Smoking-related interstitial pneumonias and pulmonary Langerhans cell histiocytosis

The relationship between cigarette smoke and interstitial lung diseases (ILDs) is not clear. Respiratory bronchiolitis (RB), usually found as an incidental histologic abnormality in otherwise asymptomatic smokers, is characterized by the accumulation of cytoplasmic golden-brown-pigmented macrophages within respiratory bronchioles. A small proportion of smokers have a more exaggerated response that, in addition to the bronchiole-centered lesions, provokes interstitial and air space inflammation and fibrosis extending to the nearby alveoli. This set of histologic changes is called RBILD, and results in clinical symptoms. Desquamative interstitial pneumonia (DIP) is characterized by panlobular involvement, diffuse mild-to-moderate interstitial fibrosis, and massive alveolar filling with macrophages. It is well known that the histopathologic patterns of RB-ILD and DIP may overlap, and that the key features for differentiating these disorders are the distribution and the extent of the lesions: bronchiolocentric in RB-ILD and diffuse in DIP. It has been proposed that RB, RB-ILD, and DIP may be different components of the same histopathologic disease spectrum, representing various degrees of severity of the same process caused by chronic smoking, although this is still controversial. Pulmonary Langerhans' cell histiocytosis is also strongly related to cigarette smoking and is characterized by the proliferation of specific histiocytes, known as Langerhans' cells, and their infiltration of organ systems. Although RB, RB-ILD, DIP, and Pulmonary Langerhans' cell histiocytosis are considered as discrete entities of smokers, it is not infrequent to find a mixture of pathologic features rendering the histopathologic diagnosis difficult.