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Analyzing the impact of molecular testing on the cytological diagnosis of thyroid nodules: Insights from our
Dokpe Y Emechebe1, Sushant A Patil2, Timothy Collins3
1Department of Pathology and Laboratory Medicine, School of Medicine, Emory University Hospital, Atlanta, Georgia, USA.
Background:
Fine-needle aspiration cytology (FNAC) is a preferred method for evaluation of thyroid nodules. Under The Bethesda System for Reporting Thyroid Cytopathology, approximately 15%-30% of FNAC results fall into an indeterminate category: atypia of undetermined significance (AUS), follicular neoplasm (FN), and suspicious for malignancy (SFM), Bethesda classes III, IV, and V respectively. Molecular testing of indeterminate nodules helps evaluate the risk of malignancy and guide management decisions. This retrospective study assesses the impact of molecular testing on thyroid nodule classification in our institution, with an emphasis on indeterminate results.
Methods:
A 9-year retrospective analysis (January 2015-December 2023) was conducted at the University of North Carolina Health System. FNAC cases were classified per The Bethesda System. Molecular testing results and, when available, surgical pathology outcomes were reviewed. The study compared pre- and post-implementation data of routine reflex molecular testing of thyroid nodule diagnosis.
Results:
A total of 3992 thyroid aspirates were evaluated: 490 (12.3%) nondiagnostic (class I), 2096 (52.5%) benign (class II), 1041 (26.1%) AUS (class III), 136 (3.4%) FN (class IV), 89 (2.2%) SFM (class V), and 140 (3.5%) malignant (class VI). Indeterminate cytology (classes III-V) accounted for 32% of all aspirates (n = 1266). Before molecular testing, the AUS rate was 19.8% with an AUS:malignant ratio of 5.4. Post-implementation, the AUS rate rose to 30.1%, with a ratio of 8.9. This increase was statistically significant (p = .029).
Conclusion:
Implementation of molecular testing was associated with a significant rise in indeterminate cytologic diagnoses, particularly AUS.

