Molecular genotyping of the non‐invasive encapsulated follicular variant of papillary thyroid carcinoma

Aims The non‐invasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has been managed as a low‐risk malignancy. Recently, a proposal was made to reclassify this tumour type as a premalignant lesion and rename it non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP). This study aims to provide the first comprehensive study on molecular genotype–phenotype correlations of encapsulated FVPTC. Methods and results This study was performed on 177 consecutive FVPTCs from January 2014 to April 2016. These were classified as non‐invasive encapsulated FVPTC (n = 74) invasive encapsulated FVPTC (n = 51), and infiltrative FVPTC (n = 52), according to standard criteria, by two independent pathologists. Genetic alterations and other clinicopathological information were compared. BRAFV600E was found in 12.2% (non‐invasive) and 11.8% (invasive) of encapsulated FVPTCs, and in 34.6% of infiltrative FVPTCs (P = 0.001). Mutation in encapsulated FVPTCs was limited to cases with rare or abortive papillae. RET–PTC1 and RET–PTC3 rearrangements were present (11.5%) only in infiltrative FVPTCs. In contrast, NRAS, HRAS and KRAS mutations were observed more often in encapsulated FVPTCs (48.6% in non‐invasive and 66.7% in invasive) than in infiltrative FVPTCs (15.4%) (P < 0.001). Preoperative cytological examination did not distinguish between non‐invasive and invasive encapsulated FVPTCs, whereas infiltrative FVPTC was more likely to be Bethesda class V/VI than the encapsulated type (60.4% versus 38.1%; P = 0.01). Conclusions There were no differences in clinicopathological or molecular profiles between non‐invasive and invasive encapsulated FVPTCs, except in vascular and capsular invasion. Therefore, the diagnosis of NIFTP, like that of follicular adenoma, may require surgical resection and exclusion of those tumours with any papillae.