EWSR1-WT1 gene fusions in neoplasms other than desmoplastic small round cell tumor: a report of three unusual tumors involving the female genital tract and review of the literature.

Desmoplastic small round cell tumor (DSRCT) is a high-grade round cell sarcoma that typically arises in the abdominopelvic cavity of young males, co-expresses keratins and desmin, and carries a pathognomonic EWSR1-WT1 gene fusion. The EWSR1-WT1 gene fusion is generally considered specific for DSRCT, although there are two reports of this fusion in tumors otherwise lacking features of DSRCT. We report three female genital tract tumors with EWSR1-WT1 fusions but showing morphologic and immunohistochemical features incompatible with DSRCT. The tumors occurred in the uterine cervix, uterine corpus/ovaries, and vagina, respectively, of 46, 30, and 20-year-old women. Two tumors consisted of a sheet-like to fascicular proliferation of relatively uniform spindled to occasionally more epithelioid cells arrayed about thick-walled, hyalinized, and capillary-sized vessels, with distinctive areas of pseudovascular change, and absence of desmoplastic stroma. The third tumor resembled a monomorphic spindle cell sarcoma with necrosis. All had diffuse desmin and variable but more limited keratin expression, two of three expressed smooth muscle actin, and all were negative for h-caldesmon, CD10, estrogen receptor, myogenin, N-terminus WT-1, and S100 protein. One patient received neoadjuvant chemotherapy and radiation therapy followed by resection and is disease-free 42 months after diagnosis. Another patient was managed by resection only and is disease-free 9 months after initial diagnosis. The remaining patient recently underwent resection of multifocal pelvic disease. Comprehensive differential gene expression analysis on two tumors compared to two classic DSRCTs with known EWSR1-WT1 fusions resulted in 1726 genes that were differentially expressed (log2 fold change >2 or < -2) and statistically significant (FDR < 5%). In combination with previous reports, our findings suggest pleiotropy of the EWSR1-WT1 fusion is possible and not limited to DSRCT. Subsets of non-DSRCT EWSR1-WT1 positive tumors may represent discrete entities, but further study is necessary.

Timing of robotic hysterectomy after cervical excisional procedure.

INTRODUCTION: While traditional teaching has been to wait 6 weeks between cervical excisional procedure and hysterectomy, studies have produced conflicting evidence, with data supporting a delay of anywhere between 48 hours to 6 weeks depending on surgical approach. Our study sought to evaluate if the time between cervical excisional procedure and robotic hysterectomy impacts peri-operative complication rates. METHODS: A retrospective cohort of patients who underwent robotic hysterectomy from August 2006 to December 2013 for cervical dysplasia or International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA1-B1 cervical cancer at a single tertiary care center was performed. Patients were categorized into three groups: early surgical intervention (<6 weeks from excisional procedure), delayed surgical intervention (≥6 weeks from excisional procedure), and no excisional procedure. Secondary analysis was performed by hysterectomy type (simple vs radical). Peri-operative outcomes and complications were compared. Statistical analysis included Chi-square, Fisher's exact test, and Wilcoxon rank sum test. RESULTS: A total of 160 patients were identified. Of these, 32 (20.0%) had early surgical intervention, 52 (32.5%) had delayed surgical intervention, and 76 (47.5%) had no excisional procedure. There was no difference between groups in complication rates, including average estimated blood loss (82 vs 55 vs 71 mL; p=0.07), urologic injury (0% in all groups; p=1.0), anemia (3% vs 0% vs 1%; p=0.47), infection (0% vs 2% vs 3%; p=1.0), vaginal cuff separation (0% in all groups; p=1.0), or venous thromboembolism (0% vs 0% vs 1%; p=1.0). Additionally, there were no differences in length of stay (p=0.18) or 30-day readmission rates (p=1.0). Finally, there were no significant differences in peri-operative outcomes when stratified by radical versus simple hysterectomy. DISCUSSION: Waiting 6 weeks between cervical excisional procedure and robotic hysterectomy does not impact peri-operative complication rates. This suggests that the time from excisional procedure should not factor into surgical planning for those who undergo robotic hysterectomy.

Distance from a Comprehensive Cancer Center: A proxy for poor cervical cancer outcomes?

