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;
Université Pierre & Marie Curie Université Paris 06, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Département d'Anatomopathologie, Paris, France;
Blood. 2014 Aug 14;124(7):1119-26. doi: 10.1182/blood-2013-12-543793. Epub 2014 Jun 3.
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.
组织细胞增生症是一组异质性疾病，主要包括朗格汉斯细胞组织细胞增生症（LCH）和非 LCH。LCH 与非 LCH 的关联是罕见的。我们报告了 23 例经活检证实的 LCH 合并 Erdheim-Chester 病（ECD）（混合性组织细胞增生症）的患者，并讨论了这种关联的意义。我们比较了这些患者的临床表型与 56 例孤立性 LCH 患者和 53 例孤立性 ECD 患者的表型。诊断时的平均年龄为 43 岁。ECD 先于（n=12）或与（n=11）LCH 同时发生，但从未先于 LCH 发生。尽管表现多样，但混合性组织细胞增生症患者的表型更接近孤立性 ECD，而不是孤立性 LCH（主成分分析）。只有 50%的患者（16 例中的 8 例）对干扰素 alpha-2a 治疗有反应，LCH 和 ECD 均得到改善。我们在 16 例 LCH 病变中的 11 例（69%）和 11 例 ECD 病变中的 9 例（82%）中发现了 BRAF(V600E)突变。8 例患者的 ECD 和 LCH 活检均有突变。我们的发现表明 LCH 和 ECD 的关联并非偶然，并提示这些疾病之间存在 BRAF(V600E)突变的关联。
