Neuroendocrine Tumors

What is a neuroendocrine tumor (NET)?

Neuroendocrine tumors (NETs) are a group of uncommon tumors that start in your neuroendocrine cells. These cells combine the traits of nerve cells and hormone-producing endocrine cells. Most neuroendocrine tumors are malignant (cancerous).

There are several types of neuroendocrine tumors with symptoms that are easy to mistake for other less serious conditions. The characteristics of NETs — including how aggressive (fast-growing) they are, the symptoms they cause and what treatments work best — vary significantly based on the tumor.

Types of neuroendocrine tumors

Researchers classify NETs based on whether they release hormones:

• Functional NETs release hormones and can cause hormone-related symptoms.
• Non-functional NETs don’t release hormones. They can still cause symptoms if they impact an organ.

Researchers also classify neuroendocrine tumors based on where the tumor starts in your body. The most common types include:

• Gastrointestinal neuroendocrine tumors (GI-NETs): NETs most commonly start in your gastrointestinal (GI) tract. Most start in your intestines, rectum or appendix. GI-NETs used to be called carcinoid tumors.
• Lung neuroendocrine tumors: These tumors start in your lungs or bronchi, the tubes that carry air from your windpipe to your lungs. They’re the second most common type of NET and were also once called carcinoid tumors.
• Pancreatic neuroendocrine tumors (P-NETs): These tumors start in your pancreas and are a type of pancreatic cancer. P-NETs are the third most common type of NET.

Less often, NETs may start in your:

• Thyroid gland.
• Parathyroid glands.
• Pituitary gland.
• Adrenal glands.
• Thymus.

How common are neuroendocrine tumors?

NETs affect about 6 in 100,000 people worldwide. Although neuroendocrine cancer is rare, more people are being diagnosed. This is likely thanks to improved diagnostic tests that identify NETs more quickly.

Although anyone can develop neuroendocrine tumors, they’re rare in children, teens and young adults. On average, most people diagnosed are between the ages of 50 and 60.

What are the symptoms of neuroendocrine tumors?

Often, neuroendocrine tumors don’t cause symptoms until a tumor impacts an organ. When this happens, symptoms vary based on location. NET symptoms may include:

• Fatigue.
• Stomach pain.
• Diarrhea.
• Nausea and vomiting.
• Shortness of breath.
• Coughing (sometimes with blood).

It’s important to remember that having these symptoms doesn’t always mean you have cancer. Talk to a healthcare provider if you’re experiencing symptoms that don’t improve.

What causes neuroendocrine tumors?

NETs form when neuroendocrine cells begin to divide and multiply uncontrollably. Eventually, they become tumors that can affect the organs where the cells are located. Researchers don’t know what triggers the abnormal cell growth that causes neuroendocrine tumors.

Risk factors

Researchers have linked NETs to rare inherited syndromes that involve mutations (changes) in certain genes. Your risk of developing a neuroendocrine tumor increases if you have one of these conditions: 

• Multiple endocrine neoplasia (MEN): This condition causes overactive tumors to form in various organs and endocrine system glands. Type 1 (MEN1) is the most common cancer syndrome associated with NETs. It’s especially common in people with pancreatic NETs (P-NETs).
• Von Hippel-Lindau syndrome: This condition increases your risk of benign and cancerous tumor growth in various parts of your body.
• Neurofibromatosis type 1: This condition causes tumors to grow on your skin and nerves, affecting your eyes and other parts of your body.
• Tuberous sclerosis complex: This condition causes benign tumors that can form anywhere on your body but most commonly in your brain.
• Cowden syndrome: This condition causes benign tumor-like growths and increases your risk of some cancers.

What are the complications of a neuroendocrine tumor?

Carcinoid syndrome happens when a neuroendocrine tumor in your GI tract or lungs releases too many hormones. It can cause a range of unpleasant symptoms, including flushing (sudden warmth and redness) of your head and neck, wheezing and diarrhea.

Untreated carcinoid syndrome can lead to additional complications. In rare cases, it can be life-threatening. Getting treated for NETs also helps with carcinoid syndrome.

How are neuroendocrine tumors diagnosed?

As the early signs and symptoms of NETs are common across several other conditions, it may take a while to receive a diagnosis. If your provider suspects a NET, they’ll choose diagnostic procedures based on the kind of tumor they think you might have. Tests include:

• Biochemical tests: These tests measure the amount or activity of a particular enzyme or protein in your blood or urine (pee). They can reveal signs of a functional (hormone-secreting) NET.
• Imaging tests: Your healthcare provider may perform imaging tests, like a CT scan, MRI or X-ray, that can show tumors inside your body. PET scans can show signs of cancer spread.
• Endoscopy: An endoscopy uses a scope that goes inside your body to view tumors and remove tissue. Depending on the tumor’s location, you may need a specific type of endoscopy, like an esophagogastroduodenoscopy or a colonoscopy.
• Endoscopic ultrasound: Your provider may combine an imaging procedure with an endoscopy to diagnose a NET. For example, they might use endoscopic ultrasonography to diagnose a neuroendocrine tumor in your pancreas. 
• Biopsy: Providers do biopsies to obtain fluid or tissue samples. They’ll examine the sample beneath a microscope to check for cancer cells. This analysis also reveals important information about the type of NET and how aggressive it is. 

