Contents Preface... Acknowledgments... v xiii SECTION I 1. Introduction... 3 Knowledge-Based Diagnosis... 4 Systematic Examination of the Lymph Node... 7 Cell Type Identification... 9 Cell Size and Cellularity... 9 Immunohistology... 10 Cytological Preparations... 11 The Pattern Approach to Diagnosis... 14 Selected Reading... 18 2. Handling of the Lymph Node Biopsy... 19 Introduction... 19 The Biopsy... 19 Lymph Node Triage... 20 3. Immunohistology and Other Diagnostic Techniques... 23 Introduction... 23 Immunohistology... 24 BCellMarkers... 26 TCellMarkers... 33 Natural Killer and T/NK Cell Markers... 38 Precursor B- and T Cell Markers... 38 Monocyte/ Macrophage Markers... 39 Langerhans Cell, Follicular Dendritic Cell, and Interdigitating Dendritic Reticulum Cell Markers... 41 Markers of Reed Sternberg Cells in Hodgkin Lymphoma... 42 Miscellaneous Markers... 45 Myeloid Cell Markers... 46 Mast Cell Markers... 47 Diagnostic Approach with Immunohistochemical Stains... 47 Staining for Follicular Dendritic Cells... 47 Immunohistological Identification of Diffuse Lymphoid Infiltrates... 49 Histochemical Stains... 51 Flow Cytometry... 53 Molecular Diagnostics... 57 Detection of Clonality... 57 Immunoglobulin Heavy- and Light-Chain Genes... 57 T Cell Receptor Chain Genes... 58 vii
viii Contents Genotype Subgroups... 59 Conventional Cytogenetics... 60 Fluorescence In Situ Hybridization (FISH)... 60 Southern Blot Analysis... 60 Polymerase Chain Reaction (PCR)... 60 Gene Expression Profiling... 61 4. Anatomical and Functional Compartments... 63 B Cell Differentiation and Corresponding B Cell Lymphomas... 64 The Cortex... 64 The Lymphoid Follicle... 64 T Cell Differentiation... 69 The Paracortex... 73 High-Endothelial Venules... 79 Medullary Area... 79 Connective Tissue Framework... 80 SECTION II 5. Nodular Lymphoid Infiltrates... 83 Follicular Pattern... 84 Neoplastic Follicles... 85 Follicular Lymphoma (FL)... 85 Follicular Hyperplasia Versus Follicular Lymphoma... 91 Other Follicular Patterns... 97 Mantle Pattern... 100 Mantle Cell Lymphoma... 100 Marginal Zone Pattern... 105 Nodal Marginal Zone Lymphoma (Monocytoid B Cell Lymphoma)... 107 Nodular Pattern... 111 Heterogenous Nodules... 111 Pseudofollicular Pattern... 111 Hodgkin Lymphoma (HL)... 112 Classical Hodgkin Lymphoma (CHL)... 116 Post-transplant Lymphoproliferative Disorders... 127 Colonization of Follicles by Neoplastic Cells... 131 Homogenous Nodules... 132 Reactive Hyperplasia... 134 Follicular and Paracortical Hyperplasia... 136 Non-specific Follicular Hyperplasia... 137 Progressive Transformation of Germinal Centers (PTGC)... 137 Rheumatoid Lymphadenopathy... 138 Toxoplasma Lymphadenopathy... 139 Human Immunodeficiency Virus/Acquired Immunodeficiency Disease Syndrome (HIV/AIDS) Lymphadenitis... 142 Kimura Disease... 144 Castleman Disease... 145 Syphilis Lymphadenopathy... 151 Kikuchi Disease... 153
Contents ix Systemic Lupus Erythematosus... 157 Infectious Mononucleosis Lymphadenopathy... 158 Other Viral Lymphadenopathies... 161 Paracortical Nodules/Expansion... 165 Dermatopathic Lymphadenopathy (DL)... 165 Drug-Induced Lymphadenopathy... 166 The Diagnostic Approach to Nodular Infiltrates in Lymph Nodes... 167 Are They Follicles or Nodules?... 168 Are the Follicles Reactive or Neoplastic?... 168 Are Follicles Infrequent and Constricted?... 168 Are the Follicles Exceptionally Large?... 169 Do the Enlarged Germinal Centers Contain Atypical Cells?... 169 Are the Nodules Homogenous or Heterogenous in Composition?... 169 Homogenous Nodules... 169 Heterogenous Nodules... 169 If There Is Marked Follicular Hyperplasia, Can a Specific Diagnosis Be Made?... 170 Do the Vague Nodules Represent Paracortical Nodules?... 171 6. Diffuse Lymphoid Infiltrations... 175 B Cell Neoplasms... 176 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).. 176 Lymphoplasmacytic Lymphoma (LPL)... 