Primary fallopian tube lesions in BRCA mutation carriers undergoing risk-reducing surgery.

Abstract

1512 Background: The fallopian tube (FT) has been identified as a likely site of occult disease in patients (pts) undergoing risk- reducing salpingo-oophorectomy (RRSO) for the prevention of primary ovarian cancer. In recent studies, thorough pathologic examination of the adnexa has identified tubal intraepithelial carcinoma (TIC) in 4%-10% of BRCA-positive pts undergoing RRSO. Our objective was to review the incidence of primary FT lesions in BRCA-positive women undergoing RRSO at a single comprehensive cancer center. Methods: Pts undergoing RRSO between January 2005 and August 2009 were identified from operative records. Clinical and pathologic information were collected from the medical record. In all cases, the FTs were entirely submitted, serially sectioned, and the fimbriated end extensively examined by a GYN specialty pathologist. IHC was used only to confirm clinical diagnoses in equivocal cases. Results: We identified 158 pts with BRCA mutations documented in the medical record. Eighty-three (52%) pts were Jewish, 42 (27%) were Catholic, 33 (21%) were of other religions. The median age at time of surgery was 48 years (range, 33-79 years). Fifty-nine pts had a BRCA1 mutation, 56 had a BRCA2 mutation, and 43 had a documented germline BRCA mutation, not otherwise specified. All mutations were known to be deleterious. The most frequent mutations found were BRCA1 185delAG (23, 15%), BRCA2 6174delT (18, 11%), and BRCA1 5382insC (8, 5%). Two cases of TIC (1.3%) were identified. Three additional pts (2%) were found to have epithelial dysplasia/p53 signature lesions of the FT. Immunohistochemical stains confirmed that these three lesions had p53 overexpression without increased proliferation or nuclear atypia. No cases of invasive ovarian or tubal carcinoma were identified, and all proximal FTs were normal. Conclusions: The incidence of TIC in this study is lower than in previously published reports while considering that all pts had deleterious BRCA mutations and comprehensive processing of the FTs. This may be due to a different mutational spectrum, tissue processing protocols, or sample ascertainment biases. Refining the estimates of TIC and occult malignancies has useful implications for cancer prevention. No significant financial relationships to disclose.