Bronchoalveolar lavage cytology in pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is an uncommon disease in which alveoli are progressively filled with surfactant-related material. Although a definitive diagnosis is usually made by an open lung biopsy, bronchoalveolar lavage (BAL) cytology may play a decisive role in the clinical work-up of these patients, and, in some cases, may spare a patient a more invasive diagnostic procedure. The authors present three patients in whom BAL cytology specimens contained the characteristic (although not specific) globules of amorphous proteinaceous PAS-positive material accompanied by only rare background macrophages and inflammatory cells. The patients include a 40-year-old man with an 8-year history of fever of unknown origin, a 30-year-old man with a chronic nonproductive cough, and a 6-year-old boy diagnosed at 5 months of age with osteopetrosis and hypogammaglobulinemia who subsequently developed a disseminated Mycobacterium avium-intracellulare infection. All specimens stained with Gomori methenamine silver (3) and Ziehl-Neelsen (2) were negative for microbial organisms, Ultrastructural examination of two specimens revealed the characteristic lamellar structures of surfactant, increasing diagnostic specificity. Lung biopsies and/or autopsy subsequently confirmed the diagnosis in all three cases. The characteristic cytologic and ultrastructural features of PAP in BAL specimens are presented along with the morphologic differential features of other entities which potentially could be confused with PAP.