Pulmonary alveolar proteinosis: a spectrum of cytologic, histochemical, and ultrastructural findings in bronchoalveolar lavage fluid

Pulmonary alveolar proteinosis (PAP) is defined as abundant extracellular proteinaceous periodic acid-Schiff (PAS)-positive material which represents surfactant distending alveolar spaces. While this lesion is defined by histologic findings, there are characteristic radiologic features and cytologic findings in bronchoalveolar lavage (BAL) specimens that together may provide a confident diagnosis. The BAL specimens from all patients for which a diagnosis of PAP was made or suggested on either cytologic or biopsy specimens at University of North Carolina Hospitals from 1990-1999 were reviewed. There were 23 cytologic specimens from 11 patients. Patient ages ranged from 6 wk to 76 yr. All 23 specimens had slides prepared for Papanicolaou stain, 22 specimens (all patients) had Diff-Quik stains, 10 specimens (6 patients) had PAS stains, and 8 specimens (5 patients) had lipid stains. Nine patients had lung biopsies in addition to cytologic specimens. The clinical charts of all patients were reviewed. Twenty-one cytologic specimens were described as cloudy or milky, and 2 were bloody. By chart review and/or biopsy results, 8 patients were felt to have definite PAP. The initial lavage specimens from 6 of these patients showed classic cytologic findings of PAP, consisting of paucicellular specimens dominated by adundant extracellular granular to globular material which was basophilic on Diff-Quik stain, pale to focally eosinophilic on Pap stain, and PAS-positive, diastase-resistant. Five of these patients had biopsies; 3 showed PAP, and 2 were insufficient. Later BAL specimens after therapeutic lavage from these patients were often less characteristic, with scant extracellular material present. The other 2 patients with PAP clinically and by biopsy had atypical cytologic findings, with one showing numerous macrophages with scant PAS-positive material and abundant lipid mimicking lipid pneumonia, and one showing moderate eosinophils in addition to the extracellular proteinacous material. The remaining 3 patients were felt not to have PAP clinically or by biopsy (1 lymphocytic interstitial pneumonitis, 1 rheumatoid lung, and 1 hemosiderosis), and their BAL specimens predominantly contained macrophages with rare proteinaceous extracellular globules. Electron microscopy was performed in 5 patients (4 considered to have PAP, and 1 with lymphocytic interstitial pneumonitis) and in all cases showed whorled myelin figures characteristic of surfactant. The PAP cases and the non-PAP case had identical ultrastructural findings. We conclude that BAL specimens with classic cytologic features and supporting clinical and radiographic evidence may be diagnosed as PAP. Atypical specimens should be approached with caution, and may represent either PAP or other pulmonary diseases with secondary accumulation of surfactant. Cytology specimens taken subsequent to therapeutic lavage from PAP patients may also not be diagnostic.