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IgG4-Related Disease: Pathological Features and Differential Diagnosis

Chapter

Abstract

The broad recognition of IgG4-related disease has led to a consensus statement regarding its pathology. This widely accepted multi-organ condition must be diagnosed based on morphological features and immunohistochemical findings. The changes that occur are basically similar in any organ manifestation, with several site-specific findings being recognized. This newly formed systemic condition has a broad range of differential diagnoses, including multicentric Castleman’s disease, granulomatosis with polyangiitis, and malignant lymphoma, for which tissue examinations play a critical role. Since the demand to diagnose this condition by biopsy is increasing, more knowledge and experience need to be accumulated on this approach. Two aspects need to be considered when collecting biopsy samples from patients with suspected IgG4-related disease; one is to obtain additional evidence to support the diagnosis, while the other is to exclude the possibility of this condition. Unlike other inflammatory conditions, which are difficult to rule out using small tissue samples, IgG4-related disease may be excluded on the basis of biopsy findings because there are known histological findings (e.g., necrosis, granuloma, and abscess) that are unlikely to be found in this condition and strongly suggest other diagnoses. Although follow-up biopsies are currently not required, on-treatment biopsies may contribute to a clinical decision being reached, particularly in terms of steroid withdrawal.

Keywords

IgG4 Pathology Sialadenitis Pancreatitis Cholangitis 

References

  1. 1.
    Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539–51.CrossRefPubMedGoogle Scholar
  2. 2.
    Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015;385:1460–71.CrossRefPubMedGoogle Scholar
  3. 3.
    Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Shimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40:352–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Irie H, Honda H, Baba S, Kuroiwa T, Yoshimitsu K, Tajima T, et al. Autoimmune pancreatitis: CT and MR characteristics. AJR Am J Roentgenol. 1998;170:1323–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Sahani DV, Kalva SP, Farrell J, Maher MM, Saini S, Mueller PR, et al. Autoimmune pancreatitis: imaging features. Radiology. 2004;233:345–52.CrossRefPubMedGoogle Scholar
  7. 7.
    Inoue D, Yoshida K, Yoneda N, Ozaki K, Matsubara T, Nagai K, et al. IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 2015;94:e680.CrossRefGoogle Scholar
  8. 8.
    Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92.CrossRefPubMedGoogle Scholar
  9. 9.
    Zen Y, Quaglia A, Portmann B. Immunoglobulin G4-positive plasma cell infiltration in explanted livers for primary sclerosing cholangitis. Histopathology. 2011;58:414–22.CrossRefPubMedGoogle Scholar
  10. 10.
    Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localised non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol. 2011;64:237–43.CrossRefPubMedGoogle Scholar
  11. 11.
    Kitagawa S, Zen Y, Harada K, Sasaki M, Sato Y, Minato H, et al. Abundant IgG4-positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Küttner’s tumor). Am J Surg Pathol. 2005;29:783–91.CrossRefPubMedGoogle Scholar
  12. 12.
