Pancreatic neuroendocrine tumours are rare growths that develop in the hormone-making cells of the pancreas, behaving very differently from the more common types of pancreatic cancer and often growing much more slowly.

Understanding Pancreatic Neuroendocrine Tumours

Pancreatic neuroendocrine tumours, often called pancreatic NETs or islet cell tumours, are uncommon growths that start in the endocrine cells of the pancreas. These endocrine cells are the ones responsible for making hormones that help control important body functions like digestion and blood sugar levels. The pancreas itself is a flat, pear-shaped gland that sits behind the stomach and in front of the spine, about six inches long. While most pancreatic cancers come from the cells that make digestive enzymes, pancreatic NETs are completely different and make up only about one to two percent of all pancreatic cancers.^[1][2]

These tumours can be either benign, meaning they are not cancerous, or malignant, meaning they are cancerous and can spread to other parts of the body. When pancreatic NETs are malignant, doctors sometimes call them pancreatic endocrine cancer or islet cell carcinoma. The good news is that pancreatic NETs generally have a better outlook than the more common type of pancreatic cancer. They tend to grow more slowly, which gives doctors more time to treat them and patients more time to manage their condition.^[3][5]

Pancreatic NETs are divided into two main groups based on whether they produce extra hormones or not. Functional tumours make too much of a particular hormone, which causes specific symptoms related to that hormone. Nonfunctional tumours do not produce excess hormones, so their symptoms usually come from the tumour itself as it grows and takes up space or spreads to other organs. Most pancreatic NETs that doctors see are functional tumours, though nonfunctional tumours are becoming more common as imaging technology improves and doctors find them by accident during scans done for other reasons.^[3][5]

Epidemiology

Pancreatic neuroendocrine tumours are quite rare in the general population. A conservative estimate suggests that about 25 to 30 people per 100,000 in the United States have these tumours at any given time. The number of people being diagnosed with pancreatic NETs has been increasing over the years, but this is likely because medical imaging has improved and doctors are getting better at finding these tumours rather than because more people are actually developing them.^[7]

There do not appear to be clear differences in who gets pancreatic NETs based on race, sex, where someone lives, or their economic status. These tumours can affect anyone, though they are still uncommon overall. The fact that they represent such a small fraction of all pancreatic cancers means that many people, including some healthcare providers, may not be familiar with them. This can sometimes make it harder for patients to get the specialized care they need.^[7]

Causes

Researchers do not yet know the exact cause of pancreatic neuroendocrine tumours. Unlike some other cancers, there is no clear single factor that makes someone develop a pancreatic NET. Scientists understand some of the genetic causes behind both familial cases, where the condition runs in families, and sporadic cases, where it appears without any family history. However, the molecular processes that actually lead to these tumours forming in the pancreas remain largely unknown.^[7]

What doctors do know is that these tumours start when the endocrine cells in the pancreas begin to grow and divide in an uncontrolled way. These cells normally form small clusters throughout the pancreas called islets of Langerhans, and when they become tumours, they can either stay in one place or spread to other organs like the liver, bones, or lungs.^[2][3]

Risk Factors

While the exact cause of pancreatic NETs is not known, certain conditions do increase a person’s risk of developing these tumours. One of the most important risk factors is having certain inherited genetic syndromes. About five to ten percent of people with pancreatic NETs, particularly those with insulinomas or glucagonomas, also have a condition called multiple endocrine neoplasia type 1, or MEN1. This is a genetic disorder that causes tumours to develop in several hormone-producing glands throughout the body.^[2][3]

Having a family history of these inherited syndromes is a significant risk factor. During diagnosis, doctors will often ask whether anyone in a patient’s biological family has had certain inherited disorders that make pancreatic NETs more likely. If there is a family history, genetic testing might be recommended to see if the patient carries any of these genetic changes. However, it is important to remember that most pancreatic NETs occur sporadically, meaning they happen in people with no family history of the condition.^[2]

Symptoms

The symptoms of pancreatic neuroendocrine tumours vary widely depending on whether the tumour is functional or nonfunctional and, if functional, which hormone it is producing too much of. Some people with pancreatic NETs have no symptoms at all, especially in the early stages. These tumours might be discovered accidentally when a patient has a CT scan or other imaging test done for a completely different reason.^[1][5]

When symptoms do occur, they can be quite varied and sometimes confusing. Common symptoms include heartburn, weakness, fatigue, muscle cramps, indigestion, diarrhea, weight loss, skin rash, constipation, pain in the abdomen or back, yellowing of the skin and the whites of the eyes (called jaundice), dizziness, blurred vision, and headaches. Some people also experience increased thirst and hunger, which can be signs of blood sugar problems. These symptoms can develop slowly over time, and many people initially dismiss them as normal signs of aging or stress.^[1][2]

