Endocrine Abstracts

Background: Somatic and bi-allelic DICER1 mutations have been reported in subsets of sporadic thyroid tumors, affirming a clear involvement of this gene in the development of thyroid tumors. As a recent study has highlighted associations between DICER1 mutations and macrofollicular patterns, abortive changes, and papillary structures, we aimed to investigate these observations in a bi-institutional cohort.

Methods: A total of 61 thyroid lesions (54 tumors and 7 cases of thyroid follicular nodular disease; TFND), including 26 DICER1 mutated cases and 35 DICER1 wildtype controls underwent histological re-investigation and clinical follow-up.

Results: DICER1 mutated cases showed a statistically significant association with younger age at surgery (29.2±12.5 vs 51.3±18.8, P=0.0001), a predominant macrofollicular growth pattern (20/26 mutated cases vs 18/35 wildtype; P=0.01) and abortive changes (20/26 mutated cases vs 2/35 wildtype; P=0.0001). Similar results were obtained when excluding TFND cases. We also present clinical and histological triaging criteria for DICER1 sequencing of somatic tissues, which led to the identification of DICER1 variants in 16 out of 26 cases (62%) when followed. In cases with available germline data (n=12), 3 cases (25%) were found to carry germline DICER1 mutations. This observation smggests that the majority of DICER1 variants are somatic – however, it implies that sequencing of constitutional tissues could be clinically motivated.

Conclusion: We conclude that DICER1 mutations are amassed in younger patients with macrofollicular-patterned tumors and, most strikingly, abortive changes. Considering the rate of germline involvement, our findings hold potential clinical value, allowing the pathologist to triage cases for genetic testing based on histological findings.