Thyroid Nodules with Atypia of Unknown Significance (TBSRTC III): Evaluating the Role of Repeat FNA, Molecular Testing, and Surgery Across Five Hospitals

Summary: Introduction: Thyroid nodules are prevalent and predominantly benign; however, about 5% harbor malignancy. Nodules suspicious on sonography undergo fine-needle aspiration (FNA) and are evaluated using The Bethesda System for Reporting Thyroid Cytopathology classification (TBS). Management strategies for indeterminate TBS III nodules (atypia of unknown significance/AUS) include surveillance, repeat FNA, molecular testing, or diagnostic lobectomy Materials and Methods: We conducted a retrospective analysis of thyroid nodules that underwent FNA across five hospitals from August 2018 to March 2024, identifying 2661 nodules, including 200 with an AUS diagnosis. After excluding individuals under 18, repeated FNAs of the same nodule, and cases without follow-up, 139 AUS nodules remained. Demographics, sonographic findings, molecular reports, repeat FNAs, and surgical outcomes were extracted through chart reviews. Results: The cohort was 80.2% female with an average age of 56.7 years (range 18-84 years). Repeat FNA was performed on 39 AUS nodules, with 49% diagnosed as benign and 36% as AUS upon reevaluation. Molecular testing on 76 nodules (including Thyroseq, Afirma, and ThyGeNext) showed 67% benign outcomes. From 63 nodules that underwent partial or total thyroidectomy, the risk of malignancy (ROM) was 32% among surgically treated nodules and 20% when benign repeat FNAs and molecular tests were considered. Ultrasound features, including nodule size (1.1-6.5 cm) and TIRADS scoring, did not reliably predict ROM. Conclusions: For AUS nodules, repeat FNA, molecular testing, and surgical evaluation remain vital management options. Repeat FNA, the most cost-effective approach, provided definitive diagnoses in 50% of cases. The ROM for AUS nodules ranged from 20-32%, aligning with prior studies. Ultrasonography proved ineffective in predicting ROM in these nodules.