Histiocytosis - cutaneous manifestations of hematopoietic neoplasm and non-neoplastic histiocytic proliferations

Abstract

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 and related histiocytoses (R group) according to the current classification. Charcteristic clinical presentations noted were a rust-brown color or xanthomatous aspect in many cases of histicytoses. Histological criteria for differentiation are described. Immunohistochemistry shows positivity for S100 and CD1a in Langerhans-cell histiocytoses of the L group while CD68 positivity with S100 and CD1a negativity is typical in histiocytoses of the C-group of cutaneous and mucocutaneous histiocytoses. Rosai-Dorfman disease in the R group shows positivity for S100 and CD68 while CD1a is negative. We further review the pathogenesis of Langerhans-cell histiocytoses based on insights on the central role of the 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.

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