PMF. . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
t14.21 Hematologic and Morphologic Features of PMF . . . . . . . . . . . 292
t14.22 Causes of Bone Marrow Osteosclerosis. . . . . . . . . . . . . . . . . . . . 294
t14.23 Causes of Bone Marrow Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . 295
t14.24 Key Tips in the Bone Marrow Diagnosis
of Myeloproliferative Neoplasms, Unclassifi able . . . . . . . . . . . 296
t14.25 Key Diagnostic Features of CEL, NOS . . . . . . . . . . . . . . . . . . . . 297
t14.26 Key Features of CNL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
t14.27 Overview of Mast Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
t14.28 Estimated Incidence of Mastocytosis in Adults . . . . . . . . . . . . 304
t14.29 Categorization of Bone Marrow Mastocytosis. . . . . . . . . . . . . . 304
t14.30 Clinical, Physical, and Radiologic Features
of Bone Marrow Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
t14.31 Hematologic and Morphologic Findings
in Systemic Mastocytosis and Variants . . . . . . . . . . . . . . . . . . . . 304
t14.32 Diagnostic Criteria for Various
Bone Marrow Mastocytosis Entities . . . . . . . . . . . . . . . . . . . . . . 305
t14.33 Familial MPNs: ET, PV, PMF. . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
t14.34 Diff erential Diagnosis of MPNs . . . . . . . . . . . . . . . . . . . . . . . . . . 312
t14.35 Components of the Diagnostic Interpretation. . . . . . . . . . . . . . 313
15: Myeloid and Lymphoid Neoplasms with Eosinophilia
(MLNE) and Abnormalities of PDGFRA, PDGFRB,
or FGFR1
t15.1 Reported Cytogenetic Abnormalities Involving PDGFRB . . . 325
t15.2 Reported Cytogenetic Abnormalities Involving PDGFRA . . . 326
t15.3 Reported Cytogenetic Abnormalities Involving FGFR1 . . . . 327
16: Myelodysplastic Syndromes
t16.1 Approach to the Diagnosis of MDS . . . . . . . . . . . . . . . . . . . . . . . 331
t16.2 Prognostic Factors in Myelodysplasia . . . . . . . . . . . . . . . . . . . . . 333
t16.3 Prognostic Factor Scoring Systems in Myelodysplastic
Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
t16.4 Prototypic Blood and Bone Marrow Features of MDS. . . . . . . 334
t16.5 Dysplastic Features in Myelodysplasia . . . . . . . . . . . . . . . . . . . . 336
t16.6 Minimal Diagnostic Criteria in MDS . . . . . . . . . . . . . . . . . . . . . 340
t16.7 Cytogenetic Abnormalities in MDS. . . . . . . . . . . . . . . . . . . . . . . 341
t16.8 Frequency of Cytogenetic Abnormalities Based on WHO
Subtype of MDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
t16.9 Flow Cytometric Immunophenotyping in MDS . . . . . . . . . . . . 342
t16.10 WHO Classifi cation of Myelodysplastic Syndromes (MDS). . 344
t16.11 Unique Types of Myelodysplasia . . . . . . . . . . . . . . . . . . . . . . . . . 350
t16.12 Myeloid Neoplasms with Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . 351
t16.13 Diff erential Diagnosis of Myelodysplasia . . . . . . . . . . . . . . . . . . 354
t16.14 Blasts in Blood: Key Age-Based Considerations . . . . . . . . . . . . 355
t16.15 Components of the Diagnostic Interpretation in MDS . . . . . . 355
17: Myelodysplastic/Myeloproliferative Neoplasms
t17.1 Myelodysplastic/Myeloproliferative Neoplasms. . . . . . . . . . . . 361
t17.2 Diagnostic Approach to Myelodysplastic/Myeloproliferative
Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
t17.3 Criteria for Dysplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
t17.4 WHO Criteria for Juvenile Myelomonocytic Leukemia. . . . . . 367
tS17.1 Frequency of Mutations in Neurofi bromatosis Type 1, Noonan
Syndrome, and Juvenile Myelomonocytic Leukemia . . . . . . . . 368
t17.5 WHO Criteria for Atypical Chronic Myelogenous Leukemia,
BCR-ABL1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
t17.6 Diff erential Diagnosis of Myelodysplastic/Myeloproliferative
Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374
t17.7 Components of the Diagnostic Interpretation. . . . . . . . . . . . . . 374
18: Acute Myeloid Leukemia
