Blood Journal
Leading the way in experimental and clinical research in hematology

Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation

  1. Baptiste Hervier1,2,3,
  2. Julien Haroche1,2,3,
  3. Laurent Arnaud1,2,3,
  4. Frédéric Charlotte2,4,
  5. Jean Donadieu5,
  6. Antoine Néel6,
  7. François Lifermann7,
  8. Carles Villabona8,
  9. Bruno Graffin9,
  10. Olivier Hermine10,
  11. Aude Rigolet1,2,
  12. Camille Roubille11,
  13. Eric Hachulla12,
  14. Thierry Carmoi13,
  15. Maud Bézier14,
  16. Véronique Meignin14,
  17. Marie Conrad15,
  18. Laurence Marie16,
  19. Elise Kostrzewa17,
  20. Jean-Marie Michot18,
  21. Stéphane Barete19,
  22. Valerie Taly20,
  23. Karine Cury19,
  24. Jean-François Emile21,22, and
  25. Zahir Amoura1,2,3,
  26. on behalf of the French Histiocytoses Study Group
  1. 1Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Service de Médecine Interne 2, Centre National de Référence des Maladies Auto-Immune et Systémiques Rares, Paris, France;
  2. 2Université Pierre & Marie Curie Université Paris 06, Paris, France;
  3. 3INSERM, Unité Mixte de Recherche-S 945, Paris, France;
  4. 4AP-HP, Hôpital Pitié-Salpêtrière, Département d’Anatomopathologie, Paris, France;
  5. 5AP-HP, Hôpital Armand Trousseau, Service d’Hématologie Pédiatrique, Centre de Référence des Histiocytoses, Paris, France;
  6. 6Hôtel Dieu, Service de Médecine Interne, Nantes, France;
  7. 7Hôpital Général de Dax, Service de Médecine Interne, Dax, France;
  8. 8Hospital de Bellvitge, Feixa Llarga s/n, Endocrinology Department, L’Hospitalet de Llobregat, Barcelona, Spain;
  9. 9Hôpital d’Instruction des Armées Legouest, Service de Médecine Interne, Metz, France;
  10. 10AP-HP, Hôpital Necker-Enfants Malades, Service d’Hématologie, Paris, France;
  11. 11Hôpital Saint-Eloi, Service de Médecine Interne, Montpellier, France;
  12. 12Centre Hospitalier Régional Universitaire, Service de Médecine Interne, Lille, France;
  13. 13Hôpital d’Instruction des Armées du Val de Grâce, Service de Médecine Interne, Paris, France;
  14. 14AP-HP, Hôpital Saint-Louis, Service de Dermatologie and Département d’Anatomopathologie, Paris, France;
  15. 15Centre Hospitalier Universitaire, Réanimation Polyvalente, Nancy, France;
  16. 16Centre Hospitalier Raincy-Montfermeil, Service de Médecine Interne, Montfermeil, France;
  17. 17Centre Hospitalier Universitaire, Service de Dermatologie, Bordeaux, France;
  18. 18AP-HP, Université Paris XI-Hôpital du Kremlin-Bicêtre, Service de Médecine Interne, Le Kremlin-Bicêtre, France;
  19. 19AP-HP, Hôpital Tenon, Service de Dermatologie, Paris, France;
  20. 20Université Paris Sorbonne Cité, INSERM UMR-S775, Centre Universitaire des Saint Pères, Paris, France;
  21. 21AP-HP, Hôpital Ambroise Paré, Département d’Anatomopathologie, Boulogne, France; and
  22. 22Université de Versailles, Versailles, France

Key Points

  • The association of both Langerhans cell histiocytosis and Erdheim-Chester disease is not exceptional.

  • This association is linked to BRAFV600E mutation.


Histiocytoses are a group of heterogeneous diseases that mostly comprise Langerhans cell histiocytosis (LCH) and non-LCH. The association of LCH with non-LCH is exceptional. We report 23 patients with biopsy-proven LCH associated with Erdheim-Chester disease (ECD) (mixed histiocytosis) and discuss the significance of this association. We compare the clinical phenotypes of these patients with those of 56 patients with isolated LCH and 53 patients with isolated ECD. The average age at diagnosis was 43 years. ECD followed (n = 12) or was diagnosed simultaneously with (n = 11) but never preceded LCH. Although heterogeneous, the phenotype of patients with mixed histiocytosis was closer to that of isolated ECD than to that of isolated LCH (principal component analysis). LCH and ECD improved in response to interferon alpha-2a treatment in only 50% of patients (8 of 16). We found the BRAFV600E mutation in 11 (69%) of 16 LCH lesions and in 9 (82%) of 11 ECD lesions. Eight patients had mutations in both ECD and LCH biopsies. Our findings indicate that the association of LCH and ECD is not fortuitous and suggest a link between these diseases involving the BRAFV600E mutation.

  • Submitted December 18, 2013.
  • Accepted May 16, 2014.
View Full Text

To view this item, select one of the options below

If you already have a subscription, you may gain access using your ASH username and password.

Sign In for Institutional Administrators

If you are a Librarian or institutional account administrator you can use this link to manage your account and view usage reports.


Purchase Short-Term Access

Pay per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00.
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

OpenAthens Users

Log in through your institution

Sign Up

Subscribe to the Journal - Subscribe to the print and/or online journal.

Access for Patients

Access for Patients - Patients desiring access should contact the journal.