Pulmonary Alveolar Proteinosis Workup
- Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...
Serologic studies are generally not useful for pulmonary alveolar proteinosis (PAP). Flexible bronchoscopy with bronchoalveolar lavage (BAL) remains the criterion standard. Elevated levels of the proteins SP-A and SP-D in serum and BAL fluid may be useful. Elevated titer of neutralizing autoantibody against GM-CSF (immunoglobulin G [IgG] isotype) in serum and BAL fluid may be useful. Recent studies have proposed that deficiency of GM-CSF causes pulmonary alveolar proteinosis (PAP); all patients studied had the antibody to GM-CSF.[11, 12] Serum lactate dehydrogenase (LDH) level is usually elevated, but this finding is nonspecific.
Recent studies have shown a correlation between the levels of some tumor markers such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) and severity of PAP.
The diagnosis can be made by BAL only if PAS staining is requested. Therefore, PAP is probably underdiagnosed.
Lung biopsy findings are classic for PAP. Alveoli are filled with nonfoamy material. Transbronchial biopsies are adequate, and open lung biopsy is not required.
Chest radiography in pulmonary alveolar proteinosis (PAP) shows bilateral perihilar infiltrates with consolidation in a "bat-wing" configuration, which may mimic pulmonary edema, although with a typical absence of cardiomegaly or pleural effusion. Unilateral involvement occurs occasionally, and lymphadenopathy is rarely present. Typically, changes progress over weeks to months into a diffuse reticulogranular pattern.
High-resolution computed tomography (HRCT) scan of the chest demonstrates areas of patchy ground-glass opacification with smooth interlobular septal thickening and intralobular interstitial thickening, which produces a polygonal pattern referred to as "crazy paving." The crazy-paving pattern also can be observed in exogenous lipoid pneumonia, sarcoidosis, mucinous bronchoalveolar cell carcinoma, and acute respiratory distress syndrome (ARDS).[14, 15] PAP may also present as ground-glass opacity (GGO), mimicking carcinoma. HRCT findings have been able to show several distinctive differences between exogenous lipoid pneumonia and PAP, which had previously only been distinguished pathologically.
Bronchoscopy with transbronchial biopsy and BAL may be helpful. Transbronchial biopsies of affected lung segments, coupled with findings on BAL, are sufficient to make the diagnosis. Use PAS reagent for BAL. Bronchoalveolar lavage fluid appears "milky." Papanicolaou staining may reveal green and orange globules that are diagnostic for PAP. Electron microscopy of BAL may reveal characteristic multilamellar structures.
Transbronchial biopsy may increase the yield. Surgical lung biopsy rarely is necessary for definitive diagnosis.
Light microscopy of the lung parenchymal tissue shows alveoli filled with a granular PAS base-reactive and diastase-resistant eosinophilic material. Electron microscopy of the material in the alveoli shows multilamellated structures and membranous vesicles.
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