M. Affi1, B. Javorsky1, T. Yen1, K. Doffek1, B. Hunt1, P. Tolat1, T. Carroll1, T. Giorgadze1, A. Carr1, D. Evans1, T. Wang1 1Medical College Of Wisconsin,Milwaukee, WI, USA
Introduction: Up to 30% of thyroid nodules evaluated by fine needle aspiration (FNA) are indeterminate on cytology. Use of a 167 gene mRNA-based gene-expression classifier (GEC) test has been shown to have a high negative predictive value for benign nodules and a 40% malignancy rate for GEC-suspicious nodules. The aim of this study was to determine the rate of malignancy in thyroid nodules indeterminate on initial cytology that underwent repeat FNA in anticipation of GEC testing.
Methods: This is a retrospective review of all patients with thyroid nodules with indeterminate cytology ('atypia/follicular cells of unknown significance’ or ‘suspicious for follicular neoplasm’) and who underwent GEC testing between 10/12-5/16. Prior to GEC testing, repeat FNA was performed and cytology results were reviewed by an independent cytologist; only indeterminate samples underwent GEC testing. Patients with GEC-benign nodules were recommended for surveillance. Patients with re-classified cytology that was 'suspicious for malignancy' or GEC-suspicious nodules were referred for thyroidectomy. The rate of clinically significant malignancy (>1cm) in patients undergoing thyroidectomy was determined, based on both initial cytology and results of GEC testing.
Results: 89 patients met inclusion criteria. Independent review of cytology yielded 35 (39%) benign, 48 (54%) indeterminate, 2 (2%) suspicious for malignancy, and 4 (5%) non-diagnostic samples. Of the 35 patients with benign cytology, 2 (6%) underwent thyroidectomy with benign final histopathology. The 2 patients with suspicious cytology had a clinically significant papillary thyroid cancer on final histopathology. Of the remaining 52 samples, 46 had sufficient mRNA for GEC analysis; 17 (37%) were GEC-benign and 29 (63%) were GEC-suspicious. None of the patients with GEC-benign lesions have had surgery; to date, 6 (35%) patients have had no changes on follow-up ultrasound. Of 26 patients with GEC-suspicious samples who underwent thyroidectomy, 18 (69%) had benign pathology, 5 (19%) had a clinically significant malignancy, and 3 (12%) patients had an incidental malignancy. Overall, 32 (36%) patients underwent thyroidectomy; based on the original institutional cytological diagnosis of ‘indeterminate,’ the rate of clinically significant malignancy was 22% (7/32).
Conclusion: Of the 89 patients with indeterminate initial cytology, repeat FNA with cytological review and GEC testing altered the management of 52 (58%) patients. The clinically significant malignancy rate for GEC-suspicious thyroid nodules was 19%, much lower than the reported 40% rate and equivalent to our institutional rate of malignancy in patients with indeterminate nodules who underwent surgery. Further follow-up of nonsurgical patients with GEC-benign nodules is required to determine the true benefit of GEC testing in patients with cytologically indeterminate thyroid nodules at our institution.