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Book Details
Abstract
Diagnostic Immunohistochemistry presents the latest information and most reliable guidance on immunohistological diagnoses in surgical pathology. David J. Dabbs, MD and other leading experts bring you state-of-the-art coverage on genomic and theranostic applications, molecular anatomic pathology, immunocytology, Non-Hodgkin’s lymphoma, and more. Additional features such as tables discussing antibody specifications, differential diagnosis boxes, ancillary anatomic molecular diagnostics, and full-color histological images ensure user-friendly coverage that makes key information easy to find and apply. This concise and complete resource is today’s indispensable guide to the effective use of immunohistochemical diagnosis.
- Discusses diagnostic pitfalls through immunohistologic differential diagnosis wherever appropriate so you can provide the most accurate diagnoses.
- Presents chapters arranged by organ system for comprehensive coverage of all relevant information in a convenient and intuitive organization.
- Provides quick reference graphs for antibodies throughout the text that illustrate the frequency of immunostaining for a variety of antibodies in tumors.
- Includes Key Diagnostic Points boxes in every chapter for a quick summary of text areas that are of particular importance.
- Features an expert author for each chapter to ensure coverage of the current state of the art.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Inside Front Cover | ifc1 | ||
| Diagnostic Immunohistochemistry, 4/e | i | ||
| Copyright Page | iv | ||
| Dedication | v | ||
| Contributors | vii | ||
| Foreword | xi | ||
| Preface | xiii | ||
| How to Use This Book | xv | ||
| Table Of Contents | xvii | ||
| 1 Techniques of Immunohistochemistry: | 1 | ||
| Overview | 1 | ||
| Basic Principles of Immunohistochemistry | 2 | ||
| Antibodies as Specific Staining Reagents | 3 | ||
| Blocking Nonspecific Background Staining | 4 | ||
| Detection Systems | 5 | ||
| Direct-Conjugate–labeled Antibody Method | 6 | ||
| Indirect, or Sandwich, Procedure | 6 | ||
| Unlabeled Antibody Methods | 6 | ||
| Enzyme Bridge Technique | 6 | ||
| Peroxidase-Antiperoxidase Method | 7 | ||
| Biotin-Avidin Procedure | 7 | ||
| Avidin-Biotin Conjugate Procedure | 8 | ||
| Biotin-Streptavidin Systems | 8 | ||
| Alkaline Phosphatase Labels, Double (Multiplex) Stains, and Polyvalent Detection Systems | 8 | ||
| Alkaline Phosphatase AntiAlkaline Phosphatase Method | 8 | ||
| Polymer-Based Labeling Methods | 9 | ||
| Tyramine Signal Amplification | 10 | ||
| Other Methods with Limited or Research Applications | 11 | ||
| Titration of Primary Antibody and Detection System | 12 | ||
| Establishing a New Immunohistochemistry Stain in the Laboratory | 13 | ||
| Quality Control and Standardization | 14 | ||
| Sample Preparation | 14 | ||
| Validation of Reagents, Protocols, Controls, and Staining Results | 15 | ||
| Internal Reference Standards for Quantification and the Evaluation of Sample Preparation | 19 | ||
| Tissue Fixation, Processing, and Antigen Retrieval Techniques | 19 | ||
| Antigen Retrieval | 20 | ||
| Heating Conditions | 20 | ||
| Chemical Composition and pH of the Antigen Retrieval Solution | 21 | ||
| Test-Battery Approach for Antigen Retrieval Technique | 22 | ||
| Techniques, Protocols, and Troubleshooting | 22 | ||
| Antigen Retrieval by the Microwave Heating Method | 23 | ||
| Blocking Nonspecific Binding | 23 | ||
| Washing Steps | 23 | ||
| Incubation of Primary Antibody | 23 | ||
| Incubation of Detection Reagents | 24 | ||
| Substrate and Chromogen | 24 | ||
| Counterstaining and Mounting Slides | 24 | ||
| Double or Multiplex Immunoenzymatic Techniques | 25 | ||
| Automation | 27 | ||
| Quantification: Development of Reference Standards and Standard Curves for Calculation of Antigen Content in Tissue Section | 29 | ||
| Protein “Spots” | 29 | ||
| Faux Tissues and Histoids | 29 | ||
| Quantitative Internal Reference Standards | 30 | ||
| Quantitative In Situ Proteomics | 30 | ||
| Technical Issues: Troubleshooting | 30 | ||
| Absence of Staining of Both Specimen and Control | 31 | ||
| Specimen with Appropriate Positive Staining of Positive Control | 33 | ||
| Weak Staining of Specimen with Appropriate Staining of Positive Control | 35 | ||
| Background Staining | 35 | ||
| Artifactual Staining | 36 | ||
| Summary of Amplification Methods | 36 | ||
| Predetection Amplification | 36 | ||
| Detection-Phase Amplification | 36 | ||
| Postdetection Amplification | 37 | ||
| Conclusion | 38 | ||
| References | 38 | ||
| 2 Molecular Anatomic Pathology: | 39 | ||
| General Principles of Molecular Biology | 39 | ||
| Deoxyribonucleic Acid | 39 | ||
| Ribonucleic Acid | 40 | ||
| Protein | 41 | ||
| Genetic Polymorphism and Mutations | 41 | ||
| Specimen Requirements for Molecular Testing | 42 | ||
| Common Techniques for Molecular Analysis | 42 | ||
| Polymerase Chain Reaction | 42 | ||
| Reverse Transcription Polymerase Chain Reaction | 43 | ||
| Real-Time Polymerase Chain Reaction | 44 | ||
| PCR–Restriction Fragment Length Polymorphism Analysis | 45 | ||
| Single-Strand Conformation Polymorphism | 45 | ||
| Allele-Specific Polymerase Chain Reaction and Allele-Specific Hybridization | 45 | ||
| DNA Sequencing Analysis: Conventional Sequencing | 46 | ||
| Next-Generation Sequencing | 47 | ||
| Fluorescence In Situ Hybridization | 48 | ||
| Comparative Genomic Hybridization | 49 | ||
| DNA Microarrays | 49 | ||
| Detection of Small-Scale Mutations | 49 | ||
| Detection of Chromosomal Rearrangements | 50 | ||
| Detection of Chromosomal Deletions/Loss of Heterozygosity Analysis | 51 | ||
| Detection of Microsatellite Instability | 52 | ||
| DNA-Based Tissue Identity Testing | 54 | ||
| Summary | 55 | ||
| References | 55 | ||
| 3 Immunohistology of Infectious Diseases | 56 | ||
| Overview | 56 | ||
| Viral Infections | 56 | ||
| Hepatitis B | 57 | ||
| Herpesviruses | 57 | ||
| Adenoviruses | 59 | ||
| Parvovirus B19 Infection | 60 | ||
| Viral Hemorrhagic Fevers | 60 | ||
| Polyomaviruses | 61 | ||
| Other Viral Infections | 62 | ||
| Bacterial Infections | 62 | ||
| Helicobacter pylori Infection | 63 | ||
| Whipple Disease | 63 | ||
| Rocky Mountain Spotted Fever | 63 | ||
| Bartonella Infections | 64 | ||
| Syphilis | 64 | ||
| Mycobacterium tuberculosis Infection | 64 | ||
| Other Bacterial Infections | 65 | ||
| Fungal Infections | 65 | ||
| Protozoal Infections | 66 | ||
| Emerging Infectious Diseases | 67 | ||
| Hantavirus Pulmonary Syndrome | 67 | ||
| West Nile Virus Encephalitis | 67 | ||
| Enterovirus 71 Encephalomyelitis | 67 | ||
| Nipah Virus Infection | 68 | ||
| Ehrlichioses | 68 | ||
| Pathologists, Immunohistochemistry, and Bioterrorism | 68 | ||
| Anthrax | 69 | ||
| Tularemia | 70 | ||
| Plague | 70 | ||
| Beyond Immunohistology: Molecular Diagnostic Applications | 70 | ||
| Summary | 72 | ||
| References | 72 | ||
| 4 Immunohistology of Neoplasms of Soft Tissue and Bone | 73 | ||
| Overview | 73 | ||
| Biology of Antigens and Antibodies | 73 | ||
| Intermediate Filament Proteins | 73 | ||
| Keratins | 74 | ||
| Neurofilament Proteins | 74 | ||
| Glial Fibrillary Acidic Protein | 75 | ||
| Vimentin | 75 | ||
| Epithelial Markers | 75 | ||
| Epithelial Membrane Antigen | 75 | ||
| Other Epithelial Markers | 75 | ||
| Markers of Muscle Differentiation | 76 | ||
| Desmin | 76 | ||
| Actins | 77 | ||
| Other Sarcomeric Contractile Proteins | 77 | ||
| Caldesmon | 77 | ||
| Calponin | 77 | ||
| Markers of Skeletal Muscle Differentiation | 78 | ||
| Myoglobin | 78 | ||
| MYOD1 and Myogenin | 78 | ||
