Additional Information
Book Details
Abstract
User-friendly and concise, the new edition of this popular reference is your #1 guide for the appropriate use of immunohistochemical stains. Dr. David J. Dabbs and leading experts in the field use a consistent, organ system approach to cover all aspects of the field, with an emphasis on the role of genomics in diagnosis and theranostic applications that will better inform treatment options. Each well-written and well-researched chapter is enhanced with diagnostic algorithms, charts, tables, and superb, full-color histologic images, making this text a practical daily resource for all surgical pathologists.
- Features a systematic approach to the diagnostic entities of each organ system, including detailed differential diagnoses, diagnostic algorithms, and immunohistograms that depict immunostaining patterns of tumors.
- Covers many more antigens than other texts, and discusses antibody specifications with tables that convey information on uses, clones, vendors, sources, antibody titers, and types of antigen retrieval.
- Discusses diagnostic pitfalls through immunohistologic differential diagnosis wherever appropriate so you can provide the most accurate diagnoses.
- Contains new material on non-lymphoid malignancies, Hodgkin/non-Hodgkin lymphoma, and an expanded chapter on digital imaging and quantilative immunohistochemistry.
- Provides new grading schemes for several organs, along with new antibodies to cover more genomic immunohistochemistry applications.
- Offers more emphasis in the breast section of "eyes on" tissue for molecular/IHC prognostics compared to the current trend of gene-expression profiling of breast cancer.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Inside Front Cover | ifc1 | ||
| Diagnostic Immunohistochemistry | i | ||
| Copyright Page | iv | ||
| Dedication | v | ||
| Contributors | vi | ||
| Preface | viii | ||
| How to Use This Book | ix | ||
| Table Of Contents | xi | ||
| 1 Techniques of Immunohistochemistry | 1 | ||
| Overview | 1 | ||
| Basic Principles of Immunohistochemistry | 2 | ||
| Antibodies as Specific Reagents for Detection of Proteomic Targets | 3 | ||
| Blocking Nonspecific Background Staining | 4 | ||
| Detection Systems | 4 | ||
| Direct-Conjugate-Labeled Antibody Method | 5 | ||
| Indirect, or Sandwich, Procedure | 6 | ||
| Unlabeled Antibody Methods | 6 | ||
| Enzyme Bridge Technique | 6 | ||
| Peroxidase-Anti-Peroxidase Method | 6 | ||
| Biotin-Avidin Procedure | 6 | ||
| Avidin-Biotin Complex Procedure | 7 | ||
| Biotin-Streptavidin Systems | 7 | ||
| Alkaline Phosphatase Labels, Double Labeling (Multiplex) Tests, 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 | 10 | ||
| Titration of Primary Antibody and Detection System | 11 | ||
| Establishing a New Immunohistochemical Test in the Laboratory | 12 | ||
| Quality Control and Standardization | 13 | ||
| Sample Preparation | 13 | ||
| Validation of Reagents, Protocols, Controls, and Testing Results | 14 | ||
| Internal Reference Standards for Quantification and the Evaluation of Sample Preparation | 19 | ||
| Tissue Fixation, Processing, and Antigen Retrieval Techniques | 20 | ||
| Antigen Retrieval | 20 | ||
| Heating Conditions | 22 | ||
| Chemical Composition and pH of the Antigen Retrieval Solution | 23 | ||
| Test-Battery Approach for Antigen Retrieval Technique | 24 | ||
| Techniques, Protocols, and Troubleshooting | 24 | ||
| Antigen Retrieval by the Microwave Heating Method | 24 | ||
| Blocking Nonspecific Staining | 25 | ||
| Washing Steps | 25 | ||
| Incubation of Primary Antibody | 25 | ||
| Incubation of Detection Reagents | 25 | ||
| Chromogens and Substrates | 26 | ||
| Counterstaining and Mounting Slides | 27 | ||
| Double Labeling or Multiplex Immunoenzymatic Techniques | 29 | ||
| Automation | 31 | ||
| Quantification: Development of Reference Standards and Standard Curves for Calculation of Antigen Content in Tissue Section | 33 | ||
| Protein “Spots” | 34 | ||
| Faux Tissues and Histoids | 34 | ||
| Quantitative Internal Reference Standards | 34 | ||
| Quantitative In Situ Proteomics | 34 | ||
| Technical Issues: Troubleshooting | 34 | ||
| Absence of Immunoreactivity in Both Test Specimen and Control | 36 | ||
| Negative Test Specimen With Appropriate Immunoreactivity in Positive Control | 37 | ||
| Weak Immunoreactivity in Test Specimen With Appropriate Reactivity in Positive Control | 39 | ||
| Background Staining | 39 | ||
| Artefactual Staining | 39 | ||
| Summary of Amplification Methods | 40 | ||
| Predetection Amplification | 40 | ||
| Detection-Phase Amplification | 40 | ||
| Postdetection Amplification | 41 | ||
| Future Directions: Companion Diagnostics Present New Challenges for Immunohistochemistry | 41 | ||
| The “First” Predictive Biomarker | 41 | ||
| Predictive Biomarkers: Companion Versus Complementary | 41 | ||
| Method: Control and Validation | 42 | ||
| Other Types of Methods for Companion Diagnostics | 43 | ||
| Multiple Marker Analysis | 44 | ||
| New Approaches to Multiplex Immunohistochemistry | 44 | ||
| Spatially Resolved, Multiplexed Digital Immunohistochemistry in Formalin-Fixed Paraffin-Embedded Sections | 45 | ||
| Status in 2017—The End of the Beginning | 46 | ||
| Conclusion | 46 | ||
| Selected References | 46 | ||
| References | 46.e1 | ||
| 2 Molecular Anatomic Pathology | 47 | ||
| General Principles of Molecular Biology | 47 | ||
| Deoxyribonucleic Acid | 47 | ||
| Ribonucleic Acid | 48 | ||
| Protein | 49 | ||
| Genetic Polymorphism and Mutations | 49 | ||
| Specimen Requirements for Molecular Testing | 49 | ||
| Common Techniques for Molecular Analysis | 50 | ||
| Polymerase Chain Reaction | 50 | ||
| Reverse Transcription Polymerase Chain Reaction | 50 | ||
| Real-Time Polymerase Chain Reaction | 51 | ||
| Polymerase Chain Reaction–Restriction Fragment Length Polymorphism Analysis | 52 | ||
| Single-Strand Conformation Polymorphism | 52 | ||
| Allele-Specific Polymerase Chain Reaction and Allele-Specific Hybridization | 53 | ||
| DNA Sequencing Analysis: Conventional Sequencing | 53 | ||
| Next-Generation Sequencing | 54 | ||
| Fluorescence in situ Hybridization | 55 | ||
| Comparative Genomic Hybridization | 56 | ||
| DNA Microarrays | 57 | ||
| Detection of Small-Scale Mutations | 57 | ||
| Detection of Chromosomal Rearrangements | 58 | ||
| Detection of Chromosomal Deletions/Loss of Heterozygosity Analysis | 58 | ||
| Detection of Microsatellite Instability | 59 | ||
| DNA-Based Tissue Identity Testing | 59 | ||
| Summary | 62 | ||
| Selected References | 62 | ||
| References | 62.e1 | ||
| 3 Immunohistology of Infectious Diseases | 63 | ||
| Viral Infections | 63 | ||
| Hepatitis B | 64 | ||
| Herpesviruses | 64 | ||
| Adenoviruses | 66 | ||
| Parvovirus B19 Infection | 67 | ||
| Viral Hemorrhagic Fevers | 67 | ||
| Polyomaviruses | 68 | ||
| Other Viral Infections | 68 | ||
| Bacterial Infections | 69 | ||
| Helicobacter pylori Infection | 69 | ||
| Whipple Disease | 70 | ||
| Rocky Mountain Spotted Fever | 70 | ||
| Bartonella Infections | 71 | ||
| Syphilis | 71 | ||
| Mycobacterium tuberculosis Infection | 71 | ||
| Other Bacterial Infections | 72 | ||
| Fungal Infections | 72 | ||
| Protozoal Infections | 73 | ||
| Emerging Infectious Diseases | 74 | ||
| Hantavirus Pulmonary Syndrome | 74 | ||
| West Nile Virus Encephalitis | 74 | ||
| Enterovirus 71 Encephalomyelitis | 74 | ||
