IgG4-Related Disease and Malignant Tumor

  • Yuichiro Senba
  • Koki Mise
  • Keiichi Sumida
  • Noriko Hayami
  • Tatsuya Suwabe
  • Yoshifumi Ubara
  • Kazuo Takeuchi


IgG4-related disease (IgG4-RD) is considered to be a benign disease responsive to glucocorticoid therapy, but recently cases complicated by malignant tumors have been described. The potential association between IgG4-RD and malignancy that is suggested by these cases has attracted growing attention. We describe a patient with mucinous cystadenocarcinoma of the appendix, during the course of which autoimmune pancreatitis developed and improved with glucocorticoid therapy. After cessation of the glucocorticoid treatment, the appendix cancer recurred, accompanied by the return of an elevated serum IgG4 concentration. The patient ultimately succumbed to the peritoneal dissemination of his appendiceal cancer. A postmortem examination revealed numerous IgG4-positive plasma cells within the kidneys, and findings consistent with IgG4-RD were also noted in the pancreas, submandibular glands, and prostate. This case and others similar to it in the literature suggest that the potential relationship between IgG4-RD and malignancy requires further investigation.


Common Bile Duct Peritoneal Dissemination Autoimmune Pancreatitis Bile Duct Wall Mucinous Cystadenocarcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Loos M, Esposito I, Hedderich DM, Ludwig L, Fingerle A, Friess H, et al. Autoimmune pancreatitis complicated by carcinoma of the pancreatobiliary system: a case report and review of the literature. Pancreas. 2011 Jan;40(1):151–4.PubMedCrossRefGoogle Scholar
  2. 2.
    Ochoa ER, Harris NL, Pilch BZ. Marginal zone B-cell lymphoma of the salivary gland arising in chronic sclerosing sialadenitis (küttner tumor). Am J Surg Pathol. 2001 Dec;25(12):1546–50.PubMedCrossRefGoogle Scholar
  3. 3.
    Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M, et al. Umehara H Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2009 Aug;68(8):1310–5. Epub 2008 Aug 13.Google Scholar
  4. 4.
    Kamisawa T, Chen PY, Tu Y, Nakajima H, Egawa N, Tsuruta K, et al. Pancreatic cancer with a high serum IgG4 concentration. World J Gastroenterol. 2006 Oct 14;12(38):6225–8.PubMedGoogle Scholar
  5. 5.
    Okazaki K, Kawa S, Kamisawa T, Naruse S, Tanaka S, Nishimori I, et al. Research committee of intractable diseases of the pancreas clinical diagnostic criteria of autoimmune pancreatitis: revised proposal. J Gastroenterol. 2006 Jul;41(7):626–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol. 2010 Dec;34(12):1812–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Yamamoto M, Takahashi H, Tabeya T, Suzuki C, Naishiro Y, Ishigami K, et al. Risk of malignancies in IgG4-related disease. Mod Rheumatol. 2012;22:414–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Shiokawa M, Kodama Y, Yoshimura K, Kawanami C, Mimura J, Yamashita Y, et al. Risk of cancer in patients with autoimmune pancreatitis. Am J Gastroenterol. 2013;108:610–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Miyoshi H, Uchida K, Taniguchi T, Yazumi S, Matsushita M, Takaoka M, et al. Circulating naïve and CD4 + CD25 high regulatory T cells in patients with autoimmune pancreatitis. Pancreas. 2008 Mar;36(2):133–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Zen Y, Fujii T, Harada K, Kawano M, Yamada K, Takahira M, et al. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology. 2007 Jun;45(6):1538–46.PubMedCrossRefGoogle Scholar
  11. 11.
    Tabata T, Hazama S, Yoshino S, Oka M. Th2 subset dominance among peripheral blood T lymphocytes in patients with digestive cancers. Am J Surg. 1999 Mar;177(3):203–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Szaflarska A, Szczepanik A, Siedlar M, Czupryna A, Sierzega M, Popiela T, et al. Preoperative plasma level of IL-10 but not of proinflammatory cytokines is an independent prognostic factor in patients with gastric cancer. Anticancer Res. 2009 Dec;29(12):5005–12.PubMedGoogle Scholar
  13. 13.
    Ichihara F, Kono K, Takahashi A, Kawaida H, Sugai H, Fujii H. Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers. Clin Cancer Res. 2003 Oct 1;9(12):4404–8.PubMedGoogle Scholar
  14. 14.
    Teng MW, Ngiow SF, von Scheidt B, McLaughlin N, Sparwasser T, Smyth MJ. Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth. Cancer Res. 2010 Oct 15;70(20):7800–9. Epub 2010 Oct 5.Google Scholar
  15. 15.
    Kamisawa T, Tsuruta K, Okamoto A, Horiguchi S, Hayashi Y, Yun X, et al. Frequent and significant K-ras mutation in the pancreas, the bile duct, and the gallbladder in autoimmune pancreatitis. Pancreas. 2009 Nov;38(8):890–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Kamisawa T, Horiguchi S, Hayashi Y, Yun X, Yamaguchi T, Tsuruta K, et al. K-ras mutation in the major duodenal papilla and gastric and colonic mucosa in patients with autoimmune pancreatitis. J Gastroenterol. 2010 Jul;45(7):771–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Granville CA, Memmott RM, Balogh A, Mariotti J, Kawabata S, Han W, et al. A central role for Foxp3+ regulatory T cells in K-Ras-driven lung tumorigenesis. PLoS One. 2009;4(3):e5061. Epub 2009 Mar 30.PubMedCrossRefGoogle Scholar
  18. 18.
    Kamisawa T, Sasaki T. IgG4-related sclerosing disease, including its relation to carcinogenesis. Gan To Kagaku Ryoho. 2011 Mar;38(3):347–52.PubMedGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Yuichiro Senba
    • 1
  • Koki Mise
    • 1
  • Keiichi Sumida
    • 1
  • Noriko Hayami
    • 1
  • Tatsuya Suwabe
    • 1
  • Yoshifumi Ubara
    • 1
  • Kazuo Takeuchi
    • 2
  1. 1.Nephrology CenterToranomon HospitalTokyoJapan
  2. 2.Gastroenterology DepartmentToranomon HospitalTokyoJapan

Personalised recommendations