Complete remission of critical neurohistiocytosis by vemurafenib

OBJECTIVE: To describe a patient with life-threatening brainstem neurohistiocytosis who recovered completely upon targeted treatment with the V600E mutation-specific BRAF inhibitor vemurafenib. METHODS: We report clinical, histiologic, genetic, and sequential imaging findings, including fluorodeoxyglucose (FDG)-PET, over a follow-up period of 11 months. RESULTS: The patient presented with central hyperventilation, skeletal and perirenal Erdheim-Chester disease, and cutaneous Langerhans cell histiocytosis. A BRAF V600E hotspot mutation was detected in all afflicted tissues. Therapy with vemurafenib led to complete and stable clinical remission of CNS lesions and systemic disease that could be demonstrated by brain MRI and whole-body FDG-PET. CONCLUSIONS: Neurologic involvement in Erdheim-Chester disease usually confers a poor prognosis. In this patient, vemurafenib was well-tolerated and highly efficacious for severe brainstem involvement in Erdheim-Chester disease with overlapping Langerhans cell histiocytosis. This case illustrates the heterogeneous phenotypic spectrum of neurohistiocytosis and underscores the importance of genetic testing. CLASSIFICATION OF EVIDENCE: This article provides Class IV evidence. This is a single observational study without controls.