Abstract
Pulmonary Langerhans cell histiocytosis (PLCH) is a diffuse cystic lung disease that
is strongly associated with exposure to cigarette smoke. Recently, activating pathogenic
mutations in the mitogen-activated protein kinase pathway have been described in the
dendritic cells in patients with PLCH and have firmly established PLCH to be an inflammatory
myeloid neoplasm. Disease course and prognosis in PLCH are highly variable among individual
patients, ranging from spontaneous resolution to development of pulmonary hypertension
and progression to terminal respiratory failure. A subset of patients with PLCH may
have extrapulmonary involvement, typically involving the skeletal system in the form
of lytic lesions, skin lesions, or the central nervous system most commonly manifesting
in the form of diabetes insipidus. Smoking cessation is the cornerstone of treatment
in patients with PLCH and can lead to disease regression or stabilization in a substantial
proportion of patients. Further insight into the underlying molecular pathogenesis
of PLCH has paved the way for the future development of disease-specific biomarkers
and targeted treatment options directed against the central disease-driving mutations.
Keywords
PLCH - pneumothorax - MAPK - BRAF - cladribine - smoking
