Borderline nuclear change; can a subgroup be identified which is suspicious of high‐grade cervical intraepithelial neoplasia,i.e. CIN 2 or worse?

Borderline nuclear change; can a subgroup be identified which is suspicious of high‐grade cervical intraepithelial neoplasia, i.e. CIN 2 or worse? Only 10% of first borderline smears are associated with a histological high‐grade (HG) abnormality, i.e. CIN 2,3, invasive malignancy or glandular neoplasia on subsequent investigation. The advantages of highlighting this subgroup are obvious but is this possible? From 1996 and 1997, 242 borderline smears with histological follow‐up were examined by two independent experienced observers (observer 1 and 2) without prior knowledge of further investigation results. For each smear a profile of nuclear details was produced, also noting the type of cell mainly affected by the process; then the observers were asked to assess the degree of worry of HG disease for each smear i.e. whether the smear fell into group 1 borderline changes indicative of low‐grade (normal, inflammatory, CIN1/HPV) disease (BL/LG) or group 2 difficult borderline smear, HG disease (CIN 2,3, invasive neoplasia or glandular neoplasia) cannot be excluded (BL/HG). Observer 1 selected a group of BL/HG with a PPV for HG disease of 38%, with observer 2 having a PPV of 50%; this compared with the overall laboratory HG disease PPV for borderline smears of 14%. Both observers found the most useful criterion to be the increase in nuclear:cytoplasmic ratio. Our results show that it is possible to separate a small group of borderline smears which should be classified as ‘borderline/high grade lesion difficult to exclude’ (BL/HG). Both observers had some success in arriving at this classification although their method of selecting out this group was quite different.     

Significance of Borderline Nuclear Abnormality In Cervical Smears

Women with cervical smears showing borderline nuclear abnormality (BNA), or reactive changes in the form of squamous metaplasia (SM) or endocervical cell hyperplasia (ECH), were age-matched with healthy controls to determine the outcome of these conditions. No significant difference in the risk of dyskaryosis was observed in cases showing reactive changes and the controls. In contrast, there was a 23% excess of cases showing dyskaryosis in the repeat smears of cases of BNA over the controls. An odds ratio of 8.3 was obtained, showing dyskaryosis in subsequent smears after a diagnosis of BNA.     

Achievable standards, Benchmarks for reporting, and Criteria for evaluating cervical cytopathologySecond edition including revised performance indicators

Endocervical cells are not essential for an adequate smear, except where the previous abnormality was seen in endocervical cells. When three consecutive smears are reported as inadequate, the recommendation for colposcopy should be made at the discretion of the pathologist in the light of a review of the relevant slides and the clinical history of the woman concerned. The cellularity of previous sequential smears should not be combined in order to judge the present smear test as negative. There should be no more than three abnormal smears (including borderline) over any 10-year period without a recommendation for colposcopy. At least three negative smears, at least 6 months apart, should be reported before a woman is returned to routine recall following a smear showing mild dyskaryosis or borderline nuclear change. There is no evidence that demonstrates that selective double screening is any more effective in preventing false-negatives than rapid review and this practice cannot therefore be justified. Sensitivity should be based on all abnormalities detected on primary screening rather than on moderate dyskaryosis or worse. Ranges for reporting rates are based on the 10-90th percentiles of the range for laboratories reporting over 10000 screening smears per year in KC61 returns, but apply to all laboratories reporting screening smears.     

Fine needle aspiration cytology of lobular breast carcinoma. Comparison with other breast lesions