| Nipah Virus Infection | 75 | ||
| Zika Virus Infections | 75 | ||
| Middle East Respiratory Syndrome Coronavirus | 75 | ||
| Ehrlichioses | 76 | ||
| Pathologists, Immunohistochemistry, and Bioterrorism | 76 | ||
| Anthrax | 77 | ||
| Tularemia | 77 | ||
| Plague | 78 | ||
| Beyond Immunohistology: Molecular Diagnostic Applications | 78 | ||
| Selected References | 81 | ||
| References | 81.e1 | ||
| 4 Immunohistology of Neoplasms of Soft Tissue and Bone | 82 | ||
| Overview | 82 | ||
| Biology of Antigens and Antibodies | 82 | ||
| Intermediate Filament Proteins | 82 | ||
| Keratins | 83 | ||
| Neurofilament Proteins | 83 | ||
| Glial Fibrillary Acidic Protein | 83 | ||
| Vimentin | 84 | ||
| Epithelial Markers | 84 | ||
| Epithelial Membrane Antigen | 84 | ||
| Other Epithelial Markers | 84 | ||
| Markers of Muscle Differentiation | 84 | ||
| Desmin | 84 | ||
| Actins | 85 | ||
| Other Sarcomeric Contractile Proteins | 86 | ||
| Caldesmon | 86 | ||
| Calponin | 86 | ||
| Markers of Skeletal Muscle Differentiation | 86 | ||
| Myoglobin | 86 | ||
| MYOD1 and Myogenin | 86 | ||
| S100 Protein | 87 | ||
| SOX10 | 87 | ||
| Potential Markers of Nerve Sheath Differentiation | 87 | ||
| CD56 (Neural Cell Adhesion Molecule) and CD57 (NKH1/LEU19 and LEU7/HNK-1) | 87 | ||
| Collagen Type IV and Laminin | 88 | ||
| Claudin-1 | 88 | ||
| Markers of Endothelial Differentiation | 88 | ||
| Factor VIII-Related Antigen (Von Willebrand Factor) | 88 | ||
| CD34 | 89 | ||
| CD31 | 89 | ||
| Friend Leukemia Virus Integration 1 | 89 | ||
| V-E26 Transformation-Specific Avian Erythroblastosis Virus E26 Oncogene Homolog | 89 | ||
| Glucose Transporter Type 1 | 90 | ||
| Prospero-Related Homeobox 1 | 90 | ||
| Claudin-5 | 90 | ||
| Thrombomodulin | 91 | ||
| Ulex europaeus I Agglutinin | 91 | ||
| Podoplanin | 91 | ||
| Wilms Tumor 1 | 91 | ||
| Vascular Endothelial Growth Factor Receptor 3 | 91 | ||
| Fibrohistiocytic Markers | 92 | ||
| CD68 | 92 | ||
| CD163 | 92 | ||
| Lysozyme (Muramidase) | 92 | ||
| Factor XIIIa | 92 | ||
| NKI/C3 | 92 | ||
| Markers of Melanocytic Differentiation | 92 | ||
| Human Melanoma Black 45 | 92 | ||
| Melan A | 93 | ||
| Microphthalmia-Associated Transcription Factor | 93 | ||
| Tyrosinase | 93 | ||
| Other Useful Markers in Evaluation of Soft Tissue and Bone Tumors | 93 | ||
| β-Catenin | 93 | ||
| Anaplastic Lymphoma Kinase | 94 | ||
| CD99 | 94 | ||
| Neuroblastoma Marker | 94 | ||
| Transcription Factor E3 | 94 | ||
| Murine Double-Minute 2 Homolog and Cyclin-Dependent Kinase 4 | 95 | ||
| Retinoblastoma | 95 | ||
| SMARCB1 | 95 | ||
| STAT6 | 96 | ||
| B-Cell Chronic Lymphocytic Leukemia/Lymphoma 2 | 96 | ||
| Markers Identified Through Gene-Expression Profiling | 96 | ||
| Transducin-Like Enhancer of Split 1 | 96 | ||
| Mucin 4 | 96 | ||
| Immunohistochemical Markers for Evaluation of Bone Tumors: Proposed Markers of Osteoblastic Differentiation | 97 | ||
| Osteocalcin | 97 | ||
| Osteonectin | 97 | ||
| Brachyury | 97 | ||
| Specific Soft Tissue and Bone Tumors | 98 | ||
| Vascular Tumors | 98 | ||
| Benign Vascular Tumors | 98 | ||
| Hemangioma/Lymphangioma | 98 | ||
| Locally Aggressive and Rarely Metastasizing Vascular Tumors | 99 | ||
| Kaposiform Hemangioendothelioma | 99 | ||
| Pseudomyogenic Hemangioendothelioma | 100 | ||
| Malignant Vascular Tumors | 100 | ||
| Epithelioid Hemangioendothelioma | 100 | ||
| Angiosarcoma | 103 | ||
| Kaposi Sarcoma | 105 | ||
| Skeletal Muscle Tumors | 105 | ||
| Benign Skeletal Muscle Tumors | 105 | ||
| Rhabdomyoma | 105 | ||
| Rhabdomyosarcoma | 106 | ||
| Embryonal Rhabdomyosarcoma. | 106 | ||
| Alveolar Rhabdomyosarcoma. | 107 | ||
| Pleomorphic Rhabdomyosarcoma. | 108 | ||
| Spindle Cell/Sclerosing Rhabdomyosarcoma. | 108 | ||
| Epithelioid Rhabdomyosarcoma. | 109 | ||
| Fibroblastic Tumors | 109 | ||
| Fibromatoses | 109 | ||
| Angiomyofibroblastoma | 110 | ||
| Solitary Fibrous Tumor | 111 | ||
| Low-Grade Fibromyxoid Sarcoma | 112 | ||
| Sclerosing Epithelioid Fibrosarcoma | 112 | ||
| Myxoinflammatory Fibroblastic Sarcoma | 113 | ||
| Angiomatoid Fibrous Histiocytoma | 113 | ||
| Inflammatory Myofibroblastic Tumor | 113 | ||
| Infantile Fibrosarcoma | 114 | ||
| Myxofibrosarcoma | 115 | ||
| Smooth Muscle Tumors | 115 | ||
| Benign Smooth Muscle Tumors | 115 | ||
| Leiomyosarcoma | 115 | ||
| Pleomorphic Leiomyosarcoma. | 115 | ||
| Other Morphologic Variants of Leiomyosarcoma. | 116 | ||
| Epstein-Barr Virus-Associated Smooth Muscle Tumors | 116 | ||
| Perivascular Epithelioid Cell Family of Tumors | 117 | ||
| Nerve Sheath Tumors | 118 | ||
| Benign Peripheral Nerve Sheath Tumors | 118 | ||
| Neurofibroma and Schwannoma | 118 | ||
| Perineurioma | 119 | ||
| Granular Cell Tumor | 119 | ||
| Malignant Peripheral Nerve Sheath Tumors | 120 | ||
| Epithelioid Malignant Peripheral Nerve Sheath Tumor | 122 | ||
| Adipocytic Tumors | 122 | ||
| Spindle Cell Lipoma and Pleomorphic Lipoma | 122 | ||
| Well-Differentiated and Dedifferentiated Liposarcoma | 122 | ||
| Pleomorphic Liposarcoma | 123 | ||
| Myxoid Liposarcoma | 123 | ||
| Other Primary Neoplasms of Soft Tissue | 124 | ||
| Desmoplastic Small Round Cell Tumor | 124 | ||
| Ossifying Fibromyxoid Tumor | 125 | ||
| Synovial Sarcoma | 125 | ||
| Epithelioid Sarcoma | 126 | ||
| Clear Cell Sarcoma of Tendons and Aponeuroses | 126 | ||
| Clear Cell Sarcoma–Like Tumor of the Gastrointestinal Tract | 127 | ||
| Alveolar Soft Part Sarcoma | 127 | ||
| Extraskeletal Myxoid Chondrosarcoma | 129 | ||
| Neuroblastoma | 129 | ||
| Myoepithelial Tumors | 129 | ||
| Soft Tissue Osteosarcoma | 130 | ||
| Deep (“Aggressive”) Angiomyxoma | 130 | ||
| Extrarenal Malignant Rhabdoid Tumor | 130 | ||
| Cartilaginous Tumors of Bone | 130 | ||
| Chondroblastoma | 130 | ||
| Chondrosarcoma | 131 | ||
| Mesenchymal Chondrosarcoma | 131 | ||
| Clear Cell Chondrosarcoma | 131 | ||
| Fibrous Tumors of Bone | 131 | ||
| Chondromyxoid Fibroma | 131 | ||
| Desmoplastic Fibroma of Bone | 131 | ||
| Bone-Forming Tumors | 131 | ||
| Osteosarcoma | 131 | ||
| Other Selected Bone Tumors | 132 | ||
| Ewing Sarcoma | 132 | ||
| Chordoma | 133 | ||
| Giant Cell Tumors of Bone and Soft Tissue | 134 | ||
| Langerhans Cell Histiocytosis | 135 | ||
| Erdheim-Chester Disease | 135 | ||
| Adamantinoma | 135 | ||
| Summary | 135 | ||
| Acknowledgment | 135 | ||
| Selected References | 136 | ||
| References | 136.e1 | ||
| 5 Immunohistology of Bone Marrow, Spleen, and Histiocytic Disorders | 137 | ||
| Overview | 137 | ||
| Bone Marrow Antigens | 137 | ||
| Markers Commonly Used to Identify Immature Populations | 137 | ||
| CD34 | 137 | ||
| CD99 | 137 | ||
| CD117 | 137 | ||
| Terminal Deoxynucleotidyl Transferase | 138 | ||
| Granulocytic/Myeloid Antigens | 138 | ||
| CD33 | 138 | ||
| Myeloperoxidase | 138 | ||
| Lysozyme | 138 | ||
| Megakaryocytic Markers | 138 | ||
| CD42b | 138 | ||
| CD61 | 138 | ||
| Erythroid Markers | 138 | ||
| CD71 | 138 | ||
| E-cadherin | 138 | ||
| Hemoglobin/Glycophorin A | 138 | ||
| Other Important Hematopoietic Markers | 139 | ||
| CD1a | 139 | ||
| CD21 | 139 | ||
| CD35 | 139 | ||
| CD25 | 139 | ||
| CD43 | 139 | ||
| CD68 | 139 | ||
| CD123 | 139 | ||
| CD138/Lambda and Kappa Light Chain | 139 | ||
| CD163 | 140 | ||
| CD207/Langerin | 140 | ||
| BRAF V600E | 140 | ||
| Tryptase | 140 | ||
| Normal Bone Marrow: Immunohistochemical Identification of Normal Components | 140 | ||
