Immunohistochemistry Helps to Distinguish Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features/Noninvasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma with Other Follicular Thyroid Lesions

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). 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. 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%). 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.