The 2001 Bethesda System: Gynae Cytology Reporting PDF

THE BETHESDA SYSTEM 2001 GYNAE CYTOLOGY REPORTING CONTENTS 1. Introduction 2. Evolution of reporting systems 3. Bethesda 2001 4. Differences between BTS 1991 and 2001 5. Sample adequacy 6. Interpretation 7. Management algorithm 8. Summary REPORTING SYSTEMS - EVOLUTION  PAP classification 1941 -...

THE BETHESDA SYSTEM 2001 GYNAE CYTOLOGY REPORTING CONTENTS 1. Introduction 2. Evolution of reporting systems 3. Bethesda 2001 4. Differences between BTS 1991 and 2001 5. Sample adequacy 6. Interpretation 7. Management algorithm 8. Summary REPORTING SYSTEMS - EVOLUTION  PAP classification 1941 - Class 1-V  Dysplasia-CIS classification 1953 - divided into 4 grades i.e mild, moderate, severe, CIS  CIN classification (Richart 1968) - graded as CIN 1,2,3  BTS 1988,1991, 2001 Previous reporting system - PAP classification 1941  Class 1 - absence of atypical/abnormal cells.  Class 11 - atypical cytology but no evidence of malignancy (benign).  Class 111- suspicious for malignancy.  Class 1V - strongly suggestive of malignancy.  Class V - definitely malignant. NOTE: 1. He did not classify precursor lesions 2. Only meant to convey whether cancer present or not 3. As cervical precursor lesions became known and understood, this classification became obsolete. Previous reporting system - Dysplasia – CIS classification 1953  Dysplasia - all other disturbances of differentiation of the squamous epithelium lining the surface and the glands - divided into 4 grades i.e. mild, moderate, severe, CIS. NOTE: 1. Dr Ober suggested the term dysplasia 2. Dr Reagen popularised it. Previous reporting system - CIN terminology (Richart 1968)  A term for intraepithelial lesions antedating invasive cancer and graded as - CIN 1 - CIN 2 - CIN 3 NOTE: 1. Dr Richart realised that cervical lesions form a continuum 2. Dysplasia-CIS was rather artificial as CIS lesion do not behave like invasive lesion Bethesda system 1988, 1991- benefits  A uniform descriptive diagnostic terminology  Facilitate communication between labs  Facilitate communication between labs and clinicians  Stresses on adequacy of specimen  Enables audit/performance standards measurement Bethesda system 2001  1988 – Recommendations -developed as a uniform system of terminology that would provide clear guidance for clinical management.  1991 – 1st review - modify based on actual lab and clinical experience after its implementation.  2001 – 2nd review -most important contribution – creation of standardised framework for lab reports that included a descriptive report and an evaluation of specimen adequacy. - reflects important advances in biological understanding of cervical neoplasia and cervical screening technology - participation by 9 forum groups involving >20 countries Comparison of WHO and BTS WHO HPE terms Bethesda term  CIN1/Mild dysplasia  LSIL  CIN2/Moderate dysplasia  HSIL  CIN3/Severe dysplasia  HSIL  CIN3/Ca in Situ  HSIL  1991 2001 None Conventional Satisfactory for Type of sample Smear evaluation Liquid-based Satisfactory Satisfactory for for evaluation evaluation but Borang Permohon - limited by:.. an dan Unsatisfactory Adequac Laporan PAP Smear Interpret for evaluation Unsatisfactory y of ation Sample / Result for evaluation Within normal limits Negative for intraepithelial lesion or Benign cellular changes due to: malignancy Reactive changes associated with:.. Organism present Infection Other non-neoplastic findings  SAMPLE ADEQUACY SQUAMOUS CELLULARITY –CONVENTIONAL SMEAR  Estimated minimum of 8,000 to 12,000 well- preserved and well-visualized squamous cells.  Squamous metaplastic cells is counted as squamous cells during cellularity assessment.  