Contents. vii. Preface... Acknowledgments... v xiii

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1 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 Cytological Preparations The Pattern Approach to Diagnosis Selected Reading Handling of the Lymph Node Biopsy Introduction The Biopsy Lymph Node Triage Immunohistology and Other Diagnostic Techniques Introduction Immunohistology BCellMarkers TCellMarkers Natural Killer and T/NK Cell Markers Precursor B- and T Cell Markers Monocyte/ Macrophage Markers Langerhans Cell, Follicular Dendritic Cell, and Interdigitating Dendritic Reticulum Cell Markers Markers of Reed Sternberg Cells in Hodgkin Lymphoma Miscellaneous Markers Myeloid Cell Markers Mast Cell Markers Diagnostic Approach with Immunohistochemical Stains Staining for Follicular Dendritic Cells Immunohistological Identification of Diffuse Lymphoid Infiltrates Histochemical Stains Flow Cytometry Molecular Diagnostics Detection of Clonality Immunoglobulin Heavy- and Light-Chain Genes T Cell Receptor Chain Genes vii

2 viii Contents Genotype Subgroups Conventional Cytogenetics Fluorescence In Situ Hybridization (FISH) Southern Blot Analysis Polymerase Chain Reaction (PCR) Gene Expression Profiling Anatomical and Functional Compartments B Cell Differentiation and Corresponding B Cell Lymphomas The Cortex The Lymphoid Follicle T Cell Differentiation The Paracortex High-Endothelial Venules Medullary Area Connective Tissue Framework SECTION II 5. Nodular Lymphoid Infiltrates Follicular Pattern Neoplastic Follicles Follicular Lymphoma (FL) Follicular Hyperplasia Versus Follicular Lymphoma Other Follicular Patterns Mantle Pattern Mantle Cell Lymphoma Marginal Zone Pattern Nodal Marginal Zone Lymphoma (Monocytoid B Cell Lymphoma) Nodular Pattern Heterogenous Nodules Pseudofollicular Pattern Hodgkin Lymphoma (HL) Classical Hodgkin Lymphoma (CHL) Post-transplant Lymphoproliferative Disorders Colonization of Follicles by Neoplastic Cells Homogenous Nodules Reactive Hyperplasia Follicular and Paracortical Hyperplasia Non-specific Follicular Hyperplasia Progressive Transformation of Germinal Centers (PTGC) Rheumatoid Lymphadenopathy Toxoplasma Lymphadenopathy Human Immunodeficiency Virus/Acquired Immunodeficiency Disease Syndrome (HIV/AIDS) Lymphadenitis Kimura Disease Castleman Disease Syphilis Lymphadenopathy Kikuchi Disease

3 Contents ix Systemic Lupus Erythematosus Infectious Mononucleosis Lymphadenopathy Other Viral Lymphadenopathies Paracortical Nodules/Expansion Dermatopathic Lymphadenopathy (DL) Drug-Induced Lymphadenopathy The Diagnostic Approach to Nodular Infiltrates in Lymph Nodes Are They Follicles or Nodules? Are the Follicles Reactive or Neoplastic? Are Follicles Infrequent and Constricted? Are the Follicles Exceptionally Large? Do the Enlarged Germinal Centers Contain Atypical Cells? Are the Nodules Homogenous or Heterogenous in Composition? Homogenous Nodules Heterogenous Nodules If There Is Marked Follicular Hyperplasia, Can a Specific Diagnosis Be Made? Do the Vague Nodules Represent Paracortical Nodules? Diffuse Lymphoid Infiltrations B Cell Neoplasms Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Lymphoplasmacytic Lymphoma (LPL) Diffuse Large B Cell Lymphoma (DLBCL) Clinical Subtypes Burkitt Lymphoma B Cell Lymphoma, Unclassifiable, with Features Intermediate Between DLBCL and BL Nodal Involvement by Primary Extranodal Lymphomas and Leukemias T Cell and NK Cell Neoplasms T-Lymphoblastic Leukemia/Lymphoma (Precursor T Cell Lymphoblastic Leukemia/Lymphoma) Peripheral T Cell Lymphoma, Not Otherwise Specified (PTCL-NOS) Angioimmunoblastic T Cell Lymphoma Anaplastic Large Cell Lymphoma (ALCL), ALK-Positive Immunohistology Anaplastic Large Cell Lymphoma, ALK-Negative Adult T Cell Leukemia/Lymphoma Nodal Involvement by the Cutaneous T Cell Lymphomas Histiocytic and Dendritic Neoplasms Histiocytic Sarcoma Langerhans Cell Histiocytosis Interdigitating Dendritic Cell (IDC) Sarcoma Follicular Dendritic Cell (FDC) Sarcoma Hodgkin Lymphoma Diagnostic Approach to Diffuse Infiltrates in lymph Nodes Is the Infiltrate Truly Diffuse? Does the Diffuse Infiltrate Involve the Node Partially or Completely? Is the Infiltrate Monomorphous or Polymorphous? Are the Cells Small or Large?. 281

4 x Contents 7. Defining Microscopic Features Granulomas and Foam Cells Infective Granulomatous Lymphadenitis Mycotic Lymphadenitis Protozoan and Parasitic Lymphadenitides Non-infective Granulomatous Lymphadenitis Granulomas, Non-necrotizing Foreign Body and Lipid Granulomatous Lymphadenitis Lipid Lymphadenopathy Sinus Pattern Sinus Histiocytosis Rosai Dorfman Disease (Sinus Histiocytosis with Massive Lymphadenopathy) Necrosis, Apoptosis, and Infarction Clear Cells Mast Cell Disease Hairy Cell Leukemia Spindled Cells Inflammatory Myofibroblastic Tumor Palisaded Myofibroblastoma Kaposi Sarcoma Vascular Prominence Bacillary Angiomatosis Vascular Transformation of Lymph Node Sinuses Hemorrhage Starry Sky Pattern Mottled Pattern Fibrosis/Hyalinization Signet Ring Cells Bizarre or Multinucleated Cells Extramedullary Hematopoiesis Prominent Eosinophils Prominent Neutrophils Prominent Plasma Cells Infiltration of Pericapsular Fat Extraneous Cells Pigmented Cells, Epithelial Cells, Foreign Material, Dermatopathic Lymphadenitis, Hemosiderin Inclusions of Benign Extraneous Cells Nodal Involvement by Leukemias and Extranodal Lymphomas Nodal Involvement by Leukemia Myeloid Leukemia/Myeloid Sarcoma Primary Myelofibrosis B and T Cell Prolymphocytic Leukemias NK Cell Lymphoproliferative Disorders Nodal Involvement by Extranodal Lymphomas Splenic B Cell Marginal Zone Lymphoma Hairy Cell Leukemia (HCL) Heavy-Chain Disease

5 Contents xi Plasma Cell Neoplasms Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Primary Cutaneous Diffuse Large B Cell Lymphoma (DLBCL) Leg Type Lymphomatoid Granulomatosis Extranodal NK/T Cell Lymphoma Nasal Type Blastic Plasmacytoid Dendritic Cell Neoplasm EBV-Associated T Cell Lymphoproliferative Disorders EBV-Positive T Cell Lymphoproliferative Disorders of Childhood Needle Core Biopsies and Aspirates Needle Core Biopsies Advantages of Needle Core Biopsies Disadvantages of Needle Core Biopsies Handling of Needle Core Biopsies Diagnostic Approach to Needle Core Biopsies of Lymph Nodes and Potential Pitfalls Fine-Needle Aspiration Samples Polymorphous Infiltrates Monomorphous Infiltrates Subject Index

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