BRAF-MEK inhibition in a giant BRAF-mutant Rathke cleft cyst: Diagnostic challenges and clinical implications for...

Rathke cleft cysts are benign sellar lesions with a substantial risk of postoperative recurrence. In contrast to papillary craniopharyngiomas, oncogenic BRAF mutations are exceptionally reported in Rathke cleft cysts (RCCs), and the therapeutic relevance of targeted inhibition remains unknown.

A 51-y-old man presented with a giant cystic suprasellar lesion involving the optochiasmatic and subfrontal regions. Following incomplete surgical resection, histopathological analysis confirmed the diagnosis of Rathke's cleft cyst. Molecular profiling identified a somatic BRAF p. V600E mutation present in a subclonal population. Rapid recurrence occurred 3 months postoperatively. Combined BRAF/MEK inhibition with dabrafenib and trametinib was initiated, leading to a marked reduction in cyst volume on serial MRI, further enhanced after dose escalation. Treatment was well tolerated, with complete symptom resolution and no endocrine impairment.

This report describes the first adult BRAF-mutant RCC responding to BRAF/MEK-targeted therapy, supporting molecular profiling to guide personalized management in recurrent or high-risk RCCs.