Comprehensive Cytopathology, 4th Edition

Description

In the newly updated edition of Comprehensive Cytopathology, a team of international experts provides criteria and techniques in diagnosis, testing, and new insights in cytology. This accessible guide to diagnostic investigation and screening is ideal for daily laboratory use, taking a systematic approach to helping you understand major diagnostic criteria as well as the pitfalls and limitations of cytology. Quickly find the answers you need through a consistent chapter structure.Realize every possibility. Appropriate histopathological correlations and a consideration of the possible differential diagnosis accompany the cytological findings.Remain at the forefront of your field. Content has been fully revised and updated to include over 1800 full-color images and 2 new chapters: The Bethesda System for Reporting Thyroid Cytopathology, and Digital Pathology. Five Chapters - Benign Proliferative Reactions, Intraepithelial Neoplasia, Invasive Carcinoma; Central Nervous System; Eye; Pancreas; and HPV - have new, original texts.Access expanded coverage of immunocytochemistry and molecular techniques in cytology, as well as digital pathology and its applications to telecytology (including CAP requirements).Equip yourself to handle any situation with guidance on diagnoses in cytology of all body sites (including the female genital tract); fine-needle aspiration of various organs; and special techniques.Offer your patients a definitive diagnosis with updated coverage on molecular testing, as well as the most current concepts, data and references.View entire cytology slides at various magnifications! Ninety-three virtual microscope images have been added to the eBook and expertconsult.com site, as have 7 brand-new videos demonstrating specific imaging techniques in cytopathology. Understand the diagnostic aspects of cytology in both benign and malignant conditions in the various body sites and organs.Compare and contrast various diagnoses with help from Key Features boxes for numerous diagnostic entities.Stay on top of latest guidelines for cervical cancer screening and The Bethesda System for Reporting Thyroid Cytopathology. Front cover Comprehensive Cytopathology, 4/e Copyright page Table of Contents List of Contributors Preface Dedication Acknowledgments List of Virtual Images Guidelines How to View the Slide 1 General Cytology 1 The Cell: Contents Basic Structure and Function of Mammalian Cells Overview Nucleus Contents of the Nucleus DNA. Nuclear Proteins. Nuclear Morphology Chromatin. Hematoxylin Nucleoli Nuclear Envelope and Nuclear Shape Cytoplasm and Plasmalemma Cytoplasmic Stain Endoplasmic Reticulum Golgi Apparatus Mitochondria Lysosomes Cytoskeleton, Centrosome Cell Membrane, Receptors, and Signal Transduction Cell Junctions Cell Growth and Division Influence of Epigenetic Modifications on Gene Expression and Cell Function The Molecular Basis of Neoplasia Overview Principles of Malignant Transformation Cancer-related Genes The Major Pathways of Carcinogenesis Carcinogenesis Induced by Papillomavirus Infections Basic Structure of the Virus and its Genome Epidemiology of HPV Infections The Role of the High-Risk HPV E6 and E7 Genes Progression of HPV-infected Epithelial Cells to Invasive Cancer Cells Concluding Remarks References 2 Basic Cytogenetics and the Role of Genetics in Cancer Development Contents Introduction Historical Background Basic Knowledge of Cytogenetics Cell Cycle The Interphase The Mitosis Prophase Metaphase Anaphase Telophase The Meiosis The Chromosome Structure Methodology The Karyotype The Standardized Reporting Karyotyping In Situ Hybridization The FICTION Technique Array-based Karyotyping Acquired Chromosomal Aberrations in Cancer Lymphoma Follicular Lymphoma Mantle Cell Lymphoma Marginal Zone B-cell Lymphoma Small Lymphocytic Lymphoma Lymphoplasmacytic Lymphoma Diffuse Large B-cell Lymphoma Burkitt’s Lymphoma Anaplastic Large Cell Lymphoma Soft-tissue Tumors Soft-tissue Tumors with Single Karyotypic Abnormalities Soft-tissue Tumors with Complex Karyotypes Carcinomas Thyroid Carcinoma Papillary Thyroid Carcinoma. Follicular Thyroid Carcinoma. Clinical Applications of Conventional Cytogenetics and FISH in Cytology FISH Strategy Application Lymphoma Sarcomas Multiple Myeloma Concluding Remarks References 3 Cytologic Screening Programs Contents Principles of Screening Cervical Cancer and Screening Cervical Cancer Incidence and Mortality Worldwide Efficacy of Screening Design of Screening Programs Features of Successful Screening Programs Limitations of Screening Programs Errors and Failures in the Program Socioeconomic and Cultural Problems Screening Programs and HPV Vaccine Impacts of HPV Vaccine on Screening Programs Screening Programs and HPV DNA Tests Pros and Cons of HPV Primary Screening The Role of the Laboratory in Screening Programs Early Detection of Cancer in Other Sites New Developments in Cytological Screening Liquid-based Cytology Automated Cytology Concluding Remarks References 4 Diagnostic Quality Assurance in Cytopathology Contents Introduction Quality Assurance Measures Laboratory Directors Cytotechnologists Physical Laboratory Facilities Safety Precautions Equipment Specimen Collection Preparation, Fixation, and Staining Procedures Slide Evaluation Workload Cytologic Terminology Laboratory Records, Logs, and Files Internal Quality Assurance Mechanisms CLIA 88 Requirements In Addition to the Following: New Rules Require: Rapid Re-evaluation College of American Pathology (CAP) Checklist ASCUS/SIL Ratios HPV Rates Test Validation Telepathology/Cytology Joint Commission Computer-assisted Quality Assurance Mechanisms Focal Point System ThinPrep Imaging System Workload Policy External Quality Assurance Mechanisms Cap Laboratory Inspection Proficiency Testing Continuing Education Practices Concluding Remarks References 5 Evaluation of the Non-gynecologic Sample in Smears and Liquid-based Preparations Contents Introduction Non-gynecologic Cytology Specimen Type Comparison of Non-Gynecologic Processing Techniques Fine-Needle Aspiration Cytology Exfoliative Cytology The Conclusions of the Study were as Follows: Immunocytochemistry and Molecular Analysis Specimen Cross-Contamination Specimen Processing Specimen Staining Specimen Mishandling Concluding Remarks References 2 Diagnostic Cytology A Female Genital Tract 6 The Bethesda System for Reporting Cervical Cytology Contents The Bethesda System: Historical Perspective The 2001 Bethesda System TBS 2001 Process Report Format Specimen Adequacy Bethesda 2001 Specimen Adequacy Categories Squamous Cellularity Quality Indicators Patient/Specimen Identification and Technical Interpretability Clinical Information Sampling of the Transformation Zone Management Guidelines Impact on Laboratory Practice General Categorization Interpretation/Result Negative for Intraepithelial Lesion or Malignancy (NILM) Endometrial Cells Epithelial Cell Abnormalities: Squamous Cell Atypical Squamous Cells (ASC) Atypical Squamous Cells of Undetermined Significance (ASC-US). Atypical Squamous Cells, cannot Exclude High-grade Squamous Intraepithelial Lesions (ASC-H). Laboratory Reporting of ASC Clinical Management of ASC Squamous Intraepithelial Lesions (SIL) Conceptual Basis for Two-tiered Terminology of SIL. Morphologic Features. HSIL cannot Exclude Invasion. Squamous Cell Carcinoma. Management of SIL Low-Grade SIL. High-Grade SIL. Epithelial Cell Abnormalities: Glandular Cell Background Reporting Glandular Cells in TBS 2001 Atypical Glandular Cells (AGC) Atypical Endocervical Cells, NOS. Atypical Endocervical Cells, Favor Neoplastic. Atypical Endometrial Cells. Endocervical Adenocarcinoma (In Situ and Invasive). Endometrial Adenocarcinoma. Extrauterine Adenocarcinoma. Diagnostic Difficulties Management Educational Notes/Suggestions Ancillary Testing Automated Review Interobserver Reproducibility in Cervical Cytology The Bethesda System and Reporting Anal–Rectal Cytology Concluding Remarks References 7 Microbiology, Inflammation, and Viral Infections Contents Introduction Key Features of Vulvovaginitis Vaginal Microbiology General Features Background Changes Inflammation and Cellular Obscuring Postmenopausal Atrophy and Atypia Bleeding Cellular Changes Degeneration Degenerative, Regenerative (Repair), and Metaplastic Changes in Inflammation Squamous Epithelium Squamous Epithelial Cell Changes Endocervical Columnar Epithelium Columnar Cell Hyperplasia. Hyperplastic Polyp. Tubal Metaplasia. Columnar Epithelial Cell Changes Endometrium Infections of the Female Genital Tract Bacterial Infections Micrococcus Vaginitis (Toxic Shock) Lactobacillus Vaginitis (Cytolytic Vaginosis) Gonococcus Vaginitis Curved Anaerobic Bacterial Vaginitis Vaginal Lactobacillosis Foreign-body Vaginitis Allergic and Acute Vaginitis Desquamative Inflammatory Vaginitis (DIV) Granuloma Inguinale Tuberculosis (Granulomatous Cervicitis) Malacoplakia Langerhans Cell Histiocytosis Actinomyces Cytomorphology of Actinomyces. Key Features of Genital Actinomyces IUD-associated Cellular Changes. Key Features of IUD-associated Cellular Changes Leptotrichia buccalis Mycoplasma Follicular Cervicitis Key Features of Follicular Cervicitis Viral Infections General Features of Viral Infection Inclusion Formation. Hydropic or Ballooning Degeneration. Necrosis. Giant Cell Formation. Cellular Proliferation. Cellular Cohesion. Cytoskeleton Changes. Oncogenesis. Specific Infections Herpes Simplex Virus. Herpes