Pulmonary Alveolar Proteinosis Workup

Updated: Dec 18, 2019
  • Author: Roger B Olade, MD, MPH; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
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Workup

Laboratory Studies

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 titers of neutralizing autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) (immunoglobulin G [IgG] isotype) in serum and BAL fluid may be useful.

It has been proposed that deficiency of GM-CSF causes PAP; all patients studied had the antibody to GM-CSF. [27, 28]  Serum lactate dehydrogenase (LDH) is usually elevated, but this finding is nonspecific.

There appears to be a correlation between the levels of some tumor markers (eg, carcinoembryonic antigen [CEA], neuron-specific enolase [NSE], and squamous cell carcinoma [SCC]) and the severity of PAP. [29]

The diagnosis can be made by BAL only if periodic acid-Shiff 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.

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Imaging Studies

Chest radiography in pulmonary alveolar proteinosis (PAP) shows bilateral perihilar infiltrates [3, 4] 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) scanning of the chest demonstrates areas of patchy ground-glass opacification (GGO) 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). [30, 31] PAP presenting as ground-glass opacity (GGO) mimics carcinoma. [32] HRCT findings have been able to show several distinctive differences between exogenous lipoid pneumonia and PAP, which had previously only been distinguished pathologically. [33]

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Procedures

Bronchoscopy with transbronchial biopsy and bronchoalveolar lavage (BAL) may be helpful. Transbronchial biopsies of affected lung segments, coupled with findings on BAL, are sufficient to make the diagnosis. Use periodic acid-Shiff (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.

Pulmonary alveolar proteinosis. Cytologic appearan Pulmonary alveolar proteinosis. Cytologic appearance of intra-alveolar granular material from a bronchoalveolar lavage sample (diastase-periodic acid-Shiff [DPAS], x400).
Pulmonary alveolar proteinosis. Bronchoalveolar la Pulmonary alveolar proteinosis. Bronchoalveolar lavage sample depicting dense globules with sharp borders seen in patients with pulmonary alveolar proteinosis (PAP) (Papanicolaou, x400).
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Histologic Findings

Light microscopy of the lung parenchymal tissue shows alveoli filled with a granular periodic acid-Shiff (PAS) base-reactive and diastase-resistant eosinophilic material.

Pulmonary alveolar proteinosis. Intra-alveolar mat Pulmonary alveolar proteinosis. Intra-alveolar material is strongly periodic acid-Schiff (PAS) positive (diastase-PAS, x200).

Electron microscopy of the material in the alveoli shows multilamellated structures and membranous vesicles. Eosinophilic granular material is present within the alveolar spaces (see the following images). 

Pulmonary alveolar proteinosis. Alveoli are filled Pulmonary alveolar proteinosis. Alveoli are filled with an eosinophilic granular material. Note the preservation of the normal lung architecture (hematoxylin and eosin, x200).
Pulmonary alveolar proteinosis. High magnification Pulmonary alveolar proteinosis. High magnification illustrating the granular material and alveolar macrophages surrounded by intact alveolar septal tissue with minimal reaction (hematoxylin and eosin, x400).
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