Risk of Malignancy in Bethesda Category III Thyroid Nodules with Nuclear Atypia: A Retrospective Study Based on Thyroidectomy Findings

Abstract

Background: Thyroid nodules with cytological features of atypia of undetermined significance (AUS), particularly those with nuclear atypia, represent a diagnostic challenge due to their variable malignancy risk. The 2023 revision of the Bethesda System has refined AUS subcategories to improve malignancy risk stratification. The aim of this study was to evaluate the risk of malignancy in Bethesda Category III thyroid nodules with nuclear atypia by correlating cytological findings with post-thyroidectomy histopathological results.

Material and Methods: This retrospective observational study included 156 patients who underwent thyroid fine-needle aspiration cytology between 2020 and 2024 and were diagnosed with AUS featuring nuclear atypia. All patients subsequently underwent thyroidectomy. Malignancy rates were determined based on final histopathological diagnoses. Statistical analysis was performed using SPSS version 29.0, applying Chi-square and Fisher’s exact tests, with a significance threshold set at p < 0.05.

Results: The overall malignancy rate was 34.6%, increasing to 39.7% when NIFTP cases were included Fifty papillary carcinomas were identified, 28 of which were <1 cm. In 23 patients who received repeated AUS diagnoses, the malignancy rate reached 73.9% (p = 0.011). No statistically significant differences were found between benign and malignant groups in terms of age (p = 0.655), gender (p > 0.05), or lymphocytic thyroiditis (p = 0.3). The reported malignancy rates were exclusively to the cohort of Bethesda Category III nodules with nuclear atypia, which constituted the entire study population.

Conclusion: Thyroid nodules classified as AUS with nuclear atypia are associated with a higher-than-expected risk of malignancy, especially in cases with repeated AUS diagnoses. These findings underscore the importance of subclassifying AUS cases to improve risk stratification and guide clinical decision-making.