Simplex Genitalis Virus, Type 2. Key Features of Herpes Genitalis Infection Cytomegalovirus. Herpes Zoster. Human Papillomavirus (HPV). Papillomavirus and Cancer. Historical Perspective. HPV and Cervical Dysplasia. Molecular Testing and Ancillary Techniques. Polyomavirus. Molluscum Contagiosum. Adenovirus. Chlamydial Infection Fungal Infections Key Features of Candida Infection Parasitic Infections Trichomonas vaginalis Cytomorphologic Features. Key Features of Trichomonas vaginalis Enterobius vermicularis. Trichuriasis Entamoeba histolytica Entamoeba gingivalis Filariasis Ascariasis Cysticercosis Arthropods Acquired Immunodeficiency Syndrome (AIDS) Concluding Remarks References 8 Benign Proliferative Reactions, Intraepithelial Neoplasia, and Invasive Cancer of the Uterine Cervix Contents Introduction and History The Normal Uterine Cervix Anatomy Cytology Normal Ectocervix Basal/Parabasal Cells Key Features Parabasal Cells (Fig. 8-3). Intermediate Cells Key Features of Intermediate Cells (Fig. 8-4). Superficial Cells Key Features of Superficial Cells (Fig. 8-5). Normal Endocervix Key Features of Normal Endocervix (Fig. 8-6) Benign Squamous Changes Atrophy Key Features of Atrophy (Figs 8-7, 8-8) Hyperkeratosis Key Features of Hyperkeratosis (Fig. 8-10) Parakeratosis Key Features of Parakeratosis (Fig. 8-11) Squamous Metaplasia Reserve Cell Hyperplasia Key Features of Reserve Cells Immature Squamous Metaplasia Key Features of Immature Squamous Metaplasia (Fig. 8-13) Mature Squamous Metaplasia Key Features of Mature Squamous Metaplasia (Fig. 8-14) Reactive and Reparative Changes Key Features of Reactive and Reparative Changes (Fig. 8-15) Intrauterine Contraceptive Devices Key Features of Reactive Changes due to IUD (Fig. 8-16) Treatment Effect Key Features of Treatment Effect (Fig. 8-17) Follicular Cervicitis Key Features of Follicular Cervicitis (Fig. 8-18) Characteristic Squamous Changes in Specific Cervical/Vaginal Infections Bacterial Vaginosis Key Features of Bacterial Vaginosis (Fig. 8-19) Candidiasis Key Features of Candidiasis (Fig. 8-20) Actinomycosis Key Features of Actinomycosis (Fig. 8-21) Trichomoniasis Key Features of Trichomoniasis (Figs 8-15, 8-22) Herpes Virus Key Features of Herpes Virus Infection (Fig. 8-23) HPV and Squamous Lesions of the Cervix Epidemiology of HPV and its Role in Cervical Neoplasia Biology of HPV in the Female Genital Tract Testing for HPV in Cervical Specimens Epithelial Cell Abnormalities Squamous Intraepithelial Lesions Low-grade Squamous Intraepithelial Lesions (LSIL) High-grade Squamous Intraepithelial Lesions (HSIL) Histology Current Terminology for Histology of Preinvasive Squamous Lesions Terminology for the Cytology of SIL Low-grade Squamous Intraepithelial Lesion (LSIL) Cytology – Definition. Key Features of LSIL LSIL Cytomorphology. LSIL: Morphologic Differences by Preparation Type. LSIL: Spectrum of Changes. LSIL Look-A-Likes. High-grade Squamous Intraepithelial Lesion (HSIL) Cytology – Definition. Key Features of HSIL HSIL Cytomorphology. HSIL: Morphologic Differences by Preparation Type. HSIL: Spectrum of Changes. HSIL Look-A-Likes. Atypical Squamous Cells of Undetermined Significance (ASC) Definition Key Features of ASC ASC-US ASC-H ASC: Background ASC-US Cytomorphology ASC-H Cytomorphology ASC: Look-A-Likes. ASC: Spectrum of Changes Squamous Cell Carcinoma (SCC) Histology Superficially Invasive Squamous Carcinoma (SISCA). Invasive Squamous Carcinoma (SCC). Cytology – Definition Key Features of SCC Non-keratinizing SCC Keratinizing SCC Key Features of Small Cell Carcinoma SCC Cytomorphology SCC: Morphologic Differences by Preparation Type SCC: Spectrum of Changes SCC: Look-A-Likes. Rare Variants of SCC Immunohistochemistry and Cervical Cytology Concluding Remarks References 9 Glandular Neoplasms of the Uterine Cervix Contents Introduction Endocervical Canal Normal Histology and Cytology Human Papillomavirus, Other Cofactors, and their Role in Endocervical Carcinogenesis Endocervical Adenocarcinoma in Situ Key Features of Endocervical Adenocarcinoma in Situ Endocervical Adenocarcinoma Key Features of Endocervical Adenocarcinoma Atypical Glandular Cells Key Features of “Atypical Endocervical Cells, Not Otherwise Specified” Benign and Non-glandular Neoplastic Processes that Mimic Endocervical and Endometrial Neoplasia Tubal Metaplasia Key Features of Tubal Metaplasia High-grade Squamous Dysplasias Presenting as Atypical Glandular Cells Key Features of High-grade Squamous Dysplasias Involving Endocervical Gland Necks Atypical Repair Key Features of Atypical Repair Intrauterine Device Effect Key Features of IUDs Direct Sampling of Endometrium Key Features of Directly Sampled Endometrium Endocervical Polyps Key Features of Endocervical Polyp Change Diagnostic Accuracy of Cervical Cytology Regarding Glandular Lesions Management of Glandular Neoplastic Lesions and Atypical Glandular Cells Concluding Remarks References 10 Endometrial Hyperplasia and Carcinoma, Extrauterine Cancer, and Unusual Tumors Contents Introduction Endometrial Physiology Reproductive Age The Climacteric Post-reproductive Years (Menopause) Overview of Endometrial Carcinoma Types I and II Endometrial Adenocarcinoma Molecular Pathology of Endometrial Adenocarcinoma Clinical Epidemiology of Endometrial Adenocarcinoma Presentation and Spread of Endometrial Adenocarcinoma The Histopathology of Endometrial Adenocarcinoma Sensitivity and Specificity of Sampling Techniques for Endometrial Disease Cervicovaginal Cytology Direct Endometrial Sampling Normal-appearing Endometrial Cells and Gestational Changes Cytomorphology of Exfoliated Endometrial Cells in CV Cytology Key Features of Exfoliated Endometrial Cells in CV Cytology Cytomorphology of Lower Uterine Segment Sampling in CV Cytology Key Features of LUS Sampling in CV Cytology Differential Diagnoses of Endometrial Cells in CV Cytology Significance and Reporting of Endometrial Cells Cytologic Findings during Gestation Key Features of Cytologic Findings During Gestation Cytomorphology of Direct Endometrial Sampling The Detection of Endometrial Abnormalities Detection of Endometrial Disease by CV Cytology Benign Endometrial Disease in CV Cytology Endometrial Hyperplasia and CV Cytology Key Features of Endometrial Hyperplasia in CV Cytology Endometrial Carcinoma in CV Cytology Detection of Endometrial Carcinoma Using CV Cytology. Key Features of Endometrial Carcinoma in CV Cytology Detection of Endometrial Disease by Direct Endometrial Sampling Benign Endometrial Disease in Direct Endometrial Cytology Endometrial Hyperplasia in Direct Endometrial Cytology Endometrial Carcinoma in Direct Endometrial Cytology Unusual Uterine Tumors Sarcomas of the Uterus Lymphomas and Leukemias Malignant Melanoma Trophoblastic Neoplasia Extrauterine Cancer Carcinoma of the Fallopian Tube Ovarian and Peritoneal Carcinomas Concluding Remarks References 11 Vulva, Vagina, and Anus Contents Introduction Vulva Sample Collection Methods Histology Infectious and Inflammatory Diseases Key Features of Pemphigus Vulgaris on Vulvar Scrape Non-neoplastic Epithelial Disorders of the Vulva Vulvar Intraepithelial Neoplasia Key Features of Classic VIN on Vulvar Scrape Benign Neoplasms and Tumor-like Conditions Malignant Neoplasms Squamous Cell Carcinoma Key Features of Squamous Cell Carcinoma on Vulvar Scrape Verrucous Carcinomas Basal Cell Carcinoma Paget’s Disease Key Features of Paget’s Disease in Vulvar Scrape Carcinoma of the Bartholin’s Glands Melanomas Key Features of Melanoma in Vulvar Scrape Vagina Sample Collection Methods Histology Infectious and Inflammatory Diseases Vaginal Smears from Post-hysterectomy Patients Cysts Diethylstilbestrol-related Abnormalities Benign Neoplasms and Tumor-like Conditions Vaginal Intraepithelial Neoplasia Malignant Neoplasms Squamous Cell Carcinoma Key Features of VaIN and Vaginal SCC Verrucous Carcinoma Primary Adenocarcinoma Embryonal Rhabdomyosarcoma Key Features of Rhabdomyosarcoma on Vaginal Scrape Rare Primary Neoplasms Metastatic Tumors Anus Epidemiology and Pathogenesis of Anal Cancer Screening Programs for Anal Intraepithelial Neoplasia and Cancer Adequacy and Sample Collection Methods Histology of Anal Squamous Cell Carcinoma and Anal Intraepithelial Neoplasia Anal Cytology and Salient Features Key Features of AIN in anal Pap Anal Cytologic Screening Guidelines Concluding Remarks References 12 Peritoneal Washings and Ovary Contents Peritoneal Washings Sampling Techniques Specimens Cytology Correlation with Histology Atypical Cells and Pitfalls for Diagnosis Papillary Structures Key Features of Papillary Carcinoma Incidental Lesions Ancillary Techniques Diagnostic Accuracy Ovary Sampling Techniques Basic Histology Non-neoplastic Cysts Follicular Cyst Key Features of Follicle Cyst Luteinized Cyst Key Features of Luteinized Cyst Endometriotic Cyst Key Features of Endometriotic Cyst Neoplastic Cysts Benign Serous Tumors Key Features of Benign Serous Tumors Benign Mucinous Tumors Key Features of Benign Mucinous Tumors Borderline and Malignant Epithelial Tumors Mature Cystic Teratoma Key Features of Mature Cystic Teratoma Immature Teratoma Key Features of Immature Teratoma Dysgerminoma Key Features of Dysgerminoma Granulosa Cell Tumors Key Features of Adult GCTs Juvenile Granulosa Cell Tumors Key Features of Juvenile GCTs Rare Tumors Ancillary Techniques Diagnostic Accuracy Concluding Remarks Peritoneal Washings Ovary References B Cytology of Other Body Sites 13 Respiratory Tract Contents