Evaluation of the Afirma Gene Expression Classifier in Repeat Indeterminate Thyroid Nodules

Abstract

Context.— Molecular testing in indeterminate thyroid nodules is a rapidly evolving field with variable reported outcomes. Objective.— To report our experience at a tertiary thyroid referral center with the Afirma Gene Expression Classifier (Veracyte, San Francisco, California) in repeat fine-needle aspirations of thyroid nodules with a previous indeterminate cytologic result. Design.— Results of cytopathology and the Afirma test were collected from August 2013 to March 2015, as were diagnoses from surgical resection when performed. Results.— One hundred and fifteen thyroid nodules were evaluated by Afirma. The fine-needle aspiration diagnostic categories for these nodules were 100 (87%) Bethesda III, 10 (9%) Bethesda IV, 3 (2%) Bethesda II, 1 (1%) Bethesda V, and 1 (1%) Bethesda I. Afirma results for 52 of the nodules (45%) were benign, 57 (50%) were suspicious, and 6 (5%) specimens yielded no result because of low messenger RNA content. Three of the benign nodules (6%) were treated surgically, and all were benign on final surgical pathology. Forty-six (81%) of the suspicious nodules were treated surgically; final surgical pathology revealed 30 (65%) were benign and 16 (35%) malignant, yielding a positive predictive value of 35%. Conclusions.— In our experience, 50% of the indeterminate nodules were classified as suspicious by Afirma, with a 35% rate of malignancy in these nodules at surgical resection, in comparison with a historical rate of malignancy at our institution of 11% for Bethesda III nodules and 23% for Bethesda IV. Our use of Afirma is consistent with prior reports in that it has a low positive predictive value in indeterminate thyroid nodules.