| S-100 Protein | 78 | ||
| Potential Markers of Nerve Sheath Differentiation | 79 | ||
| CD56 (Neural Cell Adhesion Molecule) and CD57 (NKH1/LEU19 and LEU7/HNK-1) | 79 | ||
| Collagen Type IV and Laminin | 79 | ||
| Claudin-1 | 79 | ||
| SOX10 | 80 | ||
| Markers of Endothelial Differentiation | 80 | ||
| Factor VIII–Related Antigen (Von Willebrand Factor) | 80 | ||
| CD34 | 80 | ||
| CD31 | 81 | ||
| Friend Leukemia Virus Integration 1 | 81 | ||
| V-ETS Avian Erythroblastosis Virus E26 Oncogene Homolog (ERG) | 81 | ||
| Glucose Transporter Type 1 | 82 | ||
| Prospero-Related Homeobox 1 | 82 | ||
| Claudin-5 | 82 | ||
| Thrombomodulin | 83 | ||
| Ulex Europaeus I Agglutinin | 83 | ||
| Podoplanin | 83 | ||
| Wilms Tumor 1 | 83 | ||
| Vascular Endothelial Growth Factor Receptor 3 | 83 | ||
| Fibrohistiocytic Markers | 83 | ||
| CD68 | 84 | ||
| CD163 | 84 | ||
| Lysozyme (Muramidase) | 84 | ||
| Factor XIIIa | 84 | ||
| NKI/C3 | 84 | ||
| Markers of Melanocytic Differentiation | 84 | ||
| Human Melanoma Black 45 | 84 | ||
| MELAN A | 85 | ||
| Microphthalmia-Associated Transcription Factor | 85 | ||
| Tyrosinase | 85 | ||
| Other Useful Markers in Evaluation of Soft Tissue and Bone Tumors | 85 | ||
| β-Catenin | 85 | ||
| Anaplastic Lymphoma Kinase | 86 | ||
| CD99 | 86 | ||
| Neuroblastoma Marker (NB84) | 86 | ||
| Transcription Factor E3 | 87 | ||
| Murine Double-Minute 2 Homolog | 87 | ||
| Cyclin-Dependent Kinase 4 | 87 | ||
| Retinoblastoma | 87 | ||
| SMARCB1 | 87 | ||
| B-Cell Chronic Lymphocytic Leukemia/Lymphoma 2 | 88 | ||
| Markers Identified through Gene-Expression Profiling | 88 | ||
| Transducin-Like Enhancer of Split 1 | 88 | ||
| Mucin 4 | 88 | ||
| Immunohistochemical Markers for Evaluation of Bone Tumors: Proposed Markers of Osteoblastic Differentiation | 88 | ||
| Osteocalcin | 89 | ||
| Osteonectin | 89 | ||
| Brachyury | 89 | ||
| Specific Soft Tissue and Bone Tumors | 89 | ||
| Vascular Tumors | 91 | ||
| Benign Vascular Tumors | 91 | ||
| Hemangioma/Lymphangioma | 91 | ||
| Locally Aggressive and Rarely Metastasizing Vascular Tumors | 94 | ||
| Kaposiform Hemangioendothelioma | 94 | ||
| Pseudomyogenic Hemangioendothelioma | 94 | ||
| Malignant Vascular Tumors | 94 | ||
| Epithelioid Hemangioendothelioma | 94 | ||
| Angiosarcoma | 95 | ||
| Kaposi Sarcoma | 97 | ||
| Skeletal Muscle Tumors | 97 | ||
| Benign Skeletal Muscle Tumors | 97 | ||
| Rhabdomyoma | 97 | ||
| Rhabdomyosarcoma | 98 | ||
| Embryonal Rhabdomyosarcoma. | 98 | ||
| Alveolar Rhabdomyosarcoma. | 100 | ||
| Pleomorphic Rhabdomyosarcoma. | 100 | ||
| Spindle Cell Rhabdomyosarcoma. | 100 | ||
| Sclerosing Rhabdomyosarcoma. | 101 | ||
| Epithelioid Rhabdomyosarcoma. | 101 | ||
| Fibroblastic Tumors | 102 | ||
| Fibromatoses | 102 | ||
| Angiomyofibroblastoma | 102 | ||
| Solitary Fibrous Tumor | 103 | ||
| Low-Grade Fibromyxoid Sarcoma | 104 | ||
| Sclerosing Epithelioid Fibrosarcoma | 105 | ||
| Myxoinflammatory Fibroblastic Sarcoma | 105 | ||
| Angiomatoid Fibrous Histiocytoma | 106 | ||
| Inflammatory Myofibroblastic Tumor | 106 | ||
| Infantile Fibrosarcoma | 107 | ||
| Myxofibrosarcoma | 107 | ||
| Smooth Muscle Tumors | 107 | ||
| Benign Smooth Muscle Tumors | 107 | ||
| Leiomyosarcoma | 108 | ||
| Pleomorphic Leiomyosarcoma. | 109 | ||
| Other Morphologic Variants of Leiomyosarcoma. | 109 | ||
| Epstein-Barr Virus–associated Smooth Muscle Tumors | 109 | ||
| Perivascular Epithelioid Cell Family of Tumors | 109 | ||
| Nerve Sheath Tumors | 110 | ||
| Benign Peripheral Nerve Sheath Tumors | 110 | ||
| Neurofibroma and Schwannoma | 110 | ||
| Perineurioma | 111 | ||
| Granular Cell Tumor | 113 | ||
| Malignant Peripheral Nerve Sheath Tumors | 113 | ||
| Epithelioid Malignant Peripheral Nerve Sheath Tumor | 114 | ||
| Adipocytic Tumors | 115 | ||
| Spindle Cell Lipoma and Pleomorphic Lipoma | 115 | ||
| Well-Differentiated and Dedifferentiated Liposarcoma | 115 | ||
| Pleomorphic Liposarcoma | 115 | ||
| Myxoid Liposarcoma | 115 | ||
| Other Primary Neoplasms of Soft Tissue | 117 | ||
| Desmoplastic Small Round Cell Tumor | 117 | ||
| Ossifying Fibromyxoid Tumor | 117 | ||
| Synovial Sarcoma | 117 | ||
| Epithelioid Sarcoma | 119 | ||
| Clear Cell Sarcoma of Tendons and Aponeuroses | 120 | ||
| Clear Cell Sarcoma–Like Tumor of the Gastrointestinal Tract | 121 | ||
| Alveolar Soft-Part Sarcoma | 121 | ||
| Extraskeletal Myxoid Chondrosarcoma | 122 | ||
| Neuroblastoma | 123 | ||
| Myoepithelial Tumors | 123 | ||
| Soft Tissue Osteosarcoma | 123 | ||
| DEEP “Aggressive” Angiomyxoma | 123 | ||
| Extrarenal Malignant Rhabdoid Tumor | 124 | ||
| Cartilaginous Tumors of Bone | 124 | ||
| Chondroblastoma | 124 | ||
| Chondrosarcoma | 124 | ||
| Mesenchymal Chondrosarcoma | 124 | ||
| Clear Cell Chondrosarcoma | 125 | ||
| Fibrous Tumors of Bone | 125 | ||
| Chondromyxoid Fibroma | 125 | ||
| Desmoplastic Fibroma of Bone | 125 | ||
| Bone-Forming Tumors | 125 | ||
| Osteosarcoma | 125 | ||
| Other Selected Bone Tumors | 126 | ||
| Ewing Sarcoma | 126 | ||
| Chordoma | 127 | ||
| Giant Cell Tumors of Bone and Soft Tissue | 128 | ||
| Langerhans Cell Histiocytosis | 128 | ||
| Erdheim-Chester Disease | 128 | ||
| Adamantinoma | 128 | ||
| Summary | 129 | ||
| Acknowledgment | 129 | ||
| References | 129 | ||
| 5 Immunohistology of Hodgkin Lymphoma | 130 | ||
| Overview | 130 | ||
| Biology of Antigens and Antibodies | 130 | ||
| Principal Antibodies (CD45, CD20, BSAP/PAX5, CD30, CD15) | 130 | ||
| B-Cell Receptor (CD79a), Transcription Factors (Oct-2, BOB.1, PU.1, JunB), and Immunoglobulins (J-Chain, IgD) | 132 | ||
| Germinal Center/Post–Germinal Center Markers (BCL-6, IRF4, PRDM1, CD138) | 134 | ||
| Tumor Necrosis Factor Superfamily (CD40, CD95) | 134 | ||
| Epithelial Membrane Antigen | 134 | ||
| T-Cell and Cytotoxic Markers (CD2, CD3, CD4, CD5, CD8, CD57, Granzyme B, Perforin, TIA-1) | 134 | ||
| Epstein-Barr Virus | 135 | ||
| Dendritic or Antigen-Presenting Cell Markers (Fascin, CLIP-170/Restin) | 135 | ||
| CD74 | 136 | ||
| Other Biologic Markers in Hodgkin Lymphoma | 136 | ||
| Cytokines and Chemokines in Hodgkin Lymphoma | 137 | ||
| Antibody Specifications | 137 | ||
| Immunostaining Pitfalls | 138 | ||
| CD15 Antigen | 138 | ||
| CD30 Antigen | 139 | ||
| CD45 (Leukocyte Common Antigen) | 139 | ||
| CD20 and T-Cell Antigens | 139 | ||
| Diagnostic Immunohistochemistry | 139 | ||
| Non-Hodgkin Lymphomas | 139 | ||
| Anaplastic Large Cell Lymphoma | 139 | ||
| Lymphoepithelioid Cell Variant of Peripheral T-Cell Lymphoma (Lennert Lymphoma) | 140 | ||
| Peripheral T-Cell Lymphoma Not Otherwise Specified | 141 | ||
| Angioimmunoblastic T-Cell Lymphoma | 142 | ||
| Nodal Involvement by Cutaneous CD30-Postive Lymphomas | 142 | ||
| Primary Mediastinal B-Cell Lymphoma | 142 | ||
| T-Cell–Rich B-Cell Lymphoma | 142 | ||
| Hodgkin-Like Posttransplant Lymphoproliferative Disorder (HL-PTLD) | 143 | ||
| Classic Hodgkin Lymphoma in Chronic Lymphocytic Leukemia and Hodgkin-Like Cells in Chronic Lymphocytic Leukemia | 143 | ||
| Nonlymphoid Tumors | 143 | ||
| Pseudoneoplastic Look-Alikes | 143 | ||
| Infectious Mononucleosis | 143 | ||
| Cytomegalovirus Lymphadenitis | 143 | ||
| Interfollicular Lymphadenitis | 144 | ||
| Granulomatous Lymphadenitis | 144 | ||
| Molecular Anatomic Pathology | 144 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 144 | ||
| Theranostic Applications | 145 | ||
| CD20 and Monoclonal Antibody (Rituximab) Therapy | 145 | ||
| CD40 | 145 | ||
| CD30 | 145 | ||
| Anti–Epstein-Barr Virus Therapy | 145 | ||
| Interleukin-2 Receptor | 145 | ||
| Chemokine Receptor 4 (CCR4) | 145 | ||
| Galectin | 145 | ||
| Macrophages and Prognosis | 145 | ||
