Well differentiated neuroendocrine tumour of the colon and rectum

by Ipshita Kak MD FRCPC
July 19, 2025

A well differentiated neuroendocrine tumour is a type of tumour that starts from specialized neuroendocrine cells in the lining of the colon or rectum. Neuroendocrine cells receive signals from the nervous system and release hormones into the bloodstream. Tumours that form from these cells are called neuroendocrine tumours. When the tumour cells look organized and similar to normal neuroendocrine cells, the tumour is called well differentiated. This is different from poorly differentiated tumours, which are more aggressive.

Well differentiated neuroendocrine tumours can form anywhere in the colon or rectum, but they are more common in the rectum. Most of these tumours are small and grow slowly. However, some can grow larger or spread to other parts of the body over time. For this reason, well differentiated neuroendocrine tumours are considered cancerous, but they are usually less aggressive than other types of colon cancer.

Is a well differentiated neuroendocrine tumour the same as cancer?

Yes, a well differentiated neuroendocrine tumour is considered a type of cancer, but it usually behaves less aggressively than other forms of colorectal cancer. These tumours can grow and, in some cases, spread to other parts of the body. However, many of them remain small and confined to the bowel wall for years, especially when diagnosed early. The risk of spread and the need for additional treatment depend on the tumour’s size, grade, and stage.

What are the symptoms of a well differentiated neuroendocrine tumour?

Many people with a well differentiated neuroendocrine tumour have no symptoms. These tumours are often discovered by chance during a colonoscopy or imaging done for another reason. When symptoms do occur, they may include:

• Rectal bleeding or blood in the stool.

• A change in bowel habits such as constipation or diarrhea.

• Abdominal pain or discomfort.

• A feeling of fullness or pressure in the rectum.

Rarely, if the tumour produces certain hormones, it can lead to a group of symptoms known as carcinoid syndrome. This includes flushing, diarrhea, and wheezing. However, this is very uncommon in tumours of the colon and rectum.

What causes a well differentiated neuroendocrine tumour?

The exact cause of these tumours is not fully understood. Most cases seem to happen by chance, although certain risk factors may increase the likelihood of developing a neuroendocrine tumour. These include:

• A family history of cancer.

• Smoking.

• Alcohol use.

• Obesity.

Most people diagnosed with these tumours are in their 50s or 60s, and the condition is slightly more common in men.

How is this diagnosis made?

The diagnosis is usually made after a tissue sample is removed during a colonoscopy or surgery and examined under a microscope by a pathologist. The pathologist will look at the structure of the tumour cells and perform special tests to confirm that the tumour is neuroendocrine in nature. These tests may include immunohistochemistry to look for markers like synaptophysin and chromogranin A, which are commonly found in neuroendocrine cells.

What does a well differentiated neuroendocrine tumour look like under the microscope?

Under the microscope, the tumour is made up of cells that are relatively uniform in size and shape. They have round or oval nuclei with a characteristic pattern known as “salt and pepper” chromatin. The tumour cells are arranged in patterns such as nests, cords, or ribbons. The tumour may be classified as grade 1, grade 2, or rarely grade 3 depending on how fast the cells are dividing. This is determined by counting how many cells are dividing (called the mitotic rate) and by measuring a protein called Ki-67 (see Tumour grade below).

Tumour grade

Tumour grade describes how quickly the tumour cells are growing and dividing. This information is important because higher grade tumours are more likely to grow faster and spread to other parts of the body.

Well differentiated neuroendocrine tumours of the colon and rectum are divided into three grades: grade 1, grade 2, and grade 3. The grade can only be determined after a pathologist examines the tumour under a microscope.

To determine the grade, the pathologist looks at how many tumour cells are dividing to form new cells. This process of cell division is called mitosis. When looking through the microscope, dividing cells are called mitotic figures, and the mitotic rate is the number of these cells seen in a specific area of the tissue sample.

In some cases, the pathologist will also perform a test called immunohistochemistry for Ki-67. Ki-67 is a protein that shows up in cells that are preparing to divide. The Ki-67 index is the percentage of tumour cells that produce this protein. A low percentage means the tumour is growing slowly, while a high percentage means it is growing more quickly.

Both the mitotic rate and the Ki-67 index are used to assign a grade to the tumour:

• Grade 1 (G1): These tumours are growing slowly. They have fewer than 2 dividing cells per high-power field or a Ki-67 index of less than 3%.

• Grade 2 (G2): These tumours are growing at a moderate rate. They have between 2 and 20 dividing cells per high-power field or a Ki-67 index between 3% and 20%.

• Grade 3 (G3): These tumours are growing more rapidly. They have more than 20 dividing cells per high-power field or a Ki-67 index greater than 20%.

The tumour grade helps your doctor understand how the tumour is likely to behave and whether additional treatment or closer follow-up may be needed.

What does invasion mean in a well differentiated neuroendocrine tumour?

Invasion refers to how deeply the tumour cells have grown into the wall of the colon or rectum. A well differentiated neuroendocrine tumour begins from special hormone-producing cells called neuroendocrine cells. These cells are normally found in small glands that sit on the inside surface of the colon and rectum, in a thin layer of tissue called the mucosa.

