Somatostatinoma of the Ampulla of Vater: A Systematic Review.

BACKGROUND AND AIMS: Somatostatinoma of the ampulla of Vater (SAV) is a rare neuroendocrine tumor that usually appears with atypical clinical manifestations and is associated with Von Recklinghausen's disease. The aims of this study were to systematically review the literature regarding SAV and to highlight the clinicopathological characteristics and optimal therapeutic management of this rare entity. METHODS: A systematic search of the literature in PubMed/Medline and Scopus databases was performed by two independent investigators, including all case reports and case series concerning SAVs from 1980 until September 2021. RESULTS: In total, 37 articles were retrieved, including 43 patients, with a male to female ratio of 1.8:1 and a mean age of 46.8 ± 11.3 years (mean, SD). For 23 out of 43 patients (53.5%), Von Recklinghausen's disease was proved. The main clinical manifestations were abdominal pain (41.9%), jaundice (27.9%), weight loss (20.9%) and bowel disorders (20.9%). Typical histological findings included psammoma bodies, nests or clusters of epithelial cells with eosinophilic cytoplasm, while somatostatin staining was positive in 35 patients (81.4%), chromogranin-A in 21 patients (48.8%) and synaptophysin in 18 patients (41.9%). Surgery was the initial therapeutic approach in 34 patients (79.1%), whereas Whipple's procedure was the preferred surgical approach in 23 patients (53.4%). The longest survival among included patients was 13 years and only two postoperative deaths (4.7%) were reported. CONCLUSIONS: Somatostatinomas of the ampulla of Vater are rare malignancies that require increased physicians' suspicion and accurate surgical approach in order to achieve optimal therapeutic results.

Familial Duodenal Somatostatinomatosis Not Associated With a Known Genetic Syndrome.

ABSTRACT: We report a father and his daughter who both had multiple somatostatinomas in the duodenal bulb without a known syndrome. The father, at age 68 years, was incidentally found to harbor 4 approximately 1.5-cm well-differentiated neuroendocrine tumors in the duodenal bulb. His preoperative somatostatin level was elevated. He underwent partial duodenectomy and regional lymph node dissection; one lymph node was positive for metastasis. One year postoperatively, a recurrence was found in the surgical bed; he was treated with octreotide for 2 years, which stabilized the recurrent tumor. Ten years postoperatively, the mucosa of his remaining duodenum was normal. His daughter, at age 53 years, was found to harbor multiple small neuroendocrine tumors in the duodenal bulb. Immunostaining of available specimens showed that the neuroendocrine tumors from the father and daughter both were strongly positive for somatostatin. Micronodules of somatostatin-expressing neuroendocrine cells were found in the parts of the specimens uninvolved with the tumors. Both patients exhibited no evidence of known syndromes associated with somatostatinoma. The daughter did not harbor mutations in 93 genes commonly found in genetic tumor syndromes. The 2 cases thus suggest a novel, autosomal dominant, genetic syndrome of familial duodenal somatostatinomatosis.

Duodenal somatostatinoma presenting as obstructive jaundice with the coexistence of a gastrointestinal stromal tumour in neurofibromatosis type 1: a case with review of the literature.

Somatostatinomas are rare neuroendocrine tumours, mostly located in the pancreas or duodenum, with an estimated incidence of 1 in 40 million. Duodenal somatostatinomas (DSs) are usually found in association with neurofibromatosis type 1 (NF1), tuberous sclerosis and Von Hippel-Lindau syndrome. Gastrointestinal stromal tumours (GIST) have also been described in NF1, but the association with somatostatinoma is very uncommon. We report the case of a patient with NF1 who presented with obstructive jaundice due to multiple firm nodules around the ampulla of Vater. A pancreaticoduodenectomy was performed and revealed a 1 cm duodenal/ampullary mass which stained positive for somatostatin, together with a GIST also found on the duodenal wall. Despite its rarity, ampullary somatostatinomas should be considered in the differential diagnosis of biliary tract dilation in patients with NF1.

Novel insights into the polycythemia-paraganglioma-somatostatinoma syndrome.

Worldwide, the syndromes of paraganglioma (PGL), somatostatinoma (SOM) and early childhood polycythemia are described in only a few patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A). This study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings into perspective these experiences with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11-46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8-38) and SOMs at 29 years (range 22-38). PGLs were multiple, recurrent and metastatic in 100, 100 and 29% of all cases, and SOMs in 40, 40 and 60%, respectively. All PGLs were primarily norepinephrine-producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA). Therefore, [18F]-FDOPA PET/CT, not [68Ga]-(DOTA)-[Tyr3]-octreotate ([68Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges.