    Geyer JT, Ferry JA, Harris NL, Stone JH, Zukerberg LR, Lauwers GY, et al. Chronic sclerosing sialadenitis (Küttner tumor) is an IgG4-associated disease. Am J Surg Pathol. 2010;34:202–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Cheuk W, Yuen HK, Chan JK. Chronic sclerosing dacryoadenitis: part of the spectrum of IgG4-related Sclerosing disease? Am J Surg Pathol. 2007;31:643–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol. 2010;34:1812–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Moriyama M, Furukawa S, Kawano S, Goto Y, Kiyoshima T, Tanaka A, et al. The diagnostic utility of biopsies from the submandibular and labial salivary glands in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz’s disease. Int J Oral Maxillofac Surg. 2014;43:1276–81.CrossRefPubMedGoogle Scholar
  16. 16.
    Sato Y, Ohshima K, Takata K, Huang X, Cui W, Ohno K, et al. Ocular adnexal IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease. J Clin Exp Hematop. 2012;52:51–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Inoue D, Zen Y, Abo H, Gabata T, Demachi H, Kobayashi T, et al. Immunoglobulin G4-related lung disease: CT findings with pathologic correlations. Radiology. 2009;251:260–70.CrossRefPubMedGoogle Scholar
  18. 18.
    Zen Y, Inoue D, Kitao A, Onodera M, Abo H, Miyayama S, et al. IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol. 2009;33:1886–93.CrossRefPubMedGoogle Scholar
  19. 19.
    Zen Y, Kitagawa S, Minato H, Kurumaya H, Katayanagi K, Masuda S, et al. IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol. 2005;36:710–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Cheuk W, Chan JK. Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity. Semin Diagn Pathol. 2012;29:226–34.CrossRefPubMedGoogle Scholar
  21. 21.
    Chang SY, Keogh KA, Lewis JE, Ryu JH, Cornell LD, Garrity JA, et al. IgG4-positive plasma cells in granulomatosis with polyangiitis (Wegener’s): a clinicopathologic and immunohistochemical study on 43 granulomatosis with polyangiitis and 20 control cases. Hum Pathol. 2013;44:2432–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Klöppel G, Detlefsen S, Chari ST, Longnecker DS, Zamboni G. Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions. J Gastroenterol. 2010;45:787–93.CrossRefPubMedGoogle Scholar
  23. 23.
    Kawaguchi K, Koike M, Tsuruta K, Okamoto A, Tabata I, Fujita N. Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol. 1991;22:387–95.CrossRefPubMedGoogle Scholar
  24. 24.
    Zamboni G, Lüttges J, Capelli P, Frulloni L, Cavallini G, Pederzoli 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.CrossRefPubMedGoogle Scholar
  25. 25.
    Zen Y, Ishikawa A, Ogiso S, Heaton N, Portmann B. Follicular cholangitis and pancreatitis – clinicopathological features and differential diagnosis of an under-recognized entity. Histopathology. 2012;60:261–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Zen Y, Nakanuma Y, Portmann B. Immunoglobulin G4-related sclerosing cholangitis: pathologic features and histologic mimics. Semin Diagn Pathol. 2012;29:205–11.CrossRefPubMedGoogle Scholar
  27. 27.
    Zen Y, Harada K, Sasaki M, Sato Y, Tsuneyama K, Haratake J, et al. IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated sclerosing cholangitis: do they belong to a spectrum of sclerosing pancreatitis? Am J Surg Pathol. 2004;28:1193–203.CrossRefPubMedGoogle Scholar
  28. 28.
    Umemura T, Zen Y, Hamano H, Kawa S, Nakanuma Y, Kiyosawa K. Immunoglobin G4-hepatopathy: association of immunoglobin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology. 2007;46:463–71.CrossRefPubMedGoogle Scholar
  29. 29.
    Deshpande V, Sainani NI, Chung RT, Pratt DS, Mentha G, Rubbia-Brandt L, et al. IgG4-associated cholangitis: a comparative histological and immunophenotypic study with primary sclerosing cholangitis on liver biopsy material. Mod Pathol. 2009;22:1287–95.CrossRefPubMedGoogle Scholar
  30. 30.
    Naitoh I, Zen Y, Nakazawa T, Ando T, Hayashi K, Okumura F, et al. Small bile duct involvement in IgG4-related sclerosing cholangitis: liver biopsy and cholangiography correlation. J Gastroenterol. 2011;46:269–76.CrossRefPubMedGoogle Scholar