Introduction Sampling and Cytopreparatory Techniques Sputum Fresh and Unfixed Sputum Prefixed Sputum Sputum Prefixed with Alcohol and Carbowax (Saccomanno Technique) Induced Sputum Bronchial Cytology Bronchial Washings Bronchial Brushings Bronchoalveolar Lavage Liquid-based Cytology Fine-needle Aspiration Indications and Contraindications: CT- or EBUS-guided FNA Anatomy and Histology Cytology of Normal and Benign Conditions Normal Epithelial Cells Squamous Cells Ciliated Bronchial Columnar Cells Goblet Cells Epithelial Cells from Terminal Bronchioles and Alveoli Reactive Changes and Other Benign Conditions Squamous Cells Bronchial Cells Hyperplasia of Bronchial Epithelium. Hyperplasia of Type II Pneumocytes. Squamous Metaplasia and Reserve Cell Hyperplasia Bronchopulmonary Dysplasia Epithelial Cellular Changes Following Radiation Therapy, Chemotherapy, and Toxic Chemicals Sarcoidosis Other Cellular Components Non-cellular Inanimate Components Cytology of Respiratory Infections Viral Infections Bacterial Infections Gram-positive and Gram-negative Bacteria Fungal Infections Pulmonary Blastomycosis Pulmonary Cryptococcosis Pulmonary Coccidioidomycosis Pulmonary Histoplasmosis Pulmonary Candidiasis Pulmonary Paracoccidioidomycosis Pulmonary Aspergillosis Pulmonary Mucormycosis Pneumocystis jirovecii Pneumonia Other Fungi Mycobacterial Infections Parasitic Infections Pulmonary Strongyloidiasis Other Parasites Benign Neoplasms of the Lung Hamartoma Other Pathology of Lung Cancer Cytology of Lung Cancer Squamous Cell Carcinoma Squamous Cell Carcinoma in Situ Invasive Squamous Cell Carcinoma Key Features of Well-differentiated Squamous Cell Carcinoma Key Features of Poorly Differentiated Squamous Cell Carcinoma Adenocarcinoma Key Features of Acinar Adenocarcinoma Bronchioloalveolar Carcinoma Key Features of Bronchioloalveolar Carcinoma Large-cell Undifferentiated Carcinoma (synonyms: Large-cell Carcinoma; Pleomorphic Carcinoma) Key Features of Large Cell Undifferentiated Carcinoma Small-cell Undifferentiated Carcinoma (synonym: Small-cell Carcinoma) Key Features of Small-cell Undifferentiated Carcinoma Adenosquamous Carcinoma Carcinoid Adenoid Cystic Carcinoma Other Primary Neoplasms of the Lung Lung Carcinoma and Molecular Testing Neoplasms Metastatic to the Lung Diagnostic Accuracy Sensitivity and Specificity of Specimens of Bronchial Material Concluding Remarks References 14 Alimentary Tract (Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Biliary Tract) Contents Introduction Esophagus Normal Histology and Cytology Infectious Esophagitis Candida Esophagitis Key Feature of Candida Esophagitis Herpetic Esophagitis Key Features of Herpes Esophagitis Cytomegalovirus Esophagitis Key Features of CMV Esophagitis Other Infections Esophageal Changes Associated with Ablative Therapy, Chemotherapy, and Radiation Therapy Barrett’s Esophagus, Dysplasia, and Adenocarcinoma Cytomorphology Key Features of Barrett’s Glandular Dysplasia and Adenocarcinoma Beyond Morphology Squamous Cell Carcinoma Cytomorphology Key Features of Squamous Cell Carcinoma Beyond Morphology Small-cell Carcinoma Cytomorphology Beyond Morphology Other Malignancies Stomach Normal Histology and Cytology Helicobacter Gastritis Cytomorphology Beyond Morphology Adenocarcinoma Cytomorphology Key Features of Adenocarcinoma, Intestinal Type Key Features of Adenocarcinoma, Signet-Ring Type Beyond Morphology Gastrointestinal Stromal Tumors Cytomorphology Key Features of Gastric GISTs Beyond Morphology Carcinoid Tumor (Endocrine Tumors) Key Features of Carcinoid Tumor Duodenum Normal Histology and Cytology Cytomegalovirus Giardiasis Cytomorphology Beyond Morphology Cryptosporidiosis Cytomorphology Beyond Morphology Mycobacterium Cytomorphology Beyond Morphology Adenocarcinoma Malignant Lymphoma Metastatic Tumors Large Intestine Inflammatory Bowel Disease Cytomorphology Adenocarcinoma Anus Cytomorphology Adequacy Diagnostic Criteria Beyond Morphology Reliability Biliary Tract Normal Histology and Cytology Adenocarcinoma Cytomorphology Key Features of Biliary Duct Adenocarcinoma Beyond Morphology References 15 Urinary Tract Contents Introduction Screening for Bladder Cancer Examination of Symptomatic Patients Follow-up after Treatment Sampling Techniques and Preparation Sample Collection Voided and Catheterized Urine Fixation Bladder Washings Aspirates, Washings, Brushings, and Cell Blocks of Ureters and Renal Pelvis Sample Preparation Smears of Fresh and Fixed Specimens Filtration and Cytocentrifugation-based Preparations Cell Blocks Urothelium and Specialized Lining Histology Normal Cytology Key Features of Normal Voided Urine Non-neoplastic Abnormalities Developmental Abnormalities Endometriosis Nonspecific, Bacterial Inflammation, and Fungi Key Features of Cystitis Virus Infections Key Features of Viral Infections Malacoplakia Degenerative Changes Key Features of Degenerative Changes Intracytoplasmic and Intranuclear Inclusions Cytologic Changes Associated with Calculi Key Features Associated with Calculi Iatrogenic Changes Hyperplasia, Atypia, and Dysplasia Tumors of the Urinary Tract Papillary Tumors Papilloma Key Features of Papilloma Papillary Urothelial Neoplasm of Low Malignant Potential (Tumor Grade I). Key Features of Papillary Urothelial Neoplasm of Low Malignant Potential Low-Grade Papillary Urothelial Carcinoma (Papillary Urothelial Carcinoma, Grade II). Key Features of Low-grade Papillary Urothelial Carcinoma High-Grade Papillary Urothelial Carcinoma (Grade III). Key Features of High-grade Urothelial Carcinoma Urothelial Dysplasia and Carcinoma In Situ Low-grade Dysplasia High-grade Dysplasia/Carcinoma in Situ Key Features of High-grade Dysplasia/Carcinoma in Situ Invasive Urothelial Carcinoma Monitoring of Patients Squamous Cell Carcinoma Adenocarcinoma Key Features of Adenocarcinoma Renal Cell Carcinoma Prostate Adenocarcinoma Other Tumors Small-cell Carcinoma of the Bladder Sarcomas Urethral Tumors Upper Tract Urinary Tumors Iatrogenic Changes Laser-Induced Changes Irradiation Changes Key Features of Irradiation Changes Effects of Chemotherapy and Immunotherapy Cytology of Ileal Conduits Key Features of Ileal Conduits Urine Renal Allograft Monitoring Key Features of Renal Allograft Rejection Special Techniques Fluorescence in Situ Hybridization (FISH) Flow Cytometry Immunocytochemistry Morphometry BTA Stat and BTA Trak Nuclear Matrix Protein (NMP22) The ImmunoCyt Test Telomerase DNA Methylation Other Tumor Markers Diagnostic Accuracy Concluding Remarks References 16 Central Nervous System Contents Introduction Preparatory Methods Normal Cerebrospinal Fluid Cytology Ventricular Shunts Infectious Conditions Key Feature of Acute Bacterial Meningitis Viral Infections Key Feature of Viral Meningoencephalitis Key Feature of AIDS Encephalopathy Fungal Infections Key Features of Fungal Meningitis Demyelinating Diseases Key Feature of Demyelinating Diseases Vascular Disorders Trauma Key Features of Trauma and Hemorrhage Reactions to Intraventricular Shunts Key Features of Intraventricular Shunts Neoplasia Leukemia Lymphoma Key Features of Leukemia/Lymphoma Metastatic Carcinoma Meningeal Carcinomatosis Primary Central Nervous System Tumors Diagnostic Accuracy in Cerebrospinal Fluid Cytology Concluding Remarks References 17 Eye Contents Introduction Ocular Anatomy Cytologic Sampling Diagnostic Accuracy Uveal Metastases Key Features of Metastases vs. Melanoma Uveal Melanoma Key Features of Uveal Melanoma Key Features of Melanocytoma and Pigmented Adenoma Ocular Lymphoma Key Features of Ocular Lymphomas Retina Key Features of Retinoblastoma Vitreous Orbit Key Features of Orbital Neoplasms Concluding Remarks References 18 Cytology of Soft Tissue, Bone, and Skin Contents Soft Tissue Tumors Introduction Morphological Approach to Soft Tissue Lesions Grade Molecular Studies in Soft Tissue Tumors Molecular Approaches Commonly used as Diagnostic Aids Cytogenetic Analysis Fluorescence In Situ Hybridization Analysis Reverse Transcription–Polymerase Chain Reaction Analysis Sequencing Analysis Adipocytic Tumors Lipoma Key Features of Lipoma Lipoblastoma Key Features of Lipoblastoma Spindle and Pleomorphic Lipoma Key Features of Spindle Cell Lipoma Key Features of Pleomorphic Lipoma Hibernoma Key Features of Hibernoma Atypical Lipomatous Tumor/Well-differentiated Liposarcoma Key Features of Atypical Lipomatous Tumor/ Well-differentiated Liposarcoma Dedifferentiated Liposarcoma Key Features of Dedifferentiated Liposarcoma Myxoid Liposarcoma Key Features of Myxoid Liposarcoma Pleomorphic Liposarcoma Key Features of Pleomorphic Liposarcoma Fibroblastic/Myofibroblastic Lesions Nodular Fasciitis Key Features of Nodular Fasciitis Proliferative Fasciitis and Proliferative Myositis Key Features of Proliferative Fasciitis and Proliferative Myositis Myositis Ossificans Key Features of Myositis Ossificans Fibromatosis Key Features of Fibromatosis Fibrosarcoma Key Features of Fibrosarcoma Extrapleural Solitary Fibrous Tumor Key Features of Extrapleural Solitary Fibrous Tumor Myxofibrosarcoma Key Features of Myxofibrosarcoma Myofibroblastoma Key Features of Myofibroblastoma Low-grade Fibromyxoid Sarcoma Key Features of Myofibroblastic Sarcoma Sclerosing Epithelioid Fibrosarcoma Key Feature of Sclerosing Epithelioid Fibrosarcoma Fibrohistiocytic Tumors Tenosynovial Giant Cell Tumor Key Features of Tenosynovial Giant Cell Tumor Deep Benign Fibrous Histiocytoma Key Features of Deep Benign Fibrous Histiocytoma Plexiform Fibrohistiocytic