Utilities of Mutations in Preoperative Fine Needle Biopsies for Decision Making for Thyroid Nodule Management: Results from a Single-Center Prospective Cohort.

It has been advocated to apply individualized strategies to evaluate thyroid nodules due to the growing awareness that the pathogenesis of thyroid cancer is not uniform. Molecular markers in fine needle biopsies (FNBs) may be helpful for the diagnosis and management decisions. Unlike the detection of mutations, the clinical utility of rat sarcoma viral oncogene homolog () mutations has not been fully elucidated. This study aimed at presenting a real-world performance of mutations in identifying thyroid malignancies, at investigating the nature of thyroid tumors carrying mutations, and at providing an additional reference for interpreting how to utilize the presence of mutations in the decision-making process of thyroid nodule management. Between February 2015 and December 2017, 1400 sequential thyroid biopsies were performed at Boston Medical Center. Of these, 546 FNBs were evaluated for mutations by using a ThyroSeq next-generation sequencing panel. Nodules carrying mutations were prospectively followed, and medical records were collected. ThyroSeq successfully provided molecular information in 504 nodules; 173 with molecular alteration(s); and 80 positive for mutations in the , , or genes. gene mutations constituted up to 46.2% of the total molecular alterations found in the study. Fifty-six of the 80 -positive nodules underwent surgery, 33 (58.9%) were confirmed to be benign, 7 (12.5%) were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and 16 (28.6%) were thyroid carcinomas. The positive predictive value, negative predictive value, and accuracy of mutations for identifying malignancies among cytologically indeterminate nodules were 25.5%, 89.7%, and 54.0% when NIFTP was not counted as cancer. A combination of and other mutations increased the risk of malignancy. Twelve histopathologically proved -only-positive malignant nodules all showed low-risk features and favorable prognosis. isoforms added little assistance for predicting a malignancy and the response to therapy in our series. mutations represent the most frequently detected genetic alterations in our series. mutations, when occurring alone, are not helpful markers to identify malignancy among Bethesda III/IV cytologies, but may predict favorable behavior, and hence should be considered to guide initial management.