Vasoactive Intestinal Polypeptide Secreting Tumor - VIPoma

Diagnosis

Indications for Testing

• Diarrhea without evident etiology

Laboratory Testing

• Electrolytes – hypokalemia in 100% of patients
• VIP level – elevated >200 pg/mL is diagnostic if appropriate clinical setting exists
  • VIP level >75 pg/mL with secretory diarrhea is highly suggestive of VIPoma
  • VIP levels are frequently >20% to 50% above the reference range for VIPoma
  • Scan (CT/MRI) required to identify tumor location

Histology

• Nested or trabecular arrangement of small- to medium-sized cells
  • Finely granular eosinophilic cytoplasm
  • Central, round-to-oval nuclei
  • Stippled chromatin (“salt and pepper”)
• Immunohistochemistry – chromogranin A, synaptophysin, cytokeratin, Ki-67, NSE, PGP 9.5
  • Tumor-specific confirmation – VIP

Imaging Studies

• CT/MRI or endoscopic ultrasound
• Somatostatin-receptor scintigraphy

 Differential Diagnosis

• Gastroenteritis (chronic or relapsing)
• Zollinger-Ellison syndrome (gastrinoma)
• Carcinoid tumor
• Villous adenoma
• Inflammatory bowel disease
• Malabsorption
• Laxative abuse
• Factitious diarrhea
• Pancreatic cancer
• Somatostatinoma

Clinical Background

Vasoactive intestinal polypeptide secreting tumors (VIPomas) are rare pancreatic neuroendocrine tumors associated with profuse diarrhea.

Epidemiology

• Incidence – 1/10,000,000
• Age – median onset 40s
• Sex – M:F, equal
• Occurrence – sporadic, although some occur in association with multiple endocrine neoplasia type 1 (MEN1)
• 60-80% of patients have metastatic disease at presentation

Risk Factors

• Genetic – ~5% associated with MEN 1

Pathophysiology

• Most tumors occur in the body and tail of the pancreas and are unifocal
• Symptoms result from the secretion of vasoactive intestinal polypeptide (VIP)
  • VIP is an amino acid polypeptide that is a potent stimulator of intestinal secretion and inhibitor of gastric acid secretion
• Other tumors can produce VIP – ganglioneuroblastoma, bronchogenic carcinoma, pheochromocytoma, and medullary thyroid carcinoma

Clinical Presentation

• Verner-Morrison syndrome
  • Chronic watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome)
  • Profuse diarrhea (patients may exceed 6-8 L/day) causing dehydration, metabolic acidosis, and renal failure

Treatment

• Symptom control – correct electrolyte imbalance
• Somatostatin analogues – reduce symptoms (controls diarrhea in ~70% of patients)
• Resection is the only cure

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

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Test Name and Number	Comments
Pancreatic Polypeptide 0099436 Method: Quantitative Radioimmunoassay