Localized IgG4-related disease manifested on the tongue: a case report

Keywords: IgG4-related disease, localized, oral lesion, tongue, differential diagnosis, histopathology, monoclonal antibody, Rituximab


Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs. IgG4-RD may show a variety of initial symptoms. In the oral mucosa, lesions present as inflammatory fibrosis with a large number of IgG4-positive plasma cells. Evaluating treatment is a well-known problem in IgG4-RD due to the absence of an established assessment system. There are difficulties in defining the severity of the disease, which is why treatment is primarily based on its clinical manifestations.

We present a case report of localized IgG4-RD with ulcerative and proliferative manifestations on the tongue, which clinically mimicked oral squamous cell carcinoma. A tumor-like lesion on the tongue can indicate something else other than the malignant or reactive changes commonly found in the oral mucosa. Multiple differential diagnoses of these atypical oral lesions, including localized IgG4-RD, should be considered.


Download data is not yet available.


  1. Neild GH, Rodriguez-Justo M, Wall C, Connolly JO. Hyper-IgG4 disease: report and characterisation of a new disease. BMC Med 2006; 4: 23. doi: 10.1186/1741-7015-4-23

  2. Divatia M, Kim SA, Ro JY. IgG4-related sclerosing disease, an emerging entity: a review of a multi-system disease. Yonsei Med J 2012; 53: 15–34. doi: 10.3349/ymj.2012.53.1.15

  3. Stone JH, Zen Y, Deshpande V. IgG4-related disease. New England J Med 2012; 366: 539–51. doi: 10.1056/NEJMra1104650

  4. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet 2015; 385: 1460–71. doi: 10.1016/S0140-6736(14)60720-0

  5. Chen Y, Zhao J-Z, Feng R-E, Shi J-H, Li X-M, Fei Y-Y, et al. Types of organ involvement in patients with immunoglobulin G4-related disease. Chin Med J (Engl) 2016; 129: 1525–32. doi: 10.4103/0366-6999.184459

  6. Vashi B, Khosroshahi A. IgG4-related disease with emphasis on its gastrointestinal manifestation. Gastroenterol Clin N Am 2019; 48: 291–305. doi: 10.1016/j.gtc.2019.02.008

  7. Lian L, Wang C, Tian J-L. IgG4-related retroperitoneal fibrosis: a newly characterized disease. Int J Rheum Dis 2016; 19: 1049–55. doi: 10.1111/1756-185X.12863

  8. 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. Human Pathol 2005; 36: 710–17. doi: 10.1016/j.humpath.2005.05.011

  9. Takeda S-I, Haratake J, Kasai T, Takaeda C, Takazakura E. IgG4-associated idiopathic tubulointerstitial nephritis complicating autoimmune pancreatitis. Nephrol Dial Transplant 2004; 19: 474–6. doi: 10.1093/ndt/gfg477

  10. Puxeddu I, Capecchi R, Carta F, Tavoni AG, Migliorini P, Puxeddu R. Salivary gland pathology in IgG4-related disease: a comprehensive review. J Immunol Res 2018; 2018: 6936727. doi: 10.1155/2018/6936727

  11. Himi T, Takano K, Yamamoto M, Naishiro Y, Takahashi H. A novel concept of Mikulicz’s disease as IgG4-related disease. Auris Nasus Larynx 2012; 39: 9–17. doi: 10.1016/j.anl.2011.01.023

  12. Yamamoto M, Ohara M, Suzuki C, Naishiro Y, Yamamoto H, Takahashi H, et al. Elevated IgG4 concentrations in serum of patients with Mikulicz’s disease. Scandinavian J Rheumatol 2004; 33: 432–3. doi: 10.1080/03009740410006439

  13. Takahashi H, Yamamoto M, Suzuki C, Naishiro Y, Shinomura Y, Imai K. The birthday of a new syndrome: IgG4-related diseases constitute a clinical entity. Autoimmun Rev 2010; 9: 591–4. doi: 10.1016/j.autrev.2010.05.003

  14. Takano K, Yamamoto M, Takahashi H, Himi T. Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease. Auris Nasus Larynx 2017; 44: 7–17. doi: 10.1016/j.anl.2016.10.011

  15. Bhatti RM, Stelow EB. IgG4-related disease of the head and neck. Adv Anatomic Pathol 2013; 20: 10–16. doi: 10.1097/PAP.0b013e31827b619e

  16. Andrew N, Kearney D, Selva D. IgG4-related orbital disease: a meta-analysis and review. Acta Ophthalmol 2013; 91: 694–700. doi: 10.1111/j.1755-3768.2012.02526.x

  17. Yamamoto M, Takahashi H. IgG4-related disease in organs other than the hepatobiliary-pancreatic system. Semin Liver Dis 2016; 36: 274–82. doi: 10.1055/s-0036-1584317

  18. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol 2012; 22: 1–14. doi: 10.3109/s10165-011-0508-6

  19. Gonzalez-Moles MA, Bagan-Sebastian JV. Alendronate-related oral mucosa ulcerations. J Oral Pathol Med 2000; 29: 514–18. doi: 10.1034/j.1600-0714.2000.291006.x

  20. Kharazmi M, Sjöqvist K, Rizk M, Warfvinge G. Oral ulcer associated with alendronate: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 2010; 110: e11–13. doi: 10.1016/j.tripleo.2010.04.035

  21. Bortoluzzi MC, Passador-Santos F, Capella DL, Manfro G, Nodari RJ, Presta AA. Eosinophilic ulcer of oral mucosa: a case report. Ann Stomatol 2012; 3: 11–13.

