Non–Neoplastic Hematopathology and Infections

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