SAMPLE ADEQUACY SQUAMOUS CELLULARITY (REFERENCE IMAGES) 500 cells/4x field 75 cells/4x field. Smear is unsatisfactory if all fields Minimum of 16 fields needed have this level or less to call smear adequate cellularity 1000 cells/4x field Minimum of 8 fields needed to call smear adequate  SAMPLE ADEQUACY SQUAMOUS CELLULARITY LIQUID-BASED PREPARATION  At least 5000 well-visualized/well-preserved sq. cells with 5000 -20,000 cells being borderline cellularity.  Estimating cellularity (Cytyc Thin Preps,20-mm diameter circle,microscope field no.22 eyepieces,40x) 1. Identify 10 fields across a diameter of LBP incl.centre of prep. 2. Count no.of sq. cells at 40x for each field 3. Average the count 4. At least 4 cells/field to correspond to at least 5,000  SAMPLE ADEQUACY LIQUID-BASED PREPARATION Unsatisfactory due to scanty squamous Satisfactory but borderline.This would cellularity.Endocervical cells seen estimate to be 4 cells/40x corresponding to slightly over 5000 ( ThinPrep, 10x ) cells for whole smear. ( ThinPrep,10x )  SAMPLE ADEQUACY Liquid –based preparation  Estimation of specimen cellularity is performed in specimen with apparent low to borderline squamous cellularity.  Slide with fewer than 5,000 cells should be examined for reason for scanty cellularity e.g excessive blood  Repeat slide after corrective action and cellularity assessed on the repeat slide.  SAMPLE ADEQUACY Endocervical Cell / Transformation Zone Component  At least 10 well-preserved endocervical cells or squamous metaplastic cells.  To report presence/absence of EC/TZ unless a woman has had a total hysterectomy  SAMPLE ADEQUACY Obscuring Factors  Poor fixation  Thick uneven smear  Thick inflammatory exudate  Lack of clinical data  >75% sq. cells obscured, specimen is unsatisfactory  50% to 75% sq. cells obscured, satisfactory, to state obscuring factor.  To evaluate percentage of cells obscured, not slide area.  SAMPLE ADEQUACY  Any specimen with epithelial cells abnormality is by definition satisfactory for evaluation.  If there is concern specimen is compromised due to unsatisfactory nature of smear, a note may be added indicating that a more severe lesion cannot be excluded.  To indicate presence of endometrial cells or microorganism even if smear is unsatisfactory.  NILM FUNGAL CONSISTENT WITH CANDIDA SPP.  Budding yeasts 3µm to 7 µm.  Pseudohyphae formed by elongated budding, show constrictions along their length  Candida ( Torulopsis glabrata ) does not form pseudohyphae in vivo or culture. It consists of small, uniform, round budding yeast surrounded by clear halos.  NILM SHIFT IN FLORA SUGGESTIVE OF BACTERIAL VAGINOSIS  Filmy background of small coccobacilli  Individual squamous cells may be covered by a layer of bacteria obscuring cell membrane – clue cells  eg of coccobacilli ; Gardnerella vaginalis,Mobiluncus spp.  Absence of lactobacilli ( normal vaginal flora )  Bacterial vaginosis is assoc with PID, preterm birth, operative gynae infections  NILM BACTERIA MORPHOLOGICAL CONSISTENT WITH Actinomyces spp.  Tangled clumps of filamentous organisms  Radial distribution, wooly body appearance  Acute inflammatory response with presence of neutrophils.  Associated with intrauterine contraceptive device ( IUD ) usage.  NILM CELLULAR CHANGES ASSOCIATED WITH HERPES SIMPLEX VIRUS  Nuclei have ground-glass appearance due to accumulation of viral particles leading to peripheral margination of chromatin.  Dense eosinophilic intranuclear inclusions surrounded by a halo or clear zone  Large multinucleated epithelial cells with moulded nuclei  NILM Trichomonas vaginalis  Pear-shaped,oval,round cyanophilic organism.  