Duodenal Neuroendocrine Tumour

Duodenal neuroendocrine tumour is a well differentiated neuroendocrine neoplasm of the duodenum. It is the commonest duodenal neuroendocrine tumour type and arises from the bulb, the descending part or the ampulla.

Duodenal tumours form about 2% to 3% of gastrointestinal neuroendocrine tumours and their detection has risen with endoscopy. Mean age is 60 years.

Types are gastrinomas (about half; Zollinger-Ellison syndrome), non-functional tumours, somatostatinomas (often ampullary) and rarely other hormones. Ampullary tumours behave more aggressively.

Grade 1 has Ki-67 under 3%, grade 2 is 3% to 20%, and grade 3 is over 20%. Neuroendocrine carcinoma is poorly differentiated.

Lymph node involvement occurs in 40% to 60% of tumours over 2 cm, and in a smaller share of tumours of 1 to 2 cm.

Pathophysiology.

Tumours originate from enteroendocrine cells of the duodenal mucosa. Multiple gastrinomas occur in MEN1.

Often incidental. Features include abdominal pain, bleeding, obstructive jaundice or pancreatitis (ampullary), and hormone effects: Zollinger-Ellison syndrome (ulcers, diarrhoea) or, with somatostatinoma, diabetes, steatorrhoea and gallstones.

Endoscopy shows a yellow submucosal nodule, sometimes ulcerated. Biopsy with chromogranin A, synaptophysin and Ki-67. Endoscopic ultrasound assesses depth and nodes. Gallium-68 somatostatin receptor positron emission tomography, and CT or MRI, stage the disease. Measure fasting gastrin, chromogranin A and, if suspected, other hormones; test for MEN1.

Differential diagnosis.

• Brunner gland hamartoma.
• Adenoma or adenocarcinoma.
• Gastrointestinal stromal tumour.
• Pancreatic neuroendocrine tumour.
• Lymphoma.

Choose treatment by size, location, depth and grade.

• Non-ampullary tumour of 1 cm or less, grade 1, confined to the submucosa, no nodes: endoscopic resection (band assisted or submucosal dissection).
• Tumour of 1 to 2 cm: endoscopic ultrasound staged resection or local surgical excision with node sampling.
• Tumour over 2 cm, nodal disease, muscularis invasion, or ampullary location: pancreatoduodenectomy or radical local excision with lymphadenectomy.

Advanced, somatostatin-receptor-positive grade 1 or 2 disease:

• Lanreotide: 120 mg deep subcutaneously every 28 days; until progression; maximum as specialist titration; monitor glucose, gallstones and heart rate; use 60 mg starting dose in moderate to severe hepatic or renal impairment.
• Octreotide long acting: 30 mg IM every 4 weeks; until progression; ceiling 30 mg each 4 weeks unless specialist directed; monitor glucose, thyroid function and gallstones; reduce to 10 mg in severe renal impairment or cirrhosis.
• Lutetium-177 dotatate: 7.4 GBq IV every 8 weeks for 4 doses with amino acid infusion; monitor blood counts and renal function; avoid when creatinine clearance is under 30 mL/min.

Platinum based chemotherapy is used for grade 3 carcinoma.

Monitoring. Endoscopy at 6 to 12 months, then yearly for 5 years; imaging and chromogranin A at 6 to 12 months.

Referral and escalation. Neuroendocrine tumour multidisciplinary team, hepatobiliary surgery, genetics when multiple tumours or MEN1 features are present.