Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid‐based cervical cytology

K. Chummun, M. Fitzpatrick, P. Lenehan, P. Boylan, E. Mooney and G. Flannelly
Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid‐based cervical cytology Background: In 2008, the management of women in Ireland with atypical glandular cells changed to immediate referral to colposcopy. The optimal management of these women is unclear. A balance between the detection of occult disease and overtreatment is required. Methods: Our study aim was to document the experience of this policy at the National Maternity Hospital, Dublin. Information from the computerized data management system was analysed with the statistical package SPSS. Results: In 2009, 156 women attended colposcopy following a single atypical glandular cell diagnosis on liquid‐based cytology. The mean age was 41 years. Thirty (19.2%) women had abnormal vaginal bleeding, 31 (19.9%) were smokers and 34 (21.8%) had received previous treatment. The colposcopy was satisfactory in 125 (80.1%) and unsatisfactory in 31 (19.9%). Cervical histology was available for 146 (93.6%) women: 57 excisional procedures and 89 diagnostic biopsies. Abnormal histology was detected in 46 women (31.5%). Four women (2.7%) had invasive cancer, five (3.4%) had adenocarcinoma in situ, 21 (14.4%) had cervical intraepithelial neoplasia (CIN) grade 2 or 3 and 16 (11.0%) had CIN1. No abnormality was detected in 100 women (68.5%), including 35 (61.4%) of those who had undergone excisional procedures. The colposcopic impression in this group was unsatisfactory in 10 women (28.6%), glandular abnormalities in six (17.1%), high‐ and low‐grade changes in 12 (34.2%) and six (17.1%) women, respectively, and normal in one (2.9%). The findings were essentially negative in the remaining 10 women: overall, 30 (19.2%) of the 156 women referred to colposcopy had at least CIN2. Conclusion: This study confirmed significant levels of high‐grade disease in women referred to colposcopy with atypical glandular cells on cytology. Concerns about undetected endocervical disease resulted in high levels of negative excisional biopsies. Alternative strategies, including endometrial sampling, human papillomavirus testing and discussion at clinicopathological meeting, should be considered.     

The treatment of CIN: what are the risks?

The treatment of squamous cervical intraepithelial neoplasia is to remove or destroy the transformation zone (TZ). It is likely that no method of treatment is superior to another if it is performed properly and the limited available evidence supports this view. The significant advantages of excision (simplicity, cost, outpatient procedure, histological examination of the entire TZ) mean that treatment thresholds may have lowered over the last decade. Long-term pregnancy-related morbidity associated with excision has been reported recently. The evidence would suggest that this increase equates to a genuine increase in serious adverse outcome for cone biopsy but not large loop excision of the transformation zone (LLETZ). The available data also point to an increase in both incomplete excision and premature labour associated with the excision of large endocervical TZs. The clinical implications arising from this are firstly that women with large type 2 and 3 TZs need appropriate counselling before treatment and that the threshold for treating young women with mild abnormalities needs review.     

European guidelines for clinical management of abnormal cervical cytology, Part 2

The current paper presents the second part of chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening . The first part of the same chapter was published in a previous issue ( Cytopathology 2008;19:342–54). This part provides guidance on how to manage and treat women with histologically confirmed cervical intraepithelial neoplasia. The paper describes the characteristics, indications and possible complications of excisional and ablative treatment methods. The three options to monitor the outcome after treatment (repeat cytology, HPV testing and colposcopy) are discussed. Specific recommendations for particular clinical situations are provided: pregnancy, immuno-suppression, HIV infection, post-menopause, adolescence and cyto-colpo-histological disparity. The paper ends with recommendations for quality assurance in patient management and some general advice on how to communicate screening, diagnosis and treatment results to the woman concerned. Finally, a data collection form is attached.     

Women’s preferences regarding options for management of atypical,borderline or low‐grade cervical cytological abnormalities: a review of the evidence

M. Z. Sadique and R. Legood Women’s preferences regarding options for management of atypical, borderline or low‐grade cervical cytological abnormalities: a review of the evidence Objectives: To review the evidence on women’s preferences for and valuation of alternative management pathways following identification of low‐grade cytological abnormalities as part of routine cervical cancer screening. The aim was to identify empirical studies evaluating women’s preferences regarding alternative management pathways and to compare the impact of alternative elicitation methods on results. Methods: A systematic review of the literature was conducted using the online bibliographic information service PubMed database. Empirical studies were identified that elicited general preferences, utilities or valuations based on willingness to pay (WTP) with respect to management of low‐grade cytology results. Data were extracted on the methodology used and the empirical results. Results: Where quality of life data were elicited directly from patients that were undergoing management of low‐grade abnormalities utilizing direct elicitation techniques such as WTP, general preference questionnaires and the Euroqol, the studies tended towards a preference in favour of HPV testing (and colposcopy referral if HPV positive) rather than repeat cytology. In contrast, where studies included the general population and presented hypothetical scenarios of treatment pathways, and explicitly tried to incorporate assessment of process utility, the evidence indicated a slight tendency to favour repeat cytology. Conclusion: Consideration of patient preferences in the management of low‐grade cytology is important for designing screening protocols. The reviewed studies indicate that potentially different conclusions may be drawn depending on the elicitation methodology and selection of participants in the research.     

