Evaluation of molecular analysis in challenging ovarian sex cord-stromal tumours: a review of 50 cases

Molecular profiling was performed in 50 problematic ovarian sex cord-stromal tumours (SCSTs) most of which were seen in consultation. Following analysis, 17 were classified as adult granulosa cell tumour (AGCT), 16 of which showed a FOXL2sequence variant (mutation); the initial favoured diagnosis in five of the cases was benign thecoma/fibrothecoma. Thirteen tumours ultimately classified as cellular fibroma or thecoma were FOXL2sequence variant negative which was helpful in excluding AGCT. All six Sertoli–Leydig cell tumours (SLCTs) demonstrated DICER1‘hot spot’ sequence variants, and one case each of AGCT and SLCT showed high grade histological transformation associated with a concurrent TP53sequence variant. All eight unclassified SCSTs were negative for FOXL2mutations and the six tested cases were DICER1wild type; however, three tumours demonstrated MET, CTNNB1or TP53sequence variants. Four cases were classified as juvenile granulosa cell tumour, and one of these harboured a GNASsequence variant. The single gynandroblastoma and microcystic stromal tumours in the series demonstrated FOXL2and CTNNB1alterations, respectively. In summary, molecular analysis aids in accurate classification of challenging ovarian SCSTs and sometimes leads to revision of the favoured provisional diagnosis. TP53sequence variants may be associated with dedifferentiation in both SLCTs and AGCTs.