Overview
The Disease Pattern
Pulmonary Langerhans cell histiocytosis (PLCH) is a clonal proliferation of abnormal myeloid dendritic cells in the lung.
Pulmonary Langerhans cell histiocytosis (PLCH) is a clonal proliferation of abnormal myeloid dendritic cells in the lung. Activating mutations in the MAPK-ERK pathway, most commonly BRAF V600E, drive the process. Cigarette smoke exposure is strongly associated with pulmonary disease and may promote the inflammatory environment in which the abnormal cells accumulate. The cells cluster around small airways and injure the bronchiolar wall and nearby alveoli. Early lesions appear as cellular nodules. As the disease progresses, nodules may cavitate, scar, and leave irregular cysts. This explains the characteristic evolution seen on high-resolution CT: centrilobular nodules followed by upper- and mid-lung cystic destruction. The clinical picture often begins in a young adult who currently smokes or has smoked in the past. A persistent dry cough, exertional dyspnea, reduced exercise tolerance, or fatigue may be present. Pulmonary function can show obstructive, restrictive, or mixed impairment. A falling diffusing capacity for carbon monoxide (DLCO) is especially useful because it can reveal worsening gas-transfer ability even before resting oxygen saturation becomes markedly abnormal. Smoking history is a diagnostic clue, not a complete explanation. The disease...