Lymph Node Lesions



Pathological examination of involved tissue occupies an extremely important place in establishing the diagnosis of IgG4-related disease (IgG4-RD). However, the histological picture in IgG4-RD can vary significantly from organ to organ in this disease even while adhering to basic tenets. Consequently, the pathological diagnosis of this condition is often challenging even in the setting of adequate tissue specimens. This is particularly true with regard to the assessment of lymph nodes in patients who may have IgG4-RD. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity. At least five histological subtypes have already been identified. Lymph node biopsies are often performed because of suspicion that the lymphadenopathy might reflect a malignant lymphoma or other lymphoproliferative disorder.

In general, if the IgG4+/IgG+ plasma cell ratio is ≥40 %, the possibility of IgG4-RD is high, but cases of patients with diagnosis other than IgG4-RD who fulfill this criterion are well described in the literature. In practice, patients with hyper-interleukin (IL)-6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. For this reason, it is important that the diagnosis of IgG4-RD relies not only on the pathological findings, but be the result of a careful clinicopathologic collaboration that considers the overall clinical context and appropriate serologic (in particular, serum IL-6, C-reactive protein, IgG4 concentration) and radiologic data as well.


Germinal Center Plasma Cell Infiltration Elevated Serum IgG4 Mature Plasma Cell Infiltrate Plasma Cell 
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.
    Sato Y, Notohara K, Kojima M, et al. IgG4-related diseases: historical overview and pathology of hematological disorders. Pathol Int. 2010;60(4):247–58.PubMedCrossRefGoogle Scholar
  2. 2.
    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(4):589–99.PubMedCrossRefGoogle Scholar
  3. 3.
    Hamano H, Arakura N, Muraki T, et al. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41(12):1197–205.PubMedCrossRefGoogle Scholar
  4. 4.
    Masaki Y, Kurose N, Umehara H. IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century. J Clin Exp Hematopathol. 2011;51(1):13–20.CrossRefGoogle Scholar
  5. 5.
    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(12):1084–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Kojima M, Nakamura N, Tsukamoto N, et al. Atypical lymphoplasmacytic and immunoblastic proliferation of autoimmune disease: Clinicopathologic and immunohistochemical study of 9 cases. J Clin Exp Hematopathol. 2010;50(2):113–9.CrossRefGoogle Scholar
  7. 7.
    Strehl JD, Hartmann A, Agaimy A. Numerous IgG4-positive plasma cells are ubiquitous in diverse localized non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders. J Clin Pathol. 2011;64(3):237–43.PubMedCrossRefGoogle Scholar
  8. 8.
    Asano N, Sato Y. Rheumatoid lymphadenopathy with abundant IgG4+ plasma cells: a case mimicking IgG4-related disease. J Clin Exp Hematopathol. 2012;52(1):57–61.CrossRefGoogle Scholar
  9. 9.
    Sato Y, Inoue D, Asano N, et al. Association between IgG4-related disease and progressively transformed germinal centers of lymph node. Mod Pathol. 2012;25(7):956–67.PubMedCrossRefGoogle Scholar
  10. 10.
    Sato Y, Kojima M, Takata K, et al. Immunoglobulin G4-related lymphadenopathy with inflammatory pseudotumor-like features. Med Mol Morphol. 2011;44(3):179–82.PubMedCrossRefGoogle Scholar
  11. 11.
    Moran CA, Suster S, Abbondanzo SL. Inflammatory pseudotumor of lymph nodes: a study of 25 cases with emphasis on morphological heterogeneity. Hum Pathol. 1997;28(3):332–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Kojima M, Nakamura S, Shimizu K, et al. Inflammatory pseudotumor of lymph node: clinicopathologic and immunohistological study of 11 Japanese cases. Int J Surg Pathol. 2001;9(3):207–14.PubMedCrossRefGoogle Scholar
  13. 13.
    Frizzera G. A typical lymphoproliferative disorders. In: Knowles DM, editor. Neoplastic hematopathology. 2nd ed. Baltimore: Lippincott Williams & Wilkins; 2000. p. 569–622.Google Scholar
  14. 14.
    Nishimoto N, Terao K, Mima T, et al. Mechanisms and pathological significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman’s disease. Blood. 2008;112(10):3959–64.PubMedCrossRefGoogle Scholar
  15. 15.
    Yamamoto M, Tabeya T, Naishiro Y, et al. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases. Mod Rheumatol. 2011;22(3):419–25.PubMedCrossRefGoogle Scholar
  16. 16.
    Bertolini JN, Benson EM. The role of human interleukin-6 in B-cell isotype regulation and differentiation. Cell Immunol. 1990;125(1):197–209.PubMedCrossRefGoogle Scholar
  17. 17.
    Kawano Y, Noma T, Kou K, et al. Regulation of human IgG subclass production by cytokines: human IgG subclass production enhanced differentially by interleukin-6. Immunology. 1995;84(2):278–84.PubMedGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Department of PathologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan

Personalised recommendations