ArticleDiagnostic cytopathology2026
Performance of Two-Tiered Subclassification of Atypia of Undetermined Significance in Thyroid Fine-Needle Aspiration Without Routine Molecular Testing.
Article in Diagnostic cytopathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Performance of Two-Tiered Subclassification of Atypia of Undetermined Significance in Thyroid Fine-Needle Aspiration Without Routine Molecular Testing.Diagnostic cytopathology · 2026Article
- Clinical and ultrasound-based optimization of post-FNA management decisions in Bethesda III/IV thyroid nodules: a retrospective study.Frontiers in endocrinology · 2026Article
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Abstract
backgroundThe third edition of the Bethesda system for reporting thyroid cytopathology recommends a simplified two-tiered subclassification of atypia of undetermined significance (AUS), dividing cases into AUS with nuclear atypia (AUS-Nuclear) and other atypia (AUS-Other). This study aims to evaluate the performance of these subcategories in estimating the risk of malignancy (ROM) in a setting without routine molecular testing.
methodsA retrospective review was conducted on consecutive thyroid fine-needle aspiration (FNA) cases diagnosed as AUS between 2018 and 2023. Surgical pathology reports were matched with the FNA-targeted nodules to enable cyto-histologic correlation. ROM and risk of neoplasm (RON) were calculated for all AUS cases and for each subcategory.
resultsAmong 16,030 thyroid FNA cases, 617 (3.8%) were diagnosed as AUS. Histologic follow-up was available in 190 cases. Final diagnoses included non-neoplastic lesions (42.6%), benign neoplasms (17.4%), low-risk neoplasms (5.3%), and malignant neoplasms (34.7%). The ROM for AUS-Nuclear was significantly higher at 54.7%, compared to 14.7% for AUS-Other (p < 0.001). Similarly, the RON was significantly higher in the AUS-Nuclear group (67.4%) than in the AUS-Other group (47.4%) (p = 0.005).
conclusionAUS-Nuclear carries a substantially higher ROM than AUS-Other, with a ROM (54.7%) comparable to the reported positive predictive values of molecular assays such as Afirma GSC (47%, 95% CI: 36%-58%) and ThyroSeq v3 (66%, 95% CI: 56%-75%). These findings support the clinical utility of the two-tiered AUS subclassification in enhancing risk stratification, particularly in settings where molecular testing is not routinely available.
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