Neuroendocrine tumors of the pancreas are rare neoplasms representing approximately 2% of all pancreatic tumors9. Due to the progress of diagnostic imaging and radioimmunoassay, its diagnosis has become more frequent. Recent epidemiological studies suggest increased frequency12. Among the functioning tumors, vipoma (tumor cells producing vasoactive intestinal polypeptide) is also known as WDHA syndrome (watery diarrhea, hypokalaemia, and achlorhydria), Werner Morrison´s syndrome and pancreatic cholera; it is still rare neoplasia, mainly characterized by profuse diarrhea with hydro-electrolytic disorders. It has an estimated incidence of 0,2 to 0,5 per million inhabitants per year3. Approximately 90% of these tumors originate in the pancreas; however, there are descriptions located in other segments of the gastrointestinal tract, bronchus, adrenal, sympathetic ganglia and liver. There are few cases described in the medical literature of extra-pancreatic location in adults8. Due to its low incidence, it is unknown the true epidemiological data of this unique neoplasm.
The objective of this report is to present another case of extra-pancreatic vipoma.
Man of 54 years old had for four months diarrhea, watery stools, often in every three hours lasting 15 days; had 14 kg weight loss during this period, with asthenia, anorexia, malaise, muscle weakness and cramps. Laboratory tests showed VIP (intestinal polypeptide active vessel) 242 pg/ml (<75); Na=138; K=1.6; and creatinine=1.53. Ultrasonography showed hypoechoic image on segment IV of 4.2 cm, confirmed by CT with the presence of several hypervascular images in liver segments IV, III, II (Figure 1). Ultrasonography guided biopsy was performed in one liver nodule that revealed metastatic neuroendocrine carcinoma by immunohistochemistry. Laparotomy confirmed multiple liver metastases (Figure 2). Intraoperative ultrasonography showed nodule in pancreatic body. Bodycaudal pancreatectomy with splenectomy (Figure 3) and left hepatic trisegmentectomy were performed (Figure 4). No tumor was found in the pancreatic parenchyma. Histopathology showed acinar atrophy and hyperplasia of islets in the caudal region. In peri-pancreatic adipose tissue was confirmed the presence of five nodes with well-differentiated neuroendocrine carcinoma infiltrating the adipose tissue adjacent the neoplastic infiltration beyond perineural and angiolymphatic (Figure 5). Hepatic lesions confirmed the diagnosis of metastatic well-differentiated neuroendocrine carcinoma. Immunohistochemical analysis showed positivity for sinaftofisin, chromogranin and intestinal polypeptide active vessel (VIP). Ki-67 was positive in 10%. Patient had no major complications. There was immediate regression of diarrhea and electrolyte abnormalities. After 12 months, returned again with the same initial clinical picture. Liver CT images showed multiple metastatic nodulation diffusely distributed. Therapy with somatostatin analogue with prolonged action (LAR) and chemotherapy with inhibitors of mTOR (everolimus) was started with regression of liver lesions and clinical symptoms. At the third year postoperatively he was without clinical signs of disease recurrence.
Although there is a previous report, this neoplasm was first described by Werner and Morrison in 1958 in two patients with profuse diarrhea and hypokalemia associated with malignancy of non insulin-producing pancreatic islets. Its pathophysiological aspects were more well-known since 1973, the time in which Bloom et al.2 associated WDHA syndrome with increased serum vasoactive intestinal polypeptide5, a fact later confirmed by the studies of Kane et al.7 reproducing this syndrome after intravenous administration of VIP in five volunteers6. It is an aminoacid peptide produced by the delta-2 pancreatic islet cells and is also present in the central and peripheral nervous system and considered as a neurotransmitter. High concentrations are found in the gastrointestinal tract. Among its effects are described: stimulation of the smooth muscles of the gastrointestinal tract; increasing intestinal and pancreatic secretions; vasodilation; inhibition of gastric acid secretion; increased glycogenolysis and hypercalcemia4. Classically, vipomas present profuse diarrhea with consequent electrolyte repercussions, weight loss, and, more rarely, skin lesions, tachycardia and low back pain. Relatively often, these patients are initially investigated by a number of more common diseases whose main symptom is diarrhea. Much of this neoplasm originates in the pancreas and is sporadic; but may also be associated with multiple endocrine neoplasia11. However, these tumors can arise in the ganglia of the sympathetic nervous system, especially in children. Extra-pancreatic vipomas can be classified by their origin in neurogenic and non-neurogenic, the latter very little reported in literature5. From the clinical, laboratory and histopathological findings, it is not possible to differentiate neurogenic extra-pancreatic tumors. The neurogenic appears to have less severe clinical picture, lower VIP levels when compared to gastrointestinal disturbances, lack of production of pancreatic polypeptide and histopathological different characteristics8. The clinical diagnosis is confirmed by the increase in the level of serum VIP and radiological findings, mostly performed by computed tomography or magnetic resonance, localizing the tumor in the pancreas topography in most cases, due to the fact that most of these tumors have more than 3 cm. Likewise, more than 60% of these tumors have liver or lymph node metastasis at the time of diagnosis1. The therapeutic approach is to initially control the electrolyte disturbances, use of somatostatin analogues and subsequently surgical approach. Similar to others gastroenteroneuroendocrine diseases, also to other cancers, surgical resection is the best way to control the clinical symptoms and prolong survival10; it also can be performed cytoreductive operation, resection of liver metastases and even liver transplantation. The completion of adjuvant chemotherapy appears to play an important role in controlling the disease and have been described in addition to biotherapy with somatostatin analogues for long-term use to increase survival with good quality of life6 , 9. In this patient, besides the surgical treatment of liver metastases and the recurrence of the disease, there was considerable gain in life expectancy with the use of adjuvant chemotherapy.
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