A Pattern Approach to Lymph Node Diagnosis (eBook)

While a pattern approach to diagnosis is taught and practiced with almost every other tissue or organ in the body, the lymph node remains a mystery to most residents starting out in pathology and those pathologists with limited experience in the area. A Pattern Approach to Lymph Node Diagnosis demonstrates that a systematic approach to lymph node examination can be achieved through recognition of morphological patterns produced by different disease processes. It presents a combination of knowledge-based assessment and pattern recognition for diagnosis covering the major primary neoplastic and non neoplastic diseases and metastatic tumors in lymph nodes. This volume demonstrates that lymph node compartments can be recognized histologically especially with the aid of immunohistological markers and how this knowledge can be employed effectively to localize and identify pathological changes in the different compartments in order to facilitate histological diagnosis. It also defines histological features that, because of their pathological occurrence in lymph nodes, are useful pointers to specific diagnoses or disease processes. The volume is organized in accordance with the primary pattern of presentation of each diagnostic entity. Differential diagnosis is discussed and each diagnostic entity is accompanied by color illustrations that highlight the diagnostic features. Immunohistochemistry, clinical aspects, relevant cytogenetics and molecular information of each entity is provided by an author who is an expert in lymphoproliferative diseases. An algorithmic approach to diagnosis is adopted at the end of each section by listing a set of questions that help to consider diagnostic entities that can present with the morphological features observed. A Pattern Approach to Lymph Node Diagnosis is an essential text for residents and fellows in pathology and general pathologists making first hand lymph node diagnoses as well as to hematologists and physicians who treat patients with lymphoprolifeative diseases.

Preface 5
Contents 7
Acknowledgments 12
Section I 13
1 Introduction 14
Knowledge-Based Diagnosis 15
Systematic Examination of the Lymph Node 18
Cell Type Identification 20
Cell Size and Cellularity 20
Immunohistology 21
Cytological Preparations 22
The Pattern Approach to Diagnosis 25
Selected Reading 29
2 Handling of the Lymph Node Biopsy 30
Introduction 30
The Biopsy 30
Lymph Node Triage 31
3 Immunohistology and Other Diagnostic Techniques 33
Introduction 33
Immunohistology 34
B Cell Markers 36
Immunoglobulins 36
CD20 39
CD79a 40
PAX5 40
CD23 40
Cyclin D1 (Bcl1) 40
Bcl2 41
Bcl6 41
CD10 (CALLA) 41
MUM1/IRF4 42
CD45RA (4KB5, MB1, KiB3, MT2) 42
CDw75 (LN1) 42
CD38 42
CD138 43
ZAP-70 43
T Cell Markers 43
T Cell Receptor 44
CD1a 44
CD2 44
CD3 45
CD4 45
CD5 45
CD7 45
CD8 46
CD43 (Mt1) 46
CD45RO (UCHl1, OPD4) 46
Cytotoxic Molecules (TIA-1, Granzyme B, Perforin) 46
PD-1 (CD279, CXCR5) 47
CXCL13 47
Natural Killer and T/NK Cell Markers 48
CD56 (Neural Cell Adhesion Molecule 1) 48
CD57 48
Precursor B- and T Cell Markers 48
Terminal Deoxynucleotidyl Transferase (TdT) 48
CD34 49
Monocyte/ Macrophage Markers 49
CD68 49
CD163 49
Mac387 50
Ham56 50
Lysozyme (Muramidase) 50
-1-Antitrypsin and -1-Antichymotrypsin 50
Langerhans Cell, Follicular Dendritic Cell, and Interdigitating Dendritic Reticulum Cell Markers 51
CD21 51
