Squamous cell carcinoma of the oral cavity

by Jason Wasserman MD PhD FRCPC
June 16, 2022

What is squamous cell carcinoma of the oral cavity?

Squamous cell carcinoma is a type of oral cavity cancer. This area includes the lips, tongue, floor of the mouth, gingiva (gums), buccal mucosa (inner cheeks), and palate (roof of the mouth). Squamous cell carcinoma often develops from a pre-cancerous disease called squamous dysplasia which may be present for many years before turning into squamous cell carcinoma.

What causes squamous cell carcinoma of the oral cavity?

Smoking, high levels of alcohol consumption, chronic inflammatory conditions such as lichen planus, and immunosuppression all increase the risk of developing both squamous cell carcinoma and squamous dysplasia.

How is the diagnosis of squamous cell carcinoma in the oral cavity made?

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.

How do pathologists grade squamous cell carcinoma in the oral cavity?

Pathologists use the term differentiated to divide squamous cell carcinoma of the oral cavity into three grades – well-differentiated, moderately differentiated, and poorly differentiated. The grade is based on how much the tumour cells look like normal squamous cells. A well-differentiated tumour (grade 1) is made up of tumour cells that look almost the same as normal squamous cells. A moderately differentiated tumour (grade 2) is made up of tumour cells that clearly look different from normal squamous cells, however, they can still be recognized as squamous cells. A poorly differentiated tumour (grade 3) is made up of tumour cells that look very little like normal squamous cells. These cells can look so abnormal that your pathologist may need to order an additional test such as immunohistochemistry to confirm the diagnosis. The grade is important because less differentiated tumours (moderately and poorly differentiated tumours) behave in a more aggressive manner and are more likely to spread to other parts of the body.

What does the depth of invasion mean?

All squamous cell carcinomas in the oral cavity start from a thin layer of tissue called the epithelium that covers the entire inside surface of the oral cavity. Below the epithelium are other types of tissue that are often described together as stroma or submucosa. Pathologists use the word invasion to describe the movement of tumour cells from the epithelium into the tissue below and the depth of invasion is a measurement of the farthest the tumour cells have travelled.

The depth of invasion is important because tumours with a depth of invasion greater than 0.5 centimetres are more likely to spread to lymph nodes in the neck (see Lymph nodes below). The depth of invasion is also used to determine the pathologic tumour stage (see Pathologic stage below).

What perineural invasion?

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 the tumour cells can use the nerve to spread into surrounding tissues. This increases the risk that the tumour will re-grow after treatment.

What is 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 specialized vessels called lymphatics. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood or lymphatic vessel. Lymphovascular invasion is important because these cells are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.

What is a margin?

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.

The types of margins described in your report will depend on the parts of the oral cavity involved and the type of surgery performed. Margins are usually only 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.

What are lymph nodes?

Lymph nodes are small immune organs located throughout the body. Tumour 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 tumour 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 tumour cells. Lymph nodes that contain tumour cells are often called positive while those that do not contain any tumour cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain tumour cells.

What is a tumour deposit?

A group of tumour 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).

What does extranodal extension (ENE) mean?

All lymph nodes are surrounded by a capsule. Extranodal extension (ENE) means that tumour 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).

How do pathologists determine the pathologic stage (pTNM) for squamous cell carcinoma of the oral cavity?

​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.