J Gastric Cancer.  2018 Mar;18(1):99-107. 10.5230/jgc.2018.18.e8.

IgG4-related Disease in the Stomach which Was Confused with Gastrointestinal Stromal Tumor (GIST): Two Case Reports and Review of the Literature

• Seo HS
• Jung YJ
• Park CH
• Song KY
• Jung ES

• KMID: 2414551
• DOI: http://doi.org/10.5230/jgc.2018.18.e8

Abstract

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibro-inflammatory disorder characterized by specific pathological findings and elevated serum IgG4 level. IgG4-RD in the stomach is rare, and occasionally diagnosed as gastric subepithelial tumor (SET) by endoscopy or computed tomography scan. Two female patients in the age group of 40-50 years were diagnosed with 4 cm sized gastric SET. One underwent laparoscopic gastric wedge resection. Another one had a history of subtotal gastrectomy for early gastric cancer and idiopathic thrombocytopenic purpura with oral steroids administration. She underwent a completion total gastrectomy with splenectomy for the gastric SET and ITP. The pathology showed storiform fibrosis, and IgG4 was positive in immunohistochemistry (IHC) stain. IgG4-RD is known as a medical disease that could be treated with oral steroids. The difficulty in preoperative diagnosis of the disease occasionally causes unnecessary gastric resection. Thus, preoperative diagnostic methods for IgG4-RD such as deep biopsy with IHC stain or magnetic resonance imaging are needed.

Keyword

Immunoglobulin G; Gastrointestinal stromal tumors

MeSH Terms

Biopsy
Diagnosis
Endoscopy
Female
Fibrosis
Gastrectomy
Gastrointestinal Stromal Tumors*
Humans
Immunoglobulin G
Immunoglobulins
Immunohistochemistry
Magnetic Resonance Imaging
Pathology
Purpura, Thrombocytopenic, Idiopathic
Splenectomy
Steroids
Stomach Neoplasms
Stomach*
Immunoglobulin G
Immunoglobulins
Steroids

Figure

• 

  Fig. 1 Case 1. (A) Endoscopy, a 4 cm sized fixed and hard submucosal lesion at gastric angle; (B) EUS, a 4.3 cm sized mixed echoic submucosal lesion; (C) CT, a well-defined heterogeneously enhancing wall mass; (D) Gross specimen, an ill-demarcated round tan-brown colored firm mass; (E) H&E stain, ×12.5, transmural diffuse fibrosis with dense lymphoplasmacytic infiltrate prominent lymphoid follicles; (F) H&E stain, ×100, storiform fibrosis with numerous plasma cells and no definite obliterative phlebitis; (G) IHC stain, ×200, IgG4 and IgG positive cells.EUS = endoscopic ultrasonography; CT = computed tomography; H&E = hematoxylin and eosin; IHC = immunohistochemistry; Ig = immunoglobulin.

• 

  Fig. 2 Case 2. (A) Endoscopy, a 4 cm sized fixed and hard submucosal lesion at remnant body; (B) EUS, a 4.1 cm sized heterogeneous hypoechoic mass; (C) CT, a 2.7 cm sized mass at wall; (D) Gross specimen, a well-demarcated round tan-brown colored firm mass; (E) H&E stain, ×12.5, transmural diffuse fibrosis with dense lymphoplasmacytic infiltrate prominent lymphoid follicles; (F) H&E stain, ×100, storiform fibrosis with numerous plasma cells; (G) Elastic stain, ×200, non-obliterative phlebitis; (H) IHC stain, ×200, IgG4 and IgG positive cells.EUS = endoscopic ultrasonography; CT = computed tomography; H&E = hematoxylin and eosin; IHC = immunohistochemistry; Ig = immunoglobulin.

Reference

1. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012; 366:539–551. PMID: 22316447.

2. Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003; 38:982–984. PMID: 14614606.

3. 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; 251:260–270. PMID: 19221056.

4. 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; 344:732–738. PMID: 11236777.

5. Zen Y. The pathology of IgG4-related disease in the bile duct and pancreas. Semin Liver Dis. 2016; 36:242–256. PMID: 27466794.

6. Kawano M, Yamada K. IgG4-related kidney disease and IgG4-related retroperitoneal fibrosis. Semin Liver Dis. 2016; 36:283–290. PMID: 27466797.

7. Perugino CA, Wallace ZS, Meyersohn N, Oliveira G, Stone JR, Stone JH. Large vessel involvement by IgG4-related disease. Medicine (Baltimore). 2016; 95:e3344. PMID: 27428181.

8. Williams MM, Mashaly H, Puduvalli VK, Jin M, Mendel E. Immunoglobulin G4-related disease mimicking an epidural spinal cord tumor: case report. J Neurosurg Spine. 2017; 26:76–80. PMID: 27517527.

9. Kim JH, Byun JH, Lee SS, Kim HJ, Lee MG. Atypical manifestations of IgG4-related sclerosing disease in the abdomen: imaging findings and pathologic correlations. AJR Am J Roentgenol. 2013; 200:102–112. PMID: 23255748.

10. Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015; 385:1460–1471. PMID: 25481618.

11. Aalberse RC, Stapel SO, Schuurman J, Rispens T. Immunoglobulin G4: an odd antibody. Clin Exp Allergy. 2009; 39:469–477. PMID: 19222496.

