Larynx -

Squamous cell carcinoma

This article was last reviewed and updated on November 9 2019.
by Jason Wasserman, MD PhD FRCPC

Quick facts:

  • Squamous cell carcinoma of the larynx is a type of throat cancer.

  • The larynx includes the vocal cords, aryepiglottic folds, arytenoids, ventricle, and commisures.

  • Squamous cell carcinoma is the most common type of throat cancer in adults.

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.

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.

  1. Supraglottis - The supraglottis is the first section of the larynx. The supraglottis includes the following smaller parts:

    • Epiglottis.

    • Aryepiglottic folds.

    • Arytenoids.

    • False vocal cords.

    • Ventricle.

  2. Glottis - The glottis is the second section and it is in the middle of the larynx. The glottis It includes the following smaller parts:

    • True vocal cords.

    • Posterior commisure.

    • Anterior commisure. 

  3. Subglottis- The subglottis is the third and last section of the larynx. It has no smaller parts.

 

The inner surface of the larynx is lined by cells called squamous cells. These cells form a barrier on the surface of the larynx called the epithelium. The tissue below the epithelium is called stroma.

What is squamous cell carcinoma?

Squamous cell carcinoma is a type of throat cancer. Squamous cell carcinoma starts in the larynx from the squamous cells in the epithelium.

 

Squamous cell carcinoma 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 glottis.  

 

Squamous cell carcinoma in the larynx often starts from a pre-cancerous disease called keratinizing squamous dysplasia. Keratinizing squamous dysplasia may be present for many years before turning into squamous cell carcinoma.

 

When examined under a microscope, the abnormal cells in keratinizing squamous dysplasia are only found in the epithelium on the surface of the larynx. In order to become squamous cell carcinoma, the cancer cells have to move from the epithelium into the stroma below. The movement of cancer cells from the epithelium into the stroma below is called invasion.

Most squamous cell carcinomas of the larynx are described as keratinizing because the cancer cells produce a protein called keratin which is normally found in the skin but not in the larynx.

What causes squamous cell carcinoma?

Smoking and high levels of alcohol consumption increase the risk for 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 tissue is then sent to a pathologist for examination under a microscope. 

 

Treatment for squamous cell carcinoma

Treatment options for squamous cell carcinoma include surgery to remove the diseased tissue and radiation. The type of surgery offered and the amount of tissue removed will depend on the part of the larynx involved and the size of the area with disease.  

Histologic grade

Pathologists use the word grade to describe the difference between the cancer cells in squamous cell carcinoma and the squamous cells normally found in the larynx. The grade is divided into three levels 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.

Why is this important? 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.

Tumour size

This is the size of the tumour measured in centimeters. 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.

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 tumour will only be described in your report after the entire tumour has been removed.

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

Keratinizing squamous dysplasia and squamous carcinoma in situ (CIS)

Squamous cell carcinoma in the larynx often starts from a pre-cancerous disease called keratinzing squamous dysplasia. Pathologists divide squamous dysplasia into three categories: mild, moderate, and severe. Another name for severe dysplasia is squamous carcinoma in situ.

 

Sometimes mild dysplasia is called low grade dysplasia while moderate and severe dysplasia are grouped together and called high grade dysplasia.

Your pathologist will carefully examine the tissue removed for squamous dysplasia. If severe or high grade dysplasia is seen it will be included into your pathology report. If severe or high grade dysplasia is seen close to the cut edge of the tissue (see Margins below) the distance between the dysplasia and the cut edge will be included in your report.

Why is this important? Severe keratinizing squamous dysplasia or carcinoma in situ at the cut edge of the tissue (see Margins below) is associated with an increased risk that the tumour will grow back again after treatment. Your doctor may talk with you about additional treatment to reduce the risk.

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.


Why is this important? 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.


Why is this important? 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. 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. 

Your pathologist will carefully examine all the margins in your tissue sample to see how close the cancer cells are to the edge of the cut tissue. Margins will only be described in your report after the entire tumour has been removed.

A margin is considered positive when there are cancer cells at the very edge of the cut tissue.

A negative margin means there were no cancer cells at the very edge of the cut tissue. If all the margins are negative, most pathology reports will say how far the closest cancer cells were to a margin. The distance is usually described in millimeters.

Why is this important? A positive margin is associated with a higher risk that the tumour will grow back (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 a 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.

Why is this important? Larger tumour deposits are associated with 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.

 

Why is this important? 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 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 worse prognosis.

 

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.


Tumour stage (pT) for squamous cell carcinoma

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

Squamous cell carcinoma of the larynx is given a nodal stage between 0 and 3. 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 (the laterality).

If no cancer cells are found in any of the lymph nodes examined, the nodal stage is N0.

 

If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.

Metastatic stage (pM) for squamous cell carcinoma

Squamous cell carcinoma of the larynx is given an metastatic stage between 0 and 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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