The Bethesda system for reporting cervical cytology : definitions, criteria, and explanatory notes

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Foreword References Introduction References The 2014 BETHESDA SYSTEM FOR REPORTING CERVICAL CYTOLOGY Acknowledgements Contents Abbreviations 1: Specimen Adequacy 1.1 Background 1.1.1 Explanatory Notes 1.2 Minimum Squamous Cellularity Criteria 1.2.1 Cellularity Liquid-Based Preparations (Figs. 1.1–1.11): Conventional Preparations (Figs. 1.12–1.16): 1.2.2 Explanatory Notes 1.3 Endocervical/Transformation Zone (EC/TZ) Component (Figs. 1.17–1.22) 1.3.1 Explanatory Notes 1.4 Obscuring Factors (Figs. 1.23 and 1.24) 1.4.1 Explanatory Notes 1.5 Interfering Substances (Figs.  1.6 and 1.25) 1.5.1 Lubricants (Fig. 1.25) 1.5.2 Excessively Bloody Specimens (Fig. 1.6) 1.6 Human Papillomavirus Testing on Unsatisfactory Specimens 1.7 Management Guidelines Related to Adequacy 1.8 Report Formatting 1.9 Sample Reports References 2: Non-neoplastic Findings 2.1 Negative for Intraepithelial Lesion or Malignancy 2.2 Background 2.3 Normal Cellular Elements 2.3.1 Squamous Cells 2.3.1.1 Superficial Cell 2.3.1.2 Intermediate Cell 2.3.1.3 Parabasal Cell 2.3.2 Glandular Cells 2.3.2.1 Endocervical Cell 2.3.2.2 Endometrial Cell 2.3.3 Lower Uterine Segment and Directly Sampled Endometrial Cells (Figs. 2.7–2.9) 2.3.3.1 Criteria 2.3.3.2 Explanatory Notes 2.4 Nonneoplastic Cellular Variations 2.4.1 Squamous Metaplasia (Figs. 2.10–2.13) 2.4.1.1 Criteria 2.4.1.2 Explanatory Notes 2.4.2 Keratotic Cellular Changes (Figs. 2.14–2.17) 2.4.2.1 Typical Parakeratosis (Figs. 2.15 and 2.16) 2.4.2.1.1 Criteria 2.4.2.2 Hyperkeratosis (Fig. 2.17) 2.4.2.2.1 Criteria 2.4.2.3 Explanatory Notes 2.4.3 Tubal Metaplasia (Figs. 2.18–2.21) 2.4.3.1 Definition 2.4.3.2 Criteria 2.4.3.3 Explanatory Notes 2.4.4 Atrophy (Figs. 2.22–2.27) 2.4.4.1 Definition 2.4.4.2 Criteria 2.4.4.3 Explanatory Notes 2.4.5 Pregnancy-Related Cellular Changes (Figs. 2.28–2.30) 2.4.5.1 Hormonal Changes (Fig. 2.28) 2.4.5.1.1 Criteria 2.4.5.2 Decidua (Fig. 2.29a) 2.4.5.2.1 Criteria 2.4.5.3 Cytotrophoblast 2.4.5.3.1 Criteria 2.4.5.4 Syncytiotrophoblast (Fig. 2.29b) 2.4.5.4.1 Criteria 2.4.5.5 Arias-Stella Reaction (Fig. 2.30) 2.4.5.5.1 Criteria 2.4.5.6 Explanatory Notes 2.5 Other Nonneoplastic Findings 2.5.1 Reactive/Reparative Cellular Changes 2.5.1.1 Definition 2.5.2 Reactive Cellular Changes Associated with Inflammation (Includes Typical Repair) (Figs. 2.31–2.40) 2.5.2.1 Criteria 2.5.2.2 Explanatory Notes 2.5.3 Lymphocytic (Follicular) Cervicitis (Figs. 2.41 and 2.42) 2.5.3.1 Criteria 2.5.4 Reactive Cellular Changes Associated with Radiation (Figs. 2.43 and 2.44) 2.5.4.1 Criteria 2.5.4.2 Explanatory Notes 2.5.5 Reactive Cellular