Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy

Abstract

Due to the extremely indolent behavior, a subset of noninvasive encapsulated follicular variant papillary thyroid carcinomas has been classified as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)" since 2016 and is no longer considered carcinoma. Since the introduction of this new terminology, changes and refinements have been made in diagnostic criteria. Initially, the incidence of NIFTP was estimated substantial. However, the reported incidence of NIFTP varies greatly among studies and regions, with higher incidence in North American and European countries than in Asian countries. Thus, the changes in the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) differ inevitably among regions. Because more conservative surgery is recommended for NIFTPs, distinguishing NIFTPs from papillary thyroid carcinomas in preoperative fine-needle aspiration cytology became one of the major concerns. This review will provide comprehensive overview of updates on diagnostic criteria, actual incidence and preoperative cytologic diagnoses of NIFTP, and its impact on the ROM in TBSRTC.

Papillae, psammoma bodies, and/or many nuclear pseudoinclusions are helpful criteria but should not be required for a definitive cytologic diagnosis of papillary thyroid carcinoma: An institutional experience of 207 cases with surgical follow up

“…A recently published epidemiology study using SEER‐22 data, by Chen et al., reported that NIFTP comprised a small fraction of previously diagnosed thyroid cancers, which was significantly less than was anticipated by EPS: 2.2% to 2.6% of thyroid cancers in 2018–2019 vs. 18.6% of PTC estimated by EPS 50 . These data suggest that the impact of NIFTP is not as considerable as initially estimated, and variations in incidence may be a result of variation of cancer rates in different populations, and/or variations in the interpretation of PTC nuclear atypia, which is still subjective despite efforts to objectify it 51 . Therefore, each center should consider basing their clinical decisions on their own data, including incidence of NIFTP in their patient population, and their thresholds for diagnosing PTC 52 …”

“…50 These data suggest that the impact of NIFTP is not as considerable as initially estimated, and variations in incidence may be a result of variation of cancer rates in different populations, and/or variations in the interpretation of PTC nuclear atypia, which is still subjective despite efforts to objectify it. 51 Therefore, each center should consider basing their clinical decisions on their own data, including incidence of NIFTP in their patient population, and their thresholds for diagnosing PTC. 52…”

ThyroSeq overview on indeterminate thyroid nodules: An institutional experience

“…14,20 NIFTP typically shows subtle PTC-like nuclear features which could overlap anywhere on the spectrum of classical PTC and reactive nuclear atypia, though it is generally thought that these tumors need to be managed conservatively with lobectomy instead of total thyroidectomy due to their uncertain malignant potential but likely indolent behavior. 15,19,22,23 While a nuclear scoring scheme could introduce a more structured approach to classification, concerns about intra-and interobserver variability and inconsistent reports remain. 14,24,25 Zajkowska and Strickland addressed the problem with the NIFTP entity.…”

“…This uncertainty caused by this wide range and ROM variability demonstrate why molecular techniques are needed to better define the diagnosis and the risks when entities like NIFTP are considered 14,20 . NIFTP typically shows subtle PTC‐like nuclear features which could overlap anywhere on the spectrum of classical PTC and reactive nuclear atypia, though it is generally thought that these tumors need to be managed conservatively with lobectomy instead of total thyroidectomy due to their uncertain malignant potential but likely indolent behavior 15,19,22,23 . While a nuclear scoring scheme could introduce a more structured approach to classification, concerns about intra‐ and inter‐observer variability and inconsistent reports remain 14,24,25 .…”

Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy

“…The method of estimating the cancer risk, which is based on histologic follow-up, overestimates the ROM, particularly for the categories I–III, where there is selection bias given the relatively small proportion of nodules that undergo excision. Although NIFTP is a surgical disease and cannot be preoperatively diagnosed on CNB or FNA specimens, the morphologic features of NIFTP tend to lead to classification on CNB/FNA as either category III, IV, or V, thereby impacting the resultant ROM calculations [ 13 , 14 , 17 , 18 ]. The ROM for each category is shown when including and excluding NIFTP in malignancy, information that might help guide more conservative clinical management of some nodules.…”