12. Khosroshahi A, Wallace ZS, Crowe JL, Akamizu T, Azumi A, Carruthers MN, et al. International consensus guidance statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol. 2015; 67:1688–1699. PMID: 25809420.

13. 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; 25:1181–1192. PMID: 22596100.

14. 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. PMID: 25881845.

15. Vlachou PA, Khalili K, Jang HJ, Fischer S, Hirschfield GM, Kim TK. IgG4-related sclerosing disease: autoimmune pancreatitis and extrapancreatic manifestations. Radiographics. 2011; 31:1379–1402. PMID: 21918050.

16. Takahashi N, Kawashima A, Fletcher JG, Chari ST. Renal involvement in patients with autoimmune pancreatitis: CT and MR imaging findings. Radiology. 2007; 242:791–801. PMID: 17229877.

17. 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; 261:625–633. PMID: 21803920.

18. Inoue D, Yoneda N, Yoshida K, Nuka H, Kinoshita J, Fushida S, et al. Imaging and pathological features of gastric lesion of immunoglobulin G4-related disease: a case report and review of the recent literature. Mod Rheumatol. 2016; 1–5.

19. Shinji A, Sano K, Hamano H, Unno H, Fukushima M, Nakamura N, et al. Autoimmune pancreatitis is closely associated with gastric ulcer presenting with abundant IgG4-bearing plasma cell infiltration. Gastrointest Endosc. 2004; 59:506–511. PMID: 15044886.

20. Fujita T, Ando T, Sakakibara M, Hosoda W, Goto H. Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: a case report. World J Gastroenterol. 2010; 16:2183–2186. PMID: 20440861.

21. Kaji R, Okabe Y, Ishida Y, Takedatsu H, Kawahara A, Aino H, et al. Autoimmune pancreatitis presenting with IgG4-positive multiple gastric polyps. Gastrointest Endosc. 2010; 71:420–422. PMID: 19846081.

22. Baez JC, Hamilton MJ, Bellizzi A, Mortele KJ. Gastric involvement in autoimmune pancreatitis: MDCT and histopathologic features. JOP. 2010; 11:610–613. PMID: 21068496.

23. Chetty R, Serra S, Gauchotte G, Markl B, Agaimy A. Sclerosing nodular lesions of the gastrointestinal tract containing large numbers of IgG4 plasma cells. Pathology. 2011; 43:31–35. PMID: 21240062.

24. Rollins KE, Mehta SP, O'Donovan M, Safranek PM. Gastric IgG4-related autoimmune fibrosclerosing pseudotumour: a novel location. ISRN Gastroenterol. 2011; 2011:873087. PMID: 21991533.

25. Na KY, Sung JY, Jang JY, Lim SJ, Kim GY, Kim YW, et al. Gastric nodular lesion caused by IgG4-related disease. Pathol Int. 2012; 62:716–718. PMID: 23005600.

26. Bateman AC, Sommerlad M, Underwood TJ. Chronic gastric ulceration: a novel manifestation of IgG4-related disease? J Clin Pathol. 2012; 65:569–570. PMID: 22259178.

27. Kim DH, Kim J, Park DH, Lee JH, Choi KD, Lee GH, et al. Immunoglobulin G4-related inflammatory pseudotumor of the stomach. Gastrointest Endosc. 2012; 76:451–452. PMID: 21981816.

28. Woo CG, Yook JH, Kim AY, Kim J. IgG4-related disease presented as a mural mass in the stomach. J Pathol Transl Med. 2016; 50:67–70. PMID: 26420251.

29. Yang L, Jin P, Sheng JQ. Immunoglobulin G4-related disease (IgG4-RD) affecting the esophagus, stomach, and liver. Endoscopy. 2015; 47(Suppl 1 UCTN):E96–E97. PMID: 25734809.

30. Inoue K, Okubo T, Kato T, Shimamura K, Sugita T, Kubota M, et al. IgG4-related stomach muscle lesion with a renal pseudotumor and multiple renal rim-like lesions: a rare manifestation of IgG4-related disease. Mod Rheumatol. 2018; 28:188–192. PMID: 26381653.

31. Cheong HR, Lee BE, Song GA, Kim GH, An SG, Lim W. Immunoglobulin G4-related inflammatory pseudotumor presenting as a solitary mass in the stomach. Clin Endosc. 2016; 49:197–201. PMID: 26867551.

32. Bulanov D, Arabadzhieva E, Bonev S, Yonkov A, Kyoseva D, Dikov T, et al. A rare case of IgG4-related disease: a gastric mass, associated with regional lymphadenopathy. BMC Surg. 2016; 16:37. PMID: 27255154.

33. Otsuka R, Kano M, Hayashi H, Hanari N, Gunji H, Hayano K, et al. Probable IgG4-related sclerosing disease presenting as a gastric submucosal tumor with an intense tracer uptake on PET/CT: a case report. Surg Case Rep. 2016; 2:33. PMID: 27059471.

34. Søreide K, Sandvik OM, Søreide JA, Giljaca V, Jureckova A, Bulusu VR. Global epidemiology of gastrointestinal stromal tumours (GIST): a systematic review of population-based cohort studies. Cancer Epidemiol. 2016; 40:39–46. PMID: 26618334.

35. Ko SY, Lee JS, Kim JJ, Park SM. Higher incidence of gastroesophageal reflux disease after gastric wedge resections of gastric submucosal tumors located close to the gastroesophageal junction. Ann Surg Treat Res. 2014; 86:289–294. PMID: 24949319.