Histopathology of pulmonary alveolar proteinosis spontaneously occurring in aged KK mice

Histopathological findings of pulmonary alveolar proteinosis occurring spontaneously in aged KK mice (72 weeks of age) were described. The lung tissues examined were obtained from the mice used for a one-year toxicity study of some oral hypoglycemic drugs, but there was no relationship between the incidence of the disease and the drug treatment. The disease occurred in 67 of 319 males (21.0%) and 124 of 284 females (43.7%). The gross lesions of the lungs were solitary or multiple nodules. Microscopically, the lesions developed in the peribronchial areas and were well-circumscribed. The initial lesions consisted of the aggregation of foamy cells in the alveoli. In the advanced lesions, amorphous substance resulting from destructed foamy cells and proteinous material accumulated in the alveoli. In the more advanced lesions, neutrophils and nuclear fragments were contained in the proteinous material and some of the alveolar walls were thickened with cell infiltration, fibrosis and so-called epithelialization. The etiology of the present condition was unknown.