Gastrointestinal: A case of type 1 gastric neuroendocrine tumor with multiple endocrine neoplasia type 1.

Abstract

A 53 years old man, with a history of autoimmune thyroiditis, developed acid reflux without obvious cause and was found to have hypergastrinemia 2 years ago. Gastroscopy showed a polypoid mucosal lesion in gastric body, which was treated with argon therapy (Fig. 1a,b). Biopsy revealed the presence of a WHO grade 1 neuroendocrine tumour (G1 NET) with increased serum gastrin level (320.30 pg/mL) and a weakly positive IgG anti-parietal cell antibody. The lesion had dilated blood vessels by NBI (Fig. 1c), and mini-probe endosonography showed thickened fundal gastric mucosa with a 1.9 × 1.3 mm hypoechoic lesion in the muscularis mucosa (Fig. 1d). Furthermore, two round-like hypoechoic masses can be seen in the body of the pancreas (Fig. 1e). Somatostatin receptor scintigraphy showed high signal uptak in the antrum, pancreatic lesions, duodenum, and thyroid (Fig. 1f). Whole exome sequencing found a pathogenic variant of multiple endocrine neoplasia type 1 (MEN1) gene, which is located on Chromosome 11(Fig. 2). The patient's daughter was asked to undergo genetic testing, and MEN1 gene mutation was not found. According to the classification of gastric neuroendocrine tumors, type 2 gastric neuroendocrine tumor is associated with MEN1. Serum gastrin levels in type 2 NETs are significantly elevated (often higher than 1000 pg/mL), and endoscopy often finds ulcer formation, manifesting as hypertrophic gastritis. The gastroscopy of our patient did not find peptic ulcer or thickening of gastric folds, and gastrin was not high enough to suspect gastrinoma, combined with the positive anti-parietal cell antibody confirmed the existence of autoimmune gastritis, which can be diagnosed as type 1 g-NET. MEN1; NM_130799.2:c.851C > A(p.Ala284Glu) heterozygous variant was detected by whole exome sequencing, and the pathogenicity of this variant has been reported. According to the ACMG guideline, this variant was identified as a suspected pathogenic variant, PS4_Supporting+PM1 + PM2 + PM6 + PP2 + PP3. In summary, our patient was considered to have type 1 gastric neuroendocrine tumor with MEN-1, which is extremely rare. MEN1 is inherited in an autosomal dominant fashion. Our patient has no family history of MEN1, and his daughter also had no MEN1 gene mutation. Therefore, the diagnosis cannot be denied just because there is no family history. For patients who do not meet the diagnostic criteria of MEN1 but are accompanied by atypical endocrine tumors, it is recommended to conduct genetic analysis for early diagnosis, early treatment, and close follow-up of confirmed patients.