Erdheim-Chester Disease

  • Eli L. Diamond
  • Benjamin H. Durham


Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis and a rare disorder primarily affecting adults. Clinical manifestations vary widely, as does the severity of clinical phenotypes. The disease is defined by infiltration of involved tissues with CD1a (-) histiocytes, inflammation, and fibrosis, although the histopathologic profile of ECD lesions can vary between patients and affected organs. The identification of recurrent somatic alterations in mitogen-activating protein kinase (MAPK) pathway genes in ECD tissue, including the BRAF V600E mutation in ~50% of cases, has led to a reconceptualization of ECD as a myeloid neoplasm. Furthermore, these discoveries have opened the door to new therapeutic strategies holding promise for unprecedented efficacy in the treatment of ECD. Unanswered questions remain about how best to evaluate and implement these new therapies.


Erdheim-Chester disease Histiocytosis Mitogen-activated protein kinases Molecular targeted therapy 


  1. 1.
    Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer. 2005;45(3):256–64.PubMedCrossRefGoogle Scholar
  2. 2.
    Emile JF, Abla O, Fraitag S, Horne A, Haroche J, Donadieu J, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood. 2016;127:2672–81.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Chester W. Uber lipoidgranulomatose. Virchows Arch Pathol Anat. 1930;279:561–602.CrossRefGoogle Scholar
  4. 4.
    Haroche J, Cohen-Aubart F, Charlotte F, Maksud P, Grenier PA, Cluzel P, et al. The histiocytosis Erdheim-Chester disease is an inflammatory myeloid neoplasm. Expert Rev Clin Immunol. 2015;11(9):1033–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Haroche J, Charlotte F, Arnaud L, von Deimling A, Helias-Rodzewicz Z, Hervier B, et al. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 2012;120(13):2700–3.PubMedCrossRefGoogle Scholar
  6. 6.
    Emile JF, Charlotte F, Amoura Z, Haroche J. BRAF mutations in Erdheim-Chester disease. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2013;31(3):398.CrossRefGoogle Scholar
  7. 7.
    Blombery P, Wong SQ, Lade S, Prince HM. Erdheim-Chester disease harboring the BRAF V600E mutation. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2012;30(32):e331–2.CrossRefGoogle Scholar
  8. 8.
    Diamond EL, Durham BH, Haroche J, Yao Z, Ma J, Parikh SA, et al. Diverse and targetable kinase alterations drive histiocytic neoplasms. Cancer Discov. 2016;6(2):154–65.PubMedCrossRefGoogle Scholar
  9. 9.
    Diamond EL, Dagna L, Hyman DM, Cavalli G, Janku F, Estrada-Veras J, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood. 2014;124(4):483–92.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Sohn MH, Kim MW, Kang YH, Jeong HJ. Tc-99m MDP bone and Ga-67 citrate scintigraphy of Erdheim-Chester disease in a child. Clin Nucl Med. 2006;31(2):90–2.PubMedCrossRefGoogle Scholar
  11. 11.
    Joo CU, Go YS, Kim IH, Kim CS, Lee SY. Erdheim-Chester disease in a child with MR imaging showing regression of marrow changes. Skelet Radiol. 2005;34(5):299–302.CrossRefGoogle Scholar
  12. 12.
    Tran TA, Pariente D, Lecron JC, Delwail A, Taoufik Y, Meinzer U. Treatment of pediatric Erdheim-Chester disease with interleukin-1-targeting drugs. Arthritis Rheum. 2011;63(12):4031–2.PubMedCrossRefGoogle Scholar
  13. 13.
    Song SY, Lee SW, Ryu KH, Sung SH. Erdheim-Chester disease with multisystem involvement in a 4-year-old. Pediatr Radiol. 2012;42(5):632–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Tran TA, Fabre M, Pariente D, Craiu I, Haroche J, Charlotte F, et al. Erdheim-Chester disease in childhood: a challenging diagnosis and treatment. J Pediatr Hematol Oncol. 2009;31(10):782–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Clerico A, Ragni G, Cappelli C, Schiavetti A, Gonfiantini M, Uccini S. Erdheim-Chester disease in a child. Med Pediatr Oncol. 2003;41(6):575–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Alimohamadi M, Hartmann C, Paterno V, Samii M. Erdheim-Chester disease mimicking an intracranial trigeminal schwannoma: case report. J Neurosurg Pediatr. 2015;15(5):493–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Kim S, Lee M, Shin HJ, Lee J, Suh YL. Coexistence of intracranial Langerhans cell histiocytosis and Erdheim-Chester disease in a pediatric patient: a case report. Childs Nerv Syst (ChNS: Official Journal of the International Society for Pediatric Neurosurgery). 2016;32(5):893–6.CrossRefGoogle Scholar
  18. 18.
