Vasoactive Intestinal Polypeptide Secreting Tumor - VIPoma

Diagnosis

Indications for Testing

Chronic, profuse, secretory diarrhea

Criteria for Diagnosis

• Documented elevated (>200 pg/mL) vasoactive intestinal polypeptide (VIP) concentration (National Cancer Institute [NCI], 2018) in patient with large-volume secretory diarrhea (Vinik, North American Neuroendocrine Tumor Society [NANETS], 2010)
  • VIP level >75 pg/mL highly suggestive
• Large-volume diarrhea (Kulke, NANETS, 2010)
  • 70-80% of patients with VIPoma have more than 3L/day
  • Virtually all patients with VIPoma have >700mL/day
• Hypokalemia
• Achlorhydria

Laboratory Testing

• Electrolytes
  • Hypokalemia in 100% of patients
• VIP level

Histology

• Definitive diagnosis requires biopsy and pathologist examination
  • Useful immunohistochemical stains may include chromogranin A, synaptophysin, and cytokeratin​
  • For detailed descriptions, including recommended tests, refer to ARUP’s Immunohistochemistry Stain Offerings

Imaging Studies

• Computed tomography (CT)/magnetic resonance imaging (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

Monitoring

Plasma chromogranin – often used to monitor functional and nonfunctional PNETs after resection (Vinik, NANETS, 2010)

Background

Epidemiology

• Incidence – 1/10 million (rare cause of functioning PNETs)
• Age – median onset 40s
• Sex – M:F, equal
• Occurrence – sporadic, although some VIPomas occur in association with multiple endocrine neoplasia type 1 (MEN1)

Risk Factors

Genetic – ~5% associated with MEN1 (Jensen, 2012)

Pathophysiology

• Most tumors occur in the body and tail of the pancreas and are unifocal (other locations include adrenal, paraganglia)
• Symptoms result from the secretion of the peptide hormone VIP, 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 (pancreatic cholera)
  • Chronic watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome)
  • Profuse diarrhea (may exceed 6-8L/day) causes dehydration, metabolic acidosis, and renal failure