Development of a technical external quality assurance scheme in non-gynaecological cytology in UK.

Technical external quality assurance (EQA) schemes are well established for histopathology and cervical cytology but, to date, sadly lacking for diagnostic cytology (DC). This timely review redresses the balance by describing the development and evaluation of a technical EQA scheme for DC available to the UK, Europe and beyond.

Intra-operative frozen section analysis for suspected early-stage ovarian cancer: 11 years of Gateshead Cancer Centre experience.

OBJECTIVE: In centres in which intra-operative frozen section (FS) analysis is not performed, 'apparent' early-stage ovarian cancer diagnosed after surgery on paraffin section may require further restaging laparotomy or adjuvant chemotherapy. Previous studies on FS analysis have reported high sensitivity, specificity and overall accuracy. The objective of this article is to present the largest published dataset on the accuracy of FS analysis over an 11-year period from a single institution. DESIGN: Diagnostic test accuracy. SETTING: Northern Gynaecological Oncology Centre and Department of Cellular Pathology, Gateshead, UK. POPULATION: 1439 intra-operative FS analyses performed between January 2000 and December 2010 for suspected ovarian cancer. METHODS: Prospectively collected data on FS analysis were compared with gold standard paraffin section. MAIN OUTCOME MEASURES: Sensitivity, specificity, likelihood ratios and post-test probability. RESULTS: The overall sensitivity and specificity of FS analysis were 91.2% and 98.6%, respectively. Positive and negative likelihood ratios were 64.7% and 0.09%, respectively. The pre-test probability of an ovarian tumour being borderline or malignant was 45.8%. When FS analysis was reported to be positive, the post-test probability increased to 98% (confidence interval, 97-99%). Conversely, when FS analysis was reported to be negative, the post-test probability decreased to 7% (confidence interval, 6-9%). The majority of false test results were either borderline tumours or of mucinous differentiation. CONCLUSIONS: Intra-operative FS analysis has excellent diagnostic test accuracy and assists gynaecological oncologists to perform the appropriate surgery in 95% of cases, thereby preventing the morbidity of surgical staging in benign cases and the morbidity of restaging procedures or chemotherapy in early-stage malignant tumours.

Comparison of examination of the entire uterine cervix with routine cervical sampling in hysterectomy specimens from women with endometrial cancer.

BACKGROUND: Cervical involvement by endometrial cancer alters the FIGO stage and determines clinical management, but there are no accepted guidelines for cervical sampling of these cases. AIM: To assess whether sampling more than two "routine" blocks of the cervix (anterior and posterior) alters the pathological staging of hysterectomy specimens for endometrial cancer. METHODS: Histological involvement of the cervix was prospectively compared in hysterectomies performed for proven endometrial cancer (n = 61). Specimens had two "routine" blocks taken from anterior and posterior cervix; all of the remaining cervix was also processed for histological assessment. RESULTS: 61 cases of endometrial cancer had the entire uterine cervix processed. There were 54 cases of endometrioid adenocarcinoma and 7 special types. Twelve cases had cervical involvement (stage 2A or 2B), and seven cases were stage 3A or above, of which three also had cervical involvement. In none of the 61 cases did the additional cervical blocks (n = 544) taken alter the staging made on the "routine" blocks. CONCLUSION: Sampling of two blocks from the cervix appears sufficient for histological staging of endometrial cancer in hysterectomy specimens.

Computerized nuclear morphometry for the prediction of inguinal lymph nodes metastases in squamous cell carcinoma of the vulva.

This study evaluated the sensitivity and specificity of computerized morphometry in predicting lymph nodes metastases (LNM) in patients with squamous cell carcinoma (SCC) of the vulva. Histologic samples obtained from 20 consecutive cases of SCC of the vulva with positive inguinal LNM were morphometrically assessed and compared with samples from 20 consecutive cases of vulvar SCC negative for LNM. Computerized morphometry was performed on tumor cells and on adjacent nonneoplastic epithelial cells located 2-4 mm from the tumor margins. Computerized morphometric variables of tumor cell nuclei in patients with negative LNM significantly differed from those in patients with positive LNM. Morphometric differences in nuclear size and contour regularity were detected when comparing the nonneoplastic nuclei adjacent to the tumor of both groups. Multivariate analysis showed that the only independent predictors of LNM were the depth of the invasion (P= 0.005) and the mean nuclear roundness of the nonneoplastic nuclei adjacent to the tumors (P= 0.008). Using these variables, a discriminant score revealed a sensitivity of 90% and a specificity of 86.4% for predicting LNM in SCC of the vulva. Our data suggest that cells from the primary tumors with LNM differ morphometrically from primary tumors with no LNM. In addition, normal epithelial cells adjacent to the tumor express morphometric changes between the two groups. The results of our study justify the need for a prospective study of a larger number of patients to evaluate the reproducibility and the clinical use of the data.

