Blood and Bone Marrow Pathology: Expert Consult: Online and Print, 2nd Edition

cover......Page 1
Blood and\rBone Marrow\rPATHOLOGY......Page 2
Blood and Bone Marrow Pathology......Page 4
Copyright......Page 5
Preface......Page 6
Contributors......Page 7
Dedication to Sunitha N. Wickramasinghe......Page 10
toc 1......Page 11
toc 2......Page 12
Red cell parameters......Page 13
Red cell life span......Page 14
Functions of red cells......Page 15
Reticulocytes......Page 16
Morphology and composition......Page 17
Functions......Page 18
Functions......Page 20
Functions......Page 21
Monocytes......Page 22
Lymphocytes......Page 23
Morphology and composition......Page 25
Functions......Page 26
References......Page 27
2 Normal bone marrow cells:......Page 29
Postnatal changes in the distribution of hemopoietic marrow......Page 30
Hemopoietic stem cells and progenitor cells......Page 31
Regulation of erythropoiesis......Page 32
Light microscope cytology......Page 33
Megakaryopoiesis......Page 34
Neutrophil granulopoiesis......Page 35
Light microscope cytology......Page 36
Cytochemistry......Page 37
Antigen expression......Page 38
Eosinophil granulopoiesis......Page 39
Eosinophil granules and ultrastructure......Page 40
Lymphopoiesis......Page 41
Antigen expression......Page 43
Plasma cells......Page 45
Light microscope cytology, cytochemistry and antigen expression......Page 46
Osteoclasts......Page 47
Adipocytes......Page 48
Morphological assessment......Page 49
Phenotypic assessment......Page 51
References......Page 52
Bone marrow structure......Page 55
Marrow cellularity......Page 56
Erythropoiesis......Page 57
Granulopoiesis......Page 59
Megakaryopoiesis......Page 61
Macrophages, monocytes and dendritic cells......Page 63
Lymphocytes......Page 64
Hemopoietic stem cells and early precursor cells......Page 67
Stromal cells......Page 68
Collagen......Page 69
Blood vessels......Page 70
References......Page 71
Characteristics of hematopoietic stem and progenitor cells......Page 73
Functional characterization......Page 74
The hematopoietic stem cell niche......Page 75
Vascular niche......Page 76
Polycomb genes......Page 77
Hedgehog signaling......Page 78
TGFβ superfamily......Page 79
References......Page 80
Principles of bone marrow examination......Page 87
Morphologic changes in erythroblasts......Page 88
Morphologic changes in the neutrophil series......Page 89
Plasma cells......Page 90
Macrophages (histiocytes)......Page 91
Hemophagocytic syndromes......Page 92
Osteoblasts and osteoclasts......Page 93
Iron stores......Page 94
Infections and the bone marrow......Page 95
Changes in the bone marrow......Page 97
Bone marrow granulomas......Page 98
Metastatic tumors in bone marrow......Page 101
Bone marrow fibrosis......Page 102
Gaucher disease......Page 103
Niemann–Pick disease......Page 104
Bone marrow necrosis......Page 105
Gelatinous transformation......Page 106
Vascular and embolic lesions......Page 107
Post-mortem bone marrow changes......Page 108
References......Page 109
Recommended reading......Page 110
Clinical features of anemia......Page 111
The blood count and red cell indices in anemia......Page 112
Red cell morphology in anemia......Page 113
Normocytic anemias......Page 116
The classification of anemia......Page 117
References......Page 118
Hereditary spherocytosis......Page 120
SLC4A1 gene mutations......Page 121
SPTB gene mutations......Page 123
Paroxysmal exertion-induced dyskinesia......Page 124
References......Page 125
Clinical features......Page 126
Blood cell morphology......Page 127
Biochemical investigation of erythroenzyme disorders......Page 131
Molecular basis of erythroenzyme disorders......Page 132
References......Page 133
Normal human hemoglobin: structure and synthesis......Page 135
Inherited disorders of hemoglobin......Page 137
Genetic basis of disease......Page 138
Pathophysiology......Page 139
Genotype-phenotype correlation......Page 140
Diagnosis......Page 142
Clinical features and management......Page 143
β Thalassemia in association with other hemoglobin variants......Page 144
The δβ-, γδβ-thalassemias and HPFH syndromes......Page 145
Pathophysiology......Page 146
Bart’s hydrops fetalis......Page 147
α Thalassemia with mental retardation (ATR) syndromes......Page 148
Genetic basis and pathophysiology......Page 149
