Novel BRAF gene fusions and activating point mutations in spindle cell sarcomas with histologic overlap with infantile fibrosarcoma.

Infantile fibrosarcoma (IFS)/cellular congenital mesoblastic nephroma (cCMN) commonly harbors the classic ETV6-NTRK3 translocation. However, there are recent reports of mesenchymal tumors with IFS-like morphology harboring fusions of other receptor tyrosine kinases or downstream effectors, including NTRK1/2/3, MET, RET, and RAF1 fusions as well as one prior series with BRAF fusions. Discovery of these additional molecular drivers contributes to a more integrated diagnostic approach and presents important targets for therapy. Here we report the clinicopathologic and molecular features of 14 BRAF-altered tumors, of which 5 had BRAF point mutations and 10 harbored one or more BRAF fusions. Of the BRAF fusion-positive tumors, one harbored two BRAF fusions (FOXN3-BRAF, TRIP11-BRAF) and another harbored three unique alternative splice variants of EPB41L2-BRAF. Tumors occurred in ten males and four females, aged from birth to 32 years (median 6 months). Twelve were soft tissue based; two were visceral including one located in the kidney (cCMN). All neoplasms demonstrated ovoid to short spindle cells most frequently arranged haphazardly or in intersecting fascicles, often with collagenized stroma and a chronic inflammatory infiltrate. No specific immunophenotype was observed; expression of CD34, S100, and SMA was variable. To date, this is the largest cohort of BRAF-altered spindle cell neoplasms with IFS-like morphology, including not only seven novel BRAF fusion partners but also the first description of oncogenic BRAF point mutations in these tumors.

Perioperative Management of Patients with Colovesical Fistula.

BACKGROUND: Colovesical fistula (CVF) is an uncommon complication of diverticulitis. Substantial heterogeneity exists in the perioperative management of this condition. We seek to evaluate the role of bladder leak testing, closed suction drainage, prolonged bladder catheter usage, and routine postoperative cystogram in the management of CVF. STUDY DESIGN: This is a retrospective study from a single academic health center investigation patients undergoing operation for diverticular CVF from 2005 to 2015 (n = 89). RESULTS: Patients undergoing operative repair for diverticular CVF resection had a mortality of 4% and overall morbidity of 46%. Intraoperative bladder leak test was performed in 36 patients (40%) and demonstrated a leak in 4 patients (11%). No patients with a negative intraoperative bladder leak test developed a urinary leak. Overall, five (6%) patients developed postoperative bladder leak. Three were identified by elevated drain creatinine and two by cystogram. The diagnostic yield of routine cystogram was 3%. All bladder leaks were diagnosed between postoperative day 3 and 7. Of patients with a postoperative bladder leak, none required reoperation and all resolved within 2 months. CONCLUSIONS: There is significant variability in the management of patients undergoing operation for CVF. Routine intraoperative bladder leak test should be performed. Cystogram may add cost and is low yield for routine evaluation for bladder leak after operation for CVF. Urinary catheter removal before postoperative day 7 should be considered.