Objective Adult type granulosa cell tumor (aGCT) of the ovary is characterized by late recurrence, and no effective treatment strategy is established. The diagnosis of aGCT is difficult because of its rarity. Recently, FOXL2 C402G mutation was detected in 92% of aGCTs, and the presence of TERT promoter mutation was reported to be associated with worse prognosis. We analyzed the mutational status of FOXL2 and TERT promoter of aGCT tumor samples to investigate the impact on accurate diagnosis and prognosis.

Methods FOXL2 and TERT promoter mutational status of the 64 primary and 8 recurrent aGCT FFPE samples were assessed by allelic discrimination assay. H&E slides of the primary samples which had wild-type(wt) FOXL2 were reviewed by two gynecologic pathologists and the cases with ambiguous morphology were excluded as aGCt mimicking tumor. The characteristics and prognosis of molecularly/pathologically confirmed aGCTs (MP-aGCTs) were analyzed in each clinical parameters and mutational status.

Results Median follow-up duration was 73 months. Three primary samples were diagnosed as aGCT mimicking tumor. Of the 61 MP-aGCTs, 46 (75%) harbored FOXL2 mutation and 10 (16%) cases had TERT promoter mutation. Clinical stage and older age were the prognostic factor for recurrence. TERT promoter mutation was highly identified in older patients and larger tumors. The presence of heterozygous FOXL2 C402G mutation showed the tendency of worse prognosis.

Conclusions The importance of mutational analysis in the diagnosis, long term observation of the patients, and the functional analysis of FOXL2 C402G mutation was highlighted.