Well-differentiated neuroendocrine tumors
Well-differentiated neuroendocrine tumors (formerly carcinoid tumors) arise from enterochromaffin and islet-type cells of the gut and pancreas, are graded G1 to G3 by Ki-67 and mitotic count, and may be functional (gastrinoma, insulinoma, glucagonoma, VIPoma, somatostatinoma, or carcinoid syndrome) or nonfunctional. Diagnosis rests on biopsy with neuroendocrine markers plus Ki-67 grading and somatostatin-receptor imaging, and management ranges from surgical resection to somatostatin analogues, peptide receptor radionuclide therapy, and targeted agents.
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What this article covers
- Overview
Definition: well-differentiated neuroendocrine tumors (NETs), formerly called carcinoid tumors, are indolent epithelial neoplasms arising from enterochromaffin cells of the digestive tract or…
- Epidemiology
Most common site: the gastrointestinal tract, particularly the appendix, small bowel, and rectum; the lungs are also a common primary site.
- Risk factors
Hereditary syndromes: multiple endocrine neoplasia type 1 (MEN1) is the strongest predisposing syndrome, particularly for pancreatic and duodenal NETs (gastrinoma, insulinoma); also von Hippel-Lindau…
- Pathophysiology
Cell of origin: NETs arise from the diffuse neuroendocrine system, enterochromaffin cells of the gut mucosa or islet cells of the pancreas (previously called islet cell tumors).
- Clinical features
Nonfunctional/incidental presentation, most common: discovered incidentally on imaging or endoscopy, or through evaluation of hepatic lesions; when symptomatic, presentation reflects mass effect…
- Differential diagnosis
Pheochromocytoma: episodic flushing, palpitations, headache, and hypertension from catecholamine excess, distinguished by elevated metanephrines and typically without diarrhea (Pheochromocytoma).
- Diagnosis
Biopsy with neuroendocrine immunohistochemistry establishes the diagnosis, and Ki-67/mitotic count establishes the grade: chromogranin A and synaptophysin positivity confirm neuroendocrine origin…
- Management
Localized disease: surgical resection is first-line and potentially curative.
- Complications
Carcinoid heart disease: right-sided valvular fibrosis, most often tricuspid regurgitation and pulmonic stenosis, from chronic serotonin exposure, progressing to right heart failure if unrecognized.
- Prognosis
Grade and stage are the dominant prognostic factors: low-grade (G1), localized, resected disease carries an excellent prognosis, while higher Ki-67 grade, mitotic count, and metastatic spread progressively worsen outcomes.
- Prevention
Surveillance in hereditary syndromes: MEN1 patients are screened with periodic CT or MRI, gastroscopy, endoscopic ultrasound, or somatostatin-receptor imaging; MEN1 genetic testing is performed in…
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Related articles
- Carcinoid syndrome
Carcinoid syndrome is the clinical syndrome of episodic flushing, secretory diarrhea, and late right-sided valvular heart disease caused by serotonin and other vasoactive amines escaping hepatic first-pass metabolism, almost always because a well-differentiated neuroendocrine tumor has spread to the liver or arises outside the portal circulation. Diagnosis rests on an elevated 24-hour urinary 5-HIAA with tumor localization by somatostatin-receptor PET, and management combines somatostatin analogues for symptom control and antiproliferative effect with tumor-directed therapy and peri-procedural crisis prevention.
- Pancreatic neuroendocrine tumors (PanNETs)
Pancreatic neuroendocrine tumors (PanNETs) are islet-cell tumors that may be functional, producing a hormone-excess syndrome such as insulinoma or gastrinoma, or nonfunctioning and detected by mass effect or incidentally. First-line treatment is surgical resection when localized, with somatostatin analogues and acid suppression used to control hormone-excess symptoms before or in place of surgery.
- Peptic ulcer disease
Peptic ulcer disease is a mucosal break in the stomach or duodenum caused chiefly by Helicobacter pylori infection or NSAID use, diagnosed by upper endoscopy with biopsy of gastric ulcers to exclude malignancy. Treatment eradicates H. pylori when present, stops the ulcerogenic drug, and heals the ulcer with a proton pump inhibitor, while its complications of bleeding, perforation, and obstruction drive most of its morbidity.
- Hypoglycemia in adults
Hypoglycemia is a plasma glucose below 70 mg/dL, most often a complication of insulin or sulfonylurea therapy for diabetes, and in a person without diabetes it requires a Whipple triad-based evaluation for insulinoma or another endogenous cause. An alert patient is treated with 15 to 20 g of fast-acting oral carbohydrate, while a patient unable to swallow safely receives intramuscular glucagon 1 mg or intravenous dextrose 50% 25 g.
- Von Hippel-Lindau disease
Von Hippel-Lindau disease is an autosomal dominant tumor-suppressor syndrome in which loss of functional pVHL causes accumulation of hypoxia-inducible factor and a lifelong predisposition to hemangioblastomas, clear-cell renal cell carcinoma, pheochromocytoma, and pancreatic cysts and neuroendocrine tumors. Diagnosis is clinical or by VHL germline testing, and management is a lifelong, age-staged surveillance program combined with nephron-sparing or HIF-2 alpha-directed treatment of lesions as they arise.
- Neurofibromatosis type 1
Autosomal dominant neurocutaneous disorder from NF1 tumor suppressor mutations causing cafe-au-lait macules, neurofibromas, Lisch nodules, and optic glioma; diagnosed clinically by consensus criteria and managed with surveillance, surgery for symptomatic tumors, and selumetinib for inoperable plexiform neurofibromas.
- Pheochromocytoma and paraganglioma
Pheochromocytoma and paraganglioma are catecholamine-secreting tumors of adrenal medullary chromaffin cells and extra-adrenal sympathetic ganglia, causing sustained or paroxysmal hypertension with headache, sweating, and palpitations, diagnosed by plasma free or 24-hour urine fractionated metanephrines before any imaging is obtained. First-line treatment is surgical resection preceded by alpha blockade with phenoxybenzamine (or off-label doxazosin) for 10 to 14 days, with a beta blocker added only after alpha blockade is established.