Vasoactive Intestinal Polypeptide Secreting Tumor - VIPoma

Diagnosis

Indications for Testing

  • Diarrhea without evident etiology

Laboratory Testing

  • Electrolytes – hypokalemia in 100% of patients
  • VIP level >75 pg/mL with secretory diarrhea is highly suggestive of VIPoma

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

Clinical Background

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

Epidemiology

  • Incidence – 1/10,000,000 (rare cause of functioning PNETs)
  • 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

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
Test Name and Number Recommended Use Limitations Follow Up
Electrolyte Panel 0020410
Method: Quantitative Ion-Selective Electrode/Enzymatic

Initial testing in evaluation of diarrhea

   
Vasoactive Intestinal Peptide 0099435
Method: Quantitative Radioimmunoassay

Measure VIP to aid in diagnosing VIPoma

   
Chromogranin A by Immunohistochemistry 2003830
Method: Immunohistochemistry

Aid in histologic identification of neuroendocrine tissue

Stained and returned to client pathologist; consultation available if needed

   
Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Aid in histologic identification of neuroendocrine tissue

Stained and returned to client pathologist; consultation available if needed

   
Pan Cytokeratin (AE1,3) by Immunohistochemistry 2003433
Method: Immunohistochemistry

Aid in histologic diagnosis of VIPoma

Stained and returned to client pathologist; consultation available if needed

   
Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

Aid in grading of neuroendocrine tumors

Determine mitotic rate of tissue

Stained and resulted by ARUP

   
Neuron Specific Enolase, Polyclonal (NSE P) by Immunohistochemistry 2004052
Method: Immunohistochemistry

Aid in histologic identification of neural and neuroendocrine tissue

Stained and returned to client pathologist; consultation available if needed

   
Protein Gene Product (PGP) 9.5 by Immunohistochemistry 2004091
Method: Immunohistochemistry

Aid in histologic diagnosis of VIPoma

Stained and returned to client pathologist; consultation available if needed

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Pancreatic Polypeptide 0099436
Method: Quantitative Radioimmunoassay