The co-occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome

Abstract

The DICER1 gene encodes an endoribonuclease involved in the production of mature microRNAs which regulates gene expression through several mechanisms. Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Pleuropulmonary blastoma is the most frequent lesion seen in this syndrome. Thyroid abnormalities are also a common finding, essentially concerning multinodular goiter. However, differentiated thyroid carcinoma is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 RNase IIIb catalytic domain in several tumor types, including ovarian Sertoli-Leydig cell tumors. We report two cases of differentiated thyroid carcinoma associated with ovarian Sertoli-Leydig cell tumor and with a heterozygous DICER1 gene mutation, occurring in two unrelated young girls without pleuropulmonary blastoma. Both thyroid carcinomas showed an E1813 mutation in exon 25 while the ovarian tumors harboured a somatic mutation in E1705 in exon 24 and a D1709 mutation in exon 25. Our observations confirm that the occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome. We contend that the possibility of a relationship between sporadic thyroid carcinoma in young patients and somatic DICER1 gene mutation needs further investigation.

Cytomorphologic features of thyroid disease in patients with DICER1 mutations: A report of cytology–histopathology correlation in 7 patients

“…DICER1 mutations were associated with MNG with relatively high penetrance, and DICER1-asociated thyroid cancer (PTC and FC) was reported in increasing numbers. 15,[19][20][21][22][23][24][25][26][27][28] Notably, a large number of neoplasms developed in children who had received chemotherapy for a DICER1-related tumor. Thyroid FNA cytology is a critical diagnostic tool for the evaluation of thyroid gland Cancer Cytopathology October 2020…”

Sertoli-Leydig Cell Tumor

“…[10][11][12] In the literature, there are some studies suggesting the coexistence of SLCT and thyroid anomalies and other probable accompanying neoplasias may be part of a syndrome associated with germline DICER 1 mutation. 10,13,14 Prognosis of SLCT is considerably correlated with tumor differentiation grade, tumor extension as well as presence of subtypes accompanied by retiform and heterologous elements. 1,9 Majority of the cases are grade I at diagnosis and their prognosis is usually favorable.…”

Recently characterized molecular events in uncommon gynaecological neoplasms and their clinical importance

“…However, the DICER1 syndrome also includes commoner conditions, such as thyroid multinodular goitre (MNG), and differentiated thyroid cancers. Certain gynaecological tumours, such as ovarian SCSTs (especially SLCT; see below), ERMS of the uterine cervix, and (rarely) ovarian ERMS, are also typically seen . Although these gynaecological tumours are relatively rare, their occurrence in families with known germline mutations in DICER1 , together with the presence of typical somatic DICER1 mutations in trans , reveal that they can be caused by germline mutations in this gene.…”

“…Certain gynaecological tumours, such as ovarian SCSTs (especially SLCT; see below), ERMS of the uterine cervix, and (rarely) ovarian ERMS, are also typically seen. [31][32][33] Although these gynaecological tumours are relatively rare, their occurrence in families with known germline mutations in DICER1, together with the presence of typical somatic DICER1 mutations in trans, reveal that they can be caused by germline mutations in this gene. The molecular link between thyroid MNG and SLCT was originally discovered by Rio Frio et al 34 in families containing women affected by both conditions.…”