What is the recommended staging work‑up and management strategy for a duodenal neuroendocrine tumor, including criteria for endoscopic versus surgical resection and options for advanced disease?

Duodenal Neuroendocrine Tumor: Staging Work-up and Management

Initial Staging Work-up

For any duodenal NET, immediately refer to a specialized multidisciplinary team and obtain histological confirmation with Ki-67 grading before planning definitive treatment. 1, 2

Histopathological Assessment

• Obtain tissue via endoscopic biopsy or surgical resection for every suspected duodenal NET 2, 3
• Perform immunohistochemical staining for chromogranin A and synaptophysin (positive in 90-100% of NETs) 2, 3
• Ki-67 proliferation index is mandatory for WHO 2010 grading: G1 ≤2%, G2 3-20%, G3 >20% 1, 2
• Grade and tumor size are the strongest predictors of recurrence-free survival in duodenal NETs 4

Biochemical Testing

• Measure plasma chromogranin A (sensitivity 60-80% for well-differentiated NETs) 2
• Obtain 24-hour urinary 5-HIAA (elevated in ~70% of midgut NETs) 2
• Measure fasting serum gastrin in all duodenal NETs, as approximately 50% of gastrinomas arise in the duodenum 3, 5
• Screen for MEN-1 syndrome with clinical examination and family history, as duodenal gastrinomas are frequently associated with this syndrome 1, 2

Imaging Protocol

Combine functional somatostatin-receptor imaging with anatomical imaging for comprehensive staging. 1, 2, 6

• First-line: Gallium-68 DOTA-peptide PET/CT (90-95% sensitivity for staging and detecting unknown primaries) 2, 6
• If Gallium-68 unavailable: somatostatin-receptor scintigraphy (Octreoscan) plus CT (80-90% sensitivity) 1, 2
• Contrast-enhanced CT or MRI of abdomen/pelvis for anatomical localization and liver metastasis assessment 2, 6
• Endoscopic ultrasound (EUS) is essential to determine tumor size, depth of invasion (mucosal vs. deeper layers), and lymph node involvement 7, 8
• Upper endoscopy to evaluate the entire duodenum and exclude synchronous lesions 3, 7

TNM Staging

• Apply UICC TNM (7th edition) site-specific staging system 1
• Also stage according to ENETS criteria when different from UICC 1
• Document tumor size, depth of invasion, lymph node status, and distant metastases 1, 2

Management Strategy by Tumor Characteristics

Criteria for Endoscopic Resection

Endoscopic resection is appropriate for duodenal NETs ≤10 mm, well-differentiated (G1), confined to mucosa/submucosa on EUS, with no lymph node involvement. 1, 7, 8

• Endoscopic mucosal resection is safe and preferred for tumors ≤1 cm with no muscularis invasion 7, 8
• Perform follow-up EUS at 6 months to confirm no recurrence 7
• Critical caveat: Duodenal NETs have approximately 60% nodal metastases and 30% liver metastases at presentation overall, so careful staging is essential even for small tumors 3

Criteria for Surgical Resection

Surgery is indicated for duodenal NETs >10-20 mm, tumors with invasion beyond submucosa, presence of lymph node metastases, or any gastrinoma regardless of size. 1, 8

Surgical Options by Tumor Location and Size:

• For tumors 10-20 mm: Requires interdisciplinary discussion; consider transduodenal local excision with lymph node sampling 1, 8
• For tumors >20 mm or poorly differentiated: Pancreatoduodenectomy (Whipple procedure) is the treatment of choice 1, 9, 8
• For all localized sporadic gastrinomas: Surgical resection regardless of size, as these are frequently malignant 1, 8
• For periampullary location: Pancreatoduodenectomy is typically required due to anatomical constraints 1, 5

Management of Advanced Disease

Surgery should be considered even with resectable liver metastases or involvement of surrounding structures, as resection improves survival and symptom control. 1, 9

Treatment Options for Unresectable/Metastatic Disease:

• Somatostatin analogues (octreotide or lanreotide) for symptom control and disease stabilization 1
• Everolimus or sunitinib for progressive, well-differentiated pancreatic NETs (also applicable to duodenal NETs in some protocols) 1
• Peptide receptor radionuclide therapy (PRRT) for somatostatin receptor-positive disease 1
• Chemotherapy for poorly differentiated G3 neuroendocrine carcinomas or aggressive clinical course 1
• Locoregional treatments including hepatic ablation or (chemo)embolization for liver-dominant disease 1

Key Management Pitfalls

• Do not perform endoscopic resection without EUS confirmation of depth of invasion and lymph node status 7, 8
• Tumor size and grade are more predictive of recurrence than margin status or lymph node involvement, so prioritize complete pathological assessment 4
• Duodenal NETs between 10-20 mm require individualized assessment—neither routine endoscopic nor automatic surgical resection is appropriate without multidisciplinary review 8
• Always evaluate for MEN-1 syndrome before planning surgery, as this affects surgical strategy and surveillance 1, 2
• Functional imaging must accompany anatomical imaging, as anatomical CT/MRI alone may miss receptor-positive disease 2, 6

Follow-up Protocol

• Serial chromogranin A measurements every 3-6 months for G1/G2 tumors 2
• CT or MRI every 3-6 months for NET G1/G2; every 2-3 months for G3 2
• Somatostatin receptor imaging may be indicated after primary resection for surveillance 1, 2
• Follow-up upper endoscopy as appropriate after endoscopic resection 1, 7