IgG4-related Lung and Pleural Disease: A Clinicopathologic Study of 21 Cases

Abstract

Immunoglobulin G4 (IgG4)-related disorders can occur in the respiratory system. However, the clinicopathologic characteristics have not been well clarified. In this study, we examined clinical and pathologic features of, and follow-up data on, IgG4-related lung and pleural lesions. The patients group consisted of 17 males and 4 females with an average age of 69 years (range: 42 to 76). Pulmonary lesions in 16 patients and pleural lesions in 5 patients were examined. Histologically, all lesions showed diffuse lymphoplasmacytic infiltration. Irregular fibrosis and obliterative vascular changes were more common in solid areas. Nine cases (43%) had eosinophilic infiltration with more than 5 cells per high-power field. Immunostaining revealed numerous IgG4-positive plasma cells in inflamed areas. Sclerosing inflammation was distributed with intrapulmonary connective tissue. Pulmonary lesions showed a variety of morphologic changes according to the predominant area of inflammation. Serum IgG4 concentrations were elevated in 9 of 11 patients tested (average 6.9 g/L; range 0.3 to 18.0 g/L; normal range <1.35 g/L). Extra-pulmonary and extra-pleural IgG4-related lesions were identified in 9 patients (43%), and developed simultaneously or asynchronously during follow up. All patients treated with steroids responded, but some radiologic abnormalities remained in 3 patients. Interestingly, 1 patient was found to have a primary adenocarcinoma against a background of IgG4-related lung disease during follow up. In conclusion, IgG4-related diseases show a greater variety of pulmonary and pleural lesions than previously thought. It is important, therefore, to know the morphologic variety and clinicopathologic characteristics of this disorder.

A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

“…IgG4-related PD has been described as inflammatory pseudotumor, interstitial pneumonitis, organizing pneumonia, and lymphomatoid granulomatosis [48]. Most (81%) patients with IgG4-related PD have been reported to be men, with a median age at diagnosis of 69 years [48], features similar to those of IgG4RD.…”

“…Most (81%) patients with IgG4-related PD have been reported to be men, with a median age at diagnosis of 69 years [48], features similar to those of IgG4RD. Some patients present initially with respiratory symptoms, such as dry cough or dyspnea, whereas 75% of patients are asymptomatic and the disease is found incidentally by abnormal shadows on chest X-rays.…”

“…Some patients present initially with respiratory symptoms, such as dry cough or dyspnea, whereas 75% of patients are asymptomatic and the disease is found incidentally by abnormal shadows on chest X-rays. Although IgG4-related PD is associated with a variety of radiologic abnormalities [49], diffuse lymphoplasmacytic infiltration has been observed in all lesions, with irregular fibrosis and obliterative vascular changes being more common in solid areas [48]. Hilar and pancreatic accumulation of gallium-67 has been reported as characteristic of the active stage of AIP when serum IgG4 concentrations are high [50].…”

IgG4 plasma cells in inflammatory myofibroblastic tumor: inflammatory marker or pathogenic link?

“…[14][15][16][17]24 In contrast to IMT, IgG4SD is an inflammatory disorder that is accompanied by an elevated serum IgG4 and is histologically characterized by an infiltrative inflammatory fibro-sclerosing process that usually contains abundant IgG4 positive plasma cells. According to current understanding, IgG4SD affects various organs such as the lungs, liver, thyroid, pancreas, and biliary tract, and soft tissues, including the mediastinum, retroperitoneum, and orbit.…”

“…[7][8][9][10][11][12][13] IgG4-related sclerosing disease (IgG4SD) is a steroid-responsive multiorgan system disorder that encompasses a spectrum of clinical conditions, includ ing autoimmune pancreatitis, sclerosing cholangitis, chronic sclerosing sialadenitis, tubulointerstitial nephritis, cutaneous pseudolymphoma, and sclerosing processes in the lung and pleura, liver, breast, and meninges. 5,[14][15][16][17] The histological findings of fibrosis and chronic inflammation are relatively nonspecific, and there are no known unique genetic markers. A large proportion of the plasma cells in IgG4SD express IgG4 antibody, a finding that in recent literature has been the subject of interest as a pathologic discriminator for IgG4SD.…”