Your diagnosis

Non-keratinizing squamous cell carcinoma of the oropharynx

This article will help you read and understand your pathology report for non-keratinizing squamous cell carcinoma of the oropharynx.

by Jason Wasserman, MD PhD FRCPC, updated December 31, 2020

oropharynx squamous cell carcinoma

Quick facts:
  • Non-keratinizing squamous cell carcinoma is a type of throat cancer that starts in the oropharynx.
  • The oropharynx is made up of the tonsils, base of tongue, and soft palate.
  • Most tumours in this area are caused by a virus called human papillomavirus (HPV).
  • Pathologists look HPV in cancer cells by performing a test for a protein called p16.
The anatomy of the oropharynx

The tonsils, base of tongue, and soft palate form an area of the body called the oropharynx. The oropharynx includes special tissue that is designed to help protect us from infections that may try to enter our body through our mouth or nose.

The surface of the oropharynx is lined by  squamous cells that form a barrier called the epithelium. The tissue below the epithelium is called stroma. The stroma in the oropharynx is made up mostly of immune cells which makes this tissue look very similar to a lymph node.

What is non-keratinizing squamous cell carcinoma?

Non-keratinizing squamous cell carcinoma is a type of throat cancer. The tumour develops from the squamous cells in the epithelium of the oropharynx.

Non-keratinizing squamous cell carcinoma is the most common type of cancer in the oropharynx. The tumour is called non-keratinizing because the tumour cells do not undergo a process called keratinization. This process is commonly seen in other tumours made up of squamous cells.

Even through the tumour starts in the throat, the cancer cells commonly spread to lymph nodes in the neck. The movement of cancer cells from the main tumour to a lymph node or other area of the body is called metastasis. When this happens, you may notice an abnormal lump or growth in your neck.

What causes non-keratinizing squamous cell carcinoma?

Most cases of non-keratinizing squamous cell carcinoma in the oropharynx are caused by a virus called human papillomavirus (HPV). This virus infects the squamous cells and over time changes them into cancer cells.

Squamous cells infected with HPV produce large amount of a protein called p16 which pathologists can see using a test called immunohistochemistry.

How do pathologists make this diagnosis?

The diagnosis of non-keratinizing squamous cell carcinoma is usually made after a small tissue sample is removed in a procedure called a biopsy. The biopsy may be taken from the oropharynx or it may be taken from the neck. A special test called immunohistochemistry may be ordered to confirm the diagnosis and to look for p16 protein inside tumour cells.

For some patients, surgery may be performed to remove the entire tumour. Other patients may receive radiation therapy with or without surgery to remove the tumour. If the tumour is removed, it will be sent to a pathologist who will prepare another pathology report. This report will confirm or revise the original diagnosis and provide additional important information such tumour size and spread of tumour cells to lymph nodes. This information is used to determine the cancer stage and to decide if additional treatment is required.

p16

p16 is a protein that is produced by both normal, healthy cells and tumour cells. Pathologists perform a special test called immunohistochemistry in order to be able to see the p16 protein inside  cells.

Tumours made up of cells that produce extra p16 are described as positive (or reactive) while those that do not produce extra p16 are reported as negative (non-reactive).

Cancer cells that have been infected with human papillomavirus (HPV) produce extra p16 which builds up inside the cancer cells. For this reason, most non-keratinizing squamous cell carcinomas in the oropharynx are positive (reactive) for p16.

This test result will be used by your other doctors to guide your treatment because p16 positive tumours respond better to radiation compared to p16 negative tumours.

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.

The tumour size is used to determine the tumour stage (see Pathologic stage below) and larger tumours are associated with worse prognosis.

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 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. A negative margin means that no tumour cells were seen at any of the cut edges of tissue.

Margin

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.

The number of lymph nodes that contain cancer cells 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.

The size of the largest tumour deposit is only important for tumours not caused by HPV (p16 negative tumours). For these tumours, 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.

Extranodal extension is only important for tumours not caused by HPV (p16 negative tumours). For these tumours, 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 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.

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

Non-keratinizing squamous cell carcinoma of the oropharynx is given a tumour stage between 1 and 4. The tumour stage is based on the size of the tumour and whether the tumour has grown to include parts of the mouth or throat outside of the oropharynx.

  • T1 – The tumour is 2 cm or smaller.
  • T2 – The tumour is greater than 2 cm but not larger than 4 cm.
  • T3 – The tumour is larger than 4 cm but is still only located within the oropharynx.
  • T4 – The tumour has spread into tissues outside of the oropharynx such as the deep muscles of the tongue, the larynx, or the bone of the lower jaw (the mandible).

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

Tumours that are associated with HPV or that test positive for p16 are given an nodal stage between 0 and 2 based on the number of lymph nodes that contain cancer cells.

  • N0 – No cancer cells are found in any of the lymph nodes examined.
  • N1 – Cancer cells are found in 1 to 4 lymph nodes examined.
  • N2 – Cancer cells are found in more than 4 lymph nodes examined.

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

These tumours are given a metastatic stage (pM) 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 assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as pMX.

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