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Definition
Pulmonary IgG4 disease is a form of systemic hyper IgG4 disease. It is frequently associated with disease in other organs.
Patients may have an allergic disposition with bronchial asthma, allergic or chronic rhinitis or allergies. They may present with cough or bloody sputum. Pulmonary disease has been reported in association with autoimmune pancreatitis, sclerosing sialadenitis or retroperitoneal fibrosis. There may be associated lymphadenopathy or sclerosing sialadenitis. Serum IgG and IgG4 levels are raised. The histological subtypes listed below show no significant histological differences.
Four patterns have been described:
Pleural involvement may produce visceral or parietal nodules.
The lesions are solid gray nodules, located either peripherally or centrally in the lungs. Alveolar interstitial type produces firm lung parenchyma. Multiple round ground glass opacities are associated with ill-defined nodules up to 1.5 cm in diameter. Pleural disease is seen as pleural thickening extending into the lung parenchyma.
The IgG4/IgG plasma cell ratio is typically more than 30%, compared to less than 10% in other inflammatory conditions.
The histological appearances in the lung may resemble organising pneumonia (OP), non-specific interstitial pneumonia (NSIP), plasma cell granuloma or lymphomatoid granulomatosis. Typical features include:
Granulomata are rare and, when present, are small and vague.
Numerous plasma cells stain for IgG4, representing form 40% to 90% of IgG positive plasma cells. The are not clonal by in situ hybridisation.
0 | 1 | 2 | 3 | |||
Pulmonary disease associated with auto-immune pancreatitis | 1/61 | 5/61 | ||||
Pulmonary disease resembling that seen in association with auto-immune pancreatitis but unknown auto-immune pancreatitis status | 5/121 | 7/121 | ||||
Pulmonary disease associated with Rosai Dorfman disease | 2/81 | 1/81 | 5/81 | |||
Erdheim-Chester disease |
3/31 | |||||
Pulmonary Sjogren syndrome | 19/191 |
|||||
Inflammatory myofibroblastic tumour |
6/101 |
4/101 |
||||
Extranodal marginal zone lymphoma |
3/31 | |||||
Alveolar haemorrhage | 3/31 | |||||
Desquamative interstitial pneumonia | 2/21 | |||||
Lymphoid hyperplasia | 4/51 | 1/51 | ||||
Lymphocytic interstitial pneumonia | 1/31 | 2/31 | ||||
Non-necrotizing granulomas | 2/31 | 1/31 | ||||
Bronchiolitis / follicular bronchiolitis | 10/111 | 1/111 | ||||
Hypersensitivity pneumonitis | 7/81 | 1/81 | ||||
Usual interstitial pneumonia | 3/81 | 3/81 | 2/81 | |||
Nonspecific interstitial pneumonia |
22/291 | 4/291 | 3/291 | |||
Pleuritis, fibrinous, and fibrous |
4/51 | 1/51 | ||||
Rheumatoid arthritis nodules | 1/11 | |||||
Inflammatory myofibroblastic tumour | 4/101 | 2/101 | 1/101 | 3/101 | ||
Organising pneumonia | 10/131 | 2/131 | 1/131 | |||
Diffuse alveolar damage |
4/51 | 1/51 | ||||
Necrotizing granulomatous inflammation |
1/11 | |||||
Metastatic calcification |
1/11 | |||||
Cytomegalovirus pneumonitis |
1/11 | |||||
Rosai-Dorfman disease shows a lymphangitic distribution with emperipolesis and an increase in IgG4-positive plasma cells. There may be an overlap with hyper IgG4 disease.
Multicentric Castleman's disease: the proportion of IgG4-positive plasma cells has not been documented and raised serum IgG4 has been reported. There may be overlap cases.
NSIP: The presence of eosinophils, obliterative vascular changes and lymphoid follicles is an indication to stain for IgG4.
Inflammatory pseudotumours with numerous plasma cells positive for IgG4 are probably a manifestation of IgG4 disease. Other cases are not IgG4-related and are of fibrohistiocytic subtype
Inflammatory myofibroblastic tumour is a true neoplasm; there are fascicles of spindle cells; a case with many IgG4-psoitive plasma cells has been reported.
Many patients undergo resection on suspicion of a carcinoma. Treatment is with corticosteroids.
Unlike salivary gland and pancreatic disease, progression to lymphoma or carcinoma has not been established in the lungs.
©SMUHT/PW Bishop