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

Pulmonary alveolar proteinosis (PAP) is defined as abundant extracellular p roteinaceous periodic acid-Schiff (PAS)-positive material which represents surfactant distending alveolar spaces. While this lesion is defined by hist ologic findings, there are characteristic radiologic features and cytologic findings in bronchoalveolar lavage (BAL) specimens that together may provi de a confident diagnosis. The BAL specimens fro,ll all patients for which a diagnosis of PAP was made or suggested on either cytologic or biopsy specimens at University of Nort h Carolina Hospitals from 1990-1999,were reviewed. There were 23 cytologic specimens from ii patients. Patient ages ranged from 6 wk to 76 yr: All 23 specimens had slides prepared for Papanicolaou stain, 22 specimens (all pat ients) 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 wer e 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 hav e definite PAP. The initial lavage specimens fr om 6 of these patients show ed classic cytologic findings of PAP, consisting of paucicellular specimens dominated by adundant extracellular granular to globular material which wa s 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 were insufficient. Later BAL specimens after therapeutic lavagefrom these patients were often less characteristic, with scant extra cellular material present. The other 2 patients with PAP clinically and by biopsy had atypical cytologic findings, with one showing numerous macrophag es with scant PAS-positive material and abundant lipid mimicking lipid pneu monia, and one showing moderate eosinophils in addition to the extracellula r proteinacous material. The remaining 3 patients were felt not to have PAP clinically or by biopsy (1 lymphocytic interstitial pneumonitis, 1 rheumat oid lung, and 1 hemosiderosis), and their BAL specimens predominantly conta ined macrophages with are proteinaceous extracellular globules. Electron mi croscopy was performed in 5 patients (4 considered to have PAP, and I with lymphocytic interstitial pneumonitis) and in all cases showed whorled myeli n 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 supporti ng clinical and radiographic evidence may be diagnosed as PAP. Atypical spe cimens should be approached,vith caution, and may represent either PAP or o ther pulmonary diseases with secondary accumulation of surfactant. Cytology specimens taken subsequent to therapeutic lavage from PAP patients may als o not be diagnostic. (C) 2001 Wiley-Liss, Inc.