| Summary | 145 | ||
| References | 147 | ||
| 6 Immunohistology of Non-Hodgkin Lymphoma | 148 | ||
| Overview | 148 | ||
| Antigens for Evaluation of Hematologic Disorders | 148 | ||
| B-Cell–Associated Antigens | 148 | ||
| CD20 | 148 | ||
| Pax-5 | 150 | ||
| CD79a | 150 | ||
| Bcl-6 | 150 | ||
| MUM1/IRF4 | 150 | ||
| OCT-2 and BOB.1 | 150 | ||
| Other Important Markers | 151 | ||
| CD138 | 151 | ||
| CD30 | 151 | ||
| Anaplastic Lymphoma Kinase | 151 | ||
| Terminal Deoxynucleotidyl Transferase | 151 | ||
| CD34 | 151 | ||
| CD43 | 152 | ||
| Cyclin D1 | 152 | ||
| BCL2 | 152 | ||
| CD117 | 152 | ||
| T-Cell–Associated Antigens | 152 | ||
| CD2 | 152 | ||
| CD3 | 152 | ||
| CD4/CD8 | 152 | ||
| CD5 | 153 | ||
| CD7 | 153 | ||
| TIA1, Granzyme B, and Perforin | 153 | ||
| CD56/CD57 | 153 | ||
| β-F1 | 153 | ||
| Establishing the Diagnosis of Lymphoma: Differential Diagnostic Considerations | 154 | ||
| Low-Grade Lymphoma Versus Chronic Lymphoid Hyperplasia | 154 | ||
| High-Grade Malignant Lymphoma Versus Acute Immune Hyperplasia | 154 | ||
| Immunohistochemical Evaluation of Small B-Cell Lymphomas | 157 | ||
| General Immunohistochemical Approach to Diagnosis of Small B-Cell Lymphoid Lesions | 158 | ||
| General Prognostic and Therapeutic Issues | 159 | ||
| Follicular Lymphoma | 160 | ||
| Prognostic and Therapeutic Studies | 160 | ||
| Pitfalls | 160 | ||
| Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | 160 | ||
| Prognostic and Therapeutic Studies | 161 | ||
| Pitfalls | 161 | ||
| Mantle Cell Lymphoma | 161 | ||
| 7 Immunohistology of Melanocytic Neoplasms | 189 | ||
| Overview | 189 | ||
| Biology of Antigens and Antibodies | 189 | ||
| Filamentous Proteins in Melanocytic Neoplasms | 189 | ||
| Cell Membrane Proteins | 189 | ||
| Epithelial Determinants | 190 | ||
| Epithelial Membrane Antigen | 190 | ||
| Carcinoembryonic Antigen | 190 | ||
| Tumor-associated Glycoprotein-72 and BER-EP4 and MOC-31 Antigens | 191 | ||
| Placental-like Alkaline Phosphatase | 191 | ||
| Hematopoietic Markers | 191 | ||
| NB84 | 192 | ||
| Calcium-Binding Proteins | 192 | ||
| S-100 Protein | 192 | ||
| Calretinin | 192 | ||
| Melanocyte-Specific Monoclonal Antibodies | 193 | ||
| gp100 and Pmel-17–Related Monoclonal Antibodies | 193 | ||
| Tyrosinase-Related Antibodies | 195 | ||
| Microphthalmia Transcription Factor Protein | 195 | ||
| p16 | 196 | ||
| PNL2 | 196 | ||
| SOX9 | 196 | ||
| SOX10 | 196 | ||
| Soluble Adenylyl Cyclase | 196 | ||
| Ki-67 | 196 | ||
| Neuroendocrine Markers in Melanocytic Lesions | 196 | ||
| Sentinel Lymph Node Biopsies for Metastatic Melanoma | 197 | ||
| Application of Immunohistochemistry to Selected Differential Diagnoses | 198 | ||
| Melanoma Versus Melanocytic Nevus Variants | 198 | ||
| Proliferative Dermal Nodules in Congenital Nevi Versus Melanoma | 198 | ||
| Primary Versus Secondary Intracutaneous Melanoma | 198 | ||
| Melanoma In Situ Versus Pigmented Actinic Keratosis | 199 | ||
| Melanocytic Neoplasms Versus Histiocytic Proliferations | 199 | ||
| Recognition of Rhabdoid and Sarcomatoid Malignant Melanomas | 200 | ||
| Amelanotic Melanoma Versus Other Epithelioid Malignancies | 200 | ||
| Metastatic Melanoma Versus Malignant Glioma | 201 | ||
| Melanoma Versus Soft Tissue Sarcomas | 202 | ||
| Melanoma Versus Cutaneous Granular Cell Tumor | 202 | ||
| Prognostic Markers and Targeted Therapy for Melanoma | 202 | ||
| Summary | 203 | ||
| References | 203 | ||
| 8 Immunohistology of Metastatic Carcinoma of Unknown Primary Site | 204 | ||
| Overview | 204 | ||
| Cancer of Unknown Primary Site: Clinical Aspects and Economic Considerations | 204 | ||
| Diagnostic Approach to the Study of CUPS: Specimen Preparation | 206 | ||
| Determining Site of Origin: Stepwise Approach | 207 | ||
| Step One: Screening Immunohistochemistry | 207 | ||
| Line of Differentiation: Lymphoid | 207 | ||
| Line of Differentiation: Melanocytic | 208 | ||
| Line of Differentiation: Mesenchymal | 208 | ||
| Line of Differentiation: Epithelial | 208 | ||
| Step Two: The Cytokeratins— An Overview | 208 | ||
| Distribution of Keratin Antigens in Tissues | 209 | ||
| Simple Epithelial Keratins | 209 | ||
| Cytokeratin 19 (CK19). | 210 | ||
| Cytokeratin 7 (CK7). | 210 | ||
| Diagnostic Utility of CK7. | 214 | ||
| Cytokeratin 20 (CK20). | 214 | ||
| Keratins of Stratified Epithelia: Complex Keratins | 216 | ||
| Cytokeratin 5 (CK5) and Cytokeratin 5/6 (Ck5/6). | 216 | ||
| Keratins in Nonepithelial Cells | 217 | ||
| Step Three: Carcinoma Subsets with Frequent Vimentin Coexpression | 219 | ||
| Step Four: Supplemental Epithelial Markers | 220 | ||
| Carcinoembryonic Antigen | 220 | ||
| Epithelial Membrane Antigen | 222 | ||
| BerEP4, Bg8, and MOC-31 | 223 | ||
| Step Five: Focusing on Tumor Differentiation—Cell-Specific Products | 224 | ||
| Neuroendocrine Antibodies | 224 | ||
| Chromogranins | 224 | ||
| Synaptophysin | 224 | ||
| Neural Cell Adhesion Molecule (CD56) and Leu-7 (CD57) | 224 | ||
| Neuron-Specific Enolase | 224 | ||
| Peptide Hormones | 225 | ||
| Cytokeratin Profile of Neuroendocrine Carcinoma | 225 | ||
| Thyroglobulin | 225 | ||
| Thyroid Transcription Factor 1 and Other Lung Markers | 225 | ||
| Calretinin and Wilms Tumor 1 Protein | 226 | ||
| Gross Cystic Disease Fluid Protein and Mammaglobin | 227 | ||
| Hormone Receptors: Estrogen and Progesterone | 228 | ||
| Villin | 229 | ||
| CDX-2 Protein | 229 | ||
| HepPar1 | 231 | ||
| Arginase-1 | 232 | ||
| Deleted in Pancreatic Carcinoma, Locus 4: SMAD4 | 232 | ||
| Prostate Carcinoma Antigens | 232 | ||
| Prostate-Specific Antigen and Prostatic Acid Phosphatase | 232 | ||
| Prostate-Specific Membrane Antigen, Prostein (p501S), NKX3-1 | 233 | ||
| Alpha-Methylacyl-Co-A Racemase | 233 | ||
| Uroplakin III and Thrombomodulin | 233 | ||
| Renal Cell Carcinoma Antigen | 234 | ||
| CD10 | 234 | ||
| Paired Box Gene 2 (PAX2) | 235 | ||
| Paired Box Gene 8 (PAX8) | 235 | ||
| Melan-a and Inhibin in Adrenocortical Tumors | 235 | ||
| Germ Cell Tumor Markers | 236 | ||
| CD5 | 237 | ||
| Combined Antibody (Panel) Approach to Solving Diagnostic Problems | 237 | ||
| Special Clinical Presentations | 237 | ||
| Metastatic Carcinoma in the Pleura Versus Epithelial Mesothelioma | 237 | ||
| Mediastinal Tumors: Type and Site of Origin | 240 | ||
| Peritoneal Carcinomatosis | 241 | ||
| Paget Disease | 241 | ||
| Molecular Approach for Determining Site of Origin | 242 | ||
| Summary | 244 | ||
| References | 244 | ||
| 9 Immunohistology of Head and Neck Lesions | 245 | ||
| Overview | 245 | ||
| Squamoproliferative Lesions | 245 | ||
| Reactive Changes | 245 | ||
| Dysplasia and Conventional Squamous Cell Carcinoma | 245 | ||
| Oropharyngeal Squamous Cell Carcinoma | 250 | ||
| Spindle Cell Squamous Cell Carcinoma | 252 | ||
| Nasal Cavity and Paranasal Sinuses | 254 | ||
| Olfactory Neuroblastoma | 255 | ||
| Sinonasal Undifferentiated Carcinoma | 259 | ||
| Mucosal Melanoma | 260 | ||
| Small Cell Neuroendocrine Carcinoma | 263 | ||
| Pituitary Adenoma | 264 | ||
| Rhabdomyosarcoma | 266 | ||
| Ewing Sarcoma/Primitive Neuroectodermal Tumor | 270 | ||
| Sinonasal Intestinal-Type Adenocarcinoma | 272 | ||
| Glomangiopericytoma (Sinonasal-Type Hemangiopericytoma) | 275 | ||
| Theranostic Applications | 277 | ||
| Nasopharynx | 278 | ||
| Nasopharyngeal Carcinoma | 278 | ||
| Nasopharyngeal Angiofibroma | 280 | ||
| Nasopharyngeal Papillary Adenocarcinoma | 282 | ||
| Oral Cavity | 284 | ||
| Granular Cell Tumor | 284 | ||
| Ectomesenchymal Chondromyxoid Tumor | 286 | ||
| Larynx/Hypopharynx | 287 | ||
| Typical Carcinoid | 287 | ||
| Atypical Carcinoid | 287 | ||
| Small Cell Carcinoma, Neuroendocrine Type | 288 | ||
