Non-neoplastic Hematopathology and Infections

Many infectious agents disseminate in blood and the lymphatic system, and many of these infections are also tropical diseases that affect a large segment of the world's population, including travelers, immigrants, and refugees. The authors have carefully incorporated in this new book those diseases found in both Western and Eastern hemispheres, in order to assist pathologists and medical laboratory professionals all over the world to better diagnose and treat infections that may be expected, or indeed quite unusual for a given geographic region. The book features a wide range of non-neoplastic hematologic disorders, as well as reactive patterns of non-infectious and infectious agents, all thoroughly illustrated with photographs, tables and text. In addition to the comprehensive and state-of-the-art diagnostic materials, the epidemiology, pathobiology, clinical and pathologic manifestations in blood and lymphatic organs, as well as approaches to treatment, are also described.

Hernani Cualing MD, is Associate Professor in the Department of Pathology and Cell Biology and Director of the Hematopathology Fellowship Training Program at the University of South Florida College of Medicine in Tampa, Florida. He is also an active hematopathologist at the Moffitt Cancer Center and Research Institute there. In addition to his research into such topics as mantle cell and T cell lymphomas, Dr. Cualing has long been fascinated with the analysis, diagnosis, and treatment of non-neoplastic and infectious blood, marrow, and lymph diseases.

Parul Bhargava, MD, is Medical Director in the Hematology Laboratory at Beth Israel Deaconess Medical Center-Needham Campus in Boston, and a staff and faculty physician in the Pathology department there. Her primary research interests are in studying hematopoietic neoplasms and newer markers in Hodgkin Lymphoma, but she also has a strong, separate clinical interest in studying the effects of immunodeficiency and infections, particularly HIV, on the hematopoietic system.

Ramon L. Sandin, MD, MS, FCAP, ABP-MM, is a Clinical Pathologist and Medical Director of Clinical Microbiology and Virology in the Department of Hematopathology, Laboratory Medicine, and in the Blood and Marrow Transplant Program at the Moffitt Cancer Center in Tampa, Florida 33612-9497. His special areas of expertise and research interests are in clinical microbiology and virology, and laboratory diagnosis of infectious diseases. This includes 'wet' laboratory work-ups and tissue section diagnosis as well as molecular diagnostic techniques.

