Characterizing thyroid carcinomas in the elderly: Histological subtypes and TERT promoter mutation analysis based on the latest WHO classification

Abstract

While most thyroid cancers have a favorable outcome, their presentation in the elderly (>= 70 years) is often aggressive, leading to a poor prognosis and creating a clinical dilemma in balancing treatment intensity against comorbidities. A more precise understanding of the biological drivers is crucial for optimal management. This study aimed to characterize these aggressive tumors by correlating high-risk histological subtypes-specifically poorly differentiated (PDTC) and differentiated high-grade thyroid cancer (DHGTC)-with the presence of telomerase reverse transcriptase (TERT) promoter mutations. We conducted a retrospective analysis of 293 consecutive patients, aged 70 or older, who underwent thyroidectomy between 2019 and 2023. Comprehensive clinicopathological data, including TNM and AJCC staging, were collected, and molecular analysis for TERT mutations was performed via pyrosequencing. PDTC/DHGTC accounted for 6.1 % of tumors in this cohort, while TERT promoter mutations were detected in 15.0 % of cases. Importantly, results revealed a statistically significant association between TERT promoter mutations and established markers of poor prognosis. TERT-mutated tumors were larger and presented at a more advanced T stage. These patients had a significantly higher incidence of both regional lymph node involvement and distant metastatic disease or recurrence, resulting in a higher overall AJCC stage. On a histological level, the TERT mutation was a strong predictor of aggressive PDTC/DHGTC subtypes and was closely linked to increased mitotic activity and tumor necrosis. In conclusion, our findings demonstrate that PDTC/DHGTC subtypes are not uncommon in elderly patients and that TERT promoter mutations occur at a relatively high frequency. The strong association of TERT mutations with aggressive tumor characteristics suggests that combined histological and molecular assessment may provide enhanced prognostic precision in this high-risk group.