332 Thyroid Nodules with Bethesda III or IV Cytology on Fine Needle Aspiration: Correlation with Molecular Classifier, Radiology, Clinical Management, and Outcome

Document Type

Conference Proceeding

Publication Date

3-23-2026

Publication Title

Lab Invest

Keywords

adult, aged, classifier, conference abstract, controlled study, cytology, diagnosis, diagnostic accuracy, diagnostic value, female, fine needle aspiration biopsy, follicular carcinoma, histology, histopathology, human, major clinical study, male, retrospective study, surgery, thyroid gland, thyroid imaging reporting and data system, thyroid nodule, thyroid papillary carcinoma, thyroidectomy

Abstract

Disclosures: Ali Rizk: None; Sarah Kisha: None; Kerem Ozcan: None; Lisi Yuan: None Background: Thyroid fine-needle aspiration (FNA) plays a key role in evaluating thyroid nodules; however, indeterminate categories such as Atypia of Undetermined Significance (AUS) and Follicular Neoplasm (FN) continue to pose diagnostic and management challenges. The recent subclassification of AUS into AUS–O and AUS–N aims to improve risk stratification, but its practical impact remains unclear. Molecular testing such as Afirma and ultrasound risk stratification using TIRADS have been increasingly used to enhance diagnostic accuracy. This study correlates cytologic categories with Afirma results, TIRADS scores, and final histopathology to evaluate the diagnostic value of each parameter and their combined performance in risk stratification and patient management. Design: We retrospectively reviewed thyroid FNA cases over one year period 8/2024-8/2025. Afirma genomic classifier results and TIRADS scores were collected. In patients who underwent thyroidectomy, final histopathologic diagnoses were obtained. Correlations among cytology, Afirma, TIRADS, and histology were analyzed. Results: 412 thyroid nodules with Bethesda III or IV cytology were identified, including 327 AUS and 85 FN. Among 327 AUS, 248 were classified as AUS-O; 79 were classified as AUS-N. The Afirma testing rate was similar among AUS-O, AUS-N, and FN (approximately 70%); however, the Afirma suspicious rate increased from 25.6% to 37.7% and 40.3%, respectively. The resection rate also increased from 10.1% in AUS-O, to 20.3% in AUS-N and 22.4% in FN. When Afirma testing returned suspicious, the resection rate significantly increased from one in third in AUS-O/ to more than half in AUS-N and FN. In patients underwent surgical removal, the malignance rate increased from 37.5% in AUS-O, to 50% in AUS-N and 72.2% in FN. TIRADS score of 4 was the most common among different intermediate categories. In FN category, oncocytic FN notably showed higher Afirma testing rate but lower Afirma suspicious rate and resection rate. 19 out of 85 FN were resected, including 9 papillary thyroid carcinomas (1 Warthin-like) and 4 follicular carcinomas. [Formula presented] [Formula presented] Conclusions: Comparing to AUS-O, AUS-N significantly increased the overall risk, including Afirma suspicious rate, resection rate, and malignancy rate, but with similar TIRADS scores. The Afirma suspicious rate and resection rate of AUS-N were on a par with FN, but the malignancy rate was significantly higher in FN. Oncocytic FN do not carry a higher risk in our study.

Volume

106

Issue

3

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