A Family with Sertoli–Leydig Cell Tumour, Multinodular Goiter, and DICER1 Mutation

Abstract

Background DICER1 syndrome is an autosomal dominant tumour predisposition syndrome associated with a wide variety of cancerous and noncancerous conditions, including ovarian sex cord–stromal tumours and thyroid conditions, including multinodular goiter. The most common ovarian sex cord–stromal tumour associated with DICER1 syndrome is Sertoli–Leydig cell tumour, with germline DICER1 mutations present in more than 50% of cases. We present a case in which a patient in her late 30s was diagnosed with a Sertoli–Leydig cell tumour in the background of a strong family history of multinodular goiter and Sertoli–Leydig cell tumour with a germline mutation in DICER1.Case Presentation A 38-year-old woman with history of multinodular goiter was found to have stage iiic ovarian Sertoli–Leydig cell cancer after presenting with abdominal pain. She underwent multiple surgeries and chemotherapy. The patient developed rapid disease progression and died 7 months after diagnosis. Seven years earlier, a daughter had experienced the same disease and was found to have a germline DICER1 mutation. The mother had not undergone testing before her own diagnosis.Summary The co-occurrence of Sertoli–Leydig cell tumour and multinodular goiter is highly suggestive of DICER1 syndrome. The recognition of DICER1 syndrome within a family is essential for increased awareness and potential early recognition of complications. Most conditions associated with DICER1 syndrome occur in childhood, and most of the current screening recommendations are specific for childhood and young adulthood. Cancer risks and findings for the adult population are not as well defined. Clinicians who encounter DICER1 syndrome should review recommendations for genetic testing and surveillance and enrol patients in the DICER1 registry.

Inherited Follicular Epithelial-Derived Thyroid Carcinomas: From Molecular Biology to Histological Correlates

“…Although cases of TC reported in children had been attributed to the chemotherapy and/or radiation they had received for DICER1-associated tumors [213][214][215], germline DICER1 mutations are associated with an increased risk of developing familial differentiated TC, even in the absence of prior treatment with chemotherapy [216]. Familial MNG and ovarian Sertoli-Leydig cell tumors [216][217][218][219][220][221][222] as well as cooccurrence of Sertoli-Leydig cell tumor with TC are highly suggestive of DICER1 syndrome [223]. The diagnosis of poorly differentiated thyroid carcinoma (PDTC) in childhood or adolescence is a rare event that should also suggest the possibility of a DICER1 syndrome [224].…”

Sertoli-Leydig cell tumor, thyroid follicular carcinoma and rhabdomyosarcoma of the uterine cervix in a prepubertal girl with pathogenic germline variant in DICER1 gene

“…Only a few children with SLCT and thyroid pathology, with or without associating genitourinary ERMS, has been reported to date. [6][7][8][9][10][11] Our patient developed embryonal RMS of the cervix and was treated by endoscopic surgery and chemotherapy.…”

Sertoli-Leydig cell tumor with DICER1 mutation

“…Sertoli-Leydig cell tumors (SLCT) are mixed sex cord-stromal tumors that comprise < 0.2% of ovarian neoplasms and typically present in the first two decades of life. Approximately 50% are associated with DICER1 mutations ( Haley et al, 2019 ); ( Schultz et al, 2017 ); ( Seidler et al, 2020 ). DICER1 syndrome is an autosomal dominant pleiotropic tumor predisposition syndrome ( Haley et al, 2019 ); ( Schultz et al, 2017 ); ( Schultz et al, 2017 ); ( Stewart et al, 2019 ).…”

“…Approximately 50% are associated with DICER1 mutations ( Haley et al, 2019 ); ( Schultz et al, 2017 ); ( Seidler et al, 2020 ). DICER1 syndrome is an autosomal dominant pleiotropic tumor predisposition syndrome ( Haley et al, 2019 ); ( Schultz et al, 2017 ); ( Schultz et al, 2017 ); ( Stewart et al, 2019 ). We report a case of a SLCT in a patient who was subsequently identified to have a germline DICER1 mutation.…”