Small intestine neuroendocrine tumours are rare cancers that develop from specialised hormone-producing cells in the digestive system, often growing slowly and presenting unique challenges in diagnosis and management for patients and healthcare teams alike.
Understanding Small Intestine Neuroendocrine Tumours
Small intestine neuroendocrine tumours, sometimes called small bowel NETs, are uncommon cancers that begin in the neuroendocrine cells of the small intestine. These cells are special because they work like a bridge between the nervous system and the hormone system. They produce hormones that help control how the digestive system works, including the release of digestive juices and the movement of food through the intestines.[1]
The small intestine, also called the small bowel, is the longest part of the digestive tract, measuring about six metres in adults when stretched out. It has three sections: the duodenum, which connects to the stomach; the jejunum in the middle; and the ileum, which joins to the large bowel. Most small bowel neuroendocrine tumours develop in the ileum and jejunum, though some can appear in the duodenum.[1]
These tumours belong to a larger family of cancers called neuroendocrine neoplasms (NENs). There are two main types within this family: neuroendocrine tumours (NETs) and neuroendocrine carcinomas (NECs). NETs tend to grow slowly and are called “well-differentiated,” while NECs grow rapidly and are “poorly differentiated.” Understanding which type you have is important because they behave very differently and require different treatment approaches.[1]
How Common Are Small Intestine Neuroendocrine Tumours?
Small intestine neuroendocrine tumours are genuinely rare conditions. In England, around 610 people receive this diagnosis each year. When looking at all cancers that can start in the small bowel, neuroendocrine cancers account for about 40 out of every 100 cases, making them one of the more common types of small intestinal cancer despite being rare overall.[1]
These tumours affect about 4 in every 100,000 people. In the United States, approximately 8,000 adults are diagnosed with gastrointestinal neuroendocrine tumours each year, with small intestine cases making up a significant portion. The condition typically appears in people aged 55 to 65, though it can develop at any age. Women are slightly more likely than men to develop these tumours, and they are more common in white populations than in Black populations.[5]
Interestingly, the number of diagnosed cases has been rising in recent years. This increase does not necessarily mean more people are developing the disease. Instead, it reflects improvements in diagnostic technology and greater awareness among healthcare professionals, allowing doctors to identify tumours that might have been missed in the past.[3]
What Causes These Tumours?
Medical researchers have not identified a single, clear cause for small intestine neuroendocrine tumours. Unlike some other cancers where specific triggers like smoking or sun exposure play obvious roles, the origins of these tumours remain largely mysterious. Scientists continue to investigate why neuroendocrine cells in some people begin growing abnormally and forming tumours.[1]
However, research has found links between these tumours and certain conditions affecting stomach acid production. People with hypochlorhydria (low stomach acid), atrophic gastritis (inflammation that damages the stomach lining), pernicious anaemia (a vitamin B12 deficiency disorder), or Zollinger-Ellison syndrome (a condition causing excessive stomach acid) may face increased risk.[4][5]
The small intestinal tumours are often described as “midgut carcinoids” because they originate from the embryological midgut portion of the digestive system. They are characterised by their ability to release serotonin, a hormone that can cause various symptoms when released into the bloodstream in large amounts.[2]
Risk Factors for Small Bowel Neuroendocrine Tumours
While the exact causes remain unclear, certain factors can increase the likelihood of developing small intestine neuroendocrine tumours. Having a family history of cancer, particularly neuroendocrine cancers, is considered a risk factor. However, it is more common for only one person in a family to develop this condition. Rarely, more than one family member may be affected, but this is the exception rather than the rule.[1]
People with specific inherited genetic syndromes face higher risks. Multiple endocrine neoplasia type 1 (MEN1) is a condition where the thyroid, parathyroid, adrenal glands, pancreas, or pituitary become overactive or develop tumours. Another condition, neurofibromatosis type 1 (NF1), causes tumours to grow on skin and nerves and can affect the eyes and other body parts. Both of these syndromes are associated with increased risk of developing neuroendocrine tumours.[4][5]
Von Hippel-Lindau disease is another rare inherited condition where benign tumours grow in various parts of the body, and people with this syndrome may also have elevated risk. Interestingly, some people who have already had one small bowel NET may develop another in the future, though this is not common.[1][5]
Recognising the Symptoms
