Answer: Pulmonary Alveolar Proteinosis

Histology: Characteristic microscopic features of pulmonary alveolar proteinosis are alveoli filled with a finely granular acellular eosinophilic material. This material is strongly PAS positive and is diastase resistant. Foamy macrophages and cholesterol clefts are often found within the granular material. The alveolar walls are usually unremarkable. By electron microscopy the alveolar deposit consists of numerous osmiophilic bodies. In those instances where alveolar proteinosis is a manifestation of pneumoconiosis, refractile crystaline material may be present in the pulmonary interstitium.

Discussion: Alveolar proteinosis (lipoproteinosis) can be divided into primary and secondary forms. The secondary forms of alveolar proteinosis include a variety of different injuries or insults to the lung. Acute silicosis related to a high concentration of inhaled particles may produce a lipoproteinosis pattern. Other patients with “secondary” lipoproteinosis have leukemia, lymphoma or other diseases characterized by immunosuppression. Yet additional patients have had unusual pulmonary infections including nocardia, fungi and mycobacteria. In children the lipoproteinosis pattern should raise the question of inherited deficiency of surfactant protein B. The differential diagnosis of lipoproteinosis includes pneumocystis pneumonia and pulmonary edema. The granular intra-alveolar material in alveolar proteinosis is unlike the bubbly or amorphous frothy material seen in pneumocystis infection. Furthermore, pulmonary edema fluid has a less granular appearance and is only weakly PAS positive. Obstructive lipoid pneumonia would have an alveolar infiltrate of multinucleate and foamy macrophages.