Tumor Key Features of Plexiform Fibrohistiocytic Tumor Undifferentiated Pleomorphic Sarcoma Tumors of Muscle Origin Smooth Muscle Tumors Leiomyoma Key Features of Leiomyoma Leiomyosarcoma Key Features of Leiomyosarcoma Epithelioid Muscle Tumors Key Features of Epithelioid Muscle Tumors Pericytic (Perivascular) Tumors Glomus tumor. Key Features of Glomus Tumor Skeletal Muscle Tumors Rhabdomyoma Key Features of Rhabdomyoma Rhabdomyosarcoma (RMS) Key Features of Embryonal RMS Key Features of Alveolar RMS Key Features of Pleomorphic RMS Vascular Tumors Hemangioma Key Features of Hemangioma Epithelioid Hemangioma Key Features of Epithelioid Hemangioma Juvenile Hemangioma Key Features of Juvenile Hemangioma Lymphangioma Key Features of Lymphangioma Kaposi Sarcoma Key Features of Kaposi Sarcoma Epithelioid Hemangioendothelioma Key Features of Epithelioid Hemangioendothelioma Angiosarcoma Key Features of Spindle Cell Angiosarcoma Key Features of Epithelioid Angiosarcoma Other Intramuscular Myxoma Key Features of Intramuscular Myxoma Deep (“Aggressive”) Angiomyxoma Key Features of Angiomyxoma Pleomorphic Hyalinizing Angiectatic Tumor of Soft Parts Key Features of Pleomorphic Hyalinizing Angiectatic Tumor of Soft Parts Angiomatoid Fibrous Histiocytoma Key Features of Angiomatoid Fibrous Histiocytoma Ossifying Fibromyxoid Tumor Key Features of Ossifying Fibromyxoid Tumor Synovial Sarcoma Key Features of Synovial Sarcoma Epithelioid Sarcoma Key Features of Epithelioid Sarcoma Alveolar Soft Part Sarcoma Key Features of Alveolar Soft Part Sarcoma Clear Cell Sarcoma of Soft Tissue Key Features of Clear Cell Sarcoma of Soft Tissue Extraskeletal Myxoid Chondrosarcoma Key Features of Myxoid Chondrosarcoma Desmoplastic Small Round Cell Tumor Key Features of Desmoplastic Small Round Cell Tumor Extrarenal Rhabdoid Tumor Key Features of Extrarenal Rhabdoid Tumor Neoplasms with Perivascular Epithelioid Cell Differentiation Key Features of Perivascular Epithelioid Cell Differentiation Bone Lesions Cartilage Tumors Chondroma Key Features of Chondroma Chondroblastoma Key Features of Chondroblastoma Chondrosarcoma Key Features of Mesenchymal Chondrosarcoma Key Features of Dedifferentiated Chondrosarcoma Key Features of Clear Cell Chondrosarcoma Benign Bone Lesions Osteomyelitis Key Features of Osteomyelitis Langerhans Cell Histiocytosis Key Features of Langerhans Cell Histiocytosis Osteogenic Tumors Osteoblastoma Key Features of Osteoblastoma Osteosarcoma Key Feature of Osteosarcoma Fibrohistiocytic Tumors Undifferentiated High-grade Pleomorphic Sarcoma Key Features of Undifferentiated High-grade Pleomorphic Sarcoma Ewing Sarcoma/Primitive Neuroectodermal Tumor Key Features of ES/PNET Hematopoietic Tumors Plasma Cell Neoplasm Key Features of Plasma Cell Neoplasm Lymphoma Key Features of Lymphoblastic Lymphoma Osteoclastic Giant Cell-rich Tumors Giant Cell Tumors Key Features of Giant Cell Tumors Notochordal Tumors Chordoma Key Features of Chordoma Epithelial Tumors Epithelioid and Epithelial Neoplasms of Bone Adamantinoma Key Features of Adamantinoma Skin Techniques Non-neoplastic Non-neoplastic Lesions Infectious Conditions Neoplastic Basal Cell Carcinoma Key Features of Basal Cell Carcinoma Squamous Cell Carcinoma Key Features of Squamous Cell Carcinoma Sebaceous Carcinoma Key Features of Sebaceous Carcinoma Carcinoma In Situ Key Features of Carcinoma in Situ Paget’s Disease Key Features of Paget’s Disease Pilomatrixoma Key Features of Pilomatrixoma Cylindroma Key Features of Cylindroma Eccrine Spiradenoma Key Features of Eccrine Spiradenoma Chondroid Syringoma Key Features of Chondroid Syringoma Syringocystadenoma Papilliferum Key Features of Syringocystadenoma Papilliferum Eccrine Porocarcinoma (Hidradenoma) Key Features of Eccrine Porocarcinoma Merkel Cell Carcinoma Key Features of Merkel Cell Carcinoma Mucinous Carcinoma Key Features of Mucinous Carcinoma Hematopoietic Lesions Key Feature of Hematopoietic Lesions Dermatofibrosarcoma Protuberans Key Features of Dermatofibrosarcoma Protuberans Metastases Concluding Remarks References 19 Pleural, Peritoneal, and Pericardial Effusions Contents Introduction Sampling Technique Collecting Serous Effusions Gross Appearance of Serous Effusions Cytopreparatory Technique Preliminary Steps Wet-film Technique Liquid-based Preparations Cell block Technique Tinted Formalin Thrombin Solution Toluidine Blue Stain Key Features of Processing Serous Effusions Usefulness of Stained Wet Films Key Features of Stained Wet Films Usefulness of Cell block Preparations Key Features of Cell Blocks The Serous Cavities Types of Effusions Transudates and Exudates Normal Cells Range of Normal Cells Mesothelial Cells Cytology “Atypical” and “Reactive” Mesothelial Cells Mesothelial Cells in Wet Films Cell Block Preparations Diagnostic Pitfalls Key Features of Mesothelial Cells Red Blood Cells Cytology Key Features of Red Blood Cells Neutrophil Leukocytes Cytology Key Features of Neutrophilic Leukocytes Eosinophilic Leukocytes Eosinophilic Pleural Effusion Eosinophilic Peritoneal Effusion Eosinophilic Pericardial Effusion Cytology Key Features of Eosinophilic Leukocytes Basophil Leukocytes and Mast Cells Cytology Key Features of Basophilic Leukocytes and Mast Cells Histiocytes (Macrophages) Cytology Key Features of Histiocytes Lymphoid Cells Cytology Key Features of Lymphoid Cells Megakaryocytes Key Features of Megakaryocytes Non-neoplastic Effusions Nonspecific Inflammation Key Features of Non-Neoplastic Effusions Specific Inflammatory Pictures Rheumatoid Disease Histopathology. Cytology. Necrotic Background Material. Key Features of Rheumatoid Effusions Systemic Lupus Erythematosus Cytology. Key Features of SLE Congestive Heart Failure Key Cytologic Features of Congestive Heart Failure Pneumonia Key Cytologic Feature of Congestive Heart Failure Infarct Key Features of Infarct Pneumothorax Key Cytologic Features of Pneumothorax-related Effusion Tuberculosis Key Cytologic Features of Tuberculous Effusions Hepatic Cirrhosis Key Features of Hepatic Cirrhosis Parasitic, Protozoal, Fungal, and Viral Infections Parasitic Infections Echinococcosis (Hydatid Disease). Paragonimiasis. Strongyloidiasis. Trichomoniasis. Giardiasis. Balantidiasis. Schistosomiasis (Bilharziasis). Amebiasis. Filariasis. Visceral Leishmaniasis (Kala-Azar). Key Features of Parasitic Infestations Fungal Infections Key Features of Fungal Infections Viral Infection Key Features of Viral Infections Fistula Key Features of Fistula Red Blood Cell Changes Key Feature of Red Blood Cell Changes Endometriosis Key Features of Endometriosis in Serous Effusions Charcot–Leyden Crystals Key Features of Charcot–Leyden Crystals Ferruginous (Asbestos) Bodies Key Features of Ferruginous (Asbestos) Bodies Reaction to Ionizing Radiation and Chemotherapy Key Feature of Reaction to Ionizing Radiation and Chemotherapy Neoplastic Effusions General Identification of Neoplastic Cells Key Features of Identification of Neoplastic Cells Differential Diagnosis of Types of Neoplasms and Determination of Primary Sites of Neoplasms Key Features Related to Types of Neoplasm Adenocarcinoma Cell Clusters Vacuolation of Adenocarcinoma Cells Ciliated Adenocarcinoma Cells Key Features of Adenocarcinoma Cells Squamous Cell Carcinoma Cytology Key Features of Squamous Cell Carcinoma Small-cell Carcinoma Cytology Key Features of Small-Cell Carcinoma Urothelial Carcinoma Key Features of Urothelial Carcinoma Melanoma Key Features of Melanoma Mesothelioma Cytology Morphologic Variants Special Techniques Electron Microscopy. Histochemistry. Immunocytochemistry. Key Features of Mesothelioma of Epithelial Type Carcinoma of the Lung Key Features of Carcinoma of the Lung Carcinoma of the Breast Cytology Key Features of Carcinoma of the Breast Neoplasms of the Ovary Cytology Key Features of Ovarian Neoplasms Pseudomyxoma Peritonei Key Features of Pseudomyxoma Peritonei Carcinoma of the Gastrointestinal Tract Key Features of Carcinoma of Gastrointestinal Tract Miscellaneous Carcinomas Lymphoma and Leukemia Key Features of Lymphoma and Leukemia Chronic Idiopathic Myelofibrosis Key Features of Chronic Idiopathic Myelofibrosis Some Neoplasms Rarely Seen in Serous Effusions Molecular tests Reporting of Results and Statistics Reporting Reliability of Positive and Negative Reports Concluding Remarks References C Fine-needle Aspiration of Various Organs and Body Sites 20 Fine-needle Aspiration Biopsy Techniques Contents History of Aspiration Biopsy Required Skills Fine-needle Aspiration Biopsy Method Training and Planning Informed Consent Basic Equipment Ancillary Equipment and Special Procedures Ultrasound-guided Fine-needle aspiration The Aspiration Technique Performing the Aspiration Smear Preparation Routine Smears Bloody Smears Assisting at Image-guided Aspirations Handling Micro-core Biopsies Fixatives and Stains Routine Monolayer Preparations Cell Block Special Stains Ancillary Techniques and Applications Immunohistochemistry Molecular Methods Electron Microscopy Organization of the Aspiration Biopsy Service Appendix Equipment Staining Methods Papanicolaou Stain Materials Rapid Papanicolaou Stain Diff-Quik Stain Materials Method Hematoxylin and Eosin Stain Materials Method Supravital Stains Cell block Preparation Thrombin Clot Technique Materials Method Preparation of Cytospins for Tumor Markers Fluorescent in Situ Hybridization (FISH) Saponization Materials Method References 21 Imaging Techniques Contents Introduction Imaging Methods Conventional