FOXL2 mutation analysis of both the morphologically low-grade and high-grade areas in 4 of 5 cases confirmed the presence of missense point mutation, c.402C>G, p.(Cys134Trp), providing conclusive evidence that the high-grade component represents transformation of typical AGCT rather than the coexistence of another sex cord-stromal tumor, such as juvenile granulosa cell tumor, which has been suggested for such neoplasms.
Based on the literature review, FOXL2 immunostaining is a highly specific marker for sex cord-stromal tumors (SCSTs), but it is not specific for AGCTs, one subtype of SCSTs.
Four of 11 tumors with satisfactory analysis showed a FOXL2 mutation; 3 of these cases were reported initially as unclassified SCST and 1 as Sertoli-Leydig cell tumor.
FOXL2 immunostaining was present in 95 of 119 (80%) SCSTs, including >95% of aGCTs, juvenile granulosa cell tumors, fibromas, and sclerosing stromal tumors.
Mutational analysis (c.402C>G) of the FOXL2 gene and immunohistochemical expression of the FOXL2 protein in testicular adult type granulosa cell tumors and incompletely differentiated sex cord stromal tumors.