by Jason Wasserman MD PhD FRCPC
February 9, 2023
Adenocarcinoma is the most common type of colon cancer. It starts from the glands normally found on the inside surface of the colon. Any part of the colon, from the cecum to the rectum, can be involved.
Because adenocarcinoma is the most common type of cancer in the colon, it is often simply called ‘colon cancer’. Less common types of colon cancer include well differentiated neuroendocrine tumour and poorly differentiated neuroendocrine carcinoma.
Adenocarcinoma in the colon is believed to be caused by a combination of environmental and genetic factors. Established risk factors include excess consumption of processed meats, red meats, and alcohol. People with excess body fat are also at increased risk of developing adenocarcinoma. Prolonged inflammation in the colon, which can be seen in inflammatory bowel disease (ulcerative colitis and Crohn’s disease), is also associated with an increased risk of developing adenocarcinoma.
Symptoms of adenocarcinoma depend on the location of the tumour within the colon. Tumours in the left colon (descending colon) or rectum can cause changes in bowel habits, bloody stools, abdominal pain, or bloating. Tumours in the right colon (ascending colon) may not cause any symptoms until the tumour is very large or has spread to other parts of the body.
The diagnosis of adenocarcinoma is usually made after a small tissue sample is removed during an examination called a colonoscopy. The procedure used to remove the tissue may be called a biopsy or polypectomy. The tissue sample is then sent to a pathologist for examination under the microscope.
When examined under the microscope, adenocarcinoma of the colon is made up of groups of tumour cells arranged in glands (that may look similar to the normal glands in the colon), nests, or sheets. Pathologists use the term mucinous differentiation to describe tumours that contain a large amount of extracellular mucin. Mucin is a specialized type of protein made by both normal cells and tumour cells. Extracellular means that the mucin was seen outside of the tumour cells. If more than 50% of the tumour is made up of mucin, the tumour is called mucinous adenocarcinoma.
Pathologists use the term differentiated to divide adenocarcinoma of the colon into four grades – well differentiated, moderately differentiated, poorly differentiated, and undifferentiated. The grade is based on the percentage of the tumour forming round structures called glands. The grade is important because poorly differentiated and undifferentiated tumours behave in a more aggressive manner and are more likely to spread to other parts of the body.
For adenocarcinoma of the colon, well differentiated means that more than 95% of the tumour is made up of glands. Pathologists also describe these tumours as grade 1.
For adenocarcinoma of the colon, moderately differentiated means that 50 to 95% of the tumour is made up of glands. Pathologists also describe these tumours as grade 2.
For adenocarcinoma of the colon, poorly differentiated means that less than 50% of the tumour is made up of glands. Pathologists also describe these tumours as grade 3.
For adenocarcinoma of the colon, undifferentiated means that no glands were seen anywhere in the tumour. Pathologists also describe these tumours as grade 4.
In pathology, the term invasion is used to describe the spread of cancer cells into organs or tissues surrounding the location where the tumour started. Because adenocarcinoma starts in a thin layer of tissue on the inside surface of the colon called the mucosa, invasion is defined as the spread of cancer cells into the other layers of tissue in the colon (see picture below) or any other organs outside of the colon. Invasion can only be seen after the tumour has been examined under a microscope by a pathologist.
When examining the tumour under the microscope, your pathologist will look to see how far the cancer cells have spread from the mucosa into the surrounding tissue. This is called the level of invasion. The level of invasion is important because tumours that invade deeper into the wall of the colon are more likely to spread to other parts of the body such as lymph nodes, the liver, or the lungs. The level of invasion is also used to determine the pathologic tumour stage (pT).
Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery.
Lymphovascular invasion means that cancer cells were seen inside of a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the liver. The presence of cancer cells inside a large vein past beyond the wall of the colon (outside of the thick bundle of muscle) is associated with a high risk that the cancer cells will eventually be found in the liver.
In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.
Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) depends on the type of tumour being removed and the location of the tumour.
Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.
A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved. For example, additional treatment may not be necessary for a benign (non-cancerous) type of tumour but may be strongly advised for a malignant (cancerous) type of tumour.
Tumour budding is a term pathologists use to describe either single cancer cells or small groups of cancer cells seen at the edge of the tumour. Tumour budding is believed to be a sign that the tumour is becoming less differentiated. A score is assigned, either low, intermediate, or high, based on the number of buds seen under the microscope. A high score is associated with an increased risk that cancer cells will spread to another part of the body.
If you received treatment (either chemotherapy or radiation therapy or both) for your cancer prior to the tumour being removed, your pathologist will carefully examine the area of the tissue where the tumour was previously identified to see if any cancer cells are still alive (viable).
The most commonly used system describes the treatment effect on a scale of 0 to 3 with 0 being no viable cancer cells (all the cancer cells are dead) and 3 being extensive residual cancer with no apparent regression of the tumour (all or most of the cancer cells are alive).
A tumour deposit is a group of cancer cells that are separate from the main tumour but not in a lymph node. Tumour deposits are associated with a higher risk that the tumour cells will spread to another part of the body such as the liver or lungs after treatment. Tumour deposits are also used to determine the pathologic tumour stage (pT).
Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body such as a lymph node is called a metastasis.
Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.
If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells will also be included.
The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.
Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.
Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.
All lymph nodes are surrounded by a thin layer of tissue called a capsule. Extranodal extension means that cancer cells within the lymph node have broken through the capsule and have spread into the tissue outside of the lymph node. Extranodal extension is important because it increases the risk that the tumour will regrow in the same location after surgery. For some types of cancer, extranodal extension is also a reason to consider additional treatment such as chemotherapy or radiation therapy.
Mismatch repair (MMR) is a system inside all normal, healthy cells for fixing mistakes in our genetic material (DNA). The system is made up of different proteins and the four most common are called MSH2, MSH6, MLH1, and PMS2.
The four mismatch repair proteins MSH2, MSH6, MLH1, and PMS2 work in pairs to fix damaged DNA. Specifically, MSH2 works with MSH6 and MLH1 works with PMS2. If one protein is lost, the pair cannot function normally. A loss of one of these proteins increases the risk of developing cancer.
Pathologists order mismatch repair testing to see if any of these proteins are lost in a tumour. If mismatch repair testing has been ordered on your tissue sample, the results will be described in your pathology report.
Mismatch repair (MMR) testing is performed on colon cancers to identify patients who may have Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC). Lynch syndrome is a genetic disorder that increases the risk of developing various types of cancer, including colon cancer, endometrial cancer, ovarian cancer, gastric cancer, and others.
The most common way to test for mismatch repair proteins is to perform a test called immunohistochemistry. This test allows pathologists to see if the tumour cells are producing all four mismatch repair proteins. Most reports will list all four proteins and say whether each is “retained” (normal production) or “deficient” (lost or not produced).
The pathologic stage for adenocarcinoma of the colon is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M) to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means a more advanced disease and a worse prognosis.
The pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.
Adenocarcinoma of the colon is given a tumour stage between 1 and 4 based on the distance the cancer cells have spread from the mucosa into the wall of the colon or surrounding tissues (depth of invasion).
Adenocarcinoma of the colon is given a nodal stage between 0 and 2 based on whether any cancer cells were found in any of the lymph nodes examined or the finding of tumour deposits. If no cancer cells were found in any of the lymph nodes examined, the nodal stage is N0. If no lymph nodes were sent for pathologic examination, the nodal stage cannot be determined and is listed as NX.
Adenocarcinoma of the colon is given a metastatic stage of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the liver). The M stage can only be assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the M stage cannot be determined and is listed as X.