Squamous cell carcinoma of the larynx

What is squamous cell carcinoma of the larynx?

Squamous cell carcinoma is a type of laryngeal (throat) cancer. Squamous cell carcinoma starts from the squamous cells in the epithelium on the inner surface of the larynx. It is the most common type of cancer in the larynx. This type of cancer can start anywhere in the larynx although the most common site is the vocal cord.

Most of the time squamous cell carcinoma develops from a pre-cancerous disease called squamous dysplasia. This condition may be present for many years before turning into squamous cell carcinoma. Squamous dysplasia is divided into three levels (mild, moderate, and severe) and the risk of developing cancer is highest with severe squamous dysplasia. Another name for severe squamous dysplasia is squamous carcinoma in situ.

The larynx

When we breathe, air travels from our mouth and nose to our lungs. On its way to the lungs, air passes through a part of the throat called the larynx. You cannot see your larynx because it starts at the very back of the tongue.

Most of the larynx is a hollow tube filled with air. The larynx helps us breathe and create sound when we talk. For this reason, diseases involving the larynx often make it difficult to breathe or talk normally. The inside surface of the larynx is lined by specialized cells called squamous cells. These cells form a barrier called the epithelium. The tissue below the epithelium is called the stroma.

The larynx is divided into three sections from top to bottom and each section is made up of smaller parts. Most pathology reports will describe the sections or parts of the larynx examined.

Supraglottis

The supraglottis is the first section of the larynx. The supraglottic larynx is made up of several smaller parts including:

• Epiglottis.
• Aryepiglottic folds.
• Arytenoids.
• False vocal cords.
• Ventricle.

Glottis

The glottis is the second section and it is in the middle of the larynx. The glottis is made up of several smaller parts including:

• True vocal cords.
• Posterior commissure.
• Anterior commissure.

Subglottis

The subglottis is the third and last section of the larynx. Unlike the other sections of the larynx, the subglottis is not made up of many smaller parts. The subglottic larynx connects with the trachea (windpipe).

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 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.

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 larynx 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 the difference between the cancer cells in squamous cell carcinoma and the normal, healthy squamous cells found in the larynx. 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 more likely to spread to other parts of the body such as lymph nodes. For this reason, 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 measured in centimetres. 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.

Parts of the larynx involved by tumour

As described above, the larynx is divided into three sections: supraglottis, glottis, and subglottis. Your pathologist will examine the tissue removed to determine where the tumour started and if it involves more than one section of the larynx.

The section of the larynx with the largest amount of tumour is usually the section where the tumour started. Most tumours in the larynx start in the glottis. A tumour start starts in either the supraglottis or glottis and grows down into the subglottis is called transglottic.

The parts of the larynx involved by the tumour are used to determine the tumour stage (see Pathologic stage below). A tumour that involves more than one part of the larynx or that shows transglottic spread is given a higher tumour stage and is associated with a worse prognosis.

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 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. 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 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. The size of the largest tumour deposit is used to determine the nodal stage (see Pathologic stage below) and larger tumour deposits are associated with worse prognosis.

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 used to determine the nodal stage (see pathologic stage below) and is a risk factor for developing new tumours. For these reasons, extranodal extension is often considered when making decisions about radiation therapy to the neck.

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 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. A negative margin means that no tumour cells were seen at any of the cut edges of tissue.

Pathologic stage (pTNM)

​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 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, 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, 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, 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.

by Jason Wasserman MD PhD FRCPC (updated July 28, 2021)