Identification of Recurrent TERT Promoter Mutations in Intrathyroid Thymic Carcinomas

Intrathyroid thymic carcinoma (ITTC) is a rare malignant neoplasm considered to be a eutopic thymic carcinoma (TC) arising ectopically in the thyroid. Histopathologically, ITTC resembles squamous cell carcinoma of the thymus with positive TC markers such as CD5 and c-KIT. Despite these similar histological findings, ITTC is clinically less aggressive than TC. In this study, we compared clinical, histological, and genetic characteristics of ITTCs and TCs. We collected 9 ITTCs and 8 TCs with their clinicopathological profiles. Immunohistochemistry for CD5, p63, CD117/c-KIT, Ki-67, p53, TTF-1, thyroglobulin, PAX8, EGFR, and PD-L1/CD274 plus in situ hybridization for EBER was performed. We further investigated mutation status ofKIT,EGFR,BRAF, andTERTpromoter using Sanger sequencing. In our study, ITTCs affected significantly younger patients than TCs. After a mean follow-up of 86 months, all patients with ITTC were alive, while two patients with TC had died. Immunohistochemistry showed ITTCs and TCs had a similar immunophenotype except for EGFR and p53. Genetic analysis did not identifyKITorBRAFmutations in any ITTCs or TCs.EGFRmutations were positive in 11% (1/9) of ITTCs and 25% (2/8) of TCs. Notably,TERTpromoter C228T mutation was identified in 22% (2/9) of ITTCs but none of the TCs. There were no significant differences in age, tumor size, or sex betweenTERT-mutated andTERT-wild-type ITTCs. Collectively, ITTC and TC have similar histopathologic and immunophenotypic features but different clinical outcomes. RecurrentTERTpromoter mutation may be a key event related to cancer progression in ITTCs and warrants further investigation.