BRAF Mutations in Erdheim-Chester Disease

Abstract

TO THE EDITOR: Blombery et al recently published the case report of a patient with Erdheim-Chester disease (ECD). It confirms results from our series of 24 patients for whom we reported a frequency of 54% of p.V600E mutations in patients with ECD. In our article, we also showed by immunohistochemistry that the foamy histiocytes of ECD were the mutated cells. Since publication of our article, we have analyzed more patients. We used a pyrosequencing method that proved to be more sensible than Sangersequencingonmelanomasamples. TheactualfrequencyofBRAF p.V600E mutations in our series is 19 (51%) of 37 ECD samples. This frequency is not different from the 91 (47%) of 195 samples in the published cases of Langerhans cell histiocytosis (LCH). BRAF mutations are present in half the samples of ECD and LCH, but absent in most other histiocytoses. This suggests that ECD and LCH may have a specific common cellular origin. Interestingly, in LCH, BRAF mutations are present in cells at different maturation stages; however, BRAF mutations were not detected in blood monocytes. Finally, the high frequency of mutations and the poor prognosis of ECD argue for a clinical evaluation of BRAF inhibitors in patients with resistant and progressive life-threatening ECD.