Serum IGF-I levels are similar in Samoan, Maori and European populations despite differences in body composition.

OBJECTIVE: To determine if serum IGF-I concentrations are similar in healthy adult subjects from the Samoan, Maori and European populations in New Zealand. DESIGN: Serum IGF-I concentration was measured in 75 healthy adults, aged 18-50 years, of Samoan (n=23), Maori (n=22) and European (n=30) descent. Body composition was assessed using standard anthropomorphic measures. In addition all subjects had body composition assessed by Dual energy X-ray absorptiometry (DXA). RESULTS: Weight, body mass index (BMI), and fat mass were significantly greater in Maori and Samoan subjects than European subjects (ANOVA p=0.006, p=0.0003, p=0.03, respectively). However, serum IGF-I concentration was similar between the groups (European 186.8 SEM 14.9 microg/l, Maori 204.8 SEM 17.1 microg/l, Samoan 180.0 SEM 17.5 microg/l, p=0.58). IGF-I levels were similar between ethnic groups after adjustment (ANCOVA) for age, sex or BMI (p=0.5) or age, sex and fat mass (p=0.44). In multivariate analysis the only independent predictor of IGF-I was age (p<0.001) and explained 22% of the variance in IGF-I level. CONCLUSIONS: Serum IGF-I concentrations were similar in Maori, Samoan and European population groups in New Zealand, despite significant differences in anthropomorphic variables and body composition.

Evidence for direct learning curve for technique on change of cervical sampling device.

The recommended sampling device within the NHS Cervical Screening Programme is the Aylesbury spatula. A local decision was taken to decrease brush usage (either alone or in combination) by 50% from an initial level of 41.8%, with an initial inadequate smear rate of 9.93%. This was managed by controlling smear taking equipment through provision of smear taking kits. The monthly inadequate rate unexpectedly rose to 17.8% before dropping back to previous levels. Brush usage overall fell to 35.2%, with a corresponding increase in spatula use. The possible reasons for this are discussed. The facts suggest that these changes were directly linked, and that there is a learning curve with change of sampling device and that a rise in the inadequate rate should be expected under these circumstances.

The feasibility of a one-stop colposcopy clinic in the management of women with low grade smear abnormalities: a prospective study.

OBJECTIVES: To assess the feasibility of a one-stop colposcopy clinic for the management of women with low-grade smear abnormalities. Secondly, to determine whether the approach of immediate information of biopsy results combined with treatment if indicated helps to reduce patient anxiety and improve overall patient satisfaction with the colposcopy process. DESIGN: Prospective study following the introduction of a "one-stop" process for the management of women with low grade smear abnormalities. SUBJECTS: First 118 women managed in a "one-stop" clinic during an 8-month period. METHODS: Assessment of patient anxiety via self-completed questionnaires and comparison of anxiety scores with a control group managed via a standard clinic. RESULTS: The median waiting time for results in the one-stop clinic was 120 min (range: 100-165). All women in both groups felt anxious at the time of the clinic visit. However, after 1 week the majority of patients managed via the one-stop process felt slight anxiety only (P=0.0001) as opposed to those patients in the control group who remained anxious (P=NS). In addition, all women said they would prefer the one-stop approach for further smear abnormalities if a further colposcopic examination was warranted. CONCLUSION: A one-stop colposcopy clinic is feasible for the management of women with low-grade smear abnormalities. In addition, it delivers a quality service, optimises patient management, reduces anxiety and is the patient's choice.

Risk factors in stage III epithelial ovarian cancer: previous sterilisation is an adverse independent prognostic indicator.

