Squamous cell carcinoma - Oropharynx -

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

by Jason Wasserman, MD PhD FRCPC, reviewed on August 17, 2020

oropharynx squamous cell carcinoma

Quick facts:
  • 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 specialized cells called  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 squamous cell carcinoma?

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

Squamous cell carcinoma is the most common type of cancer in the oropharynx. Most of these tumours are described as non-keratinizing because the tumour cells do not make large amounts of a protein called keratin that is made by squamous cells in other parts of the body.

Even through the tumour starts in the oropharynx, 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 squamous cell carcinoma?

Most cases of 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 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.

What to look in your pathology report after a biopsy

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 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 pathology report after the tumour is removed entirely

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). 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.

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.

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 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 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 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 included in your report after the entire tumour has been removed.

Tumour stage (pT) for squamous cell carcinoma

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 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 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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