    Krishna VV, James TE, Chang KT, Yen SS. Erdheim-Chester disease with rare radiological features in a 14-year old girl with pre-B acute lymphocytic leukemia and diabetes mellitus. J Radiol Case Rep. 2014;8(8):7–15.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Haroche J, Arnaud L, Cohen-Aubart F, Hervier B, Charlotte F, Emile JF, et al. Erdheim-Chester disease. Rheum Dis Clin N Am. 2013;39(2):299–311.CrossRefGoogle Scholar
  20. 20.
    Furmanczyk PS, Bruckner JD, Gillespy T 3rd, Rubin BP. An unusual case of Erdheim-Chester disease with features of Langerhans cell histiocytosis. Skelet Radiol. 2007;36(9):885–9.CrossRefGoogle Scholar
  21. 21.
    Tsai JW, Tsou JH, Hung LY, Wu HB, Chang KC. Combined Erdheim-Chester disease and Langerhans cell histiocytosis of skin are both monoclonal: a rare case with human androgen-receptor gene analysis. J Am Acad Dermatol. 2010;63(2):284–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Naruse H, Shoda H, Okamoto A, Oka T, Yamamoto K. A case of Osteoarthropathy due to Erdheim-Chester disease with overlapping Langerhans' cell infiltration. Intern Med. 2010;49(12):1225–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Caoduro C, Ungureanu CM, Rudenko B, Angoue O, Blagosklonov O, Paycha F, et al. 18F-fluoride PET/CT aspect of an unusual case of Erdheim-Chester disease with histologic features of Langerhans cell histiocytosis. Clin Nucl Med. 2013;38(7):541–2.PubMedCrossRefGoogle Scholar
  24. 24.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: WHO Press; 2008.Google Scholar
  25. 25.
    Durham BH, Diamond EL, Abdel-Wahab O. Histiocytic neoplasms in the era of personalized genomic medicine. Curr Opin Hematol. 2016;23(4):416–25.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Diamond EL, Abdel-Wahab O, Pentsova E, Borsu L, Chiu A, Teruya-Feldstein J, et al. Detection of an NRAS mutation in Erdheim-Chester disease. Blood. 2013;122(6):1089–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Aitken SJ, Presneau N, Tirabosco R, Amary MF, O’Donnell P, Flanagan AM. An NRAS mutation in a case of Erdheim-Chester disease. Histopathology. 2015;66(2):316–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Emile JF, Diamond EL, Helias-Rodzewicz Z, Cohen-Aubart F, Charlotte F, Hyman DM, et al. Recurrent RAS and PIK3CA mutations in Erdheim-Chester disease. Blood. 2014;124(19):3016–9.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Gianfreda D, Nicastro M, Galetti M, Alberici F, Corradi D, Becchi G, et al. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood. 2015;126(10):1163–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Hyman DM, Diamond EL, Vibat CR, Hassaine L, Poole JC, Patel M, et al. Prospective blinded study of BRAFV600E mutation detection in cell-free DNA of patients with systemic histiocytic disorders. Cancer Discov. 2015;5(1):64–71.PubMedCrossRefGoogle Scholar
  31. 31.
    Diamond EL, Abdel-Wahab O, Durham BH, Dogan A, Ozkaya N, Brody L, et al. Anakinra as efficacious therapy for two cases of intracranial Erdheim-Chester disease. Blood. 2016;128:1896–8.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Nelson DS, Quispel W, Badalian-Very G, van Halteren AG, van den Bos C, Bovee JV, et al. Somatic activating ARAF mutations in Langerhans cell histiocytosis. Blood. 2014;123(20):3152–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Takeuchi K, Choi YL, Togashi Y, Soda M, Hatano S, Inamura K, et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clin Cancer Res. 2009;15(9):3143–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Takeuchi T, Sato M, Sonomura T, Itakura T. Erdheim-Chester disease associated with intramedullary spinal cord lesion. Br J Radiol. 2012;85(1011):e62–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Mano H. ALKoma: a cancer subtype with a shared target. Cancer Discov. 2012;2(6):495–502.PubMedCrossRefGoogle Scholar
  36. 36.
    Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I, et al. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun. 2014;5:3116.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Berres ML, Merad M, Allen CE. Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to Histiocytosis X? Br J Haematol. 2015;169(1):3–13.PubMedCrossRefGoogle Scholar
  38. 38.
