BRAF V600E Immunohistochemical Expression in Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features

Background: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced to avoid overtreatment of indolent tumours, although risks of misclassification and rare metastasis remain. According to the 2022 WHO (World Health Organization) classification, BRAF V600E-mutated cases should be reclassified as classical papillary thyroid carcinoma (PTC) with predominant follicular architecture. VE1 immunohistochemistry is a reliable surrogate for detecting the BRAF V600E mutation. Objectives: To determine the frequency of BRAF V600E mutation among NIFTP using VE1 immunohistochemistry, and to assess its correlation with clinicopathological characteristics. Materials and methods: Forty-six tumours originally diagnosed as NIFTP during the period from 2020 to 2024 were retrospectively identified. All haematoxylin-eosin slides were re-evaluated according to the WHO 2022 criteria. VE1 immunohistochemistry was performed on all cases (rabbit monoclonal anti-BRAF V600E, BIO-SB, USA). VE1 status was then correlated with clinicopathological features. RESULTS: VE1 staining reclassified 13% of suspected NIFTPs. 2.2% showed capsular invasion highlighted by VE1 and were reclassified as invasive encapsulated follicular variant of PTC (IEFVPTC), while 11% demonstrated diffuse cytoplasmic VE1 positivity indicative of BRAF V600E mutation. No significant association was observed between VE1 positivity and clinicopathological parameters (P-value > 0.05); however, VE1-positive cases tended to be larger and more frequent in males. Conclusions: VE1 immunohistochemistry identified a small but clinically important subset of tumours originally labelled as NIFTP that belong to the PTC category. Routine VE1 staining reduces the risk of undertreating aggressive BRAF-driven disease and provides a rapid, economical quality control step to ensure adherence to the WHO 2022 criteria.