Contributors	p. xix
Foreword	p. xxiii
Preface	p. xxv
Acknowledgments	p. xxvii
Introduction	p. xxix
Non-neoplastic Hematology	p. 1
Non-neoplastic Disorders of White Blood Cells	p. 3
Overview of WBC Production and Function	p. 3
Quantitative Disorders of WBCS	p. 6
Qualitative Disorders of WBCS	p. 21
References	p. 26
Non-neoplastic Disorders of Platelets	p. 31
Platelet Production Structure and Function	p. 31
Quantitative Disorders of Platelets	p. 33
Qualitative Disorders of Platelets	p. 39
References	p. 43
Approach to Disorders of Red Blood Cells	p. 45
Introduction	p. 45
The Anemias	p. 45
The Approach to Anemia	p. 50
The Polycythemias	p. 63
References	p. 63
Microcytic, Normocytic, and Macrocytic
Anemias	p. 65
Microcytic Anemias	p. 65
Normocytic Anemias	p. 74
Macrocytic Anemias	p. 81
References	p. 86
Disorders of Hemoglobin	p. 89
Overview	p. 89
Quantitative Disorders of Hemoglobin	p. 89
Qualitative Disorders of Hemoglobin	p. 97
Mixed-Quantitative Qualitative Disorders of Hemoglobin	p. 104
Double Heterozygous States	p. 105
Approach to Diagnosis of Hemoglobin Disorders	p. 106
References	p. 111
Infectious Aspects of Hematology	p. 113
Apicomplexal Parasites of Peripheral Blood, Bone Marrow, and Spleen: The Genera Plasmodium, Babesia, and Toxoplasma	p. 115
Plasmodium	p. 115
Babesia	p. 125
Toxoplasma	p. 128
References	p. 134
Blood and Tissue Flagellates of the Class Kinetoplastidea: The Genera Leishmania and Trypanosoma	p. 139
Leishmaniasis	p. 139
Chagas' Disease	p. 145
African Trypanosomiasis	p. 150
References	p. 155
Proteobacteria and Rickettsial Agents: Human Granulocytic Anaplasmosis and Human Monocytic Ehrlichiosis	p. 159
Microbiology and Epidemiology of HGA and HME	p. 159
Clinical Syndromes	p. 160
Differential Diagnosis	p. 160
Diagnostic Approach	p. 161
Prevention and Treatment	p. 163
References	p. 163
Clinically Significant Fungal Yeasts	p. 165
Introduction	p. 165
Histoplasma capsulatum var. capsulatum (H. capsulatum)	p. 166
Blastomyces dermatitidis	p. 170
Coccidioides immitis	p. 174
Cryptococcus neoformans	p. 178
Candida albicans and other Candida Species	p. 183
Malassezia furfur	p. 188
References	p. 193
Hematologic Aspects of Tropical Infections	p. 195
Anemia in Tropical Infections	p. 195
Vascular Purpuras	p. 202
References	p. 203
Non-neoplastic Lymph Node Pathology and Infections	p. 205
Classification of Reactive Lymphadenopathy	p. 207
Introduction	p. 207
References	p. 229
Lymph Node Biology, Markers and Disease	p. 231
Peripheral Lymphoid Tissue	p. 231
Pathophysiology	p. 231
Cortex	p. 232
Paracortex	p. 240
Sinus Histiocytes	p. 242
Epithelioid Histiocytes and Granulomas	p. 243
Nodal Framework	p. 243
References	p. 246
Lymphadenopathy with Predominant
Follicular Patterns	p. 249
Germinal Center Hyperplasia	p. 249
Regressive Transformation of Germinal Center (Atrophic) Pattern	p. 256
Progressive Transformation of Germinal Center Pattern	p. 267
Marginal Zone Hyperplasia and Mantle Cell Hyperplasia	p. 273
Reactive Follicular Pattern, Mixed with Other Patterns, Specific Entities	p. 276
Mixed Pattern with Follicular Hyperplasia, Microgranulomas, Monocytoid Hyperplasia	p. 278
Follicular Hyperplasia with Capsular Fibrosis and Plasmacytosis-Syphilis	p. 282
References	p. 284
Reactive Lymphadenopathy with Paracortical Pattern, Noninfectious Etiology	p. 291
Paracortical Hyperplasia	p. 291
Dermatopathic Lymphadenopathy	p. 297
Reactive Immunoblastic Proliferation	p. 301
Postvaccinal Lymphadenitis	p. 307
Drug-Induced Lymphadenopathy	p. 309
Anticonvulsant (Phenytoin)-Related Lymphoproliferative Disorder	p. 309
Methotrexate-Related Lymphoproliferative Disorder	p. 312
References	p. 315
Reactive Lymphadenopathy with Diffuse Paracortical Pattern-Infectious Etiology	p. 323
Introduction	p. 323
Infectious Mononucleosis Lymphadenitis	p. 323
Cytomegalovirus Lymphadenitis	p. 329
Herpes Simplex Virus Lymphadenitis	p. 333
Varicella Zoster Lymphadenitis	p. 337
References	p. 340
Reactive Lymphadenopathy with Sinus Pattern	p. 347
