Squamous cell carcinoma of the larynx

By Jason Wasserman MD PhD FRCPC
February 7, 2023

What is squamous cell carcinoma of the larynx?

Squamous cell carcinoma (SCC) is a type of throat cancer and the most common type of cancer in the larynx.

Where in the larynx does squamous cell carcinoma start?

The tumour starts from specialized squamous cells that cover the inside surface of the larynx.  Squamous cell carcinoma can start anywhere in the larynx although the most common site is the glottis which includes the vocal cords. Less common sites include the supraglottis and subglottis.

What causes squamous cell carcinoma of the larynx?

Tobacco smoking and high levels of alcohol consumption increase the risk of developing squamous cell carcinoma of the larynx.

What precancerous conditions can lead to squamous cell carcinoma of the larynx?

Most squamous cell carcinomas of the larynx develop from a pre-cancerous disease called keratinizing squamous dysplasia. Like squamous cell carcinoma, keratinizing squamous dysplasia is associated with tobacco smoking and high levels of alcohol consumption.

How is the diagnosis of squamous cell carcinoma in the larynx made?

The diagnosis of squamous cell carcinoma is usually made after a small sample of tissue is removed in a procedure called a biopsy. The biopsy is usually performed because your doctor saw an abnormal-looking area of tissue during an examination of your larynx. Your pathology report will probably say what part of the larynx was sampled in the biopsy. The diagnosis can also be made after the entire tumour is removed in a procedure called an excision or resection.

What does squamous cell carcinoma of the larynx look like under the microscope?

When examined under the microscope, the tumour is made up of abnormal-looking squamous cells. The tumour starts in a thin layer of tissue called the epithelium on the inside surface of the larynx but tumour cells will also be seen in a layer of tissue called the stroma below the epithelium. The movement of tumour cells into the stroma is called invasion and it is required to make the diagnosis of squamous cell carcinoma.

What does differentiated mean and why is the level of differentiation important for squamous cell carcinoma of the larynx?

Pathologists use the term differentiated to divide squamous cell carcinoma of the larynx 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 is made up of tumour cells that look almost the same as normal squamous cells. A moderately differentiated tumour 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 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 transglottic mean and why is that important for squamous cell carcinoma of the larynx?

The larynx is divided into three parts: supraglottis, glottis, and subglottis. The term transglottic is used to describe a tumour that involves more than one part. For example, a tumour would be described as transglottic if it involved both the supraglottis and glottis. A transglottic tumour is associated with a worse prognosis and is given a higher pathologic tumour stage (pT). Transglottic extension can only be assessed after the entire tumour has been removed.

What does perineural invasion mean and why is it important?

Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. 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 important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery.

What does lymphovascular invasion mean and why is it important?

Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs.

What is a margin?

In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) depends on the type of tumour being removed and the location of the tumour.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved. For example, additional treatment may not be necessary for a benign (non-cancerous) type of tumour but may be strongly advised for a malignant (cancerous) type of tumour.

Were lymph nodes examined and did any contain tumour cells?

Lymph nodes are small immune organs found throughout the body. Tumour cells can spread from a tumour to lymph nodes through small vessels called lymphatics. For this reason, lymph nodes are commonly removed and examined under a microscope to look for tumour cells. The movement of tumour cells from the tumour to another part of the body such as a lymph node is called metastasis.

Tumour cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be tumour cells in the lymph node.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain tumour cells. If tumour cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding tumour cells in a lymph node increases the risk that tumour cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

What is a neck dissection?

A neck dissection is a surgical procedure performed to remove lymph nodes from the neck. 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.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains tumour cells. For example, a lymph node that contains tumour cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any tumour cells. For example, a lymph node that does not contain tumour cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.

What does extranodal extension mean?

All lymph nodes are surrounded by a thin layer of tissue called a capsule. Extranodal extension means that tumour cells within the lymph node have broken through the capsule and have spread into the tissue outside of the lymph node. Extranodal extension is important because it increases the risk that the tumour will regrow in the same location after surgery. For some types of tumours, extranodal extension is also a reason to consider additional treatment such as chemotherapy or radiation therapy.

