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Lymphomas in IgG4-related disease: clinicopathologic features in a Western population

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Abstract

Lymphomas that occur in the setting of IgG4-related disease (IgG4-RD) are uncommon. Most reported cases derive from Asia and are MALT lymphomas occurring in orbital IgG4-RD. The spectrum of lymphomas among IgG4-RD patients in the Western world remains poorly defined. The aim of this study was to report our experience with lymphomas occurring in IgG4-RD. Eight cases were identified from the pathology and consultation files. The median age was 61 years (range 22–68) at IgG4-RD diagnosis and 63.5 years (range 33–79) at lymphoma diagnosis, with a M:F ratio of 4:4. The diagnosis of lymphoma and IgG4-RD was concurrent in three cases and asynchronous in five (interval 4.3–16.4 years). Concurrent cases included a MALT lymphoma and a diffuse large B cell lymphoma (DLBCL) occurring with IgG4-related sialadenitis and a follicular lymphoma occurring with orbital IgG4-RD. Asynchronous cases included a lymphoplasmacytic lymphoma with large cell transformation and intervening IgG4-related pancreatitis, a MALT lymphoma after lacrimal IgG4-RD, two DLBCLs after multiorgan IgG4-RD, and a DLBCL after IgG4-related sialadenitis. Our findings suggest that lymphomas in IgG4-RD are more varied in location and type than the experience reported from Asia to date. Pathologists should be aware of the potential for lymphoma to develop in patients with IgG4-RD and should have a high degree of suspicion when lymphadenopathy or extranodal masses persist despite appropriate therapy for IgG4-RD. The co-occurrence of IgG4-RD and lymphoma that is reported here and previously suggests a possible etiologic association.

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References

  1. Stone JH, Zen Y, Deshpande V (2012) IgG4-related disease. N Engl J Med 366(6):539–551. https://doi.org/10.1056/NEJMra1104650

    Article  PubMed  CAS  Google Scholar 

  2. Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, Stone JH (2015) IgG4-related disease: clinical and laboratory features in one hundred twenty-five patients. Arthritis Rheumatol 67(9):2466–2475. https://doi.org/10.1002/art.39205

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Deshpande V, Zen Y, Chan JK, et al. (2012) Consensus statement on the pathology of IgG4-related disease. Mod Pathol 25(9):1181–1192. https://doi.org/10.1038/modpathol.2012.72

  4. Cheuk W, Chan JK (2012) Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity. Semin Diagn Pathol 29(4):226–234. https://doi.org/10.1053/j.semdp.2012.07.001

    Article  PubMed  Google Scholar 

  5. Ferry JA (2013) IgG4-related lymphadenopathy and IgG4-related lymphoma: moving targets. Diagn Histopathol 19(4):128–139. https://doi.org/10.1016/j.mpdhp.2013.01.005

    Article  Google Scholar 

  6. Cheuk W, Yuen HKL, Chu SYY, Chiu EKW, Lam LK, Chan JKC (2008) Lymphadenopathy of IgG4-related sclerosing disease. Am J Surg Pathol 32(5):671–681. https://doi.org/10.1097/PAS.0b013e318157c068

    Article  PubMed  Google Scholar 

  7. Asano N, Sato Y (2012) Rheumatoid lymphadenopathy with abundant IgG4(+) plasma cells : a case mimicking IgG4-related disease. J Clin Exp Hematop 52(1):57–61. https://doi.org/10.3960/jslrt.52.57

    Article  PubMed  Google Scholar 

  8. Sato Y, Kojima M, Takata K, Morito T, Mizobuchi K, Tanaka T, Inoue D, Shiomi H, Iwao H, Yoshino T (2010) Multicentric Castleman’s disease with abundant IgG4-positive cells: a clinical and pathological analysis of six cases. J Clin Pathol 63(12):1084–1089. https://doi.org/10.1136/jcp.2010.082958

