A rare presentation of IgG4 related disease as a gastric antral lesion: Case report and review of the literature

Highlights

• •IgG4RD is a newly recognized systemic disease affecting nearly every organ.
• •IgG4RD presenting as a gastric mass is extremely rare.
• •Preoperative biopsy is mandatory for definitive diagnosis.
• •When diagnosed before surgery, the treatment is medical with IV steroids.

Abstract

Introduction

Immunoglobulin G4 related disease is a recently recognized systemic fibro-inflammatory disorder affecting virtually every organ in the body, characterized by lympho-plasmacytic dense infiltrates rich in IgG4 positive plasmacytes along with storiform fibrosis, inconstantly associated with elevated serum IgG4 levels. Few cases of Immunoglobulin G4 related disease occurring solely in the stomach have been published.

Presentation of case

We herein present a rare case of a 57 year old male patient presenting with an incidentally discovered asymptomatic pre-pyloric submucosal gastric lesion confused with a gastro-intestinal stromal tumor with failed endoscopic biopsy attempts due to tumor mobility. The patient underwent wedge resection of the lesion which was diagnosed postoperatively as Immunoglobulin G4 related disease.

Discussion

Immunoglobulin G4 related disease presenting as a solitary lesion in the stomach is a very rare condition. It should be kept in the differential diagnosis of a submucosal mass or polyp. The treatment is medical with systemic steroid therapy.

Conclusion

Obtaining a tissue biopsy is of extreme importance to avoid unnecessary surgery.

1. Introduction

Immunoglobulin G4 related disease (IgG4RD) is a recently recognized systemic fibro-inflammatory disorder affecting virtually every organ in the body: the pancreas, biliary tree, stomach, kidneys, retroperitoneum, prostate, aorta, lymph nodes, meninges, thyroid, salivary glands, lungs, breast, pericardium and skin [1,2]. Histologically, irrespective to disease site, it is characterized by lympho-plasmacytic dense infiltrates rich in IgG4 positive plasmacytes along with storiform fibrosis and obliterative phlebitis [3]. IgG4RD is associated but not always with elevated serum IgG4 levels. The clinical manifestation depends on the site of occurrence, the infiltrates causing swelling, enlargement, thickening or nodules in the affected organs [4]. It typically affects the pancreas causing autoimmune pancreatitis (AIP) with diffuse IgG4 deposition in adjacent organs such as the stomach [3]. IgG4 related sclerosing disease can be associated in the stomach with gastritis and gastric ulcer [5,6], atypically and very rarely it may present as a focal submucosal gastric mass [7]. We herein present a rare case of IgG4RD presenting as an isolated submucosal pre-pyloric mass. This work has been reported in line with the SCARE criteria [8].

2. Case presentation

A 57 year old man was referred to our clinic for a gastric antral lesion discovered incidentally on a thoraco-abdominal CT scan performed on a routine follow up of prostate cancer. The patient was feeling well and he denied any nausea, vomiting, abdominal pain, fatigue or satiety. His past medical history was remarkable for hypertension and prostate cancer operated 5 years ago and classified as T3N1 with R0 resection, treated post-operatively by hormonal ablation therapy. Physical examination showed a comfortable obese man with a BMI of 31 kg/m², blood pressure of 130/70 mm Hg, heart rate of 80 bpm. The abdomen was soft, non-tender and not distended. There was no palpable mass, no enlarged liver nor spleen. His laboratory examination tests were normal with a hemoglobin level 14 g/dl, platelet count: 409,000/mm³, leucocyte count: 7100/mm³ with neutrophils, lymphocytes and monocytes at 58.1%, 30% and 8.2% respectively, LDH: 179 U/L. Liver function tests were all normal. Abdominal CT showed an 18 mm well defined lesion at the gastric antrum with arterial enhancement, suggestive of GIST (Fig. 1). An endoscopic ultrasound (EUS) was performed using a linear-array US scope (EG-3870UTK, Pentax Medical & Hitachi Hi Vision 8500 US machine). On endoscopic vision, the lesion was identified under the Incisura Angularis on the lesser curvature of the stomach. EUS revealed an intraparietal lesion developing from the muscularis propria, measuring 17.7 × 16 mm on largest diameters, oval, with sharp margins and regular edges, mainly hypoechoic, with heterogeneous content (Fig. 2). This lesion extended into the extra-digestive area without infiltrating other structures. No lymphadenopathy was noted. A trial of EUS guided FNA, using the 22 G ProCore Needle from Cook (EchoTip^® ProCore™; Cook Endoscopy, IN, USA) was attempted but ended in failure due to the hypermobility of the lesion and its difficult location. A retrospective review of the scans done earlier showed the same mass to be present since 4 years.

