A 68-year-old man was referred to the endoscopy department for an oesophagogastroduodenoscopy (OGD) due to the incidental finding of a small nodule in the gastric fundus. He had a past medical history of lung adenocarcinoma for which he underwent a lobectomy in 2016. A follow-up computed tomography (CT) scan revealed a 12 mm enhancing nodule in the gastric fundus. The patient was asymptomatic and, on direct questioning, reported no upper gastrointestinal symptoms such as dyspepsia, heartburn, pain, nausea or vomit. The OGD revealed a centimetric round lesion located at the transition between the gastric fundus and the body, covered with normal appearing mucosa, compatible with a sub-epithelial lesion (Fig. 1). The remaining gastric mucosa of the fundus and the body was normal, while the antral mucosa was erythematous with small erosions. Biopsies for histology and H. pylori were taken according to the Sydney protocol (2 in the antrum, 1 at the angular incisura and 2 in the body at lesser and greater curves). Microscopic examination showed H. pylori-associated chronic gastritis in the antrum and corpus, active, with moderate glandular atrophy and multifocal intestinal metaplasia in the antrum (Fig. 2). A sequential eradication regimen was prescribed with amoxicillin followed by metronidazole and clarithromycin. H. pylori eradication was confirmed through a fecal test 2 months after the completion of the eradication regimen. To further characterize the sub-epithelial lesion, a diagnostic endoscopic ultrasonography (EUS) was scheduled. This was performed using a radial echoendoscope (GF UE160-AL5; Olympus, Tokyo, Japan) which showed a round lesion, with definite margins, homogeneously hypoechoic with visible internal vascularization, a hard texture at elastography, measuring 11 mm x 9 mm. The lesion originated from the submucosal layer (3rd layer) of the stomach with no involvement of the other layers of the gastric wall (Fig. 3). No lymph nodes were observed in abdominal and mediastinal stations. Following multidisciplinary discussion, considering the size of the lesion, its characteristics and the absence of signs of extraluminal involvement, the patient was referred for endoscopic resection. The lesion was removed using a 27 mm hot snare (Sensation; Boston Scientific, Natick, Massachusetts, USA) after submucosal injection of saline solution and methylen blue. Two metal hemostatic clips were positioned on the resection base to close the mucosal defect. The procedure was uneventful and the patient was discharged home 1 h afterwards. The specimen was sent for pathology examination. Serum gastrin and Chromogranin A levels were within normal range.
Histologic examination of the specimen revealed a 1 cm well circumscribed tumor located mainly within the submucosa layer closer to the muscularis propria. Neoplastic cells showed a predominantly trabecular to solid architecture with both nested and gyriform patterns seen focally. These cells were large with clear and granular cytoplasm and round or oval nuclei with clumped or finely granular ("salt and pepper") chromatin and small nucleoli. Numerous nodular lymphoid aggregates, some of which with germinal centers, were also seen within the tumor (Fig. 4). Mitotic activity was inconspicuous with a mitotic count of 1 mitosis in 10 high power fields (2 mm2). There was no evidence of vascular or perineural invasion. The fundic mucosa above the tumor was flattened and contained some lymphoid aggregates with germinal centers located in close proximity to the muscularis mucosae at the base of the lamina propria (Fig. 5). They were consistent with acquired mucosa-associated lymphoid tissue (MALT). There was no active inflammation with polymorph in the lamina propria or inside the glandular lumina, nor evidence of H. pylori infection. Horizontal and vertical margins were free of tumor cells.
Immunohistochemical staining showed tumor cell positivity for cytokeratin and neuroendocrine markers including Chromogranin A and Synaptophysin. Tumor cells were negative for CDX2, glucagon, insulin, gastrin, somatostatin and serotonin. Ki67 staining showed a proliferative index of 5% (Fig. 6). Lymphoid aggregates consisted of a central part of mature CD20 positive B cells surrounded by CD3and CD2 positive T cells. On the periphery of the aggregates, a fair number of plasma cells were highlighted by anti-CD138 staining.
All these findings led to the final diagnosis of a G-NET G2 pT1.