Abstract:
Purpose: Sertoli Leydig cell tumors (SLCT) are rare sex cord-stromal tumors of the ovary. Dicer1 mutations have been shown to be present in a majority of SLCT, while only few reported cases have harbored Foxl2 mutations. It was our aim to classify SLCTs according to their molecular profile and clinicopathological features.
Methods: Formalin-fixed, paraffin-embedded tissue blocks from a cohort of 45 SLCT diagnosed between 1995 and 2016 were available after specialized gynecopathological review. Dicer1 mutation status was determined by Sanger Sequencing while Foxl2 402G>C mutation status was determined by TaqMan allelic discrimination assay. Clinical data sets were updated allowing for correlation with mutation status.
Results: Dicer1 mutation analyses could be performed successfully in 44/45 SLCT, and 18/44 (41%) of cases were positive for at least 1 hotspot mutation. Dicer1 mutation-positive cases had a median age of 24,5 years (range 15-62 years). A majority (68,8%) of Dicer1 mutation-positive cases showed hyperandrogenic symptoms, and in 18,8% of patients, abnormal uterine bleeding was noted at presentation. Foxl2 mutation analyses was successfully done in all 45 cases, and 10/45 SLCT (22,2%) were 402G>C mutation positive. In this subgroup, the median age was 78,5 years (range 54-90 years). 4/5 (80%) of patients with Foxl2 mutation-positive SLCT had abnormal uterine bleeding at presentation.
Conclusions: This study suggests that there are different molecular subtypes of SLCT. Dicer1 mutation-positive tumors occur in younger patients presenting with hyperandrogenic symptoms, whereas Foxl2 mutation-positive SLCT occur more frequently in postmenopausal women presenting with abnormal uterine bleeding.
