Nasopharyngeal carcinoma

by Jason Wasserman MD PhD FRCPC
May 17, 2022

What is nasopharyngeal carcinoma?

Nasopharyngeal carcinoma is a type of cancer that starts from an area at the back of the nose and throat called the nasopharynx. Most cases of nasopharyngeal carcinoma are caused by a virus known as Epstein-Barr virus (EBV) which infects the cells on the inside of the nasopharynx and causes them to change into cancer cells. Subtypes of nasopharyngeal carcinoma include non-keratinizing, keratinizing, and basaloid.

How do pathologists make the diagnosis of nasopharyngeal carcinoma?

The diagnosis of nasopharyngeal carcinoma is usually made after a small sample of tissue is removed from your body in a procedure called a biopsy. The tissue is then sent to a pathologist who examines it under a microscope.

What does nasopharyngeal carcinoma look like under the microscope?

When examined under the microscope the tumour is made up of abnormal-looking squamous cells. The tumour cells are usually surrounded by a large number of immune cells such as lymphocytes and plasma cells. There are three subtypes of nasopharyngeal carcinoma: non-keratinizing, keratinizing, and basaloid. The non-keratinizing subtype is the most common.

nasopharyngeal carcinoma

This image shows the non-keratinizing subtype of nasopharyngeal carcinoma.

What other tests may be performed to confirm the diagnosis?

Your pathologist may perform a test called immunohistochemistry to confirm the diagnosis. This test allows your pathologist to ‘see’ specific types of proteins inside the tumour cells. When immunohistochemistry is performed, the tumour cells in nasopharyngeal carcinoma are usually positive for pan-cytokeratin and high-molecular-weight keratins such as CK5. The tumour cells are usually negative for other keratins such as CK7 and CK20.

What is EBER and why is it important?

Cells infected by the Epstein-Barr virus produce a chemical called Epstein-Barr virus-encoded small RNA or EBER for short. 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 if EBER is seen inside the cancer cells and negative if no EBER is seen. Most nasopharyngeal carcinomas are positive for EBER.


The brown tumour cells in this nasopharyngeal carcinoma are positive for EBER.

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

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 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 is a margin?

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 tumour 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 tumour cells are to the edge of the cut tissue. Margins will only be described in your report after a procedure has been performed to remove the entire tumour. Margins are usually not described after a biopsy.

A negative margin means there were no tumour cells at the very edge of the cut tissue. If all the margins are negative, most pathology reports will say how far the closest tumour cells were to a margin. The distance is usually described in millimetres. 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. Tumours in the nasopharynx are often removed in multiple pieces. As a result, your pathologist may not be able to reliably assess the margins.


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

How do pathologists determine the pathologic stage (pTMN) for nasopharyngeal carcinoma?

​The pathologic stage for nasopharyngeal 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 a worse prognosis.

Tumour stage (pT) for nasopharyngeal carcinoma

This tumour is given a tumour stage between 1 and 4. 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 OR it has only spread to the 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 the 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 nasopharyngeal carcinoma

This tumour is given a nodal stage between 0 and 3 based on the number of lymph nodes that contain tumour cells, the size of the largest tumour deposit, and the location of the lymph nodes with tumour cells.

  • N0 – No tumour cells were found in any of the lymph nodes examined.
  • N1 – Tumour cells were found in one or more lymph nodes but the size of the tumour deposit was not larger than 6 centimetres.
  • N2 – Tumour cells were found in lymph nodes on both sides of the neck (bilateral lymph nodes) but the size of the tumour deposit was not larger than 6 centimetres.
  • N3 – Tumour cells were found in a lymph node and the size of the tumour deposit was larger than 6 centimetres.
Metastatic stage (pM) for nasopharyngeal carcinoma

Nasopharyngeal carcinoma is given a metastatic stage of 0 or 1 based on the presence of tumour 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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