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.

Somatostatinoma duodenal / Duodenal somastotinoma

Alrededor del 70%de los tumores endocrinos bien diferenciados asientan en el tracto gastrointestinal. Los tumores duodenales bien diferenciados constituyen solo el 2,6 % de todos los tumores neuroendocrinos (NET).El somatostatinoma es un tumor raro que se localiza en páncreas o duodeno con una incidencia de 1:40 millones.La neurofibromatosis tipo I es una enfermedad autosómica dominante, la mutación en el gen supresor de tumores NF1 favorece la aparición de neoplasias en estos pacientes.

About 70% of well-differentiated endocrine tumors arise from the gastrointestinal tract. Duodenal well-differentiated tumors account for only 2.6% of all neuroendocrine tumors. Somatostatinomas are rare neuroendocrine tumors (NETs) with an incidence of 1 in 40 million. These unusual tumors arise predominantly in the pancreas and peripancreatic duodenum. Neurofibromatosis type I is an autosomal dominant disease, the mutation in the tumor suppressor gene NF1 favors the appearance of neoplasms in these patients.

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.

Pancreatic somatostatinoma diagnosed preoperatively: report of a case.

CONTEXT: Somatostatinoma is a rare neoplasm of the pancreas. Preoperative diagnosis is often difficult. CASE REPORT: We report a 72-year-old woman with a pancreatic head tumor measuring 37 mm in diameter, and enlargement of the lymph nodes on the anterior surface of the pancreatic head and the posterior surface of the horizontal part of the duodenum. Laboratory data showed an elevated plasma somatostatin concentration. Examination of a biopsy specimen of the pancreatic head mass obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) showed histopathological features of a neuroendocrine tumor. Immunohistochemical staining showed that the tumor cells were positive for somatostatin, leading to a preoperative diagnosis of pancreatic somatostatinoma. The patient underwent pylorus-preserving pancreaticoduodenectomy. The plasma somatostatin concentration decreased progressively after surgery. CONCLUSIONS: A rare case of pancreatic somatostatinoma with lymph node metastases was presented. Immunohistochemical analysis of a biopsy specimen obtained by EUS-FNA was useful for preoperative diagnosis.

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.

Somatostatin-producing duodenal carcinoma: clinicopathological description of a case.

Somatostatinomas are rare functioning neoplasms usually arising in the pancreas and duodenum. They are seldom associated with typical clinical symptoms. Their diagnosis is confirmed only by histological and immunohistochemical studies and the presence of specific hormones. Two distinct clinicopathological forms of somatostatinoma exist: duodenal and pancreatic somatostatinomas. Clinically, compared to pancreatic somatostatinomas, duodenal somatostatinomas are more often associated with nonspecific symptoms and neurofibromatosis, but less often with somatostatinoma syndrome or metastasis. We report a case of somatostatin-producing duodenal carcinoma in a 45-year-old female with neither neurofibromatosis nor somatostatinoma syndrome. Abdominal computed tomography showed a 18 mm mass in the duodenum which had given rise to multiple lymph node metastases. Although the endoscopic biopsies were free of malignancy, the patient subsequently underwent Whipple's operation for the duodenal mass. Immunohistochemical analysis confirmed the diagnosis of somatostatin-producing carcinoma.

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.

The immunohistochemistry aspects in two cases of neurofibromatosis-associated abdominal tumors.

Type 1 neurofibromatosis associates various abdominal tumors as gastrointestinal stromal tumors, duodenal or pancreatic carcinoid, and adrenal tumors like pheochromocytoma. We present the immunohistochemistry report in two cases with different profile regarding the evolution. One case is a 7th decade women diagnosed with unilateral pheochromocytoma and GISTs, with a good prognosis after surgery. The other case is a 41-year-old male diagnosed with duodenal metastatic somatostatinoma after an intestinal occlusive syndrome and later the hormonal profile leaded to the diagnosis of pheochromocytoma. The patient had a fulminate evolution within six months from diagnosis.

Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances.

Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behaviour and most important, in their response to certain anti-tumour treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume.

