Genomic Alterations in Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by inflammatory lesions with clonal histiocytes. LCH is driven by activating mitogen-activated protein kinase (MAPK) pathway mutations. BRAF^V600E is the most common mutation and is associated with more extensive disease at presentation and risks of front-line treatment failure, liver disease, and LCH-associated neurodegeneration. Genetic ancestry influences LCH with highest incidence in Hispanic populations. MAPK inhibitors are effective, but do not achieve cure in most cases. Clinical trials prospectively testing risk-stratification based on somatic mutation and/or detectable mutation in peripheral blood may improve outcomes for LCH patients.