Accuracy of frozen section diagnosis of ovarian borderline tumor.

OBJECTIVE: The objective of this study was to determine the incidence of invasive cancer in ovarian masses diagnosed as borderline tumor (BT) at the time of frozen section. METHODS: We performed a retrospective review of all patients diagnosed with ovarian BT on frozen section (FS) at our institution between 2000 and 2010. Clinical and pathologic data were extracted. Univariate and multivariate analyses were performed using standard two-sided statistical tests. RESULTS: A total of 120 patients were identified, of which 104 (86.7%) had BT on frozen section that was confirmed on final pathology. In 15 (12.5%) patients, BT was diagnosed on FS but was reclassified as invasive cancer on final pathology. One patient (0.8%) had BT on FS but benign pathology on final diagnosis. Histologies included serous in 79 (65.8%), seromucinous in 13 (10.8%), mucinous in 21 (17.5), endometrioid in 5 (4.2%), and clear cell in 2 (1.7%) patients. Reclassification of pathologic diagnosis was related to histologic subtype, but only for endometrioid and clear cell tumors (P<0.001). The rate of invasive cancer for serous micropapillary tumors on frozen section was 42.8% compared with 2.8% for serous non-micropapillary tumors (P<0.001). Tumor size >8 cm was associated with a 22.4% incidence of invasive cancer on final pathology compared to 3.2% in tumors ≤ 8 cm (P=0.004). CONCLUSION: Comprehensive surgical staging can be considered in BT >8 cm in diameter, as well as those with micropapillary serous, endometrioid, and clear cell histology diagnosed at the time of frozen section analysis.

Clinicopathologic significance of DNA mismatch repair protein defects and endometrial cancer in women 40years of age and younger.

BACKGROUND: The hereditary basis of endometrial cancer is apparent in young women with endometrial cancer. The objective of this study was to examine risk factors and outcomes in patients 40 years of age and younger with endometrial cancer. METHODS: We performed a retrospective cohort study of patients aged 40 years or less who were diagnosed with endometrial carcinoma between 1/93 and 5/08. Clinical and pathologic data were extracted from medical records. Paraffin-embedded slides from hysterectomy specimens were obtained and DNA mismatch repair (MMR) immunohistochemistry was performed. Cases were analyzed according to the presence of DNA MMR protein defects. Standard two-sided statistical tests were performed. RESULTS: Of the 56 identified patients, the median age was 36 years (range, 24-40). The majority of the endometrial carcinomas were of endometrioid histology (91%), stage I (71%), and FIGO grade 1 (59%). Abnormal DNA MMR was found in 9 cases (16%). Cases with abnormal DNA MMR had lower body mass index (BMI) (P=0.05), and had a family history suggestive of Lynch syndrome (P=0.001). Tumors were more likely to have advanced stage disease (P<0.001), be high grade (P<0.001), have deep myometrial invasion (P<0.001), and have lymphovascular invasion (P=0.002). Cases with abnormal DNA MMR had significantly worse overall survival (P=0.028) and progression-free survival (P=0.042). CONCLUSIONS: Endometrial cancer is rare in women aged 40 years or less. In this group of patients, loss of DNA MMR was associated with lower BMI, worse clinicopathologic factors, and worse outcome. These results may have implications when young women diagnosed with endometrial cancer are counseled regarding prognosis.

Surgical cytoreduction in stage IV endometrioid endometrial carcinoma.

OBJECTIVE: To evaluate the role of surgical cytoreduction and the amount of residual disease in patients with newly diagnosed stage IV endometrioid endometrial carcinoma (EC). METHODS: Patients with stage IV EC of endometrioid histology who underwent surgery at our institution from 1977 to 2003 were identified. Patients with microscopic stage IV disease were excluded. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier method and compared with log-rank test. RESULTS: A total of 58 patients were identified, of which 9 (15.5%) had no gross residual (NGR) after surgery, 11 (19.0%) had residual disease ≤1 cm, 32 (55.1%) had residual disease >1 cm, and 6 (10.3%) had no cytoreduction attempted. The median PFS was 11.1 months (95% CI, 9.8-12.3) and the median OS was 19.2 months (95% CI, 8.5-29.9) for the cohort. The median PFS was 40.3 months (95% CI, 0-93.9) for patients with NGR disease, 11 months (95% CI, 9.9-12.1) for patients with any residual disease, and 2.2 months (95% CI, 0.1-4.2) for patients who did not have attempted cytoreduction (P<0.001). The median OS was 42.2 months (95% CI, not estimable) for patients with NGR disease, 19 months (95% CI, 13.9-24.1) for patients with any residual disease, and 2.2 months (95% CI, 0.1-4.2) for patients that did not have attempted cytoreduction (P<0.001). CONCLUSION: Though stage IV endometrioid EC has a poor prognosis, surgical cytoreduction to no gross residual disease in a highly select group of patients is associated with improved survival.