OBJECTIVE: To analyze the detailed cytomorphology of lobular breast carcinoma and to compare the cytologic smears of benign, borderline and infiltrating duct carcinoma. STUDY DESIGN: Fine needle aspiration cytology (FNAC) smears of histopathologically proven infiltrating lobular carcinoma (ILC), infiltrating ductal carcinoma (IDC), borderline lesions and benign breast lesions were selected for study. Detailed cytomorphologic analysis of the smears was carried out on hematoxylin and eosin- and May-Grünwald-Giemsa--stained slides, and a comparison of results was done. The various cytologic features were also graded semi-quantitatively with the numerical score; logistic regression analysis was done. RESULTS: There were 25 cases of ILC, 30 of IDC, and 10 borderline and 18 benign lesions. Cytologic diagnosis of malignancy on FNAC smears of ILC was offered in 19 cases; of them, 2 cases were diagnosed as ILC. The remaining six cases were diagnosed as borderline (four) and benign lesions (two). Overall sensitivity in detection of malignancy in ILC cases was 76%. FNAC smears of ILC showed moderate (52%) to abundant (32%) cellularity. The cells of ILC were arranged both in clusters and in dissociation (72%). Individual cells were monomorphic (40%) to mildly pleomorphic (60%), and the cells were smaller. The cells showed a smooth, regular nuclear margin; bland chromatin; and indistinct nucleoli. Indian file arrangement was frequently observed (28%). Nuclear molding (28%) and intranuclear inclusions (16%) were also noted. Intracytoplasmic lumina were seen in occasional cases. Logistic regression analysis was carried out, and a comparison between lobular carcinoma and ductal carcinoma, and borderline and benign lesions was done. Logistic regression analysis of cytomorphologic features showed that cellularity and nuclear margin irregularities were the two most important features to distinguish ILC from IDC. In comparison to borderline lesions, cell dissociation was more common in ILC. The salient cytologic features that helped to distinguish ILC from benign lesions was cell size, cellularity, cell uniformity and chromatin pattern. CONCLUSION: There are overlapping cytologic features between ILC, IDC and borderline breast lesions on FNAC smears. Logistic regression analysis may be helpful in this regard.     

A review of post-trachelectomy isthmic and vaginal smear cytology

Currently in the UK cervical cancer has a peak incidence in women aged 35-39. Fertility-conserving surgical treatment by radical trachelectomy is established in the management of early disease. This study aimed at establishing the value of cytology in follow-up after trachelectomy. The cytological features of isthmic-vaginal smears post-trachelectomy for cervical cancer are presented together with a discussion of relevant clinical issues. One hundred and ninety seven smears from 32 women were reviewed. Two of the 32 patients developed pelvic recurrences. In both cases recurrence was detected cytologically long before development of a clinical or radiological abnormality. There is, however, a potential for overcall due to the presence of endometrial cells. These were present in large numbers and varying configurations in 58% of smears and led to a false positive report of malignancy in 2% of smears. The rate of referral for a cytologist opinion was significantly higher in smears containing endometrial cells (26%) than those without (13%). While all smears contained squamous cells, 41% contained squamous cells only and it is proposed that such smears should be reported as unsatisfactory in the first 2 years after surgery and negative thereafter, although the absence of glandular cells should be recorded. When an abnormality is reported, smear review and multidisciplinary discussion may avoid unnecessary investigations.     

The use of the 'borderline' category in the reporting of cervical cytopathology in the UK: results of a survey conducted under the aegis of the British Society for Clinical Cytology

Objective: To determine how the ‘borderline’ category was used by cytopathologists in the UK when reporting cervical smears. Methods: A questionnaire was sent by email to members of the British Society for Clinical Cytology. Results: There is wide variation in the use of the ‘borderline’ category in the UK but the majority of respondents (77.6%) used it when reporting smears that were either on the borderline between negative and low grade squamous dyskaryosis (‘borderline ?low grade’), or on the borderline between negative and high grade squamous dyskaryosis (‘borderline ?high grade’), or on the borderline between negative and glandular dyskaryosis ‘borderline ?glandular dyskaryosis’). A significant minority (15.7%), however, did not use ‘borderline’ when reporting smears that showed an abnormality that was possibly high grade squamous dyskaryosis. A majority (79.1%) of respondents thought that it would be useful to have separate reporting categories for ‘borderline ?low grade’ and ‘borderline ?high grade’. Conclusions: There is diversity in the use of the category ‘borderline’ in the UK. The proposed revised BSCC terminology with separate categories for borderline ?low grade, borderline ?high grades and borderline ? glandular dyskaryosis reflects the opinion of the majority of respondents to the questionnaire.     

