ESPE Abstracts

DICER1, a gene located on chromosome 14q32.13, encodes a protein ribonuclease (RNase) IIIb that plays a central regulatory role in miRNA processing. DICER1 syndrome has an autosomal dominant inheritance and predisposes affected individuals to a wide variety of tumors, both benign and malignant. We describe the case of a 6-year-old girl, carrier of a DICER1 germline mutation, and affected by a differentiated thyroid carcinoma. At the age of 6 a first thyroid ultrasound revealed the presence of a solid isoechoic nodule of 21 x 29 x 38 mm with intranodular vascular signals in the left thyroid lobe. At blood tests: TSH 4.13 (0.27-4.2) mU/L, FT4 1.11 (0.93-1.7) ng/dL; negative thyroid autoimmunity, calcitonin 5.3 (vn <6.9) ng/L. Thyroid cytology by needle aspiration was compatible with follicular neoformation, TIR3b sec. Italian Consensus-IS. Genetic analysis by next generation sequencing (NGS) was negative for KRAS and BRAF. The patient underwent at the age of 6 a left lobe-isthmectomy; the histological examination showed a follicular carcinoma, described as encapsulated with focal infiltration of the capsule and angioinvasive; TNM stage pT2, pNX. In consideration of the age and the histological result, genetic investigation was performed by NGS which highlighted a heterozygous germline variant in the DICER1 gene determining the formation of a putative truncated protein p.(Gln249*), classified as pathogenic. After 8 months the patient underwent completion of the thyroidectomy due to the appearance of a solid nodule in the right thyroid lobe; histological examination showed the presence of a papillary microcarcinoma. The patient's father and younger sister were found to be carriers of the same mutation in the DICER1 gene; a first thyroid ultrasound performed in the younger sister showed the presence of a solid nodule. The patient's older sister at the age of 9 underwent surgery to remove the left ovary for a Sertoli cell tumor; a first thyroid US, perfomed at the age of twenty, showed a multinodular goiter; her genetic analysis for DICER1 is currently pending. DICER1-related pediatric thyroid involvement consists of benign nodular follicular disease, follicular adenoma, differentiated thyroid carcinoma, as well as poorly differentiated thyroid carcinoma. Recently, many progresses have been made in understanding the features of patient affected by DICER1 syndrome, especially the possibile associated tumors and relative age of onset, although the natural history, the growth rate and the prevalence of DICER1-associated tumors remain to be investigated as well as specific sureveillance protocols are needed.