Variant Pulmonary Alveolar Proteinosis: A Syndrome with Distinct Clinical and Pathologic Features.
Michiya Nishino, Eugene J Mark, Osamu Matsubara, Benjamin D Medoff, Walter J O'Donnell, Paul F Currier, Richard L Kradin. Massachusetts General Hospital, Boston; National Defense Medical College, Tokorozawa, Saitama, Japan
Background: Pulmonary alveolar proteinosis (PAP) is a rare condition in which pulmonary macrophages fail to clear surfactant from the lungs, resulting in the alveolar accumulation of lipoproteinaceous debris. The histopathology of PAP is typified by the diffuse filling of alveoli and terminal bronchioles with eosinophilic, periodic acid-Schiff (PAS)-positive acellular material. We describe distinctive morphologic variants of PAP with heterogeneous clinicopathologic features.
Design: The clinicopathologic features of five cases of lung disease with prominent lipoproteinaceous alveolar exudates resembling pulmonary alveolar proteinosis were examined by light microscopic, ultrastructural, and immunohistochemical analysis. Serum antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) were assayed in one patient.
Results: These cases of “variant proteinosis” were distinguished by an abundance of degenerating foamy alveolar macrophages, weak PAS staining of intraalveolar lipoproteinaceous material despite accumulation of surfactant apoprotein A, and a paucity of lamellated surfactant bodies by ultrastructural examination. Large, lamellated concretions of surfactant were visible by light microscopy in one case. Cholesterol crystals were frequent. Only one patient showed the computed tomography finding of mosaiform “crazy-paving”, and only this patient had the opalescent bronchoalveolar lavage fluid characteristic of alveolar proteinosis. Circulating antibodies to GM-CSF were not detected. Three patients showed either a partial or near complete resolution of disease in response to high-dose corticosteroid therapy, a treatment approach that is generally ineffective in pulmonary alveolar proteinosis. In one patient, therapeutic lung lavage based on a presumptive diagnosis of pulmonary alveolar proteinosis exacerbated respiratory distress and hypoxemia.
Conclusions: Distinguishing “variant proteinosis” from classical PAP can be clinically important. Despite the otherwise typical appearance of granular lipoproteinaceous alveolar material in lung biopsies, the presence of abundant degenerating foamy macrophages, atypical histochemical, ultrastructural, and radiographic features, and the absence of antibodies to GM-CSF suggest a steroid-responsive form of proteinosis that is likely pathogenetically distinct and may not be amenable to whole-lung lavage.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 265, Wednesday Morning