Background: About 15-30% of fine needle aspirates [FNA] of thyroid nodules are classified as indeterminate cytology, necessitating the use of molecular tests to improve diagnostic yield. The Afirma Gene Expression Classifier [GEC] has been used to classify indeterminate nodules as benign or suspicious, based on the mRNA expression of 167 genes associated with thyroid cancer. Previous studies indicate that an Afirma-benign thyroid nodule has a 94-95% negative predictive value, while an Afirma-suspicious nodule confers a 37-38% positive predictive value [PPV] for malignancy. The current study is a retrospective, single institution external validation study of the performance of Afirma GEC in indeterminate thyroid nodules.
Methods: A retrospective review was performed identifying indeterminate thyroid nodules diagnosed at a single institution over a five-year period from October 1, 2012 to October 1, 2017. This included FNA categorized as Bethesda Class III or IV, which are defined as atypia of undetermined significant [AUS], or follicular neoplasm/suspicious for follicular neoplasm [FN/SFN] with or without Hurthle cell features at our institution. Afirma tests results were noted when done, and surgical pathology recorded when thyroid surgery was done.
Results: 395 patients with 409 unique indeterminate thyroid nodules were examined. Of the 409 indeterminate thyroid nodules identified, 309 (80%) were categorized as AUS and 100 (20%) as FN/SFN cytology respectively. In AUS nodules, 226 cases had Afirma testing performed with the following results: 101 (45%) were classified as benign, 123 (54%) were classified as suspicious, while 2 (1%)had no result due to RNA degradation. In the 79 cases of FN/SFN nodules with Afirma testing done, 24 (30%) were classified as benign while 55 (70%) were classified as suspicious. Of the 123 Afirma-suspicious AUS nodules, 86 cases had thyroid surgery, with 29 (PPV 34%) found to have thyroid cancer on histopathologic diagnosis. In the 101 Afirma-benign AUS cases, 10 had thyroid surgery with 2 cases (20%) of thyroid cancer. Of the 55 Afirma-suspicious FN/SFN nodules, 35 cases had thyroid surgery with 11cases (31%) found to have thyroid cancer. For the 24 Afirma-benign FN/SFN nodules, 4 cases underwent thyroid surgery and were found to be benign.
Conclusions: Afirma GEC is a useful adjunct for workup of thyroid nodules with indeterminate cytology. At our institution, the PPV for an Afirma-suspicious AUS and FN/SFN nodules are 34% and 31%, respectively, which are slightly lower than PPV of 38% and 37% reported in the literature. Performance of thyroid molecular diagnostic testing varies by institution and clinical decision making should be based on awareness of test performance at one’s institution.