Pulmonary IgG4 disease


Pulmonary IgG4 disease is a form of systemic hyper IgG4 disease.  It is frequently associated with disease in other organs.


This is a disease of adults.  There is a male predominance.

Clinical features

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.

Macroscopic appearances

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.


IgG4 plasma cell score

  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

Pulmonary Sjogren syndrome



Inflammatory myofibroblastic tumour



Extranodal marginal zone lymphoma

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


Metastatic calcification


Cytomegalovirus pneumonitis


Differential diagnosis


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.


1 Shrestha B, Sekiguchi H, Colby TV, Graziano P, Aubry MC, Smyrk TC, et al. Distinctive pulmonary histopathology with increased IgG4-positive plasma cells in patients with autoimmune pancreatitis: report of 6 and 12 cases with similar histopathology. Am J Surg Pathol. 2009 Oct;33(10):1450-62.

2 Zen Y, Inoue D, Kitao A, Onodera M, Abo H, Miyayama S, et al. IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol. 2009 Dec;33(12):1886-93.


This page last revised 27.3.2010


©SMUHT/PW Bishop