Cytomorphologic Features of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): A Comparison with Infiltrative Follicular Variant of Papillary Thyroid Carcinoma

The change in nomenclature from noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has been proposed to more accurately reflect the indolent behavior of this neoplasm and has implications for diagnosis and treatment. However, the ability to recognize NIFTP and reliably distinguish it from infiltrative follicular variant of papillary thyroid carcinoma (IFVPTC) presents a significant challenge for cytopathologists. To identify cytologic features useful in this distinction, all cases of NIFTP and IFVPTC with a preceding diagnostic FNA were reviewed. Twenty-two cases of NIFTP and twenty cases of IFVPTC were identified. The cytomorphologic features of NIFTP and IFVPTC were compared. The majority of NIFTP cases were diagnosed as either follicular neoplasm/lesion (FN/L) (11/22) or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (10/22). None were diagnosed as suspicious for malignancy (SUS) and only 1 of 22 was diagnosed as PTC on cytology. In contrast, the majority of the IFVPTC cases were diagnosed as PTC on FNA (12/22) ( P = 0.0004). Among the IFVPTCs, 5/20 were classified as FN/L, 2/20 as SUS, and only 1/20 was diagnosed as AUS/FLUS. No particular cytomorphologic features could reliably distinguish NIFTP from IFVPTC; however, the presence of microfollicular architecture ( P = 0.03) and absence of pseudoinclusions ( P = 0.008) were significantly associated with NIFTP. Nuclear crowding and overlapping ( P = 0.03) as well as grooves and irregular nuclear contours ( P = 0.0004) were significantly associated with IFVPTC. Eight IFVPTC cases were positive for BRAFV600E mutation, while all tested NIFTP cases were negative. Additional studies are required to further explore cytomorphologic features and molecular signatures that may assist in the preoperative diagnosis of NIFTP.