Gastric NETs (gNETs) make up less than 1% of gastric neoplasms and are generally slow-growing tumors. They may occur sporadically or secondary to chronic hypergastrinemia that results in hyperplasia and transformation of enterochromaffin cells in the gastric fundus. Based on clinical characteristics, gNETs have been classified into four types. Types 1 and 2 account for the majority of gNETs and are caused by hypergastrinemia, type 1 in association with pernicious anemia (75%) and type 2 in association with Zollinger-Ellison syndrome (5%). Types 3 and 4 arise sporadically, are independent of gastrin production, and account for up to 20% of gNETs.
Type 1 gNETs are associated with chronic atrophic gastritis, gastric achlorhydria, and consequent secondary hypergastrinemia. Initial diagnostic workup includes CBC, serum vitamin B12 level, and intrinsic factor antibody to help diagnose pernicious anemia, followed by serum gastrin level (obtained 1 week or more after the patient has stopped taking protein pump inhibitors). Staging involves upper endoscopy and EUS. For low-grade tumors (proliferation index of Ki-67 less than 3% or mitotic index of less than 2 mitoses/10 high-power fields [HPF] on histopathological analysis), somatostatin receptor–based imaging (somatostatin receptor scintigraphy or gallium-68 dotatate PET/CT) should be performed. For high-grade tumors (Ki-67 greater than 20% or greater than 20 mitoses/10 HPF), FDG-PET/CT is preferred to evaluate the extent of disease.
Type 2 gNETs are associated with Zollinger-Ellison syndrome caused by a gastrin-secreting NET (gastrinoma) most commonly located in the pancreas or duodenum. Although 75% of gastrinomas are sporadic, gNET caused by gastrinomas occur almost exclusively in patients with multiple endocrine neoplasia type 1 (MEN 1) in which chromosomal loss of 11q13 has been reported.
For types 1 and 2 gNETs, small lesions may be successfully treated with endoscopic resection followed by endoscopic surveillance every 6–12 months, or with observation. Antrectomy reduces serum gastrin levels and may lead to regression of small tumors. It can be considered in patients with type 1 gastric NETs to reduce recurrence risk and frequency of post-therapy monitoring. Patients with tumors larger than 2 cm should undergo endoscopic or surgical resection (see Small Intestinal Adenocarcinomas below). Type 2 gNETs with underlying gastrinoma and Zollinger-Ellison syndrome may be treated with somatostatin analog (octreotide) therapy.
Types 3 and 4 gNETs are most often solitary, larger than 2 cm, and have a strong propensity for hepatic or pulmonary metastases and with associated carcinoid syndrome at initial presentation. In patients with type 3 or 4 gNETs, gallium-68 dotatate CT scan should be obtained to evaluate for metastatic disease.
Localized sporadic type 3 or type 4 gNETs should be treated with partial or total gastrectomy and regional lymphadenectomy. Advanced, low-grade gNETs can be monitored with serial scans, if asymptomatic. Octreotide may provide symptomatic relief for patients with gNETs that are functional (carcinoid syndrome). Advanced high-grade gastric neuroendocrine carcinomas are treated in a fashion similar to small cell lung cancers.