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ESSENTIALS OF DIAGNOSIS
GEP-NETs are neuroendocrine tumors that originate in the gastrointestinal tract.
About 60% GEP-NETs are nonsecretory or secretory without clinical manifestations; they may be detected incidentally or may present with weight loss, abdominal pain, or jaundice.
Carcinoid tumors arise from the intestines or lung, secrete serotonin, and may metastasize.
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GENERAL CONSIDERATIONS
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GEP-NETs are a subset of neuroendocrine tumors (NETs) that arise from the stomach, intestines, or endocrine pancreas. Pancreatic neuroendocrine tumors (pNETs) arise from different islet cells: the A cells (20%) secrete glucagon, the B cells (70%) secrete insulin,2 the D cells (5%) secrete somatostatin or gastrin, and the F cells secrete pancreatic polypeptide. Gastrin-producing cells are also found in the duodenum. Serotonin-producing cells are found throughout the gut, particularly near the terminal ileum.
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The reported incidence of GEP-NETs has increased to about 37 per million yearly in the United States due to the incidental detection of small tumors on abdominal scans. About 40% are functional, producing hormones that also serve as tumor markers, important for diagnosis and follow-up. At presentation, 65% of GEP-NETs are unresectable or metastatic. Up to 25% of GEP-NETs are associated with one of four different inherited disorders: MEN 1, von Hippel-Lindau disease (VHL), neurofibromatosis 1 (NF-1), and tuberous sclerosis complex (TSC). In MEN 1, GEP-NETs are usually gastrinomas, carcinoids, or nonfunctioning tumors and are a common cause of death. In VHL, GEP-NETs are usually benign and multiple.
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Insulinomas are the most common functional type of GEP-NET and are usually small, intrapancreatic, and benign (90%) and secrete excessive amounts of insulin. Insulinomas also produce proinsulin and C-peptide. Insulinomas are solitary in 95% of sporadic cases but are multiple in about 90% of cases arising in MEN 1. (See Chapter 27.)
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Gastrinomas secrete excessive quantities of the hormone gastrin (as well as “big” gastrin). About 50% of gastrinomas are malignant and metastasize to the liver. Gastrinomas are typically found in the duodenum (49%), pancreas (24%), or lymph nodes (11%). Sporadic gastrinoma is rarely suspected at the onset of symptoms; typically, there is a 5-year delay in diagnosis. About 22% of gastrinomas arise in patients with MEN 1, who usually present at a younger age, often with multiple tumors; hyperparathyroidism can occur many years before or after the discovery of a gastrinoma.
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Glucagonomas are rare and usually malignant, despite their benign histologic appearance. They usually arise as a large intrapancreatic tumor with 60% having liver metastases apparent by the time of diagnosis. Besides glucagon, they usually secrete additional hormones, including gastrin.
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Somatostatinomas are very rare and usually single. They arise in the pancreas (50%) or small intestine. They secrete somatostatin.
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VIPomas are quite rare and usually single intrapancreatic tumors with metastases usually evident (80%) at diagnosis. They produce vasoactive intestinal polypeptide (VIP).
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CCKomas are rare tumors of the endocrine pancreas that secrete cholecystokinin.
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