Molecular genotyping of noninvasive encapsulated follicular variant of papillary thyroid carcinoma

Summary

Aim

Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has been managed as low-risk malignancy. Recently, a proposal was made to reclassify this tumor type as a premalignant lesion and rename it noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). However, a comprehensive study on molecular genotype-phenotype correlations of encapsulated FVPTC is lacking.

Methods and results

This study consisted of 177 consecutive FVPTCs from January 2014 to April 2016. These were classified into noninvasive (n=74), invasive (n=51) encapsulated FVPTC, and infiltrative FVPTC (n=52) according to standard criteria by two independent pathologists. Genetic alterations and other clinicopathologic information were compared. A BRAF^V600E mutation was found in 12.2% (noninvasive) and 11.8% (invasive) of encapsulated FVPTCs and 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 FVPTC. In contrast, N-, H-, and KRAS mutations were observed predominantly in encapsulated FVPTCs (48.6% in noninvasive and 66.7% in invasive) compared to infiltrative FVPTCs (15.4%) (P<0.001). Preoperative cytologic examination was indistinguishable between noninvasive and invasive encapsulated FVPTCs, while infiltrative FVPTC was more likely to be Bethesda class V/VI than the encapsulated type (60.4% vs. 38.1%; P=0.01).

Conclusion

There were no differences in clinicopathologic or molecular profiles between noninvasive and invasive encapsulated FVPTCs except in vascular and capsular invasion. Therefore, the diagnosis of NIFTP, like follicular adenoma, may require surgical resection and exclusion of those tumors with any papillae.

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