Radiography and Fluoroscopy Computed Tomography Magnetic Resonance Ultrasound Positron Emission Tomography/ Image Fusion Complications of Image-guided FNAB Image-guided FNAB of Specific Organs Thyroid, Peripheral Lymph Nodes, Salivary Gland, and Superficial Soft Tissue Masses Thyroid Salivary Glands Superficial Lymph Nodes Breast Lungs and Pleura Mediastinum Abdominal and Pelvic Organs Liver Pancreas Kidney Concluding Remarks References 22 Salivary Glands and Rare Head and Neck Lesions Contents Salivary Glands Introduction Technique Anatomy and Histology Cytology Non-neoplastic Lesions Cysts Cytology. Key Features of Non-neoplastic Cysts Sialoadenosis Cytology. Nodular Oncocytic Hyperplasia Cytology. Inflammatory Lesions Acute Sialoadenitis Key Features of Acute Bacterial Sialoadenitis Chronic Sialoadenitis Cytology. Key Features of Non-obstructive Chronic Sialoadenitis Lymphocyte-dominated Benign Lesion Lymphadenitis Benign Lymphoepithelial Lesion Cytology. Key Features of Lymphoepithelial Lesions Warthin’s Tumor Neoplasms Benign Tumors Pleomorphic Adenoma (Mixed Tumor) Cytology. Key Features of Pleomorphic Adenoma Myoepithelioma Cytology. Key Features of Myoepithelioma Adenolymphoma (Warthin’s Tumor, Papillary Cystadenolymphoma) Cytology. Key Features of Adenolymphoma (Warthin’s Tumor) Oncocytoma (Oxyphilic Adenoma) Cytology. Key Features of Oncocytoma Basal Cell Adenoma Cytology. Key Features of Basal Cell Adenoma Clear Cell Adenoma Sebaceous Cell Adenoma Key Features of Sebaceous Cell Adenoma Malignant Tumors Adenoid Cystic Carcinoma Cytology. Key Features of Adenoid Cystic Carcinoma Mucoepidermoid Carcinoma Cytology. Key Features of Mucoepidermoid Carcinoma Low Grade High Grade Acinic Cell Carcinoma Cytology. Key Features of Acinic Cell Carcinoma Well to Moderately Well Differentiated Poorly Differentiated Polymorphous Low-grade Adenocarcinoma Cytology. Key Features of Polymorphous Low-grade Adenocarcinoma Myoepithelial Carcinoma Cytology. Key Features of Myoepithelial Carcinoma Salivary Duct Carcinoma Cytology. Key Features of Salivary Duct Carcinoma Carcinoma Ex Pleomorphic Adenoma (Adenocarcinoma Arising in a Mixed Tumor) Malignant Mixed Tumor Squamous Cell Carcinoma Adenocarcinoma Not Otherwise Specified Epithelial–Myoepithelial Carcinoma Cytology. Key Features of Epithelial–Myoepithelial Carcinoma Large-cell Undifferentiated Carcinoma Cytology. Key Features of Large-cell Carcinoma Lymphoepithelial Carcinoma Cytology. Key Features of Lymphoepithelial Carcinoma Mammary Analogue Secretory Carcinoma Cytology. Key Features of Mammary Analogue Secretory Carcinoma Small-cell Undifferentiated Neuroendocrine Carcinoma Cytology. Key Features of Small-cell Undifferentiated Neuroendocrine Carcinoma Metastasizing Pleomorphic Adenoma Cytology. Key Features of Metastasizing Pleomorphic Adenoma Mesenchymal Tumors Metastatic Tumors Diagnostic Accuracy Rare Head and Neck Lesions Introduction Benign Malignant Benign Lesions Ectopic Cervical Thymic Tissue Cytology. Key Features of Ectopic Cervical Thymic Tissue Cervical Rib Key Features of Cervical Rib Chondromas Cytology. Key Features of Chondroma Parathyroid Lesions Cytology. Key Features of a Parathyroid Adenoma Nodular Fasciitis Cytology. Key Features of Nodular Fasciitis Proliferative Myositis Cytology. Key Features of Proliferative Myositis Carotid Body Tumor Cytology. Key Features of Carotid Body Tumor Pilomatrixoma (Calcifying Epithelioma of Malherbe) Cytology. Key Features of Pilomatrixoma Meningioma Cytology. Key Features of Meningioma Rhabdomyoma Cytology. Key Features of Rhabdomyoma Fibromatosis Colli Cytology. Key Features of Fibromatosis Colli Malignant Tumors Olfactory Neuroblastoma Key Features of Olfactory Neuroblastoma Carcinomas in Thyroglossal Cysts Key Features of Papillary Thyroid Carcinoma of the Thyroglossal Cyst Neuroendocrine Carcinoma of the Skin (Merkel Cell Tumor) Cytology. Key Features of Neuroendocrine Carcinoma of the Skin Concluding Remarks References 23 The Bethesda System for Reporting Thyroid Cytopathology Contents Historical Background The Bethesda System Non-diagnostic/Unsatisfactory Benign Atypia of Undetermined Significance (AUS)/Follicular Lesion of Undetermined Significance (FLUS) Suspicious for a Follicular or Hürthle Cell Neoplasm/Follicular Neoplasm Suspicious for Malignancy Malignant Experience with TBSRTC Supplemental testing and TBSRTC Scientific Basis Clinical Testing Somatic Mutation Panel Gene Expression Classifier Limitations of Genetic Testing Concluding Remarks Clinical Impact of TBSRTC References 24 Thyroid Contents Introduction The Thyroid Nodule Methods for Assessing Thyroid Nodules FNA Technique Fine-needle Sampling without Aspiration Ultrasound FNA/FNWA Core Needle Biopsy Frozen Sections Slide Preparation Specimen Adequacy Normal Thyroid Key features of normal thyroid gland Metabolic Disorders Amyloidosis Key features of amyloidosis Black Thyroid Syndrome Fatty Infiltration of the Thyroid Gland Squamous Metaplasia of the Thyroid Gland Thyroiditis Acute Thyroiditis Key features of acute thyroiditis Subacute Thyroiditis Subacute Granulomatous Thyroiditis (De Quervain’s Thyroiditis) Key features of De Quervain’s thyroiditis Subacute Lymphocytic Thyroiditis (Silent Thyroiditis) Chronic Thyroiditis Chronic Granulomatous Thyroiditis Riedel’s Disease Focal Lymphocytic “Nonspecific” Thyroiditis Hashimoto’s Thyroiditis Juvenile Lymphocytic Thyroiditis Key features of Hashimoto’s thyroiditis (juvenile lymphocytic thyroiditis) Hypertrophic Lymphocytic Thyroiditis, Key features of Hashimoto’s thyroiditis (hypertrophic lymphocytic thyroiditis) Fibrous Lymphocytic Thyroiditis Hyperplasia Toxic Diffuse Hyperplasia (Graves’ Disease) Key features of Graves’ disease Diffuse Colloidal Hyperplasia Key features of diffuse colloidal hyperplasia Nodular Hyperplasia Dyshormonogenic nodular hyperplasia Key features of nodular hyperplasia Hypocellular nodules Hypercellular nodules Hypocellular nodules Cystic Nodules Key features of cystic nodules Thyroid Tumors Follicular Neoplasm Follicular Thyroid Adenoma and Carcinoma FTA FTC Key features of follicular neoplasm Colloidal FTC FVPC Clear-cell variant Hürthle Cell Neoplasm (Oncocytic Neoplasm) Key features of Hürthle cell neoplasm Hyalinizing Trabecular Tumor Key features of hyalinizing trabecular tumor Papillary Thyroid Carcinoma Key features of PTC Variants of Papillary Thyroid Carcinoma Papillary microcarcinoma, FVPTC Medullary Thyroid Carcinoma Key features of MTC Poorly differentiated Thyroid Carcinoma Key features of PDTC Undifferentiated (Anaplastic) Thyroid Carcinoma Key features of UTC Malignant Lymphoma of the Thyroid Key features of malignant lymphoma Thyroid Metastases Unusual Thyroid Lesions Complications Ancillary Studies Immunohistochemistry Molecular Testing BRAF The RET The RAS The PAX8/PPARγ Other Molecular Alterations Other Technologies Argyrophilic Nucleolar Concluding Remarks References 25 Lymph Nodes: Contents Introduction Techniques Collection and Cytologic Preparation Flow Cytometry Overview Lineage-associated Markers Sample Preparation and Processing Test CD Panel Selection and Staining Data Acquisition Analysis for Clonality Pitfalls in Flow Cytometric Immunophenotyping Molecular and Other Ancillary Studies Normal Lymph Node: Structure and Immunophenotypes Histology Cytology Non-neoplastic Lymphadenopathy Reactive Lymphadenopathy Key Features of Follicular Hyperplasia Immune Diseases Lymphadenitis Viral Infections Suppurative Lymphadenitis Granulomatous Lymphadenitis Key Features of Granulomatous Lymphadenitis The Classification of the Lymphoid Neoplasms Practical Guidelines for the Cytopathologist Non-Hodgkin Lymphoma Lymphomas Composed of Predominantly Small or Small- and Medium-sized Cells Low-grade Follicular Lymphoma Cytomorphology and Ancillary Studies. Primary Cutaneous Follicular Center Cell Lymphoma. Follicular Lymphoma “in situ” (Intrafollicular Neoplasia). Differential Diagnosis. Key Features of Low-grade Follicular Lymphoma (Grades 1 and 2) Marginal Zone/MALT Lymphoma Cytomorphology. Ancillary Studies. Differential Diagnosis. Key Features of Marginal Zone/MALT Lymphoma Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia Cytomorphology and Ancillary Studies. Differential Diagnosis. Key Features of Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia Lymphoplasmacytic Lymphoma/ Waldenström Macroglobulinemia Cytomorphology and Ancillary Studies. Differential Diagnosis. Key Features of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Mantle Cell Lymphoma Cytomorphology and Ancillary Studies. Differential Diagnosis. Key Features of Mantle Cell Lymphoma Lymphomas Composed of Predominantly Large Cells Large B-cell Lymphoma (Diffuse Large B-cell/Grade 3 Follicular) Clinical. Cytomorphology and Ancillary Studies. Differential Diagnosis. Anaplastic Large-cell Lymphoma Clinical. Cytomorphology and Ancillary Studies. Differential Diagnosis. Key Features of Anaplastic Large-cell Lymphoma Peripheral T- and NK/T-cell Lymphomas Cytomorphology and Ancillary Studies. Differential Diagnosis. Lymphomas Composed of Blastoid Cells Burkitt Lymphoma/Leukemia Cytomorphology and Ancillary Studies. Differential Diagnosis. Key Features of Burkitt Lymphoma/Leukemia Precursor Lymphoblastic Leukemia/Lymphoma Cytomorphology and Ancillary Studies. Differential Diagnosis. Key Features of Precursor Lymphoblastic Leukemia/Lymphoma Blastoid Variant of Mantle Cell Lymphoma Clinical. Cytomorphology. Differential Diagnosis. Hodgkin