Abstract
Background and Objectives: We aimed to assess the diagnostic value of various immunohistochemical (IHC) markers and panels for differentiation among benign follicular nodules (BFNs), noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), noninvasive encapsulated follicular variants of papillary thyroid carcinoma (NEFVPTCs), and infiltrative FVPTC (IFVPTC). Materials and Methods: Sixty-three cases were classified as BFNs, NIFTPs, NEFVPTCs, or IFVPTCs and were evaluated using the following markers: CK19, CD56, galectin-3, CITED1, HBME-1, VE1, and TROP-2. Results: The IHC results for NIFTP and NEFVPTC exhibited no statistically significant differences. In differentiating IFVPTCs from BFNs and NIFTPs/NEFVPTCs, galectin-3 and TROP-2 were the markers with the highest sensitivity plus high specificity, respectively. In various combinations, panel co-expression of two markers, including galectin-3 and/or HBME-1 and/or TROP-2, and the combination of galectin-3 and TROP-2 co-expression could achieve 100% in all aspects. In terms of discrimination of BFNs from NIFTP/NEFVPTC, CK19 was the single most sensitive marker (81.3%), while CD56 was the most specific (100%). The panel consisting of CK19 and/or HBME-1 exhibited the greatest sensitivity (96.9%), but the panel with CD56 and/or HBME-1 exhibited the greatest specificity (90.5%). Conclusions: Our results broaden the use of IHC markers for differential diagnoses among the four groups of follicular-based lesions. In addition, the similar IHC profiles of NIFTP and NEFVPTC also suggest the original criterion of <1% papillae within tumors, providing a reliable NIFTP diagnosis. Their close relationship may represent a spectrum of progressing neoplasia.
Highlights
The only case of NEFVPTC in our study with a positive result for VE1 may require deeper sections in paraffin blocks to identify more papillae owing to the similar IHC findings obtained, both NIFTP and NEFVPTC were grouped for comparison with benign follicular nodules (BFNs) and infiltrative follicular variant of PTC (FVPTC) (IFVPTC) using the aforementioned markers, both alone and in various combinations to determine their diagnostic value
Corresponding to the aforementioned studies, the results in our study suggest that VE1 was highly specific but insufficiently sensitive to distinguish IFVPTC from NIFTP/NEFVPTC
Our study is limited by the relatively small sample number and the absence of a correlation for molecular testing in this cohort; it possesses novelty and strength, and it broadens the use of IHC markers to differentiate IFVPTCs from BFNs, alone or in combination
Summary
Thyroid carcinomas are prime examples of intensified surveillance resulting in an increased incidence of early cancers exhibiting indolent behavior. This phenomenon is commonly described as cancer overdiagnosis, and is mainly attributable to the enhanced screening of papillary thyroid carcinoma (PTC), comprising ~80% of thyroid epithelial malignancies, the follicular variant of PTC (FVPTC). Studies have demonstrated that FVPTC and its subtype, encapsulated FVPTC (EFVPTC), exhibit indolent behavior and are genetically distinct from infiltrative tumors. Owing to the recognition of overdiagnosis and overtreatment in indolent cancers of the thyroid, an international multidisciplinary study proposed new terminology—noninvasive follicular thyroid neoplasm with papillarylike nuclear features (NIFTP)—for noninvasive EFVPTC and established reproducible criteria [1]
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