This article was last reviewed on April 25, 2019 by Ipshita Kak MD FRCPC
The normal colon
The colon is a part of the gastrointestinal tract which also includes the mouth, esophagus, stomach, small bowel, and anus. The colon is a long hollow tube that starts at the small bowel and ends at the anal canal. The colon is divided into sections which include the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum.
The functions of the colon are to absorb water from the food that we eat and to move waste out of the body.
The colon is made up of five layers of tissue:
What is adenocarcinoma?
Adenocarcinoma of the colon is a type of cancer that develops from the glands in the mucosa on the inner surface of the colon. It can develop anywhere along the length of the colon (from the cecum to the rectum). Adenocarcinoma is the most common type of cancer to arise in the colon and is typically just called ‘colon cancer’.
In many cases, this cancer starts in a precancerous condition called an adenoma. An adenoma is considered a precancerous condition because it has the potential to turn into a cancer overtime.
In contrast to cancer, the abnormal cells in an adenoma are only found within the mucosa on the inside of the colon. Once the cells travel beyond the mucosa into the submucosa the diagnosis becomes adenocarcinoma. The movement of abnormal cells into the tissue outside the mucosa is called invasion.
The diagnosis of adenocarcinoma is usually made after a small tissue sample is removed in a procedure called a biopsy. The tissue is then sent to a pathologist for examination under the microscope. Most patients are then offered surgery where the entire tumour is removed and sent to pathology.
Adenocarcinoma may also be diagnosed in a polyp that is removed in a procedure called a polypectomy.
Grade is a word pathologists use to describe how different the cancer looks compared to the normal tissue in the colon. Because the normal epithelial cells in the colon form glands, adenocarcinoma is usually divided into four grades based on how much of the tumour is made of glands:
Why is this important? Grade is important because poorly differentiated and undifferentiated tumours are associated with worse prognosis and are more likely to spread (metastasize) to distant sites in the body.
After the tumour has been removed fully, your pathologist will measure it in three dimensions although only the largest dimension is typically included in your report. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in greatest dimension.
All adenocarcinomas start in the mucosa on the inside surface of the colon. The layers of tissue below the mucosa include the submucosa, muscularis propria, subserosal adipose tissue, and serosa. The movement of cancer cells from the mucosa into the tissue below is called invasion.
Tumour extension is a way of describing how far the cancer cells have traveled from the mucosa into the tissue below. Your pathologist will carefully examine your tissue to find the cancer cells that have traveled the furthest from the mucosa.
Why is this important? Cancer cells that travel deeper in the wall are more likely to come back in the area of the original tumour (local recurrence) after treatment or to spread (metastasize) to a lymph node or distant site such as the lungs. Tumour extension is also is used to determine the tumour stage (see Pathologic stage below).
Nerves are like long wires made up of groups of cells called neurons. Nerves send information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion is a term pathologists use to describe cancer cells attached to a nerve.
Perineural invasion is important because cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour.
Why is this important? Perineural invasion is associated with a higher risk that the tumour will come back in the same area of the body (local recurrence) after treatment.
Lymphatics and blood vessels are channels that normal cells use to travel around the body. The presence of cancer cells within a lymphatic or blood vessel is called lymphovascular invasion and is associated with a higher risk that the tumour will metastasize to either a lymph node or a distant site such as the lungs.
Why is this important? 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 the colon, a margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The colon is a long tube and your surgeon will need to cut out a portion of the tube in order to remove the tumour from your body. The two cut ends of the tube are called the proximal and distal margins. The radial margin is any tissue around the tube that needs to be cut.
In the colon, a margin is considered positive when there are cancer cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.
Your report will describe if any adenomas or other pre-cancerous conditions were seen at the margin.
Margins will only be described in your report after the entire tumour has been removed.
A tumour deposit is a group of cancer cells that are separate from the main tumour but not in a lymph node. The presence of tumour deposits is associated with a higher risk that the cancer will travel (metastasize) to a distant body site such as the lungs after treatment.
Tumour budding refers to either single cancer cells or small groups of cancer cells seen at the edge of the tumour. 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 increased risk that cancer cells will be found in a distant location (metastasize).
Cancer arising in a polyp
Occasionally the cancer cells are still contained to the polyp that gave rise to the tumour. If the cancer cells are limited to the inner surface of the polyp and the polyp is removed completely, there is very little chance that the cancer will come back.
The risk that the cancer will come back in the future is increased if your pathologist sees any of the following features under the microscope:
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).
Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called a metastasis.
Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.
Your pathologist will carefully examine all lymph nodes for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative.
Why is this important? Finding cancer cells in a lymph node is important because it is associated with a higher risk that the cancer cells will be found in other lymph nodes or in a distant organ such as the lungs.
Pathologic stage (pTNM)
The pathologic stage for colonic adenocarcinoma 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 more advanced disease and worse prognosis.
Tumour stage (pT) for adenocarcinoma
Adenocarcinoma is given a tumour stage between 1 and 4 based on the distance the cancer cells have traveled from the mucosa into the wall of the colon or surrounding tissues (tumour extension).
Nodal stage (pN) for adenocarcinoma
Adenocarcinoma is given an 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.
Metastatic stage (pM) for adenocarcinoma
Adenocarcinoma is given a metastatic stage between 0 and 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.
Mismatch repair testing
Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes and each gene tells the cell how to produce piece of the machine called a protein.
If the DNA becomes damaged or if it cannot be read accurately, the cell will be unable to produce the proteins it requires to function normally. An area of damaged DNA is called a mutation and mutations are one of the most common causes of cancer in humans.
For most patients, colonic adenocarcinoma arises as a result of both environmental factors (for example smoking) and genetic factors. These tumours are called ‘sporadic’ because they cannot be totally predicted.
Some patients, however, inherit particular genes that put them at a much higher risk for developing colonic adenocarcinoma. These people are said to have a ‘syndrome‘ and the most common syndrome associated with colonic adenocarcinoma is called Lynch.
Lynch syndrome is caused by the inherited loss of one of 4 special proteins (MSH2, MSH6, MLH1, and PMS2) that normally function to remove mutations from the DNA in your cells. When one of these proteins is lost, mutations start to accumulate and the normal cell can eventually turn into cancer.
As a precaution, pathologists test all colonic adenocarcinomas in patients younger than 70 years of age for Lynch syndrome using a test called ‘mismatch repair’. Some hospitals, however, will perform this case for all colonic adenocarcinomas regardless of the age of the patient.
This test looks at the activity of the 4 special proteins and if one or more of them is lost, the patient may be diagnosed with Lynch syndrome or additional testing will be performed on the tumour.
Why is this important? The diagnosis of Lynch syndrome is important not only for the patient but also for the patient’s family who may also be at risk of cancer as a result of the syndrome.
The sporadic loss of just one of these proteins is occasionally seen in patients who do not have Lynch syndrome and these tumours are associated with better prognosis than tumours without any protein loss.