Lymphoma Classic Hodgkin Lymphoma Clinical. Cytomorphology and Ancillary Studies. Differential Diagnosis. Key Features of Classic Hodgkin Lymphoma Nodular Lymphocyte-predominant Hodgkin Lymphoma Clinical. Cytomorphology and Ancillary Studies. Differential Diagnosis. Key Features of Nodular Lymphocyte-predominant Hodgkin Lymphoma Other Hematopoietic Neoplasms Langerhans Cell Histiocytosis Clinical. Cytomorphology and Axillary Studies. Differential Diagnosis. Myeloid Sarcoma Cytomorphology and Axillary Studies. Differential Diagnosis. Histiocytic and Dendritic Cell Neoplasms Primary and Metastatic Non-hematopoietic Neoplasms Challenges and Diagnostic Pitfalls Sampling Error Hodgkin Lymphoma and Non-lymphoid Neoplasms Lack of Architecture Presence of Benign Host Cells Aberrant Phenotypes Concluding Remarks References 26 Breast Contents Introduction Indications and Advantages Limitations of FNA of the Breast Role of FNA in the ERA of Core Needle Biopsy Accuracy, False-negative and False-positive Rates, and the Triple Test Technique Cell block Preparation Liquid-based Cytology Complications of FNA of the Breast Anatomy and Histology of the Breast The Breast Fine-needle Aspiration Cytology Report Benign Breast Lesions Breast Cysts Inflammatory Lesions, Mastitis, and Abscess Formation Granulomas Mammary Duct Ectasia (Plasma Cell Mastitis, Comedomastitis) Subareolar Abscess Key Features of Subareolar Abscess Lipomas Fat Necrosis Key Features of Fat Necrosis Fibrocystic Change Key Features of Fibrocystic Change Ductal Epithelial Hyperplasia (Proliferative Breast Disease) Atypical Ductal Hyperplasia Key Features of Atypical Ductal Hyperplasia Juvenile Papillomatosis Fibroadenoma Key Features of Fibroadenomas Adenosis Tumor and Sclerosing Adenosis Nodular Pseudoangiomatous Stromal Hyperplasia Nipple Adenoma Adenomyoepithelioma Pleomorphic Adenoma Benign Lesions during Pregnancy and Postpartum Key Features of Lactating Adenomas Granular Cell Tumor of the Breast Localized Amyloid Tumor of the Breast Papilloma Complex Sclerosing Lesion, Radial Scar, and Sclerosing Papilloma Benign Spindle-Cell Lesions Gynecomastia and Other Lesions of the Male Breast Malignant Breast Lesions Intraductal Carcinoma Intracystic Carcinoma Ductal Carcinoma, NOS Key Features of Ductal Carcinoma Medullary Carcinoma Key Features of Medullary Carcinoma Mucinous (Colloid) Carcinoma Key Features of Mucinous (Colloid) Carcinoma Tubular (Well-differentiated) Carcinoma Key Features of Tubular Carcinoma Papillary Carcinoma Key Features of Papillary Carcinoma Micropapillary Carcinoma Key Features of Micropapillary Carcinoma Secretory Carcinoma Apocrine Carcinoma Lobular Carcinoma Key Features of Lobular Carcinoma Inflammatory Carcinoma Paget’s Disease Metaplastic Carcinoma Squamous Cell Carcinoma of the Breast Adenoid Cystic Carcinoma Radiation- and Chemotherapy-induced Changes of the Breast Phyllodes Tumor Key Features of Phyllodes Tumor Sarcomas of the Breast Breast Angiosarcoma Other Sarcomas Breast Lymphoma Breast Plasmacytoma Metastatic Malignancies to the Breast Cytologic Prognostication Hormone Receptor Determinations in Fine-needle Aspirates of the Breast Nipple Discharge Cytology Ductal Lavage Cytology References 27 Mediastinum Contents Introduction Anatomic Compartments and Clinical Correlation Roles of Fine-needle Aspiration Cytology Technical Considerations Non-neoplastic Lesions Benign Mediastinal Cysts Reactive Mesothelial Hyperplasia Reactive Lymphoid Hyperplasia Acute Mediastinitis and Chronic Sclerosing Mediastinitis Granulomatous Lymphadenitis Nodular Hyperplasia of Thyroid Castleman’s Disease Extramedullary Hemopoiesis Neoplastic Lesions Thymoma Thymoma with Predominance of Medullary Component Thymoma with Predominance of Cortical Component Key Features of Thymoma with Predominance of Medullary Component Key Features of Thymoma with Predominance of Cortical Component Thymic Carcinoma Key Features of Thymic Carcinoma Thymic Neuroendocrine Tumors Key Features of Thymic Carcinoid Seminoma Key Features of Seminoma Embryonal Carcinoma Key Features of Embryonal Carcinoma Yolk Sac Tumor Key Features of Yolk Sac Tumor Choriocarcinoma Teratoma Key Features of Teratoma Precursor T-Lymphoblastic Lymphoma Key Features of Precursor T-lymphoblastic Lymphoma Primary Mediastinal Large B-cell Lymphoma Key Features of Primary Mediastinal Large B-cell Lymphoma Anaplastic Large-cell Lymphoma Key Features of Anaplastic Large-cell Lymphoma Hodgkin’s Lymphoma Key Features of Hodgkin’s Lymphoma Neurilemmoma and Neurofibroma Key Features of Neurilemmoma Neuroblastoma, Ganglioneuroblastoma, and Ganglioneuroma Key Features of Neuroblastoma Paraganglioma Soft Tissue Tumors Follicular Dendritic Cell Sarcoma Key Features of Follicular Dendritic Cell Sarcoma Parathyroid Adenoma Metastatic Carcinomas Diagnostic Pitfalls and Algorithms Diagnostic Pitfalls and Practical Points Diagnostic Algorithms (Fig. 27-23) Approach to Small-cell-rich Mediastinal Lesions (Table 27-3) Approach to Large-cell-rich Mediastinal Lesions (Table 27-4) Approach to Spindle Cell-rich Mediastinal Lesions (Table 27-5) Concluding Remarks References 28 Kidneys, Adrenals, and Retroperitoneum Contents Kidneys Imaging Techniques Anatomy and Histology Cytology of the Normal Kidney Immunocytochemistry of Normal Kidney Structures Renal Cysts Congenital Cysts Acquired or Simple Cysts Association of Renal Malignancy with Renal Cysts Inflammatory Disorders of the Kidney Xanthogranulomatous Pyelonephritis Cytology. Abscess of the Kidney Cytology. Tumors of the Kidney Benign Renal Tumors Angiomyolipoma Cytology. Key Features of Angiomyolipoma Benign Epithelial Tumors Oncocytoma Cytology. Immunocytochemistry. Key Features of Oncocytoma Renal Adenoma Cytology. Metanephric Adenoma Cytology. Key Features of Metanephric Adenoma Malignant Epithelial Tumors Genetics and Molecular Biology Hereditary Kidney Cancer Von Hippel–Lindau: Clear Cell Renal Carcinoma Genetics. Hereditary Papillary Renal Carcinoma Genetics. Birt–Hogg–Dube Syndrome Genetics. Cytology. Hereditary Leiomyomatosis Renal Cell Carcinoma Genetics. Xp11.2 Translocation Renal Cell Carcinoma Genetics. Cytology. Classification of Renal Tumors Clear Cell (Conventional) Renal Cell Carcinoma Histology. Grading of Renal Cell Carcinoma. Cytology. Immunocytochemistry. Key Features of Clear Cell RCC Chromophobe Cell Renal Carcinoma Cytology. Genetics. Immunohistochemistry. Differential Diagnosis. Key Features of Chromophobe Cell Renal Carcinoma Papillary Renal Cell Carcinoma Genetics. Cytology. Immunohistochemistry. Key Features of Papillary Renal Cell Carcinoma Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Key Features of Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Sarcomatoid Renal Cell Carcinoma Cytology. Differential Diagnosis. Key Features of Sarcomatoid Renal Cell Carcinoma Collecting Duct Carcinoma of the Kidney Cytology. Immunohistochemistry. Key Features of Collecting Duct Carcinoma Renal Medullary Carcinoma Cytology. Immunohistochemistry. Genetics. Differential Diagnosis. Key Features of Renal Medullary Carcinoma Rare Renal Cortical Tumors Carcinoid Tumor of the Kidney Cytology. Juxtaglomerular Cell Tumor Cytology. Immunocytochemistry in Renal Neoplasms Pitfalls Tumors of the Renal Pelvis Urothelial Carcinoma Cytology. Key Features of Urothelial Carcinoma Squamous Cell Carcinoma Adenocarcinoma Adenosquamous Carcinoma Undifferentiated Carcinoma Metastases to the Kidney Lymphoma of the Kidney Primary Sarcoma of the Kidney Adrenals Imaging Techniques Anatomy and Histology Cytology of the Normal Adrenal Gland Immunohistochemistry Cytology of Benign Entities Adrenal Cysts Adrenal Myelolipoma Adrenal Hyperplasia Benign Adrenal Cortical Nodules Histology. Cytology. Adrenocortical Carcinoma Cytology. Immunohistochemistry. Key Features of Adrenocortical Carcinoma Tumors Metastatic to the Adrenals Tumors of the Medulla Pheochromocytomas Cytology. Key Features of Pheochromocytoma Neuroblastoma, Ganglioneuroblastoma, and Ganglioneuroma Cytology. Retroperitoneum Imaging Techniques Anatomy Neoplastic Lesions Benign Tumors and Masses Retroperitoneal Sarcomas Liposarcoma Leiomyosarcoma Malignant Fibrous Histiocytoma Round Cell Sarcomas Embryonal Rhabdomyosarcomas Intra-abdominal Desmoplastic Small-cell Tumor Alveolar Soft Part Sarcoma Lymphoma Metastatic Tumors Cytology. Germ Cell Tumors Cytology. Diagnostic Accuracy of FNA in Kidneys, Adrenals, and Retroperitoneum Concluding Remarks References 29 Liver Contents Introduction Imaging Techniques Normal Liver Histology Cytology Non-neoplastic Mass Lesions Hydatid Cyst Cytology Key Features of Hydatid Liver Cyst Clonorchiasis Cytology Amebic Abscess Cytology Pyogenic Abscess Cytology. Granulomas Cytology Benign Mesenchymal Tumors Cavernous Hemangioma Cytology Key Features of Cavernous Hemangioma Hepatic Angiomyolipoma Key Features of Hepatic Angiomyolipoma Physical Features of Liver Aspirates Benign Hepatocellular Lesions Fatty Metamorphosis Cytology Viral Hepatitis Cytology Alcoholic Hepatitis Cytology Cholestasis Cytology Focal Nodular Hyperplasia Key Features of Focal Nodular Hyperplasia Liver Cell Adenoma Cytology Key Features of Liver Cell Adenoma Cirrhosis Cytology Macroregenerative Nodule Key Features of Macroregenerative Nodule Borderline Nodule Key Features of Borderline Nodule Hepatocellular Carcinoma Cytology Well-differentiated Hepatocellular Carcinoma. Classic Well-differentiated Hepatocellular Carcinoma. Microtrabecular Well-differentiated