ConditionCancer
Neuroendocrine Tumors (NETs)
Neuroendocrine tumors (NETs) are uncommon tumors that arise from neuroendocrine cells, which release hormones in response to nerve signals. They occur most often in the small intestine, rectum, appendix, pancreas, stomach and lungs. Many grow slowly and cause vague symptoms for years; some release hormones that cause flushing, diarrhea or low blood sugar. They range from slow-growing, well-differentiated NETs to aggressive neuroendocrine carcinomas. Surgery can cure localized tumors, and many treatments control advanced disease for years.
Also called: NETs, neuroendocrine neoplasms (NENs), carcinoid tumors (older term), GEP-NETs, pancreatic NETs
At a glance
- What they are
- Tumors of hormone-producing neuroendocrine cells, from slow-growing to aggressive.
- Common sites
- Small intestine, rectum, appendix, pancreas, stomach, lungs.
- Functioning NETs
- Release hormones causing syndromes such as carcinoid syndrome, insulinoma or gastrinoma.
- Symptoms
- Often none or vague; flushing, diarrhea, wheezing, abdominal pain, bowel blockage, low blood sugar, ulcers.
- Diagnosis
- CT or MRI, somatostatin receptor PET scan, blood and urine markers, biopsy with grading (Ki-67).
- Treatment
- Surgery; somatostatin analogs; targeted drugs; PRRT (lutetium-177 dotatate); chemotherapy for high-grade tumors.
When to get help
Call 911 or go to the ER
- Severe flushing with very low blood pressure, wheezing or a racing heart, especially during surgery or a procedure (carcinoid crisis)
- Confusion, sweating, shaking or loss of consciousness from very low blood sugar
- Severe abdominal pain with vomiting and a swollen belly (possible bowel obstruction)
See a doctor within a day or two
- Black stools, vomiting blood or severe heartburn and ulcers that do not heal
- Repeated episodes of low blood sugar, especially when fasting or after exercise
- Leg swelling and breathlessness in someone with carcinoid syndrome (possible heart valve involvement)
Book a routine appointment
- Frequent facial flushing with diarrhea that does not have an obvious cause
- Recurrent unexplained abdominal pain or diarrhea, especially with weight loss
- A NET found incidentally after appendix removal or on a scan
What neuroendocrine cells are
Neuroendocrine cells are spread throughout the body, especially in the digestive tract and lungs. They release hormones such as serotonin, insulin, gastrin and glucagon. When these cells grow abnormally, they form neuroendocrine tumors. Some keep producing hormones in excess (functioning NETs); most do not cause hormone symptoms (non-functioning NETs).
Types by location
| Site | Notes |
|---|---|
| Small intestine (ileum) | Often spreads to the liver; can cause carcinoid syndrome |
| Appendix | Often found after appendectomy; usually small and cured by surgery |
| Rectum | Often small and found at colonoscopy |
| Stomach | Several types, some linked to atrophic gastritis |
| Pancreas | Functioning (insulinoma, gastrinoma, glucagonoma, VIPoma) or non-functioning |
| Lung | Typical and atypical carcinoids; small-cell and large-cell carcinomas are high-grade |
| Skin | Merkel cell carcinoma |
Grade and differentiation
- Well-differentiated NETs (grade 1 to 3): grade is based on the Ki-67 index and mitotic rate; grade 1 grows slowly, grade 3 faster.
- Poorly differentiated neuroendocrine carcinomas (NECs): aggressive, behave more like small-cell lung cancer, and are treated with chemotherapy.