Clinicopathological significance of borderline nuclear change – high grade dyskaryosis not excluded

During a recent discussion on classification of cervical cytology, the introduction of a 'Borderline Nuclear Change - High Grade Dyskaryosis Not Excluded' (BNCH) category was proposed. BNCH cases diagnosed prospectively were retrieved from laboratory records. Questionnaires were sent to referring practitioners regarding clinicopathological outcome. Cytopathological features resulting in the BNCH classification were recorded on slide review. A total of 103 reports on conventional cervical smears diagnosed as BNCH from 1999 to 2002 were retrieved, comprising 0.096% of 107 634 smears. Of 86/103 cases with clinical follow-up, CIN2 or worse was present in 30 (35%); 15 (17%) showed a borderline/low-grade abnormality and 41 (48%) were negative. No individual cytopathological feature was predictive of high-grade disease on follow-up. The yield of high-grade abnormalities on follow-up of BNCH supports the introduction of this terminology.     

Cytology of polychrome-stained equine synovial fluid smears. Comparison with clinical findings, histologic specimens, Wright-Giemsa-stained smears and outcome.

Polychrome-stained equine synovial fluid specimens from 34 normal joints and 129 joints with clinical abnormalities were examined cytologically. The smears from joints with abnormalities were categorized as within normal limits (4.7%), slight abnormality (27.9%), proliferative synovitis (21.7%), neutrophilic pattern (20.2%), elongated cell pattern (10.1%), other moderate to marked abnormality (11.6%) and unsatisfactory (3.9%). Cytologic abnormalities that were not restricted to a single category included spindle cells, crystals, stellate cells and cartilage fragments. Multinucleate cells and mononucleate cells with dense cytoplasm and a delicate periphery were seen in smears from cases with clinical diagnoses of osteochondrosis or fracture; interpretation of these cells as osteoclasts and their mononucleate precursors was supported by positive staining with tartrate-resistant acid phosphatase. Smears within the same cytologic category were not found to correspond with a single clinical diagnosis. The identification of several cytologic patterns in cases with the same clinical diagnosis suggests that multiple stages of disease were sampled. Except in cases with the cytologic neutrophilic pattern, there was not a consistent relationship between the histologic features in synovial biopsy specimens and the cytologic findings; the morphologic variation within synovial membrane sections and between sections from different locations was sometimes marked. When compared with air-dried, Wright-Giemsa-stained smears, the polychrome-stained smears were more sensitive in the detection of cytologic abnormalities and were less often falsely negative or unsatisfactory. Following surgery, cases with clinical diagnoses of osteochondrosis (29 cases) and fracture (25 cases) were analyzed according to clinical outcome and cytologic category. While 80% of the horses with proliferative synovitis in cytologic specimens were sound, only 67% of those with the elongated cell pattern, 50% of those with slight abnormality and 33% of those with other moderate to marked abnormality were sound. A statistically significant relationship (P less than .02) was found in cases with a diagnosis of osteochondrosis: animals with a proliferative synovitis pattern were almost three times as likely to be sound as compared to those with slight abnormality. These findings indicate that polychrome-stained equine synovial fluid smears (1) provide information that is different from that found in corresponding histologic sections and (2) are superior to air-dried, Wright-Giemsa-stained smears for cytologic examination. The polychrome-stained equine synovial fluid smears were found to provide information supportive of clinical, radiographic and prognostic data.     

O-2Preliminary results of the ARTISTIC study: a randomised trial in screening to improve cytology

Annually in the UK around 250 000 cervical smears show low-grade abnormalities. Alternative management policies following a low-grade smear are cytological surveillance or referral for colposcopy. Their effectiveness and cost-effectiveness, and the potential for human papillomavirus (HPV) testing to triage women to either management, has been debated. Trial of management of borderline and other low-grade abnormal smears (TOMBOLA) (a large RCT) addresses these uncertainties, considering clinical, psychosocial and economic outcomes. 4439 women aged 20–59, resident in Grampian, Tayside or Nottingham with a low-grade smear were randomised to cytological surveillance (six-monthly smears in primary care) or hospital-based colposcopy. At colposcopy, women with visible abnormality were randomised to immediate treatment or biopsy and recall for treatment if necessary. Recruitment HPV status was assessed using PCR techniques. Women were followed for three years to an exit colposcopy. Cumulative incidence of CIN2 or more severe disease (CIN2+) in the colposcopy arm was 7.9% per year, higher than in cytological surveillance (5.8%; OR = 1.43, 95% CI 1.23–1.67). This difference was less marked for CIN3+ (OR = 1.27, 1.04–1.55), suggesting spontaneous regression of some CIN2, and that initial colposcopy can lead to over-treatment. There was little difference in psychosocial outcomes between arms. In comparison of biopsy and recall versus immediate treatment, there was no difference in cumulative incidence of CIN2+ or psychosocial outcomes. There was over-treatment and increased frequency/duration of bleeding with immediate treatment. There was no compelling economic reason to favour any one management method. Testing for HPV does not appear to be effective in triage. Based on these findings, we make management recommendations for women with low-grade smears.     

A retrospective clinical audit of cervical smears reported as 'glandular neoplasia'.

The aims of this study were to review the diagnostic pathway of women with smears reported as 'glandular neoplasia' and to outline the management, colposcopy findings, treatment and final histological diagnosis in these women. The design was a retrospective review. A total of 114 women were identified over a 5-year period from the cytology database at the Royal Liverpool University Hospital Cytology Department, whose hospital case notes were available for review. Methods included a review of the case notes for the demographic details, indication for smear, colposcopic findings, investigation and/or treatment procedures, histology, final diagnosis and current disease status. Of 114 smears reported as 'glandular neoplasia', 67 were reported as consistent with cervical glandular intra-epithelial neoplasia (CGIN), six with endocervical adenocarcinoma, 36 with endometrial adenocarcinoma and five with other glandular neoplastic abnormalities. The average age was 46.5 years. 79 (69.3%) smears were routine call/recall and 36 (30.7%) women were symptomatic. The positive predictive value (PPV) for a significant histological abnormality in the CGIN smear group was 80.6% (23.9% invasive carcinomas, 43.3% CGIN and 13.4% CIN) and the PPV of an 'endometrial adenocarcinoma' smear was 86.1%. Smears indicating glandular neoplasia are associated with a high probability of clinically significant lesions, the PPV of a CGIN smear being over 80%. Immediate referral for colposcopy and assessment by an experienced colposcopist is recommended.     

Proffered papers 9.30–10.00 Monday 15 September 2003 2 Clinicopathologic significance of the ‘borderline nuclear change – high grade dyskaryosis not excluded’ report

Both the original Bethesda system and the current UK classifications of cervical cytology have proved robust but each has a major weakness in the area of abnormalities of uncertain significance. Cytologists recognize that sometimes it is simply impossible to differentiate between reactive and dyskaryotic material. For this reason, the Australian version of the Bethesda system introduced a new category of ‘high grade inconclusive’ with a recommendation for referral to colposcopy. Approximately 60% of such cases are found to have high grade lesions at colposcopy (Schoolland M, Sterrett G, Knowles S et al.). The present UK system even with the proposed changes requires of the pathologist, a decision as to whether such cases are probably high grade (=a report of moderate dyskaryosis) or not (= a report of borderline). This continues to ignore the fact that sometimes you just cannot tell, even on review. We have taken a consecutive series of 50 referral smears, reported as moderate dyskaryosis, where the histological outcome (by loop cone) is known. These cases were rescreened and then reviewed blind by a pathologist with extensive experience of the Australian NH & MRC modified Bethesda system. On review, the material was reclassified along NH & MRC lines. The results were compared with the biopsy findings in order to determine whether the category of ‘inconclusive’ might be of value in the context of the NHSCSP.     

Rapid review in cervical cytology: a retrospective review of cases detected on rapid review within a DGH cytology department and subsequent outcome

We retrospectively reviewed smears detected by rapid review within a district general hospital (DGH) laboratory over a period of 33 months and the subsequent histological or cytological outcome. Sixty-three cases had adequate follow-up data: 32 subsequently had two negative smears and 31 had a histological abnormality on subsequent biopsy. Twenty were high-grade lesions (CIN2, CIN3 or a glandular lesion) and eight of these were preceded by a low-grade smear abnormality. We reviewed and compared the pattern and distribution of smear abnormalities in these 63 cases. Abnormalities were often present within few cells (76%, n = 48 with 50 abnormal cells or less) or in micro-biopsies (27%, n = 17). There was no statistical difference in the pattern and distribution of smear abnormality between the rapid review-detected smears with a biopsy-proven abnormality and those with negative follow-up smears. Overall, the positive predictive value for high-grade CIN detected by rapid review (75%) was within NHSCSP achievable standards targets. This review of rapid review-detected abnormalities and the biopsy and cytological follow-up reiterates the importance of the method in cervical screening.     