Changes Associated with Intrauterine Contraceptive Device (Figs. 2.45–2.47) 2.5.5.1 Criteria 2.5.5.2 Explanatory Notes 2.6 Glandular Cells Status Post Hysterectomy (Figs. 2.48 and 2.49) 2.6.1 Criteria 2.6.2 Explanatory Notes 2.7 Organisms 2.7.1 Trichomonas vaginalis (Figs. 2.50–2.53) 2.7.1.1 Criteria 2.7.1.2 Explanatory Notes 2.7.2 Fungal Organisms Morphologically Consistent with Candida Species (Figs. 2.54–2.56) 2.7.2.1 Criteria 2.7.2.2 Explanatory Notes 2.7.3 Shift in Flora Suggestive of Bacterial Vaginosis (Figs. 2.57 and 2.58) 2.7.3.1 Criteria 2.7.3.2 Explanatory Notes 2.7.4 Bacteria Morphologically Consistent with Actinomyces (Figs. 2.60–2.62) 2.7.4.1 Criteria 2.7.4.2 Explanatory Notes 2.7.5 Cellular Changes Consistent with Herpes Simplex Virus (Fig. 2.63) 2.7.5.1 Criteria 2.7.5.2 Explanatory Notes 2.7.6 Cellular Changes Consistent with Cytomegalovirus (Fig. 2.64) 2.7.6.1 Criteria 2.7.6.2 Explanatory Notes 2.8 Sample Reports References 3: Endometrial Cells: The How and When of Reporting 3.1 Other 3.2 Background 3.3 Exfoliated Endometrial Cells (Figs. 3.1–3.4) 3.3.1 Criteria 3.4 Explanatory Notes 3.5 Sample Reports References 4: Atypical Squamous Cells 4.1 Epithelial Cell Abnormalities 4.2 Background 4.3 Atypical Squamous Cells 4.3.1 Definition 4.4 Atypical Squamous Cells – Undetermined Significance (ASC-US) (Figs. 4.1–4.19) 4.4.1 Definition 4.4.2 Criteria 4.4.3 Explanatory Notes 4.5 Common Patterns Classified as ASC-US (Figs. 4.15–4.19) 4.5.1 Atypical Parakeratosis (APK) (Figs. 4.15 and 4.16) 4.5.2 Atypical Repair (Figs. 4.17 and 4.18) 4.5.3 Atypia in Postmenopausal Women and in Atrophy (Fig. 4.19) 4.5.4 Other Patterns 4.6 Atypical Squamous Cells – Cannot Exclude an HSIL (ASC-H) (Figs. 4.20–4.33) 4.6.1 Definition 4.7 Common ASC-H Patterns 4.7.1 Small Cells with High N/C Ratios (“Atypical Immature Metaplasia”) (Figs. 4.20–4.26) 4.7.1.1 Criteria 4.7.1.2 Explanatory Notes 4.7.2 “Crowded Sheet Pattern” (Fig. 4.27) 4.7.2.1 Criteria 4.7.2.2 Explanatory Notes 4.8 ASC-H Mimics 4.8.1 Non-squamous Cells (Figs. 4.30–4.33) 4.8.2 Artifacts (Fig. 4.34) 4.9 Management 4.10 Quality Assurance 4.11 Sample Reports References 5: Epithelial Cell Abnormalities: Squamous 5.1 Epithelial Cell Abnormalities 5.2 Background 5.3 Low-Grade Squamous Intraepithelial Lesion (LSIL) (Figs. 5.1–5.13) 5.3.1 Criteria 5.4 Problematic Patterns in LSIL 5.4.1 Keratinized Squamous Cells (Fig. 5.8) 5.4.2 Borderline Changes (Figs. 5.9–5.11) 5.5 Mimics of LSIL 5.5.1 Pseudokoilocytosis (Fig. 5.7) 5.5.2 Herpes Cytopathic Effect (Fig. 5.12) 5.5.3 Radiation Changes (Fig. 5.13) 5.6 Management of LSIL 5.7 High-Grade Squamous Intraepithelial Lesion (HSIL) (Figs. 5.14–5.48) 5.7.1 Criteria 5.8 Problematic Patterns in HSIL 5.8.1 Syncytial