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Surgical Pathology Criteria
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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

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]
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