Overview

What are pancreatic neuroendocrine tumors?

Pancreatic neuroendocrine tumors (also called islet cell tumors or pNETS) are a set of tumors that start in your pancreas’ endocrine cells. pNETs are rare. The most recent data estimates 5 in 1 million people have pancreatic endocrine tumors. They can be hard to diagnose since their symptoms can look and feel like other less serious illnesses. Many times healthcare providers find pancreatic NETs during tests for other conditions. If diagnosed early on, more than 90% of people with pancreatic neuroendocrine tumors are alive five years after diagnosis.

Who is affected by pancreatic neuroendocrine tumors?

Most people with pNETs are older, with the average age of diagnosis being 60. They're slightly more common in people assigned male at birth than in people assigned female at birth.

How does pNET affect my body?

Your pancreas is a pear-shaped gland tucked beside your stomach and small bowel. It helps you to digest food and regulate your blood sugar levels. Your endocrine cells are in charge of regulating your blood sugar, producing and releasing several different hormones that keep your blood sugar levels from dropping or spiking. Your pancreas is part of your endocrine system.

Pancreatic neuroendocrine tumors happen when something triggers a change in your endocrine cells’ DNA. Your endocrine cells start to multiply and divide, becoming tumors that can grow so large they keep your pancreas from functioning. These tumors also can flood your body with excess hormones. Pancreatic NETs that release hormones are called functioning tumors. Tumors that don’t release hormones are called non-functioning tumors.

Your pancreatic endocrine cells release different types of hormones. As a result, there are different pNET types. For example, some endocrine cells release insulin, which lowers blood sugar levels. When those cells multiply and become tumors, the condition is called insulinoma. Each pNET type has different symptoms.

What are other pNET types?

Insulinomas are the most common functioning pNET type. Functioning pNETs release hormones, and insulinomas represent about 70% of all pancreatic endocrine tumors. Other pNET types include:

Glucagonomas: These tumors come from cells that make glucagon, which boosts your blood sugar.
Gastrinomas: These tumors come from cells that make gastrin, which tells your body to make stomach acid.
Somatostatinomas: These tumors come from cells that make somatostatin. Somatostatin helps regulate insulin and glucagon.
VIPomas: These tumors come from cells that make vasoactive intestinal peptide (VIP), which manages the flow of certain chemicals in your small intestine.

What is the difference between pNET and pancreatic cancer (adenocarcinoma)?

Both cancers start in your pancreas, but in different places. Pancreatic neuroendocrine tumors start in your endocrine cells, which produce hormones to regulate blood sugar and digestion. Pancreatic cancer starts in your exocrine cells, which produce enzymes that break down food in your small intestine.

Pancreatic cancer is more common than pNET and less likely to be diagnosed early on. pNETs are less common but have a much better prognosis, or expected outcome, than pancreatic cancer.

What’s the difference between pNETs and pancreatic islet cell tumors?

They are the same. Pancreatic neuroendocrine tumors used to be called pancreatic islet cell tumors.

Symptoms and Causes

Is pancreatic neuroendocrine cancer hereditary?

Approximately 10 % of pancreatic neuroendocrine tumors are linked to conditions or syndromes that people inherit from their parents. Researchers don’t know what triggers pNET in people who don’t have a family medical history of hereditary conditions.

What hereditary conditions are linked to pNETs?

Researchers link pNETS to three conditions or syndromes. In these conditions or syndromes, something changes the DNA in genes that are supposed to suppress cancer cells’ growth. This change paves the way for pNETs. Those cancers or syndromes include:

Multiple Endocrine Neoplasia Type 1 (MEN1): This syndrome involves non-functioning pNETs. Non-functioning pNETs don’t release hormones but can grow large enough to affect your pancreas. These tumors can start when you're younger and grow undiscovered until they’re large enough to cause belly pain, loss of appetite and unintended weight loss.
Von Hippel-Lindau (VHL): Like MEN1, this syndrome involves non-functioning, slow-growing pNETs. VHL symptoms can include headaches, problems with balance and dizziness.
Neurofibromatosis type 1 (NF1): NF1 affects cell growth. People with NF1 develop tumors all over their bodies.

What are pancreatic neuroendocrine tumor symptoms?

Pancreatic NETs cause lots of everyday symptoms like nausea and diarrhea. They can cause less common problems such as flushing of the skin or stomach ulcers, which can cause anemia. Not every symptom means you have pancreatic neuroendocrine cancer. Talk to your healthcare provider if you have symptoms that don’t go away within a short while or get worse.

Pancreatic NET symptoms vary based on the tumor type. For example, gastrinomas make gastrin, a hormone that tells your stomach when it’s time to make more stomach acid to digest food. Too much gastrin causes ulcers.

What are other gastrinoma symptoms?