| Salivary Glands | 290 | ||
| Pleomorphic Adenoma | 290 | ||
| Myoepithelioma | 293 | ||
| Mucoepidermoid Carcinoma | 294 | ||
| Polymorphous Low-Grade Adenocarcinoma | 296 | ||
| Adenoid Cystic Carcinoma | 298 | ||
| Epithelial-Myoepithelial Carcinoma | 301 | ||
| Hyalinizing Clear Cell Carcinoma | 303 | ||
| Salivary Duct Carcinoma | 304 | ||
| Low-Grade Cribriform Cystadenocarcinoma | 307 | ||
| Mammary Analogue Secretory Carcinoma | 308 | ||
| Theranostic Applications | 310 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 310 | ||
| Ear and Temporal Bone | 310 | ||
| Glial Heterotopia | 310 | ||
| Ceruminous Adenoma | 311 | ||
| Paraganglioma | 312 | ||
| Ectopic Meningioma | 314 | ||
| Middle Ear Adenoma | 315 | ||
| Endolymphatic Sac Tumor | 318 | ||
| Metastatic Tumors | 319 | ||
| Lung Carcinoma | 319 | ||
| Metastatic Renal Cell Carcinoma | 320 | ||
| Metastatic Breast or Prostate Adenocarcinoma | 320 | ||
| Summary | 321 | ||
| Acknowledgements | 321 | ||
| References | 321 | ||
| 10 Immunohistology of Endocrine Tumors | 322 | ||
| Overview | 322 | ||
| Biology of Antigens and Antibodies | 322 | ||
| Hormones | 322 | ||
| Enzymes | 322 | ||
| Chromogranins, Secretogranins, and Other Granule Proteins | 323 | ||
| Synaptophysin and Other Synaptic Vesicle Proteins | 324 | ||
| CD57 | 324 | ||
| Neural Cell Adhesion Molecule (CD56) | 324 | ||
| Intermediate Filaments | 325 | ||
| Transcription Factors | 325 | ||
| Somatostatin Receptors | 325 | ||
| Cell-Cycle Markers | 325 | ||
| Pitfalls of Immunohistochemistry of Endocrine Tumors | 326 | ||
| Tumors of Specific Sites | 326 | ||
| Adenohypophysis | 326 | ||
| Molecular Approaches | 328 | ||
| Pineal Gland | 329 | ||
| Follicular Cells and Their Neoplasms | 329 | ||
| Thyroglobulin, T3 and T4, Thyroid Peroxidase, and Thyroid Transcription Factors 1 and 2 | 329 | ||
| Intermediate Filaments | 331 | ||
| Oncogenes and Tumor Suppressor Genes | 333 | ||
| HBME-1 | 334 | ||
| Galectin-3 | 334 | ||
| Other Markers and Marker Panels | 335 | ||
| C Cells and Medullary Thyroid Carcinoma | 337 | ||
| Molecular Approaches | 340 | ||
| Papillary Carcinoma | 340 | ||
| Follicular Adenoma and Carcinoma | 341 | ||
| Poorly Differentiated and Undifferentiated Thyroid Carcinoma | 341 | ||
| Medullary Thyroid Carcinoma | 342 | ||
| Testing for Panels of Mutations | 342 | ||
| Microarray Gene Profiling | 342 | ||
| Theranostics | 342 | ||
| Parathyroid Glands | 343 | ||
| Molecular Approaches | 344 | ||
| Adrenal Gland | 345 | ||
| Cortex | 345 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic and Theranostic Applications. | 348 | ||
| Adrenal Medulla and Extraadrenal Paraganglia | 348 | ||
| Neuroblastoma | 349 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic Applications. | 351 | ||
| Gastrointestinal Endocrine Cells | 352 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic Applications | 353 | ||
| Pancreatic Endocrine Cells | 353 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic Applications | 355 | ||
| Pulmonary Endocrine Cells | 356 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic Applications | 358 | ||
| Endocrine Tumors in Other Sites | 358 | ||
| Cervix | 358 | ||
| Prostate | 359 | ||
| Molecular Approaches | 360 | ||
| Skin | 360 | ||
| Molecular Approaches and Theranostics | 361 | ||
| Breast | 361 | ||
| 11 Immunohistology of the Mediastinum | 363 | ||
| Overview | 363 | ||
| Biology of Antigens and Antibodies | 363 | ||
| Normal Thymus | 363 | ||
| Thymic Epithelial Neoplasms | 365 | ||
| Thymoma | 365 | ||
| Thymoma Variants | 367 | ||
| Micronodular Thymoma with Lymphoid Hyperplasia | 368 | ||
| Adenomatoid Spindle Cell Thymoma | 368 | ||
| Spindle Cell Thymoma with Papillary or Pseudopapillary Features | 368 | ||
| Thymoma with Pseudosarcomatous Stroma | 368 | ||
| Thymoma with Signet-Ring Cell–Like Features | 368 | ||
| Ancient (“Sclerosing”) Thymoma | 368 | ||
| Rhabdomyomatous Thymoma | 368 | ||
| Plasma Cell–Rich Thymoma | 368 | ||
| Desmoplastic Spindle Cell Thymoma | 368 | ||
| Primary Thymic Carcinoma | 369 | ||
| Thymic Carcinoma Variants | 370 | ||
| Micronodular Thymic Carcinoma with Lymphoid Hyperplasia | 370 | ||
| Hepatoid Thymic Carcinoma | 371 | ||
| Papillary Thymic Carcinoma | 371 | ||
| Mucinous Adenocarcinoma of the Thymus | 371 | ||
| Thymic Carcinoma with Rhabdoid Features | 371 | ||
| Thymic Clear Cell Carcinoma | 371 | ||
| Spindle Cell Thymic Carcinoma | 371 | ||
| Salivary Gland–Type Carcinomas of the Thymus | 371 | ||
| Mediastinal Neuroendocrine Neoplasms | 371 | ||
| Thymic Neuroendocrine Carcinomas | 371 | ||
| Mediastinal Paragangliomas | 373 | ||
| Parathyroid Tumors of the Mediastinum | 373 | ||
| Mesothelial Neoplasms of the Mediastinum | 373 | ||
| Mesenchymal Neoplasms of the Mediastinum | 373 | ||
| Fibrous, Fibrohistiocytic, and Myofibroblastic Mediastinal Proliferations | 373 | ||
| Myogenic Neoplasms of the Mediastinum | 375 | ||
| Adipocytic Neoplasms of the Mediastinum | 377 | ||
| Neuroectodermal Tumors of the Mediastinum | 377 | ||
| Vascular and Perivascular Neoplasms of the Mediastinum | 378 | ||
| Mediastinal Germ Cell Tumors | 379 | ||
| Histiocytic Tumors of the Mediastinum | 380 | ||
| Lymphoproliferative Disorders of the Mediastinum | 380 | ||
| Castleman Disease | 381 | ||
| Lymphoblastic Lymphoma | 382 | ||
| Mediastinal Large B-Cell Lymphoma and Mediastinal Gray-Zone Lymphoma | 382 | ||
| Hodgkin Lymphoma | 384 | ||
| Other Mediastinal Lymphoproliferative Disorders | 384 | ||
| Anaplastic Large Cell Lymphoma | 384 | ||
| Mucosa-Associated Lymphoid Tissue Lymphoma | 385 | ||
| Granulocytic Sarcoma (Extramedullary Myelogenous Leukemia) | 385 | ||
| Extraosseous Plasmacytoma | 385 | ||
| Mediastinal Dendritic Cell Tumors | 385 | ||
| Prognostic Markers for Mediastinal Neoplasms | 385 | ||
| Summary | 385 | ||
| References | 385 | ||
| 12 Immunohistology of Lung and Pleural Neoplasms | 386 | ||
| Overview | 386 | ||
| Primary Lung Neoplasms | 387 | ||
| Biology of Antigens and Antibodies | 387 | ||
| Antibodies Used to Detect Nonneuroendocrine Lung Neoplasms | 387 | ||
| Neuroendocrine Lung Neoplasms | 400 | ||
| Antibodies Used to Detect Neuroendocrine Lung Neoplasms | 401 | ||
| Rare Primary Lung Neoplasms | 404 | ||
| Sarcomatoid Carcinoma | 404 | ||
| Pleomorphic Carcinoma | 405 | ||
| Pulmonary Blastoma | 405 | ||
| Primary Sarcoma | 405 | ||
| Kaposi Sarcoma | 405 | ||
| Hemangioendothelioma | 406 | ||
| Angiosarcoma | 406 | ||
| Lymphoproliferative Disorders of the Lung | 407 | ||
| Bronchial-Associated Lymphoid Tissue | 407 | ||
| Lymphocytic Interstitial Pneumonia-Pneumonitis | 408 | ||
| Nodular Lymphoid Infiltrates of Uncertain Nature | 408 | ||
| Lymphomas of the Lung | 409 | ||
| Pulmonary Non-Hodgkin Lymphoma | 409 | ||
| Marginal Zone B-Cell Lymphoma, Mucosal-Associated Lymphoid Tissue Type | 409 | ||
| Multiple Myeloma | 409 | ||
| Chronic Lymphocytic Leukemia–Small Cell Lymphocytic Lymphoma | 409 | ||
| Mantle Cell Lymphoma | 411 | ||
| Follicular Lymphoma | 411 | ||
| Primary Pulmonary Hodgkin Lymphoma | 411 | ||
| Rare Primary Lymphomas in the Lung and Chest Cavity | 411 | ||
| Lymphomatoid Granulomatosis | 411 | ||
| Intravascular Lymphoma | 412 | ||
| Primary Effusion Lymphoma | 412 | ||
| Pyothorax-Associated Lymphoma | 413 | ||
| Secondary Lymphomas that Involve the Lung and Leukemic Infiltrates | 413 | ||
| Erdheim-Chester Disease | 413 | ||
| Pulmonary Langerhans Cell Histiocytosis (Pulmonary Histiocytosis X, Pulmonary Eosinophilic Granuloma) | 413 | ||
| Clear Cell Neoplasm/Sugar Tumor and Perivascular Epithelioid Cell Tumors | 414 | ||
| Lymphangioleiomyomatosis | 415 | ||
