Serous Tubal Intraepithelial Carcinoma in a Risk-reducing Salpingo-oophorectomy Specimen From a RAD51D Mutation Carrier: A Case Report

Abstract

The RAD51D gene codes a protein-paralog of the RAD51 DNA recombinase, which catalyzes DNA strand exchange during homologous recombination. Similar to BRCA1/BRCA2, mutations in RAD51D both predispose to ovarian carcinoma and impart sensitivity to poly (ADP-ribose) polymerase inhibitors in preclinical studies. Based on cancer risk prediction models, RAD51D mutations pose a moderate-to-high risk for ovarian cancer warranting consideration for risk-reducing surgery. We report a case of serous tubal intraepithelial carcinoma in a patient undergoing risk-reducing total hysterectomy with bilateral salpingo-oophorectomy for a RAD51D pathogenic variant. The histopathologic and p53-immunophenotypic features of this lesion are similar to those reported previously in BRCA1/BRCA2 mutation carriers and those of serous tubal intraepithelial carcinoma associated with sporadic high-grade serous carcinomas. These features include marked increase in nuclear-to-cytoplasmic ratio, loss of cell polarity, absence of ciliation, prominent nucleoli, mitotic activity, epithelial stratification, surface exfoliative changes, and complete loss of p53 staining. Although familial ovarian cancers with mutations in RAD51D-or other genes in the Fanconi anemia pathway-are much less common those with BRCA1/BRCA2 mutations, our findings support a common phenotype for early serous cancers in this pathway.

Pathologic Findings at Risk Reducing Surgery in BRCA and Non-BRCA Mutation Carriers: A Single-Center Experience

“…In a recent prospective observational study, the largest single institution series including 27 non BRCA gene mutation carriers, Rush et al [ 40 ] reported a diagnosis of STIC in a carrier of a PALB2 mutation with a strong family history of both BC and EOC; another case report by Gregory-Davis et al [ 45 ] reported a diagnosis of STIC in a RAD51D mutation carrier; HGSC and a low grade serous carcinoma were reported by Schoolmeester et al [ 46 ] in two patients, carrying mutations in RAD51C and CHEK 2, respectively. All these results must be taken with caution, because these mutations have a very low incidence, and large case-control studies are needed to validate the findings; however, we still cannot exclude the possibility of these genes conferring a moderate risk of developing EOC [ 47 ].…”