    Badalian-Very G. A common progenitor cell in LCH and ECD. Blood. 2014;124(7):991–2.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Allen CE, Parsons DW. Biological and clinical significance of somatic mutations in Langerhans cell histiocytosis and related histiocytic neoplastic disorders. Hematology Am Soc Hematol Educ Program. 2015;2015:559–64.PubMedGoogle Scholar
  40. 40.
    Collin M, Bigley V, McClain KL, Allen CE. Cell(s) of origin of langerhans cell histiocytosis. Hematol Oncol Clin North Am. 2015;29(5):825–38.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Allen CE, Li L, Peters TL, Leung HC, Yu A, Man TK, et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol. 2010;184(8):4557–67.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Berres ML, Lim KP, Peters T, Price J, Takizawa H, Salmon H, et al. BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med. 2014;211:669–83.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Chakraborty R, Hampton OA, Shen X, Simko SJ, Shih A, Abhyankar H, et al. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis. Blood. 2014;124(19):3007–15.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Hervier B, Haroche J, Arnaud L, Charlotte F, Donadieu J, Neel A, et al. Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation. Blood. 2014;124(7):1119–26.PubMedCrossRefGoogle Scholar
  45. 45.
    Haroche J, Abla O. Uncommon histiocytic disorders: Rosai-Dorfman, juvenile xanthogranuloma, and Erdheim-Chester disease. Hematology Am Soc Hematol Educ Program. 2015;2015:571–8.PubMedGoogle Scholar
  46. 46.
    Breuil V, Brocq O, Pellegrino C, Grimaud A, Euller-Ziegler L. Erdheim-Chester disease: typical radiological bone features for a rare xanthogranulomatosis. Ann Rheum Dis. 2002;61(3):199–200.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Garcia-Gomez FJ, Acevedo-Banez I, Martinez-Castillo R, Tirado-Hospital JL, Cuenca-Cuenca JI, Pachon-Garrudo VM, et al. The role of 18FDG, 18FDOPA PET/CT and 99mTc bone scintigraphy imaging in Erdheim-Chester disease. Eur J Radiol. 2015;84(8):1586–92.PubMedCrossRefGoogle Scholar
  48. 48.
    Garcia-Gomez FJ, Cambil-Molina T, Rios-Martin JJ, de la Riva-Perez PA, Calvo-Moron C, Castro-Montano J. Bone scintigraphy as cornerstone in the diagnosis of Erdheim-Chester disease. Rev Esp Med Nucl Imagen Mol. 2016;35(3):193–6.PubMedGoogle Scholar
  49. 49.
    Gotthardt M, Welcke U, Brandt D, Tontsch D, Barth PJ, Schaefer J, et al. The role of bone scintigraphy in patients with Erdheim-Chester disease. Clin Nucl Med. 2000;25(6):414–20.PubMedCrossRefGoogle Scholar
  50. 50.
    Wilejto M, Abla O. Langerhans cell histiocytosis and Erdheim-Chester disease. Curr Opin Rheumatol. 2012;24(1):90–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Allmendinger AM, Krauthamer AV, Spektor V, Aziz MS, Zablow B. Atypical spine involvement of Erdheim-Chester disease in an elderly male. J Neurosurg Spine. 2010;12(3):257–60.PubMedCrossRefGoogle Scholar
  52. 52.
    Caglar E, Aktas E, Aribas BK, Sahin B, Terzi A. Erdheim-Chester disease in thoracic spine: a rare case of compression fracture. Spine J (Official Journal of the North American Spine Society). 2016;16(4):e257–8.CrossRefGoogle Scholar
  53. 53.
    Klieger MR, Schultz E, Elkowitz DE, Arlen M, Hajdu SI. Erdheim-Chester disease: a unique presentation with multiple osteolytic lesions of the spine and pelvis that spared the appendicular skeleton. AJR Am J Roentgenol. 2002;178(2):429–32.PubMedCrossRefGoogle Scholar
  54. 54.
    Nagatsuka H, Han PP, Taguchi K, Tsujigiwa H, Gunduz M, Fukunaga J, et al. Erdheim-Chester disease in a child presenting with multiple jaw lesions. J oral Pathol Med (Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology). 2005;34(7):420–2.CrossRefGoogle Scholar
  55. 55.
    Petrikowski CG, McGaw WT. Erdheim-Chester disease of the jaws: literature review and case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90(3):389–98.PubMedCrossRefGoogle Scholar
  56. 56.
