Non–Neoplastic Hematopathology and Infections

"An ambitious book . . . comprehensive in coverage of the widerange of non–neoplastic hematopathology. It has a particularemphasis on tropical and non–tropical infectious diseases includingparasitic diseases. It should be especially useful forhematologists, hematopathologists, general pathologists, andinfectious disease specialists, but should also be useful forinternists, primary care physicians, and those in training. Itparticularly emphasizes morphologic aspects of infections which mayhave hematologic manifestations or present diagnosticproblems."
James Warren Smith, MD, Nordschow Professor Emeritusof Laboratory Medicine, former chair, Department of Pathology andLaboratory Medicine, Indiana University School of Medicine; pastpresident, Binford–Dammin Society of Infectious DiseasePathologists United States & Canadian Academy of Pathology

Most books on hematopathology are neoplastic in scope and offerlittle non–neoplastic content. In Non–Neoplastic Hematopathologyand Infections, the authors fully describe the hematologicmanifestations in tissue and blood of infectious agents, includingmany rare and exotic diseases found in both Western and Easternhemispheres, in order to assist pathologists and medical laboratoryprofessionals all over the world in better diagnosing and treatingsuch infections.

Thoroughly illustrated with photographs, tables and text, thisbook features a wide range of non–neoplastic hematologic disorders,as well as reactive patterns of non–infectious and infectiousagents. Comprehensive and state–of–the–art diagnostic materials aredescribed, as are the epidemiology, pathobiology, clinical andpathologic manifestations in blood and lymphatic organs aswell as the approaches to treatment.

In addition, Non–Neoplastic Hematopathology andInfections:

Contains detailed information on the pathology and patterns ofblood, lymph node, and a number of bone marrow and splenicinfections and infectious agent manifestations Thoroughly updates the classic pathology of reactivelymphadenopathies and extends this pattern–based approach totropical and emergent infections Promotes the multidisciplinary integration ofhematopathologists and microbiologists in the analysis anddiagnostic work–up of tissue and blood Complements current major treatises on such tropical diseasesas Manson′s, Ashworth′s, and Doerr′s and updates the classic tomesof William St. Clair Symmers and current texts on neoplastichematopathology

Non–Neoplastic Hematopathology and Infections is animportant book for any medical professional interested innon–neoplastic hematology, infections and tissue hematopathology,infectious diseases and tropical medicine, and tropicalhematopathology.

Contributors, xix

Foreword, xxiii

Preface, xxv

Acknowledgments, xxvii

Introduction, xxix

PART I Non–neoplastic Hematology 1

CHAPTER ONE Non–neoplastic Disorders of White Blood Cells3
Rebecca A. Levy, Vandita P. Johari, and LironPantanowitz

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 Platelets31
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 Cells45
Jason C. Ford

Introduction, 45

The Anemias, 45

The Approach to Anemia, 50

The Polycythemias, 63

References, 63

CHAPTER FOUR Microcytic, Normocytic, andMacrocytic 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, BoneMarrow, and Spleen: The Genera Plasmodium, Babesia, and Toxoplasma115
Lynne S. Garcia

Plasmodium, 115

Babesia, 125

Toxoplasma, 128

References, 134

CHAPTER SEVEN Blood and Tissue Flagellates of the ClassKinetoplastidea: The Genera Leishmania and Trypanosoma139
Raul E. Villanueva and Stephen D. Allen

Leishmaniasis, 139

Chagas′ Disease, 145

African Trypanosomiasis, 150

References, 155

CHAPTER EIGHT Proteobacteria and RickettsialAgents: Human Granulocytic Anaplasmosis and HumanMonocytic 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 Yeasts165
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 Infections195
Deniz Peker

Anemia in Tropical Infections, 195

Vascular Purpuras, 202

References, 203

PART III Non–neoplastic Lymph Node Pathology and Infections205

CHAPTER ELEVEN Classification of Reactive Lymphadenopathy207
Hernani D. Cualing

Introduction, 207

References, 229

CHAPTER TWELVE Lymph Node Biology, Markers and Disease231
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 PredominantFollicular 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, SpecificEntities, 276

