by Jason Wasserman MD PhD FRCPC
April 18, 2022
Colorectal mucinous adenocarcinoma is a type of colon cancer. In order to make this diagnosis, at least 50% of the tumour must be made up of extracellular mucin. Mucinous adenocarcinoma accounts for approximately 10 to 20% of all colon cancers in adults. Compared to other types of colon cancer, mucinous adenocarcinoma is more likely to possess changes in genes associated with the mismatch repair (MMR) system. These changes are associated with an increased risk of developing cancer.
The diagnosis of mucinous adenocarcinoma of the colon 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.
Once the entire tumour is removed it will be sent to a pathologist who will look for additional features such as the tumour grade, depth of invasion, perineural invasion, lymphovascular invasion, tumour budding, and cancer cells in lymph nodes or surrounding tissues. Tests to look for mismatch repair (MMR) proteins may also be performed. These features are explained in greater detail in the sections below.
When examined under the microscope, mucinous adenocarcinoma is made up of groups of tumour cells surrounded by extracellular mucin. The mucin is called extracellular because it is outside of the tumour cells. Pathologists often use the term ‘pools’ to describe large areas of extracellular mucin. The groups of tumour cells may be arranged in round structures called glands (that may look similar to the normal glands in the colon) or they may be arranged in nests or sheets. Some tumour cells in mucinous adenocarcinoma may contain a large amount of intracellular mucin (mucin inside the cell) which pushes the nucleus to the edge of the cell. These cells are called signet ring cells and they are commonly seen in mucinous adenocarcinoma of the colon.
Pathologists use the term differentiated to divide mucinous adenocarcinoma 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. A well-differentiated tumour (grade 1) is more than 95% glands. A moderately differentiated tumour (grade 2) is 50 to 95% glands. A poorly differentiated tumour (grade 3) is less than 50% glands. An undifferentiated tumour (grade 4) does not make any glands. The grade is important because less differentiated tumours (for example poorly differentiated and undifferentiated tumours) behave in a more aggressive manner and are more likely to spread to other parts of the body.
Pathologists use the word invasion to describe the spread of tumour cells from the inside of the colon into the surrounding tissues. Mucinous adenocarcinoma starts from the glands on the inside surface of the colon. The glands are part of a thin layer of tissue called the mucosa. The layers of tissue below the mucosa include the submucosa, muscularis propria, subserosal adipose tissue, and serosa. As the tumour grows the cells can spread into these layers. Eventually, the tumour cells can break through the outside surface of the colon and spread directly into nearby organs and tissues.
The level of invasion is the deepest point of invasion and it can only be measured after the tumour is examined under the microscope by a pathologist. 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. The level of invasion is also used to determine the pathologic tumour stage (pT).
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 a term pathologists use to describe tumour cells attached to a nerve. Perineural invasion is important because tumour cells that have become attached to a nerve can grow along the nerve and into surrounding tissues. This increases the risk that the tumour will re-grow after treatment.
Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood vessel or lymphatic channel. Lymphovascular invasion is important because once the tumour cells are inside a blood vessel or lymphatic channel they are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.
The presence of tumour 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.
A margin is called negative if no cancer cells are seen at the cut edge of the tissue. 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.
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 cancer will spread to another body site such as the lungs after treatment.
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. 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).
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 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.
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. The examination of lymph nodes is also used to determine the nodal stage (see Pathologic stage below).
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.
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.
If the tumour cells are not producing one of the proteins, your report will describe this protein as “lost” or “deficient”. Because the mismatch repair proteins work in pairs (MSH2 + MSH6 and MLH1 + PMS2), two proteins are often lost at the same time.
If the tumour cells in your tissue sample show a loss of one or more mismatch repair proteins, you may have inherited Lynch syndrome and should be referred to a genetic specialist for additional tests and advice.
The pathologic stage for mucinous 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 a worse prognosis.
Mucinous adenocarcinoma is given a tumour stage between 1 and 4 based on the distance the cancer cells have travelled from the mucosa into the wall of the colon or surrounding tissues (tumour extension).
Mucinous adenocarcinoma 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.
Mucinous adenocarcinoma 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.