    Valdez IH, Katz RW, Travis WD. Premature alveolar bone loss in Erdheim-Chester disease. Oral Surg Oral Med Oral Pathol. 1990;70(3):294–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Blomstrand L, Thor A, Hagberg H. Erdheim-Chester disease presenting as periodontal disease: experience of treatment with cladribine, interferon-a, local radiotherapy and anakinra. Acta Oncol. 2016;55(2):248–50.PubMedCrossRefGoogle Scholar
  58. 58.
    Fink MG, Levinson DJ, Brown NL, Sreekanth S, Sobel GW. Erdheim-Chester disease. Case report with autopsy findings. Arch Pathol Lab Med. 1991;115(6):619–23.PubMedGoogle Scholar
  59. 59.
    Loeffler AG, Memoli VA. Myocardial involvement in Erdheim-Chester disease. Arch Pathol Lab Med. 2004;128(6):682–5.PubMedGoogle Scholar
  60. 60.
    Serratrice J, Granel B, De Roux C, Pellissier JF, Swiader L, Bartoli JM, et al. “Coated aorta”: a new sign of Erdheim-Chester disease. J Rheumatol. 2000;27(6):1550–3.PubMedGoogle Scholar
  61. 61.
    Rodriguez Sanchez D, Saura Espin D, Bas BA. Erdheim-Chester syndrome with Periaortitis. Revista espanola de cardiologia. 2016;69(1):72.PubMedCrossRefGoogle Scholar
  62. 62.
    Windisch C, Petersen I, Schulz B, Winkens T, Lopatta E, Oelzner P, et al. Erdheim-Chester disease with vascular involvement mimics large vessel vasculitis. Postgrad Med J. 2016;92:687–8.CrossRefGoogle Scholar
  63. 63.
    Raptis DA, Raptis CA, Jokerst C, Bhalla S. Erdheim-Chester disease with interatrial septum involvement. J Thorac Imaging. 2012;27(5):W105–7.PubMedCrossRefGoogle Scholar
  64. 64.
    de Miguel CJ, Aguilera Del Hoyo LF, Garcia Del Salto L, Cueva Perez E, Casado Cerrada J, Nieto Llanos S, et al. Case 224: cardiac involvement in Erdheim-Chester disease. Radiology. 2015;277(3):916–21.CrossRefGoogle Scholar
  65. 65.
    Arnaud L, Hervier B, Neel A, Hamidou MA, Kahn JE, Wechsler B, et al. CNS involvement and treatment with interferon- are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients. Blood. 2011;117(10):2778–82.PubMedCrossRefGoogle Scholar
  66. 66.
    Hwang BY, Liu A, Kern J, Goodwin CR, Wolinsky JP, Desai A. Epidural spinal involvement of Erdheim-Chester disease causing myelopathy. J Clin Neurosci (Official Journal of the Neurosurgical Society of Australasia). 2015;22(9):1532–6.CrossRefGoogle Scholar
  67. 67.
    Albayram S, Kizilkilic O, Zulfikar Z, Islak C, Kocer N. Spinal dural involvement in Erdheim-Chester disease: MRI findings. Neuroradiology. 2002;44(12):1004–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Querat C, Thai-Van H, Durand DV, Cotton F, Gallego S, Truy E. Hearing rehabilitation with a binaural cochlear implant in a patient with Erdheim-Chester disease. Cochlear Implants Int. 2015;16(5):295–300.PubMedCrossRefGoogle Scholar
  69. 69.
    Pego-Reigosa R, Branas-Fernandez F, Martinez-Vazquez F, Rivas-Bande MJ, Sanjuanbenito L, Garcia-Villanueva M, et al. Erdheim-Chester disease with spinal cord manifestations. Eur Neurol. 2000;43(4):242–4.PubMedCrossRefGoogle Scholar
  70. 70.
    Lalitha P, Reddy M, Reddy KJ. Extensive intracranial juvenile xanthogranulomas. AJNR Am J Neuroradiol. 2011;32(7):E132–3.PubMedCrossRefGoogle Scholar
  71. 71.
    Sagnier S, Debruxelles S, Lepreux S, Sibon I. Erdheim-Chester disease: an unusual cause of intracranial Vasculitis and progressive leukoencephalopathy. J stroke Cerebrovasc Dis (The Official Journal of National Stroke Association). 2016;25(5):e63–5.CrossRefGoogle Scholar
  72. 72.
    Grois N, Fahrner B, Arceci RJ, Henter JI, McClain K, Lassmann H, et al. Central nervous system disease in Langerhans cell histiocytosis. J Pediatr. 2010;156(6):873–81, 81 e1.Google Scholar
  73. 73.
    Diamond EL. Diffuse reduction of cerebral grey matter volumes in Erdheim-Chester disease. Orphanet J Rare Dis. 2016;11(1):109.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Merritt H, Pfeiffer ML, Richani K, Phillips ME. Erdheim-Chester disease with orbital involvement: case report and ophthalmic literature review. Orbit. 2016;35(4):221–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Karcioglu ZA, Sharara N, Boles TL, Nasr AM. Orbital xanthogranuloma: clinical and morphologic features in eight patients. Ophthal Plast Reconstr Surg. 2003;19(5):372–81.PubMedCrossRefGoogle Scholar
  76. 76.
    Abdellatief A, Mason CM, Ytterberg SR, Boorjian SA, Salomao DR, Pulido J. Choroidal involvement in Erdheim-Chester disease. Ophthalmic Surg Lasers Imaging Retina. 2015;46(6):674–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Courtillot C, Laugier Robiolle S, Cohen Aubart F, Leban M, Renard-Penna R, Drier A, et al. Endocrine manifestations in a monocentric cohort of 64 patients with Erdheim-Chester disease. J Clin Endocrinol Metab. 2016;101(1):305–13.PubMedCrossRefGoogle Scholar
  78. 78.
    Sedrak P, Ketonen L, Hou P, Guha-Thakurta N, Williams MD, Kurzrock R, et al. Erdheim-Chester disease of the central nervous system: new manifestations of a rare disease. Am J Neuroradiol. 2011;32(11):2126–31.PubMedCrossRefGoogle Scholar
  79. 79.
    Mukherjee A, Dhull VS, Karunanithi S, Sharma P, Durgapal P, Kumar R. Pineal gland involvement in Erdheim-Chester disease detected on (18)F-FDG PET-CT imaging: a case report and review of literature. Clin Imaging. 2014;38(3):367–71.PubMedCrossRefGoogle Scholar
  80. 80.
    Yelfimov DA, Lightner DJ, Tollefson MK. Urologic manifestations of Erdheim-Chester disease. Urology. 2014;84(1):218–21.PubMedCrossRefGoogle Scholar
  81. 81.
    Chasset F, Barete S, Charlotte F, Cohen-Aubart F, Arnaud L, Le Pelletier F, et al. Cutaneous manifestations of Erdheim-Chester disease (ECD): clinical, pathological, and molecular features in a monocentric series of 40 patients. J Am Acad Dermatol. 2016;74(3):513–20.PubMedCrossRefGoogle Scholar
  82. 82.
    Caputo R, Marzano AV, Passoni E, Berti E. Unusual variants of non-Langerhans cell histiocytoses. J Am Acad Dermatol. 2007;57(6):1031–45.PubMedCrossRefGoogle Scholar
  83. 83.
    Barnes PJ, Foyle A, Hache KA, Langley RG, Burrell S, Juskevicius R. Erdheim-Chester disease of the breast: a case report and review of the literature. Breast J. 2005;11(6):462–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Provenzano E, Barter SJ, Wright PA, Forouhi P, Allibone R, Ellis IO. Erdheim-chester disease presenting as bilateral clinically malignant breast masses. Am J Surg Pathol. 2010;34(4):584–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Ferrozzi F, Bova D, Tognini G, Zuccoli G. Pseudotumoral bilateral involvement of the breast in Erdheim-Chester disease: CT appearance. J Comput Assist Tomogr. 2000;24(2):281–3.PubMedCrossRefGoogle Scholar
  86. 86.
    Sheu SY, Wenzel RR, Kersting C, Merten R, Otterbach F, Schmid KW. Erdheim-Chester disease: case report with multisystemic manifestations including testes, thyroid, and lymph nodes, and a review of literature. J Clin Pathol. 2004;57(11):1225–8.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Yamamoto T, Mizuno K. Erdheim-Chester disease with intramuscular lipogranuloma. Skelet Radiol. 2000;29(4):227–30.CrossRefGoogle Scholar
  88. 88.
    Taguchi S, Kishida Y, Tamura K, Nose Y, Sato T, Ishikawa A, et al. Intrapelvic bulky tumor as an unusual presentation of Erdheim-Chester disease. Internal Med (Tokyo, Japan). 2015;54(24):3241–5.CrossRefGoogle Scholar
  89. 89.
    Nadjiri J, Woertler K, Specht K, Harrasser N, Toepfer A. Erdheim-Chester disease with bilateral Achilles tendon involvement. Skelet Radiol. 2016:1–6.Google Scholar
  90. 90.
    Pan A, Doyle T, Schlup M, Lubcke R, Schultz M. Unusual manifestation of Erdheim-Chester disease. BMC Gastroenterol. 2011;11:77.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Ivan D, Neto A, Lemos L, Gupta A. Erdheim-Chester disease: a unique presentation with liver involvement and vertebral osteolytic lesions. Arch Pathol Lab Med. 2003;127(8):e337–9.PubMedGoogle Scholar
  92. 92.
    Moore FO, Berne JD, Fox AD. Mesenteric panniculitis and Erdheim-Chester disease: xanthogranulomatous diseases confused with malignancy. J Am Coll Surg. 2007;204(2):326–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Namwongprom S, Nunez R, Kim EE, Macapinlac HA. Tc-99m MDP bone scintigraphy and positron emission tomography/computed tomography (PET/CT) imaging in Erdheim-Chester disease. Clin Nucl Med. 2007;32(1):35–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Lin E. FDG PET/CT for biopsy guidance in Erdheim-Chester disease. Clin Nucl Med. 2007;32(11):860–1.PubMedCrossRefGoogle Scholar
  95. 95.
    Stenova E, Steno B, Povinec P, Ondrias F, Rampalova J. FDG-PET in the Erdheim-Chester disease: its diagnostic and follow-up role. Rheumatol Int. 2012;32(3):675–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. 2013;121(9):1495–500.PubMedCrossRefGoogle Scholar
  97. 97.
    Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Toledano D, et al. Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2015;33(5):411–8.CrossRefGoogle Scholar
  98. 98.
    Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, et al. Vemurafenib in multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015;373(8):726–36.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Cohen-Aubart F, Emile JF, Maksud P, Galanaud D, Idbaih A, Chauvet D, et al. Marked efficacy of vemurafenib in suprasellar Erdheim-Chester disease. Neurology. 2014;83(14):1294–6.PubMedCrossRefGoogle Scholar
  100. 100.
    Euskirchen P, Haroche J, Emile JF, Buchert R, Vandersee S, Meisel A. Complete remission of critical neurohistiocytosis by vemurafenib. Neurol Neuroimmunol Neuroinflamm. 2015;2(2):e78.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Franconieri F, Martin-Silva N, de Boysson H, Galateau-Salle F, Emile JF, Bienvenu B, et al. Superior efficacy and tolerance of reduced doses of vemurafenib plus anakinra in Erdheim-Chester disease: towards the paradigm of combined targeting and immune therapies. Acta Oncol. 2016;55(7)930–2.Google Scholar
  102. 102.
    Tzoulis C, Schwarzlmuller T, Gjerde IO, Softeland E, Neckelmann G, Biermann M, et al. Excellent response of intramedullary Erdheim-Chester disease to vemurafenib: a case report. BMC Res Notes. 2015;8:171.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Borys D, Nystrom L, Song A, Lomasney LM. Erdheim Chester disease with appendicular skeletal, renal and pleural involvement responding to Zelboraf (BRAF inhibitor) treatment: case report. Skelet Radiol. 2016;45(10):1397–402.CrossRefGoogle Scholar
  104. 104.
    Braiteh F, Boxrud C, Esmaeli B, Kurzrock R. Successful treatment of Erdheim-Chester disease, a non-Langerhans-cell histiocytosis, with interferon-alpha. Blood. 2005;106(9):2992–4.PubMedCrossRefGoogle Scholar
  105. 105.
    Suzuki HI, Hosoya N, Miyagawa K, Ota S, Nakashima H, Makita N, et al. Erdheim-Chester disease: multisystem involvement and management with interferon-alpha. Leuk Res. 2010;34(1):e21–4.PubMedCrossRefGoogle Scholar
  106. 106.
    Haroche J, Amoura Z, Trad SG, Wechsler B, Cluzel P, Grenier PA, et al. Variability in the efficacy of interferon-alpha in Erdheim-Chester disease by patient and site of involvement: results in eight patients. Arthritis Rheum. 2006;54(10):3330–6.PubMedCrossRefGoogle Scholar
  107. 107.
    Hervier B, Arnaud L, Charlotte F, Wechsler B, Piette JC, Amoura Z, et al. Treatment of Erdheim-Chester disease with long-term high-dose interferon-alpha. Semin Arthritis Rheum. 2012;41(6):907–13.PubMedCrossRefGoogle Scholar
  108. 108.
    Esmaeli B, Ahmadi A, Tang R, Schiffman J, Kurzrock R. Interferon therapy for orbital infiltration secondary to Erdheim-Chester disease. Am J Ophthalmol. 2001;132(6):945–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Arnaud L, Hervier B, Neel A, Hamidou MA, Kahn JE, Wechsler B, et al. CNS involvement and treatment with interferon-alpha are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients. Blood. 2011;117(10):2778–82.PubMedCrossRefGoogle Scholar
  110. 110.
    Aouba A, Georgin-Lavialle S, Pagnoux C, Martin Silva N, Renand A, Galateau-Salle F, et al. Rationale and efficacy of interleukin-1 targeting in Erdheim-Chester disease. Blood. 2010;116(20):4070–6.PubMedCrossRefGoogle Scholar
  111. 111.
    Aubert O, Aouba A, Deshayes S, Georgin-Lavialle S, Rieu P, Hermine O. Favorable radiological outcome of skeletal Erdheim-Chester disease involvement with anakinra. Joint Bone Spine. 2013;80(2):206–7.PubMedCrossRefGoogle Scholar
  112. 112.
    Darstein F, Kirschey S, Heckl S, Rahman F, Schwarting A, Schuchmann M, et al. Successful treatment of Erdheim-Chester disease with combination of interleukin-1-targeting drugs and high-dose glucocorticoids. Intern Med J. 2014;44(1):90–2.PubMedCrossRefGoogle Scholar
  113. 113.
    Sevcikova S, Kubiczkova L, Sedlarikova L, Rihova L, Kryukov F, Szturz P, et al. Impact of anakinra treatment on cytokine and lymphocytes/ monocytes profile of an Erdheim-Chester patient. Klin Onkol. 2014;27(4):276–82.PubMedCrossRefGoogle Scholar
  114. 114.
    Podesta MA, Graziani G, Reggiani F, Buemi M, Badalamenti S, Ponticelli C. Improvement of Erdheim-Chester disease-related renal failure after treatment with anakinra. Kidney Res Clin Pract. 2014;33(3):165–7.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Courcoul A, Vignot E, Chapurlat R. Successful treatment of Erdheim-Chester disease by interleukin-1 receptor antagonist protein. Joint Bone Spine. 2014;81(2):175–7.PubMedCrossRefGoogle Scholar
  116. 116.
    Killu AM, Liang JJ, Jaffe AS. Erdheim-Chester disease with cardiac involvement successfully treated with anakinra. Int J Cardiol. 2013;167(5):e115–7.PubMedCrossRefGoogle Scholar
  117. 117.
    Cohen-Aubart F, Maksud P, Saadoun D, Drier A, Charlotte F, Cluzel P, et al. Variability in the efficacy of the IL1 receptor antagonist anakinra for treating Erdheim-Chester disease. Blood. 2016;127(11):1509–12.PubMedCrossRefGoogle Scholar
  118. 118.
    Haroche J, Amoura Z, Charlotte F, Salvatierra J, Wechsler B, Graux C, et al. Imatinib mesylate for platelet-derived growth factor receptor-beta-positive Erdheim-Chester histiocytosis. Blood. 2008;111(11):5413–5.PubMedCrossRefGoogle Scholar
  119. 119.
    Janku F, Amin HM, Yang D, Garrido-Laguna I, Trent JC, Kurzrock R. Response of histiocytoses to imatinib mesylate: fire to ashes. J Clin Oncol. 2010;28(31):e633–6.PubMedCrossRefGoogle Scholar
  120. 120.
    Dagna L, Corti A, Langheim S, Guglielmi B, De Cobelli F, Doglioni C, et al. Tumor necrosis factor alpha as a master regulator of inflammation in Erdheim-Chester disease: rationale for the treatment of patients with infliximab. J Clin Oncol (Official Journal of the American Society of Clinical Oncology). 2012;30(28):e286–90.CrossRefGoogle Scholar
  121. 121.
    Ferrero E, Belloni D, Corti A, Doglioni C, Dagna L, Ferrarini M. TNF-alpha in Erdheim-Chester disease pericardial effusion promotes endothelial leakage in vitro and is neutralized by infliximab. Rheumatology. 2014;53(1):198–200.Google Scholar
  122. 122.
    Ferrantini M, Capone I, Belardelli F. Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use. Biochimie. 2007;89(6–7):884–93.PubMedCrossRefGoogle Scholar
  123. 123.
    Tran TA, Pariente D, Guitton C, Delwail A, Barat-Houari M, Meinzer U. Treatment of Erdheim-Chester disease with canakinumab. Rheumatology. 2014;53(12):2312–4.PubMedCrossRefGoogle Scholar
  124. 124.
    Jendro MC, Zeidler H, Rosenthal H, Haller H, Schwarz A. Improvement of Erdheim-Chester disease in two patients by sequential treatment with vinblastine and mycophenolate mofetil. Clin Rheumatol. 2004;23(1):52–6.PubMedCrossRefGoogle Scholar
  125. 125.
    Broccoli A, Stefoni V, Faccioli L, Agostinelli C, Spinardi L, Pastore Trossello M, et al. Bilateral orbital Erdheim-Chester disease treated with 12 weekly administrations of VNCOP-B chemotherapy: a case report and a review of literature. Rheumatol Int. 2012;32(7):2209–13.PubMedCrossRefGoogle Scholar
  126. 126.
    Boissel N, Wechsler B, Leblond V. Treatment of refractory Erdheim-Chester disease with double autologous hematopoietic stem-cell transplantation. Ann Intern Med. 2001;135(9):844–5.PubMedCrossRefGoogle Scholar
  127. 127.
    Bourke SC, Nicholson AG, Gibson GJ. Erdheim-Chester disease: pulmonary infiltration responding to cyclophosphamide and prednisolone. Thorax. 2003;58(11):1004–5.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Yano S, Kobayashi K, Kato K, Tokuda Y, Ikeda T, Takeyama H. A case of Erdheim-Chester disease effectively treated by cyclophosphamide and prednisolone. Nihon Kokyuki Gakkai Zasshi. 2007;45(1):43–8.PubMedGoogle Scholar
  129. 129.
    Gaspar N, Boudou P, Haroche J, Wechsler B, Van Den Neste E, Hoang-Xuan K, et al. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement. Haematologica. 2006;91(8):1121–5.PubMedGoogle Scholar
  130. 130.
    Ho P, Smith C. High-dose methotrexate for the treatment of relapsed central nervous system erdheim-chester disease. Case Rep Hematol. 2014;53(1):198–200.Google Scholar
  131. 131.
    Jeon IS, Lee SS, Lee MK. Chemotherapy and interferon-alpha treatment of Erdheim-Chester disease. Pediatr Blood Cancer. 2010;55(4):745–7.PubMedCrossRefGoogle Scholar
  132. 132.
    Myra C, Sloper L, Tighe PJ, McIntosh RS, Stevens SE, Gregson RH, et al. Treatment of Erdheim-Chester disease with cladribine: a rational approach. Br J Ophthalmol. 2004;88(6):844–7.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Adam Z, Sprlakova A, Rehak Z, Koukalova R, Szturz P, Krejci M, et al. Partial regression of CNS lesions of Erdheim-Chester disease after treatment with 2-chlorodeoxadenosine and their full remission following treatment with lenalidomide. Klin Onkol. 2011;24(5):367–81.PubMedGoogle Scholar
  134. 134.
    Azadeh N, Tazelaar HD, Gotway MB, Mookadam F, Fonseca R. Erdheim Chester disease treated successfully with cladribine. Respiratory Med Case Rep. 2016;18:37–40.CrossRefGoogle Scholar
  135. 135.
    Mascalchi M, Nencini P, Nistri M, Sarti C, Santoni R. Failure of radiation therapy for brain involvement in Erdheim Chester disease. J Neuro-Oncol. 2002;59(2):169–72.CrossRefGoogle Scholar
  136. 136.
    Miller RC, Villà S, Kamer S, Pasquier D, Poortmans P, Micke O, et al. Palliative treatment of Erdheim–Chester disease with radiotherapy: a rare cancer network study. Radiother Oncol. 2006;80(3):323–6.PubMedCrossRefGoogle Scholar
  137. 137.
    Haroche J, Amoura Z. mTOR: a new target in Erdheim-Chester disease? Blood. 2015;126(10):1151–2.PubMedCrossRefGoogle Scholar
  138. 138.
    Callahan MK, Rampal R, Harding JJ, Klimek VM, Chung YR, Merghoub T, et al. Progression of RAS-mutant leukemia during RAF inhibitor treatment. N Engl J Med. 2012;367(24):2316–21.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Montella L, Insabato L, Palmieri G. Imatinib mesylate for cerebral Langerhans'-cell histiocytosis. N Engl J Med. 2004;351(10):1034–5.PubMedCrossRefGoogle Scholar
  140. 140.
    Utikal J, Ugurel S, Kurzen H, Erben P, Reiter A, Hochhaus A, et al. Imatinib as a treatment option for systemic non-Langerhans cell histiocytoses. Arch Dermatol. 2007;143(6):736–40.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of NeurologyMemorial Sloan Kettering Cancer CenterNew YorkUSA

Personalised recommendations