Clinical features......Page 151
Management......Page 153
Other hemoglobin variants......Page 154
Hemoglobin variants with abnormal oxygen binding......Page 155
Acknowledgment......Page 156
References......Page 157
Clinical and laboratory features of hemolytic anemia......Page 160
FcR-mediated red cell clearance......Page 161
Complement-mediated red cell destruction......Page 162
Specificity of IgG autoantibodies in AIHA......Page 163
Management of patients with warm AIHA......Page 164
Paroxysmal cold hemoglobinuria......Page 165
Hemolytic disease of the newborn......Page 166
Drug-dependent antibody......Page 167
Thrombotic thrombocytopenic purpura–hemolytic uremic syndrome......Page 169
Other causes of hemolytic anemia......Page 170
References......Page 171
Introduction......Page 176
Major pathways of iron exchange......Page 177
Regulation of cellular iron homeostasis......Page 178
Developmental (transcriptional) regulation of iron uptake in the erythron......Page 179
Uptake of iron by duodenal mucosal cells......Page 180
Role of hepcidin......Page 181
Regulation of hepcidin production......Page 182
Serum ferritin......Page 183
Tissue biopsy......Page 184
Clinical features of iron deficiency anemia......Page 185
Mechanism of iron deficiency anemia......Page 186
Pathophysiology......Page 187
Reduction in iron supply to the erythroid marrow......Page 188
Iron overload......Page 189
HFE-related (Type 1) hereditary hemochromatosis......Page 190
Iron loading in other inherited disorders of iron metabolism......Page 192
Treatment......Page 193
References......Page 194
Megaloblastic hemopoiesis......Page 199
Vitamin B12......Page 200
Causes of vitamin B12 deficiency (Box 12.1)......Page 203
Folate and neural tube defects......Page 208
Causes of folate deficiency (Box 12.1)......Page 209
Lesch–Nyhan syndrome87......Page 210
Macrocytosis with normoblastic erythropoiesis3......Page 211
References......Page 212
Recommended reading......Page 214
Definition and differential diagnosis......Page 215
Viruses......Page 216
Hematology......Page 217
Clinical presentation......Page 218
Treatment of aplastic anemia......Page 219
Matched unrelated donor and cord blood transplants......Page 220
Transient erythroblastopenia of childhood......Page 221
Primary PRCA......Page 222
Treatment of pure red cell aplasia......Page 223
References......Page 224
ALA synthase 2 defect......Page 227
Putative deficit of mitochondrial glycine import......Page 230
Pseudouridine synthase 1 defect......Page 231
Secondary acquired sideroblastic anemia......Page 232
Primary acquired sideroblastic anemia......Page 233
References......Page 234
Congenital dyserythropoietic anemia, type 1 (CDA-1)......Page 236
Congenital dyserythropoietic anemia, type 2 (CDA-2)......Page 237
Congenital dyserythropoietic anemia, type 3 (CDA-3)......Page 240
Diagnosis of congenital dyserythropoietic anemia......Page 242
References......Page 245
Neutropenia......Page 246
Benign chronic neutropenias......Page 247
Neutropenia in patients with congenital chromosomal abnormalities......Page 248
Infections associated with neutropenia.......Page 249
Drug-induced neutropenia.......Page 250
Neutrophilia in acute infection or inflammation......Page 251
Inherited abnormalities......Page 252
Acquired abnormalities......Page 253
Eosinophilia and asthma......Page 255
Monocytes......Page 256
Acquired lymphopenias......Page 257
References......Page 258
Disorders of phagocyte maturation......Page 261
Deficiencies of adhesion and migration......Page 264
Phagocyte signaling abnormalities......Page 265
Deficiencies of the phagocyte respiratory burst......Page 266
References......Page 267
Introduction......Page 271
Clinical history......Page 272
Cytochemistry......Page 273
Acute myeloid leukemia with recurrent genetic abnormalities......Page 274
Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); (PML-RARA)......Page 275
AML with t(6;9)(p23;q34); (DEK-NUP214)......Page 276
Acute myeloid leukemia with gene mutations......Page 277
AML with mutated NPM1......Page 278
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC)......Page 279
Acute myelomonocytic leukemia (AMML)......Page 280
Acute megakaryoblastic leukemia......Page 281
Transient abnormal myelopoiesis (TAM)......Page 282
Myeloid leukemia associated with Down syndrome......Page 283
