EU guidelines for reporting gynaecological cytology Amanda Herbert Guy s & St Thomas Foundation NHS Trust 5th EFCS Annual Tutorial, Trondheim, Norway 28 th May 1 st June 2012
EU guidelines aim to harmonize cervical cytology terminology throughout Europe EU guidelines can be downloaded in full from the internet Terminology chapter is also published as Herbert et al. Cytopathology 2007; 18:213-9 and is available to download free
Comparison between EU guidelines and other terminology systems EU guidelines recommend that all systems should be translatable into the Bethesda system (TBS 2001) and the CIN classification retained for histology Three-tier systems (as used in the UK) are acceptable if compatible with TBS Atypical and borderline are almost synonymous; but their use may be slightly different in practice Classification, language, free text reports, management can all make a difference
Sample adequacy TBS was the first system to provide criteria for sample adequacy EU and TBS require results to include a statement on adequacy of the sample..and a reason if the specimen is deemed to be inadequate (too few cells, cells poorly fixed or obscured by blood or exudate) Evidence of TZ sampling should be recorded but is not a requirement for adequacy
Sample adequacy EU guidelines recommend TBS criteria for adequacy as a minimum (conventional: at least 8,000-12,000 squamous cells; LBC: at least 5,000 squamous cells on a slide (3.8 cells per x40 high-power field) Local guidelines may be used where fixed intervals for screening are in place or where quality indicator comments (exudate, blood, cell content) are not provided in the report.
Sample adequacy TBS recognises a grey area between 5,000 and 20,000 cells on LBC slides (i.e. between 4 and 12 squamous cells per x40 field) Satisfactory but limited by is no longer recognised in TBS or EU guidelines Some centres chose to carry out cell counts because studies have linked the likelihood of abnormal cells being present to cellularity of the slide.
Negative for intraepithelial neoplasia or malignancy - TBS No malignant or dyskaryotic cells seen - BSCC / NHSCSP Benign cellular findings need not be reported if recognised as such and carry no risk of SIL / cancer Post-partum or atrophic changes Repair changes Microglandular hyperplasia Tubo-endometrioid metaplasia Tubal metaplasia Lower uterine segment, irradiation changes Inflammation Intrauterine contraceptive device (IUD) Benign glandular cells in post-hysterectomy specimens. The presence of Trichomonas vaginalis, Candida, Actinomyceslike organisms and Herpes virus multinucleated cells may be reported as they have potential clinical relevance.
Negative for intraepithelial neoplasia or malignancy - TBS No malignant or dyskaryotic cells seen - BSCC / NHSCSP Benign cellular findings need not be reported if recognised as such and carry no risk of SIL / cancer Post-partum or atrophic changes Repair changes Microglandular hyperplasia Tubo-endometrioid metaplasia Tubal metaplasia Lower uterine segment, irradiation changes Inflammation Intrauterine contraceptive device (IUD) Benign glandular cells in post-hysterectomy specimens. The presence of Trichomonas vaginalis, Candida, Actinomyceslike organisms and Herpes virus multinucleated cells may be reported as they have potential clinical relevance.
