Somatic tumour testing establishes that bilateral DICER1‐associated ovarian Sertoli–Leydig cell tumours represent independent primary neoplasms

Abstract

Aims Sertoli–Leydig cell tumours (SLCTs) are rare ovarian neoplasms that are commonly associated with somatic or germline DICER1 mutations, especially when of the moderately or poorly differentiated type. A large majority are unilateral, but bilateral neoplasms have been reported, sometimes in the context of germline DICER1 mutations (DICER1 syndrome). It is currently unknown whether these represent independent neoplasms or metastasis from one ovary to the other and we aimed to elucidate this. Methods and results We report three cases of bilateral ovarian SLCT (all in patients with DICER1 syndrome) and review all reported cases of bilateral neoplasms. In the three cases (all moderately or poorly differentiated neoplasms), the time interval between the discovery of the tumours in each ovary ranged from 2.7 years to 6 years. In all cases, different DICER1 somatic hotspot mutations within the two tumours provided definitive proof that they represent independent neoplasms; this may be important clinically. Our literature review revealed that, when this information was available, all patients with bilateral SLCT had a germline DICER1 mutation. Conclusions Bilateral ovarian SLCTs represent independent rather than metastatic neoplasms, and essentially always occur in the context of DICER1 syndrome.

Pediatric Sertoli-Leydig Cell Tumors of the Ovary

“…The ages of our patients ranged from 4 to 16 years (median, 14 y), similar to the study from the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) that showed a median age of 13.9 (range, 0.4 to 17.5) years in ovarian SLCTs of children and adolescents (n=44) 24 . SLCTs are almost always unilateral, and bilaterality may be associated with germline DICER1 mutation 25 . The study in ovarian SLCTs of children and adolescents from EXPeRT showed that 43 patients (43/44; 97.7%) had unilateral tumors and 1 patient (1/44; 2.3%) presented with a synchronous bilateral tumor 24 .…”

“…24 SLCTs are almost always unilateral, and bilaterality may be associated with germline DICER1 mutation. 25 The study in ovarian SLCTs of children and adolescents from EXPeRT showed that 43 patients (43/44; 97.7%) had unilateral tumors and 1 patient (1/44; 2.3%) presented with a synchronous bilateral tumor. 24 In our study, all of 8 SLCTs were confined to 1 ovary.…”

Imaging, clinical, and pathologic findings of Sertoli-leydig cell tumors

“…Two of our samples harbored a DICER1 hotspot mutation, which was the p. E1705K mutation. It was established by previous studies [12][13][14][15] that p. D1709N was the most common mutation hotspot in SLCTs, followed by p. E1813K. Other mutations included p. E1705K, p. D1709G, p. D1709V, p. G1809R, p. D1810Y, p. E1813Q, and p. E1813D.…”

Phenotypic Similarities Within The Morphologic Spectrum Of DICER1-Associated Sarcomas and Pleuropulmonary Blastoma -- Histopathologic Features Suggesting Genetic Testing and Counselling

“…While Apellaniz-Ruiz in their review showed that nearly all gynecologic ERMSs (except vaginal tumours) were DICER1 -associated, Doros et al detected DICER1 mutation in only 3.8% (2/52) cases of sporadic ERMS and the Children's oncology group cohort of pediatric rhabdomyosarcomas showedDICER1 germline mutation in 4.4%. 10,[17][18][19][20] DICER1 -associated central nervous system sarcomas also have a high association with rhabdomyosarcomatous differentiation. 8,21,22 Our CNS case mimicked mesenchymal chondrosarcoma, though it expressed ERMS markers.…”