Aggregates/Hyperchromatic Crowded Groups (Figs 5.15–5.17 and 5.29) 5.8.2 SIL with Endocervical Gland Involvement (Figs. 5.31–5.34) 5.8.3 HSIL: Pattern Resembling Endometrial Cells and Repair (Figs. 5.35–5.37) 5.8.4 Single and Rare Small HSIL Cells (Figs. 5.27 and 5.28) 5.8.5 HSIL: Abnormal Stripped Nuclei (Figs. 5.22b, 5.38 and 5.39) 5.8.6 Streams of HSIL Cells, Usually Within Mucus (Figs. 5.40 and 5.41) 5.8.7 Keratinizing High-Grade Lesions (Figs. 5.26, 5.42–5.44) 5.8.8 HSIL in Atrophy (Figs. 5.45 and 5.46) 5.8.9 LSIL with Some Features Suggestive of the Presence of a Concurrent HSIL (Figs. 5.42, 5.47, and 5.48) 5.9 Mimics of HSIL 5.9.1 Isolated Cells 5.9.2 Isolated Epithelial Cells (Figs. 5.49–5.52) 5.9.3 Inflammatory Cells Such as Histiocytes or Lymphocytes (Figs. 2.41, 2.42, 3.6, and 3.8) 5.9.4 Decidualized Stromal Cells (Figs. 2.28 and 5.53) 5.9.5 Hyperchromatic Crowded Groups (HCGs) 5.10 HSIL with Features Suspicious for Invasion (Figs. 5.44 and 5.55) 5.11 Management of HSIL 5.12 Squamous Cell Carcinoma 5.12.1 Definition 5.12.2 Keratinizing Squamous Cell Carcinoma (Figs. 5.56–5.59) 5.12.2.1 Criteria 5.12.3 Nonkeratinizing Squamous Cell Carcinoma (Figs. 5.60–5.63) 5.12.3.1 Criteria 5.12.4 Explanatory Notes 5.12.5 Problematic Patterns and Pitfalls Associated with Squamous Cell Carcinoma 5.12.5.1 Low Cellularity Specimens and Cases with Obscuring Blood (Figs. 5.64 and 5.65) 5.12.5.2 Atypical Repair (Fig. 5.66) 5.12.5.3 Tumor Diathesis Mimics (Figs. 5.67 and 5.68) 5.12.6 Squamous Cell Carcinoma Versus Adenocarcinoma (Fig. 5.69) 5.13 Sample Reports References 6: Epithelial Abnormalities: Glandular 6.1 Epithelial Cell Abnormalities 6.2 Background 6.3 Atypical Endocervical Cells 6.3.1 Definition 6.3.2 Atypical Endocervical Cells: NOS (Figs. 6.1–6.7) 6.3.2.1 Criteria 6.3.3 Atypical Endocervical Cells, Favor Neoplastic (Figs. 6.9–6.11) 6.3.3.1 Definition 6.3.3.2 Criteria 6.3.4 Explanatory Notes 6.3.5 Mimics of Atypical Glandular Cells (Fig. 6.12–6.14) 6.3.5.1 High-Grade Squamous Intraepithelial Lesion (Figs. 5.15–5.17, 5.25, 5.29, 5.31, 5.33, and 5.34) 6.4 Atypical Endometrial Cells (Figs. 6.15–6.18) 6.4.1 Definition 6.4.2 Criteria Preparation-Specific Criteria 6.4.3 Explanatory Notes 6.5 Management of AGC 6.6 AGC Reporting Rates and Outcomes 6.7 Endocervical Adenocarcinoma In Situ (AIS) (Figs. 6.21–6.32) 6.7.1 Definition 6.7.2 Criteria Preparation-Specific Criteria 6.7.3 Explanatory Notes 6.7.4 Management of Endocervical Adenocarcinoma in situ 6.8 Coexisting Squamous and Glandular Lesions (Figs. 6.33 and 6.34) 6.9 Adenocarcinoma 6.9.1 Endocervical Adenocarcinoma (Figs. 6.35–6.45) 6.9.1.1 Criteria 6.9.1.2 Explanatory Notes 6.9.2 Endometrial Adenocarcinoma (Figs. 6.46–6.54) 6.9.2.1 Criteria 6.9.2.2 