Pulmonary alveolar proteinosis is a rare lesion characterized by accumulation of a granular eosinophilic material in the alveoli. It can be seen as a primary “idiopathic” disease or associated with other conditions, such as infections, massive inhalation of inorganic dusts, malignancy, immune deficiency, lysinuric protein intolerance, and in lung transplants. Overproduction of surfactant by type 2 pneumocytes, or its impaired clearance by alveolar macrophages, have been proposed as mechanisms for this entity. Microscopic examination reveals that the alveoli and alveolar ducts are occupied by an eosinophilic material with a superficial resemblance to pulmonary edema; however, the material seen in proteinosis is finely granular, is periodic acid—Schiff (PAS) positive, and contains occasional cholesterol crystals and foamy macrophages.

Differential diagnosis includes pulmonary edema, Pneumocystis carinii pneumonia, and alveolar mucinosis. Pulmonary edema is generally homogeneous and lacks the granularity, cholesterol clefts, and foamy macrophages seen in proteinosis. The intra-alveolar eosinophilic material seen in Pneumocystis pneumonia is foamy and corresponds to the cysts of the microorganism. The diagnosis can sometimes be made by bronchoalveolar lavage (BAL). Examination of sputum may suggest the diagnosis by identification of PAS-positive macrophages.