• Kazushige UchidaEmail author
  • Kazuichi Okazaki


Lymphadenopathy is well known as a common extrapancreatic lesion in type 1 autoimmune pancreatitis (AIP). Generally, steroid therapy is effective similar to type 1 AIP. Lymphadenopathy appears synchronously or metachronously with type 1 AIP. IgG4-related lymphadenopathy may sometimes mimic or be misdiagnosed as lymphoma, multicentric Castleman disease, or disseminated malignancy (e.g., pancreatic cancer). In IgG4-related lymphadenopathy, five histological patterns are recognized: type I, multicentric Castleman disease-like; type II, follicular hyperplasia; type III, interfollicular expansion; type IV, progressive transformation of germinal center; and type V, nodal inflammatory pseudotumor-like. Generally, IgG4-related disease (RD) (especially type 1 AIP) appears to have 3 major histopathological features, including (1) dense lymphoplasmacytic infiltrate, (2) storiform fibrosis, and (3) obliterative phlebitis. On the other hand, IgG4-related lymphadenopathy showed no unique histological features. Fibrosis is only seen in inflammatory pseudotumor-like type. However, IgG4-RD still remains unclear. Further studies are needed to clarify the pathogenesis of lymphadenopathy, including the role of IgG4.


Autoimmune Pancreatitis Obliterative Phlebitis Extrapancreatic Lesion Multicentric Castleman Disease Polyclonal Hypergammaglobulinemia 
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  1. 1.
    Sarles H, Sarles JC, Muratore R, et al. Chronic inflammatory sclerosis of the pancreas–an autonomous pancreatic disease? Am J Dig Dis. 1961;6:688–98.PubMedCrossRefGoogle Scholar
  2. 2.
    Kawaguchi K, Koike M, Tsuruta K, et al. Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol. 1991;22:387–95.PubMedCrossRefGoogle Scholar
  3. 3.
    Yoshida K, Toki F, Takeuchi T, et al. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci. 1995;40:1561–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Ito T, Nakano I, Koyanagi S, et al. Autoimmune pancreatitis as a new clinical entity. Three cases of autoimmune pancreatitis with effective steroid therapy. Dig Dis Sci. 1997;42:1458–68.PubMedCrossRefGoogle Scholar
  6. 6.
    Horiuchi A, Kawa S, Akamatsu T, et al. Characteristic pancreatic duct appearance in autoimmune chronic pancreatitis: a case report and review of the Japanese literature. Am J Gastroenterol. 1998;93:260–3.PubMedCrossRefGoogle Scholar
  7. 7.
    Uchida K, Okazaki K, Konishi Y, et al. Clinical analysis of autoimmune-related pancreatitis. Am J Gastroenterol. 2000;95:2788–94.PubMedCrossRefGoogle Scholar
  8. 8.
    Okazaki K, Uchida K, Chiba T. Recent concept of autoimmune-related pancreatitis. J Gastroenterol. 2001;36:293–302.PubMedCrossRefGoogle Scholar
  9. 9.
    Kamisawa T, Funata N, Hayashi Y, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38:982–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Zamboni G, Luttges J, Capelli P, et al. Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens. Virchows Arch. 2004;445:552–63.PubMedCrossRefGoogle Scholar
  11. 11.
    Notohara K, Burgart LJ, Yadav D, et al. Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. Am J Surg Pathol. 2003;27:1119–27.PubMedCrossRefGoogle Scholar
  12. 12.
    Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40:352–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Hart PA, Kamisawa T, Brugge WR, et al. Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis. Gut. 2013;62:1771–6.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Kamisawa T, Funata N, Hayashi Y, et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut. 2003;52:683–7.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Mori S, Tokuda H, Sakai F, et al. Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan. Mod Rheumatol. 2012;22:727–37.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Erkelens GW, Vleggaar FP, Lesterhuis W, et al. Sclerosing pancreato-cholangitis responsive to steroid therapy. Lancet. 1999;354:43–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Nakazawa T, Ohara H, Yamada T, et al. Atypical primary sclerosing cholangitis cases associated with unusual pancreatitis. Hepatogastroenterology. 2001;48:625–30.PubMedGoogle Scholar
  18. 18.
    Hamano H, Kawa S, Ochi Y, et al. Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet. 2002;359:1403–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Saeki T, Nishi S, Imai N, et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010;78:1016–23.PubMedCrossRefGoogle Scholar
  20. 20.
