ESPE Abstracts

Background: Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestation. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumors, particularly Sertoli–Leydig cell tumor, individuals with pathogenic germline DICER1 variants could also have lung cysts, cystic nephroma, multinodular goiter, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma and brain tumors including pineoblastoma and pituitary blastoma.

Objective: The girl presenting at 16 years with complains of voice coarsening, irregular menstruation, clitoral hypertophy, pulling pains in the lower abdomen and about the multinodular goiter diagnosed during clinical examination. Anamnesis: Menarche was at the age of 11, regular menstrual cycle was until the age of 13, after irregular. The last menstruation at the age of 15. Voice coarsening was revealed from the age of 14. A multinodular goiter was identified at the age of 16 (histologically – colloid goitre). At the same time, a hormonal examination was performed: LH 17.2 IU/L (2.4–5.4), FSH 2.59 IU/L (1.9–3.7), estradiol 18.35 pmol/l (143–264), testosterone 8.85 nmol/l (0.6–2.3), DHEA-S 6.13 μmol/l (0.9–11.7), androstenedione 30.2 nmol/l (1–12, 2), TSH 1.25 mIU/l (1.3–4.9), f.T4 15.3 pmol/l (10–25). Pelvic Ultrasound: a tumor (11.0×7.5×11.0 cm) with a dense capsule, inhomogeneous with multiple cystic components was detected in the right ovary. Oncomarkers (CA19-9, HE-4, alpha fetoprotein) were negative. The patient underwent the resection of the right ovary. Histological examination: Sertoli-Leydig cell ovarian tumor with areas of hemorrhage and decay. The hereditary history: a multinodular goiter in the mother.

Methods: ‘Pituitary adenomas panal’ genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent).

Results: A heterozygous mutation p.A969CfsX5 was found in DICER1 gene.