Vaginal high-grade sarcoma in pregnancy.

BackgroundVaginal cancer is a rare malignancy making up 1-2% of all female genital tract cancers. Among vaginal cancers, sarcomas constitute 2% of malignant vaginal lesions, with leiomyosarcomas being the most common type of sarcoma. There is a paucity of data to guide treatment of vaginal sarcomas. This case report details a patient diagnosed with a gynecologic sarcoma during pregnancy who is subsequently treated for residual vaginal disease in the postpartum period with local resection and adjuvant vaginal brachytherapy.CaseA 31-year-old gravida 4 para 0 who presented at 22-weeks gestation with vaginal bleeding to an outside hospital and expelled a mass 11 cm in diameter from the vagina during her admission. Findings were consistent with a high grade gynecologic sarcoma. She underwent planned cesarean section at 36 weeks gestational age with uterine pathology showing no sarcoma. At her 3 month postpartum visit she was found to have a 1 cm posterior vaginal wall lesion which was resected and consistent with vaginal sarcoma. She underwent adjuvant brachytherapy.ConclusionThis case demonstrates the challenges with obtaining a correct pathological diagnosis for pregnant patients with vaginal sarcoma during pregnancy. Surgical resection with negative margins remains an important treatment component. Given the low incidence of disease occurrence in pregnancy and rare number of cases reported in literature, further elucidation of timing of delivery and adjuvant treatment is warranted

Expression of Stromal Progesterone Receptor and Differential Methylation Patterns in the Endometrium May Correlate with Response to Progesterone Therapy in Endometrial Complex Atypical Hyperplasia

Progesterone therapy is a viable treatment for complex atypical hyperplasia (CAH) and endometrial adenocarcinoma, though reliable molecular determinants of response are not available. To explore if analysis of pre-therapy endometrial biopsies could yield biomarkers of response to progesterone, patients with CAH or adenocarcinoma undergoing treatment with progestins were included in this cross-sectional study. Immunohistochemistry for progesterone receptor (PR) was performed. Manual PR expression scores (PRES) were first calculated for biopsies by counting PR-positive nuclei in 12 sensitive vs 9 resistant samples. Significant differences in manual PRES were detected in the stroma (p < 0.01) and total endometrium (p < 0.01) for sensitive vs resistant patients. Manual PRES in the stroma had the highest accuracy in segregating sensitive vs resistant patients (96%). Differences in epithelial PRES were not significant. To validate these findings, a correlation between manual PRES and visual PRES was performed in the 21 patients. An additional 11 patients were analyzed to test if visual PRES would be predictive of response to progesterone. Visual PRES in epithelia and stroma in the 32 specimens was calculated. Significant differences in visual PRES were detected in the stroma for sensitive vs resistant samples (p < 0.01), while differences in epithelial and total endometrium were not significant. Whole genome bisulfite sequencing was performed on DNA isolated using pre-therapy biopsies from 6 sensitive and 6 resistant patients in this cohort. Differentially methylated regions were identified in the stroma and epithelium when evaluating sensitive vs resistant samples. Pathways involved in cell adhesion demonstrated the greatest difference in methylation in these sample