Work

Combining Thyroid Imaging Report and Data System (TIRADS) and Afirma Genomic Sequencing Classifier (GSC) for potential improvement of malignant risk stratification of Bethesda III thyroid nodules

Year: 2026

Type: article

Abstract: This study retrospectively assessed the ultrasound parameters in Bethesda category III thyroid nodules accompanied by a diagnostic Afirma Genomic Sequencing Classifier (GSC) testing result and surgical/clinical follow-up, and investigated whether combining ultrasound and GSC classifications could improve risk stratification of AUS nodules. Data including radiologic TIRADS score, concurrent GSC test results, and surgical/clinical follow-up were collected from patients with thyroid nodules meeting the study criteria. The distribution of TIRADS scores was compared between GSC-suspicious vs. GSC-benign cohorts, as well as between malignant and benign nodules. The diagnostic performance of the GSC was compared between TIRADS 5 and TIRADS <5 cohorts. The study consisted of 322 AUS nodules. Compared to the GSC-benign cohort, the GSC-suspicious cohort had a greater proportion of TIRADS 5 nodules (34% vs. 24%, p=0.045), a lower proportion of TIRADS 1-3 nodules (20% vs, 30%, p=0.048), and a higher average TIRADS score (4.12 vs. 3.92, p=0.03). Compared to the benign cohort (histologically and/or clinically benign), the malignant cohort (histologically malignant) showed a higher proportion of TIRADS 5 nodules (52% vs. 24%, p=0.004). The mean TIRADS score was also significantly higher in the malignant cohort compared to the benign cohort (4.36 vs. 3.92, p=0.015). GSC testing demonstrated a significantly higher PPV in the TIRADS 5 AUS nodules than that of TIRADS<5 nodules (39% vs. 17%, p=0.016). A GSC-suspicious result combined with TIRADS 5 significantly improved the PPV, thereby enhancing risk stratification in AUS thyroid nodules, while other diagnostic parameters remained unchanged. • Clinical management of AUS (atypia of undetermined significance) thyroid nodules remains challenging. Decision-making is guided by clinical evaluation, molecular study and sonographic assessment. The American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) assigns a malignancy risk score to each category (TIRADS 1-5). Our study demonstrates that combining a suspicious result from the Afirma genomic sequencing classifier (GSC) with a TIRADS 5 classification significantly improves the positive predictive value (PPV), thus enhancing risk stratification in AUS thyroid nodules. These findings suggest that integrating ultrasound features with GSC results may improve the diagnostic accuracy of AUS thyroid nodules.

Source: Journal of the American Society of Cytopathology

DOI: 10.1016/j.jasc.2026.01.001