Nuclear pseudoinclusion is associated with BRAF V600E mutation: Analysis of nuclear features in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most prevalent thyroid neoplasm, classified into BRAF-like and RAS-like subtypes. Nuclear alterations serve as a diagnostic criterion of PTC and are fully manifested in BRAF-like. This single-center retrospective study aimed to assess the different presentation of nuclear features in 40 samples of BRAFV600E- and 40 samples of RAS-mutated PTCs using both bivariate and multivariate analytic approaches. Nuclear features are evaluated histologically using the 3-point and 8-point scoring systems established by the World Health Organization and the Asian Thyroid Working Group, respectively. We found the presence of membrane irregularities, nuclear elongation, nuclear groove, sickle-shaped nuclei, nuclear pseudoinclusion, and higher nuclear scores are significantly associated with BRAFV600E. Multivariate analysis showed that nuclear pseudoinclusion is predictive for the presence of BRAFV600E mutation (OR = 10.97, 95%CI = 2.81-42.96, p = 0.001) and has sensitivity of 55 %, specificity of 92.5 %, positive predictive value of 88 %, negative predictive value of 67.3 %, and accuracy of 73.8 %. There are various pathways and protooncogenes associated with the development of thyroid neoplasm. This study found significant differences in nuclear features between BRAFV600E and RAS-mutated PTC. BRAFV600E tend to display florid nuclear features, whereas the RAS- mutation is associated with subtle nuclear features. These findings emphasize the distinct cytological profiles of BL and RL PTC, reinforcing the need for precise subtyping to guide tailored management.