Pulmonary Langerhans cell histiocytosis – an update on pathogenesis and treatment

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare diffuse cystic lung disease that affects young to middle-aged smoking adults of both genders. The identification of molecular alterations in the canonical mitogen-activated protein kinase (MAPK) signalling pathway in most specific lesions has demonstrated the clonal/neoplastic nature of PLCH. We will summarize the progress made in the understanding of the pathogenesis of adult PLCH, and briefly highlight the recent findings useful for the management of the patients.The MAPK pathway is constantly activated in PLCH lesions. Apart from the BRAFV600E mutation, other driver somatic genomic alterations in this pathway (mainly MAP2K1 mutations/deletions and BRAF deletions) have been identified in the lesions, paving the way for targeted treatment. Smoking appears to promote the recruitment of MAPK-activated circulating myeloid precursors to the lung. The long-term survival of PLCH is more favourable with a 10-year survival >90%. Lung cancer and chronic respiratory failure are the main causes of death. Few patients develop severe pulmonary complications within the 5 years after diagnosis, justifying a close longitudinal follow-up of the patients.PLCH is a MAPK driven neoplasia with inflammatory properties. The place of targeted therapies in severe forms of PLCH warrants further evaluation.