Future studies with long-term follow-up are required to determine if pediatric BRAF V600E positive CNS-JXG neoplasms are a distinct entity in the L-group histiocytosis category or represent an expanded pediatric spectrum of ECD.
BRAF V600E is the predominant oncogenic driver of L-group histiocytoses, which includes Erdheim-Chester disease (ECD); however, limited data exist on the prevalence of this mutation in sporadic XG family lesions.
We present a patient with <i>BRAF</i>-V600E-mutant ECD with a classical pyramido-ataxic onset of disease who improved after prompt diagnosis with vemurafenib treatment as first-line therapy.
The BRAF inhibitor vemurafenib is approved by the U.S. Food and Drug Administration (FDA) for patients with ECD harboring a <i>BRAF</i> V600E mutation.
Therefore, the patient was determined to have ECD with a typical BRAF V600E mutation, as well as primary myelofibrosis, with the latter diagnosis manifesting clinically over one year after the JAK2 V617F was first detected in ctDNA.
We collected CSF from patients with BRAF V600E or K-mutated melanoma (N=8) or BRAF V600E mutated Erdheim-Chester Disease (ECD) (N=3) with suspected central nervous system (CNS) involvement on the basis of neurological symptoms (10/11), MRI imaging (8/11), or both.
Patients with Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD)</span> have a high frequency of BRAF(V600E) mutations and respond to RAF inhibitors.
However, at least in the cases of LCH and ECD, there is a very high frequency of activating mutations in MAPK pathway genes, most notably BRAF-V600E, as well as MAP2K1, in LCH and NRAS in ECD.
The oncogenic BRAF(V600E) mutation is present in biopsies and in the peripheral blood from all patients with ECD who were evaluated and is associated with OIS.
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis, associated in more than 50% of cases to BRAF(V600E) mutations in early multipotent myelomonocytic precursors or in tissue-resident histiocytes.
BRAF(V600E) mutations were detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other histiocytoses.Four patients with ECD died of disease.