CD23 51
CD35 51
D2-40 (Podoplanin) 51
Clusterin 52
Langerin (CD207) 52
S100 Proteins 52
HLA-DR 52
Markers of Reed--Sternberg Cells in Hodgkin Lymphoma 52
CD15 53
CD30 53
CD40 54
OCT2 and BOB.1 54
Latent Membrane Protein 1 (LMP1) 54
Miscellaneous Markers 55
Ki-67 55
ALK (CD246) 55
CD72 (DBA.44) 56
Myeloid Cell Markers 56
Mast Cell Markers 57
Diagnostic Approach with Immunohistochemical Stains 57
Staining for Follicular Dendritic Cells 57
Follicular Dendritic Cells in Angioimmunoblastic T Cell Lymphoma 58
Follicular Lymphoma Versus Reactive Follicles 58
Other Lymphoid Nodules 58
Immunohistological Identification of Diffuse Lymphoid Infiltrates 59
Diffuse Small Cell Infiltrates 60
Diffuse Large Cell Infiltrates 60
Diffuse Mixed Cell Infiltrates 61
Immunophenotype Subgrouping 61
Histochemical Stains 61
Periodic Acid--Schiff (PAS) Stain 61
Silver Impregnation for Reticulin 62
Methyl Green Pyronin Stain 62
Non-specific Esterases 62
Specific Naphthol AS-D Chloroacetate Esterase 62
Peroxidase Reaction 62
Sudan Black B 62
Tartrate-Resistant Acid Phosphatase 62
Flow Cytometry 63
Molecular Diagnostics 67
Detection of Clonality 67
Analysis of Antigen Receptor Genes -- Southern Blot 67
Immunoglobulin Heavy- and Light-Chain Genes 67
T Cell Receptor Chain Genes 68
Analysis of Antigen Receptor Genes -- Polymerase Chain Reaction (PCR) 68
Molecular Diagnosis of Chromosomal Translocations 69
Genotype Subgroups 69
Conventional Cytogenetics 70
Fluorescence In Situ Hybridization (FISH) 70
Southern Blot Analysis 70
Polymerase Chain Reaction (PCR) 70
Gene Expression Profiling 71
4 Anatomical and Functional Compartments 72
B Cell Differentiation and Corresponding B Cell Lymphomas 73
The Cortex 73
The Lymphoid Follicle 73
T Cell Differentiation 78
The Paracortex 82
High-Endothelial Venules 88
Medullary Area 88
Connective Tissue Framework 89
Section II 90
5 Nodular Lymphoid Infiltrates 91
Follicular Pattern 92
Neoplastic Follicles 92
Follicular Lymphoma (FL) 93
Clinical 93
Morphology 94
Grading 95
Immunohistology 97
Genetics 98
Follicular Hyperplasia Versus Follicular Lymphoma 99
Other Follicular Patterns 105
Mantle Pattern 108
Mantle Cell Lymphoma 108
Clinical 108
Morphology 109
Immunohistology 109
Genetics 110
Marginal Zone Pattern 113
Nodal Marginal Zone Lymphoma (Monocytoid B Cell Lymphoma) 115
Clinical 115
Morphology 116
Immunohistology 117
Genetics 118
Nodular Pattern 119
Heterogenous Nodules 119
Pseudofollicular Pattern 119
Hodgkin Lymphoma (HL) 120
Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) 122
Classical Hodgkin Lymphoma (CHL) 124
Nodular Sclerosis Classical Hodgkin Lymphoma (NSCHL) 125
Mixed Cellularity Classical Hodgkin Lymphoma (MCCHL) 126
Lymphocyte-Rich Classical Hodgkin Lymphoma (LRCHL) 130
Lymphocyte-Depleted Classical Hodgkin Lymphoma (LDCHL) 133
Post-transplant Lymphoproliferative Disorders 135
Plasmacytic Hyperplasia and Infectious Mononucleosis-Like PTLD 138
Polymorphic PTLD 138
Monomorphic PTLD 139
Colonization of Follicles by Neoplastic Cells 139
Homogenous Nodules 140
Reactive Hyperplasia 142
Follicular and Paracortical Hyperplasia 144
Non-specific Follicular Hyperplasia 145
Progressive Transformation of Germinal Centers (PTGC) 145
Morphology 146
Rheumatoid Lymphadenopathy 146
Toxoplasma Lymphadenopathy 147
Human Immunodeficiency Virus/Acquired Immunodeficiency Disease Syndrome (HIV/AIDS) Lymphadenitis 150
Kimura Disease 152
Castleman Disease 153
