Clinical management of indeterminate thyroid nodules needs to be revisited. New evidence for a personalized approach to the problem.

Purpose: Thyroid nodules diagnosed by fine needle aspiration cytology (FNAC) as TIR3A or Class III subgroup "other types of atypia" (indeterminate thyroid nodules - ITNs), are the only ones without a unique clinical action indicated for management. This leads to multiple FNAC repetitions (FNAC-reps) and lifelong follow-up, with huge consumption of time and resources. The aims of the study were to inquire the usefulness of repeating FNAC in ITNs and perform an evaluation of a long-term follow-up of a large cohort of ITNs.

Methods: The study was conducted in two Italian high-volume tertiary centres. We selected patients who underwent the first FNAC with subsequent diagnosis of ITN in a centre involved and who then repeated it in the same institute.

Results: We included 506 patients. The FNAC-rep determined the "change in management indications" (CMIs) in 30 cases. The binomial test showed that this proportion was not significant (p 0.36). The factors related to CMIs were age (OR = 0.97; 95%CI = 0.95-0.99; p = 0.04), margins (OR = 5.6; 95%CI = 1.7-18.1; p = 0.004), and echogenicity (hypoechoic vs. isoechoic: OR = 5.2; 95%CI = 1.87-14.5; p = 0.002| hypoechoic vs. iso-anechoic: OR = 5.9; 95%CI = 1.32-26.2; p = 0.02). Follow-up of cases without CMIs showed that 20 of 476 cases required surgery. Of these, only four were malignant and all occurred within the first 8 years of observation.

Conclusions: The study demonstrated that FNAC-rep is useless for the most of cases, hence it should only be considered for young adults having nodules with suspicious characteristics. Furthermore, a 10-year follow-up for ITNs is safe enough rather than a long-life follow-up.