Biochemical markers for gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

Biochemical markers are applied in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) for diagnostic, prognostic or predictive purposes. Chromogranin A is the most important general marker and it is recommended to be measured in every patient with a suspected NET, whereas Neuron Specific Enolase is elevated mainly in poorly differentiated NETs. Pancreatic Polypeptide is used in the diagnosis of pancreatic non-functioning NETs, whereas Chorionic Gonadotrophin has an adjunctive role. In the case of functioning tumours, specific markers should be sought and monitored during follow up. Endogenous hyperinsulinemia is suggested in the presence of non-suppressible insulin and proinsulin levels during hypoglycemia, whereas high fasting or stimulated gastrin levels along with elevated gastric acid output are diagnostic for the Zollinger-Ellison syndrome. Glucagon, vasoactive intestinal polypeptide (VIP) and somatostatin are markers for glucagonoma, VIP-oma and somatostatinoma syndromes respectively. In case of ectopic paraneoplastic syndrome, the relevant hormone serves as a diagnostic and prognostic marker.

[Diagnostics and treatment in functional pancreatic neuroendocrine tumours]. / Diagnostik und Therapie bei funktionell aktiven pankreatischen neuroendokrinen Tumoren.

Pancreatic neuroendocrine tumours (PNET) are rare entities with an annual incidence of < 100,000. About 1 - 2 % of pancreatic neoplasias are neuroendocrine tumours. About one third of these tumours secrete biologically active substances that lead to development of specific clinical syndromes. PNET may occur sporadically or in association with hereditary syndromes, such as multiple endocrine neoplasia type 1 (MEN1). Among the functional PNET, insulinomas and gastrinomas are the most common entities. In contrast, vasoactive intetinale peptide (VIP)-secreting tumours, glucagonomas, serotonin-secreting carcinoid tumors, and tumours with secretion of ectopic hormones, such as calcitonin, are extremely rare. Once diagnosis has been established on the basis of clinical and laboratory findings, localization of the source of pathologic hormone secretion is warranted. Imaging methods frequently used for localization of PNET comprise anatomical imaging modalities, computed tomography, and magnetic resonance imaging, endoscopic ultrasound, selective arterial catheterization with hepatic venous sampling, DTPA-octreotid scintigraphy and DOTA-D-Phe(1)-Tyr(3)-octreotid positron emission tomography. Therapy is based on the specific tumour entity and the extent of the disease. In the majority of patients, even in the case of malignant disease, a surgical approach is warranted, eventually combined with a medical treatment.

Tumores neuroendocrinos del páncreas / Pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors are infrequent and slow-growing neoplasms. They are classified basedon their clinical presentation as functioning and nonfunctioning tumors. The most common functionaltumors are the insulinoma and gastrinoma. They can be sporadic or be part of hereditary forms as MEN-1.The diagnosis is based on the detection of the specific clinical syndrome in association of high levels of the substance secreted by the tumor and conventional imaging studies or others such as stimulation tests, somatostatin receptor scintigraphy and endoscopic ultrasound. In general, these tumors have a better prognosis than the pancreatic adenocarcinoma and they can show metastasis to the liver and infrequently, in bones. The treatment can be managed medically diminishing the inappropriate secretion of the substances by the tumor using, for example, the somatostatin analogs. Surgery should be always considered, especially in case of insulinomas, small non-functioning tumors, and small gastrinomas that can be managed with surgery enucleation. More advanced resective surgery, such as Whipple resection, are not routinely recommended and they should be limited to selected patients. In advanced tumors, there are other treatment alternatives, for example, hepatic resection, radiofrequency, chemotherapy and new agents such as sunitinib and everolimus.