OBJECTIVES: To determine whether past history of pelvic surgery is of prognostic significance in stage III epithelial ovarian cancer. METHODS: A retrospective review of 140 women with stage III epithelial ovarian cancer. RESULTS: Sixteen women had previously undergone pelvic surgery including eight sterilisations (6%), seven hysterectomies (5%) and one ovarian cystectomy (0.7%). Women with a past history of sterilisation were significantly younger (median age, 46 years) than women without a past history of sterilisation (median age, 63 years), and also significantly younger than women with a past history of hysterectomy (median age, 58 years). In addition, the sterilisation procedure was performed at a significantly younger age than the hysterectomy procedure (p=0.008). On multivariate analysis comparing previous pelvic surgery, previous malignancy, place of surgery, interval/secondary debulking, presence of concomitant tumour, performance of bowel surgery, histological grade, histological type, size of residual disease and age, all of the following were seen to be independent variables associated with outcome survival; previous sterilisation (p=0.0012), age (p=0.0074), histological type (p=0.025), histological grade (p=0.0017) and size of residual disease (p=0.0043). CONCLUSION: Past history of sterilisation appears to be an adverse independent prognostic indicator in women presenting with stage III epithelial ovarian cancer. To have developed ovarian cancer despite the protective effects of a sterilisation procedure against environmental factors might possibly suggest a predisposition to ovarian cancer in these women. Further studies are indicated to confirm the present results.

Complete cytoreduction: is epithelial ovarian cancer confined to the pelvis biologically different from bulky abdominal disease?

OBJECTIVES: The aim of this study was to determine whether site and size of tumor masses prior to complete surgical cytoreduction affect outcome survival. METHODS: A retrospective review was performed of 53 women with stage II and III epithelial ovarian cancer following complete surgical cytoreduction. RESULTS: Fifteen cases (28%) were classified as stage II and the remaining 38 cases (72%) as stage III. The overall median survival was 58 months with overall 2- and 5-year survivals of 76 and 42%, respectively. On univariate analysis, women with well differentiated tumors did significantly better than those with moderately or poorly differentiated tumours (P = 0.0009). FIGO stage did not reach statistical significance (P = 0.066). On multivariate analysis, comparing patient's age, previous history of pelvic surgery, previous history of malignancy, performance of lymphadenectomy for visibly/palpably enlarged nodes, performance of bowel resection, presence of concomitant tumors, positive pelvic and/or para-aortic lymph nodes, histological type, histological grade, and FIGO stage, only histological grade remained an independent variable affecting outcome survival (P = 0.0004; FIGO stage, P = 0.22) (hazard ratio = 6.5: well versus poor differentiation, 95% confidence interval, 1.7-25.5). CONCLUSION: When surgical cytoreduction to no visible disease has been achieved in women with stage II and III epithelial ovarian cancer, FIGO stage, i.e., site and size of tumor masses prior to surgical cytoreduction, does not appear to influence outcome survival. The aggressiveness of the remaining microscopic disease would seem to be determined largely by histological grade. Bearing in mind the retrospective nature of this study and the relatively small cohort of patients, the results would appear to suggest that it is unlikely that there are any other significant parameters (hidden factors) affecting tumor biology which are independent of tumor grade in these patients. A possible implication of this result is that complete surgical cytoreduction confers a survival benefit by producing a biologically more homogeneous tumor.

Optimal cytoreductive surgery is an independent prognostic indicator in stage IV epithelial ovarian cancer with hepatic metastases.