When your stomach makes too much acid, it causes a condition called Zollinger-Ellison syndrome. Zollinger-Ellison syndrome causes ulcers. Ulcer symptoms include:

Pain.
Nausea.
Loss of appetite.
Blood in your stool (poop) or black, tarry stool. This can be a sign you’re bleeding from your stomach.

Severe ulcers can bleed, causing anemia. Anemia symptoms are:

Fatigue.
Shortness of breath.
Blood in your stool (poop) or black, tarry stool. This can be a sign you’re bleeding from your stomach.

Excess stomach acid can spill over into your small intestine, damaging your intestinal lining and the enzymes that help you to digest food. Symptoms are:

Diarrhea.
Unintended weight loss.

What are glucagonoma symptoms?

This tumor makes glucagon, a hormone that increases your blood sugar levels. Chronically high blood sugar (hyperglycemia) can cause diabetes. Diabetes symptoms include:

Feeling unusually thirsty and hungry.
Frequent urination.
Diarrhea.
Unintended weight loss.

What are insulinomas symptoms?

These tumors make insulin. Too much insulin can cause low blood sugar (hypoglycemia). Low blood sugar symptoms include:

Weakness.
Confusion.
Sweating.
Intense hunger.
Rapid heartbeat.
Seizures.
Loss of consciousness.
Coma.

What are somatostatinoma symptoms?

Somatostatinomas make somatostatin, a hormone that helps regulate other hormones. Somatostatinoma symptoms include:

Stomach pain.
Nausea.
Loss of appetite.
Unintended weight loss.
Diarrhea.
Diabetes.
Jaundice, which can cause your skin and eyes to turn yellow.

What are VIPoma symptoms?

VIPomas make vasoactive intestinal peptide (VIP). Excess VIP symptoms include:

Diarrhea that gets worse over time, becoming more frequent and watery.
Nausea and vomiting.
Muscle cramps.
Fatigue.
Flushing — when your face and neck feel warm and become red.

Diagnosis and Tests

How do healthcare providers diagnose pancreatic neuroendocrine tumors?

Providers diagnose pNET in steps. First, they perform a biopsy, removing cells or tissue from your pancreas so they can examine the cells or tissue under a microscope. They might use imaging tests to determine if the pNET has spread to other areas of your body.

Next, they establish whether the tumor is functional, meaning it releases hormones, or non-functional. If the tumor is functional, they’ll establish the specific pNET type by checking hormone levels. Finally, they use what they learn through tests to set a classification or grade for the tumor.

What tests do providers use to diagnose pNET?

Providers tap a range of tests to diagnose specific pancreatic neuroendocrine tumors. Those tests may include:

Physical exam and medical history: Many pNET symptoms are similar to other less serious illnesses. Your provider will ask questions about specific symptoms, how long you’ve had the symptoms and if your symptoms are getting worse.
Blood tests: These tests check on the amounts of substances that your organs and tissues release into your blood. Substance levels that spike or fall might be signs of disease.
Abdominal computed tomography (CT) scan: CT scans use a series of X-rays and a computer to produce a three-dimensional view of your organs and bones.
Magnetic resonance imaging (MRI): This test produces detailed images using a magnet, radio waves and a computer.
Neuroendocrine positron emission tomography (PET) scan: This test tracks neuroendocrine tumors with a dye called Gallium 68 dotatate that was designed to detect neuroendocrine tumor cells.
Endoscopic ultrasound (EUS): This procedure enables providers to obtain pictures of the pNET and to perform biopsies. To perform EUS, providers use a thin, tube-like instrument called an endoscope that has a light and lens for viewing inside your body and a probe that bounces soundwaves off your internal tissues. They insert the endoscope through your mouth or rectum. The probe bounces soundwaves off your tissues, creating echoes that form pictures called sonograms.
Endoscopic retrograde cholangiopancreatography (ERCP): This procedure helps determine if a PNET is blocking your bile ducts, keeping bile from flowing from your liver to your small intestine. Bile that is slowed or blocked can cause jaundice. Providers use an endoscope inserted through your mouth to your stomach to access your small intestine. Then they use the endoscope to insert a catheter into your ducts so providers can inject and track dye in your ducts. ERCP is also used to obtain tissue samples or keep your duct open.
Angiogram: Angiograms look for signs that pNETS are blocking your blood vessels. Providers inject a contrast dye into a blood vessel, taking X-rays as the dye moves through it.
Laparotomy: Providers perform surgery, cutting into your abdominal wall to look for signs of disease. They might remove tissue samples for examination under a microscope.
Intraoperative ultrasound: This procedure takes place during surgery. Providers place an ultrasound transducer on your organs or tissues. The transducer makes sound waves that create echoes, which the transducer receives and sends to a computer. The computer uses those echoes to make sonograms.
Bone scan: Bone scans check for rapidly dividing cells in your bones.

