Collagen remodeling and peripheral immune cell recruitment characterizes the cutaneous Langerhans cell histiocytosis microenvironment

Abstract

Langerhans cell histiocytosis (LCH) is a rare and potentially fatal disorder of unknown etiology arising from the accumulation of epidermal Langerhans-like cells in bone, skin, or other tissues. Tissue damage and morbidity results from lesional cytokine release, and we sought to investigate the LCH microenvironment using a combination of histological stains and immunohistochemistry. CD1a immunoreactivity was used to identify lesional cells in archival paraffin-embedded samples of cutaneous LCH. A combined Orcein and Giemsa stain identified immune cells in general (particularly granulocytes and mast cells) and extracellular matrix (particularly elastic fibers), while CD3 and CD68 staining identified T cells and macrophages, respectively. Collagen synthesis was investigated with Herovici staining, which discriminates newly synthesized from mature collagen, while cross-polar microscopy of picrosirius-stained sections identified changes in matrix organization. Immune cells were consistently identified at the periphery of cutaneous LCH lesions. We quantified an increased number of thickened and disorganized elastic fibers surrounding lesions and an absence of elastic fibers within lesions. Furthermore, lesions exhibited a decrease in mature collagen fibers and a loss of supporting collagen matrix within lesions and compromised collagen integrity in adjacent tissue. Cutaneous LCH lesions are associated with the peripheral recruitment of a variety of immune cells and are consistently characterized by localized elastosis, collagen damage, and remodeling.