Hyaline Vascular Variant (HV) 153
Plasma Cell Variant (PC) 155
Multicentric Variant (MC) 158
Syphilis Lymphadenopathy 159
Kikuchi Disease 161
Systemic Lupus Erythematosus 165
Infectious Mononucleosis Lymphadenopathy 166
Other Viral Lymphadenopathies 169
Paracortical Nodules/ Expansion 173
Dermatopathic Lymphadenopathy (DL) 173
Drug-Induced Lymphadenopathy 174
The Diagnostic Approach to Nodular Infiltrates in Lymph Nodes 175
Are They Follicles or Nodules? 176
Are the Follicles Reactive or Neoplastic? 176
Are Follicles Infrequent and ''Constricted''? 176
Are the Follicles Exceptionally Large? 177
Do the Enlarged Germinal Centers Contain Atypical Cells? 177
Are the Nodules Homogenous or Heterogenous in Composition? 177
Homogenous Nodules 177
Heterogenous Nodules 177
If There Is Marked Follicular Hyperplasia, Can a Specific Diagnosis Be Made? 178
Do the Vague Nodules Represent Paracortical Nodules? 179
6 Diffuse Lymphoid Infiltrations 182
B Cell Neoplasms 183
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) 183
Morphology 185
Immunohistology 186
Genetics 188
Lymphoplasmacytic Lymphoma (LPL) 193
Morphology 197
Immunohistology and Genetics 198
Diffuse Large B Cell Lymphoma (DLBCL) 201
Morphology 204
Immunohistology and Genetics 208
Clinical Subtypes 214
Node-Based Subtypes of DLBCL 215
EBV-Positive DLBCL of the Elderly 216
ALK-Positive Large B Cell Lymphoma 217
Large B Cell Lymphoma Arising in HHV8-Associated Multicentric Castleman Disease 219
Burkitt Lymphoma 219
Endemic BL 220
Sporadic BL 220
Immunodeficiency-Associated BL 220
Clinical 220
Morphology 221
Immunohistology 223
Genetics 223
B Cell Lymphoma, Unclassifiable, with Features Intermediate Between DLBCL and BL 224
Nodal Involvement by Primary Extranodal Lymphomas and Leukemias 225
T Cell and NK Cell Neoplasms 225
T-Lymphoblastic Leukemia/Lymphoma (Precursor T Cell Lymphoblastic Leukemia/Lymphoma) 226
Clinical 226
Morphology 227
Immunohistology and Genetics 228
Peripheral T Cell Lymphoma, Not Otherwise Specified (PTCL-NOS) 230
Clinical 231
Morphology 232
Immunohistology 234
Genetics 236
Angioimmunoblastic T Cell Lymphoma 236
Clinical 237
Morphology 240
Immunohistology and Genetics 242
Anaplastic Large Cell Lymphoma (ALCL), ALK-Positive 245
Clinical 247
Morphology 248
Immunohistology 251
Genetics 253
Anaplastic Large Cell Lymphoma, ALK-Negative 256
Adult T Cell Leukemia/Lymphoma 257
Clinical 258
Morphology 261
Immunohistology and Genetics 262
Nodal Involvement by the Cutaneous T Cell Lymphomas 262
Morphology 263
Immunohistology and Genetics 266
Histiocytic and Dendritic Neoplasms 267
Histiocytic Sarcoma 269
Clinical 270
Morphology 271
Immunohistology 272
Genetics 274
Langerhans Cell Histiocytosis 275
Clinical 277
Morphology 278
Immunohistology 278
Genetics 278
Interdigitating Dendritic Cell (IDC) Sarcoma 279
Clinical 279
Morphology 280
Immunohistology 281
Genetics 282
Follicular Dendritic Cell (FDC) Sarcoma 282
Clinical 282
Morphology 283
Immunohistology 284
Genetics 284
Hodgkin Lymphoma 285
Diagnostic Approach to Diffuse Infiltrates in lymph Nodes 285
Is the Infiltrate Truly Diffuse? 286
Does the Diffuse Infiltrate Involve the Node Partially or Completely? 287
Is the Infiltrate Monomorphous or Polymorphous? Are the Cells Small or Large? 288
7 Defining Microscopic Features 294
Granulomas and Foam Cells 294
Infective Granulomatous Lymphadenitis 294
Mycobacterial Lymphadenitis 296
Cat-Scratch Disease 296
