Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by a clonal proliferation of specialized cells with characteristics resembling antigen-presenting cells that reside in the skin and mucosa. Its clinical presentation is variable and ranges from isolated skin or bone disease to a life-threatening multisystem condition. Historically, it has been hypothesized that the disease originated from epidermal Langerhans cells. However, new evidence supports a model in which LCH occurs as a consequence of a misguided differentiation programme of myeloid dendritic cell precursors. In LCH, there is a very high frequency of activating mutations in MAPK signaling pathway genes, most notably BRAF-V600E, as well as MAP2K1. Genetic, molecular and functional data implicate activation of the MAPK (ERK) signalling pathway at critical stages in myeloid differentiation as an essential and universal driver of LCH pathology.
Category
Cancer
Brite
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Neoplasms of haematopoietic or lymphoid tissues
2B31 Histiocytic or dendritic cell neoplasms
H01512 Langerhans cell histiocytosis
