Gastrointestinal neuroendocrine tumours are rare cancers that develop in special cells scattered throughout the digestive system, most often appearing in the small intestine, rectum, and appendix, and typically growing very slowly over time.
Understanding Gastrointestinal Neuroendocrine Tumours
Gastrointestinal neuroendocrine tumours, often shortened to GI NETs and previously known as gastrointestinal carcinoid tumours, are uncommon cancers that begin in a specific type of cell found in the lining of the digestive tract. These cells are called neuroendocrine cells, which have characteristics of both nerve cells and hormone-producing cells. They are scattered throughout the chest and abdomen, but the majority are located in the gastrointestinal tract, where they play important roles in digestion by making hormones that help control digestive juices and the muscles that move food through the stomach and intestines.[1]
The gastrointestinal tract is a long, twisting tube that forms part of the body’s digestive system, running from the mouth all the way to the anus. This system includes the esophagus, stomach, small intestine, and large intestine (which includes the colon and rectum). When food enters the stomach, muscles break it down and mix it with digestive juices. The partly digested food then passes into the small intestine and later into the large intestine, where the rectum at the end stores waste until it leaves the body through the anus during a bowel movement.[1]
GI neuroendocrine tumours form in the lining of these digestive organs. Most commonly, they develop in the small intestine, rectum, and appendix, though they can also appear in the stomach, colon, and esophagus. Sometimes more than one tumour forms at the same time. These tumours can also spread beyond the digestive tract to other parts of the body, particularly the liver.[1][2]
How Common Are These Tumours?
Gastrointestinal neuroendocrine tumours are rare. They affect approximately 4 in every 100,000 people. Each year, about 8,000 adults in the United States are diagnosed with these tumours. While the number of new cases (incidence) is low, the number of people living with GI NETs (prevalence) is quite high. This difference exists partly because most of these tumours grow very slowly, allowing people to live with them for many years.[2][4]
According to recent analyses of large health databases, GI NETs have an annual incidence of approximately 4.97 cases per 1,000,000 patients in the United States. The condition typically affects people in their 50s and 60s, with a median age at diagnosis of 59 years, though it can occur in adults of any age.[11][2]
These tumours are slightly more common in white people compared to Black people. Women are somewhat more likely to develop GI NETs than men. While the incidence is rising overall, the reasons for this increase are not fully understood. It may be related to better detection methods and increased awareness among healthcare providers.[2][4]
What Causes Gastrointestinal Neuroendocrine Tumours?
Medical researchers have not identified one specific cause of gastrointestinal neuroendocrine tumours. These cancers may develop when neuroendocrine cells within the digestive tract experience changes in their genetic material, called mutations, causing them to multiply uncontrollably and form tumours.[4]
Scientists have found connections between GI NETs and certain conditions that affect the stomach. One such condition is hypochlorhydria, which means having low stomach acid. When the stomach cannot produce enough acid, it may create an environment that allows these tumours to develop more easily.[2]
Research about the biology of NETs is ongoing, and there is no single known cause that applies to everyone who develops these tumours. Most cases occur sporadically, meaning they happen by chance without an obvious inherited pattern or external trigger.[4]
Risk Factors for Developing GI NETs
While most people who develop gastrointestinal neuroendocrine tumours have no known risk factors, certain inherited conditions and medical histories can increase a person’s chance of developing these cancers. A risk factor is anything that makes it more likely for someone to get a disease, but having one or more risk factors does not mean a person will definitely develop the condition.[1]
One important risk factor is having a family history of certain inherited syndromes. Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic condition that causes glands like the thyroid, parathyroid, or adrenal glands to become overactive or form tumours. People with this condition have a higher risk of developing GI NETs. Similarly, neurofibromatosis type 1 (NF1), another rare inherited condition where tumours grow on the skin and nerves and can affect the eyes and other body parts, also increases the risk.[1][2]
Other inherited conditions that may predispose people to GI NETs include von Hippel-Lindau disease, where benign tumours grow in various parts of the body, tuberous sclerosis complex, and familial small intestinal neuroendocrine tumour syndrome. These conditions are all quite rare.[2][4]
Certain stomach conditions also increase risk. Having atrophic gastritis, a condition where the stomach lining becomes inflamed and damaged, makes it harder for the stomach to produce acid. Pernicious anemia, which is related to vitamin B12 deficiency and also affects stomach acid production, is another risk factor. Additionally, Zollinger-Ellison syndrome, a rare condition where tumours in the pancreas or duodenum cause the stomach to produce too much acid, can increase the risk of developing GI NETs.[1]
Recognizing the Symptoms
Many people with gastrointestinal neuroendocrine tumours do not experience any symptoms in the early stages of the disease. These tumours are often slow-growing and may be present for months or even years before causing noticeable problems. Some people are diagnosed with GI NETs only after having an imaging test, such as a CT scan or ultrasound, to investigate an unrelated medical condition.[1][2]
