Recurrent Papillary Craniopharyngioma with BRAF V600E Mutation Treated with Dabrafenib: A Case Report

Background Craniopharyngiomas are locally invasive tumors of the suprasellar space that present a therapeutic challenge given their location proximate to many critical structures including the pituitary stalk, optic chiasm, and hypothalamus, as well as their tendency to recur following surgical resection and radiation treatment. These tumors occur in two distinct histopathologic subtypes, adamantinomatous and papillary, with the latter harboring the V600E mutation in the BRAF gene in the overwhelming majority of cases. Here, we present a case of a patient with a recurrent papillary craniopharyngioma treated with the BRAF inhibitor dabrafenib for approximately 1 year, and observed for over 1 year following cessation of therapy with no evidence of disease progression.

Methods This is a case report.

Case Presentation A 47-year-old man with a remote history of non-Hodgkin lymphoma originally presented to an outside institution with symptoms of diabetes insipidus, visual loss, and color blindness. MRI revealed an enhancing suprasellar lesion consistent with craniopharyngioma. He underwent a right pterional craniotomy for resection. Postoperatively, he suffered pan-hypopituitarism and on imaging had a minimal amount of residual enhancement near the pituitary stalk. Papillary craniopharyngioma was confirmed on pathology. He was observed closely and had radiographic progression 2 years later. He subsequently underwent fractionated radiation therapy with control of disease for a further 3 years. When his tumor progressed further, the decision was made to explore nonsurgical intervention given his preserved vision. Tissue samples from his original resection were obtained and the presence of the BRAF V600E mutation confirmed. Treatment with the BRAF inhibitor dabrafenib was initiated and the patient was followed up closely with serial imaging. Initially, the cystic component of the tumor appeared to expand but the solid portion of the tumor appeared to hollow out, and with further dabrafenib therapy, there was dramatic reduction in tumor size by 9 months’ time. After 1 year of therapy, the decision was made to halt dabrafenib and continue with close observation. At his most recent follow-up, over 1 year following cessation of therapy, he continues to do well clinically with no evidence of disease progression.

Conclusion Craniopharyngiomas present a surgical and therapeutic challenge, given their propensity to recur after treatment and their proximity to structures placed at risk by repeated surgical intervention and local disease invasion. In the case of papillary craniopharyngiomas, which very frequently harbor the BRAF V600E mutation, treatment with a targeted BRAF V600E inhibitor such as dabrafenib represents a promising therapeutic consideration in patients for whom repeat surgery presents significant risks, and who do not require an emergent decompressive procedure. An ongoing cooperative group trial (Alliance A071601) is testing the combination of BRAF/MEK inhibition in BRAF V500E mutant craniopharyngioma patients.