Localized Gastric Wall Thickening: It's Not What You Think

Question: A 62-year-old man underwent esophagogastroduodenoscopy and colonoscopy during a health check-up. He felt well and denied any abdominal pain, fatigue, nausea, or vomiting. His past medical history was remarkable for immunoglobulin-G4–related disease (IgG4-RD) that involved the pancreas, bile ducts, lacrimal glands, salivary glands, and prostate 10 years ago, treated by prednisone 10 mg/d orally until now. Physical examination showed that the abdomen was soft and nontender with no palpable mass. Laboratory examination test results were all normal. Upper gastrointestinal endoscopy identified a nodule lesion presented as localized gastric wall thickening in the greater curvature of the lower part of the stomach (Figure A). He underwent endoscopic ultrasonography showing a 1.2 × 0.8 cm and submucosal mixed echoic lesion with posterior acoustic shadowing, which was entirely located in the submucosa layer of the gastric wall (Figure B). Abdominal computed tomography and colonoscopy were normal. The serum immunoglobulin-G4 (IgG4) level was within the normal range. What is the most likely diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Endoscopic submucosal dissection was performed to remove the mass in this patient. Microscopic examination of the specimen revealed scattered lymph follicles and a prominent inflammatory cell infiltrate including lymphocytes and plasma cells (Figure C). Clinically, gastric submucosal lesions are common. The differential diagnosis of gastric submucosal lesions usually includes gastrointestinal stromal tumor, polypoid tumors, gastric schwannoma, and neuroendocrine tumor. CD117 and smooth muscle actin are sensitive markers for gastrointestinal stromal tumors. A definite diagnosis of gastric schwannoma is characterized by spindle cells and the positive staining for S100. Synaptophysin and chromogranin are recommended markers to identify neuroendocrine tumors. Immunohistochemical stains were negative for smooth muscle actin, CD117, S100, synaptophysin, and chromogranin. Common gastric submucosal tumors were excluded from this case. IgG4 staining attracted our attention, considering his past medical history for IgG4-RD. More excitingly, numerous inflammatory cells stained positive for anti-IgG4 with a ratio of IgG4/IgG total >40%, and a number of IgG4 positive cells >100 per high-power field (Figures D, E), which was consistent with IgG4-RD. IgG4-RD, characterized by massive IgG4+ lymphocyte and plasma cell infiltration, and storiform fibrosis, which is a recently recognized systemic fibro-inflammatory disorder causing thickening, nodules, or enlargement of virtually every organ in the body, simultaneously or metachronously.1Lanzillotta M. Mancuso G. Della-Torre E. Advances in the diagnosis and management of IgG4 related disease.BMJ. 2020; 369: m1067Crossref PubMed Scopus (97) Google Scholar Atypically, involvement of the gastrointestinal tract may be rarely presented as an isolated wall thickening or mass-like lesion.2Backhus J. Seufferlein T. Perkhofer L. et al.IgG4-related diseases in the gastrointestinal tract: clinical presentation, diagnosis and treatment challenges.Digestion. 2019; 100: 1-14Crossref PubMed Scopus (11) Google Scholar If the IgG4-RD of the stomach is considered in the differential diagnosis, futile and potentially harmful surgical procedures may be avoided. Due to rarity and exclusion of neoplasm, nearly all gastric IgG4-RD lesions are difficult to identifty.3Bulanov D. Arabadzhieva E. Bonev S. et al.A rare case of IgG4-related disease: a gastric mass, associated with regional lymphadenopathy.BMC Surg. 2016; 16: 37Crossref PubMed Scopus (22) Google Scholar As seen in our patient, endoscopically and minimally invasive surgery was usually required for the final diagnosis. The final diagnosis was definite IgG4-RD of the stomach. Glucocorticoids are the first-line treatment in most patients with active untreated disease for the induction of remission.4Löhr J.M. Vujasinovic M. Rosendahl J. et al.IgG4-related diseases of the digestive tract.Nat Rev Gastroenterol Hepatol. 2022; 19: 185-197Crossref PubMed Scopus (17) Google Scholar As the first-line therapy, corticosteroid treatment is swiftly effective but disease flares are common at low doses or after tapering. Clinical experience indicates that azathioprine and methotrexate may be beneficial. Besides prednisone, use of conventional immunosuppressants was recommended for the patient. Azathioprine 50 mg/d and prednisone 10 mg/d were commenced. He underwent a blood test once per month and endoscopy semiannually. No recurrence was observed within 1-year endoscopic follow-up.