Molecular portraits of clear cell ovarian and endometrial carcinoma with comparison to clear cell renal cell carcinoma.

OBJECTIVE: Advanced clear cell gynecologic malignancies remain among the most challenging diseases to manage. We evaluated ovarian and endometrial clear cell carcinoma (OCCC and ECCC) specimens using comprehensive sequencing technology to identify mutational targets and compared their molecular profiles to histologically similar clear cell renal cell carcinoma (ccRCC). METHODS: Using next-generation sequencing (NGS), fragment analysis (FA), and in situ hybridization (ISH), 164 OCCC, 75 ECCC and 234 ccRCC specimens from 2015 to 2018 were evaluated and compared. RESULTS: The highest mutation rates in ECCC and OCCC were noted in: ARID1A (75.0%, 87.5%), TP53 (34.8%, 11.1%), PIK3CA (25.0%, 46.8%), PPP2R1A (8.7%, 16.7%), MSI-high (8.8%, 6.4%) and PTEN (8.3%, 7.1%). Among these mutations, there was no significant difference between OCCC and ECCC mutation prevalence except in TP53, with higher mutation rates in ECCC versus OCCC (34.8 vs. 11.1%, respectively, p < 0.05). ccRCC demonstrated different mutation profiles with higher mutation rates in VHL (80.3%), PBRM1 (43.9%), SETD2 (31.1%), and KDM5C (29.2%). By contrast, VHL, PBRM1, and SETD2 mutations were not found in ECCC and OCCC (0.0%). Compared to ccRCC and ECCC, OCCC was found to have a significantly higher tumor mutation burden (TMB) (19.1%). CONCLUSION: Gynecologic and renal CCC demonstrate separate and disparate somatic profiles. However, OCCC and ECCC are diseases with similar profiles. TMB and MSI analyses indicate that a subset of OCCC may benefit from immunotherapy. Prospective clinical trials are needed and are underway to examine targeted therapies in these gynecologic disease subtypes.

Utilizing Colpocleisis to Repair a Vesicovaginal Fistula in a Cervical Cancer Patient with History of Pelvic Radiation: A Case Report and Literature Review.

BACKGROUND: Vesicovaginal fistula is a rare and distressing urological condition. It is especially prevalent in developing countries with the predominant etiology secondary to obstructed labor. Radiation therapy in female patients with cervical cancer is a risk factor for vesicovaginal fistula formation in the United States. Case Presentation. A 53-year-old woman with a history of cervical cancer and radiation presented with continuous urinary incontinence. Following diagnostic vaginoscopy, a 1 cm vesicovaginal fistula was diagnosed at the vaginal apex. The patient elected for surgical repair. She subsequently underwent successful transvaginal fistula closure using colpocleisis to optimally address the systemic factors of poor wound healing associated with irradiated tissue. Because of the adjacent tissue having been compromised by pelvic radiation, we opted to use a biologic graft made of human cadaveric pericardial tissue (CPT) instead of a native tissue flap to provide additional support for the fistula repair. CONCLUSION: A transvaginal approach for surgical repair of vesicovaginal fistula can be successful in patients with a prior history of pelvic radiation. Transvaginal colpocleisis is a viable option to augment vesicovaginal fistula repair for patients with significant comorbidities when sexual intercourse is no longer desired.