This article will help you read and understand your pathology report for squamous cell carcinoma of the oral cavity.
by Jason Wasserman MD PhD FRCPC, updated March 18, 2021
The oral cavity is the beginning of the aerodigestive tract. It is used for both breathing and taking in food. The oral cavity is a complex area of the body that is made up of many parts (see picture below).
The oral cavity includes:
The surface of the oral cavity is lined by specialized cells called squamous cells that create a barrier called the epithelium. The tissue below the epithelium is called the stroma. The epithelium is separated from the stroma by a thin strip of tissue called the basement membrane. Pathologists use the word mucosa to describe all of the tissue above the stroma.
Squamous cell carcinoma is a type of oral cavity cancer. The tumour starts from the squamous cells in the epithelium. Squamous cell carcinoma is the most common type of cancer to start in the oral cavity. This tumour can start anywhere in the oral cavity although most start on the side of the tongue (lateral tongue) or the floor of the mouth.
Squamous cell carcinoma in the oral cavity often starts from a pre-cancerous disease called squamous dysplasia. Squamous dysplasia may be present for many years before turning into squamous cell carcinoma.
In squamous dysplasia, the abnormal squamous cells are only found in the epithelium on the surface of the oral cavity. In contrast, in squamous cell carcinoma, the tumour cells have spread from the epithelium into the stroma below. The movement of tumour cells from the epithelium into the stroma below is called invasion.
Smoking and high levels of alcohol consumption increase the risk of developing both squamous cell carcinoma and squamous dysplasia.
The diagnosis is usually made after a small tissue sample is removed in a procedure called a biopsy. The tissue sample is then sent to a pathologist who examines it under the microscope. Most patients will then undergo a second procedure to remove the entire tumour. That tissue is also sent to a pathologist for examination under the microscope.
When examined under the microscope, the tumour cells in squamous cell carcinoma are usually larger than normal, healthy squamous cells. The nucleus of the cell is also usually darker. pathologists describe these cells as hyperchromatic. The tumour cells may also have nuclei of different shapes and sizes. Pathologists describe these cells as pleomorphic. Most squamous cell carcinomas of the oral cavity are described as keratinizing because the tumour cells produce a protein called keratin which is normally found in the skin but not in the oral cavity.
The movement of tumour cells from the epithelium into the stroma causes the tissue in this area to react and change colour. This reaction is called desmoplasia. Pathologists use desmoplasia as a sign of invasion.
The grade is divided into three levels of differentiation based on how the cancer cells look when examined under the microscope:
The tumour grade is important because poorly differentiated tumours are often associated with a worse prognosis.
This is the size of the tumour. Tumour size will only be described in your report after the entire tumour has been removed. 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 a worse prognosis.
All squamous cell carcinomas start in the epithelium on the surface of the oral cavity. Depth of invasion is a measurement of how far the cancer cells have travelled from the epithelium into the stroma below.
Tumours with a depth of invasion greater than 0.5 centimetres are associated with a higher risk that the tumour will come back at the same site after treatment or that cancer cells will be found in a lymph node. The depth of invasion is used to determine the tumour stage (see Pathologic stage below).
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.
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.
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.
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.
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).
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 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).
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.
Your pathologist will look for three features in order to determine the tumour stage:
Based on these features, squamous cell carcinoma is given a tumour stage between 1 and 4:
Your pathologist will look for four features in order to determine the nodal stage:
Based on these features, squamous cell carcinoma is given a nodal stage between 0 and 3. The N2 and N3 stages are divided into smaller groups with letters (a, b, or c) after the number.
If no lymph nodes are submitted for pathological examination, the N-stage cannot be determined and the N stage is listed as X.
Squamous cell carcinoma is given a metastatic stage 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 sent for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.