Clinical Factors Influencing the Performance of Gene Expression Classifier Testing in Indeterminate Thyroid Nodules.

BACKGROUND

Molecular diagnostic testing is increasingly used in the management of indeterminate thyroid nodules. Limited data exist regarding the influence of clinical factors on gene expression classifier (GEC) test performance. This study examined the positive and negative predictive value of GEC as stratified by nodule size.

METHODS

A prospectively maintained pathology database from a single tertiary referral center was queried from 2012 to 2015 for indeterminate thyroid nodules that underwent GEC testing. Nodule size, patient demographics, Bethesda classification, and Hürthle cell-predominant nodules (HCNs) were evaluated as predictors of GEC performance.

RESULTS

Two hundred and thirty-one patients with 245 indeterminate nodules were examined. Assuming all nodules to be benign unless proven malignant on histopathology, the sensitivity and specificity of GEC testing were 95.2% and 60.1%, respectively. The malignancy rate among resected nodules was 25.3%. The positive predictive value was consistent across nodule sizes: 45.5% for nodules <1 cm, 42.9% for nodules 1-1.9 cm, 36.0% for nodules 2-2.9 cm, 54.2% for nodules 3-3.9 cm, and 50.0% for nodules ≥4 cm. The negative predictive value ranged from 93.3% to 100% and was not affected by nodule size. HCNs had a high rate of GEC suspicious results (77.4% vs. 50.5% for nodules without Hürthle cell predominance, p < 0.01), though this did not correspond to a difference in the rate of malignancy (25.8% vs. 25.3%).

CONCLUSIONS

Nodule size did not affect GEC test performance in the present cohort. GEC benign results remain reliable in large nodules. GEC suspicious nodules >3 cm carry a similar risk of malignancy compared to smaller nodules, and do not warrant more aggressive treatment. GEC testing has limited clinical utility for HCNs due to the high rate of false-positive results.