References......Page 284
Clinical presentation......Page 287
Cytology, cytochemistry and histopathology......Page 288
Immunophenotypic diagnosis......Page 289
B-cell lymphoblastic leukemia/ lymphoma (B-LBL)......Page 290
Molecular genetics......Page 291
Minimal residual disease monitoring......Page 294
Classification......Page 295
Cytology and histopathology......Page 296
References......Page 298
Epidemiology......Page 300
Diagnosis......Page 301
Erythrocytes......Page 303
Leukocytes......Page 304
Bone marrow examination......Page 305
Granulopoiesis......Page 306
General histologic features of myelodysplastic syndromes......Page 307
Assessment of spatial distribution of hemopoiesis in MDS......Page 308
Cytologic features in trephine biopsy sections in MDS......Page 309
Myelodysplasia in hypoplastic bone marrow......Page 310
Use of immunohistochemistry and fluorescent in situ hybridization (FISH) in trephine biopsy sections in myelodysplasia......Page 311
Flow cytometry in diagnosis of MDS......Page 312
Genetics......Page 313
Clinical course and management......Page 314
References......Page 315
Introduction......Page 318
The Philadelphia chromosome and BCR-ABL in chronic myelogenous leukemia......Page 319
JAK2V617F......Page 320
The JAK2V617F mutation in de novo acute leukemia and in MPN transformed to acute leukemia......Page 321
Myeloproliferative leukemia virus oncogene (MPL) mutations in MPN......Page 322
JAK2V617F, MPLW515L/K, BCR-ABL, KITD816V: molecular markers may be combined in an individual patient......Page 323
The casitas B-lineage lymphoma gene (CBL) aberrancies in MPN and other myeloid malignancies......Page 324
References......Page 325
Introduction......Page 329
Methemoglobinemia......Page 330
Associated with normal P50......Page 331
Erythrocytosis secondary to tumors......Page 332
Laboratory features......Page 333
Genetics in PV......Page 334
The bone marrow biopsy in PV......Page 336
Unclassifiable erythrocytosis......Page 339
References......Page 340
Introduction......Page 342
Essential thrombocythemia (ET)......Page 343
Blood and bone marrow findings......Page 344
Primary myelofibrosis (PMF)......Page 347
Blood and bone marrow findings......Page 348
References......Page 352
Clinical features and course of disease......Page 355
Genetics......Page 356
At diagnosis......Page 357
Chronic phase (CP)......Page 359
Acute phase, blast crisis (BC)......Page 360
Atypical CML......Page 361
Myelodysplastic syndromes......Page 362
References......Page 363
Myeloid and lymphoid neoplasms with PDGFRA rearrangement......Page 365
Peripheral blood......Page 366
Other tissues......Page 367
Peripheral blood......Page 368
Supplementary investigations......Page 369
Bone marrow......Page 370
Supplementary investigations......Page 371
Eosinophilic transformation of other myeloid neoplasms......Page 372
References......Page 373
Introduction......Page 374
Important messages......Page 375
General morphological aspects of SM......Page 376
Bone marrow smears......Page 378
Main subtypes of SM......Page 379
Differential diagnosis......Page 380
References......Page 382
Introduction......Page 384
Morphology and immunophenotypic features......Page 385
Prognosis......Page 389
Morphology and immunophenotypic features......Page 390
Atypical chronic myeloid leukemia with t(8;9)(p22;p24)/PCM1-JAK2......Page 391
Morphology and immunophenotypic features......Page 392
Epidemiology, clinical and laboratory features......Page 393
Differentiation of RARS-T from myeloproliferative neoplasms with thrombocytosis and ring sideroblasts......Page 394
Myelodysplastic syndrome with isolated del(5q) and JAK2V617F mutation......Page 395
Concluding remarks......Page 396
References......Page 397
Clinical features......Page 400
Other tissues......Page 401
Cytogenetics and molecular genetics......Page 402
Bone marrow......Page 404
Immunophenotype......Page 405
Clinical features......Page 406
Immunophenotype......Page 407
Bone marrow......Page 408
Bone marrow......Page 409
References......Page 410
Introduction......Page 412
Differential diagnosis of reactive lymphoid aggregates vs lymphoma......Page 413
Bone marrow trephine biopsy (BMTB)......Page 414
The World Health Organization (WHO) classification of lymphomas......Page 416
Bone marrow trephine biopsy......Page 418