t18.1 Selected Risk Factors for AML . . . . . . . . . . . . . . . . . . . . . . . . . . 378
t18.2 Class I and Class II Mutations in AML. . . . . . . . . . . . . . . . . . . . 379
t18.3 Acute Myeloid Leukemia: Diagnostic Steps. . . . . . . . . . . . . . . . 380
t18.4 Blasts, Blast Equivalents, Other Immature Cells
in Blood and Bone Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
t18.5 Clues and Confi rmatory Tests for Biologic Types of AML . . . 386
t18.6 Characteristics of AML with Variant RA RA Translocations . . 396
t18.7 Cytogenetic Abnormalities Suffi cient to Diagnose AML
with Myelodysplasia-Related Changes . . . . . . . . . . . . . . . . . . . . 401
t18.8 Comparison of Clinicopathologic Features of 2 Types
of Th erapy-Related Myeloid Neoplasms . . . . . . . . . . . . . . . . . . . 403
t18.9 Acute Myeloid Leukemia, Not Otherwise Specifi ed. . . . . . . . . 409
t18.10 Prognostic Risk of Cytogenetic Abnormalities in Patients <60
Years with De Novo AML . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
t18.11 Potential Immunophenotypic Markers with Prognostic
Signifi cance in AML at Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . 418
t18.12 Diff erential Diagnostic Possibilities for Myeloid Proliferations
with Abundant Erythroid Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 421
t18.13 Diagnosis of AML: Key Tips/Strategies . . . . . . . . . . . . . . . . . . . 423
19: Blastic Plasmacytoid Dendritic Cell Neoplasms
in Bone Marrow
t19.1 Previous Terminologies for Blastic Plasmacytoid
Dendritic Cell Neoplasm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
t19.2 Features of Blastic Plasmacytoid Dendritic Cell Neoplasm . . 433
t19.3 Diagnostic Strategies to Distinguish Blastic Plasmacytoid
Dendritic Cell Neoplasm from Morphologic Mimics . . . . . . . . 435
t19.4 Components of the Diagnostic Interpretation
of Blastic Neoplasms in Bone Marrow. . . . . . . . . . . . . . . . . . . . . 437
20: Acute Leukemias of Ambiguous Lineage
t20.1 WHO 2008 Criteria for Assigning >1 Lineage
to a Single Blast Population. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441
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CONTENTS
Contents Volume 2 (abridged)
21: Non-Neoplastic Disorders of Lymphoid Cells
[21.1] Lymphocytoses in Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450
[21.2] Lymphocyte Abnormalities in Constitutional Disorders 457
[21.3] Normal Lymphocyte Ranges in Bone Marrow. . . . . . . . . . 458
[21.4] Increased Lymphoid Cells in Bone Marrow . . . . . . . . . . . . .459
[21.5] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .470
22: Mature B- and T-Cell Lymphoproliferative Neoplasms
[22.1] Chronic Lymphoproliferative Neoplasms . . . . . . . . . . . . . . .475
[22.2] Chronic Lymphocytic Leukemia . . . . . . . . . . . . . . . . . . . . . . . .476
[22.3] B-Cell Prolymphocytic Leukemia . . . . . . . . . . . . . . . . . . . . . . .491
[22.4] Hairy Cell Leukemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493
[22.5] Peripheralizing B-Cell Lymphomas . . . . . . . . . . . . . . . . . . . . .501
[22.6] T-Chronic Lymphoproliferative Neoplasms . . . . . . . . . . . 504
[22.7] Components of the Diagnostic Interpretation in CLPN .514
[22.8] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .514
23: Plasma Cell Myeloma and Other Immunosecretory
Neoplasms
[23.1] Monoclonal Gammopathy of Uncertain Signifi cance. . . 524
[23.2] Plasma Cell Myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 526
[23.3] Monoclonal Immunoglobulin Deposition Diseases . . . . 539
[23.4] B-Cell Lymphoproliferative Disorders with Plasmacytic
Diff erentiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542
[23.5] Heavy Chain Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 544
[23.6] Transformation of WM/LPL and PCM . . . . . . . . . . . . . . . . 546
[23.7] Diff erential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547
[23.8] Components of the Diagnostic Interpretation . . . . . . . . . . 549
[23.9] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549