    Takeda S, Haratake J, Kasai T, et al. IgG4-associated idiopathic tubulointerstitial nephritis complicating autoimmune pancreatitis. Nephrol Dial Transplant. 2004;19:474–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Uchiyama-Tanaka Y, Mori Y, Kimura T, et al. Acute tubulointerstitial nephritis associated with autoimmune-related pancreatitis. Am J Kidney Dis. 2004;43:e18–25.PubMedCrossRefGoogle Scholar
  22. 22.
    Shimatsu A, Oki Y, Fujisawa I, et al. Pituitary and stalk lesions (infundibulo-hypophysitis) associated with immunoglobulin G4-related systemic disease: an emerging clinical entity. Endocr J. 2009;56:1033–41.PubMedCrossRefGoogle Scholar
  23. 23.
    Li Y, Nishihara E, Hirokawa M, et al. Distinct clinical, serological, and sonographic characteristics of Hashimoto’s thyroiditis based with and without IgG4-positive plasma cells. J Clin Endocrinol Metab. 2010;95:1309–17.PubMedCrossRefGoogle Scholar
  24. 24.
    Komatsu K, Hamano H, Ochi Y, et al. High prevalence of hypothyroidism in patients with autoimmune pancreatitis. Dig Dis Sci. 2005;50:1052–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Yoshimura Y, Takeda S, Ieki Y, et al. IgG4-associated prostatitis complicating autoimmune pancreatitis. Intern Med. 2006;45:897–901.PubMedCrossRefGoogle Scholar
  26. 26.
    Kasashima S, Zen Y, Kawashima A, et al. A clinicopathologic study of immunoglobulin G4-related sclerosing disease of the thoracic aorta. J Vasc Surg. 2010;52:1587–95.PubMedCrossRefGoogle Scholar
  27. 27.
    Kamisawa T, Chari ST, Giday SA, et al. Clinical profile of autoimmune pancreatitis and its histological subtypes: an international multicenter survey. Pancreas. 2011;40:809–14.PubMedCrossRefGoogle Scholar
  28. 28.
    Okazaki K, Uchida K, Fukui T. Recent advances in autoimmune pancreatitis: concept, diagnosis, and pathogenesis. J Gastroenterol. 2008;43:409–18.PubMedCrossRefGoogle Scholar
  29. 29.
    Vlachou PA, Khalili K, Jang HJ, et al. IgG4-related sclerosing disease: autoimmune pancreatitis and extrapancreatic manifestations. Radiographics. 2011;31:1379–402.PubMedCrossRefGoogle Scholar
  30. 30.
    Hamano H, Arakura N, Muraki T, et al. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41:1197–205.PubMedCrossRefGoogle Scholar
  31. 31.
    Cheuk W, Yuen HK, Chu SY, et al. Lymphadenopathy of IgG4-related sclerosing disease. Am J Surg Pathol. 2008;32:671–81.PubMedCrossRefGoogle Scholar
  32. 32.
    Sato Y, Kojima M, Takata K, et al. Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman’s disease. Mod Pathol. 2009;22:589–99.PubMedCrossRefGoogle Scholar
  33. 33.
    Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21–30.PubMedCrossRefGoogle Scholar
  34. 34.
    Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92.PubMedCrossRefGoogle Scholar
  35. 35.
    Grimm KE, Barry TS, Chizhevsky V, et al. Histopathological findings in 29 lymph node biopsies with increased IgG4 plasma cells. Mod Pathol. 2012;25:480–91.PubMedCrossRefGoogle Scholar
  36. 36.
    Sato Y, Notohara K, Kojima M, et al. IgG4-related disease: historical overview and pathology of hematological disorders. Pathol Int. 2010;60:247–58.PubMedCrossRefGoogle Scholar
  37. 37.
    Sato Y, Yoshino T. IgG4-Related Lymphadenopathy. Int J Rheumatol. 2012;2012:572539.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Cheuk W, Chan JK. Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity. Semin Diagn Pathol. 2012;29:226–34.PubMedCrossRefGoogle Scholar
  39. 39.
    Peterson BA, Frizzera G. Multicentric Castleman’s disease. Semin Oncol. 1993;20:636–47.PubMedGoogle Scholar
  40. 40.
    Sato Y, Kojima M, Takata K, et al. Multicentric Castleman’s disease with abundant IgG4-positive cells: a clinical and pathological analysis of six cases. J Clin Pathol. 2010;63:1084–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Koo CH, Nathwani BN, Winberg CD, et al. Atypical lymphoplasmacytic and immunoblastic proliferation in lymph nodes of patients with autoimmune disease (autoimmune disease- associated lymphadenopathy). Medicine (Baltimore). 1984;63:274–90.Google Scholar
  42. 42.
    Segal GH, Clough JD, Tubbs RR. Autoimmune and iatrogenic causes of lymphadenopathy. Semin Oncol. 1993;20:611–26.PubMedGoogle Scholar
  43. 43.
    Kojima M, Nakamura S, Shimizu K, et al. Clinical implication of idiopathic plasmacytic lymphadenopathy with polyclonal hypergammaglobulinemia: a report of 16 cases. Int J Surg Pathol. 2004;12:25–30.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Division of Gastroenterology and Hepatology, The Third Department of Internal MedicineKansai Medical UniversityOsakaJapan

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