Squamous cell carcinoma (anal canal)

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This article will help you read and understand your pathology report for squamous cell carcinoma of the anal canal.

by Catherine Forse MD FRCPC, reviewed December 27, 2020

Quick facts:

• Squamous cell carcinoma is a type of cancer of the anal canal.
• It starts from the cells that line the inside of the anal canal.
• The most common cause of squamous cell carcinoma of the anal canal is infection by human papillomavirus (HPV).

The anatomy of the anal canal

The anal canal is the last part of the gastrointestinal tract. It connects the rectum to the anus. The anus is the external opening where fecal matter is released from the body.

The anal canal is made up of 3 layers of tissue:

1. Mucosa – The mucosa is the tissue that lines the inside of the anal canal. There are three zones that make up the mucosa of the anal canal. 1) The colorectal zone is made of epithelial cells that form glands. 2) The transition zone is where the epithelial cells change from gland forming to specialized squamous cells. The transition point is called the dentate line. 3) The squamous zone is made entirely of squamous cells. The squamous zone connects with the perianal skin at the anal verge.
2. Submucosa – The submucosa contains many thick blood vessels and lymphatic channels.
3. Muscle layer – The anal canal has involuntary and voluntary muscles that help to control bowel movements. The first part of the anal canal has a muscle layer called the internal anal sphincter which is an involuntary muscle. The last parts of the anal canal are surrounded by the external anal sphincter which is a large voluntary muscle that is used to release waste during defecation.

What is squamous cell carcinoma of the anal canal?

Squamous cell carcinoma is a type of anal canal cancer. Squamous cell carcinoma starts on the inside of the anal canal from the squamous cells that form the epithelium.

What causes squamous cell carcinoma of the anal canal?

Squamous cell carcinoma in the anal canal is primarily caused by infection with the human papillomavirus (HPV).

Symptoms

Symptoms of squamous cell carcinoma in the anal canal may include bleeding from the anus, anal itching, anal pain or the ability to feel a lump around your anus.

How do pathologists make this diagnosis?

The diagnosis is usually made after a small piece of the tumour is removed in a procedure called a biopsy. The tissue is sent to a pathologist for examination under a microscope. A special test called immunohistochemistry may be performed to confirm the diagnosis.

Patients are usually offered radiation or chemotherapy for treatment. For most patients, surgery is not required; however, in some situations surgery may be needed.

If surgery is performed, the entire tumour will be sent to a pathologist who will examine parts of it under the microscope. This report will confirm or revise the original diagnosis and provide additional important information such tumour size, extension, margins, and spread of tumour cells to lymph nodes. This information is used to determine the cancer stage and to decide if additional treatment is required.

Histologic grade

Pathologists use the word grade to describe how different the cancer cells in squamous cell carcinoma look compared to the normal, healthy squamous cells found in the anal canal.
Pathologists divide the grade into three categories based on how the cancer cells look when examined under the microscope.

• Well differentiated – The cancer cells look very similar to the normal squamous cells.
• Moderately differentiated – The cancer cells are clearly abnormal but still share many features with normal squamous cells.
• Poorly differentiated – The cancer cells look very different than normal squamous cells. Special tests such as immunohistochemistry may need to be performed to prove that the cancer cells are squamous cells.

Grade is important because poorly differentiated tumours are more likely to spread to other parts of the body and to re-grow after treatment.

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

Tumour size

This is the size of the tumour. The tumour is usually measured in three dimensions but only the largest dimension may be described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe the tumour as being 4.0 cm.

Tumour extension

The anal canal is a tube and the wall of the tube is made up of three to four different layers of tissue depending on the location in the anal canal (see above). Squamous cell carcinoma starts in the epithelium on the inner surface of the anal canal. The spread of cancer cells from the epithelium into the tissue below is called invasion. Tumour extension describes how far the cancer cells have spread from the epithelium into the layers of tissue below.

