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These findings have raised the possibility of treatment with targeted therapies several trials of BRAF and MEK inhibitors are open for adults and children with LCH. The same BRAF V600E mutation has been found in many cancers however, V600E-mutated BRAF is also present in benign nevi, possibly indicating the need for additional mutations for malignant transformation. However, some controversy remains as to whether it is a true malignancy or a neoplasm with varying clinical behavior. LCH is now considered a myeloid neoplasm. This shows that multisystem LCH arises from a somatic mutation within a marrow or circulating precursor cell, while localized disease arises from the mutation occurring in a precursor cell at the local site. Studies have also demonstrated that the BRAF V600E mutation can be identified in mononuclear cells in peripheral blood and cell-free DNA, usually in patients with disseminated disease. In accordance with these findings, the pathologic histiocyte or LCH cell has a gene expression profile closely resembling that of a myeloid dendritic cell. LCH cells, known for many years to be a clonal proliferation, have now been shown to likely derive from a myeloid precursor whose proliferation is uniformly associated with activation of the MAPK/ERK signaling pathway. The term LCH cells is used because there are clear morphologic, phenotypic, and gene expression differences between normal Langerhans cells of the epidermis (LCs) and the pathologic variant of the LCH lesions (LCH cells), despite the pathologic histiocyte having the identical immunophenotypic characteristics of normal epidermal LCs, including the presence of Birbeck granules identified by electron microscopy. LCH results from the clonal proliferation of immunophenotypically and functionally immature, morphologically rounded LCH cells found in relevant lesions along with eosinophils, macrophages, lymphocytes, and, occasionally, multinucleated giant cells. The histiocytic diseases have been reclassified into five categories, with LCH in the L group. Only Langerhans cell histiocytosis (LCH), a myeloid-derived dendritic cell disorder, is discussed in detail in this summary. The histiocytic diseases in children and adults are caused by an abnormal accumulation of cells of the mononuclear phagocytic system. General Information About Langerhans Cell Histiocytosis (LCH)