Various genetic alterations observed in both benign and malignant oncocytic (Hürthle cell) neoplasms of the thyroid

ONs pose diagnostic challenges due to significant cytological and molecular overlap between benign and malignant cases. Current thyroid molecular testing reveals a broad range of genetic alterations in ONs but lack sufficient specificity to reliably distinguish benign from malignancy in most instances. In this study, genetic alterations were detected in 66.6% (24/36) of OAs, and telomerase reverse transcriptase (TERT) mutations - typically associated with malignancy - were identified in two OAs. However, notably, certain mutations were exclusive to specific groups, such as B-Raf proto-oncogene, serine/threonine kinase (BRAF), anaplastic lymphoma kinase/echinoderm microtubule-associated protein-like 4 (ALK/EML4), and paired box 8 - peroxisome proliferator activator receptor gamma (PAX8-PPARG) in OPTCs or EIF1AX in OCs. Importantly, only 3.6% (1/28) of malignant OPTC/ONs were tested negative on molecular analysis, suggesting that ONs with negative molecular test results are more likely to be benign than malignant.