Nasopharyngeal carcinoma

by Jason Wasserman MD PhD FRCPC
September 29, 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. Subtypes of nasopharyngeal carcinoma include non-keratinizing, keratinizing, and basaloid.

What causes nasopharyngeal carcinoma?

Most cases of non-keratinizing type and basaloid type 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. In contrast, keratinizing type nasopharyngeal carcinoma is typically caused by cigarette smoking and excess alcohol consumption.

What are the types of nasopharyngeal carcinoma?

There are three types of nasopharyngeal carcinoma: non-keratinizing, keratinizing, and basaloid. The type can only be determined after the tumour is examined under the microscope by a pathologist.

Non-keratinizing type

The non-keratinizing type is the most common type of nasopharyngeal carcinoma. The tumour is made up of large abnormal-looking tumour cells that are frequently surrounded by specialized immune cells called lymphocytes. This type of nasopharyngeal carcinoma is almost always associated with EBV. Another name for this type of nasopharyngeal carcinoma is non-keratinizing squamous cell carcinoma of the nasopharynx.

Keratinizing type

The keratinizing type of nasopharyngeal carcinoma is much less common than the non-keratinizing type. The tumour is made up of large abnormal-looking tumour cells that look pink because they are full of a protein called keratin. This type of nasopharyngeal carcinoma is usually associated with cigarette smoking or excessive alcohol consumption. Another name for this type of nasopharyngeal carcinoma is keratinizing squamous cell carcinoma of the nasopharynx.

Basaloid type

The basaloid type of nasopharyngeal carcinoma is the least common type. The tumour is made up of large blue cells. Most basaloid-type tumours are associated with EBV, however, some are associated with other factors such as cigarette smoking. Another name for this type of nasopharyngeal carcinoma is basaloid squamous cell carcinoma of the nasopharynx.

How is the diagnosis of nasopharyngeal carcinoma made?

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.

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 EBV 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?

Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. 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 important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery.

What does lymphovascular invasion mean?

Lymphovascular invasion means that cancer cells were seen inside of a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs.

What is a margin?

In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) depends on the type of tumour being removed and the location of the tumour.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved. For example, additional treatment may not be necessary for a benign (non-cancerous) type of tumour but may be strongly advised for a malignant (cancerous) type of tumour.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body such as a lymph node is called a metastasis.

Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there a high clinical suspicion that there may be cancer cells in the lymph node.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.

What does extranodal extension mean?

All lymph nodes are surrounded by a thin layer of tissue called a capsule. Extranodal extension means that cancer cells within the lymph node have broken through the capsule and have spread into the tissue outside of the lymph node. Extranodal extension is important because it increases the risk that the tumour will regrow in the same location after surgery. For some types of cancer, extranodal extension is also a reason to consider additional treatment such as chemotherapy or radiation therapy.

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. The pathologic stage will only be included in your report after the entire tumour has been removed. It will not be included after a biopsy.

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.