Los tumores neuroendocrinos pancreáticos son infrecuentes y de crecimiento lento. Se clasifican en tumores funcionantes o no funcionantes (TNEP-NF), de acuerdo a la presentación clínica. Los tumores funcionantes más frecuentes son los insulinomas y los gastrinomas. Pueden ocurrir en forma esporádica o asociados a síndromes hereditarios como la NEM- 1, entre otros. El diagnóstico se basa en la detección del síndrome clínico específico asociado a la demostración de niveles elevados de la sustancia secretada y exámenes imagenológicos convencionales u otros más específicos como de estimulación, cintigrafía de receptores de somatostatina y endosonografía. En general, tienen mejor pronóstico que los adenocarcinomas pancreáticos y pueden dar metástasis hepáticas y con menor frecuencia, óseas. El tratamiento puede ser médico disminuyendo la secreción inapropiada de las sustancias producidas por el tumor como los análogos de somatostatina. La cirugía siempre debe ser considerada, especialmente en caso de insulinomas, pequeños TNEP-NF, y gastrinomas pequeños, que pueden ser tratados con enucleación quirúrgica. Las cirugías resectivas más avanzadas, como la operación de Whipple no están recomendadas en forma rutinaria y sólo deben ser utilizadas en pacientes seleccionados. En casos de tumores avanzados, existen alternativas de tratamiento, como la resección hepática, radiofrecuencia, quimioterapia, y terapia con nuevos agentes en estudio como el sunitinib y everolimus.

[Symptoms and diagnosis of neuroendocrine tumors of the digestive system]. / Az emésztoszervi neuroendokrin daganatok tünetei és diagnosztikája.

Neuroendocrine tumors of the digestive system can cause very diverse clinical symptoms. Due to the secretion of biogenic amines, peptides and hormones secreted by the tumor cells, various paraneoplastic syndromes can evolve, on the other hand, the growth and spreading of hormonally inactive tumors can result in different local symptoms. Patients can be symptom-free for a long time or aspecific, often periodical symptoms can prevent recognition or lead to misdiagnosis for years. The symptomatology of hormonally active tumors, derived mainly from the pancreas is very characteristic. Carcinoid syndrome can be seen in 10-18% of patients with neuroendocrine tumors. In this review, the critical appreciation of laboratory and imaging modalities is discussed. Among the major new developments in this field, the introduction of serum chromogranin A assay and new small bowel examination methods should be mentioned. Capsule endoscopy and balloon enteroscopy can provide possibility of much more earlier diagnosis, as previously. The worldwide spreading of endoscopic ultrasound and fine needle biopsy allows the detection and clear localization of pancreatic neuroendocrine tumors.

Duodenal somatostatinoma: a case report and review.

Somatostatinomas are rare functioning carcinoid tumors that usually arise in the pancreas and duodenum. They are seldom associated with typical clinical symptoms; their diagnosis is confirmed only by histological and immunohistochemical studies and the presence of specific hormones. Two distinct clinicopathological forms of somatostatinoma exist: duodenal and pancreatic somatostatinomas. Clinically, compared to pancreatic somatostatinomas, duodenal somatostatinomas are more often associated with nonspecific symptoms and neurofibromatosis, but less often with somatostatinoma syndrome or metastasis. Histologically, duodenal somatostatinomas frequently have psammoma bodies in the tumor cells. We report a case of duodenal somatostatinoma in 58-year-old man with vague epigastric pain and nausea. He did not have diabetes, steatorrhea, or cholelithiasis. Abdominal computed tomography showed a 25-mm mass in the duodenum and 25-mm nodule in the liver. Endoscopic retrograde cholangiopancreatography showed a duodenal submucosal tumor. Although the endoscopic biopsies were free of malignancy, the patient subsequently underwent Whipple's operation for the duodenal mass. Examination revealed as a somatostatinoma using a special stain for somatostatin.

Pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms representing <5% of all pancreatic malignancies with an estimated incidence of 1-1.5 cases/100,000. PNETs are broadly classified as either functional or nonfunctional. Functional PNETs include insulinomas, gastrinomas, vasoactive intestinal peptideomas, glucagonomas, and somatostatinomas. The clinical manifestations associated with these tumors are the result of excessive hormonal secretion and action. The functional nature of these tumors makes pancreatic hormone testing critical not only for initial diagnosis but also for follow-up, because they are important tumor markers. Nonfunctional PNETs typically remain clinically silent until a substantial mass effect occurs. Although the majority of PNETs occur sporadically, it is important to recognize that these tumors may be associated with a variety of familial syndromes and in many cases genetic testing of PNET patients is warranted. This article familiarizes the reader with the clinical presentation and the biochemical, radiologic, and genetic testing indicated for diagnosis and follow-up of patients with PNET.