Functional tumours cause symptoms related to the specific hormone they overproduce. For example, insulinomas, which make too much insulin, can cause dangerous drops in blood sugar that lead to dizziness, confusion, sweating, and weakness. Gastrinomas produce excess gastrin, which makes the stomach create too much acid, leading to severe heartburn, stomach ulcers, and diarrhea. Glucagonomas make too much glucagon, causing high blood sugar, a distinctive skin rash, weight loss, and anemia. VIPomas produce too much vasoactive intestinal peptide, resulting in severe watery diarrhea that can lead to dehydration and dangerous drops in potassium levels. Somatostatinomas release excess somatostatin, which can cause diabetes, gallstones, fatty stools, and weight loss.^[2][5]

About 40 percent of pancreatic NETs are functional, meaning they produce these hormone-related symptoms. The remaining 60 percent or more are nonfunctional, and their symptoms come from the physical effects of the tumour itself. As nonfunctional tumours grow, they can press on nearby organs, block passages, or spread to other parts of the body like the liver. This can cause pain, digestive problems, or symptoms related to where the cancer has spread. Most nonfunctional tumours are malignant, meaning they have the potential to spread to other organs.^[3][5]

Prevention

Because researchers do not yet know what causes most pancreatic neuroendocrine tumours, there are no proven ways to prevent them. Unlike some other cancers where lifestyle changes like quitting smoking or maintaining a healthy weight can reduce risk, pancreatic NETs do not have clear lifestyle-related risk factors that people can modify. However, for people who have a family history of inherited syndromes that increase the risk of pancreatic NETs, genetic testing and regular monitoring may help catch tumours early when they are smaller and easier to treat.^[2]

Living a generally healthy lifestyle is always beneficial for overall health and may support the body’s natural defenses. This includes eating a balanced diet with whole, natural foods rather than highly processed ones, staying physically active, avoiding excessive alcohol consumption, and not smoking. While these habits may not specifically prevent pancreatic NETs, they can help someone feel stronger and better able to handle treatment if a tumour is discovered. For people with inherited syndromes like MEN1, working closely with healthcare providers to develop a screening plan is the best approach to early detection.^[2]

Pathophysiology

Pancreatic neuroendocrine tumours develop when the endocrine cells in the pancreas begin to grow and divide abnormally. These endocrine cells, also called islet cells or islets of Langerhans, are normally scattered throughout the pancreas in small clusters. They produce various hormones including insulin, which lowers blood sugar; glucagon, which raises blood sugar; gastrin, which stimulates stomach acid production; and several others. When these cells become cancerous or develop into tumours, they can either continue producing hormones in excess (functional tumours) or stop producing significant amounts of hormones (nonfunctional tumours).^[3]

In functional tumours, the overproduction of hormones leads to specific physical changes in the body. For instance, when an insulinoma produces too much insulin, it drives blood sugar levels dangerously low, a condition called hypoglycemia. The body responds to this by releasing stress hormones, which causes symptoms like sweating, shakiness, confusion, and in severe cases, loss of consciousness. When a gastrinoma produces too much gastrin, the stomach makes excessive amounts of acid, which can damage the stomach lining and small intestine, creating painful ulcers and causing severe diarrhea. Each type of functional tumour creates its own pattern of hormonal imbalance and resulting physical changes.^[2][5]

Nonfunctional tumours affect the body through their physical presence and growth. As these tumours enlarge, they can press on surrounding tissues and organs, causing pain, blockages, or disrupting normal function. They can grow large enough to be felt through the skin in some cases. Most significantly, many pancreatic NETs have the potential to spread, or metastasize, to other organs. The liver is the most common site for these cancer cells to spread, but they can also reach the bones and lungs. When cancer spreads to the liver, it can affect that organ’s ability to filter blood, produce proteins, and perform other vital functions. The biological behavior of pancreatic NETs is somewhat unpredictable, with factors like tumour grade, the presence of lymph node involvement, liver metastases, and larger tumour size generally indicating a less favorable outlook.^[2][7]

At the cellular level, most pancreatic NETs are relatively slow-growing, which means the cancer cells divide and multiply more gradually than in aggressive cancers. This indolent nature gives patients and doctors more time to make treatment decisions and often allows for longer survival even with advanced disease. However, the fact that most NETs have malignant potential means they require careful monitoring and treatment. The World Health Organization classifies these tumours based on their grade, which reflects how quickly the cells are dividing and growing. Higher-grade tumours, where cells are dividing more rapidly, tend to be more aggressive and harder to control.^[6][7]