CONTENTS 1. General Immunology of Lymph Node and Spleen. 1 Overview of the Immune System and Immunologic Responses . 1 Lymph Nodes . 1 Anatomy . 1 Primary Immune Response. 1 B Lymphocytes. ` 3 T Lymphocytes. 8 Natural Killer Cells. 9 Dendritic Cells . 10 Spleen . 11 Anatomy . 11 White Pulp . 11 Marginal Zone. 13 Red Pulp. 14 2. Embryology and Histology of the Lymph Node and Spleen. 19 Embryology of the Spleen . 19 Embryologic Abnormalities of the Spleen. 19 Accessory Spleen, Ectopic Spleen, and Polysplenia. 19 Wandering Spleen. 22 Abnormal Fusion: Splenogonadal, Splenorenal, Hepatolienal Fusion. 23 Asplenia. 24 Embryology of the Lymph Nodes . 24 Ectopia in Lymph Nodes . 25 Histology of Lymph Node (Normal Architecture and Function of Lymph Nodes) . 35 Capsule and Subcapsular Sinus. 36 Cortex . 36 Paracortex . 40 Medulla . 43 Vasculature. 43 Histology of the Spleen . 45 General Microanatomy. 45 Vasculature. 45 Red Pulp. 47 White Pulp . 50 3. Technical Evaluation and Overview of Lymph Node and Spleen. 57 Indications for Lymph Node Biopsy . 57 xi Benign and Reactive Conditions of Lymph Node and Spleen Indications for Splenectomy . 58 Sampling and Handling the Fresh Lymph Node . 58 Sampling and Handling the Fresh Spleen. 61 Fixation and Processing. 61 Routine and Histochemical Stains . 64 Evaluation of the Lymph Node. 65 Evaluation of the Spleen . 71 4. Ancillary Studies for Evaluation of Lymph Node and Spleen. 75 Basic Concepts. 75 Immunohistochemistry Techniques. 75 Antigen Retrieval . 76 Antibodies: Clusters of Differentiation (CD) Groups. 76 Immunohistochemistry of Lymphoid Tissues . 77 B Cells . 77 T Cells . 79 Reactive Conditions Versus Malignancies. 80 Reactive Conditions Versus Lymphomas . 82 Reactive Conditions Versus B-Cell Neoplasms. 83 Reactive Conditions Versus T-Cell Neoplasms . 85 Reactive Conditions Versus Hodgkin Lymphoma. 86 Histiocytic and Myelomonocytic Antibodies. 87 Myeloid Cell Antibodies . 87 Dendritic Cell Antibodies . 88 Potential Pitfalls in Immunohistochemistry. 89 Immunohistochemistry of the Spleen . 91 Flow Cytometry. 93 Flow Cytometry of the Spleen. 93 Ultrastructural Examination of the Lymph Node and Spleen. 94 5. General Reactive Conditions in Lymph Node and Spleen . 97 Follicular Hyperplasia. 97 Interfollicular/Immunoblastic Hyperplasia . 105 Mantle Zone (Primary Follicle) Hyperplasia . 107 Marginal Zone (Monocytoid B-Cell) Hyperplasia. 109 T-Cell Hyperplasias including Nodular Paracortical T-Cell Hyperplasia and other T-Cell Nodules. 112 Mixed Pattern Hyperplasia. 116 Atypical Lymphoid Hyperplasia. 117 Sinus Histiocytosis. 119 Granulomatous Inflammation . 119 xii Contents Plasmacytoid Dendritic Cells . 126 Necrotizing Lymphadenitis. 128 Progressive Transformation of Germinal Centers. 129 Regressive Changes in Germinal Centers . 133 Fatty Transformation of Lymph Nodes. 134 Hemorrhage and Infarction . 135 Perisplenitis (“Sugar-Coated” Spleen) . 137 6. Specific Clinical Entities. 143 Dermatopathic Lymphadenitis . 143 Kimura Disease . 145 Kawasaki Disease . 149 Kikuchi-Fujimoto Disease (Histiocytic Necrotizing Lymphadenitis). 150 Castleman Disease (Angiofollicular Lymph Node Hyperplasia), Hyaline-Vascular Type, Plasma Cell Type, and Multicentric Type . 155 Angioimmunoblastic Lymphadenopathy. 164 Rosai-Dorfman Disease (Sinus Histiocytosis with Massive Lymphadenopathy). 166 Hemophagocytic Syndromes . 169 Langerhans Cell Histiocytosis . 174 7. Congenital Immunodeficiency Diseases . 185 Severe Combined Immunodeficiency. 188 Autoimmune Lymphoproliferative Syndrome . 193 Common Variable Immunodeficiency. 197 Selective IgA Deficiency . 201 Hyper-IgM Syndrome. 201 Hyper-IgE Syndrome (Job Syndrome) . 204 X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia) and Hypogam- maglobulinemia. 205 X-Linked Lymphoproliferative Disease (Duncan Syndrome). 207 Griscelli Syndrome and Chediak-Higashi Syndrome. 210 Wiskott-Aldrich Syndrome. 211 Ataxia-Telangiectasia (including Nijmegen Breakage Syndrome and Berlin Breakage Syndrome). 214 Chronic Granulomatous Disease . 216 Tuberous Sclerosis. 219 8. Bacterial Infections. 229 Gram-Positive Bacterial Infections. 229 Staphylococcus and Streptococcus . 231 Corynebacterium. 231 Listeria Monocytogenes. 233 xiii Benign and Reactive Conditions of Lymph Node and Spleen Actinomyces, Nocardia, and Rhodococcus Equi. ..