Explanatory Notes 6.9.3 Extrauterine Adenocarcinoma (Figs. 6.55–6.59) 6.10 Sample Reports References 7: Other Malignant Neoplasms 7.1 Background 7.2 Uncommon Primary Tumors of the Cervix and Uterine Corpus (Figs. 7.1–7.9) 7.2.1 Carcinomas 7.2.1.1 Spindle Squamous Cell Carcinoma (Fig. 7.1) 7.2.1.2 Poorly Differentiated Squamous Carcinoma with Small Cells (Fig. 7.2) 7.2.2 Neuroendocrine Tumors 7.2.2.1 High-Grade Neuroendocrine Carcinoma (Small Cell Carcinoma) (Fig. 7.3) 7.2.2.2 Large Cell Neuroendocrine Carcinoma (Fig. 7.4) 7.2.2.3 Low-Grade Neuroendocrine Tumor (Carcinoid Tumor) 7.2.3 Glassy Cell Carcinoma (Fig. 7.5) 7.2.4 Mucinous Carcinoma, Gastric Type (Minimal Deviation Adenocarcinoma, Adenoma Malignum) (Fig. 7.6) 7.2.5 Malignant Müllerian Mixed Tumor (MMMT) or Carcinosarcoma (Figs. 7.7 and 7.8) 7.2.6 Clear Cell Adenocarcinoma (Fig. 7.9) 7.2.7 Sarcomas (Figs. 7.10–7.12) 7.2.8 Other Primary Tumors 7.3 Secondary or Metastatic Tumors 7.3.1 Extrauterine Carcinomas (Figs. 7.13–7.18) 7.3.2 Malignant Melanoma (Figs. 7.19 and 7.20) 7.3.3 Malignant Lymphoma (Fig. 7.21) References 8: Anal Cytology 8.1 Background 8.2 Anal Cancer 8.3 Anal Cytology 8.4 Sampling 8.5 Adequacy (Figs. 8.1– 8.5) 8.6 Interpretation 8.6.1 Negative for Intraepithelial Lesion or Malignancy (Figs. 8.1 – 8.3, and 8.6) 8.6.2 Organisms (Figs. 8.7 – 8.10) 8.6.3 Squamous Cell Abnormalities (Figs. 8.11 – 8.19) 8.6.3.1 Atypical Squamous Cells (ASC) (Figs. 8.11 and 8.12) 8.6.3.2 LSIL (Figs. 8.13 and 8.14) 8.6.3.3 HSIL (Figs. 8.15 – 8.19) 8.6.3.4 Squamous Cell Carcinoma (SCC) (Figs. 8.20 – 8.22) 8.6.4 Glandular Cell Abnormalities 8.7 Anal Cytology Statistics 8.8 Biomarkers 8.9 Clinical Management 8.10 Sample Reports References 9: Adjunctive Testing 9.1 Background 9.2 Adjunctive HPV Testing 9.2.1 Introduction 9.2.2 Applications of High-Risk Human Papillomavirus Testing (hrHPV) with or Without Genotyping 9.2.3 Description of Test Method and Results 9.2.4 Sample Reports for HPV Testing 9.3 Immunochemical Assays 9.3.1 Reporting of Molecular/Immunochemical and Cytologic Results 9.3.2 Sample Report for Adjunctive Immunocytochemical Result References 10: Computer-Assisted Interpretation of Cervical Cytology 10.1 Background 10.2 Automated Devices 10.3 Reporting the Results of Computer-Assisted Review 10.4 Automated Review Summary 10.5 Sample Reports References 11: Educational Notes and Comments Appended to Cytology Reports 11.1 Background 11.2 Educational Notes and Comments: Summary 11.3 Sample Reports References 12: Risk Assessment Approach to Management 12.1 Background 12.2 Principles of Risk Assessment 12.3 Development of Risk Thresholds for Cervical Cancer Screening 12.4 Current Options for Cervical Cancer Screening 12.5 Conclusion References Index