Cervical cytology/histology discrepancy: a 4‐year review of patient outcome

E. L. Moss, A. Moran, G. Douce, J. Parkes, R. W. Todd and C. E. W. Redman Cervical cytology/histology discrepancy: a 4‐year review of patient outcome Objective: To investigate the diagnosis, review and management of women identified as having a cytology/histology discrepancy. Methods: A review of all patients diagnosed with a discrepancy between referral smear and cervical histology was performed between January 2003 and December 2004. Cases were followed for a minimum of 4 years and patient management and outcome reviewed. Results: A significant discrepancy was identified in 79 cases, 0.1% of all smears (n = 80 926) analysed during the study period. A discrepancy between cytology and histology, obtained from large loop excision of the transformation zone (LLETZ), was confirmed by multidisciplinary review in 42 cases (53.2%). In 37 cases (46.8%) the cytological and/or histological diagnosis was revised; the cytology was significantly more likely than the histology to be amended (chi square P = 0.005), most often because cytology had been overcalled. Of the confirmed discrepancy cases, 33 (78.6%) were due to high‐grade squamous cell or glandular abnormalities on cytology with a negative, inflammatory or human papillomavirus (HPV) infection on histology (HGC/NH). HGC/NH cases were managed by cytological follow‐up in 29 (87.9%), of which 72.4% of the smears were negative when performed at least 6 months post‐excision. During the 4‐year follow‐up period six women with a confirmed HGC/NH underwent a repeat cervical excision (hysterectomy or LLETZ), and of these, HPV effect was seen in two cases but no cervical intraepithelial neoplasia was detected in any of the histological specimens. Conclusion: Cytology overcall was responsible for the majority of cytology/histology discrepancies. A confirmed discrepancy is not an indication for a further excisional biopsy but follow‐up is essential because a small percentage of patients may have disease that has been missed.     

Colposcopic management of high‐grade referral smears: a retrospective audit supporting ‘see and treat'?

OBJECTIVE: The National Health Service Cervical Screening Programme monitors the quality of colposcopy services through the annual KC65 returns. The 2002 returns demonstrated that Standard 7c, which specifies a biopsy rate > or = 90% at first colposcopy visit for high-grade referrals, was not met in the assessed 3-month period. This was investigated along with the other standards. METHODS: Retrospective colposcopy records were accessed for the 597 new referrals, excluding 10 pregnant patients, seen at the colposcopy clinic at the Royal Victoria Infirmary between 1 July 2001 and 31 December 2002, following an abnormal high-grade smear. Cytology and histopathology computer records were checked for confirmation. The results were assessed against the colposcopy standards applicable at that time and the revised standards (2004). RESULTS: Biopsies were taken from 94.47% (Standard > or = 90%) of women at index colposcopy visit including wire loop excision biopsies from 66.16% (87.97% of high-grade colposcopic appearances). Cervical intraepithelial neoplasia (CIN) on histology was found in 91.79% in the study group (Standard > or = 85%) and in 96.71% of index visit biopsies (Standard > or = 90%), meeting the applicable colposcopy standards. The revised 2004 standards specify a biopsy in > or = 95% of high-grade referrals and excision biopsies in 95% if colposcopic appearances are also high-grade, if colposcopy is low grade but the smear is severely dyskaryotic, or when the lesion extends into the canal. The positive predictive value of high-grade cytology for this entire group was 75.54% with CIN present in 90.95%. CONCLUSION: From this study it appears that high-grade cytology in this centre reliably indicates high-grade CIN. Therefore, in women referred for colposcopy following a high-grade smear, excision biopsies should be performed in a higher proportion at the first visit to comply with the revised standards.     

Direct booking colposcopy clinic — the Portsmouth experience

We present 2 years data on direct booking in our colposcopy clinic. The new booking system has improved our efficiency and helped us to achieve the national quality standards on clinic waiting time. The non-attendance (DNA) rate has also improved.     

Outcome analysis of 4 years' follow-up of patients referred for colposcopy with one smear showing mild dyskaryosis

Objective: To assess the 4‐year outcome of patients after one smear showing mild dyskaryosis with respect to smear regression rate, prevalence of cervical intraepithelial neoplasia (CIN) and the effect of age. Methods: Retrospective analysis of patients diagnosed with initial mildly dyskaryotic smear during the year 2000 with a follow‐up period of 48 months. These women had not had any previous abnormal smears. Settings: Cytopathology Department and Colposcopy Unit, King’s College Hospital, London, UK. Results: We identified 524 patients of whom 375 patients with complete follow‐up data are included. The age range was 19–67 years with a median of 29 years. There were 207 patients aged 35 years or less (55%). At 6 months, 258 smears were performed and 47.8% of them were negative (95% CI: 41.6–54.0%). The total number of negative follow‐up smears in the first year was 198 out of a total of 397 smears performed (50%). This proportion has significantly increased between 1 and 4 years’ follow‐up to 67.5% (RR: 1.24; 95% CI: 1.14–1.35). Over the 4‐year period, 791 smears were performed and 477 were negative (60.3%; 95% CI: 56.9–63.7%). Of the 477 negative smears there were only 61 smears (12.8%; 95% CI: 10–16%), in 54 patients (14%; 95% CI: 11–18%) that reverted back to low‐grade cytological abnormality. In only one case the repeat smear showed high‐grade abnormality after initial negative follow‐up; however, on biopsy, histology showed CIN I. Out of the 375 patients, 70 required treatment with excisional biopsy (19%; 95% CI: 15.0–22.9%). Histology confirmed high‐grade CIN in only 41 cases giving a prevalence of 11% (95% CI: 8.1–14.5%). There were no cases of microinvasive or invasive cancer detected. Age (≤35 years versus >35 years) did not significantly affect either cytological or histological outcome. Conclusion: Sixty per cent of follow‐up smears after initial mild dyskaryosis subsequently became negative; of them 87.2% remained negative over the 4 year follow‐up. Treatment was only required in 19% of patients, with 11% prevalence of high‐grade CIN. Age did not affect the outcome. These results are reassuring and indicate that colposcopic referral may not be necessary after only one mildly dyskaryotic smear.