VIPoma pathophysiology

A VIPoma is a rare tumor of the non-beta cells of the pancreas that results in the overproduction of the hormone vasoactive intestinal peptide (VIP). On microscopic histopathological analysis, findings of VIPoma are composition of uniform, small to intermediate-sized cells in clusters, nests, and trabecular growth patterns with hyperchromatic nuclei and scant cytoplasm. BKJHKJJFHKH

• VIPomas are neuroendocrine neoplasms arising from the pancreas in 90% of the cases, while the remaining 10% occur in extra pancreatic tissues like bronchus, colon, liver, and neural crest-derived tissues.^[1][2][3]
• When VIPoma is found in the pancreas, 75% of the tumors occur in the tail of pancreas, while 25% occur in the pancreatic head and body.
• VIPomas originate in amine precursor uptake and decarboxylation (APUD) cells of the gastroenteropancreatic endocrine system and in adrenal or extra-adrenal neurogenic sites.
• VIPoma causes cells in the pancreas to produce high levels of a hormone called vasoactive intestinal peptide (VIP).

• Vasoactive intestinal peptide hormone has three important functions^[4][5]
  • Stimulates secretions from the intestine and pancreas
  • Inhibits gastric acid secretion
  • Increases glycogenolysis
  • Causes hypercalcemia and relaxes sphincters and circular smooth muscles of gut.
• VIP hormone in CNS has effect on behavior and learning as well as secretagouge.
  • It induces release of prolactin, luteinizing hormone and growth hormone from the pituitary as well as regulates the release of insulin and glucagon from the pancreas.

• Vasoactive intestinal peptide (VIP) is a structural homologue of secretin.^[6]
• VIP innervates on both VPAC1 and VPAC2.
• When VIP binds to VPAC2 receptors in intestinal cells, a G-alpha-mediated signalling cascade is triggered.
• In a number of systems, VIP binding activates adenyl cyclase activity leading to increases in cAMP and PKA.
• The PKA then activates other intracellular signaling pathways like the phosphorylation of CREB and other transcriptional factors.
• Elevated serum VIP levels leading to increased intracellular cAMP causes increased intestinal secretion of water along with Na+, K+, HCO3 -, and Cl- in the intestinal lumen, as well as bone resorption, vasodilation, and inhibition of gastric acid secretion.

On gross pathology, circumscribed, solid mass composed of white tan, irregular and firm mass within fleshy parenchyma are characteristic findings of VIPoma.^[7]

• Histologically, a VIPoma demonstrates a composition of uniform, small to intermediate-sized cells in clusters, nests, and trabecular growth patterns with hyperchromatic nuclei and scant cytoplasm. A few nests may also exhibit psuedorosettes.^[6][3]
• Immunohistochemistry of VIPoma typically demonstrates positive immunoreactivity for vasoactive intestinal peptide, cytokeratin, neuron specific enolase, chromogranin, synaptophysin, and somatostatin, with negative reactivity for S100, calcitonin, PSA, CEA, insulin, glucagon, and growth hormone.

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