Squamous cell carcinoma

This article was last reviewed on March 13, 2020 by Jason Wasserman, MD PhD FRCPC

Quick facts:

• Squamous cell carcinoma is a type of oral cavity cancer.
• The oral cavity includes the lips, tongue, gums, floor of mouth, hard palate, and inner cheeks.
• Smoking, chewing tobacco, and betel nut all increase the risk for developing squamous cell carcinoma of the oral cavity.

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

The oral cavity

The oral cavity is the beginning of the aerodigestive tract. It is used for both breathing and taking in food. The oral cavity is a complex area of the body that is made up of many parts.

The oral cavity includes:

• Lips – The soft inner surface of the lips are part of the oral cavity. The outer surface of the lips are covered by skin and are not considered part of the oral cavity.
• Tongue – The part of the tongue that you can see when you look in your mouth is part of the oral cavity. The very back of the tongue (the part you can’t see) is part of another area of the body called the oropharynx.
• Floor of mouth – The floor of mouth is the soft tissue underneath your tongue.
• Cheeks – The inner surface of the cheeks are part of the oral cavity. The inner cheeks are also called the buccal mucosa.
• Gums – The gums are the tissue that surround and hold the teeth. The gums are also called gingiva.
• Roof of mouth – This is the top of your mouth. Only the hard part of the roof is part of the oral cavity. The soft part of the roof at the very back of your mouth near your throat is called the soft palate and it is part of another area of the body called the oropharynx.
• Retromolar trigone – This is a small triangle shaped area of tissue behind the last tooth on the bottom of your mouth.

The surface of the oral cavity is lined by specialized cells called squamous cells. that create a barrier called the epithelium. The tissue below the epithelium is called stroma. Pathologists use the word mucosa to describe tissue that includes both the epithelium and the stroma.

What is squamous cell carcinoma?

Squamous cell carcinoma  is a type of cancer that starts from the squamous cells in the epithelium. Squamous cell carcinoma is the most common type of cancer to start in the oral cavity. This tumour can start anywhere in the oral cavity although most start on the side of the tongue (lateral tongue) or the bottom (floor) of the mouth.

Squamous cell carcinoma in the oral cavity often starts from a pre-cancerous disease called squamous dysplasia. Squamous dysplasia may be present for many years before turning into squamous cell carcinoma.

When examined under a microscope, the abnormal cells in squamous dysplasia are only found in the epithelium on the surface of the oral cavity. In order to become squamous cell carcinoma, the cancer cells have to move from the epithelium into the stroma below. The movement of cancer cells from the epithelium into the stroma below is called invasion.

Smoking and high levels of alcohol consumption increase the risk for developing both squamous cell carcinoma and squamous dysplasia.

Most squamous cell carcinomas of the oral cavity are described as keratinizing because the cancer cells produce a protein called keratin which is normally found in the skin but not in the oral cavity.

The diagnosis of squamous cell carcinoma is usually made after a small tissue sample is removed in a procedure called a biopsy. The tumour is usually they removed completely and sent to pathology.

The type of surgery performed to remove a tumour from the oral cavity will depend on the location and size of the tumour. Some procedures are given special names which tell the pathologist what kind of tissue was removed.

Here is a list of some common special procedures performed to remove tumours from the oral cavity:

• Glossectomy – In this procedure part of the tongue is removed. A small part of the bottom of the mouth (the floor of the mouth) may be removed at the same time.
• Mandibulectomy – The mandible is the bone in the lower jaw. In this procedure, part of the mandible is removed along with the tissue attached to it.
• Maxillectectomy – The maxilla is the bone in the upper jaw. In this procedure part of the maxilla is removed along with the tissue attached to it.

Histologic grade

Pathologists use the word grade to describe how different the cancer cells in squamous cell carcinoma look compared the squamous cells normally found in the oral cavity.

The grade is divided into three levels of differentiation based on how the cancer cells look when examined under the microscope:

• Well differentiated – The cancer cells in this tumour look very similar to normal squamous cells.
• Moderately differentiated – The cancer cells in this tumour are abnormal but they still resemble squamous cells.
• Poorly differentiated – The cancer cells in this tumour look very little or nothing like normal squamous cells. Additional tests such as immunohistochemistry may be needed to prove the tumour is a squamous cell carcinoma.

