Noninvasive Follicular Thyroid Neoplasms With Papillary-like Nuclear Features Are Genetically and Biologically Similar to Adenomatous Nodules and Distinct From Papillary Thyroid Carcinomas With Extensive Follicular Growth

Abstract

- The morphologic similarity and RAS mutations in FAs, NIFTPs, and IE-PTC-FVs supports the genetic similarity of those follicular neoplasms in contrast to the unique presence of BRAF V600E mutations in PTC-EFGs. Using strict diagnostic criteria supported by molecular testing, tumors with extensive follicular growth can be classified into follicular type or RAS-like (FA, NIFTP, IE-PTC-FV) versus papillary type or BRAF V600E-like (PTC-EFG).

Outcome and molecular characteristics of non-invasive encapsulated follicular variant of papillary thyroid carcinoma with oncocytic features

“…The mutation landscape of O-NI-EFVPTC largely resembles those of FVPTC and NIFTP and differs significantly from Hurthle cell neoplasms. NRAS, KRAS, and HRAS hotspot mutations are detected in a significant proportion (33%) of O-NI-EFVPTC, comparable with the 37% frequency found in the FVPTC of the TCGA PTC study [6,28], 30% in the NIFTP consensus cohort [5] and 63% of NIFTP reported by Johnson et al [7]. However, the NRAS, KRAS, and HRAS mutations in O-NI-EFVPTC are significantly higher than in Hurthle cell neoplasms, being 9-11% in HCC and 0% in Hurthle cell adenoma [11,29,17].…”

“…Additional studies with longer follow up may be required to specifically address the long-term outcome of the patients with these tumors. (Table 3) [6,5,27,11]. The mutation landscape of O-NI-EFVPTC largely resembles those of FVPTC and NIFTP and differs significantly from Hurthle cell neoplasms.…”

“…FVPTC is a variant of PTC that is characterized by an exclusively follicular growth pattern, while the oncocytic variant is used to describe PTC with prominent oncocytic cytomorphology characterized by abundant eosinophilic granular cytoplasm [4,5]. Recently, compelling clinical outcome data and molecular evidence, including The Cancer Genomic Atlas (TCGA) of PTC, have demonstrated that noninvasive FVPTC follows a highly indolent clinical course and has a molecular signature resembling follicular adenoma/ follicular carcinoma with activating RAS mutations as the most frequently encountered genetic alteration [6][7][8][9]5]. In 2016, a group of 28 endocrine experts critically reexamined this entity and advocated for a nomenclature revision to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), in an effort to reduce overtreatment of this highly indolent tumor by eliminating the term "carcinoma" [5].…”

Indeterminate thyroid nodules (TIR3A/TIR3B) according to the new Italian reporting system for thyroid cytology: A cytomorphological study

“…Regarding cytohistological correlations of particular entities, we hypothesise that the similar distribution of microfollicles between FVPTC and conventional PTC may be due to the a remarkable proportion of follicular growth in our TIR3B cases proved to be conventional PTC at histology (Figure G‐H). This hypothesis is based on the fact that in conventional PTC the papillae are nearly always seen with follicle structures and follicular growth may be extensive …”

Ubiquitin Immunostaining in Thyroid Neoplasms Marks True Intranuclear Cytoplasmic Pseudoinclusions and May Help Differentiate Papillary Carcinoma from NIFTP

“…When available, next generation sequencing data was gathered on the NIFTPs. Sequencing was performed for clinical or research purposes, as previously described [17]. In brief, using a clinically validated assay, formalin-fixed, paraffin-embedded DNA was amplified for somatic mutations located within mutational hotspot regions of 50 cancerrelated genes including BRAF, HRAS, NRAS, and KRAS.…”