Hepatocellular Carcinoma. Microacinar Well-differentiated Hepatocellular Carcinoma. Clear Cell Well-differentiated Hepatocellular Carcinoma. Key Features of Well-differentiated Hepatocellular Carcinoma Moderately Differentiated Hepatocellular Carcinoma. Key Features of Moderately-Differentiated Hepatocellular Carcinoma Poorly Differentiated Hepatocellular Carcinoma. Key Features of Poorly Differentiated Hepatocellular Carcinoma Hepatocellular Carcinoma with Pleomorphic Large Cells. Fibrolamellar Carcinoma Cytology Key Features of Fibrolamellar Carcinoma Hepatoblastoma Cytology Key Features of Hepatoblastoma Pure Fetal Epithelial Type. Embryonal and Fetal Type. Mixed Epithelial and Mesenchymal Type. Tumors of Intrahepatic Bile Duct Bile Duct Adenoma Cytology Cholangiocarcinoma Cytology Primary Sarcomas Angiosarcoma Cytology Epithelioid Hemangioendothelioma Tumors Metastatic to the Liver Diagnostic Accuracy Concluding Remarks References 30 Pancreas Contents Introduction Technical Aspects Rapid On-site Interpretation Performance Characteristics Tissue Management Solid Masses Cyst Fluid Analysis Cytology Nomenclature and Reporting General Approach to Cytological Diagnosis of Pancreatic FNA Normal Pancreatic Tissue and Contaminants Acinar Epithelium Key Features of Benign Acinar Cells Ductal Epithelium Key Features of Benign Ductal Epithelium Islets of Langerhans Contaminants Key Features of Contaminants from EUS-FNA of the Pancreas Mesothelial Cells Duodenal Epithelium Gastric Epithelium Solid Pancreatic Masses Chronic Pancreatitis Clinical Features. Imaging Features. Key Features of Chronic Pancreatitis (Figs 30-11–30-13) Differential Diagnosis and Ancillary Testing. Prognosis and Therapy. Autoimmune Pancreatitis (Lymphoplasmacytic Sclerosing Pancreatitis) Clinical Features. Imaging Features. Key Features of Autoimmune Pancreatitis (Figs 30-14–30-16) Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Ductal Adenocarcinoma Clinical Features. Imaging Features. Key Features of Ductal Adenocarcinoma High-grade Adenocarcinoma (Fig. 30-17) Well-differentiated Adenocarcinoma (Figs 30-18–30-20) Key Features of Adenocarcinoma Variants Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Pancreatic Neuroendocrine Tumor Clinical Features. Imaging Features. Key Features of Pancreatic Neuroendocrine Tumor (Figs 30-26–30-30) Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Acinar Cell Carcinoma Clinical Features. Imaging Features. Key Features of Acinar Cell Carcinoma (Figs 30-33, 30-34) Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Pancreatoblastoma Clinical Features. Imaging Features. Key Features of Pancreatoblastoma (Fig. 30-35) Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Solid-pseudopapillary Neoplasm Clinical Features. Imaging Features. Key Features of Solid-pseudopapillary Neoplasm (Figs 30-36–30-39) Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Secondary Pancreatic Neoplasms Pancreatic Cysts Pseudocyst Clinical Features. Imaging Features. Key Features of Pseudocyst (Fig. 30-42) Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Lymphoepithelial Cyst Clinical Features. Imaging Features. Key Features of Lymphoepithelial Cyst (Fig. 30-43) Differential Diagnosis and Ancillary Studies. Serous Cystadenoma Clinical Features. Imaging Features. Key Features of Serous Cystadenoma (Fig. 30-44) Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Lymphangioma Clinical Features. Imaging Features. Key Features of Lymphangioma (Fig. 30-46) Differential Diagnosis and Ancillary Studies. Prognosis and Therapy. Primary Neoplastic Mucinous Cysts Mucinous Cystic Neoplasm and Intraductal Papillary Mucinous Neoplasm Mucinous Cystic Neoplasm. Clinical Features. Imaging Features. Prognosis and Therapy. Intraductal Papillary Mucinous Neoplasm. Clinical Features. Imaging Features. Prognosis and Therapy. Key Features of MCN and IPMN (Figs 30-47–30-52) Differential Diagnosis and Ancillary Studies. Concluding Remarks References 31 Pediatric Tumors Contents Introduction Incidence of Pediatric Tumors and Histologic Types Techniques in Pediatric Cytopathology Ancillary Techniques Image-guided FNA FNA Cytology: Indications, Advantages, Contraindications, and Complications Indications Advantages and Limitations Contraindications Complications Head and Neck Tumors Benign Tumors Hemangiomas and Lymphangiomas Branchial Pouch Anomalies Key Features of Branchial Pouch Cysts Maxillary Tumors Ameloblastoma Key Features of Ameloblastoma Malignant Tumors Mucoepidermoid Carcinoma Key Features of Mucoepidermoid Carcinoma Tumors of the Eyes Retinoblastoma Key Features of Retinoblastoma Tumors of the Orbit Inflammatory Pseudotumor of the Orbit Thyroid Gland Tumors Benign Tumors Nodular Follicular Hyperplasia Malignant Tumors Papillary Carcinoma Medullary Carcinoma Cervical–Thyroid Teratoma Other Malignant Tumors Lung Tumors Benign Tumors Inflammatory Pseudotumor Key Features of Inflammatory Pseudotumor Malignant Tumors Bronchial Adenoma Carcinoid Tumor. Key Features of Carcinoid Tumor Bronchogenic Carcinoma Key Features of Bronchogenic Carcinoma Sarcomas Pulmonary Blastoma Key Features of Pulmonary Blastoma Tumors of the Mediastinum Tumors of the Thymus Gland Thymic Hyperplasia Key Features of Thymic Hyperplasia Neoplasms of the Thymus Thymomas. Key Features of Thymomas Malignant Lymphomas of the Mediastinum Hodgkin’s Disease. Lymphoblastic Lymphoma. Large-cell Lymphoma. Gastrointestinal Tract Tumors Gastric Tumors Tumors of the Intestine Mesenteric Cysts of the Omentum Key Features of Mesenteric Cysts Cystic Lymphangioma Malignant Tumors Adenocarcinoma Appendicular Tumors Key Features of Carcinoid Tumor Tumors of the Liver Benign Epithelial Tumors Focal Nodular Hyperplasia Key Features of Focal Nodular Hyperplasia Regenerative Nodular Hyperplasia Hepatocellular Adenoma Benign Mesodermal Tumors Mesenchymal Hamartoma Key Features of Mesenchymal Hamartoma Infantile Hemangioendothelioma Key Features of Infantile Hemangioendothelioma Cavernous Hemangioma Malignant Tumors Hepatoblastoma Key Features of Hepatoblastoma Hepatocellular Carcinoma Undifferentiated Embryonal Sarcoma Metastasis Tumors of the Pancreas Exocrine Tumors Pancreatoblastoma (Pancreatic Adenocarcinoma of Childhood) Key Features of Pancreatoblastoma Adenocarcinoma of the Pancreas Endocrine Tumors Tumors of Lymph Nodes Benign Tumors Reactive Lymphadenopathy Malignant Tumors Non-Hodgkin’s Lymphomas B-cell Lymphoblastic Lymphomas B-cell Diffuse Large-cell Lymphoma Small Non-cleaved Cell Lymphoma (Burkitt’s Lymphoma) T-cell Lymphoblastic Lymphoma Hodgkin’s Disease Langerhans Cell Tumors Langerhans Cell Histiocytosis Eosinophilic Granuloma Hand–Schüller–Christian Disease Letterer–Siwe Disease Key Features of Langerhans Cell Histiocytosis Langerhans Cell Sarcoma Breast Tumors Fibroadenoma Key Features of Fibroadenoma Gynecomastia Key Features of Gynecomastia Fibrocystic Changes and Cysts Vascular Tumors Carcinoma Key Features of Secretory Carcinoma Sarcomas Malignant Hematopoietic Neoplasms Genital Tract Tumors Rhabdomyosarcoma Tumors of the Ovary Benign Tumors Benign Cysts. Malignant Tumors Germ Cell Tumors. Mature Teratoma. Immature Teratoma. Dysgerminoma. Yolk Sac Tumor. Embryonal Carcinoma. Granulosa Cell Tumor. Epithelial Tumors. Serous Tumors. Papillary Serous Cystadenoma. Borderline Serous Cystadenocarcinoma. Papillary Serous Cystadenocarcinoma. Mucinous Tumors Mucinous Cystadenoma. Borderline Mucinous Cystadenoma. Mucinous Cystadenocarcinoma. Other Malignant Tumors of the Ovary Male Genital Tract Tumors Tumors of the Skin Benign Epithelial Tumors Key Features of Keratinous Cysts Pilomatrixoma Key Features of Pilomatrixoma Benign MESENCHYMAL Tumors Malignant Tumors Melanoma Key Features of Melanoma Basal Cell Carcinoma Squamous Cell Carcinoma Metastatic Cutaneous Tumors Soft Tissue Tumors Non-neoplastic Soft Tissue Tumors Vascular Tumors Benign Vascular Tumors. Key Features of Hemangioma Malignant Vascular Tumors. Peripheral Neurogenic Tumors Benign Neurogenic Tumors. Key Features of Neurofibroma Malignant Neurogenic Tumors. Fibroblastic and Myofibroblastic Tumors Key Features of Fibromatosis Myogenic Tumors Rhabdomyoma Rhabdomyosarcoma Key Features of Embryonal Rhabdomyosarcoma Fibrohistiocytic Tumors Benign Fibrohistiocytic Tumors Benign Fibrous Histiocytoma. Key Features of Benign Fibrous Histiocytoma Intermediate Fibrohistiocytic Lesions. Key Features of Dermatofibrosarcoma Protuberans Malignant Fibrohistiocytic Tumors Key Features of Malignant Fibrohistiocytoma Adipose Tumors Benign Tumors Lipomas. Key Features of Lipoma Lipoblastoma. Key Features of Lipoblastoma Malignant Adipose Tumors Liposarcoma. Key Features of Myxoid Liposarcoma Myxoid Tumors Myxoma Synovial Tumors Synovial Sarcoma Key Features of Synovial Sarcoma Undifferentiated Sarcoma Bone Tumors Osteosarcoma Giant Cell Tumors Round Cell Tumors Primitive neuroectodermal tumor–Ewing’s sarcoma Melanotic Neuroectodermal Tumor of Infancy Key Features of Melanotic Neuroectodermal Tumor Urinary Tract Tumors Nephroblastoma (Wilms’ Tumor) Key Features of Wilms’ Tumor Mesoblastic Nephroma Key Features of Mesoblastic Nephroma Rhabdoid Tumor Tumors of the Urinary Bladder Inflammatory Myofibroblastic Tumor Key Features of Inflammatory Myofibroblastic Tumor Rhabdomyosarcoma Key Features of Rhabdomyosarcoma Adrenal Gland Tumors Adrenal Cortex Tumors Adenomas Key Features of Adrenocortical Adenoma Adrenocortical Carcinoma Key Features of Adrenocortical Carcinoma Medullary Tumors