Vasoactive Intestinal Polypeptide Secreting Tumor - VIPoma

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

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

Vasoactive intestinal polypeptide secreting tumors (VIPomas) are very 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 (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 vasoactive intestinal polypeptide (VIP)
    • Hormone secreted – 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 (patients may exceed 6-8 L/day) causes dehydration, metabolic acidosis, and renal failure
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.

Electrolyte Panel 0020410
Method: Quantitative Ion-Selective Electrode/Enzymatic

Recommended Use 

Initial testing in evaluation of diarrhea

Vasoactive Intestinal Peptide 0099435
Method: Quantitative Radioimmunoassay

Recommended Use 

Aid in the diagnosis of VIPoma

Chromogranin A by Immunohistochemistry 2003830
Method: Immunohistochemistry

Recommended Use 

Aid in histologic identification of neuroendocrine tissue

Stained and returned to client pathologist; consultation available if needed

Synaptophysin by Immunohistochemistry 2004139
Method: Immunohistochemistry

Recommended Use 

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

Recommended Use 

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

Recommended Use 

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

Recommended Use 

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

Recommended Use 

Aid in histologic diagnosis of VIPoma

Stained and returned to client pathologist; consultation available if needed

Guidelines

Jensen RT, Cadiot G, Brandi ML, de Herder WW, Kaltsas G, Komminoth P, Scoazec J, Salazar R, Sauvanet A, Kianmanesh R, Barcelona Consensus Conference participants. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012; 95(2): 98-119. PubMed

NCCN Clinical Practice Guidelines in Oncology, Neuroendocrine Tumors. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Aug 2017]

O'Toole D, Grossman A, Gross D, Fave GD, Barkmanova J, O'Connor J, Pape U, Plöckinger U, Mallorca Consensus Conference participants, European Neuroendocrine Tumor Society. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biochemical markers. Neuroendocrinology. 2009; 90(2): 194-202. PubMed

Protocol for the Examination of Specimens from Patients with Neuroendocrine Tumors (Carcinoid Tumors) of the Small Intestine and Ampulla. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Revised Oct 2013; Accessed: Jun 2017]

Protocol for the Examination of Specimens from Patients with Neuroendocrine Tumors (Carcinoid Tumors) of the Stomach. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Revised Jun 2014; Accessed: Jun 2017]

Protocol for the Examination of Specimens from Patients with Tumors of the Endocrine Pancreas. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jan 2016. College of American Pathologists (CAP). Northfield, IL [Revised Aug 2016; Accessed: Jun 2017]

Vinik AI, Woltering EA, Warner RR, Caplin M, O'Dorisio TM, Wiseman GA, Coppola D, Go VL, North American Neuroendocrine Tumor Society (NANETS). NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010; 39(6): 713-34. PubMed

Öberg K, Knigge U, Kwekkeboom D, Perren A, ESMO Guidelines Working Group. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012; 23 Suppl 7: vii124-30. PubMed

General References

Batcher E, Madaj P, Gianoukakis AG. Pancreatic neuroendocrine tumors. Endocr Res. 2011; 36(1): 35-43. PubMed

Kapoor R, Moseley RH, Kapoor JR, Crapo LM, Saint S. Clinical problem-solving. Needle in a haystack. N Engl J Med. 2009; 360(6): 616-21. PubMed

Oberg K. Pancreatic endocrine tumors. Semin Oncol. 2010; 37(6): 594-618. PubMed

Medical Reviewers

Salama, Mohamed E., MD, Medical Director, Hematopathology and Immunohistochemistry Staining at ARUP Laboratories; Associate Professor of Clinical Pathology, Director of Hematopathology Fellowship Program, University of Utah

Straseski, Joely A., PhD, MS, MT(ASCP), DABCC, Medical Director, Endocrinology at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Last Update: July 2017