186 Diffuse Large B Cell Lymphoma (DLBCL)... 194 Clinical Subtypes... 207 Burkitt Lymphoma... 212 B Cell Lymphoma, Unclassifiable, with Features Intermediate Between DLBCL and BL... 217 Nodal Involvement by Primary Extranodal Lymphomas and Leukemias... 218 T Cell and NK Cell Neoplasms... 218 T-Lymphoblastic Leukemia/Lymphoma (Precursor T Cell Lymphoblastic Leukemia/Lymphoma)... 219 Peripheral T Cell Lymphoma, Not Otherwise Specified (PTCL-NOS)... 223 Angioimmunoblastic T Cell Lymphoma... 229 Anaplastic Large Cell Lymphoma (ALCL), ALK-Positive... 238 Immunohistology... 244 Anaplastic Large Cell Lymphoma, ALK-Negative... 249 Adult T Cell Leukemia/Lymphoma... 250 Nodal Involvement by the Cutaneous T Cell Lymphomas... 255 Histiocytic and Dendritic Neoplasms... 260 Histiocytic Sarcoma... 262 Langerhans Cell Histiocytosis... 268 Interdigitating Dendritic Cell (IDC) Sarcoma... 272 Follicular Dendritic Cell (FDC) Sarcoma... 275 Hodgkin Lymphoma... 278 Diagnostic Approach to Diffuse Infiltrates in lymph Nodes... 279 Is the Infiltrate Truly Diffuse?... 279 Does the Diffuse Infiltrate Involve the Node Partially or Completely?... 280 Is the Infiltrate Monomorphous or Polymorphous? Are the Cells Small or Large?. 281
x Contents 7. Defining Microscopic Features... 287 Granulomas and Foam Cells... 287 Infective Granulomatous Lymphadenitis... 287 Mycotic Lymphadenitis... 294 Protozoan and Parasitic Lymphadenitides... 300 Non-infective Granulomatous Lymphadenitis... 301 Granulomas, Non-necrotizing... 304 Foreign Body and Lipid Granulomatous Lymphadenitis... 307 Lipid Lymphadenopathy... 310 Sinus Pattern... 313 Sinus Histiocytosis... 314 Rosai Dorfman Disease (Sinus Histiocytosis with Massive Lymphadenopathy).. 316 Necrosis, Apoptosis, and Infarction... 317 Clear Cells... 319 Mast Cell Disease... 320 Hairy Cell Leukemia... 321 Spindled Cells... 324 Inflammatory Myofibroblastic Tumor... 325 Palisaded Myofibroblastoma... 325 Kaposi Sarcoma... 327 Vascular Prominence... 330 Bacillary Angiomatosis... 331 Vascular Transformation of Lymph Node Sinuses... 331 Hemorrhage... 333 Starry Sky Pattern... 334 Mottled Pattern... 334 Fibrosis/Hyalinization... 335 Signet Ring Cells... 336 Bizarre or Multinucleated Cells... 337 Extramedullary Hematopoiesis... 337 Prominent Eosinophils... 337 Prominent Neutrophils... 338 Prominent Plasma Cells... 339 Infiltration of Pericapsular Fat... 339 Extraneous Cells Pigmented Cells, Epithelial Cells, Foreign Material, Dermatopathic Lymphadenitis, Hemosiderin... 340 Inclusions of Benign Extraneous Cells... 340 8. Nodal Involvement by Leukemias and Extranodal Lymphomas... 345 Nodal Involvement by Leukemia... 345 Myeloid Leukemia/Myeloid Sarcoma... 345 Primary Myelofibrosis... 346 B and T Cell Prolymphocytic Leukemias... 348 NK Cell Lymphoproliferative Disorders... 350 Nodal Involvement by Extranodal Lymphomas... 351 Splenic B Cell Marginal Zone Lymphoma... 352 Hairy Cell Leukemia (HCL)... 353 Heavy-Chain Disease... 354
Contents xi Plasma Cell Neoplasms... 355 Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma... 356 Primary Cutaneous Diffuse Large B Cell Lymphoma (DLBCL) Leg Type... 358 Lymphomatoid Granulomatosis... 359 Extranodal NK/T Cell Lymphoma Nasal Type... 359 Blastic Plasmacytoid Dendritic Cell Neoplasm... 361 EBV-Associated T Cell Lymphoproliferative Disorders... 363 EBV-Positive T Cell Lymphoproliferative Disorders of Childhood... 363 9. Needle Core Biopsies and Aspirates... 367 Needle Core Biopsies... 367 Advantages of Needle Core Biopsies... 367 Disadvantages of Needle Core Biopsies... 368 Handling of Needle Core Biopsies... 368 Diagnostic Approach to Needle Core Biopsies of Lymph Nodes and Potential Pitfalls... 368 Fine-Needle Aspiration Samples... 399 Polymorphous Infiltrates... 400 Monomorphous Infiltrates... 402 Subject Index... 405
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