| Sclerosing Hemangioma | 415 | ||
| Rhabdoid Tumor | 416 | ||
| Inflammatory Pseudotumor | 417 | ||
| Desmoplastic Small Round Cell Tumor | 417 | ||
| Epithelial-Myoepithelial Neoplasm | 417 | ||
| Granular Cell Tumor | 417 | ||
| Salivary Gland Neoplasm | 417 | ||
| Primary Intrapulmonary Thymoma | 417 | ||
| Pulmonary Meningothelial Nodules | 418 | ||
| Placental Transmogrification of Lung | 418 | ||
| Differential Diagnosis and Pitfalls of Lung Neoplasms | 418 | ||
| Squamous Cell Carcinomas of Lung | 419 | ||
| Primary Versus Metastatic Squamous Cell Carcinoma | 420 | ||
| Basaloid Carcinoma | 420 | ||
| Mucinous Forms of Primary Pulmonary Adenocarcinoma | 421 | ||
| Pulmonary Adenocarcinoma Versus Metastatic Colon Cancer | 422 | ||
| Pulmonary Adenocarcinoma Versus Breast Carcinoma | 422 | ||
| Primary Pulmonary Adenocarcinoma Versus Metastatic Renal Cell Carcinoma | 422 | ||
| Metastatic Carcinoma Versus Primary Pulmonary Adenocarcinoma | 423 | ||
| Neuroendocrine Neoplasms | 423 | ||
| Small Cell Lung Cancer Versus Merkel Cell Carcinoma | 425 | ||
| Lymphomas, Sarcomas, and Melanomas | 426 | ||
| CDX-2 Immunoreactivity | 427 | ||
| Thyroid Transcription Factor 1 Immunoreactivity | 427 | ||
| S-100 Protein Immunoreactivity | 429 | ||
| Surfactant Antibodies | 429 | ||
| Inhibin-Alpha Immunoreactivity | 430 | ||
| Hormone Receptors | 430 | ||
| Germ Cell Markers | 431 | ||
| Thymic Carcinomas | 431 | ||
| Theranostic Applications in Lung Neoplasms | 431 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 432 | ||
| Pleural Neoplasms | 437 | ||
| Biology of Antigens and Antibodies | 447 | ||
| Positive Markers | 447 | ||
| Negative Markers | 456 | ||
| Miscellaneous Antibodies | 459 | ||
| Diagnostic Considerations | 460 | ||
| Sarcomatoid Mesothelioma | 460 | ||
| Transitional Mesothelioma | 462 | ||
| Metastatic Mesothelioma | 462 | ||
| Localized Malignant Mesothelioma | 462 | ||
| Deciduoid Mesothelioma | 462 | ||
| Pleomorphic Mesothelioma | 463 | ||
| Small Cell Mesothelioma | 463 | ||
| Round Cell Mesothelioma | 463 | ||
| Rare Primary Pleural Neoplasms | 463 | ||
| Mesothelioma with Rhabdoid Features | 463 | ||
| Epithelioid Mesothelioma Expressing Mucin and Showing Crystalloid Structures | 464 | ||
| Solitary Fibrous Tumors of the Pleura | 464 | ||
| Pseudomesotheliomatous Carcinomas of the Lung | 465 | ||
| Pseudomesotheliomatous Epithelioid Hemangioendothelioma | 466 | ||
| Calcifying Fibrous Pseudotumor of the Pleura | 466 | ||
| Primary Desmoid Tumors of the Pleura | 467 | ||
| Primary Pleural Thymomas | 467 | ||
| Synovial Sarcomas | 467 | ||
| Pleuropulmonary Blastoma | 467 | ||
| Lymphomas Involving the Pleura | 467 | ||
| Diagnostic Pitfalls of Pleural Neoplasms | 468 | ||
| Mucin-Positive Epithelial Mesothelioma | 469 | ||
| Atypical Carcinoid Presenting as Mesothelioma | 471 | ||
| Lymphohistiocytoid Mesothelioma | 472 | ||
| Well-Differentiated Papillary Epithelial Mesothelioma | 472 | ||
| Cystic Mesothelioma | 473 | ||
| Adenomatoid Tumors | 473 | ||
| Mesothelial Cells in Lymph Nodes | 474 | ||
| Primary Papillary Serous Carcinoma of the Serosa | 474 | ||
| Sarcomatoid Renal Cell Carcinomas | 474 | ||
| Separation of Benign and Malignant Mesothelial Cell Proliferations | 475 | ||
| Malignant Mesothelioma vs. Reactive Mesothelial Hyperplasia | 476 | ||
| Desmoplastic Mesothelioma Versus Reactive Fibrosing Pleuritis | 477 | ||
| Molecular Biology and Theranostic Features in Diffuse Malignant Mesothelioma | 477 | ||
| Prognosis of Mesothelioma Based on Morphology and Immunohistochemical Analysis | 478 | ||
| Summary | 478 | ||
| References | 478 | ||
| 13 Immunohistology of Skin Tumors | 479 | ||
| Overview | 479 | ||
| Epithelial Tumors of the Skin | 479 | ||
| Epidermal Tumors | 479 | ||
| Sweat Duct Tumors | 481 | ||
| Sebaceous Tumors | 484 | ||
| Pilar Tumors | 485 | ||
| Endocrine Tumors | 487 | ||
| Cutaneous Lymphohematopoietic Disorders | 488 | ||
| Lymphoma and Leukemia in the Skin | 488 | ||
| Special Pseudoneoplastic Lymphoid Lesions of the Skin | 492 | ||
| Epidermotropic Infiltrates Resembling Mycosis Fungoides | 492 | ||
| Deep Lymphoid Infiltrates Simulating Small Cell or Mixed B-Cell Lymphomas | 492 | ||
| Cutaneous Large Cell Lymphoid Proliferations that Simulate Large B-Cell Lymphoma | 492 | ||
| Langerhans Cell Histiocytosis/Granulomatosis (“Histiocytosis X”) | 493 | ||
| CD-30 Lymphoproliferative Disorders | 493 | ||
| Mesenchymal Tumors of the Skin | 494 | ||
| Fibroblastic/Myofibroblastic Neoplasms | 494 | ||
| Fibrohistiocytic Neoplasms | 495 | ||
| Tumors with “Pure” or Partial Smooth Muscle Differentiation | 499 | ||
| Nerve Sheath Tumors | 500 | ||
| Vascular Neoplasms | 502 | ||
| Epithelioid Sarcoma | 505 | ||
| Small Round Cell Mesenchymal Tumors | 506 | ||
| Special Topics in Cutaneous Immunohistochemistry | 506 | ||
| Estrogen and Progesterone Receptor Proteins | 506 | ||
| Oncogenes and Other Possibly Prognostic Markers | 506 | ||
| References | 507 | ||
| 14 Immunohistology of the Gastrointestinal Tract | 508 | ||
| Overview | 508 | ||
| Biology of Antigens: General and Tissue Specific | 508 | ||
| General Cytokeratins | 508 | ||
| β-Catenin | 508 | ||
| Cytokeratin 7 | 508 | ||
| Cytokeratin 20 | 508 | ||
| CDX-2 | 508 | ||
| Chromogranin A | 508 | ||
| Cyclooxygenase 2 | 509 | ||
| KIT (CD117) | 509 | ||
| DNA Mismatch Repair Proteins MLH1, MSH2, MSH6, and PMS2 | 509 | ||
| MOC-31 | 509 | ||
| Mucin Core Polypeptides | 509 | ||
| Neuroendocrine Secretory Protein-55 | 510 | ||
| p53 Protein | 510 | ||
| p63 Protein | 510 | ||
| Synaptophysin | 510 | ||
| Villin | 510 | ||
| Diagnostic Immunohistochemistry | 510 | ||
| Epithelial Lesions of the Gastrointestinal Tract | 510 | ||
| Esophagus | 510 | ||
| Barrett Esophagus and the Gastric Cardia | 510 | ||
| Dysplasia in Barrett Esophagus | 510 | ||
| Esophageal Adenocarcinoma | 510 | ||
| Esophageal Squamous Cell Carcinoma | 511 | ||
| Squamous Cell Carcinoma Variants | 512 | ||
| Basaloid Squamous Cell Carcinoma. | 512 | ||
| Adenoid Cystic Carcinoma. | 512 | ||
| Esophageal Carcinomas with Spindle Cell or Mesenchymal Differentiation | 513 | ||
| Stomach | 513 | ||
| Nonneoplastic Conditions | 513 | ||
| Lymphocytic Gastritis. | 513 | ||
| Helicobacter pylori. | 513 | ||
| Atrophic Gastritis, Autoimmune Type. | 513 | ||
| Fundic Gland Polyps. | 514 | ||
| Gastric Adenocarcinoma | 515 | ||
| Cytokeratins. | 515 | ||
| Cytokeratin 7. | 515 | ||
| Cytokeratin 20. | 515 | ||
| Cytokeratins 7 and 20 Coordinate Staining. | 515 | ||
| CDX-2 and Villin. | 515 | ||
| Apomucins. | 515 | ||
| Estrogen and Progesterone Receptors. | 515 | ||
| Gastric Adenocarcinoma Variants | 516 | ||
| Lymphoepithelial-Like Carcinoma. | 516 | ||
| Spindle Cell Differentiation (Sarcomatoid Carcinoma). | 517 | ||
| Yolk Sac, Hepatoid, and Choriocarcinomatous Differentiation. | 517 | ||
| Gastric Adenocarcinoma with Neuroendocrine Differentiation. | 518 | ||
| Key Diagnostic Panels | 518 | ||
| Metastatic Breast Carcinoma Versus Primary Gastric Signet-Ring Cell Carcinoma. | 518 | ||
| Pancreatobiliary Versus Gastric Adenocarcinoma. | 519 | ||
| Lung Versus Gastric Adenocarcinoma. | 519 | ||
| Small Intestine | 519 | ||
| Celiac Disease | 519 | ||
| Adenocarcinoma of the Small Intestine | 519 | ||
| Appendix, Colon, and Rectum | 520 | ||
| Appendix | 520 | ||
| Hirschsprung Disease | 522 | ||
| Colonic Polyps | 522 | ||
| Dysplasia in Inflammatory Bowel Disease | 522 | ||
| Colorectal Adenocarcinoma | 522 | ||
| Cytokeratins 7 and 20. | 522 | ||
| CDX-2. | 522 | ||
| Villin. | 523 | ||
| Other Antibodies. | 523 | ||
| Colorectal Adenocarcinoma with Microsatellite Instability. | 523 | ||
