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International Journal of Hepatology
Volume 2014 (2014), Article ID 803876, 8 pages
Review Article

Cholangiocarcinoma with respect to IgG4 Reaction

1Department of Human Pathology, Kanazawa University School of Medicine, Kanazawa 920-8640, Japan
2Department of Pathology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan

Received 4 February 2014; Revised 25 May 2014; Accepted 26 June 2014; Published 15 July 2014

Academic Editor: Valérie Paradis

Copyright © 2014 Kenichi Harada and Yasuni Nakanuma. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.