  31. 31.
    Zen Y, Fujii T, Sato Y, Masuda S, Nakanuma Y. Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease. Mod Pathol. 2007;20:884–94.CrossRefPubMedGoogle Scholar
  32. 32.
    Hamano H, Kawa S, Uehara T, Ochi Y, Takayama M, Komatsu K, et al. Immunoglobulin G4-related lymphoplasmacytic sclerosing cholangitis that mimics infiltrating hilar cholangiocarcinoma: part of a spectrum of autoimmune pancreatitis? Gastrointest Endosc. 2005;62:152–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Umemura T, Zen Y, Hamano H, Ichijo T, Kawa S, Nakanuma Y, et al. IgG4 associated autoimmune hepatitis: a differential diagnosis for classical autoimmune hepatitis. Gut. 2007;56:1471–2.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Umemura T, Zen Y, Hamano H, Joshita S, Ichijo T, Yoshizawa K, et al. Clinical significance of immunoglobulin G4-associated autoimmune hepatitis. J Gastroenterol. 2011;46(S1):48–55.CrossRefPubMedGoogle Scholar
  35. 35.
    Yeoman AD, Zen Y, Heneghan MA. IgG4+ve autoimmune hepatitis is not observed among patients of non-Asian origin. Gut. 2012;61(S2):A190.Google Scholar
  36. 36.
    Björnsson E, Chari ST, Smyrk TC, Lindor K. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology. 2007;45:1547–54.CrossRefPubMedGoogle Scholar
  37. 37.
    Zen Y, Grammatikopoulos T, Heneghan MA, Vergani D, Mieli-Vergani G, Portmann BC. Sclerosing cholangitis with granulocytic epithelial lesion: a benign form of sclerosing cholangiopathy. Am J Surg Pathol. 2012;36:1555–61.CrossRefPubMedGoogle Scholar
  38. 38.
    Kasashima S, Zen Y, Kawashima A, Konishi K, Sasaki H, Endo M, et al. Inflammatory abdominal aortic aneurysm: close relationship to IgG4-related periaortitis. Am J Surg Pathol. 2008;32:197–204.CrossRefPubMedGoogle Scholar
  39. 39.
    Zen Y, Kasashima S, Inoue D. Retroperitoneal and aortic manifestations of immunoglobulin G4-related disease. Semin Diagn Pathol. 2012;29:212–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Inoue D, Zen Y, Abo H, Gabata T, Demachi H, Yoshikawa J, et al. Immunoglobulin G4-related periaortitis and periarteritis: CT findings in 17 patients. Radiology. 2011;261:625–33.CrossRefPubMedGoogle Scholar
  41. 41.
    Stone JR. Aortitis, periaortitis, and retroperitoneal fibrosis, as manifestations of IgG4-related systemic disease. Curr Opin Rheumatol. 2011;23:88–94.CrossRefPubMedGoogle Scholar
  42. 42.
    Stone JH, Khosroshahi A, Deshpande V, Stone JR. IgG4-related systemic disease accounts for a significant proportion of thoracic lymphoplasmacytic aortitis cases. Arthritis Care Res (Hoboken). 2010;62:316–22.CrossRefGoogle Scholar
  43. 43.
    Matsumoto Y, Kasashima S, Kawashima A, Sasaki H, Endo M, Kawakami K, et al. A case of multiple immunoglobulin G4-related periarteritis: a tumorous lesion of the coronary artery and abdominal aortic aneurysm. Hum Pathol. 2008;39:975–80.CrossRefPubMedGoogle Scholar
  44. 44.
    Zen Y, Onodera M, Inoue D, Kitao A, Matsui O, Nohara T, et al. Retroperitoneal fibrosis: a clinicopathologic study with respect to immunoglobulin G4. Am J Surg Pathol. 2009;33:1833–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Khosroshahi A, Carruthers MN, Stone JH, Shinagare S, Sainani N, Hasserjian RP, et al. Rethinking Ormond’s disease: “idiopathic” retroperitoneal fibrosis in the era of IgG4-related disease. Medicine (Baltimore). 2013;92:82–91.CrossRefGoogle Scholar

Copyright information

© Springer Japan 2016

Authors and Affiliations

  1. 1.Department of Diagnostic PathologyKobe University Graduate School of MedicineKobeJapan

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