Fig. 1.

Abdominal tomography examination showing the well-defined gastric antral lesion.

Fig. 2.

Endoscopic ultrasound examination of the mass showing the heterogeneous oval shaped intra-parietal lesion, measuring 17.7 × 16 mm on large diameters.

In front of a very slow evolution, the patient consented to undergo a laparoscopic partial gastrectomy, for a wedge resection of a probably benign tumor.

The laparoscopic exploration of the abdomen showed absence of peritoneal carcinomatosis and of liver metastases. The mass was identified at the level of the lesser curvature. The stomach was mobilized after division of the lesser omentum. A mechanical laparoscopic wedge resection using GIA was avoided due to the risk of having a sort of “Hourglass” stenosis at the body of the stomach. A small laparotomy incision was done and the stomach was exteriorized through a protective bag. A wedge resection of the small curvature with safety margins was done. A frozen section showed negative margins. The gastric edges were approximated using 2 layers of continuous suture by vicryl 2.0, then by silk 2.0 sutures.

The post-operative course was uneventful and the patient was discharged on the 5^th post-operative day, with a mashed diet regimen.

The definitive histopathologic examination report demonstrated the homogenous extra-mucosal lesion of 18 mm to be composed of collagen and an inflammatory infiltrate of numerous lympho-plasmacytes.

On immuno-histo-chemistry analysis, the tumor stained negative for anti CD117 (c-Kit protein), SMA, CD34, S100. Numerous inflammatory cells stained positive for anti CD138 along with anti-IgG4 with a ratio of IgG4/IgG total >40%, and a number of IgG4 positive cells >50/HPF, which proved the tumor to be an IgG4-related inflammatory pseudo-tumor (Fig. 3).

Fig. 3.

Immuno-histochemical staining for IgG4 revealing the presence of numerous positive plasmacytes.

Serum IgG4 level done 45 days post-surgery was: 118 mg/dL (normal 14–126 mg/dL) and after 5 months: 128 mg/dL. At 1 year post-surgery, the patient was doing well, with no signs of recurrence on abdominal computed tomography examination.

3. Discussion

IgG4 is the least abundant IgG in healthy individuals (< 5% of total IgG) [9]. It is linked to other autoimmune diseases like pemphigus vulgaris, pemphigus foliaceus, idiopathic membranous glomerulonephritis, and thrombotic thrombocytopenic purpura [10]. In 2001, Hamano et al linked AIP to elevated serum concentration of IgG4 [11]. Kamisawa et al detected severe or moderate infiltration by IgG4 positive plasma cells, along with storiform fibrosis in the pancreas, peri-pancreatic tissue, biliary tree, salivary glands, lymph nodes, colonic and gastric mucosa, and recognized the AIP as being a manifestation of a systematic autoimmune fibro-inflammatory process. The disease is similar to sarcoidosis in the way that one or multiple organs can be affected and they share the same histopathologic features, it can affect [10]. In opposite to most of the autoimmune diseases, IgG4 RD affects mostly men above 50 years of age [12]. IgG4RD is excessively misdiagnosed because of the emphasis on the finding of IgG4 plasma cells in biopsies and the moderately increased IgG4 serum levels. Actually the accepted criteria for IgG4RD are the comprehensive diagnostic criteria (CDC) for IgG4RD which consist of 3 items: 1) diffuse or partial enlargement, swelling, nodules or thickening lesions on single or multiple organs, 2) serum IgG4 concentration > 135 mg/dL, and 3) histopathological findings including a) massive lymphocytic and plasmacytic infiltration and sclerosis, b) increased numbers of IgG4 positive plasma cells; and IgG4 positive plasma cells/ IgG positive plasma cell ratio >40% and >10 cells per HPF. Patients who fulfill all 3 criteria have a definite diagnosis of IgG4RD, those who fulfill criteria 1 and 3 have a probable diagnosis and those who fulfill criteria 1 and 2 have a possible diagnosis [13]. However these criteria did not include the concept of IgG4-related gastrointestinal diseases [14]. The diagnosis of gastrointestinal IgG4RD do not rely solely on the presence of IgG4 positive plasma cells in the mucosa but on the association with diffuse wall thickening or polyp or masse like lesion with the typical histopathological features [15]. The imaging findings of IgG4 RD vary considerably because IgG4RD lesions lack any typical features and might thus be mistaken for malignancy leading to unnecessary surgery. This emphasizes the importance of obtaining a tissue biopsy in front of any polyp or submucosal mass. In our case, several attempts of endoscopic biopsy failed due to high tumor mobility which could have changed the therapeutic approach.

