Pulmonary Langerhans' cell histiocytosis

Pulmonary Langerhans' cell histiocytosis (PLCH) is a diffuse, smoking-related lung disease characterized pathologically by bronchiolocentric inflammation, cyst formation, widespread vascular abnormalities, and physiologically by exercise limitation. It is part of a heterogeneous group of conditions of unknown etiology characterized by an abnormal proliferation of antigen presenting cells of bone marrow derivation known as Langerhans' cells. Pulmonary involvement is not unusual in systemic forms of Langerhans' cell histiocytosis, but symptoms are rarely prominent. Localized pulmonary involvement is a rare pulmonary disease that occurs predominantly in young adults. It has several unique clinical and epidemiological features that justify its classification as a distinct clinical-pathological entity. The precise incidence and prevalence of PLCH are unknown, although studies of lung-biopsy specimens from patients with interstitial lung disease identified PLCH in only 5% of cases. Light microscopy of lung biopsy shows scattered stellate nodules that are frequently bronchiolocentric. The nodules are formed of focal collections of Langerhans' cells characterized by their morphology (nuclei with fine chromatin and grooves or folds), immunophenotype (S100 and CD1 positive) and ultrastructure (cytoplasmic Birbeck granules), interspersed with eosinophils and small lymphocytes.The infiltrate leads to progressive destruction of lung parenchyma and to the development of widespread cystic change.The pathogenesis of PLCH is not well understood but its bronchiolocentricity and tendency to regress following cessation of cigarette smoking suggests a reactive immune response in the bronchioles mediated by the Langerhans' cell, possibly through cytokine production. The outcome is highly variable, ranging from rapid spontaneous resolution to irreversible respiratory failure. Stop smoking leads to stabilization of symptoms in most patients. No treatment has been confirmed to be useful and no double-blind therapeutic trials have been reported. Lung transplantation has also been performed for treatment of PLCH but the disease may recur in the transplanted lung in up to 25% of patients.