Natural History of Cytologically Low-Risk Indeterminate Thyroid Nodules

Context: Thyroid nodules classified cytologically as low-risk indeterminate lesions (TIR3A) on fine-needle aspiration biopsy (FNAB) present a clinical challenge due to their uncertain malignancy risk. Objective: This single-center study aimed to evaluate the natural history of TIR3A nodules. Methods: FNABs performed between July 2017 and December 2019 were retrospectively retrieved and patients, with TIR3A nodules were evaluated at baseline and throughout a follow-up based on ultrasound (US) parameters and clinical data. Results: The final study group encompassed 371 patients with an initial TIR3A cytological result. Among them, 102 were directed to surgery after the first endocrinological evaluation, and 269 were directed to conservative follow-up. Repeat FNAB was performed in 120 out of 269 and 13 further patients underwent surgery following FNAB repetition. The malignancy rate among TIR3A nodules was 16.5%, with most interventions being performed for reasons unrelated to the TIR3A result. Repeat FNAB provided a more definitive diagnosis in 40% of cases, with a 5% increase in malignancy risk. The remaining patients were monitored with clinical and US follow-up. Among all patients with TIR3A cytology managed conservatively (149 without FNAB repetition and 66 with at least one FNAB repetition), no significant changes in nodule size and/or US pattern were observed during a median follow-up of 3.3 years. Conclusion: These findings suggest that active surveillance is a safe option for managing TIR3A nodules, particularly when no additional risk factors are present. The study highlights the role of repeat FNAB in reducing unnecessary surgeries and underscores the generally indolent nature of TIR3A nodules.