Subtyping borderline nuclear changes: is it of value in predicting high-grade cervical intraepithelial neoplasia on histology?

The aim was to determine the association between the subtypes of borderline nuclear changes (BNC) in cervical smears and high-grade cervical intraepithelial neoplasia (HCIN). BNC was reported in 23236 smears received in our laboratory over a 7-year period, 3278 patients were referred for colposcopy. Analysis was restricted to 2007 cases, which fitted the criteria of: (1). consistent subtyping of borderline change and (2). cervical histology result within 12 months of the last abnormal smear. BNC was reported in six categories and correlated with histology. Atypia bordering on dyskaryosis, atypical metaplastic cells and endocervical atypia, were associated with HCIN in 25%, 25.4% and 23.8% of cases, respectively. Dyskeratosis and koilocytotic atypia were associated with HCIN in 19.2% and 13.7% of cases, respectively. Some subtypes of borderline change are more frequently associated with HCIN. The difference is not sufficient to dictate clinical management.     

Five-year follow-up of women with borderline and mildly dyskaryotic cervical smears

This study investigated the 5-year follow-up status of women with cervical smears showing borderline nuclear changes (BNC) or mild dyskaryosis and the effect of koilocytosis on the outcome. Thirteen per cent of women with cervical smears showing BNC had high-grade cervical intraepithelial neoplasia (CIN). In contrast, 28% of women with cervical smears showing mild dyskaryosis had high-grade CIN. The presence of koilocytosis (24% for borderline smears and 34% for mild dyskaryotic smears) did not appear to influence the risk of developing high-grade CIN. Our results suggest that the simultaneous implementation of the British Society for Clinical Cytology proposed terminology and the colposcopy guidelines from the British Society for Colposcopy and Cervical Pathology could have an impact on colposcopy services.     

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.     

Six years' audit of laboratory workload and rates of referral for colposcopy in a cervical screening programme in three districts.

OBJECTIVE--To determine laboratory workload and rates of referral for colposcopy in a three district cervical screening programme during 1983-9 to assess the feasibility of accommodating call up of all women at risk, recall at three year intervals (now five year intervals), and investigation of women with all degrees of abnormality. DESIGN--Analysis of computerised screening histories dating back to 1977 of women screened in the Avon cervical screening programme. SETTING--Three district health authorities covering the population of Bristol and Weston-super-Mare, comprising 800,000 people, of whom 250,000 were female residents aged 20 to 64. SUBJECTS--196,977 Women aged 20 to 64 screened in cervical screening programme since 1983. RESULTS--Laboratory workload devoted to follow up of women with abnormalities increased sharply between 1987-8 and 1988-9, with increases of 54% (from 2075 to 3196) in the number of smears for follow up of severe dyskaryosis and invasive cancer, 40% (from 1925 to 2695) for mild and moderate dyskaryosis, and 49% (from 1793 to 2677) for borderline change. The increases were partly explained by the introduction in April 1988 of protocols for follow up and investigation based on guidance in an intercollegiate working party report. The proportion of women with mild and moderate dyskaryosis who were recommended for referral for colposcopy increased steadily from 9.9% in 1983-4 to 79.9% in 1988-9, and for borderline change the proportions were 3.5% and 13.6% respectively. Of all women tested in 1988-9, referral for colposcopy was recommended in 3%. CONCLUSIONS--The increase in laboratory follow up work identified, if it continued, could result in half of existing laboratory capacity in Avon being devoted to follow up work by 1993, with little prospect of maintaining call, recall, and quality control. Investigation of all women with minor cytological abnormalities is neither justifiable nor sustainable and will undermine the benefits of screening by increasing the rate of false positive results and the financial costs.     

