IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases

Institute of Liver Studies, King's College Hospital, London, UK.
The American journal of surgical pathology (Impact Factor: 4.59). 10/2009; 33(12):1886-93. DOI: 10.1097/PAS.0b013e3181bd535b
Source: PubMed

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.

  • Source
    • "Inflammatory aneurysms (IAAA) represent a subgroup of aortic aneurysms of controversial etiology and account for 5% -10% of all cases of AAA. IgG4-related systemic disease (IgG4-RSD) is a disease of unknown pathogenesis and is characterised by high serum IgG4 concentrations , sclerosing inflammation with numerous IgG4- positive plasmacytes, responsiveness to steroid therapy and occurrence (synchronous or metachronous) in multiple organs such as the pancreas [1], hepatobiliary tract [2], Salivary gland [3], lung, retroperitoneum [4] and others. IgG4-RSD usually affects middle-aged and "
    [Show abstract] [Hide abstract]
    ABSTRACT: This report describes a case of a 66-year-old male patient with accidental diagnosis of chronic contained rupture of an aortic aneurysm. Surgery was performed through a median laparotomy. A thick periaortic tissue with fibrosis and lym-phnodes covered the AAA. Immunohistochemical examination of the aneurismatic aortic wall revealed intense positi-vity for inflammatory markers and a large number of immunoglobulin G4 (IgG4) positive cells. The postoperative course was uneventful and patient was discharged in the fifth postoperative day. Patient was then followed periodically at the outpatient rheumatologic clinic. No adverse events occurred during 3 and 6 months follow up. Conclusion: Iden-tification of IgG4-inflammatory aneurysms as an expression of the IgG4-related systemic disease is essential both for clinical follow up and surgical and pharmacological treatment considering the possibility of aneurysm rupture and the involvement of other organs.
    The Journal of cardiovascular surgery 07/2013; 334025(04):126-128. DOI:10.4236/wjcs.2013.34025 · 1.37 Impact Factor
  • Source
    • "Masaki et al. [10] (2009) IgG4-associated disease Geyer et al. [11] (2010) diffuse/focal organ enlargement, with mass-forming or nodular/thickened lesions in various organs, including the central nervous system [26], lachrymal/salivary glands [10] [23], thyroid gland [27] [28], lungs [29], pancreas [30] [31], biliary duct [32], liver [33], gastrointestinal tract [34] [35], kidneys [36], prostate gland [37], retroperitoneum [38], skin [39], lymph nodes [5] [40] [41], and artery [42] [43]. These conditions are quite similar to multifocal idiopathic fibrosclerosis (MIF) [44]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team) and the other from lymph proliferation (Umehara team) supported by the "Research Program for Intractable Disease" of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as "IgG4-RD" and proposed the comprehensive diagnostic criteria (CDC) for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP), compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease) and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.
    International Journal of Rheumatology 05/2012; 2012(11):357071. DOI:10.1155/2012/357071
  • Source
    • "IgG4-related disease is a unique systemic inflammatory condition characterized by tumorous swelling of affected organs and high-serum IgG4 concentrations [1] [2] [3]. Autoimmune pancreatitis is a prototype of IgG4 disease as Hamano et al. described in a landmark paper in 2001 [4]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: IgG4 cholangiopathy can involve any level of the biliary tree which exhibits sclerosing cholangitis or pseudotumorous hilar lesions. Most cases are associated with autoimmune pancreatitis, an important diagnostic clue. Without autoimmune pancreatitis, however, the diagnosis of IgG4-cholangiopathy is challenging. Indeed such cases have been treated surgically. IgG4-cholangiopathy should be diagnosed based on serological examinations including serum IgG4 concentrations, radiological features, and histological evidence of IgG4(+) plasma cell infiltration. Steroid therapy is very effective even at disease relapse. A Th2-dominant immune response or the activation of regulatory T cells seems to be involved in the underlying immune reaction. It is still unknown why IgG4 levels are specifically elevated in patients with this disease. IgG4 might be secondarily overexpressed by Th2 or regulatory cytokines given the lack of evidence that IgG4 is an autoantibody.
    01/2012; 2012(2090-3448):472376. DOI:10.1155/2012/472376
Show more