ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.

Maspin expression in endometrial hyperplasia and carcinoma, and its relation with angiogenesis.

AIM: The purpose of this study was to evaluate the maspin expression in endometrial hyperplasia and cancer, and also to investigate its relation with angiogenesis. MATERIALS AND METHODS: A total of 19 women with complex atypical hyperplasia, 44 patients with simple hyperplasia without atypia, and 67 patients with endometrial carcinoma were included. Maspin expression was assessed by immunohistochemistry (IHC), and tested for possible significant relation with age, FIGO stage, histologic type, grade, depth of myometrial invasion (MI), lymphovascular space involvement (LVSI), lymph node metastasis, and overall survival (OS). Angiogenesis was determined by vascular endothelial growth factor (VEGF) staining. RESULTS: Maspin expression was detected in only three patients with endometrial hyperplasia (5%). In patients with endometrial cancer, cytoplasmic and nuclear maspin expressions were detected in 36 (53.7%) and 18 (26.9%) patients, respectively. No significant relation was noted between staining localizations and prognostic variables. The five-year OS rate for patients with cytoplasmic staining was 91%, compared to 87% for patients without staining (p = 0.31). These values for nuclear expression were 100% and 87%, respectively (p = 0.16). The cytoplasmic and nuclear maspin expressions were found to be significantly correlated with VEGF (r = 0.278, p = 0.02 and r = 0.295, p = 0.01, respectively). DISCUSSION: This is the first study to demonstrate the relation between maspin expression and angiogenesis in endometrial cancer. Although no survival difference was noted for cytoplasmic or nuclear maspin expressions, a tendency was detected for nuclear staining. Further series will clarify the exact prognostic role of maspin expression in gynecological malignancies including endometrial cancer.

The role of frozen section evaluation in the diagnosis of adnexal mass.

The purpose of this study was to evaluate the accuracy of frozen section diagnosis in patients who were subjected to the exploratory laparotomy for pelvic mass. Overall, 207 patients were included in this study and the mean age of the patients was 50.9 +/- 14.9 years (range, 18-84 years). Of these patients, 98 (47%) had benign, 16 (8%) had borderline, and 93 (45%) had malignant histologies at permanent section. The diagnosis at frozen section was deferred for three patients (1.4%) and these patients were excluded from the further analyses. The overall discordance rate was 5.3%. To calculate the sensitivity and specificity values, 2 x 2 contingency tables were constructed in two ways. In the first calculation, borderline histology was considered malignant, and the sensitivity and specificity rates were 97% and 92%, respectively. In the second analysis, it was accepted as benign, and these values were 100% and 98%, respectively. To determine the possible factors related with discordant diagnoses, age, menopausal status, tumoral size, laterality of tumors, and histologic diagnoses were analyzed. Significant association was noted for size and borderline and mucinous histologies. In patients with borderline histology, the discordance rate was 40%. This value for the remaining patients was 3.2% (P < 0.001). The rate of misdiagnosis was 17.4% for mucinous tumors, whereas it was 4.8% for the remaining epithelial tumors (P = 0.03). Frozen section evaluation revealed high sensitivity and specificity values in this study. To increase the accuracy of diagnosis, further diagnostic markers are needed especially for patients with large lesions, borderline tumors, and mucinous histologies.

Ascites and epithelial ovarian cancers: a reappraisal with respect to different aspects.

Ascites is a common finding in patients with epithelial ovarian cancer (EOC). Clinico-pathologic correlations with respect to the presence of ascites, positive cytology and prognostic role of ascites, and the impact of ascitic volumes were not previously studied extensively. A total of 372 patients with EOC were retrospectively evaluated with respect to presence and amount of ascites, cytologic findings, and survival. Two groups were compared by using Chi-square, Student's t and Mann-Whitney U, binary logistic regression, Kaplan Meier and Cox-regression analysis tests, where appropriate. Omental metastasis (P < 0.001; OR: 3.21, 95% CI = 1.945-5.297) and mean number of metastatic lymph nodes (P= 0.008; OR: 1.063, 95% CI = 1.016-1.112) were significantly related with presence of ascites. Evaluation of ascitic volume at different thresholds revealed lymphatic-omental metastasis, and also the disease stage to be significantly different among patient groups at lower threshold values and the positive cytology and high-grade diseases at higher threshold values. In conclusion, presence of ascites correlates with both the intraperitoneal and also the retroperitoneal tumor spread. Amount of ascites has different correlations with the clinico-pathologic factors depending on the thresholds chosen. At lower volumes, lymphatic and omental metastasis seems to correlate with the development of ascites. Once ascites develops, tumor grade seems to be important for larger ascites volumes. Neither the presence of ascites or its volume nor the cytologic positivity was an independent predictor of survival.

