Mutational Profiling Detection in FNAC Samples of Different Types of Thyroid Neoplasms Using Targeted NGS.

Thyroid neoplasms exhibit a diverse molecular landscape, and the 2022 WHO classification emphasizes the critical role of molecular profiling in thyroid cancer management; however, comprehensive mutational data from fine-needle aspiration cytology (FNAC) samples using targeted next-generation sequencing (NGS) are still limited, necessitating further investigation to guide clinical practice. To characterize the mutational landscape of thyroid neoplasms using targeted NGS of FNAC samples and to assess the clinical implications of molecular profiling. This retrospective study included 952 patients with thyroid carcinomaneoplasms who underwent surgery at Sun Yat-sen Memorial Hospital from 2021 to 2023. Preoperative ultrasound, FNAC, and targeted NGS were performed. NGS panels covering 18, 88, and pan-cancer genes were used to analyze FNAC samples. Molecular alterations were correlated with clinical and pathological features. The most frequent mutation was BRAFV600E (84.45%), followed by RET (6.41%), BRCA1/2 (4.41%) and RAS (4.41%). Patients were categorized into BRAF-like (830 cases), RAS-like (36 cases), high-risk mutations (25 cases), and other mutations (28 cases). High-risk mutations were associated with older age and larger tumor size. BRAF-like tumors had a higher lymph node metastasis rate (58.77%) compared to RAS-like tumors (33.33%). Tumor mutation burden varied significantly among different thyroid neoplasm subtypes. Molecular profiling using targeted NGS of FNAC samples provides valuable insights into the genetic landscape of thyroid neoplasms and has significant clinical implications for diagnosis and personalized treatment strategies. Further validation with paired tumor and plasma samples is warranted.