24: Bone Marrow Lymphomas
[24.1] Bone Marrow Examination for Lymphoma. . . . . . . . . . . . . 555
[24.2] Patt erns of Bone Marrow Involvement in Lymphoma. . . 556
[24.3] Incidence of Bone Marrow Involvement in NHL . . . . . . . .557
[24.4] B-NHL in Bone Marrow and Blood . . . . . . . . . . . . . . . . . . . . 558
[24.5] T-NHL in Blood and Bone Marrow . . . . . . . . . . . . . . . . . . . . .573
[24.6] Hodgkin Lymphoma in Bone Marrow. . . . . . . . . . . . . . . . . . 580
[24.7] Diff erential Diagnosis of Bone Marrow Lymphoma . . . . 584
[24.8] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 585
25: Precursor B- and T-Cell Acute Lymphoblastic
Leukemia/Lymphoma (aka Lymphoblastic Leukemia/
Lymphoma)
[25.1] Defi nition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .591
[25.2] Incidence, Epidemiology, and Pathogenesis . . . . . . . . . . . . .591
[25.3] Risk Factors and Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .591
[25.4] Approach to Diagnosis and Classifi cation . . . . . . . . . . . . . . 592
[25.5] Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 592
[25.6] Genetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601
[25.7] Minimal Residual Disease, Early Response to Th erapy, and
Relapse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 606
[25.8] Diff erential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 606
[25.9] Components of the Diagnostic Interpretation . . . . . . . . . . .610
[25.10] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .610
26: Indolent and Aggressive Natural Killer Cell Leukemias
[26.1] Chronic Lymphoproliferative Neoplasm of NK Cells. . . .617
[26.2] Aggressive NK Cell Leukemia. . . . . . . . . . . . . . . . . . . . . . . . . . .621
[26.3] Components of the Diagnostic Interpretation . . . . . . . . . . 624
[26.4] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 624
[26.5] References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 624
27: Histiocytic Disorders in Bone Marrow
[27.1] Bone Marrow Granulomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .629
[27.2] Diff use Histiocytoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .631
[27.3] Clonal Diff use Histiocytic Disorders . . . . . . . . . . . . . . . . . . . 643
[27.4] Diff erential Diagnosis of Bone Marrow Histiocytoses . . 647
[27.5] Components of Diagnostic Interpretation . . . . . . . . . . . . . . 648
[27.6] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 649
28: Bone Marrow Stroma and Bone Disorders
[28.1] Bone Marrow Stroma Disorders. . . . . . . . . . . . . . . . . . . . . . . . 653
[28.2] Disorders of Bony Trabeculae . . . . . . . . . . . . . . . . . . . . . . . . . . 673
[28.3] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 682
29: Metastatic Lesions in Bone Marrow
[29.1] Incidence and Clinical Findings . . . . . . . . . . . . . . . . . . . . . . . . 687
[29.2] Blood and Bone Marrow Findings. . . . . . . . . . . . . . . . . . . . . . 687
[29.3] Detection of Submicroscopic Metastases . . . . . . . . . . . . . . . 697
[29.4] Diff erential Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698
[29.5] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 699
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CONTENTS
30: Bone Marrow Examination in Children
[30.1] Hematologic Parameters in the Neonate and Young
Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 703
[30.2] Constitutional Hematopoietic Disorders . . . . . . . . . . . . . . . 706
[30.3] Aplastic Anemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 708
[30.4] Benign Erythroid Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 709
[30.5] Benign Granulocytic/Monocytic Disorders . . . . . . . . . . . . .710
[30.6] Benign Lymphoid Disorders Including Hematogones . . .712
[30.7] Benign Platelet/Megakaryocyte Disorders . . . . . . . . . . . . . .715
[30.8] Disorders Associated with Down Syndrome. . . . . . . . . . . . .715
[30.9] Hematologic Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .716
[30.10] Metastatic Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .719