OBJECTIVES: The aim of this study was to determine the value of optimal cytoreduction in stage IV epithelial ovarian cancer. METHODS: A retrospective review was performed of 37 women with stage IV epithelial ovarian cancer treated by radical surgery. RESULTS: Optimal surgery to less than 2 cm tumor deposits was performed in 16 of the 37 cases (43%) and tumor debulking to less than 1 cm tumor deposits in 6 cases (16.2%). Twenty-three cases (62%) were designated stage IV because of the presence of liver metastases alone. Although no patients died within 2 weeks of surgery, 7 of the 37 cases (22%) failed to survive more than 50 days after primary surgery. The overall median survival was 11 months with overall 2- and 5-year survivals of 23 and 9%, respectively. On multivariate analysis comparing age, histological type, tumor grade, place of surgery, secondary surgical procedure, performance of bowel surgery, presence of liver metastases, and optimal cytoreduction, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained highly significant (P = 0.0029 and 0.0086, respectively). Even when assessing only the 27 cases who were designated as having stage IV disease because of the presence of liver metastases, by multivariate analysis, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained significant (P = 0.023 and 0.036, respectively). Site of metastases designating stage IV status was not associated with a reduced likelihood of achieving optimal debulking (P = 0.18). CONCLUSION: Optimal cytoreduction in women with stage IV epithelial ovarian cancer with or without hepatic metastases is associated with a more favorable outcome survival.

Laparoscopic port-site metastasis of an early stage adenocarcinoma of the cervix with negative lymph nodes.

BACKGROUND: Port-site metastasis (PSM) following laparoscopic surgery for cancer is being increasingly recognized as a potential problem; the majority of cases appear following laparoscopy for a pelvic mass that subsequently proved to be malignant or in the case of a disseminated intraperitoneal disease. The rare cases of PSM following laparoscopy for endometrial and cervical cancer have all been associated with the presence of regional lymph node metastasis or disseminated disease in the peritoneal cavity. We present here a case report of PSM in the absence of spread beyond the primary tumor. CASE: A 48-year-old woman with stage IA1 adenocarcinoma of the cervix was treated with laparoscopically assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic node dissection. The pathologic study revealed an endocervical adenocarcinoma confined to the cervix with negative lymph nodes. Nine months postoperatively, a cutaneous metastasis at the port-site was diagnosed. This was treated with wide local excision of the recurrence and the port-site track. Explorative laparotomy and para-aortic node sampling showed no evidence of recurrence elsewhere. CONCLUSION: This case emphasizes the risk for PSM in laparoscopic surgery performed for early stage disease.

The hormonal receptor status of uterine carcinosarcomas (mixed müllerian tumours): an immunohistochemical study.

AIM: To investigate the role of oestrogen and progesterone receptor status in uterine carcinosarcomas (mixed Müllerian tumours) to see whether the receptors were identifiable, and if so whether they were of significance clinically. METHODS: 11 cases of uterine carcinosarcoma were identified from clinical and pathology records. An immunohistochemical method was used to demonstrate oestrogen and progesterone hormone receptors on paraffin embedded material, with suitable tissue controls, staining being recorded. RESULTS: 10 of 11 cases showed staining for one or both hormone receptors in normal tissue adjacent to tumour. In four carcinosarcoma cases, staining for one or both receptors was shown within the epithelial component (appearing to correlate with the degree of epithelial differentiation); two of these cases had staining within sarcomatous areas. Two of the three patients still alive had epithelial hormone receptor positivity. CONCLUSIONS: Receptors for oestrogen and progesterone were found in four of 11 cases of uterine carcinosarcoma, using paraffin embedded material. There may be an association between hormone receptor positivity and clinical outcome.

Rapid rescreening of cervical smears as a quality control method.

The use of a rapid rescreening method as part of an internal quality control programme is reported. During a 12-month period 33,976 smears were reviewed (90.9% of total workload). Two-hundred and nineteen reports were altered, with 23 dyskaryotic smears identified, a false-negative rate of 0.07% a false-negative dyskaryotic rate of 1.7%. Smears reported as dyskaryotic were also subjected to the rapid screening method (with 86.8% correctly identified) as well as using the method to assess smears before the usual primary screen (with 67.2% of dyskaryotic smears correctly identified). Rapid rescreening as a quality control method is effective and although it has limitations, should replace 10% proportional rescreening as the preferred daily quality control method of choice.

Internal quality assurance in cervical cytology one laboratory's experience.

The results of an internal quality assurance exercise in one cervical cytology laboratory in England are presented, using different types of partial percentage re-screening of cervical smears. An overall false negative dyskaryotic rate of up to 4.3% was demonstrated, with the final cytology report diagnosis differing from the primary screening dignosis in 1.3% of cases. These finding are discussed, with the aim of helping to foster debate on the setting of national laboratory internal quality assurance standards.