Neuroendocrine Tumors

What is a neuroendocrine tumor (NET)?

Neuroendocrine tumors are a group of uncommon tumors that start in specialized cells in your neuroendocrine system. These cells combine the traits of nerve cells and hormone-producing endocrine cells. They link your endocrine system, which manages your hormones, and your nervous system. Neuroendocrine cells are scattered throughout your body.

NET has several types and sub-types with symptoms that might be mistaken for other less serious conditions. Once considered a rare cancer, more and more people are being diagnosed with NET thanks to improved diagnostic tests that identify NET more quickly. Early diagnosis and treatment continues to increase the number of people living for years with NET.

How do neuroendocrine cells work?

Neuroendocrine cells act like traffic cops monitoring busy intersections and telling drivers when to stop and go. Like them, your endocrine cells monitor signals from your nervous system. When they get the signal, your cells tell your endocrine system to release hormones. Hormones are chemicals that coordinate different body functions, let your body know what to do and when to do it.

But your neuroendocrine cells do more than watch signals and trigger hormone flow. They also make and release hormones that control activity in the organ where they’re located. For example, the neuroendocrine cells in your gut (digestive system) make hormones that drive production of digestive juices and coordinate the muscles that move food through your bowels.

Neuroendocrine tumors happen when your endocrine cells begin to divide and multiply uncontrollably, eventually becoming tumors that can affect the organs where the cells are located.

What are the different types of neuroendocrine tumors?

Neuroendocrine tumors are classified as primary or secondary tumors. A primary tumor is cancer that hasn’t spread to other areas of your body. A secondary tumor is a NET that has spread, usually to your lymph nodes in your lymphatic system, your liver or your bones.

NET types are based on their location. For example, a neuroendocrine tumor in your gut is a neuroendocrine tumor of the gastrointestinal tract. Here are the most common primary neuroendocrine tumor types:

• Gastrointestinal (GI) tract. NETs develop most commonly in the GI tract, specifically in the large intestine (20%), small intestine (19%), and appendix (4%). The GI tract plays a central role in digesting foods and liquid and in processing waste. GI tract NETs used to be called carcinoid tumors.
• Lung. The lung is the second most common location of NETs. About 30% of NETs occur in the bronchial system, which carries air to the lungs. Lung NETs also used to be called carcinoid tumors.
• Pancreas. Approximately 7% of NETs can develop in the pancreas, a pear-shaped gland located in your abdomen between the stomach and the spine. Pancreatic NETs (PNETS), which used be called islet cell tumors, represent about 7% of all pancreatic cancers.

Who do these tumors affect?

Almost anyone can develop neuroendocrine tumors, including children, but NETs are very rarely seen in children, teenagers and young adults. The average age at diagnosis is between ages 50 to 60. Females are slightly more likely than males to develop neuroendocrine tumors.

How common is this condition?

Neuroendocrine tumors affect about 5 in 100,000 people. More than 12,000 new cases are diagnosed each year and as many as 125,000 people with these tumors are living in the U.S. today.

What are the symptoms of neuroendocrine tumors?

Neuroendocrine tumor symptoms vary based on the location of the cancerous cells. That being said, a condition called carcinoid syndrome is a symptom for neuroendocrine carcinoma of the gastrointestinal tract (GI NETs) and NETs of the lung. Like many forms of cancer, not all symptoms mean you have cancer. Talk to your healthcare provider if you notice changes in your body that are similar to symptoms listed below.

What is carcinoid syndrome?

Carcinoid syndrome happens when NETs produce more hormones than you need. Fewer than 10% of people with NETs develop carcinoid syndrome. Uncomfortable flushing of the head and neck is the most common and earliest symptom of carcinoid syndrome. Other symptoms are:

• Abdominal cramping and diarrhea.
• Fatty poops that smell bad.
• Edema or swelling of your feet and legs. This can also be a symptom of heart failure.
• Wheezing and shortness of breath.
• Some people might lose interest in sex or have erectile dysfunction.
• Jaundice, which is when the skin and whites of the eyes turn yellow.

What causes neuroendocrine tumors?

Researchers don’t know what triggers the cell growth that causes NETs. They have, however, linked NETs to inherited syndromes including:

• Multiple endocrine neoplasia type 1 (MEN1): This condition causes your thyroid, parathyroid or adrenal glands to be overactive or form tumors.
• Multiple endocrine neoplasia type 2 (MEN2): This condition causes your pancreas, pituitary or parathyroid to be overactive or form tumors.
• Von Hippel-Lindau syndrome: This is a rare condition where benign tumors grow in various parts of your body.
• Neurofibromatosis type 1: This is a rare condition where tumors grow on your skin and nerves, affecting your eyes and other parts of your body.
• Tuberous sclerosis complex: This condition’s symptoms include epilepsy, autism or developmental delay, and skin birthmarks in early childhood.

How are neuroendocrine tumors diagnosed?

