Benign thyroid nodules with RAS mutation grow faster

Context: The management of a benign thyroid nodule includes follow-up until its size requires a surgical or alternative treatment. To date, it is difficult or impossible to predict the size changes of a benign nodule in a given patient because no specific growth parameters exist. RAS mutations have been described in thyroid adenomas and hyperplastic benign nodules. Objective: The aim of this study was to establish whether the volume changes of benign nodules are associated with the presence of RAS mutation. Patients and methods: Genomic DNA obtained by fine-needle aspiration of 78 thyroid nodules with benign cytology was analysed by pyrosequencing for the presence of NRAS⁶¹ and KRAS¹³ mutations. Ultrasonographic features were obtained. The volume of nodules at baseline and their changes after a mean follow-up of 25 months were evaluated according to the presence of RAS mutation. Results: A RAS mutation was found in 24 thyroid aspirates (30·8%, 8 NRAS⁶¹ and 16 KRAS¹³). RAS mutation was not associated with ultrasonographic features, but was significantly associated with a larger size at baseline (P = 0·017). After a 25-month mean follow-up, RAS mutation-positive nodules displayed faster growth (RAS mutation-positive vs RAS mutation-negative % annual growth 27·6% ±32·2% vs 1·0% ±17·0%, P <0·001). Conclusions: Benign thyroid nodules bearing RAS mutation grow more rapidly than those with wild-type RAS. Searching for RAS mutations in thyroid nodules with benign cytology might be useful to the clinician in choosing a more appropriate and timely surgical management.