Squamous cell carcinoma of the oral cavity

What is squamous cell carcinoma?

Squamous cell carcinoma is a type of oral cavity cancer. The tumour starts from the squamous cells that cover the inner surface of the oral cavity. 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 floor of the mouth. Squamous cell carcinoma often starts from a pre-cancerous disease called squamous dysplasia. Squamous dysplasia may be present for many years before turning into squamous cell carcinoma.

The oral cavity

The oral cavity is the beginning of the aerodigestive tract. The oral cavity starts at the lips and ends where the mouth meets the throat. The oral cavity is made up of multiple parts including the lips, tongue, floor of mouth, gingiva, buccal mucosa, hard palate, and retromolar trigone.

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

What is the difference between squamous cell carcinoma and squamous dysplasia?

In squamous dysplasia, the abnormal squamous cells are only found in the epithelium on the surface of the oral cavity. In contrast, in squamous cell carcinoma, the tumour cells have spread from the epithelium into the stroma below. The movement of tumour cells from the epithelium into the stroma below is called invasion.

What causes squamous cell carcinoma?

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

How do pathologists make this diagnosis?

The diagnosis is usually made after a small tissue sample is removed in a procedure called a biopsy. The tissue sample is then sent to a pathologist who examines it under the microscope. Most patients will then undergo a second procedure to remove the entire tumour. That tissue is also sent to a pathologist for examination under the microscope.

When examined under the microscope, the tumour cells in squamous cell carcinoma are usually larger than normal, healthy squamous cells. The nucleus of the cell is also usually darker. Pathologists describe these cells as hyperchromatic. The tumour cells may also have nuclei of different shapes and sizes. Pathologists describe these cells as pleomorphic. Most squamous cell carcinomas of the oral cavity are described as keratinizing because the tumour cells produce a protein called keratin which is normally found in the skin but not in the oral cavity.

The movement of tumour cells from the epithelium into the stroma causes the tissue in this area to react and change colour. This reaction is called desmoplasia. Pathologists use desmoplasia as a sign of invasion.

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 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.

The tumour grade is important because poorly differentiated tumours are often associated with a worse prognosis.

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

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. The tumour size is used to determine the tumour stage (see Pathologic stage below) and larger tumours are associated with a 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 travelled from the epithelium into the stroma below. Tumours with a depth of invasion greater than 0.5 centimetres 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.

Cancer cells that have attached to a nerve can use the nerve to spread into tissue away from the original tumour. This increases the 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. 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. 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. The types of margins described in your report will depend on the organ involved and the type of surgery performed. Margins will only be described in your report after the entire tumour has been removed.

A negative margin means that no tumour cells were seen at any of the cut edges of tissue. A margin is called positive when there are tumour 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.

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 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. Larger tumour deposits are associated with a 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. 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 a worse prognosis.

Tumour stage (pT) for squamous cell carcinoma of the oral cavity

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 centimetres in size AND the depth of invasion is no greater than 0.5 centimetres.
• T2 – The tumour is greater than 2 centimetres but less than 4 centimetres OR the depth of invasion is greater than 0.5 centimetres but less than or equal to 1 centimetre.
• T3 – The tumour is greater than 4 centimetres OR the depth of invasion is greater than 1 centimetre.
• 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 of the oral cavity

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 a 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 of the oral cavity

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.

by Jason Wasserman MD PhD FRCPC (updated August 23, 2021)