When symptoms do occur, they are often similar to those of less serious illnesses, which can make diagnosis challenging. The specific symptoms a person experiences depend on where the tumour is located in the digestive tract and whether it is producing excess hormones.[2]
Common symptoms of GI NETs include stomach pain or abdominal cramping, which could be a sign that a tumour has blocked part of the intestines. Diarrhea is another frequent symptom, particularly in people who have developed a condition called carcinoid syndrome or who have had their gallbladder or part of their intestines removed as part of treatment. Persistent nausea and vomiting that doesn’t go away may indicate a serious problem and should be evaluated by a doctor.[2]
Unintentional weight loss is a common warning sign of GI NETs. This means losing weight quickly without trying to diet or increase exercise. Some people notice blood in their stool, which may appear bright red or dark and tarry. These changes in stool color might indicate intestinal bleeding and require immediate medical attention. Jaundice, a condition that causes the skin and the whites of the eyes to turn yellow, can occur if a tumour affects the liver or bile ducts.[2]
Fatigue is more than just feeling sleepy or tired at the end of a long day. When related to GI NETs, fatigue means feeling exhausted all the time, even after rest. This ongoing exhaustion can significantly affect daily activities and quality of life.[2]
Carcinoid Syndrome
Some people with GI neuroendocrine tumours, particularly those whose cancer has spread to the liver or other parts of the body, may develop a group of symptoms known as carcinoid syndrome. This syndrome occurs when tumours release excess amounts of hormones and other substances into the bloodstream. The most common symptoms include skin flushing, where the face and upper body become reddened and warm, painful gas and bloating, and severe diarrhea. These symptoms can be triggered by certain foods, drinks, or stressful situations.[1][3]
Prevention Strategies
Because the exact cause of gastrointestinal neuroendocrine tumours is not fully understood, there are no guaranteed ways to prevent them. However, understanding your personal risk factors and working with your healthcare provider can help with early detection and monitoring.[1]
For people with inherited conditions that increase the risk of GI NETs, such as multiple endocrine neoplasia type 1 or neurofibromatosis type 1, regular monitoring and genetic counseling may be beneficial. These individuals should discuss with their doctors whether routine screening or surveillance would be appropriate. Early detection of small tumours, before they cause symptoms or spread, often leads to better treatment outcomes.[4]
Managing conditions that affect stomach acid production may also play a role in reducing risk. If you have atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome, working with your doctor to properly manage these conditions and monitor your digestive health is important.[1]
While no specific lifestyle changes are proven to prevent GI NETs, maintaining overall digestive health through a balanced diet, avoiding smoking, limiting alcohol consumption, and staying physically active contributes to general wellbeing and may help your body better cope with various health challenges.[4]
How the Disease Affects the Body
Understanding how gastrointestinal neuroendocrine tumours affect normal body function helps explain why certain symptoms occur and why specific treatments are chosen. These tumours disrupt the body in several important ways.[2]
In healthy individuals, neuroendocrine cells in the digestive tract respond to signals from the nervous system by producing and releasing hormones that regulate digestion. These hormones control how much digestive juice is secreted and how the muscles of the stomach and intestines contract to move food through the system. When neuroendocrine cells become cancerous, they may produce too much of these hormones, leading to symptoms like excessive diarrhea, flushing, or changes in blood pressure.[1]
As GI NET tumours grow, they can physically block parts of the digestive tract. A tumour in the small intestine, for example, might partially or completely obstruct the passage of food, causing pain, bloating, and vomiting. This mechanical blockage is one reason why some people with these tumours experience severe abdominal discomfort.[2]
The behaviour of GI NETs is influenced by several factors, including how differentiated the tumour cells are and their proliferation index, which measures how quickly cells are dividing and multiplying. Well-differentiated tumours, where the cancer cells still look somewhat like normal neuroendocrine cells, typically grow slowly. Poorly differentiated tumours, also called neuroendocrine carcinomas, grow more aggressively and have worse outcomes.[3]
GI NETs commonly spread to regional lymph nodes and the liver through a process called metastasis. When tumours spread to the liver, they can cause that organ to enlarge and not function properly. Liver metastases are particularly significant because they can lead to carcinoid syndrome when large amounts of hormones produced by tumour cells enter the bloodstream without being broken down by the liver first.[3]
Some GI NETs are classified as functional tumours, meaning they actively produce and release hormones or other bioactive substances that cause specific symptoms. Others are nonfunctional, meaning they either don’t release hormones or don’t release enough to cause noticeable symptoms. Whether a tumour is functional or nonfunctional affects both the symptoms a person experiences and how the disease is detected and monitored.[4]
The slow-growing nature of most GI NETs means that many people live with these tumours for years. However, this also means that diagnosis can be delayed because symptoms may not appear until later stages. The specific location of the tumour within the gastrointestinal tract influences which symptoms develop and which organs might be affected as the disease progresses.[3]