One of the challenges with small intestine neuroendocrine tumours is that many people have no symptoms at all, especially in the early stages. Doctors sometimes discover these tumours accidentally when performing scans or tests for completely unrelated reasons. When symptoms do appear, they can be vague and similar to many less serious digestive problems, which can delay diagnosis.[1][5]
Common symptoms include persistent tummy (abdominal) pain, which can signal that the tumour is affecting the intestine or nearby structures. Weight loss without trying, feeling or being sick, and extreme tiredness that goes beyond normal sleepiness are other possible signs. Changes in bowel habits, particularly diarrhoea (frequent, watery stools), can occur. Some people notice bleeding in their digestive system, which might cause black, tarry stools or blood in vomit.[1][3]
Bowel obstruction can develop if the tumour grows large enough to block the intestine, causing severe abdominal pain, vomiting, and constipation. Some people experience jaundice, a condition where the skin and whites of the eyes turn yellow, which can indicate that the tumour has spread to affect the liver.[3][5]
A unique feature of some small bowel neuroendocrine tumours is their ability to produce excess hormones that enter the bloodstream. These are called “functioning tumours.” When hormones like serotonin are released in large amounts, they can cause a collection of symptoms known as carcinoid syndrome. This syndrome includes facial flushing (sudden redness and warmth of the face and neck), watery diarrhoea, and wheezing or bronchospasm (difficulty breathing due to narrowed airways). In some cases, it can affect the heart, leading to carcinoid heart disease. The presence of carcinoid syndrome usually means the cancer has spread to the liver.[1][2][3]
Prevention Strategies
Because medical researchers have not identified clear, modifiable causes for small intestine neuroendocrine tumours, there are no specific prevention strategies proven to reduce risk. Unlike cancers linked to lifestyle factors such as smoking or sun exposure, small bowel NETs do not have well-established preventable triggers.[1]
For people with inherited genetic syndromes that increase risk, such as multiple endocrine neoplasia type 1 or neurofibromatosis type 1, working closely with healthcare providers for regular monitoring may help detect any tumours early. Genetic counselling can provide valuable information for individuals and families affected by these conditions, helping them understand their risks and the benefits of surveillance.[4]
Maintaining overall digestive health by addressing conditions that affect stomach acid production, such as atrophic gastritis or pernicious anaemia, may be beneficial, though direct evidence linking treatment of these conditions to reduced NET risk is limited. Regular medical check-ups and promptly reporting new or persistent symptoms to a doctor remain important for early detection of any health problems.[4]
How the Disease Develops: Pathophysiology
Small intestine neuroendocrine tumours develop when neuroendocrine cells in the small bowel begin growing and dividing abnormally. Under normal circumstances, these cells produce and release hormones in controlled amounts to help regulate digestive processes. When they become cancerous, they lose this control and may produce excessive hormones while also forming masses of tissue.[1]
These tumours are typically located in the terminal ileum, the lower portion of the small intestine. They often appear as flat, firm, fibrous growths beneath the intestinal lining, commonly measuring one centimetre or less. Despite their small size, these primary tumours can be aggressive. In about one-third of cases, multiple small tumours develop in nearby areas, likely spreading through the lymphatic system.[2]
A striking feature of small bowel NETs is their tendency to spread to the mesenteric lymph nodes—small immune system structures in the double fold of tissue (mesentery) that anchors the intestines. These metastatic deposits often grow larger than the primary tumour and become surrounded by significant scarring and fibrosis (thickening and stiffening of tissue). This fibrosis is particularly troublesome because it can trap loops of intestine, causing partial or complete blockage. The scarring may also encase blood vessels in the mesentery, leading to poor blood flow and potential damage to segments of the intestine.[2]
When small bowel NETs spread beyond the intestine and lymph nodes, the liver is the most common destination. Liver involvement is significant because once hormones produced by the tumours enter the liver’s blood vessels, they can bypass the normal filtering process and enter the general circulation. This is typically when carcinoid syndrome develops, as large amounts of serotonin and other substances flood the bloodstream, causing the characteristic flushing, diarrhoea, and other symptoms.[2]
The tumours themselves are described as “endocrine tumours” because they arise from hormone-producing cells. They can occur throughout the intestinal tract and even in organs like the lungs, thymus, and pancreas. The term “carcinoid” was historically used because early observers noted these tumours behaved more benign than typical large bowel cancers. However, their potential for spread and serious complications is now well recognised, even though many grow slowly compared to other cancers.[2]
