- Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: George T Griffing, MD more...
Plasma vasoactive intestinal peptide (VIP) levels are determined by radioimmunoassay. In cases of VIPoma, VIP levels are usually 2-10 times the normal range (20-30 pmol/L). VIP levels must be determined when the patient is symptomatic because VIP release from the tumor fluctuates.
Imaging studies focus primarily on the pancreas, where 90% of VIPomas are located. Tumor localization normally is not difficult, because at the time of diagnosis, these tumors are generally larger than 3 cm in their longest dimension. Computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy are imaging modalities that can be used in the diagnosis of VIPoma. Reports have demonstrated successful VIPoma localization with99m Tc sestamibi.
No formal staging criteria for VIPoma have been generally accepted. Metastasis most often occurs to the liver or regional lymph nodes. Rarely, metastasis to skin has been reported.
A diagnosis of VIPoma is made when watery diarrhea, hypokalemia, and achlorhydria are present in the setting of elevated serum VIP concentrations. Stool volumes of less than 700 mL/day virtually exclude the diagnosis; typical stool volumes in the presence of a VIPoma exceed 3 L/day.
A normal plasma VIP level is 20-30 pmol/L or less, as determined by radioimmunoassay. VIP levels in patients with VIPoma often reach 160-250 pmol/L or higher. VIP levels should be drawn after fasting. Because VIP is degraded rapidly, a protease inhibitor, such as aprotinin, is added to the blood sample, which must be kept frozen at −70°C until processed. Because VIP secretion from the tumor may be episodic, serum VIP levels should be collected during bouts of severe diarrhea.
Hypokalemia and non–anion gap acidosis are the main diagnostic features of VIPomas. Hypokalemia may necessitate aggressive potassium replacement.
Hypercalcemia may occur in the absence of multiple endocrine neoplasia (MEN) type 1 syndrome or elevated parathyroid hormone levels. The mechanism of action is not clear but is believed to involve increased bone resorption. The dehydration from severe diarrhea certainly may exacerbate the hypercalcemia.
Hyperglycemia may be caused by the direct glycogenolytic effect of VIP on the liver and by the inhibitory effect of hypokalemia on pancreatic islet cell insulin release.
Hypochlorhydria or achlorhydria is seen in at least 75% of patients with VIPoma because VIP inhibits histamine- and pentagastrin-stimulated gastric acid secretion. This abnormality can be evaluated by measuring gastric pH or basal gastric acid output.
Renal function should be assessed by measuring blood urea nitrogen (BUN) and serum creatinine levels. Other electrolytes, including magnesium, should be checked and replaced. Stool weight with potassium measurements verifies high gastrointestinal (GI) potassium losses.
VIPomas may cosecrete other hormones, including pancreatic polypeptide, calcitonin, and neurotensin.
CT is indicated to search for neck, mediastinal, or retroperitoneal masses. No calcifications or bony infiltrations should be found. CT will successfully identify the primary tumor in most cases; it also assists in including or excluding liver metastasis.
In a series of 31 patients from China, Peng et al reported that CT successfully identified all VIPomas in the pancreatic body and tail but only 71% of VIPomas in the pancreatic head.
Magnetic Resonance Imaging
MRI may be used if CT is contraindicated (eg, if the patient is allergic to iodine contrast dyes or is in a state of renal failure). VIPomas are best observed on T1-weighted, fat-suppressed images as low-signal-intensity masses. Liver metastases may demonstrate intensive peripheral ring enhancement on immediate postgadolinium spoiled gradient-echo images.
Somatostatin Receptor Scintigraphy
Somatostatin receptor scintigraphy using radionuclide-labeled octreotide (111 In-pentetreotide (ie, DTPA-D-Phe-1-octreotide),111 In-DOTA-DPhe1 -Tyr3 -octreotide), or lanreotide (111 In -DOTA-lanreotide) may be useful for characterizing an abnormality found on a CT scan or for identifying occult or distant metastatic disease. It may also be used if postoperative changes diminish the clarity of a CT scan. Sensitivity for localization of all pancreatic endocrine tumors has been reported at 80-90%, with 92% sensitivity for tumors larger than 1 cm.
Other previously employed techniques include technetium-99m scintigraphy, 123-iodine-VIP receptor scintigraphy, and single-photon emission CT (SPECT). Investigations have suggested that in the future, the use of SPECT scanning may improve the value of somatostatin receptor scintigraphy for the localization of neuroendocrine tumors, including VIPomas.
18 F-deoxyglucose (FDG)-PET scan has also been used to diagnose neuroendocrine tumors. However, it may not be as sensitive as somatostatin receptor scintigraphy.
Chest radiography may reveal a paravertebral mass. Endoscopic retrograde cholangiopancreatography may demonstrate occlusion of the major pancreatic duct. It may also reveal calcifications in the body of the pancreas. Transabdominal ultrasonography may be used for early screening to exclude liver metastases, which may be present as hepatic calcifications.
Electrocardiography may reveal QRS widening and T-wave flattening if hypokalemia is severe. Colonoscopy may be useful as a means of evaluating for a villous adenoma as an alternative cause of potassium-losing diarrhea.
VIPomas, like other pancreatic endocrine tumors, are thought to arise from the pluripotent cells in ductal epithelium. Histologic examination usually reveals, as is typical for neuroendocrine tumors, sheets of nested, uniform-appearing cells with round nuclei and a low mitotic rate.
Immunohistochemical staining is positive for chromogranin A and VIP. Under electron microscopy, neurosecretory granules may be seen clustering around Golgi complexes and the endoplasmic reticulum. Classifying a tumor as malignant or benign on the basis of microscopic appearance alone is difficult.
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