| Erythropoiesis | 140 | ||
| Granulopoiesis | 140 | ||
| Megakaryopoiesis | 141 | ||
| Lymphoid Cells | 141 | ||
| Bone Marrow Stroma | 142 | ||
| Myeloid Diseases | 142 | ||
| Myelodysplastic Syndromes | 142 | ||
| Myelodysplastic Syndrome With Fibrosis | 143 | ||
| Hypocellular Myelodysplastic Syndrome | 143 | ||
| Myeloproliferative Neoplasms | 143 | ||
| Chronic Myeloid Leukemia, BCR-ABL1-Positive | 143 | ||
| Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis | 143 | ||
| Myelodysplastic Syndrome/ Myeloproliferative Neoplasms | 144 | ||
| Acute Leukemias | 144 | ||
| Acute Myeloid Leukemias | 144 | ||
| Acute Lymphoblastic Leukemia/Lymphoma | 145 | ||
| Extramedullary Myeloid Tumors | 145 | ||
| Mastocytosis | 146 | ||
| Spleen | 147 | ||
| Normal Architecture of Spleen | 147 | ||
| Evaluation of Myeloid Disorders in Spleen | 149 | ||
| Lymphoid Disorders in Spleen | 150 | ||
| Splenic Vascular Tumors | 150 | ||
| Peliosis | 150 | ||
| Hemangioma | 150 | ||
| Littoral Cell Angioma | 151 | ||
| Hemangioendothelioma and Angiosarcoma | 151 | ||
| Kaposi Sarcoma | 152 | ||
| Nonvascular Stromal Tumors | 152 | ||
| Inflammatory Pseudotumor | 152 | ||
| Inflammatory Myofibroblastic Tumor | 153 | ||
| Inflammatory Pseudotumor-Like Follicular Dendritic Cell Tumor | 153 | ||
| “True” Inflammatory Pseudotumor | 153 | ||
| Splenic Cysts | 153 | ||
| Splenic Hamartoma | 153 | ||
| Histiocytic and Dendritic Neoplasms | 153 | ||
| Summary | 159 | ||
| Selected References | 159 | ||
| References | 159.e1 | ||
| 6 Immunohistology of Lymph Node and Lymph Node Neoplasms | 160 | ||
| Antigens for Evaluation of Hematologic Disorders | 160 | ||
| B-Cell Associated Antigens | 160 | ||
| CD20 | 160 | ||
| PAX5 | 161 | ||
| CD79a | 161 | ||
| BCL6 | 161 | ||
| Multiple Myeloma Oncogene-1/Interferon Regulatory Family 4 | 162 | ||
| OCT2 and BOB1 | 162 | ||
| Other Important Markers | 162 | ||
| CD138 | 162 | ||
| CD30 | 162 | ||
| ALK | 163 | ||
| Terminal Deoxynucleotidyl Transferase | 163 | ||
| CD43 | 163 | ||
| Cyclin D1 | 163 | ||
| BCL2 | 163 | ||
| T-Cell Associated Antigens | 163 | ||
| CD2 | 163 | ||
| CD3 | 164 | ||
| CD4/CD8 | 164 | ||
| CD5 | 164 | ||
| CD7 | 164 | ||
| TIA1/Granzyme B/Perforin | 164 | ||
| CD56/CD57 | 164 | ||
| Beta F1 | 164 | ||
| Lymphoid Enhancer-Binding Factor 1 | 165 | ||
| Additional Markers Useful for Evaluation of Hodgkin Lymphoma | 165 | ||
| IgD | 165 | ||
| PD1 (CD279) and PDL1 | 165 | ||
| CD45 | 165 | ||
| Establishing the Diagnosis of Lymphoma: Differential Diagnostic Considerations | 165 | ||
| Low-Grade Lymphoma Versus Chronic Lymphoid Hyperplasia | 165 | ||
| High-Grade Malignant Lymphoma Versus Acute Immune Hyperplasia | 167 | ||
| Immunohistochemical Evaluation of Small B-Cell Lymphomas | 170 | ||
| General Immunohistochemical Approach to Diagnosis of Small B-Cell Lymphoid Lesions | 170 | ||
| General Prognostic and Therapeutic Issues | 171 | ||
| Follicular Lymphoma | 171 | ||
| 7 Immunohistology of Melanocytic Neoplasms | 203 | ||
| Overview | 203 | ||
| Biology of Antigens and Antibodies | 203 | ||
| Filamentous Proteins in Melanocytic Neoplasms | 203 | ||
| Cell Membrane Proteins | 204 | ||
| Epithelial Determinants | 204 | ||
| Epithelial Membrane Antigen | 204 | ||
| Carcinoembryonic Antigen | 204 | ||
| Tumor-Associated Glycoprotein-72 and BER-EP4 and MOC-31 Antigens | 205 | ||
| Placental-Like Alkaline Phosphatase | 205 | ||
| Hematopoietic Markers | 205 | ||
| NB84 | 206 | ||
| Calcium-Binding Proteins | 206 | ||
| S100 Protein | 206 | ||
| Calretinin | 206 | ||
| Melanocyte-Specific Monoclonal Antibodies | 207 | ||
| gp100 and Pmel-17–Related Monoclonal Antibodies | 207 | ||
| Tyrosinase-Related Antibodies | 209 | ||
| Microphthalmia Transcription Factor Protein | 209 | ||
| p16 | 210 | ||
| PNL2 | 210 | ||
| SOX9 | 210 | ||
| SOX10 | 211 | ||
| Soluble Adenylyl Cyclase | 211 | ||
| Ki-67 | 211 | ||
| Neuroendocrine Markers in Melanocytic Lesions | 211 | ||
| Sentinel Lymph Node Biopsies for Metastatic Melanoma | 212 | ||
| Application of Immunohistochemistry to Selected Differential Diagnoses | 213 | ||
| Melanoma Versus Melanocytic Nevus Variants | 213 | ||
| Proliferative Dermal Nodules in Congenital Nevi Versus Melanoma | 213 | ||
| Primary Versus Secondary Intracutaneous Melanoma | 214 | ||
| Melanoma in situ Versus Pigmented Actinic Keratosis | 214 | ||
| Melanocytic Neoplasms Versus Histiocytic Proliferations | 214 | ||
| Recognition of Rhabdoid and Sarcomatoid Malignant Melanomas | 214 | ||
| Amelanotic Melanoma Versus Other Epithelioid Malignancies | 214 | ||
| Metastatic Melanoma Versus Malignant Glioma | 215 | ||
| Melanoma Versus Soft Tissue Sarcomas | 215 | ||
| Melanoma Versus Cutaneous Granular Cell Tumor | 216 | ||
| Prognostic Markers and Targeted Therapy for Melanoma | 217 | ||
| Summary | 218 | ||
| Selected References | 218 | ||
| References | 218.e1 | ||
| 8 Immunohistology of Carcinoma of Unknown Primary Site | 219 | ||
| Cancer of Unknown Primary Site: Clinical Aspects and Economic Considerations | 219 | ||
| Diagnostic Approach to the Study of Cancer of Unknown Primary Site: Specimen Preparation | 221 | ||
| Determining Site of Origin: Stepwise Approach | 222 | ||
| Step One: Screening Immunohistochemistry | 222 | ||
| Line of Differentiation: Lymphoid | 222 | ||
| Line of Differentiation-Melanocytic | 222 | ||
| Line of Differentiation: Mesenchymal | 222 | ||
| Line of Differentiation: Epithelial | 224 | ||
| Step Two: The Cytokeratins—An Overview | 224 | ||
| Distribution of Keratin Antigens in Tissues | 227 | ||
| Simple Epithelial Keratins | 227 | ||
| Cytokeratin 19. | 227 | ||
| Cytokeratin 7. | 227 | ||
| Diagnostic Utility of Cytokeratin 7. | 229 | ||
| Cytokeratin 20. | 229 | ||
| Keratins of Stratified Epithelia: Complex Keratins | 230 | ||
| Cytokeratin 5 and Cytokeratin 5/6. | 231 | ||
| Keratins in Nonepithelial Cells | 232 | ||
| Step Three: Carcinoma Subsets With Frequent Vimentin Coexpression | 233 | ||
| Step Four: Supplemental Epithelial Markers | 234 | ||
| Carcinoembryonic Antigen | 234 | ||
| Epithelial Membrane Antigen | 236 | ||
| BER-EP4, Bg8 and MOC-31 | 237 | ||
| Step Five: Focusing on Tumor Differentiation-Cell Specific Products | 237 | ||
| Neuroendocrine Antibodies | 238 | ||
| Chromogranins | 238 | ||
| Synaptophysin | 238 | ||
| Neural Cell Adhesion Molecule (CD56) and Leu 7 (CD57) | 238 | ||
| Neuron-Specific Enolase | 238 | ||
| Peptide Hormones | 238 | ||
| Cytokeratin Profile of Neuroendocrine Carcinoma | 238 | ||
| Thyroglobulin | 239 | ||
| Thyroid Transcription Factor-1 and Other Lung Markers | 239 | ||
| Calretinin and Wilms Tumor Protein-1 | 239 | ||
| Gross Cystic Disease Fluid Protein and Mammaglobin | 241 | ||
| Hormone Receptors (Estrogen and Progesterone) | 242 | ||
| GATA-Binding Protein 3 | 243 | ||
| Villin | 243 | ||
| CDX2 | 243 | ||
| SATB2 | 244 | ||
| HepPar-1 | 246 | ||
| Glypican-3 | 246 | ||
| Arginase-1 | 247 | ||
| Deleted in Pancreatic Carcinoma, Locus-4 | 247 | ||
| Prostate Carcinoma Antigens | 247 | ||
| Prostate-Specific Antigen and Prostatic Acid Phosphatase | 247 | ||
| Prostate-Specific Membrane Antigen, Prostein (p501S), NKX3.1 | 248 | ||
| Alpha-Methylacyl-CoA Racemase | 248 | ||
| Uroplakin III, Uroplakin II, and Thrombomodulin | 248 | ||
| Renal Cell Carcinoma Antigen | 249 | ||
| CD10 | 249 | ||
| PAX2 | 250 | ||
