Clinical implications of oncogenic mutations in pulmonary Langerhans cell histiocytosis

Purpose of reviewLangerhans cell histiocytosis (LCH) is a neoplasm of dendritic cells with a wide clinical spectrum. Localized pulmonary LCH occurs in young adults with a history of smoking and can either resolve spontaneously or lead to progressive decline in pulmonary function. Young children can also present with localized disease - frequently bone or skin - or with multifocal or multisystem disease. Clinical outcomes in these patients also vary widely, ranging from spontaneous resolution to multiorgan failure and death. This review describes recent developments in our understanding of the underlying pathogenesis of LCH and how these discoveries and other research are affecting how the disease is classified, treated and monitored.Recent findingsSomatic mutations resulting in activation of the mitogen-activated protein kinase (MAPK) pathway were recently identified as a key pathogenetic mechanism in both pediatric and pulmonary LCH.SummaryKnowledge of underlying pathogenetic mechanisms of LCH transforming how this disease and other histocytic/dendritic disorders are classified, treated and monitored.