Occult invasive and preneoplastic lesions at risk-reducing salpingo-oophorectomy in BRCA1/2 carriers: A multicenter retrospective cohort study.

To evaluate the prevalence and spectrum of occult invasive or preneoplastic lesions detected at risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers and to describe recurrent BRCA variants in a regional multicenter cohort. This multicenter retrospective cohort study included 291 women with documented germline pathogenic BRCA1/2 alterations who underwent RRSO at three referral centers in Apulia, Italy, between 2020 and 2025. The primary endpoint was occult invasive or microinvasive tubo-ovarian malignancy at final histopathology. Secondary endpoints included serous tubal intraepithelial carcinoma (STIC), the distribution of histopathologic findings, distribution according to BRCA group, and recurrent annotated BRCA variants. After excluding one patient with ovarian metastasis, occult invasive or microinvasive tubo-ovarian malignancy was identified in 24/290 patients (8.3%), while STICs were identified in 5/290 (1.7%). STIL was observed in 3/291 patients (1.0%). Overall, 29/290 patients (10.0%; 95% confidence interval 7.1-14.0) met the composite endpoint of occult invasive or microinvasive primary tubo-ovarian malignancy or STIC. Among pathogenic variant carriers, the prevalence of the same endpoint was 20/159 (12.6%) in BRCA1 carriers and 9/131 (6.9%) in BRCA2 carriers (p = 0.119). Specific BRCA mutation was available for 154/291 patients (52.9%); BRCA1 c.5266dupC was the most frequent recurrent annotated variant, accounting for 43/154 (27.9%) annotated variants overall and 43/81 (53.1%) annotated BRCA1 variants. In this multicenter BRCA1/2 cohort, occult invasive or microinvasive primary tubo-ovarian malignancy and STIC were identified in approximately one in ten women undergoing RRSO. Most positive cases represented occult invasive or microinvasive malignancy, and BRCA1 c.5266dupC emerged as the dominant recurrent regional variant.