Cytomorphology of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features and the Impact of New Nomenclature on Molecular Testing

Abstract

The re-naming of noninvasive follicular variant papillary thyroid cancer to the apparently non-malignant, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) impacts the prevalence of malignancy rates, thereby affecting mutation frequency in papillary thyroid cancer. Preoperative assessment of such nodules could affect management in the future. The original publications following the designation of the new nomenclature have been extensively reviewed. With the adoption of NIFTP terminology, a reduction in the follicular variant of papillary thyroid cancer (FVPTC) prevalence is anticipated, as is a modest reduction of papillary thyroid cancer (PTC) prevalence that would be distributed mainly across indeterminate thyroid nodules. Identifying NIFTP preoperatively remains challenging. RAS mutations are predominant but the presence of BRAF V600E mutation has been observed and could indicate inclusion of the classical PTC. The histological diagnosis of NIFTP to designate low-risk encapsulated follicular variant papillary thyroid cancers (EFVPTCs) would impact malignancy rates, thereby altering the mutation prevalence. The histopathologic criteria have recently been refined with an exclusion of well-formed papillae. The preoperative identification of NIFTP using cytomorphology and gene testing remains challenging.

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Is Not a Cytological Diagnosis, but It Influences Cytological Diagnosis Outcomes: A Systematic Review and Meta-Analysis

“…Even though statistically significant differences between NIFTP and FVPTC were found in this meta-analysis, differencing the entities is not so straightforward in real life. The results of a previous review indicate that differentiation of NIFTP and FVPTC in cytology is challenging, and preoperative diagnoses remain imprecise since the cytological features of the entities overlap greatly [25]. In the present meta-analysis, 10 studies compared the cytomorphology of NIFTP and FVPTC [22,23,34,35,41,46,51,64,69,78].…”

“…2, Fig. [25][26][27][28][29][30][31][32][33][34][35][36]. Statistically significant differences were observed in the AUS/FLUS and FN categories.…”

“…Thyroid fine needle aspiration (FNA) biopsies are categorized using The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) [19]. NIFTP cases generally belong to the intermediate categories of TBSRTC [8,[20][21][22][23][24][25][26]. The nomenclature revision affects the calculated risks of malignancy (ROM) in the TBSRTC categories.…”

“…The nomenclature revision affects the calculated risks of malignancy (ROM) in the TBSRTC categories. Since NIFTP is no longer considered malignant, the ROM decreased especially in the intermediate categories, where the underlying prevalence of EFVPTC is high [20,25,[27][28][29]. With low rates of diagnosis of EFVPTC and NIFTP, the effect on the rates of diagnosis and ROM in the various indeterminate categories is expected to be low or negligible.…”

Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Tumour Entity with a Short History. A Review on Challenges in Our Microscopes, Molecular and Ultrasonographic Profile

“…Accordingly, the 2nd edition [ 95 , 97 ] revised the calculated risks of malignancy (ROM) in TBSRTC categories, as non-malignant NIFTP status affects ROM in majority of categories. In summary, ROMs decreased in the intermediate categories that are characterized by the high prevalence of histologically diagnosed FVPTC and NIFTP cases [ 97 , 98 , 99 , 100 ]. In a recent meta-analysis, pooled risk differences of ROM were performed in each TBSRTC category, independently resulting in the following reductions: 2.4% (I2 was 0%) in ND, 2.7% (I2 was 2%) in benign, 8.2% (I2 was 43%) in AUS/FLUS, 8.2% (I2 was 53%) in FN, 7.3% (I2 was 89%) in SM, and 1.1% (I2 was 45%) in malignant category when NIFTP was reclassified [ 93 ].…”