Young investigator challenge: The morphologic analysis of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features on liquid‐based cytology: Some insights into their identification

Abstract

KEY WORDS: Liquid-based cytology; noninvasive follicular variant of papillary thyroid cancer; noninvasive follicular thyroid neoplasm with papillary-like nuclear features; thyroid carcinoma; thyroid lesions. INTRODUCTIONOver the last decades, the exact nature of thyroid lesions diagnosed as follicular variant of papillary thyroid carcinoma (FVPTC) has been debated. [1][2][3][4][5][6][7][8] Specifically, FVPTCs appear to represent a heterogeneous group of carcinomas and a controversial entity including both encapsulated/noninvasive (NI-FVPTCs) and invasive FVPTCs Based on their multi-institutional histological series, the Endocrine International Working Group recommended the reclassification of these NI-FVPTCs as "noninvasive follicular thyroid neoplasm with papillarylike nuclear features" (NIFTP). This entity was defined by a set of morphological features including nuclear membrane irregularities, ground glass appearance of the nuclei, and larger nuclear size within a context of encapsulated follicular tumor. 10 Conversely, apart from the histological approach and definition of these NIFTPs, its cytological diagnosis is still under evaluation in that this new terminology might significantly affect both the diagnosis of thyroid lesions and the categories of the different cytological classification systems. [11][12][13][14][15][16][17][18] For these reasons, and because none of the classification systems, including The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), accounts for the allocation of NIFTPs, it is crucial to establish in which cytological categories NIFTPs should be diagnosed. 19-23Therefore, a growing number of studies currently are investigating whether these lesions can be identified by fine-needle aspiration (FNA) and more specifically their impact on the ROM in the different diagnostic categories. Nevertheless, currently, the majority of FVPTCs are frequently diagnosed in the cytological categories of follicular neoplasm (FN) or suspicious for malignancy (SM) due to the absence of the undoubtedly nuclear features of PTCs, which may support a conclusive malignant diagnosis. [11][12][13][14][15][16][17][18] For this reason, some authors have analyzed their cytological cases for specific features able to identify the correct cytological categories for NIFTPs. Despite the small number of published series regarding NIFTPs to date, the preliminary results have demonstrated that the presence of nuclear pseudoinclusions and papillary structures are typical features of PTCs whereas a predominantly follicular pattern may be linked to NIFTPs, even if all these authors have not found any differentiation between NIFTPs and I-FVPTCs on FNA. Thus, the purpose of the current study was to examine and compare the morphological features in a series of cytohistological cases processed with liquid-based cytology (LBC) and diagnosed as either NIFTPs or I-FVPTCs. To the best of our knowledge, this study represents the first and largest series on LBC cytology published to date in which all the architectura...

New Insight in a New Entity: NIFTPS and Valuable Role of Ancillary Techniques. The Role of PD-L1

“…This data could also have a significant impact on the cytological evaluation of thyroid nodules in the differential diagnosis of NIFTPs versus EFVPTCs. In fact this is in agreement with the data from Maletta et al and Bizzarro et al, who concluded that the majority of these NIFTPs are diagnosed as indeterminate lesions (Bizzarro et al, 2016, Maletta et al, 2016) on cytological samples. In this way, the data provided by Fu et al on PD-L1 as useful marker in the discrimination between EFVPTC and NIFTP on histology could be also helpful on cytology, with important implications in clinical and surgical assessment and in lowering of the possible overtreatment.…”

“…This is also supported by the fact that NI-FVPCs, recently termed as NIFTPs, and invasive FVPT (I-FVPC), also known as encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), are not prognostically and molecularly alike (Bizzarro et al, 2016, Chen et al, 2012, Ganly et al, 2015, Liu et al, 2006, Lloyd et al, 2004, Maletta et al, 2016, Nikiforov et al, 2016, Ustun et al, 2014) as clearly assessed by several scientific reports demonstrating that I-FVPCs show more frequent lymph nodes metastases, recurrences and prevalence of BRAF mutations whilst NI-FVPCs (accounting for 50%–70% of the entire subset of FVPCs) show a more favorable outcome (Nikiforov et al, 2016). According to the paper by Nikiforov et al, this new entity was defined by an encapsulated nodule with a follicular architecture and a set of morphological features of PTC (including nuclear membrane irregularities, ground glass appearance of the nuclei, larger nuclear size) (Nikiforov et al, 2016).…”

Ancillary molecular testing of indeterminate thyroid nodules

“…Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (NE‐FVPTC) was recently reclassified as NIFTP . As shown in the second edition of the Bethesda thyroid system, this new terminology has decreased the ROM in most of the TBSRTC categories, most significantly in the indeterminate categories . Some studies have demonstrated that NIFTP can indeed be differentiated from PTC in cytological samples .…”

AHNS Series: Do you know your guidelines? AHNS Endocrine Section Consensus Statement: State‐of‐the‐art thyroid surgical recommendations in the era of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features

“…Brandler et al16 found that when PTC nuclear features and microfollicles are present NIFTP should be considered. Bizzarro et al13 concluded that NIFTP usually lacks pseudoinclusions and papillary structures; nuclear size and microfollicular clusters may allow differentiation between NIFTP and invasive FVPTC. Howitt et al17 found statistically significant differences in cytomorphologic features between patients with NIFTP and those with PTC.…”