Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy

Thyroid fine-needle aspiration (FNA) biopsy is indeterminate or suspicious in up to 30% of cases and these patients are commonly subjected to at least a diagnostic hemithyroidectomy. If malignant on histology, a completion thyroidectomy is usually performed, which may be associated with higher morbidity. To determine the clinical utility of genetic testing in thyroid FNA biopsy, we conducted a prospective clinical trial.

Four hundred seventeen patients with 455 thyroid nodules were enrolled and had genetic testing for common somatic mutations (BRAF, NRAS, KRAS) and gene rearrangements (RET/PTC1, RET/PTC3, RAS, TRK1) by PCR and direct sequencing and by nested PCR, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of genetic testing in thyroid FNA biopsy were determined based on the histologic diagnosis.

One hundred twenty-five of 455 thyroid nodule FNA biopsies were indeterminate or suspicious on cytologic examination. Overall, 50 mutations were identified (23 BRAF, 4 RET/PTC1, 2 RET/PTC3, 21 NRAS) in the thyroid FNA biopsies. There were significantly more mutations detected in malignant thyroid nodules than in benign (P = 0.0001). For thyroid FNA biopsies that were indeterminate or suspicious, genetic testing had a sensitivity of 12%, specificity of 98%, PPV of 38%, and NPV of 65%.

Genetic testing for somatic mutations in thyroid FNA biopsy samples is feasible and identifies a subset of malignant thyroid neoplasms that are indeterminate or suspicious on FNA biopsy. Genetic testing for common somatic genetic alterations thus could allow for more definitive initial thyroidectomy in those with positive results.