Neuroblastoma Key Features of Neuroblastoma Tumors of the Retroperitoneum Differential Diagnosis Round Cell Tumors Fusocellular Tumors Epithelial/Epithelioid Tumors Diagnostic Accuracy of FNA Cytology Causes of Error False negatives False positives Concluding Remarks References D Effects of Therapy on All Body Sites 32 Effects of Therapy on Cytologic Specimens Contents Introduction Radiation Biology Stroma Epithelium General Cellular Changes Key Features of Radiation Therapy Female Genital Tract Acute Radiation Changes Chronic Radiation Changes Prediction of Prognosis and Recurrence Oral Mucosa Lower Respiratory Tract Urinary Tract Breast Cytology. Prostate Cytology. Thyroid Cytology. Antineoplastic Chemotherapy Key Features of Chemotherapy Bleomycin Cytology. Key Features of Bleomycin Therapy Busulfan Cytology. Key Features of Busulfan Therapy Bladder Thiotepa Cytology. Cyclophosphamide Cytology. Key Features of Cyclophosphamide Therapy Antineoplastic Biologic Response Modifiers Bacillus Calmette–Guérin Urinary Bladder Cytology. Prostate Cytology. Key Features of BCG Therapy Transplant Immunosuppressive Therapy Immunotoxicity and Neoplasia after Transplant Immunosuppressive Therapy Cyclosporine Lymphomas and Lymphoproliferative Disorders. Lymphoproliferative Disorder. Cytology. Lymphoma Cytology. Uterine Cervix. Evaluation of Allograft Transplant Rejection and Immunosuppressive Toxicity Fine-needle Aspiration of Renal Allograft Urine Cytology of Renal Allograft Thyroid-suppressive Therapy Carbimazole Cytology. Radioactive Iodine Thermal Injury Electrocautery of the Uterine Cervix Acute Phase Early Healing Repair Cryotherapy Cytology. Key Features of Cryotherapy Laser Therapy Cytology. Loop Electrosurgical Excisional Procedure Foreign Body: Intrauterine Devices Cytology. Transurethral Resection and Core Needle Biopsy of the Prostate Cytology. Hormonal Therapy Drug Resistance Assessment of Cell Death Key Features of Apoptosis Key Features of Necrosis Concluding Remarks References 3 Special Techniques in Cytology 33 Cytopreparatory Techniques Contents Introduction Specimen Evaluation Fixation Fixation Methods Wet Fixation Wet Fixation with Air Drying Spray Fixation Liquid-based Fixation for Papanicolaou Tests Lysing Fixation for Bloody Samples Procedure 1 Procedure 2 Procedure 3 Procedure 4 Procedure 5 Air Drying for Selected Cell Samples Papanicolaou Staining Methods Progressive Staining Method Stain Quality Control Regressive Staining Method The Nuclear Stain: Hematoxylin. Hematoxylin Formula. Procedure Suggested for Evaluating Hematoxylin Exhaustion Counterstains: Orange G and EA Orange G Modified Orange G Stock Solution Working Orange G Solutions Formula 1: Formula 2: Eosin Modified EA Stock Solutions. Working EA Solution Automated vs. Manual Staining Procedures Rapid Staining Procedures for Fine-needle Aspirations Diff-Quik Stain Ultrafast Papanicolaou Stain Helpful Hints: Manual Staining with the Papanicolaou Method Troubleshooting the Papanicolaou Staining Methods Progressive Method Regressive Method Progressive and/or Regressive Method Cross-contamination Method to Avoid Floaters Coverslipping Manual Coverslipping Procedures Procedure 1: Slide Technique Procedure 2: Coverslip Technique Labeling Automated Coverslipping Procedure Liquid Mounting Media De-staining and Re-staining Slides De-staining and Re-staining Procedures Collecting and Processing Non-gynecologic Cell Samples Body Cavity Fluids Methods of Cell Preparation for Body Fluids. Cerebrospinal Fluid Preparation Genitourinary Tract Samples and Other Watery Specimens Preparatory Techniques for Direct Smears and Cytospin Samples Procedure 1 for Direct Smears Procedure 2 for Cytospin Cell Preparation Respiratory Tract Specimens and Other Mucoid Samples Unfixed Mucoid Respiratory Tract Samples Ferruginous Bodies Pneumocystis carinii Cell Block Procedures Cellient Cell Block Processor Supravital Staining Staining Body Fluids Infection Control Other Factors Related to Cytopreparation Concluding Remarks References 34 Digital Pathology/Telepathology Contents Introduction to Digital Cytology: Basic Principles The Basics of Digital Pathology Methods of Obtaining, Handling, and Moving Digital Images Whole Slide Image Scanners and Parameters for Acquisition of Images Telepathology with Digital Images Applications of Digital Pathology Image Archiving Telepathology Applications Telediagnosis/Teleconsultation Rapid Cytology Assessments Primary and Secondary Diagnostic Interpretation Digital Cytology Applications in Education The Use of Digital Cytology for Proficiency Testing Administrative, Legal, and Regulatory Issues in Digital Cytology Prospects for the Future of Digital Cytology Concluding Remarks References 35 Automation in Cervical Cytology Contents Introduction Historical Attempts at Automation The Rationale for Automation Cytology Automation: Accuracy and Productivity Key Features by Which Liquid-based Preparation may Improve Accuracy Key Features by Which Computerized Automated Screening may Improve Accuracy Currently Available Automation Platforms Liquid-based Preparation Hologic ThinPrep Pap Test Becton Dickinson SurePath Other Liquid-based Methods Operating Characteristics of Liquid-based Preparation Automated Screening Devices The PapNet System Becton Dickinson FocalPoint Devices Quality Control Application. Primary Screening Application. Location-guided Screening Application. The Hologic ThinPrep Imaging System Laboratory Process Issues Associated with the Use of Automated Devices Reporting Issues Issues with Specimens that cannot be Successfully Processed Stain Use in Automated Systems Training Required for Initiation of Automated Methods Laboratory Workflow Issues Issues Associated with Automation and Screening Workload in the Cytology Laboratory Cost-effectiveness of Liquid-based Preparation and Automated Screening Devices Concluding Remarks References 36 Immunocytochemistry Contents Introduction Immunocytology: Technical Aspects Specimen Collection Fixation Standardization Issues Rehydration and Storage Antigen Retrieval Controls Immunocytology: Diagnostic Use and Interpretation Immunocytology: Challenges and Limitations Specimens of Limited Quantity Practical Use of Immunostains in Diagnostic Cytopathology Immunostains in Effusion Cytology Mesothelial Markers Calretinin. Cytokeratin 5/6. Wilms’ Tumor Gene 1. D2-40. GLUT1. Non-mesothelial (Adenocarcinoma) Markers MOC31. Ber-EP4. Monoclonal CEA (mCEA). TAG or B72.3. Immunostains in Lung Cytology Thyroid Transcription Factor-1. Napsin A. p63/p40. Immunostains in Breast Cytology Estrogen Receptor. Gross Cystic Fluid Protein 15 (GCDFP-15, BRST-2). Mammaglobin. GATA3 (GATA-binding protein 3). E-cadherin and P120 Catenin. Immunostains in Renal and Adrenal Cytology RCC. TFE3. Immunostains in Gastrointestinal Cytology CDX2. Immunostains in Ovarian and Gynecologic Cytology Ovarian Markers Wilms’ Tumor Gene Product. PAX8. Hepatocyte Nuclear Factor-1β. Gynecologic Cytology Markers Markers of Dysplasia P16INK4a. Proliferation Markers MIB1 (Ki-67). Immunostains in Lymphoproliferative Disorders. Immunostains in Infectious Disease Immunostains in Tumor of Unknown Origin Immunocytochemistry for Targeted Therapies CD117 HER2/neu Hormone Receptors (Estrogen and Progesterone Receptors) CD20 Concluding Remarks References 37 Molecular Techniques Contents Introduction Molecular Techniques in Cytopathology Cell block Technique Fluorescence In Situ Hybridization Technical Aspects of FISH Scoring of FISH Signals Polymerase Chain Reaction Microsatellite Analysis/Loss of Heterozygosity Laser Microdissection Mutation Analysis Classical Mutation Analysis Next-generation Sequencing DNA Methylation Analysis Applications in Cytology Improved Diagnosis and Classification of Cancer Urinary Cytology Malignant Mesothelioma Lung Cytology Fluorescence In Situ Hybridization. Promoter Methylation. Other Applications Oligodendroglioma Barrett’s Esophagus Biliary Tract and Pancreas FISH in Gynecologic Cytology Translocation Detection in Lymphomas and Sarcomas Molecular Analysis of Therapeutic Targets HER2 Analysis in Breast Cancer EGFR and KRAS Mutation Analysis ALK Analysis in Non-small-cell Lung Cancer Other Predictive Markers ROS1 Rearrangement HER2 Mutations BRAF Mutations Outlook of Predictive Marker Testing Concluding Remarks References 38 HPV Detection Techniques Contents HPV Biology General Information of Human Papillomavirus High-risk and Low-risk HPV Types Cutaneous Group HPV HPV and Cancer HPV in Cervical Cancer HPV is the Cause of Cervical Cancer HPV16 and HPV18 are More Oncogenic HPV16, 18, and 45 are Found in Younger Women with Cervical Cancer HPV in Head and Neck Cancer HPV Vaccines Mechanisms for HPV Oncogenesis E6 and E7 Oncoproteins Interact with Human Tumor Suppressor Genes HPV E6 Oncoprotein Induces the Degradation of P53 E7 Mediates the Degradation of Rb HPV Infection in Episomal Stage HPV Integration into the Human Genome HPV Detection Methods FDA-approved HPV Assays for Cervical Specimens Detection Principles HC2 High-risk HPV DNA Test Cervista HPV HR Assay Cobas HPV Test Aptima HPV Assay Other Commonly Used HPV Screening Assays HPV Testing Guidelines for Patient Screening and Management Additional HPV Detection Methods Commercial Genotyping Assays PCR-based HPV Detection HPV Detection in Formalin-fixed Paraffin-embedded Specimens Diagnostic Accuracy of HPV Screening Assays Concluding Remarks References Index A B C D E F G H I J K L M N O P Q R S T U V W X Y Z