    Article  PubMed  CAS  Google Scholar 

  9. Rollins-Raval MA, Felgar RE, Krasinskas AM, Roth CG (2012) Increased numbers of IgG4-positive plasma cells may rarely be seen in lymph nodes of patients without IgG4-related sclerosing disease. Int J Surg Pathol 20(1):47–53. https://doi.org/10.1177/1066896911420562

    Article  PubMed  Google Scholar 

  10. Cheuk W, Yuen HKL, Chan ACL, Shih LY, Kuo TT, Ma MW, Lo YF, Chan WK, Chan JKC (2008) Ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis: a previously undescribed complication of IgG4-related sclerosing disease. Am J Surg Pathol 32(8):1159–1167. https://doi.org/10.1097/PAS.0b013e31816148ad

    Article  PubMed  Google Scholar 

  11. Sato Y, Ohshima K-I, Ichimura K et al (2008) Ocular adnexal IgG4-related disease has uniform clinicopathology. Pathol Int 58(8):465–470. https://doi.org/10.1111/j.1440-1827.2008.02257.x

    Article  PubMed  CAS  Google Scholar 

  12. Takahashi N, Ghazale AH, Smyrk TC, Mandrekar JN, Chari ST (2009) Possible association between IgG4-associated systemic disease with or without autoimmune pancreatitis and non-Hodgkin lymphoma. Pancreas 38(5):523–526. https://doi.org/10.1097/MPA.0b013e31819d73ca

    Article  PubMed  Google Scholar 

  13. Yamamoto M, Takahashi H, Tabeya T, Suzuki C, Naishiro Y, Ishigami K, Yajima H, Shimizu Y, Obara M, Yamamoto H, Himi T, Imai K, Shinomura Y (2012) Risk of malignancies in IgG4-related disease. Mod Rheumatol 22(3):414–418. https://doi.org/10.3109/s10165-011-0520-x

    Article  PubMed  CAS  Google Scholar 

  14. Wallace ZS, Wallace CJ, Lu N, Choi HK, Stone JH (2016) Association of IgG4-related disease history of malignancy. Arthritis Rheumatol 68(9):2283–2289. https://doi.org/10.1002/art.39773

    Article  PubMed  CAS  Google Scholar 

  15. Kubota T, Moritani S, Yoshino T, Nagai H, Terasaki H (2010) Ocular adnexal marginal zone B cell lymphoma infiltrated by IgG4-positive plasma cells. J Clin Pathol 63(12):1059–1065. https://doi.org/10.1136/jcp.2010.082156

    Article  PubMed  PubMed Central  Google Scholar 

  16. Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. International Agency for Research on Cancer, Lyon

  17. Ferry JA, Klepeis V, Sohani AR, Harris NL, Preffer FI, Stone JH, Grove A, Deshpande V (2015) IgG4-related orbital disease and its mimics in a Western population. Am J Surg Pathol 39(12):1688–1700. https://doi.org/10.1097/PAS.0000000000000497

    Article  PubMed  Google Scholar 

  18. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282. https://doi.org/10.1182/blood-2003-05-1545

    Article  PubMed  CAS  Google Scholar 

  19. Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, Scott DW, Tan KL, Steidl C, Sehn LH, Chan WC, Iqbal J, Meyer PN, Lenz G, Wright G, Rimsza LM, Valentino C, Brunhoeber P, Grogan TM, Braziel RM, Cook JR, Tubbs RR, Weisenburger DD, Campo E, Rosenwald A, Ott G, Delabie J, Holcroft C, Jaffe ES, Staudt LM, Gascoyne RD (2012) Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol 30(28):3452–3459. https://doi.org/10.1200/JCO.2011.41.0985

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kanda G, Ryu T, Shirai T, Ijichi M, Hishima T, Kitamura S, Bandai Y (2011) Peripheral T-cell lymphoma that developed during the follow-up of IgG4-related disease. Intern Med 50(2):155–160. https://doi.org/10.2169/internalmedicine.50.4413