How do healthcare providers evaluate pancreatic neuroendocrine tumors?

Providers use a process called grading to describe how quickly a pNET might spread. Providers examine cells under a microscope for differences between normal and abnormal cells and to see if the abnormal cells are multiplying. The cancer grade determines whether you have pNET or pancreatic small cell carcinoma. Pancreatic small cell carcinoma is a very rare cancer that’s usually found in the head of your pancreas.

Grade 1 (also called low-grade or well-differentiated) neuroendocrine tumors have cells that look more like normal cells and are not multiplying quickly.
Grade 2 (also called intermediate-grade or moderately differentiated) tumors have features in between those of low- and high-grade tumors.
Grade 3 (also called high-grade or poorly differentiated) neuroendocrine tumors have cells that look very abnormal and are multiplying faster.

Management and Treatment

Can pNETs be cured?

Healthcare providers have several ways to treat pNET. Pancreatic neuroendocrine tumor treatments include:

Surgery: Pancreatic neuroendocrine tumor surgery ranges from surgery just to remove a tumor in one place in your pancreas to Whipple surgery, which removes part of your pancreas, your gallbladder, nearby lymph nodes and part of your stomach, small intestine and bile duct.

What other surgeries treat pNETS?

Other surgeries that treat pNETs include:

Distal pancreatectomy: This surgery removes your pancreas’ body and tail. Providers might also remove your spleen if cancer has spread from your pancreas to your spleen.
Cytoreduction: This surgery removes pancreatic cancer that’s spread to other areas of your body. Providers typically use cytoreduction to remove the pancreatic cancer in your liver.

What are other treatments for pancreatic neuroendocrine tumors?

Providers use the following treatments for PNETs:

Peptide Receptor Radionuclide Therapy (PRRT): This treatment involves injecting a drug into your bloodstream. The drug combines radioactive atoms and amino acids to target and kill pNET cells.
Hormone therapy: Healthcare providers use various types of hormones to stop the tumors from making hormones.
Chemotherapy: Providers use several types of chemotherapy drugs to kill cancer cells.
Targeted therapy: Targeted therapy uses drugs or other substances to attack cancer cells without hurting normal cells.
Liver or small bowel transplantation: Providers may perform transplantations in advanced cases where the pNet has spread to your liver or small bowel.

What is liver-directed therapy?

These are treatments providers may use if the pNET is mostly growing in your liver. Liver-directed therapy may include targeting the tumor in your liver with tiny beads or radiation or with chemotherapy. Healthcare providers may perform ablations, a treatment that uses microwaves or heat to kill tumors in your liver.

Do these treatments have potential side effects or complications?

There’s a wide range of pNET treatments, from major surgery to hormone therapy. Generally speaking, healthcare providers carefully assess treatment benefits and side effects while making treatment recommendations.

Prevention

How can I prevent pNETs?

Unfortunately, 90% of pancreatic neuroendocrine tumors happen sporadically, meaning providers can’t identify a specific cause or way to prevent them. Pancreatic neuroendocrine tumors are linked to three hereditary syndromes. Ask your healthcare provider about these syndromes. They might recommend genetic testing if your family medical history includes these syndromes. If it does, your provider might recommend being screened for pNETs even if you don’t have any symptoms.

Outlook / Prognosis

What’s pancreatic neuroendocrine tumor prognosis?

Your prognosis depends on the type of pNET and when it was diagnosed. Overall, more than 50% of people who have pancreatic neuroendocrine tumors are alive five years after diagnosis.

Can pancreatic neuroendocrine tumors spread?

Yes, pNETs can spread to your liver, lungs, peritoneum (your stomach lining) or your bones. Pancreatic neuroendocrine tumors are often diagnosed because they have spread to other areas of your body.

Living With

How do I take care of myself if I have a pancreatic neuroendocrine tumor?

Just as there’s no single pNETs type, there’s no single or best way to take care of yourself if you have pancreatic neuroendocrine tumors.

There are some 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:

Try to eat a healthy, well-balanced diet. If pNET 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.

When should I see my healthcare provider?

You should see your healthcare provider if you notice changes in your body that resemble pNET symptoms. These changes might be unrelated to your condition, but 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.

A note from Cleveland Clinic

Being diagnosed with cancer is almost always an upsetting experience. But there are special challenges when you’re diagnosed with a rare illness like a pancreatic neuroendocrine tumor. Along with feeling anxious about your diagnosis and treatment, you might feel overwhelmed as you try to process what you’re learning about your cancer. Your healthcare provider will understand if you have lots of questions about your situation. You also might feel isolated if those around you aren’t familiar with this type of cancer. If you’re feeling you’re on your own with your pNET, ask your provider about programs and services that might help you.

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Pancreatic Neuroendocrine (Islet Cell) Tumors