| Adenocarcinoma Variants and Subtypes | 525 | ||
| Signet-Ring Cell Adenocarcinoma. | 525 | ||
| Clear Cell Adenocarcinoma. | 525 | ||
| Undifferentiated Neoplasms and Carcinomas with Rhabdoid Differentiation. | 525 | ||
| Key Diagnostic Panels | 525 | ||
| Colon Versus Lung Adenocarcinoma with a Microsatellite-Stable Colorectal Adenocarcinoma. | 525 | ||
| Colorectal Adenocarcinoma Versus Müllerian Endometrioid Adenocarcinoma. | 525 | ||
| Colorectal Adenocarcinoma Versus Urothelial Carcinoma. | 526 | ||
| Colorectal Adenocarcinoma Versus Prostate Adenocarcinoma. | 526 | ||
| Anus | 526 | ||
| Squamous Cell Carcinoma | 526 | ||
| Anal Gland Adenocarcinoma | 526 | ||
| Anal Paget Disease | 526 | ||
| Neuroendocrine Lesions of the Gastrointestinal Tract | 527 | ||
| Neuroendocrine Tumors of the Esophagus | 528 | ||
| Neuroendocrine Tumors of the Stomach | 528 | ||
| Neuroendocrine Tumors of the Small Bowel | 528 | ||
| Neuroendocrine Tumors of the Appendix | 530 | ||
| Neuroendocrine Tumors of the Colon and Rectum | 531 | ||
| Key Diagnostic Panel for Metastatic Well-Differentiated Neuroendocrine Tumors of Unknown Primary | 531 | ||
| High-Grade (Poorly Differentiated) Neuroendocrine Carcinomas | 531 | ||
| Mesenchymal Lesions of the Gastrointestinal Tract | 532 | ||
| Mesenchymal Lesions Presenting as Mural Masses | 532 | ||
| Gastrointestinal Stromal Tumor | 532 | ||
| CD117 and KIT Gene. | 532 | ||
| CD117 Staining in Gastrointestinal Stromal Tumors. | 532 | ||
| CD117 in Other Lesions. | 533 | ||
| DOG-1 Staining in Gastrointestinal Stromal Tumors. | 533 | ||
| Other Antibodies. | 533 | ||
| Other Mesenchymal Lesions Presenting as Mural Masses | 534 | ||
| Schwannoma. | 534 | ||
| Granular Cell Tumor. | 534 | ||
| Desmoid-Type Fibromatosis. | 534 | ||
| Solitary Fibrous Tumor and Pseudotumor. | 534 | ||
| Smooth Muscle Neoplasms. | 535 | ||
| Melanoma. | 535 | ||
| Differential Diagnosis | 535 | ||
| Mesenchymal Lesions Presenting as Polypoid Lesions | 536 | ||
| Neural Lesions | 536 | ||
| Fibroblastic Lesions | 537 | ||
| Smooth Muscle Lesions | 537 | ||
| Genomic Applications | 537 | ||
| 15 Immunohistology of Pancreas and Hepatobiliary Tract | 540 | ||
| Pancreas | 540 | ||
| Biology of Antigens | 540 | ||
| Epithelial Markers | 540 | ||
| Glandular/Ductal Markers | 540 | ||
| Mucin-Related Glycoproteins and Oncoproteins | 540 | ||
| Mucins. | 541 | ||
| Acinar (Enzymatic) Markers | 541 | ||
| Neuroendocrine Markers | 542 | ||
| Adhesion Molecules and Other Markers | 542 | ||
| E-Cadherin | 542 | ||
| β-Catenin | 542 | ||
| Exocrine Neoplasms | 543 | ||
| Ductal Adenocarcinoma | 543 | ||
| Genomic Applications of Immunohistochemistry | 545 | ||
| Tumor Suppressor Genes. | 545 | ||
| Oncogenes. | 545 | ||
| Novel Tumor Markers. | 545 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 545 | ||
| Other Ductal Carcinomas | 546 | ||
| Undifferentiated Carcinoma | 546 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications. | 546 | ||
| Undifferentiated Carcinoma with Osteoclast-Like Giant Cells | 546 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications. | 547 | ||
| Medullary Carcinoma | 547 | ||
| Adenosquamous Carcinoma | 547 | ||
| Colloid Carcinoma | 547 | ||
| Pancreatic Intraepithelial Neoplasia | 548 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 548 | ||
| Intraductal Papillary Mucinous Neoplasms | 549 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 550 | ||
| Mucinous Cystic Neoplasm | 550 | ||
| Intraductal Tubulopapillary Neoplasm | 551 | ||
| Serous Cystadenoma | 551 | ||
| Acinar Cell Carcinoma | 552 | ||
| Pancreatoblastoma | 553 | ||
| Genomic Applications of Immunohistochemistry | 554 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 554 | ||
| Solid-Pseudopapillary Neoplasm | 554 | ||
| Genomic Applications of Immunohistochemistry | 555 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 555 | ||
| Neuroendocrine Neoplasms | 555 | ||
| Pancreatic Neuroendocrine Tumors | 556 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 557 | ||
| Poorly Differentiated (High-Grade) Neuroendocrine Carcinoma | 558 | ||
| Extrahepatic Biliary Tract (Gallbladder and Extrahepatic Bile Ducts) | 559 | ||
| Epithelial Neoplasms | 559 | ||
| Intraductal and Intracholecystic Neoplasms (Tumoral Intraepithelial Neoplasms) | 559 | ||
| 16 Immunohistology of the Prostate | 584 | ||
| Overview | 584 | ||
| Biology of Antigens and Antibodies | 584 | ||
| Principal Antibodies | 584 | ||
| Prostate-Specific Antigen | 584 | ||
| Prostate-Specific Membrane Antigen | 585 | ||
| Prostatic Acid Phosphatase/ Prostate-Specific Acid Phosphatase | 586 | ||
| Prostein/P501S | 586 | ||
| α-Methylacyl–Coenzyme-A Racemase/P504S | 586 | ||
| High-Molecular-Weight Cytokeratins | 586 | ||
| p63 | 586 | ||
| NKX3-1 | 587 | ||
| Diagnostic Immunohistochemistry of Specific Prostate Lesions | 587 | ||
| Immunohistochemistry in Small Focus of Prostate Carcinoma | 587 | ||
| Immunohistochemistry in Benign Mimics of Prostate Adenocarcinoma | 590 | ||
| Prostatic Atrophy | 590 | ||
| Adenosis | 591 | ||
| Sclerosing Adenosis | 591 | ||
| Xanthoma | 592 | ||
| Posttherapy Changes in Prostate Adenocarcinoma | 594 | ||
| Antiandrogen Therapy | 594 | ||
| Radiation Therapy | 595 | ||
| Prostatic Duct Carcinoma | 596 | ||
| Neuroendocrine Prostatic Neoplasms | 597 | ||
| Urothelial Carcinoma that Involves Prostate and Prostatic Urethra | 598 | ||
| Secondary Involvement of Prostate by Colorectal Adenocarcinoma | 602 | ||
| Prostatic Mesenchymal Tumors | 602 | ||
| Stromal Tumors of Uncertain Malignant Potential and Stromal Sarcomas | 603 | ||
| Smooth Muscle Neoplasms (Leiomyoma/Leiomyosarcoma) | 603 | ||
| Solitary Fibrous Tumor | 604 | ||
| Gastrointestinal Stromal Tumor | 605 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications | 606 | ||
| Emerging Prognostic Factors | 606 | ||
| Proliferation Index | 606 | ||
| Angiogenesis | 607 | ||
| Neuroendocrine Differentiation | 608 | ||
| Morphometry/Karyometry | 608 | ||
| Prostatic Lineage–Specific Markers | 608 | ||
| Epigenetic Changes in Prostate Cancer | 608 | ||
| ERG–ETS Gene Fusions | 608 | ||
| Pik3ca/MTOR Pathway | 608 | ||
| Other Tumor Suppressor Genes and Oncogenes | 609 | ||
| Integrated Genomics | 610 | ||
| Emerging Early Detection Markers and Targets of Therapy | 611 | ||
| Summary | 614 | ||
| References | 614 | ||
| 17 Immunohistology of the Bladder, Kidney, and Testis | 615 | ||
| Overview | 615 | ||
| Immunohistology of the Urinary Bladder | 615 | ||
| Biology of Principal Antigens/Antibodies | 616 | ||
| Cytokeratin 7 and Cytokeratin 20 | 616 | ||
| Uroplakin | 616 | ||
| Thrombomodulin | 617 | ||
| TP63 | 617 | ||
| High-Molecular-Weight Cytokeratin | 617 | ||
| GATA3 | 617 | ||
| Anaplastic Lymphoma Kinase | 617 | ||
| TP53 | 617 | ||
| CDKN2A | 618 | ||
| Retinoblastoma Protein | 618 | ||
| Diagnostic Immunohistochemistry of Specific Bladder Neoplasms | 619 | ||
| Urothelial Carcinoma and Variants | 619 | ||
| Urinary Bladder Adenocarcinoma | 622 | ||
| Small Cell Carcinoma of Urinary Bladder | 622 | ||
| Benign Mimics of Bladder Carcinoma | 623 | ||
| Nephrogenic Adenoma | 623 | ||
| Inflammatory Myofibroblastic Tumor | 624 | ||
| Genomic and Theranostic Applications | 624 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 627 | ||
| Chromosomal Numerical Alteration | 627 | ||
| Receptor Tyrosine Kinases | 627 | ||
| TP53, Cell-Cycle Regulators, and Proliferation Index Markers | 628 | ||
| Gene Expression and Genomic Analysis | 629 | ||
| Epigenetic Alterations | 630 | ||
| Ploidy and Morphometric Analysis | 630 | ||
| Emerging Biomarkers | 630 | ||
