Performance of Afirma genomic sequencing classifier and histopathological outcome are associated with patterns of atypia in Bethesda category III thyroid nodules

摘要

Background: Data on Afirma's genomic sequencing classifier (GSC) performance in atypia of undetermined significance (AUS) subcategories is limited. This study investigated GSC performance in AUS nodules with architectural atypia (AUS-A), cytological atypia (AUS-C), architectural and cytological atypia (AUS-AC), and predominantly Hurthle cells (AUS-HC). Methods: This study retrieved consecutive thyroid nodules having a recurrent cytologic diagnosis of AUS with qualifiers and a concurrent GSC diagnostic result. All nodules were followed by either surgical intervention or clinical and/or ultrasound monitoring (>= 6 months). GSC benign call rate (BCR), rate of histology-proven malignancy, and diagnostic parameters of GSC were calculated for individual AUS subcategories. Statistical analysis was performed using the Fisher exact test. Results: A total of 135 AUS nodules fulfilled inclusion criteria, including 79 AUS-A, 9 AUS-C, 29 AUS-AC, and 18 AUS-HC. BCR was 72.2, 66.7, 44.8, and 77.8 in AUS-A, AUS-C, AUS-AC, and AUS-HC, respectively. AUS-A showed a greater BCR than AUS-AC (p < .05). All GSC-benign nodules were considered benign on clinical or surgical follow-up. Among GSC-suspicious nodules, histology-proven malignancies represented 4.5 of AUS-A, 0 of AUS-C, 56.3 of AUS-AC, and 25.0 of AUS-HC cases. AUS-AC demonstrated a higher malignant rate compared with AUS-A (p < .05). GSC offers 100 NPV and a wide range (5-56) of PPV across all AUS subcategories. AUS-AC demonstrated a greater PPV compared with AUS-A (p < .05). Conclusion: BCR of GSC and malignant rates associated with suspicious GSC may differ in various AUS subcategories. GSC-suspicious nodules with both architectural and cytologic atypia are more likely to be malignant. These findings may improve clinical triage and/or management of patients with AUS thyroid nodules.