Researchers identified mutations of BRAF and mutations in other MAPK pathway genes associated with Erdheim-Chester disease (ECD), according to results from a clinical trial (NCT01417520) of 60 adults with the disease.1

ECD is a very rare, potentially fatal multiorgan myeloid neoplasm that occurs principally in adults, with approximately 600 total cases worldwide. ECD tumors have foamy macrophages that are CD68+, CD163+, CD1a, and often S100. Diagnosis occurs via clinical, radiologic, and histologic examinations and results.

This study enrolled 60 consecutive patients with ECD between 2011 and 2015; 45 patients were male. Average age at first manifestations of ECD was 46 years. It took an average of 4.2 years for the establishment of a diagnosis after initial presentation.

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In this study, clinicians detected the disease via various types of imaging studies. Researchers used biopsies to determine whether BRAF V600E and MAPK pathway mutations existed.

Nearly all (95%) patients experienced osteosclerosis as bone was the most commonly affected tissue. In one-third to two-thirds of patients, cardiac mass and periaortic involvement, diabetes insipidus, retro-orbital infiltration, lung, skin, retroperitoneal, central nervous system, and xanthelasma manifestations occurred and affected patients to varying degrees.

Patients underwent treatment with interferon α, imatinib, anakinra, cladribine, vemurafenib, and dabrafenib with trametinib, and 11 patients did not undergo treatment.

Researchers discovered a BRAF V600E mutation in 51% of 57 biopsies. One patient’s biopsied sample had an ARAF D228V mutation, and one patient’s sample had an activating ALK fusion.

Due to its extreme rarity, diagnosis of ECD is elusive and challenging. Identification of BRAF and MAPK pathway mutations in biopsied ECD tumors can improve diagnosis. Additionally, identification of these mutations could enable the development of targeted treatments. Finally, these results demonstrate that ECD is a neoplastic disease.


1. Estrada-Veras JI, O’Brien KJ, Boyd LC, et al. The clinical spectrum of Erdheim-Chester disease: an observational cohort study. Blood Adv. 2017 March. doi: [Epub ahead of print]