A 5-Year Follow-Up of a Submucosal Tumor in the Stomach

Question: An asymptomatic 51-year-old man underwent esophagogastroduodenoscopy (EGD) at a health examination in August 2015, which revealed a gastric submucosal tumor at the lesser curvature of the lower gastric body (Figures A and B). The biopsy of the lesion showed chronic inflammation of the mucosa, with no evidence of gastric carcinoma; the patient was Helicobacter pylori–negative (Figure C). No significant abnormality was found during the physical examination or using laboratory tests such as blood biochemistry index and tumor makers. One year later (2016), the patient underwent endoscopic ultrasound that revealed a mixed-echoic spindle-shaped mass that originated from the submucosal layer and deep mucosal layer, measuring 1.3 × 0.9 cm, and that was sharply demarcated (Figures D, E, and F). The surfaces of the lesion were smooth, showing no ulcers or erosion. Heterotopic pancreas was diagnosed. In the next year of subsequent follow-up (2017), EGD showed there was no significant change of the submucosal tumor (SMT) (Figures G and H), and the pathologic section of the center of the lesion revealed chronic atrophic gastritis with moderate intestinal metaplasia; the patient was H pylori–negative (Figure I). Two years later in 2019, EGD showed a submucosal tumor of about 1.4 × 0.9 cm with a congestion surface (Figures J and K). The biopsy revealed active inflammation with lymphatic tissue hyperplasia; the patient was now H pylori–positive (Figure L). After H pylori eradication, 14 C-urea breath test was negative. Following it up 2 years later (March 2021), the EGD revealed a slightly depressed center of the SMT, which measured approximately 2.0 × 1.0 cm in size, covered with a normally appearing mucosa (Figure M). Magnifying narrow-band imaging showed regular microvascular structure similar to the corpus normal mucosa, and the depressed area was covered with white exudates. The microvascular structure was invisible (Figure N). The biopsy specimen obtained from the depressed area showed chronic gastritis with lymphoid follicle, with a few atypical cells in lymphocytic infiltration (Figure O). Abdominal contrast-enhanced computed tomography demonstrated a clearly enhanced mass in the lower gastric body near the notch, measuring 1.9 × 1.0 cm. No enlarged lymph nodes were found (Figure P). The patient underwent endoscopic submucosal dissection (ESD). What is the most likely diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. The ESD specimen size is 4.0 × 3.5 cm (Figure Q), and the tumor size is 2.0 × 1.0 cm. Histologic examination showed adenocarcinoma invading the submucosal layer mixed with rich lymphoid stroma (Figures R and S). CK(AE1/AE3) highlighted irregular sheets and trabeculae of tumor cells embedded within a prominent lymphocytic infiltrate (Figure T). The diagnosis is medullary carcinoma with lymphoid infiltration (MCLI). The in situ hybridization of Epstein-Barr encoding region was positive. The macroscopic type is type 0-Is. The lymphovascular invasion is negative. There is no ulcer. Both vertical and horizontal margins are negative. The depth of submucosal invasion is 1,000 μm (pT1b). Distal gastrectomy and D2 lymph node dissection were performed. Postoperative pathology showed no tumor residue or lymph node metastasis. The stage was pT1bN0M0. No recurrence or metastasis was found in the 1-year follow-up. Gastric MCLI is a rare subtype of gastric cancer, accounting for about 9%. It is also related to Epstein-Barr virus infection at an early stage of the disease.1Takano Y. Kato Y. Sugano H. Epstein-Barr-virus-associated medullary carcinomas with lymphoid infiltration of the stomach.J Cancer Res Clin Oncol. 1994; 120: 303-308Crossref PubMed Scopus (25) Google Scholar MCLI is characterized by poorly differentiated carcinoma cells with dense, diffuse, and uniform lymphoid infiltration. Most gross appearances of MCLI show a clear boundary with a central depression.2Watanabe H. Enjoji M. Imai T. Gastric carcinoma with lymphoid stroma. Its morphologic characteristics and prognostic correlations.Cancer. 1976; 38: 232-243Crossref PubMed Scopus (297) Google Scholar,3Minamoto T. Mai M. Watanabe K. et al.Medullary carcinoma with lymphocytic infiltration of the stomach. Clinicopathologic study of 27 cases and immunohistochemical analysis of the subpopulations of infiltrating lymphocytes in the tumor.Cancer. 1990; 66: 945-952Crossref PubMed Scopus (74) Google Scholar Sometimes it is difficult to diagnose MCLI with standard biopsy because of the dense lymphoid infiltration, which makes it difficult to find carcinoma cells in such a small number of tissues acquired by biopsy. Therefore, we report an unusual case of MCLI mimicking SMT with a smooth surface. Although the patient was followed up for 5 years, 3 times biopsy showed no evidence of carcinoma. The patient was diagnosed using ESD. We suggest that MCLI should be taken into account in the differential diagnosis of SMTs. Diagnostic ESD should also be applied when clinical diagnosis is suspected but biopsy cannot confirm the diagnosis.