Healthcare providers diagnose NETs based on the kind of NET they think you might have. For example, they might use endoscopic ultrasonography to diagnose neuroendocrine of the pancreas. Most commonly used tests include:

• Biopsy: Providers do biopsies to obtain cells, fluids, tissues or growths for examination under a microscope.
• Core needle biopsy: Healthcare providers use a fine needle and syringe to extract fluid and tissue from lumps that appear abnormal.
• Urinalysis: Providers screen your urine for signs of medical conditions.
• Biochemical tests: These tests measure the amount or activity of a particular enzyme or protein in blood, urine or tissue samples.
• Computed tomography (CT) scan: CT scans uses a series of X-rays and a computer to create three-dimensional images of your soft tissues and bones.
• Magnetic resonance imaging (MRI): This is a painless test that uses a large magnet, radio waves and a computer to produce very clear images of organs and structures within your body.
• Positron emission testing (PET) scan: Providers inject a radioactive tracer into your body to detect early signs of cancer.

Are there grades of neuroendocrine tumors?

Yes, healthcare providers use a grading system to create your treatment plan. They consider factors such as how quickly your cancerous cells divide and whether your cancerous cells look more like healthy cells than cancerous cells when viewed under a microscope. Understanding the staging and grading process might be helpful information as you and your provider discuss treatment plans.

What are NETs grades?

• Grade 1 (low-grade tumor): These cells divide at a low rate and are growing slowly.
• Grade 2 (intermediate-grade tumor): These cells divide at an intermediate rate.
• Grade 3 (high-grade tumor): These cells divide at a fast rate and therefore grow quickly.

NETs are also evaluated by degrees of differentiation. Those are:

• Well-differentiated neuroendocrine tumor: Your cells look more like healthy cells than cancerous cells.
• Poorly-differentiated neuroendocrine tumor: Your cells look less like healthy cells and more like cancerous cells. Poorly-differentiated cells are then subdivided into small-cell and large-cell tumor classes.

How are neuroendocrine tumors treated?

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

• Somatostatin analogs: Somatostatin analogs are a type of treatment that may stop your body from making too many hormones. This may slow down the growth of the tumor when cancer cells have spread to other part of the body.
• Targeted therapy: Targeted therapy is a type of treatment that uses drugs that target certain genes or proteins to kill cancer cells.
• Chemotherapy: This treatment uses several types of drugs to kill cancer cells.

What are these treatments’ complications?

Treatments have different side effects or complications. Just as important, treatments can affect people in different ways. Ask your healthcare provider about treatment side effects. They'll recommend steps you can take to manage side effects.

How can I reduce my risk?

Researchers don’t know what causes neuroendocrine cells to start multiplying and become tumors. They have linked NETs to several inherited conditions. Ask your healthcare provider for help understanding inherited conditions and whether your family health history puts you at risk of developing NETs.

What can I expect if I have NET?

NETs are sometimes mistaken for other less serious conditions. 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 77% of people with NETs are alive five years after diagnosis.

Finishing treatment is a major milestone but not the end of your NET journey. NETs can grow very slowly, so your healthcare provider will want to track your well-being for several years. In some cases, having NETs might be like living with a chronic illness.

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

Neuroendocrine tumors and their treatment can take a toll of your energy and your body. There are common symptoms like fatigue — feeling extremely tired day after day — and diarrhea that you might have to manage 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:

• 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.
• Try to eat a healthy, well-balanced diet. If NET symptoms and treatment side effects make eating difficult, ask a nutritionist for suggestions on finding foods you can tolerate and that will help you keep up your strength.
• If you’re having a hard time emotionally, ask your provider about services that might help you manage your feelings so you can focus on your health.
• Alcohol can trigger some NET side effects, include carcinoid syndrome. Ask your provider about drinking alcohol in moderation.

When should I see my healthcare provider?

You should see your healthcare provider if you notice changes in your body that resemble your NET symptoms. These changes might be unrelated to your NET diagnosis, and the best way to be sure of that is to talk to your provider. You should also contact your provider if your symptoms or treatment side effects become worse.

When should I go to the emergency room?

NETs don't usually cause carcinoid syndrome. But one of its symptoms is edema or swelling in your legs that might indicate heart failure. Go to the emergency room 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 doctor about neuroendocrine tumors?

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 is NET?
• What kind of NET do I have?
• How did I develop NET?
• How long have I had NET?
• Is my tumor in one place or has it spread?
• What are my treatment options if it hasn’t spread, and if it has spread?
• What are treatment side effects?
• Are there clinical trials I can join?
• What is my prognosis?

A note from Cleveland Clinic

In a way, it might be a relief to be diagnosed with NET. Many people are diagnosed with NET after years of trying to find out why they don’t feel well. That being said, knowing you have a serious uncommon illness might replace one set of uncertainties with another. Talking to your healthcare provider about your NET diagnosis and treatment plan can help you feel more certain and in control of your health.