Molecular Profile and Clinicopathologic Features of Follicular Variant Papillary Thyroid Carcinoma

The non-invasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has an indolent clinical behavior. Recently, it was proposed that this tumor type should be reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). To characterize NIFTPs, we evaluated the molecular and clinicopathologic characteristics of each FVPTC subtype. This study enrolled 29 patients with FVPTC who underwent thyroidectomy between January 2007 and June 2017. They were classified as non-invasive encapsulated FVPTC (NIFTP, n = 10), invasive encapsulated FVPTC (n = 11), and infiltrative FVPTC (n = 8) by two independent pathologists. Genetic alterations were analyzed by targeted next-generation sequencing using formalin-fixed, paraffin-embedded tissue samples and the clinicopathologic characteristics were retrospectively reviewed. There was no difference in preoperative cytologic classification between NIFTPs and invasive encapsulated FVPTCs, whereas infiltrative FVPTC was more likely to be Bethesda class VI than the encapsulated type (50% versus 9.5%; P = 0.033). Lymph node metastasis was not found in NIFTPs. There was no BRAF^V600E mutation in NIFTPs, whereas one of 11 invasive encapsulated FVPTCs and three of 8 infiltrative FVPTCs harbored BRAF^V600E. RAS mutations were frequently detected in encapsulated FVPTCs (5 of 10 NIFTPs and 4 of 11 invasive encapsulated FVPTCs) but were only detected in one case of the infiltrative type. There were no differences in molecular or clinicopathologic profiles between non-invasive and invasive encapsulated FVPTCs, except for lymph node metastasis and the presence of BRAF^V600E. NIFTP has favorable pathologic characteristics with a high frequency of RAS mutations.