The prognostic value of endoglin (CD105) expression in ovarian carcinoma.

Intratumoral angiogenesis has become an important issue after the identification of antiangiogenic therapeutics. The purpose of this study was to investigate the prognostic value of CD105 in patients with ovarian cancer and also to compare with CD31. Fifty-eight patients were included to this study. All the paraffin blocks were reviewed, and angiogenesis was determined by immunohistochemical staining, using anti-CD105 and anti-CD31 monoclonal antibodies. The mean microvessel density (MVD) with CD105 and CD31 were 28.78 +/- 22.20 and 28.69 +/- 18.57, respectively (P = 0.97). With respect to prognostic factors, CD31 was only significant for suboptimal cytoreduction (P = 0.02), and CD105 was significant for both advanced stage and suboptimal cytoreduction (P = 0.02 and P = 0.05, respectively). For survival analysis, patients were divided into three groups by quartiles for each marker (group 1, <25%; group 2, 25-75%; and group 3, >75%). By CD31, only significant difference was noted between group 1 and group 2 (P = 0.03). In analysis with CD105, the survival rate of patients with group 3 was significantly worse than group 1 and group 2 (P = 0.01 for both). In multivariate analysis, cytoreduction and MVD determined by CD105 remained significant. In this study, endoglin was found to be an independent predictor of poor survival. Therefore, it could be used for antiangiogenic therapies.

Predictability of retroperitoneal lymph node metastasis by using clinicopathologic variables in surgically staged endometrial cancer.

The purpose of this study was to predict lymphatic involvement in endometrial cancer using clinicopathologic variables of patients treated with surgical staging. Overall, 461 patients treated with an initial surgical staging procedure including complete pelvic-para-aortic lymphadenectomy were included. The mean number of resected lymph nodes was 27 (median 26; range 15-83), and 54 patients (12%) had lymphatic involvement. Of these patients, 32 had only pelvic, 15 had both pelvic and para-aortic, and 7 had isolated para-aortic metastases. In the multivariate analysis, deep myometrial invasion (P= 0.02), lymphvascular space invasion (P= 0.001), positive peritoneal cytology (P= 0.002), and cervical involvement (P= 0.003) predicted retroperitoneal lymph node metastasis (RLN) significantly. Two hundred seventy-four patients (59.4%) had at least one of these poor prognostic factors identified by multivariate analysis. In this patient population, 53 (19.3%) had lymphatic involvement compared to 1 patient in the group of 187 patients with low-risk criteria. Ninety-eight percent of patients with RLN were predicted by this model, and with the advent of accurate diagnostic techniques, 40% of patients could be saved from undergoing lymphadenectomy.

Long-term survival after paclitaxel plus platinum-based combination chemotherapy for extraovarian peritoneal serous papillary carcinoma: is it different from that for ovarian serous papillary cancer?

The purpose of this study was to compare the effect of paclitaxel plus platinum-based chemotherapy in the treatment of extraovarian peritoneal serous papillary carcinoma (EPSPC) and ovarian serous papillary cancer (OSPC). Only the patients treated with initial surgery plus postoperative adjuvant chemotherapy and having FIGO stage IIIC disease with omental and/or peritoneal involvement were analyzed. Thirty-two patients with EPSPC and 43 with OSPC were included in this study. The median age, mean CA-125, and volume of ascitis were higher in patients with EPSPC. There was no significant difference between the two groups with respect to other prognosticators. The median overall survival (OS) durations were 30 months (95% CI 24.8-35.3) in patients with EPSPC and 28 months (95% CI 21.1-34.9) in those with OSPC (P= 0.35). The 3-year OS rates in the patients and controls were 28% and 31%, respectively (P= 0.84). In patients with EPSPC, only optimal cytoreduction was significantly related to progression-free survival and OS durations as a prognostic factor. In the EPSPC group, 65.5% of the patients (19/29) had lymphatic involvement, compared to 88.4% (38/43) in the OSPC group (P= 0.02). As an adjuvant therapy, the paclitaxel plus platinum-based combination regimen had similar effects on survival in the EPSPC and OSPC groups.