Sinuses and Vascular Supply	p. 347
Sinus Histiocytosis, Nonspecific	p. 347
Signet Ring Histiocytosis	p. 354
Sinus Histiocytosis with Massive Lymphadenopathy (or Rosai-Dorfman Disease)	p. 355
Pigmented Sinus Histiocytic Pattern Secondary to Iron Overload from Hemochromatosis, Transfusion, or Hemolysis	p. 357
Histiocytic Reaction to Foreign Matter	p. 359
Sinus Pattern from Extramedullary Hematopoiesis	p. 361
Immature "Sinus Histiocytosis" or Monocytoid B-Cell Hyperplasia	p. 363
Reactive Hemophagocytic Syndromes	p. 365
Vascular Transformation of Sinuses (VTS)	p. 366
Whipple's Disease (WD) Lymphadenopathy	p. 368
References	p. 370
Mixed Lymph Node Patterns: Stromal and Histiocytic Reactions, NonInfectious	p. 375
Proteinaceous Lymphadenopathy Including Immunoglobulin Deposition Lymphadenopathy	p. 375
Lymph Node Fibrosis or Fibrotic Changes, Nonspecific	p. 377
Inflammatory Pseudotumor of Lymph Nodes	p. 379
Fatty Replacement or Fatty Changes, Nonspecific	p. 383
Tumor Reactive Granulomatas	p. 384
References	p. 386
Mixed Lymph Node Patterns: Including Granulomatous Lymphadenopathy, Noninfectious	p. 389
Mixed Pattern with Follicular Hyperplasia and Eosinophilia	p. 389
Mixed Nonnecrotizing ''Dry'' Granulomas	p. 396
Mixed Pattern with Hemorrhage and Infarction	p. 404
Mixed Necrotizing Pattern with No or Minimal Granulomas	p. 406
Necrotizing Nonsuppurative Granulomatas	p. 410
Necrotizing Suppurative Granulomatas	p. 413
Granulomatous Change within Germinal Centers	p. 415
Mixed Pattern with Plasmacytosis	p. 418
References	p. 420
Mixed Patterns in Lymph Node, Suppurative Necrotizing Granulomatous Infectious Lymphadenopathy	p. 427
Cat-Scratch Disease	p. 427
Tularemia	p. 431
Lymphogranuloma venereum	p. 433
Chancroid, H. ducreyi	p. 434
Yersinia enterocolitica/pseudotuberculosis Lymphadenitis	p. 435
Brucellosis	p. 437
Melioidosis	p. 439
Typhoid Lymphadenitis (Salmonella typhi)	p. 442
References	p. 444
Mixed Patterns: Emergent/Tropical Infections with Characterized Lymphadenopathy	p. 447
Mixed Pattern with Granulomatas and Diagnostic Microorganisms	p. 447
Lymphadenopathy Secondary to Localized Filariasis	p. 449
Schistosomiasis	p. 453
Leishmaniasis	p. 454
Mixed Pattern with Granulomas and Foamy Macrophages	p. 457
Mixed Pattern with Deposition of Interstitial Substance	p. 459
Mixed Pattern with Caseation Necrosis	p. 461
Mixed Pattern Atypical Mycobacterial Infections in AIDS	p. 463
Mixed Pattern with Angiomatoid Change	p. 467
Mixed Pattern with Spent Granulomas and Extracellular Organisms	p. 470
African Histoplamosis Secondary to H. capsulatum var duboisii	p. 474
References	p. 476
Cytopathology of Non-neoplastic and Infectious Lymphadenopathy	p. 481
Technical Components	p. 483
Approach to Cytomorphologic Evaluation of Lymph Nodes	p. 484
FNA Reporting Terminology	p. 485
Intraoperative Touch Preparation	p. 487
Reactive Lymphoid Hyperplasia	p. 487
Inflammatory and Infectious Causes of Lymphadenopathy	p. 488
Other Causes of Lymphadenopathy	p. 497
Lymphadenopathy in the Pediatric Patient	p. 504
Use of Ancillary Studies	p. 504
Molecular Studies	p. 506
References	p. 506
Mixed Patterns In Lymph Node: Tropical Infectious Lymphadenopathy and Hematopathology, Not Otherwise Characterized	p. 511
Introduction	p. 511
Hemorrhagic Lymphadenopathy	p. 511
Sinus Pattern	p. 517
Diffuse Pattern with Depletion and Atypical Immunoblastic Reaction	p. 525
Unusual Granulomas Q Fever	p. 531
References	p. 533
Non-neoplastic Findings in Bone Marrow Transplantation	p. 537
Non-neoplastic Hematopathology of Bone Marrow Transplant and Infections	p. 539
Introduction	p. 539
Fundamental Principles of Hematopoietic Cell Transplantation (HCT)	p. 539
Characteristics of Pretransplant Bone Marrow	p. 542
Hematopoietic Regeneration	p. 542
Chimerism	p. 543
Post-Transplantation Marrow	p. 543
Complications of Hematopoietic Regeneration	p. 547
Conclusion	p. 551
References	p. 552
Index	p. 559
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