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
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
Original posting/updates: 11/20/10
Differential Diagnosis
Pulmonary edema
Pulmonary Alveolar Proteinosis
Smooth appearing fluid
Granular fluid with clumping, clefts
Foamy macrophages not prominent
Prominent foamy macrophages
Fluid PAS/d negative
Fluid PAS/d positive
Anti-GMCSF serology negative
Anti-GMCSF serology positive
Pneumocystis Pneumonia
Pulmonary Alveolar Proteinosis
Bubbly appearing fluid
Granular fluid with clumping, clefts
Pneumocystis stains positive
Pneumocystis stains negative
Foamy macrophages not prominent
Prominent foamy macrophages
Fluid PAS/d negative
Fluid PAS/d positive
Anti-GMCSF serology negative
Anti-GMCSF serology positive
Infection may be primary or secondary
Atypical Mycobacteria Pneumonia
Pulmonary Alveolar Proteinosis
Alveolar macrophages more prominent than fluid
Prominent fluid with occasional macrophages
Mycobacterial stains positive
Mycobacterial stains negative
Anti-GMCSF serology negative
Anti-GMCSF serology positive
Infection may be primary or secondary
Classification / Lists
Idiopathic Interstitial Lung Diseases
Other Diffuse Parenchymal Lung Diseases
Bibliography
Travis WD, Colby TV, Koss MN, Rosado-de-Christenson ML, Müller NL, King TE Jr. Non-neoplastic Disorders of the Lower Respiratory Tract, AFIP Atlas of Nontumor Pathology, First Series, Fascicle 2, 2002.
Gordon IO, Cipriani N, Arif Q, Mackinnon AC, Husain AN. Update in nonneoplastic lung diseases. Arch Pathol Lab Med. 2009 Jul;133(7):1096-105.
Wang BM, Stern EJ, Schmidt RA, Pierson DJ. Diagnosing pulmonary alveolar proteinosis. A review and an update. Chest. 1997 Feb;111(2):460-6.
Huizar I, Kavuru MS. Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management. Curr Opin Pulm Med. 2009 Sep;15(5):491-8.
Suzuki T, Sakagami T, Young LR, Carey BC, Wood RE, Luisetti M, Wert SE, Rubin BK, Kevill K, Chalk C, Whitsett JA, Stevens C, Nogee LM, Campo I, Trapnell BC. Hereditary Pulmonary Alveolar Proteinosis: Pathogenesis, Presentation, Diagnosis, and Therapy. Am J Respir Crit Care Med. 2010 Jul 9. [Epub ahead of print]