Stages and grades of neuroendocrine tumors

Healthcare providers use cancer staging to determine how much the cancer has spread. Staging systems for neuroendocrine tumors vary based on the tumor type and grade. 

In general, providers stage NETs on a scale from 1 to 4. The lower the number, the smaller the tumor is or the less the cancer has spread into nearby tissue. Stage 4 cancer is typically considered metastatic, which means it has spread to distant parts of your body. Still, the specific staging systems vary greatly with NETs.

“Grade” describes how abnormal the cells appear beneath a microscope and how quickly cells are dividing. Providers classify NETs as:

• Well-differentiated neuroendocrine tumors: The cells resemble and behave like normal cells and tend to grow slowly. Most Grade 1 and Grade 2 NETs are this type.
• Poorly differentiated neuroendocrine tumors: These cells look abnormal and don’t resemble or behave like normal cells. They tend to grow fast. Most Grade 3 NETs are this type.

Ask your healthcare provider what your cancer stage and grade mean for your diagnosis.

How are neuroendocrine tumors treated?

Surgery is the most common treatment for a NET. If your tumors are large or have spread, other treatments you might need include:

• Somatostatin analogs: Somatostatin analogs are medications that prevent your body from making excess hormones. They can reduce symptoms of functional NETs and slow tumor growth.
• Chemotherapy: This treatment uses several types of drugs to kill cancer cells.
• Targeted therapy: This treatment uses drugs that target certain genes or proteins on cancer cells to kill them.
• Radiation therapy: Specialized forms of internal radiation therapy may be used to treat NET. For example, peptide receptor radionuclide therapy (PRRT) delivers small amounts of a radioactive substance to hormone-secreting NETs. Y-90 treatment delivers radioactive beads to NETs that have spread to your liver.

Can I prevent neuroendocrine tumors?

As researchers don’t know what causes NETs, there’s nothing you can do to prevent them. Still, you can understand potential risk factors, like having an inherited condition like multiple endocrine neoplasia (MEN).

Ask your healthcare provider for help understanding whether your family health history puts you at risk of developing NETs.

What can I expect if I have a NET?

NETs are often mistaken for other less serious conditions, so it may take some time before you’re diagnosed. Once you learn you have a neuroendocrine tumor, your prognosis, or expected outcome, depends on several factors, including the type of NET you have and whether your tumor has spread. On average, an estimated 39% of people with NETs are alive five years after diagnosis.

But statistics on life expectancy and survival rates vary. For example, the average survival rate for people with NETs that haven’t spread is as high as 30 years. Your healthcare provider can explain what factors shape your outlook.

In the meantime, keep in mind that finishing treatment is a major milestone but not the end of your NET journey. NETs can grow very slowly and recur (return) after treatment, so your healthcare provider will want to track your well-being for several years. 

Can a neuroendocrine tumor be cured?

NETs are curable when your healthcare provider can remove all signs of the tumor with surgery. But one of the biggest challenges with this diagnosis is that although most NETs are slow-growing, they’ve often spread by the time they’re caught.

At this point, treatment can help slow tumor growth and provide symptom relief.

How do I take care of myself if I have a NET?

Neuroendocrine tumors and their treatment can take a toll on your body. You may have to manage common symptoms like fatigue — feeling extremely tired day after day — and diarrhea throughout your treatment. Try to get as much rest as you can. If diarrhea is an issue, talk to your healthcare provider about ways to reduce its frequency and severity.

Here are some other suggestions that might be helpful:

• Join support groups: Cancer can be lonely, and uncommon cancers can be lonelier still. Talk to your healthcare providers about support groups so you can connect with people who understand what you’re going through.
• Eat healthy foods and well-balanced meals: If NET symptoms and treatment side effects make eating difficult, ask a dietitian for suggestions on finding foods that will help you keep up your strength.
• Seek emotional support: If you’re having a hard time emotionally, ask your provider about mental health services that can help.
• Drink alcohol responsibly: Alcohol can trigger some NET side effects, including carcinoid syndrome. Ask your provider about drinking alcohol in moderation.

When should I see my healthcare provider?

Contact your healthcare provider if you have a NET and are noticing changes in your body that may be signs of carcinoid syndrome, like flushing, diarrhea or wheezing. You should also contact your provider if your symptoms become worse or if you’re experiencing treatment side effects.

When should I go to the emergency room?

NETs don't usually cause carcinoid syndrome. But one of the symptoms is swelling (edema) in your legs, which might indicate heart failure. Go to the emergency room immediately if you notice unusual swelling in your ankles and legs and if you suddenly feel as if you can’t breathe.

What questions should I ask my healthcare provider?

NET is a complicated disease that affects different parts of your body in different ways. Here are some questions that might help you get started on a conversation so you understand what’s happening with your body and what you can do to help yourself:

• What kind of NET do I have?
• How long have I had NET?
• Is my tumor in one place or has it spread?
• What are my treatment options?
• What are the treatment side effects?
• What is my prognosis?