Non-keratinizing squamous cell carcinoma of the nasopharynx

What is non-keratinizing squamous cell carcinoma of the nasopharynx?

Non-keratinizing squamous cell carcinoma is a type of cancer that starts from the tissue at the back of the nose and throat. This part of the body is called the nasopharynx. Most cases of nasopharyngeal carcinoma are caused by a virus known as Epstein-Barr virus (EBV) which infects the squamous cells on the surface of the tissue and causes them to change into cancer cells. This tumour is also called nasopharyngeal carcinoma.

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 the stroma. Pathologists use the word mucosa to describe tissue that includes both the epithelium and the stroma.

How do pathologists make this diagnosis?

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. The tissue is then sent to a pathologist who examines it under a microscope.

Most patients with non-keratinizing squamous cell carcinoma will be treated with radiation although you may be offered surgery first to remove the tumour. If the tumour is removed, it will be sent to a pathologist who will prepare another pathology report.

EBER

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 non-keratinizing squamous cell carcinomas are positive for EBER.

What to look for in your report after the tumour has been removed

Tumour size

This is the size of the tumour. 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.

Non-keratinizing squamous cell carcinoma is 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.

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

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 contains waste and immune cells that move 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. 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. 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 negative margin means that no tumour cells were seen at any of the cut edges of tissue. 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.

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 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.

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. 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).

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 a worse prognosis.

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 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 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 nodes but the size of the tumour deposit was not larger than 6 centimetres.
• N2 – Cancer 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 – Cancer cells were found in a lymph node and the size of the tumour deposit was larger than 6 centimetres.

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

Nasopharyngeal carcinoma is given a metastatic stage of M0 or M1 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.

by Jason Wasserman MD PhD FRCPC (updated August 4, 2021)