Final histopathological outcomes after two versus three fine-needle aspiration biopsies in bethesda iii thyroid nodules

Fine-needle aspiration biopsy (FNAB) is the primary diagnostic method for evaluating thyroid nodules. Bethesda category III (atypia of undetermined significance; AUS) remains a diagnostic gray zone in which repeat FNAB, molecular testing, surveillance, or surgery may be considered. The clinical value of performing a third FNAB after persistent Bethesda III cytology remains uncertain. This study compared final histopathological malignancy rates between patients undergoing two versus three consecutive FNAB procedures for the same thyroid nodule. This retrospective cohort study was conducted at Mersin City Training and Research Hospital between 2018 and 2025. Approximately 5,800 patients who underwent thyroid FNAB during the study period were screened. Patients were eligible when consecutive FNAB specimens were obtained from the same index nodule and all available FNAB results were Bethesda III according to the 2017 Bethesda System. A total of 194 surgically treated patients met these criteria. Group A included patients who underwent two FNAB procedures ( n = 136), whereas Group B included patients who underwent three FNAB procedures ( n = 58). The primary outcome was malignancy in the index nodule on final surgical histopathology. Demographic, ultrasonographic, cytological, surgical-indication, and histopathological variables were analyzed. All 194 patients had Bethesda III cytology on both the first and second FNABs. Among the 58 patients undergoing a third FNAB, the third specimen also remained Bethesda III. The overall malignancy rate was 37.9% (74/194), with malignancy detected in 36.8% of Group A and 41.4% of Group B (χ²=0.41, p = 0.52). The odds ratio for malignancy in Group B versus Group A was 1.21 (95% CI: 0.66–2.23). In multivariable logistic regression, three FNAB procedures were not independently associated with malignancy (adjusted OR = 1.12, 95% CI: 0.58–2.08, p = 0.71), whereas ACR-TIRADS 4 and larger nodule size were associated with malignancy. Persistent Bethesda III was the most frequent indication for surgery in both groups and was more frequent in Group B. In this retrospective, surgically selected cohort of patients with persistent Bethesda III cytology from the same thyroid nodule, final malignancy rates did not differ significantly between patients undergoing two versus three FNAB procedures. Because patients with cytological reclassification were not included, the incremental diagnostic yield of a third FNAB cannot be determined from this study. Further prospective studies including sequential cytological reclassification and nonsurgically managed patients are warranted.