Risk factors for recurrence of ovarian borderline tumors.

OBJECTIVE: The objective of this study was to identify clinicopathologic features that are associated with an increased risk of recurrence for borderline ovarian tumors (BOT). METHODS: We performed a retrospective review of all patients treated for BOT at our institution from 1979 to 2008. Progression-free survival (PFS) was defined as the time of diagnosis to time of recurrence/death or last follow-up. The Kaplan-Meier method was used to calculate the PFS rate and the Wilcoxon-Gehan test was performed to identify prognostic factors. RESULTS: A total of 266 patients were identified. The median age was 43 years (range, 15-94 years). The majority of patients (68.4%) had FIGO stage I disease and serous histology (73.7%). Only 23 (8.6%) patients developed recurrent disease. The median PFS was 19 years and the median follow-up was 4 years. Abnormal baseline CA-125 (>35 U/ml), advanced stage, age at diagnosis, and invasive implants were associated with decreased PFS. Of the 196 patients with serous BOT, those with a micropapillary pattern had a 3-year PFS of 75.9% (95%CI, 55.6-87.8) compared with 94.3% (95% CI, 88.4-97.3) for patients without micropapillary pattern (P<0.001). CONCLUSION: Age at diagnosis, an elevated preoperative CA-125, invasive implants, and micropapillary histology were clinical factors associated with increased risk of recurrence in women with BOT. Including these clinicopathologic features will likely identify patients at higher risk for recurrence, for whom development of new treatment strategies would be appropriate.

Tertiary cytoreduction in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer: an updated series.

OBJECTIVE: Surgical cytoreduction is an integral therapeutic modality for patients with epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) cancer in the primary setting. The role of surgical cytoreduction in the recurrent setting is not clearly defined and remains controversial. The objective of this study was to assess this potential survival benefit in a large cohort of patients with a long follow-up period. METHODS: We performed a retrospective chart review of all patients with recurrent EOC, FTC, or PPC who underwent tertiary cytoreduction at our institution from 2/98 to 2/08. Disease-specific survival (DSS) was calculated from the time of tertiary cytoreduction to death or last follow-up. Univariate and multivariate analyses were used to analyze outcomes and to identify potential prognostic factors. RESULTS: A total of 77 patients were identified, of which 38 (49%) have died of disease. The median time from secondary to tertiary cytoreduction was 25.7 months (range, 4.1-99.4 months). The median follow-up after tertiary cytoreduction was 28.9 months (range, 0.7-123.7 months), with a median DSS for the entire cohort of 47.7 months (95% CI, 25.5-69.9 months). On univariate analysis, residual disease after tertiary cytoreduction and TFI were found to be significant prognostic factors. On multivariate analysis, only residual disease after tertiary cytoreduction retained prognostic significance (P<0.001). CONCLUSION: Tertiary surgical cytoreduction may offer a survival benefit in a highly select group of patients with recurrent EOC, FTC, or PPC. This benefit appears to be greatest in patients in whom a complete gross resection can be achieved.

Beyond tertiary cytoreduction in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

BACKGROUND: Primary, secondary, and possibly tertiary surgical cytoreduction in patients with recurrent epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) cancer appears to be associated with a survival benefit. The objective of this study was to assess if cytoreduction of recurrences after tertiary cytoreduction offers any potential benefit in these patients. METHODS: We performed a retrospective chart review of all patients with recurrent EOC, FTC, or PPC who underwent additional cytoreductive procedures after a prior tertiary cytoreduction (quaternary cytoreduction) at our institution between 1991 and 2008. Disease-specific survival (DSS) was calculated from the time of quaternary cytoreduction to last follow-up. Univariate analyses were used to analyze outcomes and to identify potential prognostic factors. RESULTS: A total of 15 patients were identified, of which 7 (47%) have died of disease. All patients had undergone prior optimal secondary and tertiary surgical cytoreductive procedures. The size of residual disease varied from 0 (in 10 cases/67%) to >1 cm (in 2 cases, 13%). Residual disease (1 cm) and number of recurrence sites (single vs multiple) were found to be significant prognostic factors on univariate analysis. CONCLUSIONS: Cytoreductive surgery beyond tertiary cytoreduction may be a reasonable option in highly select patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, especially in the setting of a single site of recurrent disease.