Utility of Ultrasound vs. Gene Expression Classifier in Thyroid Nodules with Atypia of Undetermined Significance

Abstract

Introduction: Thyroid nodules with fine needle aspiration (FNA) cytology categorized as atypia of undetermined significance (AUS) often undergo additional diagnostic analysis with the Afirma Gene Expression Classifier (GEC) which classifies these as either high probability of being benign (GEC-B) or suspicious for malignancy (GEC-S). Our goal was to assess the clinical validity and utility of GEC in the evaluation of AUS cytology and evaluate the performance of ultrasonography (USG) for predicting malignancy in this subset. Methods: We conducted a study with a retrospective cohort of patients from January 2012- January 2014 who had FNA of thyroid nodules >1 cm in size with AUS cytology. Results: Cleveland Clinic Florida has an overall incidence of AUS of 5%. 119 cases with nodules >1 cm in size were reported as AUS. 48 (40.3%) had a GEC performed after the first FNA (AUS-1) and 27 of these were GEC-S. Of those 27, 21 went for surgery and 14 (66.6%) had thyroid cancer on histopathology. The remaining 71 with AUS-1 were sent for a 2nd FNA:19 nodules were benign and did not undergo further evaluation while the remaining 52 were reported as AUS for the second consecutive time (AUS-2). AUS-2 samples were sent for GEC. Of these 52 AUS-2, 38 (73.1%) were reported as GEC-S. 35 went for surgery and 32 (91.4%) had confirmed malignancy on histopathology. Positive Predictive Value (PPV) was 91.4% for AUS-2 vs. 66.6% for AUS -1. Moreover, AUS-2 nodules that were hypoechoic and solid on USG showed a PPV of 92% for malignancy. Conclusion: In our practice, the diagnostic accuracy to predict malignancy with GEC for AUS-1 nodules was poor (PPV 66.6%). The PPV of GEC testing was markedly higher at 91.4% performed after 2 consecutive AUS cytologies. AUS-2 nodules that were solid and hypoechoic on USG also had a high probability to be malignant (PPV 92%). We recommend repeat FNA on AUS-1 nodules rather than proceeding directly to GEC testing. Also, we suggest that among AUS-2 nodules, surgery can be recommended when USG shows solid and hypoechoic features with GEC testing reserved for the remainder.