OBJECTIVE: To evaluate the potential relationship between outcomes in cervical cancer patients based on distance from our Comprehensive Cancer Center (CCC). METHODS: A retrospective cohort study of cervical cancer patients was performed. Abstracted data included: demographics, clinicopathologic variables, treatment, and survival. Analyses both by quartiles and distance <100 and ≥100miles from our institution were performed. Data were analyzed using SAS version 9.2. RESULTS: 390 patients living a median distance of 58.1miles (range 1.2-571miles) from our CCC were identified. Patients were generally white (n=249), non-smokers (n=226), with Stage IB disease (n=222), squamous histology (n=295) and underwent primary surgical therapy (n=229). Patients were divided into both quartiles as well as two strata: <100 and ≥100miles for comparison. Progression-free survival (PFS) and overall survival (OS) favored patients living closer to our center with a lower median OS for patients living ≥100miles (65.4vs. 99.4months; p=0.040). Cox proportional hazard modeling noted that advanced stage was predictive of inferior PFS and OS, while other clinical covariates including age, BMI, race, smoking status and histology had a variable impact on outcomes and distance >100miles was associated with a higher risk of death (hazard ratio [HR]=1.68, 95% confidence interval [CI] 1.11-2.54). CONCLUSION: Overall survival for patients living >100miles from our CCC was worse when compared to patients in closer proximity. Outreach efforts and utilization of navigators may help decrease the impact of geographic and racial disparities on outcomes.

Trends in Colposcopy Volume: Where Do We Go From Here?

OBJECTIVE: To describe the change in colposcopy volume in light of recent guideline shifts, which target higher-risk women while limiting unnecessary procedures in low-risk women. METHODS: After institutional review board approval, colposcopy clinic visits at a large-volume referral center from January 2010 to December 2015 were reviewed. All women diagnosed with abnormal cervical cytology who were referred and subsequently underwent colposcopic evaluation were included. Mean monthly and annual clinic volumes were calculated. Return visit proportions were compared using chi-square test. Negative binomial regression analysis was used to examine trends. RESULTS: There were a total of 8722 colposcopy clinic visits between January 2010 and December 2015. Approximately 7395 visits (85%) were new patient visits, and 1327 visits (15%) were return visits. The percentage of return visits declined dramatically during the study period from 22.9% (2011) of total visits to 9.0% in 2015 (P < 0.001). Annual clinic volume ranged from 903 to 1884 with a mean monthly volume of 121.13 visits (SD, 42.1). Annual volume was highest in 2011 (n = 1884) and has since demonstrated a steady decline. In 2015, average monthly volume (75.3 visits) dropped to nearly one third of its peak 218 visits per month in July 2010. CONCLUSIONS: In a large referral clinic that adheres to guideline-based screening and management recommendations, monthly colposcopy volume has declined dramatically with a reduction by two thirds compared with peak volume in 2010.

Update on vaccination clinical trials for HPV-related disease.

BACKGROUND: Cervical cancer remains a major cause of cancer death in women worldwide. Moreover, human papillomavirus (HPV)-related disease of the urogenital tract (including preinvasive and invasive cervical, vaginal, vulvar, penile, and anal disease) remains a major cause of morbidity and mortality in the United States and internationally. OBJECTIVE: The goal of this article was to review the vaccines available as well as the major Phase III trials of the quadrivalent and bivalent vaccines for the prevention of HPV-related genital tract disease. METHODS: A literature search was performed through PubMed using the terms "HPV vaccination" and limited to clinical trials over the last 6 years. The most relevant and largest scale trials were included in this report. RESULTS: Prophylactic vaccination has emerged as an important tool that holds promise in decreasing the burden of HPV disease. However, HPV vaccination is known to be largely type-specific. Vaccination is most effective when administered at a younger age and before sexual activity and exposure to HPV. Large trials have been conducted and show efficacy of both the bivalent (HPV types 16 and 18) and quadrivalent (HPV types 6, 11, 16, and 18) vaccine in the prevention of preinvasive lesions and infection with these HPV types. CONCLUSIONS: Future directions include development of more affordable vaccines with extended HPV-type coverage as well as implementation of feasible worldwide vaccination programs.