| PAX8 | 250 | ||
| Melan-A and Inhibin in Adrenocortical Tumors | 250 | ||
| Germ Cell Tumor Markers | 251 | ||
| CD5 | 252 | ||
| Combined Antibody (Panel) Approach to Solving Diagnostic Problems | 252 | ||
| Special Clinical Presentations | 252 | ||
| Metastatic Carcinoma in the Pleura Versus Epithelial Mesothelioma | 252 | ||
| Mediastinal Tumors: Type and Site of Origin | 252 | ||
| Peritoneal Carcinomatosis | 256 | ||
| Paget Disease | 256 | ||
| Molecular Approach for Determining Site of Origin | 257 | ||
| Summary | 259 | ||
| Selected References | 260 | ||
| References | 260.e1 | ||
| 9 Immunohistology of Head and Neck Lesions | 261 | ||
| Squamoproliferative Lesions | 261 | ||
| Reactive Changes | 261 | ||
| Dysplasia and Conventional Squamous Cell Carcinoma | 261 | ||
| Oropharyngeal Squamous Cell Carcinoma | 264 | ||
| Spindle Cell Squamous Cell Carcinoma | 268 | ||
| Nasal Cavity and Paranasal Sinuses | 269 | ||
| Olfactory Neuroblastoma | 270 | ||
| Sinonasal Undifferentiated Carcinoma | 273 | ||
| NUT Carcinoma | 274 | ||
| Mucosal Melanoma | 276 | ||
| Sinonasal Neuroendocrine Carcinoma | 276 | ||
| Pituitary Adenoma | 280 | ||
| Rhabdomyosarcoma | 283 | ||
| Ewing Sarcoma/Peripheral Neuroectodermal Tumor | 288 | ||
| Sinonasal Intestinal-Type Adenocarcinoma | 291 | ||
| Glomangiopericytoma | 295 | ||
| Biphenotypic Sinonasal Sarcoma | 298 | ||
| Theranostic Applications | 299 | ||
| Nasopharynx | 299 | ||
| Nasopharyngeal Carcinoma | 299 | ||
| Nasopharyngeal Angiofibroma | 302 | ||
| Nasopharyngeal Papillary Adenocarcinoma | 304 | ||
| Oral Cavity | 305 | ||
| Granular Cell Tumor | 305 | ||
| Ectomesenchymal Chondromyxoid Tumor | 306 | ||
| Larynx/Hypopharynx | 308 | ||
| Well-Differentiated Neuroendocrine Carcinoma: Typical Carcinoid | 308 | ||
| Moderately Differentiated Neuroendocrine Carcinoma: Atypical Carcinoid | 308 | ||
| Small Cell Carcinoma and Large Cell Neuroendocrine Carcinoma | 309 | ||
| Salivary Glands | 311 | ||
| Pleomorphic Adenoma | 311 | ||
| Myoepithelioma | 313 | ||
| Mucoepidermoid Carcinoma | 314 | ||
| Polymorphous Adenocarcinoma | 317 | ||
| Adenoid Cystic Carcinoma | 320 | ||
| Epithelial-Myoepithelial Carcinoma | 321 | ||
| Hyalinizing Clear Cell Carcinoma | 324 | ||
| Salivary Duct Carcinoma | 326 | ||
| Intraductal Carcinoma | 329 | ||
| Secretory Carcinoma | 330 | ||
| Theranostic Applications | 332 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 332 | ||
| Ear and Temporal Bone | 332 | ||
| Ceruminous Adenoma | 332 | ||
| Paraganglioma | 334 | ||
| Meningioma | 336 | ||
| Middle Ear Adenoma | 337 | ||
| Endolymphatic Sac Tumor | 340 | ||
| Metastatic Tumors | 341 | ||
| Lung Carcinoma | 341 | ||
| Metastatic Renal Cell Carcinoma | 342 | ||
| Metastatic Breast or Prostate Adenocarcinoma | 342 | ||
| Metastatic Gynecologic Primaries | 342 | ||
| Summary | 343 | ||
| Acknowledgments | 343 | ||
| Selected References | 344 | ||
| References | 344.e1 | ||
| 10 Immunohistology of Endocrine Tumors | 345 | ||
| Overview | 345 | ||
| Biology of Antigens and Antibodies | 345 | ||
| Hormones | 345 | ||
| Enzymes | 345 | ||
| Chromogranins, Secretogranins, and Other Granule Proteins | 346 | ||
| Synaptophysin and Other Synaptic Vesicle Proteins | 347 | ||
| CD57 | 347 | ||
| Neural Cell Adhesion Molecule (CD56) | 347 | ||
| Intermediate Filaments | 348 | ||
| Transcription Factors | 348 | ||
| Somatostatin Receptors | 348 | ||
| Cell-Cycle Markers | 348 | ||
| Pitfalls of Immunohistochemistry of Endocrine Tumors | 349 | ||
| Tumors of Specific Sites | 349 | ||
| Adenohypophysis | 349 | ||
| Molecular Approaches | 351 | ||
| Pineal Gland | 352 | ||
| Follicular Cells and Their Neoplasms | 353 | ||
| Thyroglobulin, T3 and T4, Thyroid Peroxidase, and Thyroid Transcription Factors 1 and 2 | 353 | ||
| Intermediate Filaments | 356 | ||
| Oncogenes and Tumor Suppressor Genes | 357 | ||
| Hector Battifora Mesothelial Cell 1 | 358 | ||
| Galectin-3 | 359 | ||
| Trophoblastic Cell Surface Antigen 2 | 359 | ||
| Other Markers and Marker Panels | 359 | ||
| C Cells and Medullary Thyroid Carcinoma | 361 | ||
| Molecular Approaches | 365 | ||
| Papillary Carcinoma | 365 | ||
| Follicular Adenoma and Carcinoma | 366 | ||
| Poorly Differentiated and Undifferentiated Thyroid Carcinoma | 366 | ||
| Medullary Thyroid Carcinoma | 366 | ||
| Testing for Panels of Mutations | 366 | ||
| Microarray Gene Profiling | 366 | ||
| Theranostics | 367 | ||
| Parathyroid Glands | 367 | ||
| Molecular Approaches | 369 | ||
| Adrenal Gland | 370 | ||
| Cortex | 370 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic and Theranostic Applications. | 373 | ||
| Adrenal Medulla and Extraadrenal Paraganglia | 373 | ||
| Neuroblastoma | 374 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic Applications. | 375 | ||
| Gastrointestinal Endocrine Cells | 376 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic Applications | 378 | ||
| Pancreatic Endocrine Cells | 378 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic Applications | 380 | ||
| Pulmonary Endocrine Cells | 380 | ||
| Beyond Immunohistochemistry: Molecular Diagnostic Applications | 383 | ||
| Endocrine Tumors in Other Sites | 383 | ||
| Cervix | 383 | ||
| Prostate | 384 | ||
| Molecular Approaches | 386 | ||
| Skin | 386 | ||
| Molecular Approaches and Theranostics | 387 | ||
| Breast | 387 | ||
| 11 Immunohistology of the Mediastinum | 390 | ||
| Overview | 390 | ||
| Biology of Antigens and Antibodies | 390 | ||
| Normal Thymus | 390 | ||
| Thymic Epithelial Neoplasms | 392 | ||
| Thymoma | 392 | ||
| Thymoma Variants | 393 | ||
| Micronodular Thymoma With Lymphoid Hyperplasia | 393 | ||
| Adenomatoid Spindle Cell Thymoma | 394 | ||
| Spindle Cell Thymoma With Papillary or Pseudopapillary Features | 395 | ||
| Thymoma With Pseudosarcomatous Stroma | 395 | ||
| Thymoma With Signet-Ring Cell–Like Features | 395 | ||
| Ancient (“Sclerosing”) Thymoma | 395 | ||
| Rhabdomyomatous Thymoma | 395 | ||
| Plasma Cell–Rich Thymoma | 395 | ||
| Desmoplastic Spindle Cell Thymoma | 395 | ||
| Clear Cell Thymoma | 395 | ||
| Thymoma With Glandular Differentiation | 395 | ||
| Spindle Cell Thymoma With Neuroendocrine Morphology | 395 | ||
| Primary Thymic Carcinoma | 396 | ||
| Thymic Carcinoma Variants | 397 | ||
| Micronodular Thymic Carcinoma With Lymphoid Hyperplasia | 397 | ||
| Hepatoid Thymic Carcinoma | 398 | ||
| Papillary Thymic Carcinoma | 398 | ||
| Mucinous Adenocarcinoma of the Thymus | 398 | ||
| Thymic Carcinoma With Rhabdoid Features | 398 | ||
| Thymic Clear Cell Carcinoma | 398 | ||
| Spindle Cell Thymic Carcinoma | 399 | ||
| Salivary Gland–Type Carcinomas of the Thymus | 399 | ||
| Mediastinal Neuroendocrine Neoplasms | 399 | ||
| Thymic Neuroendocrine Carcinomas | 399 | ||
| Mediastinal Paragangliomas | 399 | ||
| Parathyroid Tumors of the Mediastinum | 400 | ||
| Mesothelial Neoplasms of the Mediastinum | 400 | ||
| Mesenchymal Neoplasms of the Mediastinum | 401 | ||
| Fibrous, Fibrohistiocytic, and Myofibroblastic Mediastinal Proliferations | 401 | ||
| Myogenic Neoplasms of the Mediastinum | 403 | ||
| Adipocytic Neoplasms of the Mediastinum | 404 | ||
| Neuroectodermal Tumors of the Mediastinum | 404 | ||
| Vascular and Perivascular Neoplasms of the Mediastinum | 406 | ||
| Mediastinal Germ Cell Tumors | 408 | ||
| Histiocytic Tumors of the Mediastinum | 408 | ||