Genital human papillomavirus infection in the male sexual partners of women with isolated vulvar lesions.

The purpose of this study was to detect human papillomavirus (HPV) positivity in the male sexual partners of women with isolated vulvar lesions. The male counterparts of the females were subjected to detailed physical and peniscopic evaluations. After the gross inspection, 5% acetic acid was applied and the whole genital organs were evaluated using a colposcope. Overall, 47 male sexual partners with isolated vulvar HPV lesions were included. None of the patients had condylomata acuminata. Twenty-six patients (55%) had papular or papillary lesions, and 21 (45%) had flat acetowhite lesions. Biopsies were taken from all these suspicious areas for histopathologic examination. Overall, 41 patients (87%) had the exact characteristics of HPV on biopsy specimens. Ninety-two percent of patients (24/26) having papular and/or papillary lesions on peniscopy had HPV on biopsy, while 81% of patients (17/21) who had acetowhite flat lesions had biopsy-confirmed HPV lesions. In conclusion, it is important to assess the male sexual partners of women with HPV-related lower genital tract disease. Peniscopy is valuable for detecting lesions, and histopathologic confirmation is mandatory.

Does immediate hormone replacement therapy affect the oncologic outcome in endometrial cancer survivors?

The purpose of this study was to evaluate the effect of immediate hormone replacement therapy (HRT) on oncologic outcome of patients with endometrial cancer. The patients were recruited prospectively after extensive discussion of risks and benefits of HRT. Continuous daily regimen of 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate was initiated 4-8 weeks after surgery at first postoperative visit. The patients who had the same characteristics with the HRT group were assigned as a control group. Overall, 50 patients received HRT. There was no significant difference with respect to prognosticators between the HRT users and the control group. Seven patients (14%) stopped the use of HRT. Only two patients stopped the therapy before 24 months, and all the remaining patients used HRT for at least 24 months, with a mean value of 49.1 months. Neither the patients who used HRT nor the ones who left the therapy had recurrence at the time of writing of this article. This prospective case-control study showed that immediate postoperative use of HRT did not increase the recurrence or death rates in endometrial cancer survivors.

Topotecan as a second-line therapy in patients with ovarian and primary peritoneal cancer: initial response and long-term follow-up.

The purpose of this study was to evaluate the role of topotecan at a dose of 5-day standard 1.5 mg/m2/day in patients with relapsed ovarian cancer. Two different groups of patients were included. In group 1, 23 patients who had bidemensionally measurable disease were examined, and in group 2, 11 patients were given topotecan after positive second-look laparotomy (SLL) were analyzed. Total number of cycles was 190 with a median value of six cycles. In group 1, three (13%) patients had complete response (CR) and seven (30%) had partial response (PR) with a total response rate of 43%. Six patients (27%) had stable disease (SD), and seven (30%) had progressive disease (PD). Median survival durations for patients with CR, PR, SD, and PD were 35, 14, 15, and two months, respectively. In group 2, two patients had PD during treatment. The remaining nine patients had no measurable disase or marker relapse at the end of treatment period. Median survival duration was 27 months. In conclusion, topotecan had significant antitumor activity as a second-line therapy in relapsed ovarian cancer patients with measurable disease. In a subgroup of patients with positive second-look laparotomy topotecan was also associated with long median survival duration.

Retroperitoneal leiomyomatosis: a case report.

Leiomyoma is the most common benign solid pelvic tumor seen in women. It is most commonly located in the uterus and gastrointestinal tract, but it can originate wherever smooth muscle cells exist. Although it has been reported in various atypical localizations, they are extremely rare in the retroperitoneum. Also, preoperative diagnosis is often difficult in retroperitoneal tumors. Imaging studies may demonstrate the retroperitoneal tumors; however, exact diagnosis cannot be established by imaging methods alone. Here, we report a case with retroperitoneal leiomyomatosis diagnosed by preoperative ultrasonography-guided fine-needle biopsy.