What is the pathologic stage for squamous cell carcinoma of the larynx?

​The pathologic stage for squamous cell carcinoma in the larynx 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 a more advanced disease and a worse prognosis.

Tumour stage (pT) for squamous cell carcinoma of the larynx

There are three different tumour staging systems for squamous cell carcinoma of the larynx. The system selected depends on which section of the larynx the tumour started.

For tumours that start in the supraglottis

• T1 – The tumour has not spread beyond the supraglottis and the vocal cords move normally.
• T2– The tumour has spread beyond the supraglottis to another section of the larynx or to the tissue just outside of the larynx.
• T3 – The vocal cords no longer move normally or the tumour has spread to tissues further away from the larynx.
• T4 – The tumour has spread to the muscles of the tongue, muscles at the front of the neck, the spine, and the chest, or has gone through the cartilage that sits in front of the thyroid gland.

For tumours that start in the glottis

• T1 – The tumour only involves the vocal cords.
• T2– The tumour has spread beyond the glottis to involve the supraglottis or subglottis or the vocal cords no longer move normally.
• T3 – The vocal cords no longer move normally or the tumour has spread to the tissue just outside of the larynx.
• T4 – The tumour has spread to the muscles of the tongue, muscles at the front of the neck, the spine, and the chest, or has gone through the cartilage that sits in front of the thyroid gland.

For tumours that start in the subglottis

• ​T1 – The tumour only involves the subglottis.
• T2 – The tumour has spread to the vocal cords.
• T3 – The vocal cords no longer move normally or the tumour has spread to the tissue just outside of the larynx.
• T4 – The tumour has spread to the muscles of the tongue, muscles at the front of the neck, the spine, and the chest, or has gone through the cartilage that sits in front of the thyroid gland.

Nodal stage (pN) for squamous cell carcinoma of the larynx

Squamous cell carcinoma of the larynx is given a nodal stage between 0 and 3 based on the examination of all lymph nodes received. Both N2 and N3 are further divided into sub-stages (for example N2a, N2b, etc).

The following four features are used to determine the nodal stage:

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

Using these features your pathologist will provide a nodal stage as follows:

• NX – No lymph nodes were sent for pathologic examination.
• N0 – No cancer cells are seen in any of the lymph nodes examined.
• N1 – Cancer cells are found in only one lymph node. The lymph node with cancer cells is on the same side as the tumour (ipsilateral), the tumour deposit measures 3 cm or less in size, and extranodal extension is not seen.
• N2a – There are two possible options for N2a stage disease:
  • Cancer cells are found in only one lymph node. The lymph node with cancer cells is on the same side of the tumour (ipsilateral), the tumour deposit measures 3 cm or less, and extranodal extension is seen.
  • Cancer cells are found in only one lymph node. The lymph node with cancer cells is on the same side of the tumour (ipsilateral), the tumour deposit measures more than 3 cm but not more than 6 cm, and extranodal extension is not seen.
• N2b – Cancer cells are found in more than one lymph node. All lymph nodes with cancer cells are on the same side as the tumour (ipsilateral), none of the tumour deposits are more than 6 cm in size, and extranodal extension is not seen.
• N2c – Cancer cells are found in one or more lymph nodes. At least one of the lymph nodes with cancer cells is on the opposite side as the tumour (contralateral), none of the tumour deposits are more than 6 cm in size, and extranodal extension is not seen.
• N3a – Cancer cells are found in at least one lymph node on the same (ipsilateral) or opposite side of the tumour (contralateral). The largest tumour deposit is more than 6 cm in size and extranodal extension is not seen.
• N3b – There are three possible options for N3b stage disease:
  • Cancer cells are found in only one lymph node. The lymph node with cancer cells is on the same side of the tumour (ipsilateral), the tumour deposit measures more than 3 cm, and extranodal extension is seen.
  • Cancer cells are found in more than one lymph node and extranodal extension is seen in at least one lymph node.
  • Cancer cells are found in only one lymph node. The lymph node with cancer cells is located on the opposite side of the tumour and extranodal extension is seen.

Metastatic stage (pM) for squamous cell carcinoma of the larynx

Squamous cell carcinoma of the larynx 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.