ASCUS, mature metaplastic type. Cytologic diagnosis and follow-up

OBJECTIVE: To study the cytologic criteria for follow-up of mature metaplastic cells within the atypical squamous cells of undetermined significance (ASCUS) category. STUDY DESIGN: Squamous epithelial abnormalities between January 1994 and June 1997 at our institution totaled 2,632 and included squamous carcinoma (1), high grade squamous intraepithelial lesions (278), low grade squamous intraepithelial lesions (875) and ASCUS (1,478). From the ASCUS group, 134 (9.06%) were metaplastic; 89 were selected for review. Criteria for case selection were follow-up with tissue biopsy or at least two Pap smears and no previous epithelial abnormality. Patients ranged from 27 to 70 years of age. Parameters tabulated included number of abnormal cells per slide, their architecture, cell size, shape, cytoplasmic hue and texture, nuclear size and contour, chromatin pattern and nucleoli. Additionally, specimens were reviewed for hormonal status and inflammation. The findings were correlated with follow-up data. RESULTS: Cells generally appeared single or in loose, monolayered sheets of three to seven cells per group. The cells were well demarcated, polygonal or oval and ranged from 11 to 30 microns with cyanophilic or eosinophilic thickened cytoplasm. The round to oval nuclei with slight irregularity showed a minimally increased nuclear/cytoplasmic ratio with stippled chromatin. Upon review, 69 smears were confirmed as ASCUS-M. Follow-up revealed 42 with benign findings, 9 with persistent ASCUS/ASCUS-M and 18 with low grade squamous intraepithelial lesions. CONCLUSION: In mature metaplastic cells with minimal atypia in patients with no previous or concurrent dysplasia, the follow-up details were similar to those described for ASCUS-superficial/immediate squamous cells. These patients could be followed conservatively.     

An audit of colposcopy appointment processes in women with abnormal cervical cytology

C. Kietpeerakool, M. Manopunya, P. Phuprasertsak, T. Jaijit and J. Srisomboon An audit of colposcopy appointment processes in women with abnormal cervical cytology Objectives: This study was conducted to audit the waiting times and default rates of colposcopy using the standard requirements of the National Health Service Cervical Screening Programme (NHSCSP) 2004 guidelines. Methods: The records of 291 women with abnormal cervical smears referred to the colposcopy clinic between January and December 2008 at Chiang Mai University Hospital, Thailand, were reviewed. Results: The proportion of women with abnormal cervical smears of any grade receiving colposcopy appointments within 8 weeks of referral (96.9%) achieved the minimum requirements (≥ 90%). However, the waiting times for women with high‐grade squamous intraepithelial lesion, glandular cell abnormality and invasive lesion smears were longer than recommended by NHSCSP guidelines. The default rate of 15.8% in this study was slightly higher than recommended by the guidelines (< 15%). Having no health insurance, being known to have HIV infection and waiting times longer than 4 weeks were independent predictors of default from an initial colposcopy appointment. Conclusion: The waiting times for colposcopy among women with high‐grade smear abnormality and the default rate failed to meet standard requirements. Designing an effective protocol for colposcopy appointment processes is warranted.     

Proffered papers 9.30–10.00 Monday 15 September 2003

Both the original Bethesda system and the current UK classifications of cervical cytology have proved robust but each has a major weakness in the area of abnormalities of uncertain significance. Cytologists recognize that sometimes it is simply impossible to differentiate between reactive and dyskaryotic material. For this reason, the Australian version of the Bethesda system introduced a new category of 'high grade inconclusive' with a recommendation for referral to colposcopy. Approximately 60% of such cases are found to have high grade lesions at colposcopy (Schoolland M, Sterrett G, Knowles S et al .). The present UK system even with the proposed changes requires of the pathologist, a decision as to whether such cases are probably high grade (=a report of moderate dyskaryosis) or not (= a report of borderline). This continues to ignore the fact that sometimes you just cannot tell, even on review. We have taken a consecutive series of 50 referral smears, reported as moderate dyskaryosis, where the histological outcome (by loop cone) is known. These cases were rescreened and then reviewed blind by a pathologist with extensive experience of the Australian NH & MRC modified Bethesda system. On review, the material was reclassified along NH & MRC lines. The results were compared with the biopsy findings in order to determine whether the category of 'inconclusive' might be of value in the context of the NHSCSP.     

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.