Size 15µm to 30µm  Nucleus pale,vesicular, eccentrically located  Eosinophilic cytoplasmic granules ( LBP )  Flagella ( LBP )  Leptothrix may be seen in association with Trichomonas vaginalis NILM OTHER NON-NEOPLASTIC FINDINGS  Benign cellular changes associated with  Inflammation / typical repair  Irradiation  Intrauterine contraceptive device ( IUD )  Atrophy  Presence of glandular cells post hysterectomy  Presence of endometrial cells ( in women >40 yrs of age )  NILM BENIGN CELLULAR CHANGES ASSOCIATED WITH INFLAMMATION / TYPICAL REPAIR  Typical repair  Cells in flat monolayered sheets with distinct cytoplasmic outlines  Streaming nuclear polarity  No single cell with nuclear atypia  Typical mitosis  Exuberant reactive changes may simulate  ASC-US  LSIL  ASC-H  NILM BENIGN CELLULAR CHANGES ASSOCIATED WITH IRRADIATION  Acute  Bizzare cell forms  Cellular debri  Degenerated blood  Chronic ( > 6/12 )  Cytomegaly  Nucleomegaly  Engulfed PMN Note : Chemotherapy changes are addressed under this category  NILM BENIGN CELLULAR CHANGES ASSOCIATED WITH INTRAUTERINE CONTRACEPTIVE DEVICE (IUD)  Affects endometrial or endocervical cells  Cells singly or clusters  Cytoplasmic vacuoles displacing nuclei  Nuclear degeneration  Nucleoli may be prominent  Differential : HSIL  Against : history of IUD  morph spectrum of abnormality absent  NILM BENIGN CELLULAR CHANGES ASSOCIATED WITH ATROPHY  Flat monolayer sheet of parabasal-type cells  Generalized nuclear enlargement  Atrophy with inflammation ( atrophic vaginitis )  Granular debri in background  Degenerated cells  Polymorphonuclear atrophy with inflammation leukocytes  NILM PRESENCE OF GLANDULAR CELLS POST HYSTERECTOMY  Cell type that can be seen  Endocervical-type glandular cells (cannot be differentiated from those sampled from endocervix)  Goblet / mucinous type cells  Endometrial-type cells  NILM PRESENCE OF GLANDULAR CELLS POST HYSTERECTOMY  Benign appearing glandular cells in post hysterectomy smears.  Postulates :  Development of adenosis after traumatic stimulation of stromal mesenchymal cells  Mucinous / goblet cell metaplasia in response to atrophy  Prolapse of fallopian tube after simple hysterectomy  NILM PRESENCE OF ENDOMETRIAL CELLS (WOMEN > 40yrs)  1991 Bethesda System , ‘cytologically benign appearing endometrial cells’ in postmenopausal women were reported under General categorization ‘Epithelial cell abnormality’  2001 Bethesda System, presence of normal endometrial cells in woman > 40 yrs.is reported under interpretation/result NILM.  To report presence of endometrial cells even if specimen is unsatisfactory ,but presence of benign endometrial cells does not make an unsatisfactory smear satisfactory.  NILM PRESENCE OF ENDOMETRIAL CELLS (WOMEN > 40yrs)  Optional educational comment is recommended when reporting exfoliated endometrial cells in a woman 40 years or older. “Exfoliated endometrial cells are usually derived from a benign process and only a small proportion of women with this finding have endometrial abnormalities.”  If date of LMP is provided, and specimen is obtained in first half of cycle, may comment that the finding of endometrial cells correlates with menstrual history.  NILM PRESENCE OF ENDOMETRIAL CELLS (WOMEN > 40yrs)  Ball-like clusters, rarely as single cells.  Nuclei small, round, approximate size of intermediate cell nucleus.  