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NIFTP Accounts for Over Half of "Carcinomas" Harboring RAS Mutations.

Research paper by Vera A VA Paulson, Priyanka P Shivdasani, Trevor E TE Angell, Erik K EK Alexander, Edmund E Cibas, Jeffrey F JF Krane, Neal I NI Lindeman, Justine J Barletta

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: Thyroid : official journal of the American Thyroid Association



Abstract

Molecular testing of thyroid nodules is increasingly being utilized to guide clinical management decisions. RAS mutations are the most frequent mutations detected in the context of an indeterminate fine needle aspiration (FNA) diagnosis. The term noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently introduced to promote conservative management of tumors previously classified as noninvasive follicular variant of papillary thyroid carcinoma (FVPTC). This change in terminology was based on the indolent clinical behavior of these tumors and their molecular profile, which includes frequent RAS mutations. The aim of this study was to determine the percentage of RAS-mutant "carcinomas" that would now be classified as NIFTPs.We searched for cases with known activating RAS mutations in a database of 199 thyroid carcinomas that underwent molecular characterization as part of Profile:Oncopanel between 7/2013 and 7/2015. Cases of FVPTC were re-reviewed to identify tumors that now would be categorized as NIFTP. Preceding FNA diagnoses were recorded, and cases with an indeterminate FNA result (defined as a diagnosis of atypia/follicular lesion of undetermined significance, suspicious for follicular neoplasm, or suspicious for malignancy) were identified.We identified 27 RAS-mutant thyroid tumors. Fifteen (56%) cases had an NRAS mutation, 9 (33%) had an HRAS mutation, and 3 (11%) had a KRAS mutation. Twenty-four (89%) cases had a preceding FNA, 19 (79%) of which had an indeterminate FNA diagnosis. The surgical resection specimen demonstrated FVPTC in 20 (74%) cases, classical type PTC in 2 (7%), solid variant of PTC in 1 (4%), and follicular thyroid carcinoma in 4 (15%). Of the 20 FVPTCs, 16 (80%) would now be classified as NIFTP. NIFTPs accounted for 59% of RAS-mutant carcinomas overall and 63% of RAS-mutant carcinomas with a prior indeterminate FNA diagnosis.NIFTPs accounted for over half of RAS-mutant "carcinomas" in our cohort. In cases where clinical and sonographic data support a low-risk phenotype, these results suggest that a lobectomy should be considered as the initial surgical approach for a nodule with an indeterminate FNA diagnosis and a RAS mutation.

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