A user's guide to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

The term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently introduced to replace a subset of follicular variant of papillary thyroid carcinoma (FVPTC). The goal of this change was to promote more conservative management of these tumours and spare patients the psychological burden of a cancer diagnosis. The histological diagnosis of NIFTP is stringent: the tumour needs to demonstrate encapsulation or circumscription, a purely follicular architecture and the presence of nuclear features of papillary thyroid carcinoma, while lacking capsular and vascular invasion, a significant component of solid growth and high-grade features (increased mitotic activity and necrosis). In order to ensure that these inclusion and exclusion criteria are met, the tumour must be sampled extensively, with the entire capsule/periphery submitted in all cases. When sampled by fine-needle aspiration, NIFTP is usually classified within the indeterminate categories of the Bethesda System for Reporting Thyroid Cytopathology. NIFTP is characterized genetically by frequent RAS mutations, although rarely other alterations, such as the BRAF K601E mutation and gene rearrangements in PPARG or THADA, may occur. In this review, we will examine the history of FVPTC and the findings and factors that culminated in the introduction of the NIFTP terminology. A discussion will follow with the histological, cytological and molecular characteristics of NIFTP. We will conclude by considering the potential impact of the introduction of the NIFTP terminology.