VIPoma is a rare pancreatic neuroendocrine tumour classically presenting with WDHA syndrome, elevated serum VIP and appearing as a well-defined, hypervascular mass on imaging.
Description
VIPoma, also known as Verner-Morrison syndrome, is a type of functioning neuroendocrine tumour typically arising from the pancreatic islets cells, characteristically producing excessive amounts of vasoactive intestinal peptide (VIP). VIP is a neurotransmitter with potent vasodilator and secretion-stimulating effects, which when overproduced can lead to a specific clinical syndrome characterised by watery diarrhoea, hypokalaemia, and achlorhydria (WDHA).
Pathogenesis
The pathogenesis of VIPoma involves the uncontrolled proliferation of neuroendocrine cells, typically within the pancreas, which results in excessive production and secretion of VIP. The overproduction of VIP results in the characteristic WDHA syndrome, due to its vasodilator effects, its ability to inhibit gastric acid secretion, and its stimulatory effects on intestinal water and electrolyte secretion.
Epidemiology, Risk Factors & Associations
- VIPomas are rare, with an estimated incidence of 1 per 10,000,000 individuals per year.
- They can occur at any age but are most common in adults, with a mean age of diagnosis around 50 years.
- There is no significant sex predilection.
- They may be associated with genetic syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1).
Clinical Features
- The classic clinical presentation of a VIPoma is the WDHA syndrome, which includes Watery Diarrhoea, Hypokalaemia, and Achlorhydria.
- Other symptoms can include abdominal pain, weight loss, and flushing due to the systemic effects of VIP.
Complications
- Approximately 60-80% of VIPomas are malignant, and 50-70% will have metastasised at the time of diagnosis, most commonly to the liver.
Pathological Features
Histopathology
- Macroscopic: VIPomas are typically well-defined, solitary lesions that may vary in size.
- Microscopic: On histology, VIPomas typically demonstrate a trabecular or glandular pattern, with uniform, round to oval cells and finely granular cytoplasm. Immunohistochemistry is positive for neuroendocrine markers (chromogranin A, synaptophysin) and VIP.
Serology
- Elevated serum VIP levels.
Biochemistry
- Hypokalaemia and metabolic acidosis can be seen due to the diarrhoea.
Radiological Features
General Features
- Typically, a well-defined, solitary hypervascular pancreatic mass is identified.
CT
- Non-contrast: The lesion may be seen as a hypoattenuating mass.
- Contrast-enhanced: VIPomas show marked enhancement in the arterial phase due to their hypervascular nature.
MRI
- T1WI: Lesions are typically hypointense.
- T2WI: Lesions may be mildly hyperintense.
- T1 C+: Shows enhancement in the arterial phase similar to CT.
US
- B-mode: Hypoechoic, well-defined lesion.
- Colour Doppler: May demonstrate increased vascularity.
NM
- Somatostatin receptor scintigraphy (SRS): Can show increased uptake in the tumour due to the expression of somatostatin receptors on the tumour cells.
Grading and Staging
As a type of neuroendocrine tumour, VIPomas can be classified based on their grade, which is determined by the Ki-67 index and mitotic count:
- Grade 1: Ki-67 index <2% and mitotic count <2 per 10 HPF
- Grade 2: Ki-67 index 3-20% or mitotic count 2-20 per 10 HPF
- Grade 3: Ki-67 index >20% or mitotic count >20 per 10 HPF
Diagnosis
The diagnosis of a VIPoma is typically made based on the clinical presentation of WDHA syndrome in conjunction with radiographic identification of a pancreatic tumour and elevated serum VIP levels. Histological confirmation is obtained with a biopsy of the lesion.
Differential Diagnosis
- Other neuroendocrine tumours of the pancreas: Such as insulinoma or glucagonoma. These are distinguished based on the hormones they produce and associated clinical syndromes.
- Pancreatic adenocarcinoma: Typically presents in older patients with weight loss, jaundice, and a poorly defined mass on imaging.
- Metastases to the pancreas: Often multiple lesions, associated with a known primary malignancy.
Management
Management of VIPomas involves surgical resection of the tumour when possible, which can be curative. In cases with unresectable or metastatic disease, systemic therapies, including somatostatin analogues and targeted therapies, may be used to control symptoms and slow disease progression.