Gastric Neuroendocrine Tumor: Approach to Diagnosis and Management
Gastric neuroendocrine tumors require histopathological confirmation followed by type classification (I, II, or III) based on gastrin levels and gastric pH, which directly determines treatment—ranging from endoscopic resection for type I/II to radical surgery for type III tumors. 1, 2
Initial Diagnostic Workup
Clinical Assessment
- Examine for signs of MEN-1 syndrome (multiple endocrine neoplasia) and obtain detailed family history, as gastric NETs can be part of hereditary syndromes 3
- Most gastric NETs are discovered incidentally during upper endoscopy performed for other indications 1, 4
Biochemical Testing
- Measure fasting serum gastrin levels to differentiate between hypergastrinemic (types I and II) and sporadic (type III) gastric NETs 1, 2
- Obtain plasma chromogranin A as a general NET marker 3
- Measure gastric pH to assess for achlorhydria (type I) versus normal/low pH (type III) 1, 2
- For type II tumors, check for Zollinger-Ellison syndrome with gastric acid secretion studies 3
Histopathological Confirmation
- Endoscopic biopsy is mandatory for all suspected gastric NETs 3
- Immunohistochemistry must include chromogranin A, synaptophysin, and neuron-specific enolase 3, 5
- Ki-67 proliferation index is essential for WHO grading: G1 (≤2%), G2 (3-20%), G3 (>20%) 3, 6, 7
Imaging and Staging
Multimodal Imaging Approach
- CT or MRI of abdomen for anatomical localization and assessment of liver metastases 3, 7
- Somatostatin receptor imaging (68Ga-DOTA-PET/CT or octreotide scan) to detect somatostatin receptor-positive tumors and distant metastases 3
- Endoscopic ultrasound (EUS) to assess depth of invasion and guide treatment decisions for localized tumors 3
TNM Staging
- Apply TNM classification: T1 (≤1 cm, invades lamina propria/submucosa), T2 (>1 cm or invades muscularis propria), T3 (penetrates serosa), T4 (invades adjacent structures) 3, 6
Type Classification and Treatment Algorithm
Type I Gastric NETs (Most Common, ~70%)
Pathophysiology: Chronic atrophic gastritis with hypergastrinemia and achlorhydria 1, 2
Characteristics:
- Multiple small tumors (<1-2 cm) 1, 2
- Excellent prognosis with 100% 5-year survival 2
- Low malignant potential 1, 2
Treatment:
- Endoscopic resection for tumors <1-2 cm confined to mucosa/submucosa 1, 2
- Long-term endoscopic surveillance every 6-12 months due to persistent atrophic gastropathy 2
- Consider somatostatin analogs for multiple recurrent tumors 1
- Antrectomy (to remove gastrin source) reserved for refractory cases with multiple recurrences 1
Type II Gastric NETs (Rare, ~5%)
Pathophysiology: Associated with Zollinger-Ellison syndrome and MEN-1, hypergastrinemia with normal/high gastric acid 1, 2
Treatment:
- Endoscopic resection for small tumors (<1-2 cm) 1
- Treat underlying gastrinoma with proton pump inhibitors or surgical resection 1
- Surveillance similar to type I 1
Type III Gastric NETs (~15-25%)
Pathophysiology: Sporadic, no hypergastrinemia, normal gastric mucosa 1, 2
Characteristics:
- Usually solitary, large (>2 cm) tumors 1, 2
- Aggressive behavior with high metastatic potential 2
- 5-year survival 50-75% with radical surgery 2
Treatment:
- Radical gastrectomy with lymph node dissection for resectable disease 1, 2
- Extent of resection depends on tumor location: subtotal or total gastrectomy 1
- Chemotherapy with cisplatin-etoposide for poorly differentiated G3 neuroendocrine carcinomas (42-67% response rate) 7
- Consider targeted therapy (everolimus, sunitinib) for advanced well-differentiated NETs 7
Management Based on Tumor Size and Grade
Small Tumors (<1 cm, G1)
- Endoscopic resection with band ligation or endoscopic mucosal resection 1, 4
- Surveillance endoscopy at 6-12 months 1
Intermediate Tumors (1-2 cm, G1-G2)
- Endoscopic resection if confined to submucosa (assessed by EUS) 1
- Surgical resection if muscularis propria invasion or lymph node involvement 1
Large Tumors (>2 cm) or G3
- Surgical resection with lymphadenectomy regardless of type 7, 1
- Staging with CT/MRI and somatostatin receptor imaging to exclude metastases 3
Follow-Up and Surveillance
Biochemical Monitoring
- Serial chromogranin A measurements every 3-6 months for G1/G2 tumors 7
- More frequent monitoring (every 2-3 months) for G3 tumors 6, 7
Imaging Surveillance
- CT or MRI every 3-6 months for NET G1/G2 6, 7
- Every 2-3 months for NEC G3 6, 7
- Somatostatin receptor imaging at 18-24 months if receptor-positive 7
Critical Pitfalls to Avoid
- Do not rely on chromogranin A alone for diagnosis—it can be falsely elevated by proton pump inhibitors, renal failure, and atrophic gastritis 3
- Do not perform radical surgery for type I tumors unless there are features of malignancy (>2 cm, invasion beyond submucosa, high Ki-67) 1, 2
- Do not miss the underlying cause of hypergastrinemia—failure to identify MEN-1 or Zollinger-Ellison syndrome leads to inadequate treatment 1, 2
- Do not skip Ki-67 assessment—this is mandatory for proper grading and treatment selection 3, 6, 7
- Do not use conventional imaging alone—somatostatin receptor imaging is essential for complete staging and may detect occult metastases 3