Beneath the mucosa are several other layers of tissue, including:

• Submucosa – a layer of supportive tissue just under the mucosa.

• Muscularis propria – a thick muscle layer that helps move stool through the colon.

• Subserosal tissue – a thin layer of fat below the muscle.

• Serosa – the outermost layer that covers the outside of the colon and rectum.

As the tumour grows, it can invade into these deeper layers. In more advanced cases, the tumour may grow all the way through the wall of the colon or rectum and spread directly into nearby organs or tissues.

The level of invasion refers to the deepest layer that the tumour has reached. This can only be determined by a pathologist who examines the tumour under a microscope after it is removed by surgery. This information is very important because tumours that invade deeper into the colon wall are more likely to spread to other parts of the body. The level of invasion is also used to determine the tumour stage, which helps guide treatment and predict the risk of recurrence.

What is perineural invasion?

Perineural invasion means that tumour cells are seen growing around or along a nerve. Nerves are found throughout the body, including in the colon and rectum, and they help carry signals such as pain or muscle movement. When tumour cells grow around a nerve, they may use it as a pathway to move into nearby tissues. Perineural invasion is an important feature because it may be associated with a higher risk of the tumour coming back after treatment. Not all neuroendocrine tumours show perineural invasion, and your pathology report will say whether this feature was seen.

What is lymphovascular invasion?

Lymphovascular invasion means that tumour cells have entered small blood vessels or lymphatic channels in the tissue around the tumour. These vessels are important because they can serve as pathways for tumour cells to travel to other parts of the body, including nearby lymph nodes or more distant organs. When lymphovascular invasion is seen, it may increase the risk of tumour spread. If your tumour shows lymphovascular invasion, your doctor may consider additional testing or closer follow-up to look for signs of spread.

What is a margin and why is it important?

A margin is the edge of the tissue that was removed during surgery. If the tumour is completely removed and there are no tumour cells at the margin, it is called a negative margin. This means that the tumour was likely removed entirely. If tumour cells are found at the margin, it is called a positive margin, and it may mean that some tumour was left behind. This information helps doctors decide whether additional treatment or monitoring is needed.

What does it mean if tumour cells are found in lymph nodes?

Lymph nodes are small, bean-shaped structures that help filter harmful substances and are part of the body’s immune system. They are often the first place tumour cells go when they begin to spread. During surgery, your doctor may remove one or more nearby lymph nodes to see if tumour cells have spread. These nodes are carefully examined under the microscope by a pathologist.

If no tumour cells are found, the lymph nodes are considered negative. If tumour cells are found, they are considered positive, which means the tumour has started to spread beyond its original location. The number of lymph nodes involved helps determine the stage of the disease and can guide decisions about treatment and follow-up.

How do pathologists determine the stage of a well differentiated neuroendocrine tumour?

The stage of a well differentiated neuroendocrine tumour in the colon or rectum describes how far the tumour has grown and whether it has spread to other parts of the body. The stage is important because it helps doctors understand how advanced the tumour is and guides decisions about treatment and follow-up care.

Pathologists use a system called the TNM staging system, which was developed by the American Joint Committee on Cancer. TNM stands for:

• T (Tumour) – how large the tumour is and how far it has grown into the wall of the colon or rectum or nearby tissues.

• N (Nodes) – whether the tumour has spread to nearby lymph nodes.

• M (Metastasis) – whether the tumour has spread to distant parts of the body such as the liver or lungs.

After examining the tumour and any lymph nodes removed during surgery, the pathologist assigns a number to each part. In general, a higher number means the tumour is more advanced.

Tumour stage (T)

The tumour stage is based on the size of the tumour and how deeply it has grown into the layers of the colon or rectum:

• T1 – The tumour is 2 centimetres or smaller and is located entirely within the innermost layer of the colon or rectum (the mucosa).

• T2 – The tumour is larger than 2 centimetres or has grown into the thick muscle layer of the wall (called the muscularis propria).

• T3 – The tumour has grown through the entire muscular wall and into the soft tissue just under the outer surface of the colon or rectum.

• T4 – The tumour has reached the outer surface of the colon or rectum or has grown into nearby organs such as the bladder or small intestine.

Lymph node stage (N)

The lymph node stage describes whether tumour cells have spread to nearby lymph nodes:

• N0 – No tumour cells were found in any of the lymph nodes examined.

• N1 – Tumour cells were found in at least one lymph node.

• NX – No lymph nodes were available for the pathologist to examine.

What is the prognosis for a person with a well differentiated neuroendocrine tumour?

The prognosis depends on the size, grade, and stage of the tumour. In general, most well differentiated neuroendocrine tumours of the colon and rectum have a good outcome, especially when they are small, low grade, and caught early. For example, people with low stage tumours of the rectum often live for many years after diagnosis, sometimes more than 20 years. Larger tumours or those that have spread may require additional treatment, and follow-up is important to monitor for recurrence.

Questions to ask your doctor

• Was the tumour completely removed?

• What grade was the tumour?

• Has the tumour spread to nearby lymph nodes or other organs?

• Do I need any additional treatment?

• How often should I have follow-up tests or colonoscopies?