Preoperative diagnosis of benign thyroid nodules with indeterminate cytology
Approximately 15 percent to 30 percent of thyroid nodules evaluated by fine-needle aspiration are not clearly benign or malignant. Patients with cytologically indeterminate nodules are often referred for diagnostic surgery, though most of these nodules prove to be benign. A novel diagnostic test that measures the expression of 167 genes has shown promise in improving preoperative risk assessment. The authors performed a 19-month, prospective, multicenter validation study (funded by Veracyte) involving 49 clinical sites, 3,789 patients, and 4,812 fine-needle aspirates from thyroid nodules 1 cm or larger that required evaluation. They obtained 577 cytologically indeterminate aspirates, 413 of which had corresponding histopathological specimens from excised lesions. Results of a central, blinded histopathological review served as the reference standard. After inclusion criteria were met, a gene-expression classifier was used to test 265 indeterminate nodules, and its performance was assessed. The authors found that of the 265 indeterminate nodules, 85 were malignant. The gene-expression classifier correctly identified 78 of the 85 nodules as suspicious (92 percent sensitivity; 95 percent confidence interval [CI], 84–97) with a specificity of 52 percent (95 percent CI, 44–59). The negative predictive values for atypia (or follicular lesion) of undetermined clinical significance, follicular neoplasm or lesion suspicious for follicular neoplasm, and suspicious cytologic findings were 95 percent, 94 percent, and 85 percent, respectively. An analysis of seven aspirates with false-negative results revealed that six had a paucity of thyroid follicular cells, suggesting insufficient sampling of the nodule. The authors concluded that these data support consideration of a more conservative approach for most patients with thyroid nodules that are cytologically indeterminate on fine-needle aspiration and benign according to gene-expression classifier results.
Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367(8):705–715.