Background: The 2015 American Thyroid Association (ATA) ultrasound (US) risk stratification system is used to identify thyroid nodules in which fine-needle aspiration cytology (FNAC) should be performed. In addition, this system is used to plan the long-term follow-up of patients with cytological benign thyroid nodules. The aim of our study was to evaluate the ATA US risk-adapted approach for repeating cytology in a large retrospective cohort of consecutive benign nodules with a second FNAC repeated after a median follow-up of 3.8 years (range 1.0-14.2 years). Methods: We retrospectively evaluated 1010 thyroid nodules, with an initial benign cytological diagnosis, that underwent at least one repeat FNAC during the follow-up. Results: The rate of missed cancer in the whole cohort of thyroid nodules was 1.0%, and it increased along by the US risk class (0.8% in very low/low-risk, 1.2% in intermediate-risk, and 3.1% in high-risk nodules). The 2015 ATA US risk stratification system showed a very high accuracy in selecting nodules that did not require a second FNAC (negative predictive value = 99.1%). In addition, the rate of missed cancer significantly increased along with the increase in the US risk class in nodules that showed an enlarged volume (0.4% in the low-risk class and 6.4% in the high-risk class, p = 0.005), while it was very low and not associated with the US features in the subgroup of thyroid nodules that did not grow during the follow-up (p = 0.96). Conclusions: Our results confirm the accuracy of the ATA recommendations in selecting benign nodules for FNAC repetition during the follow-up. An additional cytological evaluation maybe avoided in benign thyroid nodules with low-risk US features, regardless of the evidence of growth during the follow-up. While the utility of the routine repeat FNAC in all benign nodules with high-risk US features remains to be defined, based on our results, repetition of FNAC seems to be indicated in nodules with evidence of growth during the follow-up.

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