BRAFV600E and CTNNB1 Mutation Analysis as Useful Markers for Differentiating Rathke’s Cleft Cysts from Craniopharyngiomas

Introduction: Rathke’s cleft cysts (RCCs) and craniopharyngiomas (CPs) are lesions of the sellar region, both originating from remnants of Rathke’s diverticulum. The presence of squamous metaplasia (SM) within RCCs often creates histological overlap with papillary craniopharyngiomas (PCPs), complicating accurate diagnosis. Given the distinct treatment and clinical outcomes associated with these lesions, precise identification is essential. BRAFV600E and CTNNB1 mutations have emerged as distinguishing genetic markers for PCPs and adamantinomatous CPs (ACPs), respectively. This study aims to evaluate the utility of BRAFV600E and β-catenin immunohistochemistry in differentiating RCCs from CPs.

Methods: A retrospective analysis of 71 RCC cases (42 females, 29 males; median age, 38 years) was conducted, assessing clinical, radiological, and histopathological data. BRAFV600E immunohistochemistry was performed on all cases, with a subset of 50 cases tested for β-catenin mutation. Cases with BRAFV600E positivity and β-catenin mutation were reassessed for potential re-diagnosis as PCP or ACP.

Results: Most RCCs were intrasellar (73.2%), with 12.7% in the suprasellar region and 14.1% involving both regions. Histologically, 59.2% showed ciliated epithelium, and 54.9% exhibited SM. BRAFV600E mutation was detected in 7 out of 71 specimens (9.9%), primarily in lesions with both SM and ciliated epithelium, where mutant BRAF protein was homogeneously expressed throughout the epithelium. To avoid false positives, BRAFV600E staining in cilia and anterior pituitary nests was excluded from the analysis. Among these cases, 5 were newly diagnosed, and 2 were recurrent cases. Nuclear β-catenin localization, indicative of ACP, was observed in one case. Based on these findings, 7 cases were re-diagnosed as PCPs and 1 as ACP.

Conclusion : BRAFV600E and CTNNB1 mutation analysis is a valuable diagnostic tool for distinguishing RCCs from CPs. Given the potential for RCCs to transform into PCPs, we recommend BRAFV600E testing for all RCC cases. For BRAFV600E-positive cases, close monitoring of tumor progression is advised.