Combined presence of multiple gastrointestinal stromal tumors along with duodenal submucosal somatostatinoma in a patient with neurofibromatosis type 1.

Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, with increased risk of developing benign and malignant tumors of the gastrointestinal tract (GIT). However, the synchronous presence of multiple GIT stromal tumors and duodenal submucosal somatostatinoma, like in this 50-year-old female NF-1 patient, is very rare. She presented with hematemesis, malena, along with multiple neurofibromas all over the body. Thorough radiological and peroperative work-up revealed multiple ulcerated submucosal and serosal nodules in the proximal small intestine. Histological work-up revealed diagnosis of a duodenal submucosal somatostatinoma with multifocal serosal gastrointestinal stromal tumors. This case is being reported to highlight the rare coincidence of multiple GIT tumors in an NF-1 patient.

Case report: recurrent acute pancreatitis secondary to papillary somatostatinoma--a new association.

Acute pancreatitis may rarely be caused by papillary mass lesions such as adenocarcinomas and neuroendocrine tumours. Occasionally these papillary lesions may cause recurrent episodes of acute pancreatitis and patients presenting in this way require further pancreatic investigation. We believe this to be the first reported case of a duodenal papillary somatostatinoma causing recurrent acute pancreatitis. The patient was investigated with multiple imaging modalities, both at endoscopy and with more traditional radiology, and treated with resection by Whipple's pancreaticoduodenectomy. If diagnosed early in the absence of distant metastases the prognosis of papillary somatostatinoma with tumour resection is excellent.

Severely fluctuating blood glucose levels associated with a somatostatin-producing ovarian neuroendocrine tumor.

CONTEXT: Somatostatin-producing tumors are a rare type of neuroendocrine tumor. Their effects on blood glucose levels have been variously reported, and detailed reports have been scarce. OBJECTIVE: The aim of this study was to identify the reasons for the extraordinary blood glucose fluctuations in a case with no previous history of diabetes. PATIENTS AND METHODS: A 68-yr-old nondiabetic woman with an ovarian tumor was suffering from hyper- and hypoglycemia. Based on the results of an oral glucose tolerance test and continuous glucose monitoring, we speculated that the fluctuating blood glucose level was accompanied not only by a low insulin level but also by low counter-regulatory hormones levels, and that those broad hormonal suppressions were caused by a high somatostatin level produced in the ovarian tumor. We performed an oophorectomy and assessed the pathology of the tumor and changes in the blood glucose profile as well as hormonal levels postoperatively. RESULTS: The blood glucose level was completely normalized after the oophorectomy. Insulin secretion was also normalized. Histological examination showed that the tumor comprised a mature cystic teratoma and a stromal carcinoid. Immunohistochemically, the stromal carcinoid component was positive for somatostatin. The somatostatin level was 8505 pmol/liter preoperatively, which dropped down to 71.5 pmol/liter postoperatively. We found two previous reports of somatostatin-producing ovarian neuroendocrine tumors. Somatostatin levels among cases of ovarian origin were much higher than those among cases of gastrointestinal origins, and cases of ovarian origin all experienced blood glucose fluctuations. CONCLUSION: Extremely high somatostatin levels and blood glucose fluctuations may be characteristics of somatostatin-producing ovarian neuroendocrine tumors.

Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia.

Hypoxia-inducible factors are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. When these proteins are dysregulated, they contribute to tumorigenesis and cancer progression. However, mutations in genes encoding α subunits of hypoxia-inducible factors (HIF-α) have not previously been identified in any cancer. Here we report two novel somatic gain-of-function mutations in the gene encoding hypoxia-inducible factor 2α (HIF2A) in two patients, one presenting with paraganglioma and the other with paraganglioma and somatostatinoma, both of whom had polycythemia. The two mutations were associated with increased HIF-2α activity and increased protein half-life.

Diarrhea caused by circulating agents.

Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion.

Somatostatinoma of the first jejunal loop in a patient with neurofibromatosis von Recklinghausen and bilateral pheochromocytoma.

