K. D. Klingbeil1, R. L. Deitz1, M. L. Mao1, J. C. Farrá1, J. I. Lew1 1University Of Miami Miller School Of Medicine,Division Of Endocrine Surgery, DeWitt Daughtry Family Department Of Surgery,Miami, FL, USA
Introduction: The current management for thyroid nodules remains a challenge for physicians due to the underlying risk of malignancy. With the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), known as Bethesda III, has an unclear rate of malignancy. Gene expression classification (GEC) testing was developed to further stratify patients with AUS/FLUS nodules. Given its known variability between institutions, this study examines the utility of GEC testing in predicting malignancy in patients with AUS/FLUS thyroid nodules.
Methods: A retrospective review of prospectively collected data for patients with index thyroid nodules who underwent FNA and thyroidectomy at a single institution was performed. GEC testing utilized in patients with AUS/FLUS by FNA was reported as benign or suspicious for malignancy. Patients with AUS/FLUS nodules underwent initial thyroid lobectomy for definitive diagnosis unless there was a history of known risk factors and/or patient preference for which total thyroidectomy was performed. AUS/FLUS nodules were subdivided into malignant or benign groups based on final pathology. Among patients who underwent GEC testing, final pathology was compared to initial GEC results.
Results: Of 863 patients who underwent FNA and thyroidectomy, 224 patients (26%) were found to have AUS/FLUS nodules. Following thyroidectomy, 120 patients (54%) were shown to have thyroid cancer (Papillary, n=110; Follicular, n=8; Medullary, n=2) on final pathology. The remaining 104 patients had benign final pathology, most commonly presenting as multinodular hyperplasia, n=31. GEC testing was performed in 102 patients with AUS/FLUS testing, of which 96 had suspicious results. The rate of malignancy for patients with AUS/FLUS nodules and suspicious GEC results was 51% (49/96) whereas the rate of malignancy for AUS/FLUS nodules without GEC testing was 55% (67/122). Of the 6 patients with benign GEC results, 4 were found to be malignant (66%). The positive predictive value (PPV) for GEC testing in AUS/FLUS nodules was 51%.
Conclusion: Surgical patients with AUS/FLUS nodules had a high malignancy rate compared to the general population. GEC testing demonstrated a high frequency of suspicious results in AUS/FLUS thyroid nodules, yet had limited utility of predicting malignancy. There was no significant difference in malignancy rates when comparing AUS/FLUS nodules without GEC testing to those with suspicious GEC results. In addition, GEC testing failed to rule out malignancy in AUS/FLUS nodules with benign results. Thus, the application of GEC testing has limited utility in surgical decision-making. Surgeons should assess their local institutional experience to determine if there is added utility of GEC testing for AUS/FLUS nodules in their everyday clinical practice.