Mixed Pattern with Follicular Hyperplasia, Microgranulomas,Monocytoid Hyperplasia, 278

Follicular Hyperplasia with Capsular Fibrosis andPlasmacytosis–Syphilis, 282

References, 284

CHAPTER FOURTEEN Reactive Lymphadenopathy with ParacorticalPattern, 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 DiffuseParacortical 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 Pattern347
Hernani D. Cualing

Sinuses and Vascular Supply, 347

Sinus Histiocytosis, Nonspecific, 347

Signet Ring Histiocytosis, 354

Sinus Histiocytosis with Massive Lymphadenopathy (orRosai Dorfman Disease), 355

Pigmented Sinus Histiocytic Pattern Secondary to Iron Overloadfrom 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 andHistiocytic Reactions, NonInfectious 375
Hernani D. Cualing

Proteinaceous Lymphadenopathy Including ImmunoglobulinDeposition 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: IncludingGranulomatous 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, SuppurativeNecrotizing 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 Infectionswith 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 andInfectious 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: TropicalInfectious Lymphadenopathy and Hematopathology, Not OtherwiseCharacterized 511
Hernani D. Cualing

Introduction, 511

Hemorrhagic Lymphadenopathy, 511

Sinus Pattern, 517

Diffuse Pattern with Depletion and Atypical ImmunoblasticReaction, 525

Unusual Granulomas Q Fever, 531

References, 533

PART IV Non–neoplastic Findings in Bone MarrowTransplantation 537

CHAPTER TWENTY–THREE Non–neoplastic Hematopathology of BoneMarrow 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

Hernani Cualing MD, is Associate Professor in the Departmentof Pathology and Cell Biology and Director of the HematopathologyFellowship Training Program at the University of South FloridaCollege of Medicine in Tampa, Florida. He is also an activehematopathologist at the Moffitt Cancer Center and ResearchInstitute there. In addition to his research into such topics asmantle cell and T cell lymphomas, Dr. Cualing has long beenfascinated with the analysis, diagnosis, and treatment ofnon–neoplastic and infectious blood, marrow, and lymph diseases.

Parul Bhargava, MD, is Medical Director in the HematologyLaboratory at Beth Israel Deaconess Medical Center–Needham Campusin Boston, and a staff and faculty physician in the Pathologydepartment there. Her primary research interests are in studyinghematopoietic neoplasms and newer markers in Hodgkin Lymphoma, butshe also has a strong, separate clinical interest in studying theeffects of immunodeficiency and infections, particularly HIV, onthe hematopoietic system.

Ramon L. Sandin, MD, MS, FCAP, ABP–MM, is a ClinicalPathologist and Medical Director of Clinical Microbiology andVirology in the Department of Hematopathology, Laboratory Medicine,and in the Blood and Marrow Transplant Program at the MoffittCancer Center in Tampa, Florida 33612–9497. His special areas ofexpertise and research interests are in clinical microbiology andvirology, and laboratory diagnosis of infectious diseases. Thisincludes ′wet′ laboratory work–ups and tissue section diagnosis aswell as molecular diagnostic techniques.

"An ambitious book . . . comprehensive in coverage of the wide range of non–neoplastic hematopathology. It has a particular emphasis on tropical and non–tropical infectious diseases including parasitic diseases. It should be especially useful for hematologists, hematopathologists, general pathologists, and infectious disease specialists, but should also be useful for internists, primary care physicians, and those in training. It particularly emphasizes morphologic aspects of infections which may have hematologic manifestations or present diagnostic problems." James Warren Smith, MD, Nordschow Professor Emeritus of Laboratory Medicine, Former Chair, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine; Past President, Binford–Dammin Society of Infectious Disease Pathologists