Ovarian Sex Cord Tumor With Annular Tubules (SCTAT) Harbor Recurrent Copy Number Alterations, Including Monosomy 22

Sex cord tumor with annular tubules (SCTAT) is a rare ovarian sex cord-stromal neoplasm of low or intermediate malignant potential. Although some SCTATs are associated with Peutz-Jeghers syndrome (PJS), the majority arise in the nonsyndromic setting and typically lack STK11 mutations. As molecular alterations other than STK11 in SCTAT are largely unknown, we sought characterize the genomic landscape in these neoplasms better. SCTATs (n = 22) from 20 patients (5 with PJS, 1 with Prader-Willi syndrome, and 14 with no known syndromic status) were retrospectively identified. STK11 (LKB1) immunohistochemistry (IHC) was performed. Panel-based DNA sequencing was used to detect copy number variations and point mutations in 447 genes in 12 tumors from patients with no history of PJS, with 1 additional non-PJS tumor undergoing only targeted STK11 sequencing. Molecular profiles were compared with other ovarian sex cord-stromal tumors (n = 67). An STK11 mutation and concurrent loss of heterozygosity was in 1 of 13 sporadic tumors. STK11 IHC was intact (n = 14) or equivocal (n = 2) for STK11 wild-type tumors and lost in 1 sporadic tumor with STK11 mutation and 5 tumors from patients with known PJS. TERT promoter mutations were present in 6 of 12 tumors. Recurrent copy number alterations included monosomy 22 (8/12), as well as low-level copy number gains of FOXL2 (10/12; median, 4.3 estimated copies in FOXL2-gained tumors; range, 2.6-7.9), WT1 (9/12), and GATA4 (8/12). One tumor demonstrated biallelic inactivation of TP53 in a region of high-grade transformation characterized by significant cytologic atypia, mitotic activity, and necrosis. In conclusion, nonsyndromic SCTATs are molecularly characterized by FOXL2, WT1, and GATA4 gains, monosomy 22, and TERT promoter mutations. High-grade transformation may rarely occur, a phenomenon not previously described, and is associated with TP53 mutation. STK11 IHC appears to be a reliable surrogate for STK11 mutations and may be useful in suggesting a PJS-related tumor.