Squamous cell carcinoma of the larynx

by Jason Wasserman MD PhD FRCPC
May 12, 2022


What is squamous cell carcinoma of the larynx?

Squamous cell carcinoma is a type of laryngeal (throat) cancer. It is the most common type of cancer in the larynx. The tumour starts from 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 vocal cord. Most of the time squamous cell carcinoma develops from a pre-cancerous disease called squamous dysplasia.

What causes squamous cell carcinoma of the larynx?

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

How do pathologists make the diagnosis of squamous cell carcinoma in the larynx?

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?

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. Some 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. Other patients will be offered radiation treatment.

All squamous cell carcinomas start from squamous cells in a thin layer of tissue on the inside surface of the larynx called the epithelium. When the tumour cells are only seen in the epithelium, the condition is called squamous dysplasia. In order to make the diagnosis of squamous cell carcinoma, your pathologist must-see tumour cells in the stroma. The movement of tumour cells from the epithelium into the stroma is called invasion.

How do pathologists grade squamous cell carcinoma in 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 (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 parts of the larynx are involved by the tumour?

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.

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.

What does perineural invasion mean?

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.

perineural invasion

What does lymphovascular invasion mean?

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.

lymphovascular invasion

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.

Lymph node

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. 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 a worse prognosis.

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 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.

extranodal extension

What is a margin?

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.

Margin

 

How do pathologists determine the pathologic stage (pTNM) 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 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.

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