Non-keratinzing squamous cell carcinoma

This article was last reviewed and updated on June 23, 2019.

by Jason Wasserman, MD PhD FRCPC

Quick facts:

• Non-keratinizing squamous cell carcinoma is a cancer that starts from the tissue that covers the inside of the nose and throat.
• Another name for non-keratinizing squamous cell carcinoma is nasopharyngeal carcinoma.
• Most cases of non-keratinizing squamous cell carcinoma are caused by a virus called Epstein-Barr virus (EBV).

The nasopharynx

The nasopharynx is part of an area of the body called the upper aerodigestive tract. The upper aerodigestive tract includes the nose, mouth, and throat. The nasopharynx is located where the inside of the nose (the nasal cavity) meets the back of the throat (the pharynx).

The nasopharynx is covered by cells called squamous cells. These cells form a barrier on the surface of the nasopharynx called the epithelium. The tissue below the epithelium is called stroma. Pathologists use the word mucosa to describe tissue that includes both the epithelium and the stroma.

What is non-keratinizing squamous cell carcinoma?
Non-keratinizing squamous cell carcinoma is a type of cancer that develops from the squamous cells in the epithelium of the nasopharynx.

This tumour is called non-keratinizing because unlike other tumours that start from squamous cells, the squamous cells in non-keratinizing squamous cell carcinoma do not make large amounts of a protein called keratin.

Another name for this tumour is nasopharyngeal carcinoma.

Most cases of non-keratinizing squamous cell carcinoma that start in the nasopharynx are caused by a virus called Epstein-Barr virus (EBV). The virus infects the squamous cells and causes them to change into cancer cells.

Non-keratinizing squamous cell carcinoma can also start in an area of the body called the oropharynx. This area of the body includes the tonsils and base of tongue. Unlike tumours in the nasopharynx, non-keratinizing squamous cell carcinoma in the oropharynx is usually caused by a virus called human papillomavirus (HPV). For this reason, non-keratinizing squamous cell carcinoma of the nasopharynx and oropharynx are considered different diseases.

The diagnosis of non-keratinizing squamous cell carcinoma is usually made after a small sample of tissue is removed from your body in a procedure called a biopsy. Most patients with non-keratinizing squamous cell carcinoma will be treated with radiation although you may be offered surgery first to remove the tumour.

Tumour size

This is the size of the tumour. 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.

Tumours in the nasopharynx are often removed in multiple pieces. As a result, your pathologist may not be able to accurately measure the tumour size. In this case, an approximate tumour size may be described.

Why is this important? The tumour size is used to determine the tumour stage (see Pathologic stage below). Larger tumours are associated with 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.

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.

EBER

Cells infected by Epstein-Barr virus (EBV) produce a chemical called Epstein-Barr virus-encoded small RNA (EBER). Pathologists use a special test called in situ hybridization (ISH) to look for cells that are producing EBER.

Your report will  describe the tumour as positive (reactive) if EBER is seen inside the cancer cells and negative (non-reactive) if no EBER is seen.

Why is this important? Most non-keratinizing squamous cell carcinomas of the nasopharynx produce EBER.

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.

Why is this important? The number of lymph nodes that contain cancer cells and their location in the body is used to determine the nodal stage (see Pathologic stage below).

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).

Pathologic stage (pTMN)

​The pathologic stage for non-keratinizing 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 worse prognosis.

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

Tumour stage (pT) for non-keratinizing squamous cell carcinoma 

This tumour is given a tumour stage between T1 and T4. The tumour stage is based on how far the tumour has spread outside of the nasopharynx.

• T1 – The tumour is only seen in the nasopharynx, oropharynx, or nasal cavity.
• T2 – The tumour has spread outside of the nasopharynx into the soft tissues or muscles that surround the nasopharynx.
• T3 – The tumour has spread into the bones of the skull, the sinuses, or the bones of spine.
• T4 – The tumour has spread to the eyes, the large nerves of the head known as the cranial nerves, the parotid gland, or beyond the skull into the cranial cavity (the cavity that holds the brain).

Nodal stage (pN) for non-keratinizing squamous cell carcinoma

This tumour is given a nodal stage between N0 and N3 based on the number of lymph nodes that contain cancer cells, the size of the largest tumour deposit, and the location of the lymph nodes with cancer cells.

• N0 – No cancer cells were found in any of the lymph nodes examined.
• N1 – Cancer cells were found in one or more lymph node but the size of the tumour deposit was not larger than 6 centimeters.
• N2 – Cancer cells were found in lymph nodes on both sides of the neck (bilateral lymph nodes) but the size of the tumour desposit was not larger than 6 centimeters.
• N3 – Cancer cells were found in a lymph node and the size of the tumour deposit was larger than 6 centimeters.

Metastatic stage (pM) for non-keratinizing squamous cell carcinoma

Nasopharyngeal carcinoma is given an 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 determined 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 pMX.