Erdheim-Chester disease: a systematic review

Crit Rev Oncol Hematol. 2015 Jul;95(1):1-11. doi: 10.1016/j.critrevonc.2015.02.004. Epub 2015 Feb 17.


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. It encompasses a spectrum of disorders ranging from asymptomatic bone lesions to multisystemic, life-threatening variants. We reviewed all published reports of histologically-confirmed ECD and explored clinical, radiological, prognostic and therapeutic characteristics in a population of 448 patients, including a unique patient from our Department. To find a clinically relevant signature defining differentiated prognostic profiles, the patients' disease features were compared in relation to their CNS involvement that occurred in 56% of the entire population. Diabetes insipidus, visual disturbances, pyramidal and extra-pyramidal syndromes were the most recurrent neurological signs, whereas concomitant pituitary involvement, retro-orbital masses and axial lesions in the presence of symmetric bilateral osteosclerosis of long bones depicted the typical ECD clinical picture. Patients with CNS infiltration showed a lower occurrence of heart involvement and a higher incidence of bone, skin, retro-peritoneal, lung, aortic and renal infiltration. No difference in the therapeutic algorithm was found after stratification for CNS involvement. A better understanding of the disease pathogenesis, including BRAF deregulation, in keeping with improved prognostic criteria, will provide novel suggestions for the management of ECD.

Keywords: BRAF(V600E); CNS involvement; Erdheim–Chester disease; Histiocytosis; Vemurafenib.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Bone and Bones / pathology
  • Central Nervous System / pathology
  • Erdheim-Chester Disease / diagnosis
  • Erdheim-Chester Disease / drug therapy
  • Erdheim-Chester Disease / genetics
  • Erdheim-Chester Disease / pathology*
  • Humans
  • Kidney / pathology
  • Male
  • Myocardium / pathology
  • Point Mutation
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics


  • Adrenal Cortex Hormones
  • Proto-Oncogene Proteins B-raf