<aside> 📘 Gastric neuroendocrine neoplasms: A review. World J Clin Cases. 2021 Sep

NCCN Guidelines: Neuroendocrine and Adrenal Tumors. 2025

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Epidemiology and types

Gastric NENs (g-NENs) are rare, representing 5% to 23% of all digestive NENs in various studies.
Recent studies have reported an increase in incidence from 0.309 to 6.149 per 1,000,000 persons over the last 40 years

Types

Characteristics	Type 1	Type 2	Type 3	Type 4
Approximate Proportion	70%-80%	5%	10%-25%	Rarely
Pathogenesis	Increased gastrin levels due to atrophic gastritis. ECL origin	Increased gastrin levels due to gastrinoma, associated with Z-E syndrome, MEN-1. ECL origin	Not known. Mostly ECL origin	Not known. Non-ECL origin
Location and Characteristics	Gastric body and fundus. Often small(1-2 cm) and multiple	Gastric body and fundus. Often small and multiple	Anywhere. Large and solitary	Anywhere. Large (often larger than type 3)
Gastrin Level	Increased	Increased	Normal	Increased or normal
Prognosis	Excellent (5-yr survival 95%)	Good	Bad	Bad
Treatment	Surveillance without resection, endoscopic resection, surgery	Endoscopic or surgical resection, resection of gastrinoma.	Gastrectomy and regional lymphadenectomy, systemic chemotherapy	Gastrectomy and regional lymphadenectomy, systemic chemotherapy

Clinical presentation and diagnosis

The clinical presentation is generally nonspecific and is often diagnosed during upper gastrointestinal endoscopy performed for symptoms like abdominal pain, nausea, bleeding, or anemia.
Carcinoid syndrome is rare but may occur, manifesting as atypical carcinoid syndrome.
Bleeding is more common in type 3 g-NENs.

Diagnosis

Diagnosis of g-NENs is primarily made through upper gastrointestinal endoscopy and confirmed via histopathological examination.
Histopathologically, g-NENs show uniform tumor cells with round-oval nuclei, coarse chromatin, and fine granular cytoplasm.
Immunohistochemical staining usually shows positivity for Chromogranin A (CgA) and Synaptophysin, but CgA may be absent in type 4 g-NENs.

Grading

Grading informs the prognosis and guides the treatment strategy for g-NENs.

WHO classification	Differentiation	Mitotic rate (mitoses/mm²)	Ki-67 index
NET, Grade 1	Well	< 2	< 3%
NET, Grade 2	Well	2-20	3%-20%
NET, Grade 3	Well	> 20	> 20%
NEC, small-cell type	Poor	> 20	> 20%
NEC, large-cell type	Poor	> 20	> 20%

Imaging for Staging and Metastasis Detection

Type	Lesion Size	Recommended Evaluation/Imaging
Type 1	Lesions < 1 cm	No further evaluation needed.
	Lesions > 1 cm	Endoscopic Ultrasound (EUS) advised to assess invasion.
Type 2	Larger lesions	Cross-sectional imaging (CT, MRI, and SRI) more commonly required.
Type 3 and Type 4	N/P	68 Ga-PET-DOTANOC imaging used for staging, especially for poorly differentiated cases.