[30.11] Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .719
[30.12] Diagnostic Interpretation
of Hematologic Abnormalities. . . . . . . . . . . . . . . . . . . . . . . . . . .721
[30.13] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .721
31: Pregnancy-Associated Hematologic Disorders
[31.1] Pregnancy-Associated Physiologic Changes . . . . . . . . . . . . 727
[31.2] Pathologic Hematologic Disorders During Pregnancy. . 728
[31.3] Hemostatic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 729
[31.4] Hematologic Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 732
[31.5] Impact of Maternal Hematologic Disease on the Fetus . 733
[31.6] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 733
32: Bone Marrow Evaluation in the Elderly
[32.1] Aging-Related Hematopoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . 737
[32.2] Anemia in the Elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 737
[32.3] Other Cytopenias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 738
[32.4] Diff erential Diagnosis of Cytopenias in the Elderly . . . . . 738
[32.5] Bone Marrow Examination in the Elderly . . . . . . . . . . . . . . 738
[32.6] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 739
33: Bone Marrow Findings in Systemic Infections
[33.1] Viral Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .743
[33.2] Bacterial Infections Including Rickett sial Infections. . . . 760
[33.3] Fungal Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .762
[33.4] Protozoal and Helminthic Infections. . . . . . . . . . . . . . . . . . . .762
[33.5] Bone Marrow Granulomas in Infectious Diseases . . . . . . 764
[33.6] Hemophagocytic Lymphohistiocytosis (Infection-
Associated Type) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .765
[33.7] Peripheral Blood and Bone Marrow Pseudoinfections . . 766
[33.8] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .767
34: Bone Marrow Manifestations of Noninfectious
Systemic Diseases
[34.1] Overview of Blood Abnormalities . . . . . . . . . . . . . . . . . . . . . . 773
[34.2] Anemia of Chronic Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773
[34.3] Chronic Alcoholism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .775
[34.4] Collagen Vascular Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 777
[34.5] Renal Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 780
[34.6] Endocrine Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 783
[34.7] Gastrointestinal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 785
[34.8] Nonhematologic Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . 785
[34.9] Constitutional Disorders with Distinctive
Blood and Bone Marrow Manifestions . . . . . . . . . . . . . . . . . 787
[34.10] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 789
35: Post-Therapy Bone Marrow Findings
[35.1] Eff ects of Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 793
[35.2] Eff ects of Specifi c Th erapeutic Agents . . . . . . . . . . . . . . . . . . 799
[35.3] Eff ects of Recombinant Cytokine Th erapy. . . . . . . . . . . . . . 800
[35.4] Eff ects of Selected Other Medications . . . . . . . . . . . . . . . . . . 804
[35.5] Bone Marrow Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . 805
[35.6] Bone Marrow Reporting aft er Th erapy . . . . . . . . . . . . . . . . . .810
[35.7] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .810
36: Minimal Residual Disease
[36.1] Approach to and Utility of MRD Detection . . . . . . . . . . . . .819
[36.2] Methods of MRD Detection . . . . . . . . . . . . . . . . . . . . . . . . . . . .819
[36.3] MRD Detection in Selected Hematopoietic Disorders. . .821
[36.4] MRD Monitoring aft er Transplantation. . . . . . . . . . . . . . . . 822
[36.5] Dormancy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 823
[36.6] Clues and Caveats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 823
Appendix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . a3
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix1