title: Association of both Langerhans cell histiocytosis and Erdheim-Chester disease linked to the BRAFV600E mutation.
abstract: 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 BRAF(V600E) 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 BRAF(V600E) mutation.
authors.affiliation: Assistance 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; Université Pierre & Marie Curie Université Paris 06, Paris, France; INSERM, Unité Mixte de Recherche-S 945, Paris, France;
authors.forename: Baptiste
authors.initials: B
authors.lastname: Hervier
authors.affiliation: Assistance 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; Université Pierre & Marie Curie Université Paris 06, Paris, France; INSERM, Unité Mixte de Recherche-S 945, Paris, France;
authors.forename: Julien
authors.initials: J
authors.lastname: Haroche
authors.affiliation: Assistance 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; Université Pierre & Marie Curie Université Paris 06, Paris, France; INSERM, Unité Mixte de Recherche-S 945, Paris, France;
authors.forename: Laurent
authors.initials: L
authors.lastname: Arnaud
authors.affiliation: Université Pierre & Marie Curie Université Paris 06, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Département d'Anatomopathologie, Paris, France;
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charlotte
authors.affiliation: AP-HP, Hôpital Armand Trousseau, Service d'Hématologie Pédiatrique, Centre de Référence des Histiocytoses, Paris, France;
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.affiliation: Hôtel Dieu, Service de Médecine Interne, Nantes, France;
authors.forename: Antoine
authors.initials: A
authors.lastname: Néel
authors.affiliation: Hôpital Général de Dax, Service de Médecine Interne, Dax, France;
authors.forename: François
authors.initials: F
authors.lastname: Lifermann
authors.affiliation: Hospital de Bellvitge, Feixa Llarga s/n, Endocrinology Department, L'Hospitalet de Llobregat, Barcelona, Spain;
authors.forename: Carles
authors.initials: C
authors.lastname: Villabona
authors.affiliation: Hôpital d'Instruction des Armées Legouest, Service de Médecine Interne, Metz, France;
authors.forename: Bruno
authors.initials: B
authors.lastname: Graffin
authors.affiliation: AP-HP, Hôpital Necker-Enfants Malades, Service d'Hématologie, Paris, France;
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Assistance 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; Université Pierre & Marie Curie Université Paris 06, Paris, France;
authors.forename: Aude
authors.initials: A
authors.lastname: Rigolet
authors.affiliation: Hôpital Saint-Eloi, Service de Médecine Interne, Montpellier, France;
authors.forename: Camille
authors.initials: C
authors.lastname: Roubille
authors.affiliation: Centre Hospitalier Régional Universitaire, Service de Médecine Interne, Lille, France;
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Hôpital d'Instruction des Armées du Val de Grâce, Service de Médecine Interne, Paris, France;
authors.forename: Thierry
authors.initials: T
authors.lastname: Carmoi
authors.affiliation: AP-HP, Hôpital Saint-Louis, Service de Dermatologie and Département d'Anatomopathologie, Paris, France;
authors.forename: Maud
authors.initials: M
authors.lastname: Bézier
authors.affiliation: AP-HP, Hôpital Saint-Louis, Service de Dermatologie and Département d'Anatomopathologie, Paris, France;
authors.forename: Véronique
authors.initials: V
authors.lastname: Meignin
authors.affiliation: Centre Hospitalier Universitaire, Réanimation Polyvalente, Nancy, France;
authors.forename: Marie
authors.initials: M
authors.lastname: Conrad
authors.affiliation: Centre Hospitalier Raincy-Montfermeil, Service de Médecine Interne, Montfermeil, France;
authors.forename: Laurence
authors.initials: L
authors.lastname: Marie
authors.affiliation: Centre Hospitalier Universitaire, Service de Dermatologie, Bordeaux, France;
authors.forename: Elise
authors.initials: E
authors.lastname: Kostrzewa
authors.affiliation: AP-HP, Université Paris XI-Hôpital du Kremlin-Bicêtre, Service de Médecine Interne, Le Kremlin-Bicêtre, France;
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Michot
authors.affiliation: AP-HP, Hôpital Tenon, Service de Dermatologie, Paris, France;
authors.forename: Stéphane
authors.initials: S
authors.lastname: Barete
authors.affiliation: Université Paris Sorbonne Cité, INSERM UMR-S775, Centre Universitaire des Saint Pères, Paris, France;
authors.forename: Valerie
authors.initials: V
authors.lastname: Taly
authors.affiliation: AP-HP, Hôpital Tenon, Service de Dermatologie, Paris, France;
authors.forename: Karine
authors.initials: K
authors.lastname: Cury
authors.affiliation: AP-HP, Hôpital Ambroise Paré, Département d'Anatomopathologie, Boulogne, France; and Université de Versailles, Versailles, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.affiliation: Assistance 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; Université Pierre & Marie Curie Université Paris 06, Paris, France; INSERM, Unité Mixte de Recherche-S 945, Paris, France;
authors.forename: Zahir
authors.initials: Z
authors.lastname: Amoura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D031249:Erdheim-Chester Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf