Endocrine Abstracts

De-escalation of thyroid cancer treatment is crucial to prevent over-treatment of indolent disease. However, it also underscores the importance of identifying potential clinically aggressive cases that require completion lobectomy and adjuvant radioiodine therapy. TERT promoter mutations are molecular events closely associated to high-risk thyroid tumors with poor outcome, and may serve as markers for cases at risk of dissemination. In various international guidelines, minimally invasive follicular thyroid carcinoma and oncocytic thyroid carcinoma (miFTC/miOTC) measuring less than 2 cm (pT1a/1b) are classified as low-risk lesions. The Swedish national guidelines recommend no additional treatment beyond diagnostic lobectomy for these patients. Our study aimed to explore the association between size-based risk assessment and TERT promoter mutations. Between 2019 and 2023, 77 miFTCs/miOTCs diagnosed at our department underwent digital droplet PCR analysis of tumor DNA targeting TERT promoter mutational hotspots C228T and C250T. Histopathological, immunohistochemical and clinical variables were collected at the end of the study (January 2024). In total, TERT promoter mutations were found in 8 out of 77 cases (10.4%), 6 miFTCs, and 2 miOTCs. Mutated cases were pT2 (n=2) and pT3a (n=6), but no mutations were found among the pT1a/b tumors (n=11). Mutated tumors displayed an average size of 55.6 mm (range 37–100 mm), significantly larger than wildtype tumors with an average size of 38.2 mm (range 9–130 mm) (P-value: 0.014). There were no significant differences between patients with mutated or wildtype tumors regarding patient sex, age at surgery or the Ki-67 proliferation index. In conclusion, TERT promoter mutations in miFTC/miOTC are associated with larger tumor size. Clinical routine sequencing of pT1a/b miFTCs and miOTCs may not be beneficial. The current strategy of releasing small, low-risk lesions as outpatients without additional treatment is supported by our molecular risk stratification, indicating that TERT promoter mutational sequencing in clinical routine could be reserved for larger tumors.