  22. Didona D, Paolino G, Donati M, Didona B, Calvieri S. Eosinophilic ulcer of the tongue – case report. An Bras Dermatol 2015; 90: 88–90. doi: 10.1590/abd1806-4841.20153600

  23. Khoury P, Makiya M, Klion AD. Clinical and biological markers in hypereosinophilic syndromes. Front Med 2017; 4: 240. doi: 10.3389/fmed.2017.00240

  24. Shomali W, Gotlib J. World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management. Am J Hematol 2019; 94: 1149–67. doi: 10.1002/ajh.25617

  25. Pardanani A, Brockman SR, Paternoster SF, Flynn HC, Ketterling RP, Lasho TL, et al. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood 2004; 104: 3038–45. doi: 10.1182/blood-2004-03-0787

  26. She Y, Nong X, Zhang M, Wang M. Epstein-Barr virus infection and oral squamous cell carcinoma risk: a meta-analysis. PLoS One 2017; 12: e0186860. doi: 10.1371/journal.pone.0186860

  27. Mouthon L, Dunogue B, Guillevin L. Diagnosis and classification of eosinophilic granulomatosis with polyangiitis (formerly named Churg-Strauss syndrome). J Autoimmun 2014; 48–49: 99–103.

  28. Cottom H, Mighell AJ, High A, Bateman AC. Are plasma cell-rich inflammatory conditions of the oral mucosa manifestations of IgG4-related disease? J Clin Pathol 2015; 68: 802–7.

  29. Laco J, Kamarádová K, Mottl R, Mottlová A, Doležalová H, Tuček L, et al. Plasma cell granuloma of the oral cavity: a mucosal manifestation of immunoglobulin G4-related disease or a mimic? Virchows Archiv 2015; 466: 255–63. doi: 10.1007/s00428-014-1711-6

  30. 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.

  31. Wallace ZS, Naden RP, Chari S, Choi HK, Della-Torre E, Dicaire J-F, et al. The 2019 American College of Rheumatology/European League against rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis 2020; 79: 77–87. doi: 10.1136/annrheumdis-2019-216561

  32. Carruthers MN, Khosroshahi A, Augustin T, Deshpande V, Stone JH. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis 2015; 74: 14–18. doi: 10.1136/annrheumdis-2013-204907

  33. Khurram SA, Fernando M, Smith AT, Hunter KD. IgG4-related sclerosing disease clinically mimicking oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2013; 115: e48–51. doi: 10.1016/j.oooo.2012.04.011

  34. Kubo K, Yamamoto K. IgG4-related disease. Int J Rheumatic Dis 2016; 19: 747–62. doi: 10.1111/1756-185X.12586

  35. Galvin S, Bowe C, O Regan EM, Conlon N, Flint SR, Healy CM. Circumorificial plasmacytosis/plasma cell orificial mucositis: a case series and a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol 2016; 122: e77–81. doi: 10.1016/j.oooo.2016.05.014

  36. Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine 2012; 91: 57–66. doi: 10.1097/MD.0b013e3182431ef6

  37. Zhang J, Chen H, Ma Y, Xiao Y, Niu N, Lin W, et al. Characterizing IgG4-related disease with ¹⁸F-FDG PET/CT: a prospective cohort study. Eur J Nucl Med Mol Imaging 2014; 41: 1624–34. doi: 10.1007/s00259-014-2729-3

  38. Takano K-I, Yamamoto M, Takahashi H, Shinomura Y, Imai K, Himi T. Clinicopathologic similarities between Mikulicz disease and Küttner tumor. Am J Otolaryngol 2010; 31: 429–34. doi: 10.1016/j.amjoto.2009.08.002

  39. Putra J, Ornstein DL. Küttner Tumor: IgG4-related disease of the submandibular gland. Head Neck Pathol 2016; 10: 530–2. doi: 10.1007/s12105-016-0729-2

How to Cite
Helya Hashemi, Thor, A., Hellbacher, E., Carlson, M., Gulyás, M., & Blomstrand, L. (2021). Localized IgG4-related disease manifested on the tongue: a case report. Upsala Journal of Medical Sciences, 126(1). https://doi.org/10.48101/ujms.v126.6118
Case Reports

Most read articles by the same author(s)