Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules.

CONTEXT

• Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant.

OBJECTIVE

• To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material.

DESIGN

• A total of 24 residual needle rinse specimens with malignant (n = 6), indeterminate (n = 9), or benign (n = 9) thyroid FNA diagnoses were analyzed in our clinical molecular diagnostics laboratory using next-generation sequencing assays designed to detect gene mutations and translocations that commonly occur in thyroid cancer. Results were correlated with surgical diagnoses and clinical outcomes.

RESULTS

• Interpretable data were generated from 23 of 24 residual needle rinse specimens. Consistent with its well-known role in thyroid malignancy, BRAF V600E mutations were detected in 4 malignant cases. An NRAS mutation was detected in 1 benign case. No mutations were detected from specimens with indeterminate diagnoses.

CONCLUSIONS

• Our data demonstrate that residual thyroid FNA needle rinses are an adequate source of material for molecular diagnostic testing. Importantly, detection of a mutation implicated in thyroid malignancy was predictive of the final surgical diagnosis and clinical outcome. Our strategy to triage thyroid nodules with indeterminate cytology with molecular testing eliminates the need to perform additional FNA passes into dedicated media or to schedule additional invasive procedures. Further investigation with a larger sample size to confirm the clinical utility of our proposed strategy is underway.