Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.
J Eur Acad Dermatol Venereol. 2018 Jun;32(6):926-934. doi: 10.1111/jdv.14794. Epub 2018 Jan 31.
Histiocytoses are rare disorders characterized by the accumulation of cells derived from macrophages, dendritic cells or monocytes in various tissues. There is a broad spectrum of disease manifestations with some subtypes commonly showing skin lesions, while in others, the skin is rarely involved. Here, we describe cutaneous manifestations of histiocytoses belonging to the Langerhans group (L group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the group of Rosai-Dorfman disease (RDD) and related histiocytoses (R group) according to the current classification. Characteristic clinical presentations noted were a rust-brown colour or xanthomatous aspect in many cases of histiocytoses. Histological criteria for differentiation are described. Immunohistochemistry shows positivity for S100 and CD1a in Langerhans-cell histiocytoses (LHCH) of the L group, while CD68 positivity with S100 and CD1a negativity are typical in histiocytoses of the C group of cutaneous and mucocutaneous histiocytoses. RDD in the R group shows positivity for S100 and CD68, while CD1a is negative. We further review the pathogenesis of LHCH based on insights on the central role of the mitogen-activated protein (MAPK) kinase pathway. Common mutations in various histiocytic populations of diverse ontogeny and at different stages of differentiation may be responsible for the diverse clinical picture of this neoplastic entity. For histiocytoses of the C group and R group, a reactive origin is discussed with the exception of the disseminated form of juvenile xanthogranuloma. We suggest exploring the role of an origin from skin residing histiocytes for the isolated cutaneous manifestation in some types. With regard to therapeutic options, skin-directed therapies are the first choice in limited disease, while systemic chemotherapy has traditionally been used in extensive disease. In Langerhans-cell histiocytoses and related entities, therapy by BRAF inhibition has led to a breakthrough especially in patients with an activation of the MAPK pathway.
组织细胞增生症是一类罕见疾病，其特征为巨噬细胞、树突状细胞或单核细胞来源的细胞在各种组织中堆积。该病临床表现广泛，某些亚型常伴有皮肤损伤，而另一些亚型皮肤受累则罕见。在此，我们根据当前分类，描述属于朗格汉斯细胞组织细胞增生症（L 组）、皮肤和黏膜组织细胞增生症（C 组）和罗道尔夫-多夫曼病（RDD）及相关组织细胞增生症（R 组）的组织细胞增生症的皮肤表现。在许多组织细胞增生症病例中，观察到典型的锈褐色或黄色瘤样外观。描述了用于鉴别诊断的组织学标准。免疫组化显示 L 组朗格汉斯细胞组织细胞增生症（LHCH）中 S100 和 CD1a 阳性，而 C 组皮肤和黏膜组织细胞增生症的组织细胞增生症中 CD68 阳性、S100 和 CD1a 阴性则具有特征性。R 组中的 RDD 显示 S100 和 CD68 阳性，而 CD1a 阴性。我们进一步基于丝裂原活化蛋白（MAPK）激酶途径的核心作用，综述了 LHCH 的发病机制。不同起源和分化阶段的各种组织细胞群体中常见的突变可能导致该肿瘤实体的不同临床表现。对于 C 组和 R 组的组织细胞增生症，除了播散性幼年黄色肉芽肿外，我们讨论了其反应性起源。我们建议探索某些类型孤立性皮肤表现的皮肤驻留组织细胞起源的作用。关于治疗选择，皮肤靶向治疗是局限性疾病的首选，而全身化疗传统上用于广泛性疾病。在朗格汉斯细胞组织细胞增生症和相关实体中，BRAF 抑制治疗取得了突破，特别是在 MAPK 途径激活的患者中。