| Lymphoproliferative Disorders of the Mediastinum | 410 | ||
| Castleman Disease | 410 | ||
| Lymphoblastic Lymphoma | 410 | ||
| Mediastinal Large B-Cell Lymphoma and Mediastinal Gray-Zone Lymphoma | 410 | ||
| Hodgkin Lymphoma | 411 | ||
| Other Mediastinal Lymphoproliferative Disorders | 411 | ||
| Anaplastic Large Cell Lymphoma | 411 | ||
| Mucosa-Associated Lymphoid Tissue Lymphoma | 412 | ||
| Granulocytic Sarcoma (Extramedullary Myelogenous Leukemia) | 412 | ||
| Extraosseous Plasmacytoma | 412 | ||
| Mediastinal Dendritic Cell Tumors | 413 | ||
| Prognostic Markers for Mediastinal Neoplasms | 413 | ||
| Summary | 413 | ||
| Selected References | 413 | ||
| References | 413.e1 | ||
| 12 Immunohistology of Pulmonary and Pleural Neoplasms | 414 | ||
| Malignant Epithelial Neoplasms of the Lung | 414 | ||
| Primary Pulmonary Adenocarcinoma | 415 | ||
| Variants of Primary Adenocarcinoma of the Lung | 419 | ||
| Mucin-Rich, “Colloid” Carcinoma | 419 | ||
| Signet-Ring Cell Adenocarcinoma | 425 | ||
| Papillary Adenocarcinoma | 426 | ||
| Squamous Cell Carcinoma | 427 | ||
| Commonly Used Immunohistochemical Biomarkers in Non-Small Cell Carcinoma and Molecular Biology | 430 | ||
| Large Cell Carcinoma, Pleomorphic Carcinoma, Sarcomatoid Carcinoma, and Giant Cell Carcinoma | 432 | ||
| Large Cell Carcinoma | 432 | ||
| Sarcomatoid Carcinoma, Pleomorphic Carcinoma, and Giant Cell Carcinoma | 432 | ||
| Non-Small Cell Lung Cancer With Spindle and/or Giant Cell Components | 433 | ||
| Biphasic Neoplasms of the Lung | 433 | ||
| Pulmonary Blastoma | 437 | ||
| Immunohistochemical Features of Pulmonary Blastomas | 438 | ||
| Pulmonary Carcinosarcoma | 438 | ||
| Neuroendocrine Tumors of the Lung | 440 | ||
| Immunohistochemical Features | 442 | ||
| Pulmonary Paraganglioma | 442 | ||
| Mesenchymal Tumors of the Lung | 445 | ||
| Intrapulmonary Solitary Fibrous Tumor | 446 | ||
| Histologic Features | 447 | ||
| Immunohistochemical Features | 447 | ||
| Pulmonary Leiomyosarcoma | 448 | ||
| Immunohistochemical Features | 449 | ||
| Monophasic Synovial Sarcoma | 450 | ||
| Histopathologic Features | 451 | ||
| Immunohistochemical Features | 451 | ||
| Primary Vascular Neoplasms of the Lung | 452 | ||
| Unusual Primary Tumors of the Lung | 453 | ||
| Pneumocytoma (Sclerosing Hemangioma) | 454 | ||
| Immunohistochemical Features | 456 | ||
| Granular Cell Tumor | 456 | ||
| Immunohistochemical Features | 458 | ||
| Clear Cell: Sugar Tumor (PEComa) | 458 | ||
| 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”) | 492 | ||
| CD-30 Lymphoproliferative Disorders | 494 | ||
| Mesenchymal Tumors of the Skin | 495 | ||
| Fibroblastic/Myofibroblastic Neoplasms | 495 | ||
| Fibrohistiocytic Neoplasms | 496 | ||
| Tumors With “Pure” or Partial Smooth Muscle Differentiation | 499 | ||
| Nerve Sheath Tumors | 499 | ||
| 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 | ||
| Selected References | 508 | ||
| References | 508.e1 | ||
| 14 Immunohistology of the Gastrointestinal Tract | 509 | ||
| Biology of Antigens and Antibodies: General and Tissue Specific | 509 | ||
| General Cytokeratins | 509 | ||
| β-Catenin | 509 | ||
| Cytokeratin 7 | 509 | ||
| Cytokeratin 20 | 509 | ||
| CDX2 | 509 | ||
| Chromogranin A | 509 | ||
| Cyclooxygenase 2 | 510 | ||
| KIT (CD117) | 510 | ||
| DNA Mismatch Repair Proteins MLH1, MSH2, MSH6, PMS2 | 510 | ||
| MOC-31 | 510 | ||
| Mucin Core Polypeptides | 510 | ||
| p53 Protein | 510 | ||
| p63 and p40 Proteins | 510 | ||
| Synaptophysin | 510 | ||
| Villin | 510 | ||
| Diagnostic Immunohistochemistry: Epithelial Lesions of the Gastrointestinal Tract | 511 | ||
| Esophagus | 511 | ||
| Barrett Esophagus | 511 | ||
| Dysplasia in Barrett Esophagus | 511 | ||
| Esophageal Adenocarcinoma | 511 | ||
| Esophageal Squamous Cell Carcinoma | 512 | ||
| Squamous Cell Carcinoma Variants | 513 | ||
| Basaloid Squamous Cell Carcinoma | 513 | ||
| Adenoid Cystic Carcinoma | 513 | ||
| Esophageal Carcinomas With Spindle Cell or Mesenchymal Differentiation | 514 | ||
| Stomach | 514 | ||
| Nonneoplastic Conditions | 514 | ||
| Lymphocytic Gastritis | 514 | ||
| Helicobacter pylori | 514 | ||
| Atrophic Gastritis, Autoimmune Type | 514 | ||
| Fundic Gland Polyps | 514 | ||
| Gastric Adenocarcinoma | 514 | ||
| Cytokeratins | 516 | ||
| Cytokeratin 7 | 516 | ||
| Cytokeratin 20 | 516 | ||
| Cytokeratins 7 and 20 Coordinate Staining | 516 | ||
| CDX2 and Villin | 517 | ||
| Apomucins | 517 | ||
| Estrogen and Progesterone Receptors | 518 | ||
| Gastric Adenocarcinoma Variant: Lymphoepithelial-Like Carcinoma | 518 | ||
| Rare Gastric Adenocarcinoma Variants | 518 | ||
| Spindle Cell Differentiation (Sarcomatoid Carcinoma). | 518 | ||
| Yolk-Sac, Hepatoid, and Choriocarcinomatous Differentiation. | 518 | ||
| Gastric Adenocarcinoma With Neuroendocrine Differentiation. | 518 | ||
| Key Diagnostic Panels: Gastric Adenocarcinoma | 518 | ||
| Metastatic Breast Carcinoma Versus Primary Gastric Signet-Ring Cell Carcinoma. | 518 | ||
| Pancreaticobiliary Versus Gastric Adenocarcinoma. | 520 | ||
| Lung Versus Gastric Adenocarcinoma. | 520 | ||
| Small Intestine | 520 | ||
| Celiac Disease | 520 | ||
| Neonatal Diarrheal Illness | 520 | ||
| Adenocarcinoma of the Small Intestine | 521 | ||
| Appendix, Colon, and Rectum | 521 | ||
| Appendix | 521 | ||
| Hirschsprung Disease | 523 | ||
| Colonic Polyps | 524 | ||
| Dysplasia in Inflammatory Bowel Disease | 524 | ||
| Colorectal Adenocarcinoma | 524 | ||
| Specific Antibodies in Colorectal Adenocarcinoma | 524 | ||
| Cytokeratins 7 and 20. | 524 | ||
| CDX2. | 524 | ||
| Villin. | 525 | ||
| Other Antibodies. | 525 | ||
| Colorectal Adenocarcinoma With Microsatellite Instability | 525 | ||
| Adenocarcinoma Variants and Subtypes | 526 | ||
| Signet-Ring Cell Adenocarcinoma. | 526 | ||
| Clear Cell Adenocarcinoma. | 526 | ||
| Undifferentiated Neoplasms and Carcinomas With Rhabdoid Differentiation. | 527 | ||
| Key Diagnostic Panels: Colorectal Adenocarcinoma | 527 | ||
| Colon (Microsatellite-Stable) Versus Lung Adenocarcinoma. | 527 | ||
| Colorectal Adenocarcinoma Versus Müllerian Endometrioid Adenocarcinoma. | 527 | ||
| Colorectal Adenocarcinoma Versus Urothelial Carcinoma. | 527 | ||
| Colorectal Adenocarcinoma Versus Prostate Adenocarcinoma. | 528 | ||
| Anus | 528 | ||
| Squamous Cell Carcinoma | 528 | ||
| Anal Gland Adenocarcinoma | 528 | ||
| Anal Paget Disease | 529 | ||
| Diagnostic Immunohistochemistry: Neuroendocrine Lesions of the Gastrointestinal Tract | 530 | ||
| Neuroendocrine Tumors of the Esophagus | 530 | ||
| Neuroendocrine Tumors of the Stomach | 530 | ||
| Neuroendocrine Tumors of the Small Bowel | 531 | ||
| Neuroendocrine Tumors of the Appendix | 532 | ||
| Neuroendocrine Tumors of the Colon and Rectum | 533 | ||
| Key Diagnostic Panels: Metastatic Well-Differentiated Neuroendocrine Tumors of Unknown Primary | 533 | ||
| High-Grade (Poorly Differentiated) Neuroendocrine Carcinomas | 534 | ||
| Diagnostic Immunohistochemistry: Mesenchymal Lesions of the Gastrointestinal Tract | 534 | ||
| Mesenchymal Lesions Presenting as Mural Masses | 534 | ||
| Gastrointestinal Stromal Tumor | 534 | ||
| CD117 and KIT Gene | 534 | ||
| CD117 Staining in Gastrointestinal Stromal Tumors | 535 | ||
| CD117 in Other Lesions | 535 | ||
| DOG-1 Staining in Gastrointestinal Stromal Tumors | 536 | ||
| Other Antibodies | 536 | ||
| Other Mesenchymal Lesions Presenting as Mural Masses | 536 | ||
| Schwannoma | 536 | ||
| Granular Cell Tumor | 537 | ||
| Desmoid-Type Fibromatosis | 537 | ||
| Solitary Fibrous Tumor and Nodular Fibrous Pseudotumor | 537 | ||
| Smooth Muscle Neoplasms | 537 | ||
| Melanoma | 537 | ||
| Differential Diagnosis: Mesenchymal Lesions Presenting as Mural Masses | 538 | ||
| Mesenchymal Lesions Presenting as Polypoid Lesions | 538 | ||
| Neural Lesions | 538 | ||
| Fibroblastic Lesions | 539 | ||
| Smooth Muscle Lesions | 539 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications | 540 | ||
| Epithelial Lesions | 540 | ||
| Gastric and Gastroesophageal Junction Adenocarcinoma: Her2 Immunohistochemistry | 540 | ||
| Gastric Adenocarcinoma: Molecular Classification | 540 | ||
| Refractory Celiac Disease | 540 | ||
| Colorectal Adenocarcinoma: MSI/MMR Protein Testing | 540 | ||
| Colorectal Adenocarcinoma: KRAS Mutational Analysis | 541 | ||
| Neuroendocrine Lesions | 541 | ||
| Mesenchymal Lesions | 541 | ||
| Gastrointestinal Stromal Tumors | 541 | ||
| Desmoid-Type Fibromatosis | 541 | ||
| Summary | 541 | ||
| Selected References | 541 | ||
| References | 541.e1 | ||
| 15 Immunohistology of Pancreas and Hepatobiliary Tract | 542 | ||
| Pancreas | 542 | ||
| Biology of Antigens | 542 | ||
| Epithelial Markers | 542 | ||
| Glandular/Ductal Markers | 542 | ||
| Mucin-Related Glycoproteins and Oncoproteins | 542 | ||
| Mucins. | 543 | ||
| Acinar (Enzymatic) Markers | 543 | ||
| Neuroendocrine Markers | 543 | ||
| Adhesion Molecules, Other Markers | 544 | ||
| E-Cadherin | 544 | ||
| β-Catenin | 544 | ||
| Exocrine Neoplasms | 544 | ||
| Ductal Adenocarcinoma | 544 | ||
| Genomic Applications of Immunohistochemistry | 546 | ||
| Tumor Suppressor Genes. | 546 | ||
| Oncogenes. | 547 | ||
| Novel Tumor Markers. | 547 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 547 | ||
| Other Ductal Carcinomas | 548 | ||
| Undifferentiated Carcinoma | 548 | ||
| 16 Immunohistology of the Prostate | 588 | ||
| Chapter Outline | 588 | ||
| Overview | 588 | ||
| Biology of Antigens and Antibodies | 588 | ||
| Principal Antibodies | 588 | ||
| Prostate-Specific Antigen | 588 | ||
| Prostate-Specific Membrane Antigen | 589 | ||
| Prostatic Acid Phosphatase/Prostate-Specific Acid Phosphatase | 589 | ||
| Prostein/P501S | 589 | ||
| α-Methylacyl–Coenzyme-A Racemase/P504S | 590 | ||
| High-Molecular-Weight Cytokeratins | 590 | ||
| p63 | 590 | ||
| NKX3-1 | 590 | ||
| Diagnostic Immunohistochemistry of Specific Prostate Lesions | 591 | ||
| Immunohistochemistry in Small Focus of Prostate Carcinoma | 591 | ||
| Immunohistochemistry in Benign Mimics of Prostate Adenocarcinoma | 593 | ||
| Prostatic Atrophy | 593 | ||
| Adenosis | 593 | ||
| Sclerosing Adenosis | 595 | ||
| Xanthoma | 595 | ||
| Posttherapy Changes in Prostate Adenocarcinoma | 597 | ||
| Antiandrogen Therapy | 597 | ||
| Radiation Therapy | 598 | ||
| Prostatic Duct Carcinoma | 599 | ||
| Neuroendocrine Prostatic Neoplasms | 600 | ||
| Urothelial Carcinoma That Involves Prostate and Prostatic Urethra | 601 | ||
| Secondary Involvement of Prostate by Colorectal Adenocarcinoma | 604 | ||
| Prostatic Mesenchymal Tumors | 604 | ||
| Stromal Tumors of Uncertain Malignant Potential and Stromal Sarcomas | 604 | ||
| Smooth Muscle Neoplasms (Leiomyoma/Leiomyosarcoma) | 607 | ||
| Solitary Fibrous Tumor | 607 | ||
| Gastrointestinal Stromal Tumor | 607 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications | 608 | ||
| Carcinogenesis and Genetic Susceptibility | 610 | ||
| Environmental Factors and Prostate Cancer Susceptibility | 610 | ||
| Genetic Susceptibility | 611 | ||
| Epigenetic Changes in Prostate Cancer | 614 | ||
| ERG-ETS Gene Fusions | 614 | ||
| PIK3CA/mTOR Pathway | 614 | ||
| Other Tumor Suppressor Genes and Oncogenes | 615 | ||
| Genomics Signatures of Prostate Cancer | 615 | ||
| Emerging Clinical Genomic Molecular Classifier Assays | 621 | ||
| Emerging Early Detection Markers and Targets of Therapy | 622 | ||
| Summary | 623 | ||
| Selected References | 623 | ||
| References | 623.e1 | ||
| 17 Immunohistology of the Bladder, Kidney, and Testis | 624 | ||
| Overview | 624 | ||
| Immunohistology of the Urinary Bladder | 624 | ||
| Biology of Principal Antigens/Antibodies | 624 | ||
| Cytokeratin 7 and Cytokeratin 20 | 624 | ||
| Uroplakin | 625 | ||
| Thrombomodulin | 625 | ||
| TP63 | 625 | ||
| High-Molecular-Weight Cytokeratin | 626 | ||
| GATA3 | 626 | ||
| Anaplastic Lymphoma Kinase | 626 | ||
| TP53 | 626 | ||
| CDKN2A | 626 | ||
| Retinoblastoma Protein | 626 | ||
| Diagnostic Immunohistochemistry of Specific Bladder Neoplasms | 627 | ||
| Urothelial Carcinoma and Variants | 627 | ||
| Urinary Bladder Adenocarcinoma | 630 | ||
| Small Cell Carcinoma of Urinary Bladder | 630 | ||
| Benign Mimics of Bladder Carcinoma | 631 | ||
| Nephrogenic Adenoma | 631 | ||
| Inflammatory Myofibroblastic Tumor | 631 | ||
| Genomic and Theranostic Applications | 633 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 635 | ||
| Chromosomal Numerical Alteration | 635 | ||
| Receptor Tyrosine Kinases | 635 | ||
| TP53, Cell-Cycle Regulators, and Proliferation Index Markers | 636 | ||
| Epigenetic Alterations | 637 | ||
| Gene Expression and Genomic Analysis | 637 | ||
| Targeted Therapy and Predictive Markers in Bladder Cancer | 638 | ||
| Immunohistology of Renal Neoplasms | 640 | ||
| Renal Tumors: Specific Antibodies | 640 | ||
| Renal Cell Carcinoma Antibody | 640 | ||
| CD10/Acute Lymphocyte Leukemia Antigen | 640 | ||
| PAX2/PAX8 | 640 | ||
| Epithelial Cell-Adhesion Molecule | 641 | ||
| Kidney-Specific Cadherin | 642 | ||
| Carbonic Anhydrase IX | 642 | ||
| Glutathione S-Transferase Alpha | 643 | ||
| Immunohistology of Specific Renal Tumors | 643 | ||
| Renal Oncocytoma | 643 | ||
| Metanephric Adenoma | 643 | ||
| Clear Cell Renal Cell Carcinoma | 643 | ||
| Papillary Renal Cell Carcinoma | 644 | ||
| Chromophobe Renal Cell Carcinoma | 645 | ||
| Collecting Duct Carcinoma | 645 | ||
| Mucinous Tubular and Spindle Cell Carcinoma | 646 | ||
| Angiomyolipoma | 647 | ||
| Novel Renal Epithelial Tumors in WHO 2016 Classification | 648 | ||
| Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) Syndrome–Associated RCC | 648 | ||
| Succinate Dehydrogenase–Deficient Renal Cell Carcinoma | 648 | ||
| Tubulocystic Renal Cell Carcinoma | 648 | ||
| Acquired Cystic Disease–Associated Renal Cell Carcinoma | 648 | ||
| Clear Cell Papillary Renal Cell Carcinoma | 650 | ||
| Secondary Tumors of the Kidney | 650 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 650 | ||
| Genomic and Theranostic Applications | 651 | ||
| Immunohistology of Testicular Tumors | 654 | ||
| Biology of Principal Antigens/Antibodies | 654 | ||
| OCT4 | 654 | ||
| CD117 (c-Kit) | 654 | ||
| SALL4 | 654 | ||
| Podoplanin (D2-40/M2A) | 654 | ||
| Activator Protein 2 Gamma | 654 | ||
| Placental Alkaline Phosphatase | 654 | ||
| Alpha-Fetoprotein | 655 | ||
| Human Chorionic Gonadotropin | 655 | ||
| Human Placental Lactogen | 655 | ||
| Glypican-3 | 655 | ||
| Inhibin A | 655 | ||
| Diagnostic Immunohistochemistry of Specific Testicular Neoplasms | 655 | ||
| Germ Cell Tumors | 655 | ||
| Intratubular Germ Cell Neoplasia | 655 | ||
| Immunohistochemistry of Germ Cell Tumors | 655 | ||
| Classic Seminoma Versus Nonseminomatous Germ Cell Tumors | 656 | ||
