Lung
Noninfectious granulomatous inflammation
Granulomatosis with polyangiitis (GPA)
Author: Elliot Weisenberg, M.D.
Last author update: 1 September 2011
Last staff update: 17 April 2023 (update in progress)
Copyright: 2003-2023, PathologyOutlines.com, Inc.
PubMed search: Granulomatosis with polyangiitis [title] lung
Table of Contents
Definition / general | Terminology | Etiology | Clinical features | Laboratory | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Differential diagnosisCite this page: Weisenberg E. Granulomatosis with polyangiitis (GPA). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungnontumorgranulomatosiswithpolyangiitis.html. Accessed June 8th, 2023.
Definition / general
- Triad of necrotizing angiitis, aseptic necrosis of upper respiratory tract and lungs and focal glomerulonephritis
Terminology
- Name changed in 2011 (J Am Soc Nephrol 2011;22:587)
Etiology
- Likely a T cell mediated hypersensitivity reaction, the close relationship between c-ANCA titers suggests a pathogenic role
- c-ANCA likely directly activates neutrophils to release oxygen radicals and proteolytic enzymes damaging endothelium
Clinical features
- May also involve temporal artery, cutaneous small vessels and cause extrapulmonary masses; rarely involves eyes, skin and heart
- All ages, but most common with ages 45+; more common in males
- Rarely associated with diffuse pulmonary hemorrhage
- Should order special stains and cultures to rule out TB and fungi
- Chest Xray: waxing and waning of pulmonary infiltrates and nodules is relatively specific
- Diagnosis: biopsy of affected upper airway or skin showing inflammatory change is helpful
- Limited granulomatosis with polyangiitis : confined to lungs, no glomerulonephritis (or occurs many years later), more protracted clinical course; multiple bilateral nodules, round or infarct-like, often in lower lobes; histology similar to classic type, but must have angiitis outside of granulomas and necrotic areas for diagnosis; similar treatment
Laboratory
- c-ANCA positive in 90% with active generalized disease and 60% with limited disease
- c-ANCA positive: diffuse cytoplasmic staining directed against neutrophil serine proteinase 3; can monitor course of disease with titers, ELISA test for anti-proteinase 3 now available
- p-ANCA: perinuclear staining, directed against myeloperoxidase, is usually negative, but positive in microscopic polyarteritis, inflammatory bowel disease, crescentic glomerulonephritis; ELISA test for anti-myeloperoxidase now available
- Other causes of positive c-ANCA or p-ANCA: connective tissue disorders, chronic hypersensitivity pneumonia, postinfectious bronchitis, ulcerative colitis related lung disease, primary sclerosing cholangitis and rheumatoid arthritis (Mod Pathol 2002;15:197)
Treatment
- Cyclophosphamide, steroids and TNF-agonists
Clinical images
Contributed by Dr. Mark R. Wick
Breast mammogram
Spot film, breast
Gross description
- Well circumscribed lesion with necrotic appearance
Microscopic (histologic) description
- Liquefactive or coagulative necrosis in lungs with profuse eosinophils, multinucleated giant cells, as part of poorly formed granulomas, surrounded by pallisading histiocytes and giant cells with central necrosis
- Destructive leukocytic angiitis of arteries and veins outside of the necrotic granuloma by neutrophils, plasma cells and eosinophils
- Scanty lymphocytes and plasma cells
- Bronchial wall is rarely involved
- Fulminant subtype has predominance of exudative changes
- Fibrous scar subtype has marked collagenous stroma
- Small vessel variant involves alveolar septal capillaries instead of large arteries or veins (resembles SLE)
Microscopic (histologic) images
Contributed by Dr. Mark R. Wick
Breast
Differential diagnosis
- Fungi
- Tuberculosis