Lymphogranuloma Venereum 297
Yersinia Lymphadenitis 298
Whipple Disease 299
Mycotic Lymphadenitis 301
Histoplasma Lymphadenitis 302
Cryptococcus Lymphadenitis 303
Coccidioides Lymphadenitis 305
Pneumocystis Lymphadenitis 306
Protozoan and Parasitic Lymphadenitides 307
Non-infective Granulomatous Lymphadenitis 308
Sarcoidosis 311
Granulomas, Non-necrotizing 311
Peripheral T Cell Lymphoma, NOS -- Lymphoepithelioid Variant (Lennert Lymphoma) 311
Classical Hodgkin Lymphoma 313
Foreign Body and Lipid Granulomatous Lymphadenitis 314
Silicone Lymphadenopathy 315
Detritic Lymphadenopathy 316
Lipid Lymphadenopathy 317
Sinus Pattern 320
Sinus Histiocytosis 321
Rosai--Dorfman Disease (Sinus Histiocytosis with Massive Lymphadenopathy) 323
Necrosis, Apoptosis, and Infarction 324
Clear Cells 326
Mast Cell Disease 327
Hairy Cell Leukemia 328
Spindled Cells 331
Inflammatory Myofibroblastic Tumor 332
Palisaded Myofibroblastoma 332
Kaposi Sarcoma 334
Vascular Prominence 337
Bacillary Angiomatosis 338
Vascular Transformation of Lymph Node Sinuses 338
Hemorrhage 340
Starry Sky Pattern 341
Mottled Pattern 341
Fibrosis/ Hyalinization 342
Signet Ring Cells 343
Bizarre or Multinucleated Cells 344
Extramedullary Hematopoiesis 344
Prominent Eosinophils 344
Prominent Neutrophils 345
Prominent Plasma Cells 345
Infiltration of Pericapsular Fat 346
Extraneous Cells Pigmented Cells, Epithelial Cells, Foreign Material, Dermatopathic Lymphadenitis, Hemosiderin 347
Inclusions of Benign Extraneous Cells 347
8 Nodal Involvement by Leukemias and Extranodal Lymphomas 351
Nodal Involvement by Leukemia 351
Myeloid Leukemia/Myeloid Sarcoma 351
Primary Myelofibrosis 352
B and T Cell Prolymphocytic Leukemias 354
NK Cell Lymphoproliferative Disorders 356
Nodal Involvement by Extranodal Lymphomas 357
Splenic B Cell Marginal Zone Lymphoma 358
Hairy Cell Leukemia (HCL) 359
Heavy-Chain Disease 360
Plasma Cell Neoplasms 361
Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma 362
Primary Cutaneous Diffuse Large B Cell Lymphoma (DLBCL) -- Leg Type 364
Lymphomatoid Granulomatosis 365
Extranodal NK/T Cell Lymphoma -- Nasal Type 365
Blastic Plasmacytoid Dendritic Cell Neoplasm 367
EBV-Associated T Cell Lymphoproliferative Disorders 369
EBV-Positive T Cell Lymphoproliferative Disorders of Childhood 369
Systemic EBV-Positive T Cell Lymphoproliferative Disease of Childhood 369
Clinical 369
Morphology 370
Immunohistology 370
Genetics 370
Hydroa Vacciniforme-Like Lymphoma 371
Clinical 371
Morphology 371
Immunohistology 371
Genetics 371
9 Needle Core Biopsies and Aspirates 372
Needle Core Biopsies 372
Advantages of Needle Core Biopsies 372
Disadvantages of Needle Core Biopsies 373
Handling of Needle Core Biopsies 373
Diagnostic Approach to Needle Core Biopsies of Lymph Nodes and Potential Pitfalls 373
Does the Sample Represent Lymph Node Tissue? 374
Is Lymph Node Architecture Destroyed? 374
Is the Process Lymphoid? 374
If Lymphoid, Is the Process Follicular/Nodular or Diffuse? 374
If Follicular, Is It Reactive or Neoplastic? 374
If There Are Nodules, Are They Homogenous or Heterogenous in Composition? 374
Do All of the Follicles Appear Hyperplastic? If So, Does This Ensure That the Process Is Reactive? 375
If the Infiltrate Is Diffuse, Is It Homogenous or Heterogenous, and What Is the Cell Size? 375
Fine-Needle Aspiration Samples 404
Polymorphous Infiltrates 405
Monomorphous Infiltrates 407
Subject Index 409