Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features is Rare: A Population Based Study of Incidence

Abstract

The renaming of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was proposed by a group of experts in 2016 to prevent overtreatment of indolent, low-risk thyroid cancers. The aim of this study was to estimate the incidence and outcome for patients meeting the NIFTP criteria in a well-defined geographic region. Our cohort consisted of 134 patients with papillary thyroid carcinoma from the Region of Southern Denmark (RSD), 2007 to 2011. Patients were retrieved from the Danish Thyroid Cancer (DATHYRCA) Database. All potential NIFTP cases were reviewed by a thyroid pathologist. We identified no cases meeting all diagnostic criteria, but one probable NIFTP case from 2007 to 2011. The patient was treated according to the national guidelines and is alive and recurrence-free after 106 months of follow-up. Molecular testing showed KRAS mutation. In a population based set up the incidence rate of NIFTP is very low.

Significance of RAS Mutations in Thyroid Benign Nodules and Non-Medullary Thyroid Cancer

“…Based on available evidence from several studies of molecular profiling, a relevant portion of NIFTPs carry RAS mutations. In fact, the review of 18 studies [52,53,[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72] showed a wide range of prevalence for RAS mutations, from 20 to 100%. This could be related to the heterogeneity of tumor series coming from different geographic areas and different source (cytology samples or tumor specimens), and detection method (direct sequencing, PCR-based approaches, or next-generation sequencing [NGS] technology).…”

ThyroSeq overview on indeterminate thyroid nodules: An institutional experience

“…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. 26,27 In particular, Strickland emphasized that relying on individual nuclear features in NIFTP cannot differentiate it from benign reactive changes due to their overlapping features, and it is not reliable to even distinguish NIFTP from other PTCs.…”

“…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 . Zajkowska and Strickland addressed the problem with the NIFTP entity 26,27 .…”

Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice

“…Renshaw and Gould explained their motivation to over-diagnose uncertain cases rather than under-diagnose them in North American practice [51]. The gap between North America and the rest of the world became wider, and non-invasive encapsulated follicular variant PTC accounted for nearly 30% of PTC in North American practice [22,39,40,52,53], whereas it was low (1-5%) in most Asian thyroid practices [24,25,[41][42][43][44]48], some European institutes [14,[54][55][56], and a few US centers [25,57]. Hodak et al discussed this overdiagnosis in their excellent commentary, suggesting that for many patients with thyroid cancer, we may often be violating the important dictum primum non nocere (first, do no harm patients) [58].…”