W Glenn McCluggage1, Anne-Laure Chong2,3,4, Leanne de Kock2,3,5, William D Foulkes2,3,4. 1. Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK. 2. Department of Human Genetics, McGill University, Montreal, Quebec, Canada. 3. Cancer Axis, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada. 4. Cancer Research Program, Research Institute of the McGill University Health Centre, Montréal, Québec, Canada. 5. Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, University of Western Australia, Perth, Western Australia, Australia.
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.
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.
Authors: Annie Garcia; Lauren Desrosiers; Sarah Scollon; Stephanie Gruner; Jacquelyn Reuther; Ilavarasi Gandhi; Ninad Patil; Maren Y Fuller; Hongzheng Dai; Donna Muzny; Richard A Gibbs; Jennifer L Bercaw-Pratt; Seema L Rao; Nino Rainusso; Kevin E Fisher; Frank Y Lin; Sharon E Plon; D Williams Parsons; Angshumoy Roy Journal: Cancer Genet Date: 2022-01-05