| Targeted Therapy and Predictive Markers in Bladder Cancer | 630 | ||
| Immunohistology of Renal Neoplasms | 631 | ||
| Renal Tumors: Specific Antibodies | 632 | ||
| Renal Cell Carcinoma Antibody | 632 | ||
| CD10/Acute Lymphocyte Leukemia Antigen | 632 | ||
| PAX2/PAX8 | 633 | ||
| Epithelial Cell-Adhesion Molecule | 633 | ||
| Kidney-Specific Cadherin | 633 | ||
| Carbonic Anhydrase IX | 633 | ||
| Glutathione S-Transferase Alpha | 634 | ||
| Immunohistology of Specific Renal Tumors | 635 | ||
| Renal Oncocytoma | 635 | ||
| Metanephric Adenoma | 636 | ||
| Clear Cell Renal Cell Carcinoma | 636 | ||
| Papillary Renal Cell Carcinoma | 637 | ||
| Chromophobe Renal Cell Carcinoma | 637 | ||
| Collecting Duct Carcinoma | 638 | ||
| Mucinous Tubular and Spindle Cell Carcinoma | 638 | ||
| Angiomyolipoma | 639 | ||
| Clear Cell Papillary Renal Cell Carcinoma | 640 | ||
| Secondary Tumors of Kidney | 641 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 641 | ||
| Genomic and Theranostic Applications | 643 | ||
| Immunohistology of Testicular Tumors | 644 | ||
| Biology of Principal Antigens/Antibodies | 644 | ||
| OCT4 | 644 | ||
| CD117 (c-Kit) | 644 | ||
| SALL4 | 644 | ||
| Podoplanin (D2-40/M2A) | 644 | ||
| Activator Protein 2 Gamma | 644 | ||
| Placental Alkaline Phosphatase | 645 | ||
| α-Fetoprotein | 645 | ||
| Human Chorionic Gonadotropin | 645 | ||
| Human Placental Lactogen | 645 | ||
| Glypican-3 | 645 | ||
| Inhibin A | 645 | ||
| Diagnostic Immunohistochemistry of Specific Testicular Neoplasms | 645 | ||
| Germ Cell Tumors | 645 | ||
| Intratubular Germ Cell Neoplasia | 645 | ||
| Immunohistochemistry of Germ Cell Tumors | 646 | ||
| Classic Seminoma Versus Nonseminomatous Germ Cell Tumors | 646 | ||
| Extratesticular Primary and Metastatic Germ Cell Tumors | 647 | ||
| Spermatocytic Seminoma | 648 | ||
| Testicular Sex Cord Tumors | 649 | ||
| Leydig Cell Tumor | 649 | ||
| Sertoli Cell Tumor | 649 | ||
| Secondary Tumors of Testis | 649 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 649 | ||
| Summary | 652 | ||
| References | 652 | ||
| 18 Immunohistology of the Female Genital Tract | 653 | ||
| Overview | 653 | ||
| Vulva, Vagina, and Cervix | 653 | ||
| Immunohistochemical Markers | 653 | ||
| p16 | 653 | ||
| Vulva and Vagina | 653 | ||
| Vulvar Paget Disease | 653 | ||
| Vulvovaginal Mesenchymal Lesions | 655 | ||
| Vulvar Granular Cell Tumor | 656 | ||
| Vulvar Papillary Squamous Lesions | 656 | ||
| Vulvar Squamous Intraepithelial Lesion (Vulvar Intraepithelial Neoplasia) | 656 | ||
| Cervix | 658 | ||
| Mesonephric Remnants | 658 | ||
| Cervical Squamous Intraepithelial Lesions | 658 | ||
| Endocervical Adenocarcinoma in Situ | 660 | ||
| Invasive Endocervical Adenocarcinoma | 661 | ||
| Intestinal-Type Endocervical Adenocarcinoma | 661 | ||
| Minimal Deviation Endocervical Adenocarcinoma | 662 | ||
| Adenoid Cystic Carcinoma | 662 | ||
| Adenoid Basal Carcinoma | 663 | ||
| Neuroendocrine Carcinomas | 663 | ||
| Uterus | 664 | ||
| Immunohistochemical Markers | 664 | ||
| Epithelial Markers: Cytokeratins and Epithelial Membrane Antigen | 664 | ||
| PAX8 | 666 | ||
| Vimentin | 666 | ||
| p53 | 666 | ||
| β-Catenin and PTEN | 666 | ||
| Muscle Markers | 666 | ||
| CD10 | 666 | ||
| Wilms Tumor 1 | 667 | ||
| Endometrial Carcinoma | 667 | ||
| Endometrioid Adenocarcinoma | 667 | ||
| Endometrial Serous Carcinoma | 668 | ||
| Clear Cell Carcinoma | 671 | ||
| Other Histologic Subtypes of Endometrial Carcinoma and Secondary Carcinomas, Including Metastases | 671 | ||
| Neuroendocrine Carcinomas | 671 | ||
| Undifferentiated Carcinomas | 672 | ||
| Mixed Epithelial Carcinoma | 672 | ||
| Metastatic Carcinomas | 672 | ||
| Endometrial Carcinoma Staging | 672 | ||
| Myometrial Invasion | 672 | ||
| Lymphovascular Invasion | 672 | ||
| Lymph Node Metastasis and Sentinel Lymph Node Evaluation | 672 | ||
| Synchronous Endometrial and Ovarian, Tubal, and Peritoneal Carcinomas | 672 | ||
| Uterine Mesenchymal Tumors | 673 | ||
| Leiomyoma and Leiomyosarcoma | 673 | ||
| Endometrial Stromal Nodule and Low-Grade Endometrial Stromal Sarcoma | 673 | ||
| Carcinosarcoma | 675 | ||
| Müllerian Adenosarcoma | 675 | ||
| Other Mesenchymal Tumors | 676 | ||
| Undifferentiated Sarcoma | 676 | ||
| Perivascular Epithelioid Cell Tumors | 676 | ||
| Uterine Tumor Resembling Ovarian Sex Cord Tumor | 676 | ||
| Gastrointestinal Stromal Tumor | 676 | ||
| Inflammatory Myofibroblastic Tumor | 678 | ||
| Gestational Trophoblastic Disease | 678 | ||
| Complete Hydatidiform Mole | 678 | ||
| Placental Site Nodule | 679 | ||
| Exaggerated Placental Site | 679 | ||
| Placental Site Trophoblastic Tumor | 679 | ||
| Epithelioid Trophoblastic Tumor | 679 | ||
| Choriocarcinoma | 680 | ||
| Genomic Applications | 680 | ||
| DNA Mismatch Repair Proteins | 680 | ||
| Theranostic Applications | 682 | ||
| Endometrial Carcinoma | 682 | ||
| p53, Estrogen Receptor, and Progesterone Receptor | 682 | ||
| HER2 | 682 | ||
| Uterine Sarcoma | 683 | ||
| Estrogen Receptor, Progesterone Receptor, p53, MIB-1, and p16 | 683 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications to Diagnosis | 683 | ||
| JAZF1-SUZ12 Translocation | 683 | ||
| Gestational Trophoblastic Disease | 683 | ||
| Ovary and Fallopian Tubes | 683 | ||
| Immunohistochemical Markers | 684 | ||
| Cytokeratin | 684 | ||
| Cytokeratin 7 | 684 | ||
| Cytokeratin 20 | 684 | ||
| Antiadenocarcinoma Antibodies | 684 | ||
| PAX8 | 685 | ||
| Carbohydrate Antigen 125 | 685 | ||
| Inhibin | 685 | ||
| Calretinin | 685 | ||
| FOXL2 | 685 | ||
| Steroidogenic Factor 1 | 685 | ||
| Wilms Tumor 1 | 685 | ||
| Placental Alkaline Phosphatase | 686 | ||
| CD117 | 686 | ||
| OCT4 | 686 | ||
| Alpha-Fetoprotein | 686 | ||
| Glypican-3 | 686 | ||
| SALL4 | 686 | ||
| Human Chorionic Gonadotropin | 686 | ||
| S-100 Protein | 687 | ||
| CD45 | 687 | ||
| Markers of Neuroendocrine Differentiation | 687 | ||
| Epithelial Tumors | 687 | ||
| Serous Tumors | 687 | ||
| Most Useful Antibodies: Cytokeratin 7, Wilms Tumor 1 | 687 | ||
| Mucinous Tumors | 688 | ||
| Most Useful Antibodies: Cytokeratin 7, Cytokeratin 20, Pax-8 | 688 | ||
| Endometrioid Tumors | 690 | ||
| Most Useful Antibodies: Cytokeratins 7 and 20, CDX-2, Cytokeratin Cocktail, Epithelial Membrane Antigen, Inhibin, Pax-8 | 690 | ||
| Clear Cell Carcinoma | 692 | ||
| Most Useful Antibodies: Cytokeratins 7 and 20, Hepatocyte Nuclear Factor 1β, Wilms Tumor 1, Epithelial Membrane Antigen, Glypican-3, Pax-8 | 692 | ||
| Brenner Tumors | 693 | ||
| Most Useful Antibodies: Cytokeratins 7 and 20, Wilms Tumor 1 | 693 | ||
| Other Epithelial Tumors | 693 | ||
| Most Useful Antibodies: Cytokeratin, Epithelial Membrane Antigen, CD56, Synaptophysin, Chromogranin, Wilms Tumor 1 | 693 | ||
| Sex Cord–Stromal Tumors | 694 | ||
| Fibroma, Thecoma, and Related Tumors | 695 | ||
| Most Useful Antibodies: Inhibin, Calretinin | 695 | ||
| Granulosa Cell Tumors | 696 | ||
| Most Useful Antibodies: Cytokeratin, Epithelial Membrane Antigen, Inhibin, Calretinin, FOXL2 | 696 | ||
| Sertoli-Leydig Cell Tumor | 697 | ||
| Most Useful Antibodies: Cytokeratin, Epithelial Membrane Antigen, Inhibin, FOXL2, Calretinin | 697 | ||
| Sertoli Cell Tumor | 698 | ||
| Most Useful Antibodies: Cytokeratin, Epithelial Membrane Antigen, Inhibin, Calretinin | 698 | ||
| Sex Cord Tumor with Annular Tubules | 699 | ||
| 19 Immunohistology of the Breast | 710 | ||
| Overview | 710 | ||
| Myoepithelial Cells and Assessment of Stromal Invasion | 710 | ||
| Immunohistochemistry of Papillary Lesions | 717 | ||
| Proliferative Ductal Epithelial Lesions and In Situ Carcinoma | 719 | ||