Why is this important? Grade is important because poorly differentiated tumours are often associated with a worse prognosis.

Tumour size

This is the size of the tumour. Tumour size will only be described in your report after the entire tumour has been removed. The tumour is usually measured in three dimensions but only the largest dimension is 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.

Why is this important? The tumour size is used to determine the tumour stage (see Pathologic stage below). Larger tumours are associated with worse prognosis.

Depth of invasion

All squamous cell carcinomas start in the epithelium on the surface of the oral cavity. Depth of invasion is a measurement of how far the cancer cells have traveled from the epithelium into the stroma below.

Why is this important? Tumours with a depth of invasion greater than 0.5 centimeters (5 millimeters) are associated with a higher risk that the tumour will come back at the same site after treatment or that cancer cells will be found in a lymph node. The depth of invasion 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 means that cancer cells were seen attached to a nerve.

Why is this important? 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 come back 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. Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion.

Why is this important? 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.

Margins

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed.

Your pathologist will carefully examine all the margins in your tissue sample to see how close the cancer cells are to the edge of the cut tissue. Margins will only be described in your report after the entire tumour has been removed.

A margin is considered positive when there are cancer cells at the very edge of the cut tissue.

A negative margin means there were no cancer cells at the very edge of the cut tissue. If all the margins are negative, most pathology reports will say how far the closest cancer cells were to a margin. The distance is usually described in millimeters.

Why is this important? A positive margin is associated with a higher risk that the tumour will grow back (recur) in the same site after treatment.

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.

Lymph nodes from the neck are sometimes removed at the same time as the main tumour in a procedure called a neck dissection. The lymph nodes removed usually come from different areas of the neck and each area is called a level. The levels in the neck include 1, 2, 3, 4, and 5. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination.

Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.

Your pathologist will carefully examine each lymph node 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. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.

Tumour deposit

A group of cancer cells inside of a lymph node is called a tumour deposit. If a tumour deposit is found, your pathologist will measure the deposit and the largest tumour deposit found will be described in your report.

Why is this important? Larger tumour deposits are associated with worse prognosis. The size of the largest tumour deposit is also used to determine the nodal stage (see Pathologic stage below).

Extranodal extension (ENE)

All lymph nodes are surrounded by a capsule. Extranodal extension (ENE) means that cancer cells have broken through the capsule and into the tissue that surrounds the lymph node.

Why is this important? Extranodal extension is also associated with a higher risk of new tumours developing in the neck and is often used by your doctors to guide your treatment. Extranodal extension is also used to determine the nodal stage (see Pathologic stage below).

Pathologic stage (pTNM)

​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.

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 squamous cell carcinoma

Your pathologist will look for three features in order to determine the tumour stage:

1. The size of the tumour.
2. The depth of invasion.
3. The presence of cancer cells in nearby tissues.

Based on these features, squamous cell carcinoma is given a tumour stage between 1 and 4:

• Tis – The cancer cells are only seen in the epithelium at the surface of the tissue. They do not invade the stroma.
• T1 – The tumour is less than or equal to 2 centimeters in size AND the depth of invasion is no greater than 0.5 centimeters.
• T2 – The tumour is greater than 2 centimeters but less than 4 centimeters OR the depth of invasion is greater than 0.5 centimeters but less than or equal to 1 centimeter.
• T3 – The tumour is greater than 4 centimeters OR the depth of invasion is greater than 1 centimeter.
• T4 – The tumour invades tissues outside of the oral cavity such as the bones of the jaw or the sinuses.

Nodal stage (pN) for squamous cell carcinoma

Your pathologist will look for four features in order to determine the nodal stage:

1. The size of the tumour deposit.
2. The number of lymph nodes that contain cancer cells.
3. The presence of extranodal extension.
4. Whether the lymph nodes with cancer cells are on the same or opposite side of the neck as the main tumour (laterality).

Based on these features, squamous cell carcinoma is given an nodal stage between 0 and 3.  The N2 and N3 stages are divided into smaller groups with letters (a, b, or c) after the number.

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

Metastatic stage (pM) for squamous cell carcinoma

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 assigned if tissue from a distant site is sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.