Blood and bone marrow aspiration......Page 419
Bone marrow trephine biopsy......Page 420
Clinical features and pathology in the spleen......Page 421
Bone marrow trephine biopsy......Page 422
Bone marrow trephine biopsy......Page 423
Genetic studies......Page 424
Blood and bone marrow aspiration......Page 425
Clinical features and pathology at presenting sites......Page 426
Genetic studies......Page 427
Clinical features and pathology at presenting sites......Page 428
B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma......Page 429
Bone marrow trephine biopsy......Page 430
Genetic studies......Page 431
Clinical features and lymph node pathology......Page 432
Bone marrow trephine biopsy......Page 433
Bone marrow trephine biopsy......Page 434
Clinical and pathologic features......Page 435
BM hyperplastic, dysplastic and stromal reactions to lymphoma......Page 436
Differential diagnosis and classification of lymphoma when bone marrow trephine biopsy provides the sole source of tissue for assessment......Page 437
References......Page 438
30 Abnormalities in immunoglobulin synthesizing cells......Page 443
Biology and growth signaling......Page 444
Cytogenetic and molecular abnormalities......Page 445
Diagnostic criteria......Page 447
Recurrent infections......Page 448
Pathology......Page 449
Treatment......Page 451
Biology......Page 452
Treatment/management/disease progression......Page 453
Clinical features......Page 454
Biology......Page 455
Heavy-chain disorders......Page 456
α-Heavy-chain disease......Page 457
Cryoglobulinemia......Page 458
References......Page 459
Introduction......Page 462
Platelet aggregation......Page 463
Fibrinolysis: the plasmin system8......Page 464
Epistaxis......Page 465
Family history......Page 466
On venipuncture......Page 467
Platelet function testing......Page 468
Investigations of platelet granule structure and function......Page 469
Activated partial thromboplastin time (APTT)......Page 470
Thrombin time (TT)......Page 471
Logical use of the coagulation screen......Page 472
Specific assays of individual clotting factors......Page 473
Immunoassays......Page 474
Interpretation and clinical feasibility.......Page 475
Interpretation and clinical feasibility.......Page 476
Maximizing the clinical utility of hemostatic testing......Page 477
References......Page 478
Introduction......Page 480
Structure......Page 481
Congenital megakaryocyte hypoplasia......Page 482
Hermansky–Pudlak syndrome (HPS)......Page 483
Storage pool deficiency (SPD)......Page 485
Chediak–Higashi syndrome (CHS)......Page 486
Alpha granules......Page 487
Gray platelet syndrome......Page 489
Jacobsen–Paris–Trousseau syndrome......Page 490
Lysosomes......Page 491
Disorders of platelet membranes and membrane organization......Page 492
Wiskott–Aldrich syndrome......Page 493
May–Hegglin anomaly (MHA)......Page 494
Epstein’s syndrome (ES)......Page 496
Hereditary nephritis associated with May–Hegglin syndrome......Page 497
Gray platelet syndrome (GPS)......Page 498
Bernard–Soulier syndrome (BSS)......Page 499
Medich giant inclusion disorder......Page 501
Absence of circumferential microtubule coils in normal sized platelets......Page 503
Summary......Page 506
References......Page 507
Introduction......Page 511
Platelet structure and function......Page 512
Biological function of platelets......Page 513
Platelet aggregation (Fig. 33.5B)......Page 514
Acquired amegakaryocytic thrombocytopenia......Page 515
Laboratory diagnosis......Page 516
Pathogenesis......Page 517
Hemolytic uremic syndrome......Page 518
Thrombocytopenia secondary to alcohol......Page 519
Neonatal alloimmune thrombocytopenia......Page 520
Immune thrombocytopenic purpura (ITP)......Page 521
Clinical features of ITP......Page 522
Implicated epitopes......Page 523
Secondary immune thrombocytopenia......Page 524
Clinical features......Page 525
Pathogenesis......Page 526
Management......Page 527
Platelet abnormalities in the myeloproliferative disorders......Page 528
Drugs that interfere with platelet function......Page 529
References......Page 530
Inheritance......Page 534
The molecular basis of hemophilia A and B (FVIII and FIX genes)......Page 535
Treatment of hemophilia......Page 536
1-Deamino-8-D-arginine vasopressin (DDAVP) or desmopressin......Page 538
Inhibitors......Page 539
