39-12: Gastric Neuroendocrine Tumors

Gastric NETs make up less than 1% of gastric neoplasms. They may occur sporadically or secondary to chronic hypergastrinemia that results in hyperplasia and transformation of enterochromaffin cells in the gastric fundus. The majority of NETs are caused by hypergastrinemia and occur in association with either pernicious anemia (75%) (type 1) or Zollinger-Ellison syndrome (5%) (type 2). Type 1 tumors are associated with chronic atrophic gastritis, gastric achlorhydria, and secondary hypergastrinemia. Initial diagnostic workup includes serum gastrin level, upper endoscopy, and EUS. Gastrin level should be obtained 1 week after the patient has stopped taking protein pump inhibitors. For low-grade tumors (Ki-67 less than 3% or less than 2 mitoses/10 high-power fields [HPF]), 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.

For patients with hypergastrinemia (suspected of type 1 or type 2 carcinoid), serum vitamin B₁₂ and intrinsic factor antibody levels should be obtained to exclude pernicious anemia. Gastric NETs associated with Zollinger-Ellison syndrome occur almost exclusively in patients with multiple endocrine neoplasia type 1 (MEN 1), in which chromosomal loss of 11q13 has been reported. Gastric NETs caused by hypergastrinemia tend to be multifocal, be smaller than 1 cm, have a low potential for metastatic spread, and thus are unlikely to cause development of the carcinoid syndrome. 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. Octreotide therapy may be appropriate for patients with underlying gastrinoma and Zollinger-Ellison syndrome. Patients with tumors larger than 2 cm should undergo endoscopic or surgical resection (see Small Intestinal Adenocarcinomas below).

Type 3 gastric NETs arise sporadically, independent of gastrin production, and account for up to 20% of gastric NETs. Most sporadic gastric NETs are solitary, larger than 2 cm, and have a strong propensity for hepatic or pulmonary metastases and thus the carcinoid syndrome at initial presentation. CT or MRI should be obtained to evaluate for metastatic disease. Localized sporadic NETs should be treated with partial or total gastrectomy and regional lymphadenectomy. Advanced, low-grade gastric NETs can be monitored with serial scans, if asymptomatic. Somatostatin analogs may provide symptomatic relief for patients with functional gastric NETs. Advanced high-grade gastric neuroendocrine carcinomas are treated in a fashion similar to SCLCs.