Cite this page
FeedbackVasoactive intestinal polypeptide secreting tumors (VIPomas) are very rare pancreatic neuroendocrine tumors (PNETs) associated with profuse diarrhea. They are usually single tumors and metastatic at diagnosis. Generally, laboratory testing includes an electrolyte panel and vasoactive intestinal peptide test.
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
ARUP Laboratory Tests
Initial testing in evaluation of diarrhea
Quantitative Ion-Selective Electrode/Enzymatic Assay
Aid in the diagnosis of VIPoma
Quantitative Radioimmunoassay
Aid in monitoring; not recommended for diagnosis of carcinoid tumors
May be useful in monitoring nonsecretory sympathetic and parasympathetic neuroendocrine tumors
Immunofluorescence
Aid in histologic identification of neuroendocrine tissue
Stained and returned to client pathologist; consultation available if needed
Immunohistochemistry
Immunohistochemistry
Aid in histologic diagnosis of VIPoma
Stained and returned to client pathologist; consultation available if needed
Immunohistochemistry
Aid in grading of neuroendocrine tumors
Determine mitotic rate of tissue
Stained and resulted by ARUP
Immunohistochemistry
Aid in the diagnosis and monitoring of PNETs
Quantitative Radioimmunoassay
References
21226566
Batcher E, Madaj P, Gianoukakis AG. Pancreatic neuroendocrine tumors. Endocr Res. 2011;36(1):35-43.
26742109
Falconi M, Eriksson B, Kaltsas G, et al. ENETS Consensus Guidelines Update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology. 2016;103(2):153-171.
19196679
Kapoor R, Moseley RH, Kapoor JR, et al. Clinical problem-solving. Needle in a haystack. N Engl J Med. 2009;360(6):616-21.
20664472
Kulke MH, Anthony LB, Bushnell DL, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010;39(6):735-752.
22261919
Jensen RT, Cadiot G, Brandi ML, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012;95(2):98-119.
NCCN - Neuroendocrine Tumors
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Neuroendocrine and adrenal tumors. Version 4.2018. [Updated: May 2018; Accessed: Jul 2018]
28391265
Oberg K, Couvelard A, Delle Fave G, et al. ENETS Consensus Guidelines for standard of care in neuroendocrine tumours: biochemical markers. Neuroendocrinology. 2017;105(3):201-211.
22997445
Oberg K, Knigge U, Kwekkeboom D, et al. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii124-130.
21167379
Oberg K. Pancreatic endocrine tumors. Semin Oncol. 2010;37(6):594-618.
19713711
O'Toole D, Grossman A, Gross D , et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biochemical markers. Neuroendocrinology. 2009;90(2):194-202.
NCI - Pancreatic Neuroendocrine Tumors
Pancreatic neuroendocrine tumors (islet cell tumors) treatment (PDQ) - health professional version. National Cancer Institute. [Updated: Jan 2020; Accessed: Dec 2021]
20664471
Vinik AI, Woltering EA, Warner RR , et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010;39(6):713-734.
Medical Experts
Straseski
