Surgical implications of BRAF V600E-positive Rathke's cleft cysts: prediction of early recurrence based on reclassification to papillary craniopharyngioma.

Abstract

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 overlaps with papillary CPs (PCPs), complicating accurate diagnosis. Given the distinct treatment and clinical outcomes associated with these lesions, precise identification is essential. BRAF V600E and CTNNB1 mutations have emerged as distinguishing genetic markers for PCP and adamantinomatous CP (ACP), respectively. This study aimed to evaluate the utility of BRAF V600E and β-catenin immunohistochemistry in differentiating RCC from CP. The authors retrospectively reviewed the clinical, radiological, and histopathological data of 383 RCCs diagnosed between January 2015 and May 2024 at Beijing Tiantan Hospital. BRAF V600E and CTNNB1 immunohistochemistry were performed on all cases, with BRAF results confirmed via Sanger sequencing. Clinical outcomes were evaluated during follow-up. Sixty-nine RCC cases met the inclusion criteria (61 primary and 8 recurrent). Of these, 52 cases were in intrasellar region (75.4%), with 9 cases (13.0%) in the suprasellar region and 8 cases (11.6%) involving both regions. Histologically, 39 cases (56.5%) exhibited epithelial SM. No nuclear β-catenin accumulation localization was detected. BRAF V600E expression was observed in 7 cases (10.1%), all within areas of SM, and confirmed with Sanger sequencing. These positive cases also showed elevated Ki-67 indices, with proliferative activity concentrated at the basal layer of the epithelium with SM. Based on these molecular and histological findings, the 7 BRAF V600E-positive cases were reclassified as PCPs. Notably, Kaplan-Meier analysis demonstrated significantly worse progression-free survival in BRAF V600E-positive cases compared to wild-type cases (p = 0.023). BRAF V600E and CTNNB1 mutation analysis is a valuable diagnostic tool for distinguishing RCC from CP. Given the potential for RCC to transform into PCP, the authors recommend BRAF V600E testing for all RCC cases. For BRAF V600E-positive cases, close monitoring of tumor progression or adjuvant therapies is advised.