Adjusted Risk Stratification of Indeterminate Thyroid Nodules Using the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS).

BACKGROUND: The TI-RADS guides the initial management of thyroid nodules, but the malignancy risk across different categories of cytologically indeterminate thyroid nodules (CITNs), particularly AUS and FN, remains unclear. METHODS: We reviewed thyroid FNA specimens diagnosed as AUS or FN with TI-RADS scores of 3, 4, or 5 from 2017 to 2025. Clinical data, molecular results, and surgical outcomes were analyzed. RESULTS: A total of 919 CITNs were identified: 304 with TI-RADS 3, 454 with TI-RADS 4, and 161 with TI-RADS 5. In the absence of molecular alterations, the risk of malignancy (ROM) was low for AUS and FN in both TI-RADS 3 and 4 categories (< 10%). In contrast, TI-RADS 5 nodules diagnosed as AUS or FN had the highest ROM (56%). ROM similarly increased with the TI-RADS score. For AUS, ROM was 14% (TI-RADS 3), 31% (TI-RADS 4), and 60% (TI-RADS 5). For FN, ROM increased from 26% to 44% to 57% across TI-RADS 3, 4, and 5, respectively. Notably, even AUS nodules without detectable mutations had a high ROM of 44% in TI-RADS 5, compared to 10% and 15% in TI-RADS 3 and 4, respectively. CONCLUSION: Our findings demonstrate distinctive ROMs among AUS and FN stratified by TI-RADS category and underscore the variable utility of molecular testing. TI-RADS 5 CITNs carry a significantly higher ROM even in the absence of molecular alterations, suggesting the importance of combining TI-RADS and TBSRTC.