Actually therapeutic decisions should be taken on individual basis taking into consideration the symptomatology, the localization, the extent of the disease, and the risk of recurrence. The first line therapy is steroids, but there is no consensus on the initial treatment dose, the subsequent maintenance dose and the duration of the treatment. Other possibilities include glucocorticoid –sparing agents (Azathioprine, mycophenolate mophetil, and methotrexate) [10,15]. Some studies advise the use of 2-[¹⁸F]-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG PET SCAN) to evaluate the extent of the disease before starting the treatment, and to assess the disease response to treatment [16]. For patients with recurrent or refractory disease, treatment with rituximab could be beneficial [17].

Very rare cases of IgG4 RD arising as a gastric lesion were reported, Bulanov et al [18] reviewed including their case, 10 cases of IgG4RD presenting as gastric mass, Cheong et al [19] reviewed 9 cases including theirs with 6 cases in common. In most of the reported cases, the lesion was solitary and were treated by surgical resection because of the difficult preoperative diagnosis [18]. Bulanov reported a case of isolated gastric IgG4RD treated surgically and showed the involvement of lymph nodes of IgG4-RD [18].

In conclusion, IgG4RD presenting as a gastric mass, either solitary manifestation or associated with other manifestations of IgG4RD such as AIP, sialadenitis, Raynaud’s disease, Hashimoto’s thyroiditis, and IgG4RD in lungs, skin and lymphadenopathy is extremely rare. According to literature review, the preoperative diagnosis of this tumor remains a challenge, due to the scarcity of specific clinical and imaging signs. In the cases where diagnosis could be established preoperatively, patients should be orientated first to systemic steroid therapy as this treatment could be curative [10,15,18,19]. The present case illustrates that this diagnosis should be kept in mind and that preoperative macro-biopsy is indicated.

Conflicts of interest

We have no conflict of interest to declare.

Funding

No funding source.

Ethical approval

The submitted article is a case report, ethical approval has been exempted by our institution.

Consent

The patient was consented for operation and for publication of the case report and imaging.

Author contribution

Ali Bohlok and Melody El-Khoury wrote the manuscript. Anthony Zaarour and Pierre Eisendrath did the gastroscopy and the endoscopic ultrasound and wrote the imaging guided biopsy part of the manuscript and revised the manuscript for correction before submission. Issam El Nakadi and Berenice Tulelli operated the patient and wrote the part about the detailed operative technique. Peter Demetter and Laurine Verset did the pathologic examination of the operative specimen and explained the pathologic diagnosis in the manuscript. All authors have read and approved the manuscript before submission to your journal.

Registration of research studies

Not applicable.

Guarantor

Dr Issam El Nakadi.

Availability of data and materials

The data sets supporting the conclusions of this article are included within the article.

Provenance and peer review

Not commissioned, externally peer-reviewed.