Symptoms
Non-functioning tumors
- often none for years
- abdominal pain, bloating
- bowel obstruction
- bleeding
- weight loss, jaundice (pancreatic tumors)
- cough, wheezing or pneumonia (lung tumors)
Hormone syndromes
| Syndrome | Hormone | Symptoms |
|---|---|---|
| Carcinoid syndrome | Serotonin and others | Flushing, diarrhea, wheezing, heart valve disease; usually with liver spread |
| Insulinoma | Insulin | Low blood sugar: sweating, shaking, confusion, often when fasting |
| Gastrinoma (Zollinger-Ellison syndrome) | Gastrin | Severe, recurrent ulcers, diarrhea |
| Glucagonoma | Glucagon | Rash (necrolytic migratory erythema), diabetes, weight loss |
| VIPoma | VIP | Severe watery diarrhea, low potassium |
Risk factors
Most NETs occur sporadically. Inherited syndromes increase risk:
- multiple endocrine neoplasia type 1 (MEN1)
- von Hippel-Lindau syndrome
- neurofibromatosis type 1
- tuberous sclerosis
Diagnosis
- imaging: CT or MRI to find the tumor and spread, especially to the liver
- somatostatin receptor PET (Ga-68 or Cu-64 dotatate): highly sensitive for well-differentiated NETs and guides PRRT eligibility
- blood and urine tests: chromogranin A, 24-hour urine 5-HIAA (serotonin breakdown product), and specific hormones
- endoscopy and endoscopic ultrasound for stomach, duodenum, rectum and pancreas
- biopsy with grading (Ki-67)
- echocardiogram in carcinoid syndrome to check heart valves
Treatment
- Surgery: the main curative treatment for localized NETs, and sometimes used to remove liver metastases.
- Endoscopic removal for small rectal or stomach NETs.
- Somatostatin analogs (octreotide, lanreotide): control hormone symptoms and slow growth.
- Telotristat: for carcinoid syndrome diarrhea.
- Targeted drugs: everolimus, sunitinib, cabozantinib for advanced disease.
- PRRT (peptide receptor radionuclide therapy): lutetium-177 dotatate delivers radiation directly to tumor cells that have somatostatin receptors.
- Liver-directed therapy: embolization or ablation of liver metastases.
- Chemotherapy: for pancreatic NETs (such as capecitabine-temozolomide) and high-grade carcinomas (platinum-etoposide).
- Diazoxide and diet to manage low blood sugar from insulinoma.
Outlook
Outlook depends on the site, grade and stage. Small appendix and rectal NETs are usually cured by surgery. Many people with well-differentiated NETs that have spread live for many years with treatment. Poorly differentiated carcinomas have a poorer outlook. Specialist NET centers improve care.
Frequently asked questions
What is a neuroendocrine tumor?
A neuroendocrine tumor is a growth arising from neuroendocrine cells, which release hormones. NETs occur most often in the gut, pancreas and lungs. Many grow slowly, and some produce hormones that cause symptoms like flushing and diarrhea.
What are the symptoms of a neuroendocrine tumor?
Many cause no symptoms for years. When symptoms occur, they include abdominal pain, bowel changes, bleeding, weight loss, cough, or hormone effects such as flushing, diarrhea, wheezing, low blood sugar or severe ulcers.
Is a neuroendocrine tumor cancer?
NETs are considered malignant because they can spread, but many behave slowly. Small NETs in the appendix or rectum are often cured with surgery, while poorly differentiated neuroendocrine carcinomas are aggressive cancers.
What is the survival rate for neuroendocrine tumors?
Survival varies greatly. Localized, low-grade NETs have excellent long-term survival. Many people with advanced well-differentiated NETs live for years with treatment. High-grade neuroendocrine carcinomas have a much shorter survival on average.
Sources
This guide was written from current patient and clinical guidance, including:
- National Cancer Institute: Gastrointestinal Neuroendocrine Tumors Treatment (PDQ); Pancreatic Neuroendocrine Tumors Treatment (PDQ)
- National Comprehensive Cancer Network (NCCN): Guidelines for Patients, Neuroendocrine Tumors
- North American Neuroendocrine Tumor Society (NANETS): Guidelines
- American Cancer Society: Gastrointestinal Carcinoid Tumors
- World Health Organization Classification of Tumours: Digestive System Tumours, 5th edition