Somatostatinoma is a rare neuroendocrine tumor which especially develops in the pancreas. There are few communicated cases about extra-pancreatic localization, having as a particularity the absence of somatostatin hypersecretion syndrome and frequent association with von Recklinghausen neurofibromatosis. We present the case of a 42-year old patient with Von Recklinghausen neurofibromatosis admitted in our clinic with a chronic upper digestive obstruction syndrome. The presence of a first jejunal loop somatostatinoma was an intraoperative surprising diagnosis that imposed jejunal resection and association of complementary specific treatment. Despite the therapeutic correct management, the status of the patient deteriorated very fast, confirming the aggressiveness of this neoplasia.

Diarrhoea due to pancreatic diseases.

The exocrine pancreas provides essential digestive enzymes necessary for the proper breakdown and absorption of ingested food in humans. Any disruption of this process can lead to malabsorption and resultant diarrhoea. Typically, disruption of over 90 percent of the pancreatic parenchyma is needed to result in diarrhoea. This disruption can result from widespread pancreatic necrosis in acute pancreatitis, fibrotic replacement of the parenchyma as seen in chronic pancreatitis and in patients with pancreatic cancer where normal tissue is replaced by tumour and/or the pancreatic duct becomes obstructed. Several uncommon tumours of the pancreas can also cause diarrhoea through the secretion of hormones. This article will explore each of these diseases, including the pathogenesis and treatment.

Malignant somatostatinoma presenting with diabetic ketoacidosis and inhibitory syndrome: pathophysiologic considerations.

OBJECTIVE: To describe a patient with diabetic ketoacidosis secondary to a malignant somatostatinoma. METHODS: We present the clinical, laboratory, radiologic, and pathologic findings of a patient with diabetic ketoacidosis secondary to a malignant somatostatinoma. We also review the potential effects of somatostatin on glucose homeostasis and discuss the underlying pathophysiologic mechanisms. RESULTS: A 30-year-old woman presented with diabetic ketoacidosis and had a malignant somatostatinoma with hepatic, bone, and lymph node metastasis. She exhibited features of somatostatinoma "inhibitory syndrome" characterized by mild nonketotic hyperglycemia, hypochlorhydria, cholelithiasis, steatorrhea, anemia, and weight loss. In these tumors, the absence of ketoacidosis is thought to arise from the somatostatin-induced simultaneous suppression of the secretion of insulin and glucagon. The patient's primary tumor could not be located. CONCLUSIONS: Diabetic ketoacidosis may occur in somatostatinomas. The secretion of larger molecular weight forms of somatostatin from the tumor may contribute to the ketogenesis.

Pancreatic somatostatinoma with obscure inhibitory syndrome and mixed pathological pattern.

Somatostatinoma is a very rare neuroendocrine tumor that originates from D cells and accounts for less than 1% of all gastrointestinal endocrine tumors. The duodenum is the most frequent site for this tumor, followed by the pancreas. We here describe a 46-year-old Chinese woman who developed pancreatic somatostatinoma presenting with the characteristic "inhibitory" syndrome, but the symptoms were obscure and seemingly uncorrelated. This case is also unique for its large tumor size and mixed pathological pattern. Distal pancreatectomy was performed, and the patient has remained well since operation. As the syndromes of somatostatinoma may be obscure and atypical, clinicians should review all clinical findings to obtain an accurate diagnosis. Aggressive surgery is preferred to improve the survival.

A rare cause of obstructive jaundice and weight loss in Von Recklinghausen's disease.

We present the case of a patient with the rare triad of Von Recklinghausen's disease associated with a somatostatinoma and a gastrointestinal stromal tumour (GIST). The patient had recurrent jaundice, the typical somatostatinoma syndrome, positive MR imaging but negative 68Ga-DOTATOC PET scanning in a histopathology-proven somatostatinoma tumour.

Pancreatic somatostatinoma manifested as severe hypoglycemia.

Somatostatinoma is a rare somatostatin-producing endocrine tumor, probably malignant. Due to its nonspecific symptoms such as vague abdominal pain, weight loss, or occult clinical features, misdiagnosis occurs. We report a case of pancreatic somatostatinoma with severe hypoglycemia. The patient had experienced severe hypoglycemic attacks for 11 months periodically. Contrast computed tomography scan revealed an isodensity mass about 2 cm in the head of the pancreas. Ultimately, a local excision was carried out as the tumor was located exactly on the surface of the pancreas. Somatostatinoma was established after immunohistochemical technique. The patient led a normal life without any complaint at 1 year follow-up.