by Jason Wasserman MD PhD FRCPC
May 10, 2022
Cutaneous squamous cell carcinoma (SCC) is a very common type of skin cancer. The tumour is made up of specialized squamous cells that are normally found in the skin. In many cases, the tumour develops from a precancerous condition such as actinic keratosis or squamous cell carcinoma in situ.
Most tumours that occur in older adults develop as a result of the cells in the epidermis being damaged by UV light from the sun. Long-term exposure to UV radiation from tanning beds can cause similar damage. People who are immunosuppressed due to organ transplantation or HIV infection are also at increased risk of developing squamous cell carcinoma.
The diagnosis is usually made after a small tissue sample is removed in a procedure called a biopsy. The diagnosis can also be made after the entire tumour is removed in a procedure called an excision. If the diagnosis is made after a biopsy, your doctor will probably recommend a second surgical procedure to remove the rest of the tumour.
Pathologists use the term differentiated to divide cutaneous squamous cell carcinoma into three grades – well-differentiated, moderately differentiated, and poorly differentiated. The grade is based on how much the tumour cells look like normal squamous cells. A well-differentiated tumour (grade 1) is made up of tumour cells that look almost the same as normal squamous cells. A moderately differentiated tumour (grade 2) is made up of tumour cells that clearly look different from normal squamous cells, however, they can still be recognized as squamous cells. A poorly differentiated tumour (grade 3) is made up of tumour cells that look very little like normal squamous cells. These cells can look so abnormal that your pathologist may need to order an additional test such as immunohistochemistry to confirm the diagnosis. The grade is important because less differentiated tumours (moderately and poorly differentiated tumours) behave in a more aggressive manner and are more likely to spread to other parts of the body.
Depth of invasion is a measurement of how far the tumour cells have spread from the epidermis into the layers of tissue below (the dermis and subcutaneous tissue). For skin tumours, the depth of invasion is measured from the surface of the skin to the deepest point of invasion. Some pathology reports describe the depth of invasion as tumour thickness. Tumours that grow deeper into the dermis are more likely to spread to a lymph node or to grow back after treatment.
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 a term pathologists use to describe tumour cells attached to a nerve. Perineural invasion is important because tumour cells that have become attached to a nerve can grow along the nerve and into surrounding tissues. This increases the risk that the tumour will re-grow 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. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood vessel or lymphatic channel. Lymphovascular invasion is important because once the tumour cells are inside a blood vessel or lymphatic channel they are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.
A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any tumour cells will be left behind after the tumour is removed.
Your pathologist will carefully examine all the margins in your tissue sample to see how close the tumour cells are to the edge of the cut tissue. Margins will only be described in your report after most or all of the tumour has been removed.
A negative margin means there were no tumour cells at the very edge of the cut tissue. If all the margins are negative, most pathology reports will say how far the closest tumour cells were to a margin. The distance is usually described in millimetres.
A margin is considered 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 grow back (recur) in the same site after treatment.
Lymph nodes are small immune organs located throughout the body. Tumour cells can spread from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of tumour cells from the tumour to a lymph node is called lymph node metastasis.
Lymph nodes are not typically removed for squamous cell carcinoma of the skin. However, if lymph nodes are removed your pathologist will carefully examine each one of them 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 tumour 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.
All lymph nodes are surrounded by a capsule. Extranodal extension means that tumour 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 area of the involved lymph node.