| Tumor Type Identification by Immunohistochemistry | 721 | ||
| Cell Adhesion: Ductal Versus Lobular Carcinoma | 721 | ||
| Lobular Carcinoma Variants and Former Lobular Variants | 725 | ||
| Pleomorphic Lobular Carcinoma | 725 | ||
| Tubulolobular Carcinoma | 725 | ||
| Histiocytoid Carcinoma | 725 | ||
| Immunohistochemistry for Identifying Special Types of Breast Carcinoma | 725 | ||
| Invasive Micropapillary Carcinoma: Use of Epithelial Membrane Antigen | 725 | ||
| Basal-Like Carcinoma: Use of Basal Cytokeratins | 728 | ||
| Metaplastic Carcinoma: Use of Keratins and Melanoma and Vascular Markers | 729 | ||
| Other Spindle Cell Neoplasms: Myoepithelial and Mesenchymal Tumors | 731 | ||
| Paget Disease of the Breast | 732 | ||
| Detection of Lymphatic Space Invasion | 734 | ||
| Sentinel Lymph Node Examination | 734 | ||
| Sentinel Lymph Node Immunohistochemistry | 736 | ||
| Intraoperative Molecular Testing of Sentinel Lymph Node | 737 | ||
| Systemic Metastasis of Breast Carcinoma | 738 | ||
| Fibroepithelial Tumors | 739 | ||
| Fibroadenoma and Phyllodes Tumor | 739 | ||
| Periductal Stromal Tumor | 742 | ||
| Other Fibroepithelial Lesions | 742 | ||
| Theranostic Applications | 744 | ||
| Hormone Receptors | 744 | ||
| Preanalytic Variables | 745 | ||
| Analytic Variables | 746 | ||
| Postanalytic Interpretation | 746 | ||
| ERBB2 (HER-2/neu) | 748 | ||
| Preanalytic Issues | 749 | ||
| Analytic Issues | 749 | ||
| Postanalytic Issues | 749 | ||
| HER2 Fluorescence In Situ Hybridization and Other In Situ Hybridization Assays | 750 | ||
| Genomic Applications of Immunohistochemistry: Breast Cancer Molecular Classification and Immunogenomics | 752 | ||
| Molecular Classification: “Intrinsic” Gene Set | 752 | ||
| Luminal Tumors | 754 | ||
| Triple-Negative or Basal-Like Tumors | 754 | ||
| ERBB2 (or HER2-Enriched) Tumors | 755 | ||
| 70-Gene Profile (MammaPrint) | 755 | ||
| Wound Response Gene Set | 756 | ||
| 76–Gene Profile (Rotterdam Assay) | 756 | ||
| Recurrence Score Model (Oncotype DX) | 756 | ||
| Two-Gene Ratio, HOXB13:IL17RB Index, and Molecular Grade Index | 757 | ||
| Other Tumor Markers | 758 | ||
| TP53 | 758 | ||
| Mammostrat Panel | 759 | ||
| Ki-67 | 759 | ||
| Epidermal Growth Factor Receptor | 760 | ||
| Urokinase Plasminogen Activator and Plasminogen Activator Inhibitor 1 | 760 | ||
| Insulin-Like Growth Factor Receptor 1 | 760 | ||
| BCL2 | 760 | ||
| FOXA1 | 761 | ||
| GATA3 | 761 | ||
| Summary | 761 | ||
| References | 761 | ||
| 20 Immunohistology of the Nervous System | 762 | ||
| Overview | 762 | ||
| Clinical and Radiologic Perspective of Lesions | 764 | ||
| Nonneoplastic Brain Lesions | 767 | ||
| Reactive Changes | 767 | ||
| Gliosis | 767 | ||
| Macrophages | 767 | ||
| Perivascular Inflammation | 768 | ||
| Fibrosis | 769 | ||
| Infectious Diseases | 770 | ||
| Histopathology | 770 | ||
| Organisms | 771 | ||
| Acquired Immunodeficiency Syndrome | 772 | ||
| Primary Manifestations of Human Immunodeficiency Virus | 772 | ||
| Infections Secondary to Acquired Immunodeficiency Syndrome | 772 | ||
| Progressive Multifocal Leukoencephalopathy | 773 | ||
| Spongiform Encephalopathies | 773 | ||
| Cerebrovascular Diseases | 774 | ||
| Small Vessel Disease | 774 | ||
| Vascular Malformation | 775 | ||
| Tumors of the Nervous System | 775 | ||
| Grading Malignant Potential | 775 | ||
| Gliomas | 778 | ||
| Tumor and Tumor Margin | 778 | ||
| Astrocytomas | 780 | ||
| Pilocytic Astrocytoma (WHO Grade I) | 780 | ||
| Diffuse Astrocytoma (Low-Grade Astrocytoma; WHO Grade II) | 782 | ||
| Gemistocytic Astrocytoma (WHO Grade II) | 782 | ||
| Anaplastic Astrocytoma (WHO Grade III) | 783 | ||
| Other Variants of Astrocytoma | 784 | ||
| Theranostic Applications | 785 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 785 | ||
| Ependymomas | 785 | ||
| Low-Grade Ependymoma | 787 | ||
| Clear Cell Ependymoma | 787 | ||
| Tanycytic Ependymoma | 787 | ||
| Subependymoma (WHO Grade I) | 787 | ||
| Myxopapillary Ependymoma (WHO Grade I; Rarely Grade II) | 787 | ||
| Anaplastic Ependymoma (Malignant Ependymoma; WHO Grade III) | 789 | ||
| Oligodendroglioma | 789 | ||
| Oligoastrocytoma (Mixed Oligodendroglioma-Astrocytoma; WHO Grade II) | 790 | ||
| Anaplastic Oligodendroglioma (Malignant Oligodendroglioma; WHO Grade III) | 791 | ||
| Theranostic Applications. | 791 | ||
| 21 Immunocytology | 829 | ||
| Overview | 829 | ||
| Use of Immunocytology | 829 | ||
| Immunocytology Techniques | 829 | ||
| Specimen Collection | 829 | ||
| Fixation | 832 | ||
| Standardization Issues | 832 | ||
| Rehydration and Storage | 834 | ||
| Antigen Retrieval | 835 | ||
| Controls | 835 | ||
| Specimens of Limited Quality | 835 | ||
| Interpretation and Limitations of Immunocytology | 836 | ||
| Applications of Immunocytology | 837 | ||
| Effusion Cytology | 837 | ||
| Mesothelial Markers | 838 | ||
| Calretinin | 838 | ||
| HBME1 | 838 | ||
| Cytokeratin 5/6 | 838 | ||
| Wilms Tumor Gene 1 | 838 | ||
| D2-40 | 838 | ||
| GLUT-1 | 840 | ||
| Nonmesothelial (Adenocarcinoma) Markers | 840 | ||
| MOC-31 | 840 | ||
| BerEP4 | 840 | ||
| Monoclonal Carcinoembryonic Antigen | 840 | ||
| Tumor-Associated Glycoprotein and B72.3 | 840 | ||
| CD15 and LeuM1 | 840 | ||
| Site-Specific and Other Markers | 843 | ||
| Lung Markers | 843 | ||
| Thyroid Transcription Factor 1 | 843 | ||
| Napsin A | 843 | ||
| p63/p40 | 843 | ||
| Gastrointestinal Markers | 843 | ||
| CDX2 | 843 | ||
| Lymphoid Markers | 843 | ||
| Breast Markers | 846 | ||
| Estrogen Receptor | 846 | ||
| Gross Cystic Fluid Protein 15 (BRST-2) | 846 | ||
| Mammaglobin | 847 | ||
| E-Cadherin and p120 Catenin | 848 | ||
| Ovarian Markers | 848 | ||
| Wilms Tumor Gene Product | 848 | ||
| PAX8 | 848 | ||
| Hepatocyte Nuclear Factor 1β | 848 | ||
| Gynecologic Cytology Markers | 848 | ||
| Markers of Dysplasia | 848 | ||
| CDKN2A | 848 | ||
| ProEx C | 849 | ||
| Proliferation Markers | 850 | ||
| MIB-1 (Ki-67) | 850 | ||
| Infectious Disease Markers | 850 | ||
| Theranostic Applications of Immunocytology | 851 | ||
| CD117 | 851 | ||
| ERBB2 | 851 | ||
| CD20 | 852 | ||
| Tumors of Unknown Primary | 852 | ||
| Summary | 853 | ||
| References | 853 | ||
| 22 Immunohistology of Pediatric Neoplasms | 854 | ||
| Overview | 854 | ||
| Biology of Antigens and Antibodies | 854 | ||
| Principal Antibodies | 854 | ||
| Myogenic Regulatory Proteins | 854 | ||
| CD99 (p30/32 mic2) | 855 | ||
| FLI1 | 855 | ||
| Wilms Tumor 1 | 855 | ||
| SMARCB1 | 855 | ||
| Specific Tumors | 855 | ||
| Neuroblastoma and Neuroblastic Tumors | 855 | ||
| Rhabdomyosarcoma | 858 | ||
| Ewing Sarcoma/Primitive Neuroectodermal Tumor | 862 | ||
| Desmoplastic Small Round Cell Tumor | 865 | ||
| Malignant Rhabdoid Tumor | 868 | ||
| Wilms Tumor | 871 | ||
| Osteosarcoma | 874 | ||
| Summary | 876 | ||
| Acknowledgements | 876 | ||
| References | 876 | ||
| 23 Imaging and Quantitative Immunohistochemistry | 877 | ||
| Overview | 877 | ||
| Imaging Systems | 877 | ||
| Software Algorithms | 878 | ||
| Strengths and Limitations | 881 | ||
| Clinical Applications | 882 | ||
| Breast Biomarkers | 883 | ||
| Proliferation Index | 884 | ||
| Microvessel Density Assessment | 884 | ||
| Summary | 884 | ||
| References | 884 | ||
| Index | 885 | ||
| A | 885 | ||
| B | 888 | ||
| C | 890 | ||
| D | 897 | ||
| E | 899 | ||
| F | 901 | ||
| G | 902 | ||
| H | 904 | ||
| I | 906 | ||
| J | 908 | ||
| K | 908 | ||
| L | 908 | ||
| M | 910 | ||
| N | 915 | ||
| O | 917 | ||
| P | 917 | ||
| Q | 922 | ||
| R | 922 | ||
| S | 923 | ||
| T | 927 | ||
| U | 929 | ||
| V | 930 | ||
| W | 930 | ||
| X | 931 | ||
| Y | 931 | ||
| Z | 931 | ||
| Inside Back Cover | ibc1 |