Your pathology report will describe the tumour extension as follows:

• High-grade squamous intraepithelial lesion (HSIL) – The cancer cells are only found in the epithelium of the anal canal (see article on anal HSIL).
• Invades submucosa – Submucosal means that the cancer cells have passed the muscularis mucosae and are into the submucosa.
• Invades anal sphincter muscle – The tumour has extended through the submucosa and is now invading either the internal and/or external sphincter muscles.
• Invades the rectal muscularis propria – Some squamous cell carcinomas extend from the anal canal into the rectum. These tumours may invade the muscularis propria of the rectum.
• Invades perianal soft tissue – The anal canal is surrounded by fatty tissue that is referred to as perianal soft tissue. Once the cancer cells spread into the perianal soft tissue they are outside of the anal canal and are able to spread directly into other organs.

Although knowing the tumour extension is important, it is the tumour size which determines the pathologic tumour stage (see Pathologic stage below). Cancer cells that have spread further into the wall of the anal canal are more likely to come back after treatment in the area of the original tumour or spread to a distant site such as the lungs. The movement of cancer cells to another part of the body is called metastasis.

Tumour site

In your report, tumour site refers to whether the tumour is found in the anal canal, perianal region or another location.

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 means that cancer cells were seen attached to a nerve.

Cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour. This increases the risk that the tumour will re-grow in the same area of the body (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.

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.

When cancer cells enter a blood vessel or lymphatic, this is called lymphovascular invasion.
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.

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 a metastasis.

Your pathologist will carefully examine each lymph node for cancer cells. Lymph nodes that contain cancer cells are called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.

Finding cancer cells in a lymph node is associated with an increased risk that the cancer cells will spread to other parts of the body. The number of lymph nodes with cancer cells is also used to determine the nodal stage (see Pathologic stage below).

Margins

In the anal canal, a margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The types of margins present will depend on the type of procedure that was performed.

For abdominoperineal resection (APR) specimens where the entire anal canal has been removed, the margins will include:

• Proximal margin – This margin is located either within the sigmoid colon or rectum before the anal canal.
• Distal margin – This margin is usually in the perianal region and typically includes the anus.
• Radial margin – This is the tissue around the outside of the anal canal.

For endoscopic resections (transanal disk excisions) where only a small piece of the inside of the anal canal has been removed, the margins will include:

• Mucosal margin – This is the tissue that lines the inner surface of the anal canal.
• Deep margin – This tissue is inside the wall of the anal canal. It is located below the tumour.

In the anal canal, 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 re-grow in the same site after treatment.

Treatment effect

If you received treatment (either chemotherapy or radiation therapy) for your cancer prior to the tumour being removed, your pathologist will examine all of the tissue submitted to see how much of the tumour is still alive (viable).

The treatment effect will be reported 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 with cancer cells will also be examined for treatment effect.

Pathologic stage

The pathologic stage for squamous cell carcinoma 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 squamous cell carcinoma of the anal canal

Squamous cell carcinoma is given a tumour stage between 1 and 4 based on the size of the tumour.

• Tis – High-grade squamous intraepithelial lesion (HSIL). If your tumour is assigned a stage of “Tis” it means that no invasive cancer was found in the specimen.
• T1 – Tumour ≤ 2 cm in greatest size.
• T2 – Tumour > 2 cm but ≤ 5 cm in greatest size.
• T3 – Tumour > 5 cm in size.
• T4 – Tumour of any size with invasion of adjacent organs (vagina, bladder, urethra).

Nodal stage (pN) for squamous cell carcinoma of the anal canal

Squamous cell carcinoma of the anal canal is given a nodal stage of 0 or 1. Nodal stage 1 is divided into 1a, 1b and 1c based on where the lymph nodes invaded by cancer cells are located in the body.

• N0 – No cancer cells are seen in any of the lymph nodes examined.
• N1a – Cancer cells are found in inguinal, mesorectal, or internal iliac lymph nodes.
• N1b – Cancer cells are found in external iliac lymph nodes.
• N1c – Cancer cells in inguinal, mesorectal, or internal iliac lymph nodes and in external iliac lymph nodes.

If no lymph nodes are submitted for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.

Metastatic stage (pM) for squamous cell carcinoma of the anal canal

Squamous cell carcinoma 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 lungs). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as X.