Gastric neuroendocrine tumors in a germline mutation carrier: A case report.

Background: The molecular changes present in gastric neuroendocrine tumors (NETs) include a loss of heterozygosity or mutation of , gene mutation, heterozygous mutation, and gene missense mutation. We identified and are the first to report a case of type 1 histamine-producing enterochromaffin-like cell NETs (ECL-cell NETs) with a gene germline mutation.

Case Summary: The patient had a history of iron-deficient anemia for 5 years, and gastroscopic examination indicated multiple gastric tumors. Then, the patient underwent distal gastrectomy. Microscopically, multifocal tumor cells were found in the mucosa and submucosa; tumor cells were organoid and arranged in nests and cords, and the stroma was rich in sinusoids. The surrounding gastric mucosa showed atrophy with mild intestinal metaplasia or pseudopyloric gland metaplasia. Neuroendocrine cells could be seen with diffuse linear, nodular, and adenomatous hyperplasia. Immunohistochemically, the tumor cells diffusely expressed cytokeratin, chromogranin, synaptophysin, and CD56. Whole-genome high-throughput molecular sequencing revealed a pathogenic germline mutation in the gene, a heterozygous germline frameshift mutation in exon 11, c.6443_6444del (p.S2148Yfs*2). The final diagnosis was gastric type 1 ECL-cell NETs with a gene germline mutation, accompanied by autoimmune gastritis.

Conclusion: This is the first report of a case of type 1 gastric ECL-cell NETs with a pathogenic germline mutation of the gene. The findings of this report will expand the germline mutation spectrum of gastric NETs and increase the understanding of the molecular changes present in these tumors for their improved diagnosis in the future.