| Extratesticular Primary and Metastatic Germ Cell Tumors | 657 | ||
| Spermatocytic Seminoma | 658 | ||
| Testicular Sex Cord Tumors | 658 | ||
| Leydig Cell Tumor | 658 | ||
| Sertoli Cell Tumor | 658 | ||
| Secondary Tumors of Testis | 658 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications | 659 | ||
| Summary | 661 | ||
| Selected References | 661 | ||
| References | 661.e1 | ||
| 18 Immunohistology of the Female Genital Tract | 662 | ||
| Biology of Antigens and Antibodies | 662 | ||
| General Markers for Epithelial Tumors | 662 | ||
| Cytokeratin | 662 | ||
| Cytokeratin 7 | 662 | ||
| Cytokeratin 20 | 662 | ||
| PAX8 | 662 | ||
| Antiadenocarcinoma Antibodies | 664 | ||
| Carbohydrate Antigen 125 | 664 | ||
| Markers for Differentiation of Epithelial Tumors | 664 | ||
| p16 | 664 | ||
| p53 | 664 | ||
| Estrogen and Progesterone Receptor | 664 | ||
| Wilms Tumor 1 | 665 | ||
| Napsin A | 665 | ||
| Beta-Catenin and PTEN | 665 | ||
| Vimentin | 665 | ||
| Markers of Sex Cord–Stromal Tumors | 665 | ||
| Inhibin | 665 | ||
| Calretinin | 665 | ||
| FOXL2 | 665 | ||
| Steroidogenic Factor 1 | 665 | ||
| Markers of Germ Cell Tumors | 665 | ||
| Placental Alkaline Phosphatase | 665 | ||
| SALL4 | 666 | ||
| CD117 | 666 | ||
| OCT4 | 666 | ||
| Alpha-Fetoprotein | 666 | ||
| Glypican-3 | 666 | ||
| Human Chorionic Gonadotropin | 666 | ||
| Markers of Neuroendocrine Differentiation | 666 | ||
| Markers of Muscle Differentiation | 667 | ||
| Miscellaneous Markers | 667 | ||
| SMARCA4 (BRG1) Protein | 667 | ||
| S100 Protein | 667 | ||
| CD45 | 667 | ||
| CD10 | 667 | ||
| Lower Female Genital Tract and Uterus | 667 | ||
| Diagnostic Immunohistochemistry of Specific Lesions by Anatomic Site | 667 | ||
| Vulva, Vagina, and Cervix | 667 | ||
| Vulvar Paget Disease | 667 | ||
| Vulvovaginal Mesenchymal Lesions | 668 | ||
| Vulvar Granular Cell Tumor | 669 | ||
| Vulvar Papillary Squamous Lesions | 669 | ||
| Vulvar Squamous Intraepithelial Lesion (Vulvar Intraepithelial Neoplasia) | 669 | ||
| Cervix | 669 | ||
| Mesonephric Remnants. | 669 | ||
| Cervical Squamous Intraepithelial Lesions. | 671 | ||
| Endocervical Adenocarcinoma In Situ. | 672 | ||
| Invasive Endocervical Adenocarcinoma. | 673 | ||
| Intestinal-Type Endocervical Adenocarcinoma. | 674 | ||
| Minimal Deviation Endocervical Adenocarcinoma. | 674 | ||
| Adenoid Cystic Carcinoma. | 674 | ||
| Adenoid Basal Carcinoma. | 675 | ||
| Neuroendocrine Carcinomas. | 675 | ||
| Uterus | 676 | ||
| Endometrial Carcinoma | 676 | ||
| Uterine Endometrioid Adenocarcinoma. | 676 | ||
| Uterine Serous Carcinoma. | 680 | ||
| Clear-Cell Carcinoma. | 680 | ||
| Other Histologic Subtypes of Endometrial Carcinoma and Secondary Carcinomas, Including Metastases. | 682 | ||
| Neuroendocrine Carcinomas | 682 | ||
| Undifferentiated Carcinomas | 683 | ||
| Mixed Epithelial Carcinoma | 683 | ||
| Carcinosarcoma | 683 | ||
| Metastatic Carcinomas | 683 | ||
| Endometrial Carcinoma Staging | 683 | ||
| Myometrial Invasion. | 683 | ||
| Lymphovascular Invasion. | 683 | ||
| Lymph Node Metastasis and Sentinel Lymph Node Evaluation. | 684 | ||
| Synchronous Endometrial and Ovarian, Tubal, and Peritoneal Carcinomas | 684 | ||
| Uterine Mesenchymal Tumors | 684 | ||
| Leiomyoma and Leiomyosarcoma | 684 | ||
| Endometrial Stromal Nodule and Low-Grade Endometrial Stromal Sarcoma | 685 | ||
| High-Grade Endometrial Stromal Sarcoma | 685 | ||
| Müllerian Adenosarcoma | 685 | ||
| Other Mesenchymal Tumors | 686 | ||
| Undifferentiated Sarcoma. | 686 | ||
| Perivascular Epithelioid Cell Tumors. | 687 | ||
| Uterine Tumor Resembling Ovarian Sex Cord Tumor. | 687 | ||
| Gastrointestinal Stromal Tumor. | 687 | ||
| Inflammatory Myofibroblastic Tumor. | 689 | ||
| Gestational Trophoblastic Disease | 689 | ||
| Complete Hydatidiform Mole | 689 | ||
| Placental Site Nodule | 689 | ||
| Exaggerated Placental Site | 690 | ||
| Placental Site Trophoblastic Tumor | 690 | ||
| Epithelioid Trophoblastic Tumor | 690 | ||
| Choriocarcinoma | 690 | ||
| Genomic Applications | 691 | ||
| DNA Mismatch Repair Proteins | 691 | ||
| Theranostic Applications | 692 | ||
| Endometrial Carcinoma | 692 | ||
| p53, Estrogen Receptor, and Progesterone Receptor | 692 | ||
| HER2 | 693 | ||
| Uterine Leiomyoma | 693 | ||
| Fumarate Hydratase | 693 | ||
| Uterine Sarcoma | 693 | ||
| Estrogen Receptor, Progesterone Receptor, p53, MIB-1, and p16. | 693 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications to Diagnosis | 694 | ||
| JAZF1-SUZ12 Translocation | 694 | ||
| DNA Polymerase Epsilon Mutations | 694 | ||
| Gestational Trophoblastic Disease | 694 | ||
| Upper Female Genital Tract | 695 | ||
| Diagnostic Immunohistochemistry of Specific Lesions by Anatomic Site | 695 | ||
| Ovary and Fallopian Tubes | 695 | ||
| Epithelial Tumors | 695 | ||
| Serous Tumors. | 696 | ||
| Mucinous Tumors. | 697 | ||
| Endometrioid Tumors. | 698 | ||
| Clear-Cell Carcinoma. | 699 | ||
| Brenner Tumors. | 700 | ||
| Poorly Differentiated Epithelial Tumors. | 701 | ||
| Small Cell Carcinoma. | 701 | ||
| Sex Cord–Stromal Tumors | 702 | ||
| Fibroma, Thecoma, and Related Tumors. | 703 | ||
| Granulosa Cell Tumors. | 703 | ||
| Sertoli-Leydig Cell Tumor. | 705 | ||
| Sertoli Cell Tumor. | 706 | ||
| Sex Cord Tumor With Annular Tubules. | 706 | ||
| Leydig Cell Tumor. | 706 | ||
| Steroid Cell Tumor. | 706 | ||
| Germ Cell Tumors | 706 | ||
| Dysgerminoma. | 707 | ||
| Yolk Sac Tumor. | 708 | ||
| Embryonal Carcinoma. | 708 | ||
| Choriocarcinoma. | 709 | ||
| Teratomas. | 709 | ||
| Central-Type Primitive Neuroectodermal Tumor. | 710 | ||
| Gonadoblastoma. | 710 | ||
| Metastatic Tumors | 710 | ||
| Peritoneal Mesothelioma | 712 | ||
| Fallopian Tube and Broad Ligament | 713 | ||
| Adenomatoid Tumor | 714 | ||
| Female Adnexal Tumor of Wolffian Origin | 715 | ||
| Genomic Applications | 715 | ||
| DNA Mismatch Repair Proteins | 715 | ||
| BRCA Genes | 715 | ||
| Peutz-Jeghers Syndrome | 715 | ||
| Gorlin Syndrome | 716 | ||
| Theranostic Applications | 716 | ||
| Beyond Immunohistochemistry: Anatomic Molecular Diagnostic Applications to Diagnosis | 716 | ||
| Summary | 717 | ||
| Selected References | 717 | ||
| References | 717.e1 | ||
| 19 Immunohistology of the Breast | 718 | ||
| Myoepithelial Cells and Assessment of Stromal Invasion | 718 | ||
| Immunohistochemistry of Papillary Lesions | 726 | ||
| Proliferative Ductal Epithelial Lesions and In Situ Carcinoma | 728 | ||
| Tumor Type Identification by Immunohistochemistry | 730 | ||
| Cell Adhesion: Ductal Versus Lobular Carcinoma | 730 | ||
| Lobular Carcinoma Variants and Former Lobular Variants | 733 | ||
| Pleomorphic Lobular Carcinoma | 733 | ||
| Tubulolobular Carcinoma | 735 | ||
| Histiocytoid Carcinoma | 736 | ||
| Immunohistochemistry for Identifying Special Types of Breast Carcinomas | 736 | ||
| Invasive Micropapillary Carcinoma—Use of Epithelial Membrane Antigen | 736 | ||
| “Basal-Like” Carcinoma—Use of Basal Cytokeratins | 737 | ||
| Metaplastic Carcinoma—Use of Keratins, Melanoma, and Vascular Markers | 737 | ||
| Other Spindle Cell Neoplasms (Myoepithelial and Mesenchymal Tumors) | 738 | ||
| Paget Disease of the Breast | 741 | ||
| Detection of Lymphatic Space Invasion | 742 | ||
| Sentinel Lymph Node Examination | 742 | ||
| Sentinel Lymph Node Immunohistochemistry | 744 | ||
| Intraoperative Molecular Testing of Sentinel Lymph Node | 745 | ||
