%0 Journal Article
%T Cholangiocarcinoma with respect to IgG4 Reaction
%A Kenichi Harada
%A Yasuni Nakanuma
%J International Journal of Hepatology
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/803876
%X IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer are often accompanied by significant IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10-producing cells that directly induce IgG4 reactions. Moreover, IgG4-related disease is a high-risk factor for cancer development; IgG4-related sclerosing cholangitis (IgG4-SC) cases associated with cholangiocarcinoma or its precursor lesion biliary intraepithelial neoplasia (BilIN) have been reported. IgG4-positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from cholangiocarcinoma remains important. 1. Introduction Inflammatory biliary diseases with periductal fibrosis are categorized as sclerosing cholangitis. In addition to the prototype of sclerosing cholangitis, primary sclerosing cholangitis (PSC), IgG4-related sclerosing cholangitis (IgG4-SC) is categorized as sclerosing cholangitis. Although IgG4-SC is characterized by the infiltration of numerous IgG4-positive cells in the wall of bile ducts, this IgG4 reaction is also found in PSC, hepatolithiasis, and cholangiocarcinoma. In particular, the differentiation between IgG4-SC and cholangiocarcinoma is an important clinical issue. Moreover, carcinogenesis in IgG4-related diseases has been noted [1] and a few cholangiocarcinoma cases arising from IgG4-SC have also been reported [2, 3]. In this review, we focus on the IgG4 reaction in cholangiocarcinoma and the pathological IgG4-SC-induced carcinogenic features of cholangiocarcinoma. 2. IgG4-Related Diseases and Clinicopathological Issues IgG4 is a minor immunoglobulin subtype that does not activate complement and comprises only 3¨C6% of all circulating IgG in adults [4]. Elevated serum IgG4 levels and abundant IgG4-positive plasma cell infiltration in affected organs mark IgG4-related diseases [4¨C6]. The physiological and pathological significance of IgG4 remains unknown in
%U http://www.hindawi.com/journals/ijh/2014/803876/