DICER1 hot‐spot mutations in ovarian gynandroblastoma

Abstract

DICER1 hot-spot mutation is the key-driving event in a subset of gynandroblastomas containing components of SLCT and jGCT. Gynandroblastomas composed of SLCT and jGCT may represent morphological variants of SLCT. The molecular basis of gynandroblastoma containing a component of aGCT is different from pure aGCT.

Practical roles for molecular diagnostic testing in ovarian adult granulosa cell tumour, Sertoli–Leydig cell tumour, microcystic stromal tumour and their mimics

“…Among ovarian sex cord–stromal tumours, no FOXL2 C134W mutations have been identified in cellular fibromas, sclerosing stromal tumours, MCSTs, steroid cell tumours, Sertoli cell tumours, sex cord tumours with annular tubules (SCTATs), or gynandroblastomas . The C134W FOXL2 mutation has been identified in 1.6% (1/62) of conventional fibromas, 20% (7/35) of thecomas, 3% (2/59) of juvenile granulosa cell tumours (JGCTs), 13% (12/90) of SLCTs, 50% (6/12) of granulosa theca cell tumours, and 8% (2/24) of gynandroblastomas . These observations raise a nosological dilemma regarding the gold standard for tumour classification: morphology, immunophenotype, molecular phenotype, or some combination thereof.…”

“…DICER1 mutations have been reported in 50% (5/10) of Sertoli cell tumours, 36% (9/25) of gynandroblastomas, 11% (3/26) of JGCTs, 10% (2/20) of yolk sac tumours, 5% (1/20) of teratomas, 14% (2/14) of mixed germ cell tumours, and 20% (1/5) of gonadoblastomas with dysgerminoma …”

“…18 The C134W FOXL2 mutation has been identified in 1.6% (1/62) of conventional fibromas, 1,6,8,9,11,18 20% (7/35) of thecomas, 1,6,11 3% (2/59) of juvenile granulosa cell tumours (JGCTs), 1,6,[9][10][11][12]16,17 13% (12/90) of SLCTs, 1,6,8,9,11,18,23 50% (6/12) of granulosa theca cell tumours, 24 and 8% (2/24) of gynandroblastomas. 18,25,26 These observations raise a nosological dilemma regarding the gold standard for tumour classification: morphology, immunophenotype, molecular phenotype, or some combination thereof. In the absence of evidence on outcome or response to treatment, the approach to the answer is subjective, and may lead to observer variation in tumour classification and management.…”

“…Among ovarian tumours, no DICER1 mutations have been reported in AGCTs, 9,37 fibromas, 9 SCTATs, 9,26,39 sclerosing stromal tumours, 9 steroid cell tumours, 9 dysgerminomas, 37,39 or small-cell carcinomas, hypercalcaemic type. 39 DICER1 mutations have been reported in 50% (5/ 10) of Sertoli cell tumours, 9,26 36% (9/25) of gynandroblastomas, 25,26,50 11% (3/26) of JGCTs, 9,37,39 10% (2/20) of yolk sac tumours, 37,39 5% (1/20) of teratomas, 37,39 14% (2/14) of mixed germ cell tumours, 39 and 20% (1/5) of gonadoblastomas with dysgerminoma. 39…”

Recurrent gynandroblastoma of the ovary with germline DICER1 mutation: A case report and review of the literature

“…ATK1, FOXL2, and DICER1 gene mutations have been associated with SCSTs ( Rosario et al, 2014 , Auguste et al, 2015 ). DICER1 mutations have been associated with Sertoli-Leydig cell tumors (SLCTs) and gynandroblastomas ( Heravi-Moussavi et al, 2012 Jan 19 , Wang et al, 2018 Aug ). In addition to ovarian SCSTs, DICER1 pathogenic variants are also associated with an increased risk of benign and malignant lung, kidney, thyroid, and CNS tumors ( Schultz et al, 2018 ).…”