    Article  PubMed  Google Scholar 

  21. Ishida M, Hodohara K, Yoshida K, Kagotani A, Iwai M, Yoshii M, Okuno H, Horinouchi A, Nakanishi R, Harada A, Yoshida T, Okabe H (2013) Occurrence of anaplastic large cell lymphoma following IgG4-related autoimmune pancreatitis and cholecystitis and diffuse large B-cell lymphoma. Int J Clin Exp Pathol 6(11):2560–2568

    PubMed  PubMed Central  Google Scholar 

  22. Uehara T, Ikeda S, Hamano H et al (2012) A case of Mikulicz’s disease complicated by malignant lymphoma: a postmortem histopathological finding. Intern Med 51(4):419–423. https://doi.org/10.2169/internalmedicine.51.5713

    Article  PubMed  Google Scholar 

  23. Kim T, Grobmyer SR, Dixon LR, Allan RW, Hochwald SN (2008) Autoimmune pancreatitis and concurrent small lymphocytic lymphoma: not just a coincidence? J Gastrointest Surg 12(9):1566–1570. https://doi.org/10.1007/s11605-008-0543-6

    Article  PubMed  Google Scholar 

  24. Gupta R, Khosroshahi A, Shinagare S, Fernandez C, Ferrone C, Lauwers GY, Stone JH, Deshpande V (2013) Does autoimmune pancreatitis increase the risk of pancreatic carcinoma?: a retrospective analysis of pancreatic resections. Panceas 42(3):506–510. https://doi.org/10.1097/MPA.0b013e31826bef91

    Article  CAS  Google Scholar 

  25. Bledsoe JR, Wallace ZS, Deshpande V, Richter JR, Klapman J, Cowan A, Stone JH, Ferry JA (2017) Atypical plasmacytic proliferations and lymphomas: characterization of 11 cases. Am J Clin Pathol 148(3):215–235. https://doi.org/10.1093/AJCP/AQX067

    Article  PubMed  Google Scholar 

  26. Geyer JT, Niesvizky R, Jayabalan DS, Mathew S, Subramaniyam S, Geyer AI, Orazi A, Ely SA (2014) IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease. Mod Pathol 27(3):375–381. https://doi.org/10.1038/modpathol.2013.159

    Article  PubMed  CAS  Google Scholar 

  27. Strehl JD, Hartmann A, Agaimy A (2011) 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 64(3):237–243. https://doi.org/10.1136/jcp.2010.085613

    Article  PubMed  Google Scholar 

  28. Menon MP, Evbuomwan MO, Rosai J, Jaffe ES, Pittaluga S (2014) A subset of Rosai-Dorfman disease cases show increased IgG4-positive plasma cells: another red herring or a true association with IgG4-related disease? Histopathology 64(3):455–459. https://doi.org/10.1111/his.12274

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester, MA, USA

    Jacob R. Bledsoe

  2. Division of Rheumatology, Allergy, & Immunology, Massachusetts General Hospital, Boston, MA, USA

    Zachary S. Wallace & John H. Stone

  3. The James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Boston, MA, USA

    Vikram Deshpande & Judith A. Ferry

Authors
  1. Jacob R. Bledsoe
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  2. Zachary S. Wallace
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  3. John H. Stone
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  4. Vikram Deshpande
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  5. Judith A. Ferry
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This study was approved by the institutional review board of the Massachusetts General Hospital.

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This is not applicable. This research involved retrospective review of pathology and clinical materials, without direct involvement of human participants.

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The authors declare that they have no conflict of interest.

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Bledsoe, J.R., Wallace, Z.S., Stone, J.H. et al. Lymphomas in IgG4-related disease: clinicopathologic features in a Western population. Virchows Arch 472, 839–852 (2018). https://doi.org/10.1007/s00428-017-2286-9

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  • DOI: https://doi.org/10.1007/s00428-017-2286-9

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