| Systemic Metastasis of Breast Carcinoma | 747 | ||
| Fibroepithelial Tumors | 748 | ||
| Fibroadenoma and Phyllodes Tumor | 749 | ||
| Periductal Stromal Tumor | 750 | ||
| Other Fibroepithelial Lesions | 750 | ||
| Theranostic Applications | 751 | ||
| Hormone Receptors | 752 | ||
| Preanalytic | 753 | ||
| Analytic | 754 | ||
| Postanalytic | 755 | ||
| HER-2/neu | 757 | ||
| Preanalytic | 757 | ||
| Analytic | 757 | ||
| Postanalytic | 758 | ||
| HER2 Fluorescence In Situ Hybridization and Other In Situ Hybridization Assays | 758 | ||
| Genomic Applications of Immunohistochemistry: Breast Cancer Molecular Classification and Immunogenomics | 761 | ||
| Molecular Classification (“Intrinsic” Gene Set) | 761 | ||
| Luminal Tumors | 762 | ||
| Triple Negative or Basal-Like Tumors | 762 | ||
| ERBB2 (or HER2 Enriched) Tumors | 763 | ||
| Seventy-Gene Profile (MammaPrint) | 763 | ||
| Wound Response Gene Set | 764 | ||
| Seventy-Six-Gene Profile (Rotterdam Assay) | 764 | ||
| Recurrence Score Model (Oncotype DX) | 764 | ||
| Two-Gene Ratio and Molecular Grade Index (H/I Index and MGI) | 766 | ||
| EndoPredict | 766 | ||
| Prosigna Assay | 766 | ||
| Other Tumor Markers | 767 | ||
| p53 | 767 | ||
| Mammostrat Panel | 768 | ||
| Ki-67 | 768 | ||
| Epidermal Growth Factor Receptor | 768 | ||
| Urokinase Plasminogen Activator and Plasminogen Activator Inhibitor | 769 | ||
| Insulin-Like Growth Factor Receptor 1 | 769 | ||
| BCL2 | 769 | ||
| FOXA1 | 770 | ||
| GATA3 | 770 | ||
| Androgen Receptor | 770 | ||
| Programed Death-Ligand 1 | 770 | ||
| Summary | 771 | ||
| Selected References | 771 | ||
| References | 771.e1 | ||
| 20 Immunohistology of the Nervous System | 772 | ||
| Overview | 772 | ||
| Clinical and Radiologic Perspective of Lesions | 774 | ||
| Nonneoplastic Brain Lesions | 776 | ||
| Reactive Changes | 776 | ||
| Gliosis | 776 | ||
| Macrophages | 777 | ||
| Perivascular Inflammation | 778 | ||
| Fibrosis | 779 | ||
| Infectious Diseases | 779 | ||
| Histopathology | 779 | ||
| Organisms | 780 | ||
| Acquired Immunodeficiency Syndrome | 781 | ||
| Primary Manifestations of Human Immunodeficiency Virus | 781 | ||
| Infections Secondary to Acquired Immunodeficiency Syndrome | 782 | ||
| Progressive Multifocal Leukoencephalopathy | 782 | ||
| Spongiform Encephalopathies | 782 | ||
| Cerebrovascular Diseases | 783 | ||
| Small Vessel Disease | 783 | ||
| Vascular Malformation | 784 | ||
| Tumors of the Nervous System | 784 | ||
| Grading Malignant Potential | 784 | ||
| Gliomas | 785 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications | 786 | ||
| Tumor and Tumor Margin | 786 | ||
| Astrocytomas | 789 | ||
| Pilocytic Astrocytoma (WHO Grade I) | 789 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications. | 791 | ||
| Diffuse Astrocytoma (Low-Grade Astrocytoma; WHO Grade II) | 791 | ||
| Gemistocytic Astrocytoma (WHO Grade II) | 792 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications. | 792 | ||
| Anaplastic Astrocytoma (WHO Grade III) | 793 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications. | 793 | ||
| Other Variants of Astrocytoma | 793 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications. | 794 | ||
| Ependymomas | 795 | ||
| Classic Ependymoma | 795 | ||
| Low-Grade Ependymoma | 796 | ||
| Clear Cell Ependymoma | 797 | ||
| Tanycytic Ependymoma | 797 | ||
| Subependymoma (WHO Grade I) | 797 | ||
| Myxopapillary Ependymoma (WHO Grade I; Rarely Grade II) | 797 | ||
| Anaplastic Ependymoma (Malignant Ependymoma; WHO Grade III) | 797 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications | 798 | ||
| Oligodendroglioma | 798 | ||
| Beyond Immunohistochemistry: Theranostic and Genomic Applications | 799 | ||
| Anaplastic Oligodendroglioma (Malignant Oligodendroglioma; WHO Grade III) | 800 | ||
| 21 Immunocytology | 846 | ||
| Use of Immunocytology | 846 | ||
| Diagnostic Immunocytochemistry: Techniques | 846 | ||
| Specimen Collection | 846 | ||
| Fixation | 849 | ||
| Standardization Issues | 850 | ||
| Rehydration and Storage | 851 | ||
| Antigen Retrieval | 851 | ||
| Controls | 851 | ||
| Specimens of Limited Quality | 851 | ||
| Diagnostic Immunocytochemistry: Applications | 852 | ||
| Effusion Cytology | 852 | ||
| Mesothelial Markers | 852 | ||
| Calretinin | 852 | ||
| HBME1 | 853 | ||
| Cytokeratin 5/6 | 853 | ||
| Wilms Tumor Gene 1 | 855 | ||
| D2-40 | 855 | ||
| GLUT-1 | 855 | ||
| BAP1 | 855 | ||
| Nonmesothelial (Adenocarcinoma) Markers | 855 | ||
| MOC-31 | 855 | ||
| BerEP4 | 855 | ||
| Monoclonal Carcinoembryonic Antigen | 856 | ||
| Tumor-Associated Glycoprotein and B72.3 | 857 | ||
| CD15 and LeuM1 | 858 | ||
| Site-Specific and Other Markers | 858 | ||
| Lung Markers | 858 | ||
| Thyroid Transcription Factor 1 | 858 | ||
| Napsin A | 858 | ||
| p63/p40 | 858 | ||
| Gastrointestinal Markers | 859 | ||
| CDX2 | 859 | ||
| Lymphoid Markers | 859 | ||
| Breast Markers | 861 | ||
| Estrogen Receptor | 861 | ||
| Gross Cystic Fluid Protein 15 (BRST-2) | 861 | ||
| Mammaglobin | 861 | ||
| E-Cadherin and p120 Catenin | 862 | ||
| GATA3 | 862 | ||
| Ovarian Markers | 862 | ||
| Wilms Tumor Gene Product | 863 | ||
| PAX8 | 863 | ||
| Hepatocyte Nuclear Factor 1β | 863 | ||
| Gynecologic Cytology Markers | 863 | ||
| Markers of Dysplasia | 863 | ||
| CDKN2A | 863 | ||
| ProEx C | 863 | ||
| Proliferation Markers | 864 | ||
| MIB-1 (Ki-67) | 864 | ||
| Infectious Disease Markers | 864 | ||
| Markers for Tumors of Unknown Primary | 865 | ||
| Pitfalls in Immunocytochemistry | 867 | ||
| Beyond Immunocytochemistry: Theranostic and Genomic Applications | 868 | ||
| CD117 | 868 | ||
| ERBB2 | 868 | ||
| CD20 | 868 | ||
| PD-L1 and PD-1 | 869 | ||
| Summary | 869 | ||
| Selected References | 869 | ||
| References | 869.e1 | ||
| 22 Immunohistology of Pediatric Neoplasms | 870 | ||
| Overview | 870 | ||
| Biology of Antigens and Antibodies: Principal Antibodies | 870 | ||
| Myogenic Regulatory Proteins | 870 | ||
| CD99 (p30/32 mic2) | 871 | ||
| FLI1 | 871 | ||
| Wilms Tumor 1 | 871 | ||
| SMARCB1 | 871 | ||
| Specific Tumors | 871 | ||
| Neuroblastoma and Neuroblastic Tumors | 871 | ||
| Rhabdomyosarcoma | 874 | ||
| Ewing Sarcoma/Primitive Neuroectodermal Tumor | 879 | ||
| Desmoplastic Small Round Cell Tumor | 881 | ||
| Malignant Rhabdoid Tumor | 884 | ||
| Wilms Tumor | 887 | ||
| Osteosarcoma | 890 | ||
| Summary | 891 | ||
| Acknowledgments | 892 | ||
| Selected References | 892 | ||
| References | 892.e1 | ||
| 23 Imaging and Quantitative Immunohistochemistry | 893 | ||
| Overview | 893 | ||
| Imaging Systems | 893 | ||
| Software Algorithms | 894 | ||
| Strengths and Limitations | 897 | ||
| Clinical Applications | 898 | ||
| Breast Biomarkers | 899 | ||
| Proliferation Index | 899 | ||
| Microvessel Density Assessment | 900 | ||
| Immunoscore | 900 | ||
| Programmed Death-Ligand 1 | 900 | ||
| Summary | 900 | ||
| Selected References | 900 | ||
| References | 900.e1 | ||
| Index | 901 | ||
| A | 901 | ||
| B | 903 | ||
| C | 904 | ||
| D | 909 | ||
| E | 910 | ||
| F | 911 | ||
| G | 912 | ||
| H | 913 | ||
| I | 914 | ||
| J | 916 | ||
| K | 916 | ||
| L | 916 | ||
| M | 917 | ||
| N | 920 | ||
| O | 922 | ||
| P | 922 | ||
| Q | 925 | ||
| R | 925 | ||
| S | 926 | ||
| T | 929 | ||
| U | 930 | ||
| V | 931 | ||
| W | 931 | ||
| X | 932 | ||
| Y | 932 | ||
| Z | 932 | ||
| Inside Back Cover | ibc1 |