Scanty cytoplasm, may be vacuolated  Ill-defined cell borders  LBP : may appear atypical (enhanced chromatin detail, conspicuous nucleoli) Epithelial cell abnormalities – Squamous cell  1. Atypical squamous cells - of undetermined significance (ASC-US) - cannot exclude HSIL (ASC-H)  2. Low grade squamous intraepithelial lesion (LSIL) - encompassing HPV  3. High grade squamous intraepithelial lesion (HSIL) - with features suspicious for invasion  4. Squamous cell carcinoma (SCC) Epithelial cell abnormalities – Glandular cell  1. Atypical, NOS - endocervical cells - endometrial cells - glandular cells  2. Atypical - endocervical cells, favour neoplastic - glandular cells, favour neoplastic  3. Endocervical adenocarcinoma in situ (AIS)  4. Adenocarcinoma - endocervical, endometrial, extrauterine, NOS Ancillary testing  Briefly describe the assay performed e.g. HPV hybrid capture assay, in situ hybridisation  Report the result clearly  In view of future implementation of such testing  Involves testing for oncogenic/high risk types of HPV DNA – to determine management of ASC-US Automated review  if case is examined by automated device, specify device and result.  Type of instrumentation used  Indicate whether automated device evaluation without manual evaluation  Or automated screening combined with manual screening/review Educational notes and suggestion  May provide additional information regarding the significance or predictive value of the cytologic findings  Additional suggestions are optional  SAMPLE REPORTS 1. Sample adequacy Satisfactory for evaluation: endocervical/transformation zone component present Interpretation: Negative for intraepithelial lesion or malignancy Recommendation: Repeat smear at regular screening interval 2. Sample adequacy Unsatisfactory for evaluation of epithelial abnormality because of obscuring inflammation Comment : Trichomonas vaginalis identified. Recommendation: Repeat cervical cytology after treatment of Trichomonas vaginalis. 3. Sample adequacy Unsatisfactory for evaluation: Specimen rejected because slide was broken beyond repair Recommendation: Repeat smear  SAMPLE REPORTS 1. Sample adequacy : Satisfactory for evaluation; endocervical/transformation zone component absent. Interpretation: Negative for intraepithelial lesion or malignancy Reactive cellular changes associated with radiation. Recommendation: Repeat as scheduled 2. Sample adequacy: Satisfactory for evaluation;endocervical/transformation zone component present;partially obscuring inflammation present Intrepretation: Negative for intraepithelial lesion or malignancy Trichomonas vaginalis identified. Reactive squamous cells associated with inflammation Recommendation; Repeat smear in 6 months after treatment. MANAGEMENT QUIDELINES AND ALGORITHM FOR PAP SMEAR RESULTS  1.Flowchart for Management of Unsatisfactory Smear. PAP SMEAR UNSATISFACTORY FOR EVALUATION * NOTE Repeat smear in 3 Treat any infection. months Give a course of estrogen if there are atrophic changes. 2nd smear Negative for malignant unsatisfactory cells Satisfactory and Repeat smear in 3 negative months 3rd smear unsatisfactory Refer for colposcopy Refer to Flowchart for Management of ‘Negative For Malignant Cells’ Smear. Unsatisfactory for evaluation -Repeat smear  PAP SMEAR NEGATIVE FOR MALIGNANT CELLS (NILM) Atrophic No Specific Inflammator Endometrial changes endocervica micro- y changes cells seen (without l cells organisms inflammation seen identified ) Treat any Correlate Repeat Treat chang infection or with clinical smear in appropriately es atrophy. findings, as clinically Repeat smear 1 year resolv client’s age, indicated in 3–6 months. hormonal e and menstrual status 2nd smear with similar changes Repeat in 3-6 mths Treat any Changes chang infection or es atrophy. resolved Repeat smear resolv in 3–6 months. e 3rd smear with similar changes Refer Routine Routine Refer Gynaecolog screening screening Gynaecolog ist if schedule schedule ist necessary Negative for intraepithelial lesion or malignancy  Atrophic changes without inflammation - routine screening schedule  Atrohic changes with inflammation – clear inflammation/estrogen therapy – repeat in 3-6 months  No endocervical cells seen - repeat in 1 year  Specific organism identified – treat the infection and repeat in 3-6 months  Inflammatory changes - clear inflammation and repeat in 3-6 months  Endometrial cells seen - correlate with history; if abnormal setting - refer gynaecologist 3.Flowchart for Management of Abnormal Smear a. Atypical squamous cells PAP SMEAR ATYPICAL SQUAMOUS CELLS Cannot exclude Undetermined * NOTE HPV DNA testing should high grade significance be considered if available lesion (ASC-H) (ASC-US) If positive for high risk HPV, to refer for colposcopy Refer for Repeat smear colposcopy in 6 months ASC-US Negative for malignant cells LSIL HSIL Repeat smear in 6 months Resume routine screening if Refer for negative for colposcopy malignant cells Atypical squamous cells  ASC-H - refer for colposcopy  ASC-US – repeat in 6 months - if positive for high risk HPV,refer for colposcopy.. Persistent ASC-US - refer for colposcopy b. Low-grade Squamous Intraepithelial Lesion (LSIL) PAP SMEAR LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL) Yes No Assess Presence of at least one ment of criteria: client Age > 30 years Poor compliance Immunocompromised Symptomatic History of pre invasive Repeat smear lesion in 6 months High risk HPV positive. Immediate Negative for LSIL colposcop malignant cells y Resume routine Refer for screening colposcopy schedule Low grade squamous intraepithelial lesion (LSIL)  LSIL with at least 1 risk factor – refer for colposcopy  LSIL with no risk factor – repeat smear in 6 months  Persistent LSIL – refer for colposcopy. C. High-grade Squamous Intraepithelial Lesion (HSIL) and Squamous Cell Carcinoma PAP SMEAR HIGH-GRADE SQUAMOUS CELL SQUAMOUS CARCINOMA INTRAEPITHELIAL LESION (HSIL)/ SUSPICIOUS FOR INVASION Refer for colposcopy Refer to Gynaecological Oncologist HSIL and SCC  HSIL / suspicion for invasion – refer for colposcopy HSIL  SCC – refer to gynae oncologist HSIL with suspicion of invasion KSCC D. Flowchart for Management of Atypical Glandular Cells and Adenocarcinoma PAP SMEAR ALL ATYPICAL ATYPICAL ADENOCARCINOMAIN GLANDULAR CELLS ENDOMETRIAL CELLS SITU (AIS) (except Atypical & ADENOCARCINOMA Endometrial Cells) Refer to Gynaecologist Refer to Gynaecologist Refer to Gynaecological for: Oncologist colposcopy (with endocervical sampling) endometrial sampling (if > 35 years or abnormal bleeding) AGC and Adenocarcinoma  Atypical glandular cells, NOS – refer to gynaecologist.  Atypical glandular cells favour AGC NOS neoplastic – refer to gynaecologist  Atypical endometrial cells – refer gynaecologist  AIS – refer gynae oncologist AGC favour neoplastic  Adenocarcinoma – refer gynae oncologist AIS AGC NOS Endom Adenoca  SUMMARY How 2001 Bethesda System differs from previous 1991 Bethesda 1. Specimen adequacy ;  satisfactory for evaluation (satisfactory for evaluation + satisfactory for evaluation but limited by )  Unsatisfactory for evaluation 2. Intrepretation /result ( replaced ‘result’)  Term “Within normal limits” eliminated  Previous categories of ‘within normal limits’ and ‘benign cellular changes’ are combined into a single category ‘negative for intraepithelial lesion or malignancy (NILM)’  Term ‘organism’ replacing ‘infection’  Presence of glandular cells post hysterectomy  Presence of endometrial cells (in woman > 40 yrs of age) 3. ‘ASCUS’ changed to ‘ASC’, either ASC-US or ASC-H; Previous ASCUS favour reactive, downgrade to NILM 4. ‘AGUS’ changed to ‘AGC’; AGUS favour reactive is eliminated. 5. ‘AIS’ as separate entity. 6. 4 elements to 7 elements THANK YOU