Ovarian Sertoli-Leydig cell tumors with somatic DICER1 mutations: a clinicopathologic study of 15 cases.

Ovarian Sertoli-Leydig cell tumors (SLCTs) are a rare type of sex cord-stromal neoplasm. Approximately 60% of these tumors are associated with DICER1 mutations, which may occur in the context of the rare DICER1 syndrome. Due to the scarcity of these tumors, their comprehensive clinicopathologic spectrum and optimal management remain incompletely defined. We conducted a single-institution, retrospective clinicopathologic study on 15 patients with molecularly confirmed DICER1-related ovarian SLCTs (January 2020 - May 2025). Clinical, surgical, pathologic, and molecular data were analyzed. The median patient age at diagnosis was 21 years (range: 3-34 years). Most patients (93.3%, 14/15) were symptomatic, with abdominal distension (53.3%) and secondary amenorrhea (33.3%) being the most common presentations. The vast majority of tumors (93.3%, 14/15) were FIGO stage I, and the median largest tumor dimension was 12.0 cm. Fertility-preserving surgery was performed in 93.3% of cases; however, intraoperative tumor rupture occurred in 46.7% (7/15). Histopathologically, all tumors demonstrated classic SLCT features and were immunopositive for inhibin and calretinin. Among the cohort with somatic DICER1 mutations, only one patient (6.7%) was found to have a concurrent germline DICER1 pathogenic variant. Notably, all tumors were moderately (60.0%, 9/15) or poorly (26.7%, 4/15) differentiated, with no well-differentiated SLCTs observed. Adjuvant platinum-based chemotherapy was administered to 53.3% (8/15) of patients, primarily those with stage IC (85.7%) or higher-stage disease. After a median follow-up of 19 months, no recurrences were observed in patients with stage I disease. This study confirms that DICER1-related SLCTs predominantly occur in young women and typically present at an early stage. Our findings suggest a favorable short-term prognosis for stage I disease. We identify a strong genotype-phenotype correlation, with DICER1 mutations being exclusively associated with non-well-differentiated histology. Meticulous surgery to prevent tumor rupture is paramount, and adjuvant chemotherapy can be effectively reserved for higher-risk patients. Longer-term follow-up is needed to fully define the prognostic implications of our observations.