Spectrum of change: dysplasia, dyskaryosis, SIL, CIN Grey area: atypical, ASC-US, borderline, ASC-H, AGL
LSIL / mild dysplasia / dyskaryosis / condyloma / HPV LSIL includes changes known to be associated with infection by human papillomavirus (HPV), most obviously manifest by koilocytosis CIN1 cannot be distinguished from transient HPV infection, which is the rationale for surveillance to identify the minority of LSIL that progresses to CIN2 or worse LSIL in TBS corresponds mild dysplasia, mild dyskaryosis (Denton et al 2008) and CIN1 EU guidelines 2008
HSIL / moderate and severe dysplasia / carcinoma in situ / CIN2 and CIN3 Most terminological systems link moderate with severe dysplasia as high-grade lesions EU guidelines 2008 Linking moderate dysplasia with mild rather than severe dysplasia would need to define moderate dysplasia as such if their results were to be translatable Kocjan et al. BSCC, Bethesda or other? Terminology in cervical cytology European panel discussion. Cytopathology 2005;16:113-119
HSIL / moderate and severe dysplasia / carcinoma in situ / CIN2 and CIN3 CIN2 is an intermediate grade, in which the changes fall short of CIN3 / CIS and the diagnosis is less robust or reproducible Likelihood of progression is lower and of regression greater than CIN3 Intermediate category makes it less necessary to use terms such as LSIL-H, mild-moderate dyskaryosis/dyskaryosis, SIL/dysplasia/dyskaryosis NOS or ungraded
HSIL / moderate / severe dysplasia / ca in situ / CIN2 / 3 Problem with HSIL What do we do with cases that overlap? Mixed and indeterminate cases (SIL / dyskaryosis NOS) should be managed as high-grade Free-text reports can identify these cases if necessary Classify as moderate or qualify HSIL as favor CIN2
Adenocarcinoma, adenocarcinoma in situ (AIS) and cervical intraepithelial glandular neoplasia (CGIN) AIS / high-grade CGIN forms a recognisable sub-type of highgrade abnormalities Difficult if not impossible to separate in situ and invasive adenocarcinoma (?glandular neoplasia category in UK) No recognisable criteria for diagnosis low-grade CGIN Reports may suggest site of origin (endocervix, endometrium, extrauterine)
Severe dyskaryosis?invasive carcinoma (UK) Squamous cell carcinoma (TBS) Most systems define a category for invasive squamous cell carcinoma The diagnosis of invasion requires a histological biopsy but there are cytological changes that suggest that possibility The diagnosis may be less obvious with LBC
Borderline and atypical mean the same thing Large / mature squamous cells (ASC-US; borderline, NOS) usually normal vs. LSIL Small / immature squamous cells (ASC-H) usually normal vs. HSIL (occ. cancer) Immature metaplasia Hyperchromatic crowded groups Atypical glandular cells usually reactive vs. HSIL / glandular neoplasia Not otherwise specified Favor neoplasia
Differences between borderline and ASC / AGC Borderline and mild dyskaryosis are linked for statistics as lowgrade cytology Borderline, high-grade not excluded gets included with borderline as a whole and will be included in HPV-triage Borderline, high-grade not excluded probably used less often than ASC-H Negativity in HPV-triage will prevent investigation and followup of SIL-mimics
Principles of EU guidelines All systems describe a spectrum of change extending from HPV infection to cancer with a surrounding grey area of equivocal changes. Benign changes need not be reported as such Three-tier systems may readily be translated into TBS Categories retained for glandular neoplasia and invasive cancer CIN system is retained for for histology Management policies may cause minor differences between borderline and atypical categories Conversion tables given in Denton et al. 2008
PROPOSED BSCC TERMINOLOGY 2002 19 th March 2002 I NEGATIVE, INADEQUATE AND BORDERLINE BSCC 1986 (as modified for ABC2) BSCC 2002 Bethesda 2001 Negative No dyskaryotic cells identified Negative for intra-epithelial lesion Inadequate (give reasons) Borderline nuclear change (includes koilocytosis) Unsatisfactory (give reasons) Borderline nuclear change Borderline nuclear change (use description in free text) BNC, high-grade not excluded BNC, glandular (use free text to describe cell type) Unsatisfactory for evaluation Atypical squamous cells ASC-US ASC-H Atypical endocervical/ endometrial/ glandular cells; NOS, favour neoplastic
PROPOSED BSCC TERMINOLOGY 2002 19 th March 2002 II MILD, MODERATE AND SEVERE DYSKARYOSIS BSCC 1986 (as modified for ABC2) BSCC 2002 Bethesda 2001 Mild dyskaryosis Moderate dyskaryosis Severe dyskaryosis Ungraded dyskaryosis (code and manage as moderate dyskaryosis) Low-grade squamous dyskaryosis (NOS, or use free text description of koilocytosis and mild dyskaryosis) High-grade squamous dyskaryosis (NOS, or use free text description of moderate and severe dyskaryosis) Ungraded dyskaryosis (code and manage as high-grade) LSIL HSIL
PROPOSED BSCC TERMINOLOGY 2002 19 th March 2002 III?INVASIVE,?GLANDULAR NEOPLASIA BSCC 1986 (as modified for ABC2) BSCC 2002 Bethesda 2001? Invasive?Invasive Squamous cell carcinoma?glandular neoplasia?glandular neoplasia (use free text to describe type) Endocervical Endometrial Other NOS Adenocarcinoma AIS Endocervical Endometrial Extra-uterine NOS
Enjoy the tutorial and Trondheim!