Testing for Mutations in Thyroid Fine Needle Aspiration (FNA) Samples: Clinical Experience with 670 Samples
YE Nikiforov, NP Ohori, RR Seethala, MN Nikiforova. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: Testing for genetic mutations is a novel diagnostic tool that can be applied to thyroid nodules sampled by fine needle aspiration (FNA). The diagnostic value of this test remains not fully characterized. In this study, we report a summary of the results of molecular testing on 670 thyroid FNA samples performed at our institution.
Design: Portions of freshly obtained FNA samples from thyroid nodules were routinely collected for molecular testing. The testing was performed upon completion of cytologic evaluation and was limited to samples diagnosed as suspicious for follicular neoplasms, suspicious for malignancy, follicular lesions of undetermined significance (FLUS), and positive for malignancy by cytology. The panel of mutations included BRAF V600E, NRAS codon 61, HRAS codon 61, KRAS codon 12/13 mutations and RET/PTC1, RET/PTC3 and PAX8/PPARg rearrangements.
Results: Out of 670 thyroid nodules tested, 72 (11%) were positive for mutations: 37 revealed BRAF, 24 NRAS, 5 HRAS, 2 KRAS mutations, 2 RET/PTC1 and 2 PAX8/PPARg rearrangements. Among these 72 samples, FNA cytology was reported as positive for malignancy in 31 cases, as suspicious for follicular neoplasms in 19 cases, as suspicious for malignancy in 11 cases, and as FLUS in 11 cases. Of 60 patients with mutations who have undergone surgery to date, 54 (90%) were diagnosed with malignant tumors. All 32 nodules harboring BRAF or RET/PTC were papillary carcinomas. Samples positive for PAX8/PPARg were oncocytic carcinoma (1) and follicular variant of papillary carcinoma (1). Among 26 RAS-positive nodules, 20 (77%) were malignant (18 follicular variant of papillary carcinoma, 2 follicular carcinoma) and 24/26 (92%) were neoplasms (including 4 follicular adenomas), and 2 were hyperplastic nodules.
Conclusions: These results demonstrate that testing for mutations in thyroid FNA samples is feasible and of significant diagnostic value to further refine the cytologic diagnosis. In addition to BRAF, RET/PTC, and PAX8/PPARg which each had a positive predictive value of 100% for malignancy, RAS mutations were common and diagnostically helpful, particularly for the detection of the follicular variant of papillary carcinoma.
Monday, March 9, 2009 1:15 PM
Platform Session: Section F, Monday Afternoon