Adenocarcinoma of the colon

What is adenocarcinoma?

Adenocarcinoma is the most common type of colon cancer. The tumour arises 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. In many cases, this cancer starts in a pre-cancerous condition called an adenoma. Common types of adenomas in the colon are tubular, tubulovillous, villous, and sessile serrated.

The 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 six layers of tissue:

  1. Mucosa – The mucosa is the tissue that lines the inside surface of the colon. The mucosa includes epithelial cells that form structures called glands. The glands are surrounded and supported by a tissue called lamina propria.
  2. Muscularis mucosa – This is a thin layer of muscle that sits just below the mucosa.
  3. Submucosa – The submucosa contains many thick blood vessels and lymphatic channels.
  4. Muscularis propria – The muscularis propria is a thick bundle of muscle. The muscles in the muscularis propria help move digested food and waste along the colon.
  5. Subserosal adipose tissue – This is a layer of fat that sits directly below the muscularis propria. The subserosal adipose tissue is near the outside surface of the colon.
  6. Serosa – The serosa is a thin layer of tissue that covers the subserosal adipose tissue and the outside of the colon.

How do pathologists make this diagnosis?

The diagnosis of adenocarcinoma is usually made after a small sample of the tumour is removed in a procedure called a biopsy. A test called immunohistochemistry may be performed to confirm the diagnosis.

After the tumour has been removed completely, it will be sent to a pathologist who will prepare another pathology report. This report will confirm or revise the original diagnosis and provide additional important information such tumour size, extension, and spread of tumour cells to lymph nodes. A test to look for mismatch repair proteins may also be performed (see Mismatch repair proteins section below). This information is used to determine the cancer stage and to decide if additional treatment is required.

Tumour grade

Grade is a term 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 connect together to make glands, adenocarcinoma is usually divided into four grades based on how much of the tumour is made of glands:

  1. Well differentiated – More than 95% of the tumour is made up of glands.
  2. Moderately differentiated – 50 to 95% of the tumour is made up of glands.
  3. Poorly differentiated – Less than 50% of the tumour is made up of glands.
  4. Undifferentiated – There are no glands seen anywhere in the tumour.

Grade is important because poorly differentiated and undifferentiated tumours are associated with a worse prognosis and are more likely to spread to distant sites in the body.

Mismatch repair

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. 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 tested has been ordered on your tissue sample, the results will be described in your pathology report.

Normal DNA repair

​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 a 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. Mismatch repair proteins keep cells healthy and functioning normally by fixing these mutations when they happen.

Loss of mismatch repair

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.

Cancer caused by loss of mismatch repair

For most people, cancer develops as a result of both environmental factors (for example smoking) and genetic factors. These tumours are called ‘sporadic’ because we cannot predict exactly which people will develop them and when. Some people, however, inherit genetic changes that put them at a much higher risk of developing cancer. These people are said to have a syndrome.

The most common syndrome associated with adenocarcinoma of the colon is Lynch syndrome. Lynch syndrome is caused by a genetic change that results in the loss of one of the mismatch repair proteins. Another name for this syndrome is hereditary nonpolyposis colorectal cancer (HNPCC).

The most common genetic changes associated with Lynch syndrome involve the genes that produce MLH1 and MSH2.  A small number of people with Lynch syndrome will show genetic changes involving MSH6 and PMS2.

People with Lynch syndrome are at high risk for developing adenocarcinoma of the colon at an early age. Women with Lynch syndrome are also at risk for developing ovarian and endometrial cancer at an early age. Other types of cancers associated with Lynch syndrome include stomach, liver, bladder, skin, and brain.

Muir-Torre is a syndrome that is closely related to Lynch syndrome. People with Muir-Torre are at high risk for developing a type of skin cancer called sebaceous carcinoma. These people are also at risk for developing multiple non-cancerous skin tumours called sebaceous adenomas.

How do pathologists test for mismatch repair proteins?

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.

What to look for in your report after the tumour has been removed

Tumour size

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 the greatest dimension.

Tumour extension

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 travelled from the mucosa into the tissue below. Your pathologist will carefully examine your tissue to find the cancer cells that have travelled the furthest from the mucosa.​

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 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).

Perineural invasion

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

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. Perineural invasion is also associated with a higher risk that the tumour will come back in the same area of the body (local recurrence) after treatment.

Lymphovascular invasion

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.

lymphovascular invasion

Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Seeing lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.

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.

Tumour deposits

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 lungs after treatment.

Tumour budding

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.

Cancer arising in an adenoma

Occasionally the cancer cells are still contained in the adenoma that gave rise to the tumour. If the cancer cells are limited to the inner surface of the adenoma and the adenoma is removed completely, there is very little chance that the cancer will come back.

The risk that cancer will come back in the future is increased if your pathologist sees any of the following features under the microscope:

  • The cancer cells are very close to the cut edge of the polyp.
  • The tumour is poorly differentiated or undifferentiated (see Histologic grade above).
  • There is lymphovascular invasion (see Lymphovascular invasion above).
  • Small groups of cancer cells are breaking off from the edge of the tumour (pathologists refer to this feature as ‘high-grade tumour budding’; see Tumour budding above).
Treatment effect

​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

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.

Lymph node

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).

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 a worse prognosis.

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.

Tumour stage (pT) for adenocarcinoma

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).

  • T1 – The tumour is in the submucosa just below the mucosa on the inner surface of the colon.
  • T2 – The tumour has entered the muscularis propria of the colon.
  • T3 – The tumour that has gone through the entire muscular wall and is in the fat near the outer surface of the colon.
  • T4 – The tumour is in the serosa on the outer surface of the colon or it has gone into surrounding organs such as the bladder or abdominal wall.​
Nodal stage (pN) for adenocarcinoma

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.

Metastatic stage (pM) for adenocarcinoma

Adenocarcinoma is given a metastatic stage of 0 or1 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.

by Ipshita Kak MD FRCPC (updated July 22, 2021)
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