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Purpose  The management of thyroid nodules of indeterminate cytology is controversial. Our study aimed to establish the frequency and significance of  H-,K-,N-RAS, TERT  promoter, and  BRAF  gene mutations in thyroid nodes of indeterminate cytology and to assess their potential usefulness in clinical practice.    Methods   H -, K -, N-RAS, TERT  promoter and  BRAF  gene mutations were examined in a series of 199 consecutive nodes of indeterminate cytology referred for surgical excision.    Results  69/199 (35%) were malignant on histopathological review.  RAS  mutations were detected in 36/199 (18%), and 19/36 cases (53%) were malignant on histological diagnosis.  TERT  promoter mutations were detected in 7/199 (4%) nodules, which were all malignant lesions.  BRAF  mutations were detected in 15/199 (8%), and a  BRAF  K601E mutation was identified in 2 follicular adenomas and 1 noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Altogether, this panel was able to identify 48% of the malignant lesions, achieving a specificity, positive predictive value, and negative predictive value for malignancy of 85, 62, and 75%, respectively.    Conclusion  The residual malignancy risk in mutation-negative nodes is 25%. These nodes still need to be resected, but mutation analysis could help to orient the appropriate surgical strategy.

frontiers in endocrinology

Frequency and Significance of Ras, Tert Promoter, and Braf Mutations in Cytologically Indeterminate Thyroid Nodules: A Monocentric Case Series at a Tertiary-Level Endocrinology Unit