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 (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.

Emperipolesis and S100 expression may be seen in cutaneous xanthogranulomas: A multi‐institutional observation

“…Cutaneous RDD varies in clinical presentation, but has been described as a combination of multiple papules, plaques, nodules or pustules with red, violaceous or brown skin discoloration, most commonly presenting on the torso and face. 6,16 All of our cases were clinically described as a solitary dome-shaped nodule or papule, without accompanying lymphadenopathy or other systemic manifestations, lending further credence to the diagnosis of XG.…”

“…Scattered multinucleate cells and Touton‐like cells have also been reported in RDD; however, it is unclear what percentage of infiltrate these cells comprised . RDD traditionally consists of large polygonal histiocytes with pale cytoplasm, large vesicular nuclei, and prominent nucleoli in the context of a dense dermal lympho‐plasmacytic infiltrate (Figure A‐C) . Cutaneous RDD is also often accompanied by abundant plasma cells (near 100%), vascular proliferation (90%) and stromal fibrosis (48%).…”

“…In addition to the subtle histologic differences between cutaneous RDD and XG, clinical findings can help solidify the diagnosis. XG typically presents in young children and occasionally adults, while cutaneous RDD usually presents in the fourth to fifth decade of life in a predominantly female, Asian population . XG can present as solitary or multiple tan to yellow/orange/red papules.…”

“…and prominent nucleoli in the context of a dense dermal lymphoplasmacytic infiltrate ( Figure 3A-C). 16 Cutaneous RDD is also often accompanied by abundant plasma cells (near 100%), vascular proliferation (90%) and stromal fibrosis (48%). None of these features were observed in our cases.…”

“…XG typically presents in young children and occasionally adults, while cutaneous RDD usually presents in the fourth to fifth decade of life in a predominantly female, Asian population. 16,26 XG can present as solitary or multiple tan to yellow/orange/red papules. Cutaneous RDD varies in clinical presentation, but has been described as a combination of multiple papules, plaques, nodules or pustules with red, violaceous or brown skin discoloration, most commonly presenting on the torso and face.…”