Prophylaxis......Page 540
Platelet function analyzer (PFA-100™) closure time and bleeding time......Page 541
The subtypes of vWD......Page 542
1-Deamino-8-D-arginine vasopressin (DDAVP) or desmopressin......Page 544
Rare inherited bleeding disorders......Page 545
Factor VII deficiency......Page 546
Vitamin K-dependent factor deficiencies......Page 547
References......Page 548
35 Acquired bleeding disorders......Page 552
Laboratory monitoring8......Page 553
Warfarin and vitamin K antagonists......Page 554
Anti-platelet drugs......Page 555
Vitamin K deficiency in neonates and young infants......Page 556
Laboratory findings in liver disease......Page 557
Laboratory diagnosis......Page 558
Hemostatic defects associated with the use of extracorporeal circuits......Page 559
Acquired inhibitors......Page 560
Laboratory diagnosis of DIC......Page 561
Management of acute DIC......Page 562
Acute leukemias......Page 563
Management of acquired inhibitors......Page 564
Snake venoms and other toxic coagulopathies......Page 565
References......Page 566
Introduction......Page 570
Classic cascade mechanism of coagulation vs. cell-based models of thrombin generation......Page 571
Antithrombin......Page 572
Protein S function......Page 574
Thrombophilia......Page 575
Protein C deficiency......Page 576
Dysfibrinogenemia......Page 577
Malignancies and inflammatory conditions......Page 578
Evaluation and diagnosis: screening for thrombophilias?......Page 579
Prevention and treatment......Page 580
References......Page 581
Red cell surface antigens......Page 583
ABO and H antigens......Page 585
ABH and Lewis antigens on tumors......Page 586
Rh-deficiency syndrome, Rhnull and Rhmod......Page 587
Anti-K and HDFN......Page 588
Blood groups on red cell transporters......Page 589
Glycoproteins of the immunoglobulin superfamily......Page 590
Red cell glycoproteins that anchor the membrane to its skeleton......Page 591
Antigens on the GPIIb/IIIa (CD41/CD61 or αIIbβ3) complex......Page 592
Pathophysiology......Page 594
Glycoproteins expressing neutrophil antigens......Page 595
Transfusion-related acute lung injury (TRALI)......Page 596
References......Page 597
38 Transfusion medicine for pathologists......Page 602
Blood donor recruitment......Page 603
Physical and laboratory examination of the blood donor......Page 604
Autologous blood donation......Page 605
Red blood cells......Page 606
Platelet concentrates......Page 607
Compatibility testing (crossmatching)......Page 608
Effects of red blood cell transfusion......Page 609
Transfusion of platelets......Page 610
Irradiated blood components......Page 611
Transplantation......Page 612
Autoimmune hemolytic anemia......Page 613
Complications of transfusion: recognition and management......Page 614
Transfusion reactions......Page 615
Post-transfusion hepatitis......Page 616
Other transfusion-transmitted infectious diseases (Table 38.1)......Page 617
Platelet growth factor......Page 618
References......Page 619
Introduction......Page 623
The human leukocyte antigens......Page 624
Genomic organization......Page 625
Diversity......Page 626
Expression......Page 630
Structure of class I and class II molecules......Page 632
Peptide processing and binding......Page 634
T lymphocyte recognition of HLA molecules......Page 636
Allorecognition and transplantation......Page 637
HLA-F......Page 638
CD1 molecules......Page 639
Minor histocompatibility antigens......Page 640
Killer cell immunoglobulin-like receptors......Page 641
Leukocyte immunoglobulin-like receptors......Page 643
Sequence specific priming (SSP)......Page 644
Measurement of sensitization to histocompatibility differences......Page 645
DNA-based allele designations......Page 646
National Marrow Donor Program® (NMDP) DNA nomenclature......Page 649
Correlation between serologic specificities and DNA-based allele assignments......Page 650
Platelets......Page 651
Search strategies for donor identification......Page 652
Summary......Page 653
References......Page 654
A......Page 659
B......Page 661
C......Page 663
D......Page 666
E......Page 667
F......Page 669
G......Page 670
H......Page 671
I......Page 674
L......Page 676
M......Page 677
N......Page 680
P......Page 681
R......Page 684
S......Page 685
T......Page 686
V......Page 688
X......Page 689
Z......Page 690