Pulmonary Alveolar Proteinosis
Definition
- Chronic pulmonary disease characterized by filling of alveoli by eosinophilic proteinaceous fluid
Alternate/Historical Names
- Pulmonary alveolar phospholipoproteinosis
- Alveolar lipoproteinosis
Diagnostic Criteria
High Resolution Computed Tomography
- Bilateral ground glass opacities with prominent interlobular septa
- Creates “crazy paving” effect
Histopathology
- Amorphous granular eosinophilic proteinaceous fluid fills alveoli
- Fluid is PAS/d positive
- Stains positively for surfactant apoprotein
- Not widely available
- Fine to coarse granularity
- May have irregular clumps
- Cholesterol clefts and cracks common
- May involve bronchioles
- Scattered foamy macrophages
- Few neutrophils unless associated with an infection
- Patchy disease with areas of normal alveoli
- Interstitial inflammation and/or fibrosis is unusual in idiopathic disease
- Most adult cases idiopathic (90%), other causes should be ruled out:
- Infection
- Many cases may be secondary infection
- Mycobacteria, Pneumocystis, Nocardia
- Malignancy
- Most are leukemia or lymphoma
- Toxic/dust exposures
- Chemotherapy
- Silicon, aluminum, titanium etc.
- Immunosuppression
- Most pediatric cases involve genetic defects
- CSF2RA mutation leads to inadequate macrophage activation
- Surfactant protein-B or –C defects lead to dysfunctional surfactant production
- May be associated with interstitial fibrosis
- Most idiopathic cases appear to be due to deficient surfactant degradation by macrophages
- Autoantibodies against GMCSF or genetic defects in CSF2RA lead to inadequate activation of macrophages
- The linkage of known causes to this pathway is not clear
- Diagnosis is increasingly made by x-ray and serology without biopsy, requiring
- Ground glass opacity with prominent lobular septa
- Presence of anti-GMCSF antibodies
Gerald J Berry MD
Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
