The clinical spectrum of Erdheim-Chester disease: an observational cohort study

Juvianee I. Estrada-Veras, Kevin J. O’Brien, Louisa C. Boyd, Rahul H. Dave, Benjamin H. Durham, Liqiang Xi, Ashkan A. Malayeri, Marcus Y. Chen, Pamela J. Gardner, Jhonell R. Alvarado Enriquez, Nikeith Shah, Omar Abdel-Wahab, Bernadette R. Gochuico, Mark Raffeld, Elaine S. Jaffe and William A. Gahl

Key Points

  • ECD varies in terms of age of onset, clinical presentation, manifestations, organ involvement, disease severity, and survival.

  • ECD is a neoplasm and should be adopted by the field of hematology-oncology following the World Health Organization reclassification.


Erdheim-Chester disease (ECD) is a rare, potentially fatal multiorgan myeloid neoplasm occurring mainly in adults. The diagnosis is established by clinical, radiologic, and histologic findings; ECD tumors contain foamy macrophages that are CD68+, CD163+, CD1a, and frequently S100. The purpose of this report is to describe the clinical and molecular variability of ECD. Between 2011 and 2015, 60 consecutive ECD patients (45 males, 15 females) were prospectively evaluated at the National Institutes of Health Clinical Center. Comprehensive imaging and laboratory studies were performed, and tissues were examined for BRAF V600E and MAPK pathway mutations. Mean age at first manifestations of ECD was 46 years; a diagnosis was established, on average, 4.2 years after initial presentation. Bone was the most common tissue affected, with osteosclerosis in 95% of patients. Other manifestations observed in one-third to two-thirds of patients included cardiac mass and periaortic involvement, diabetes insipidus, retro-orbital infiltration, retroperitoneal, lung, central nervous system, skin, and xanthelasma, affecting patients in variable ways. Methods of detection included imaging studies of various modalities. Mutation in BRAF V600E was detected in 51% of 57 biopsy specimens. One patient had an ARAF D228V mutation, and 1 patient had an activating ALK fusion. Treatments included interferon α, imatinib, anakinra, cladribine, vemurafenib, and dabrafenib with trametinib; 11 patients received no therapy. The diagnosis of ECD is elusive because of the rarity and varied presentations of the disorder. Identification of BRAF and other MAPK pathway mutations in biopsy specimens improves ECD diagnosis, allows for development of targeted treatments, and demonstrates that ECD is a neoplastic disorder. This study was registered at as #NCT01417520.

  • Submitted September 29, 2016.
  • Accepted January 3, 2017.
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