Mucoepidermoid carcinoma

by Jason Wasserman MD PhD FRCPC
June 22, 2022

What is mucoepidermoid carcinoma?

Mucoepidermoid carcinoma (MEC) is a type of salivary gland cancer. The most common location for mucoepidermoid carcinoma is the parotid gland, however, any of the major or minor salivary glands can be affected. Although rare, this type of tumour can also be found in other organs such as the lungs and thyroid gland. Most tumours are low-grade and cured by surgery alone.

What does mucoepidermoid carcinoma look like under the microscope?

When examined under the microscope, mucoepidermoid carcinoma is typically made up of three different types of cells: mucous cells, intermediate cells, and epidermoid cells. The mucous cells in mucus cells are large cells that appear blue when examined under the microscope. The cells appear blue because they are filled with a protein called mucin. Pathologists often use the term goblet cells when describing these mucus-producing cells. The intermediate cells are smaller than the mucus cells and they are often harder to see. In some tumours, the intermediate cells are larger and the body of the cell appears clear. Finally, the epidermoid cells often appear pink and they may be described using terms such as eosinophilic or squamoid.

The tumour cells often connect together to form open spaces called cysts. These cysts are frequently lined by the mucus (goblet) cells. The intermediate and epidermoid cells are more likely to be arranged in groups that may be described as nests or solid.

Grade

Pathologists divide mucoepidermoid carcinoma into three grades – low, intermediate, and high. The grade is important because it is used to help predict how the tumour will behave over time. For example, low grade tumours rarely spread to other parts of the body and are typically treated by surgery alone. In contrast, high grade tumours are more likely to spread to other parts of the body such as lymph nodes.

Pathologists determine the grade for mucoepidermoid carcinoma using a system originally developed by the Armed Forces Institute of Pathology (AFIP). This system divides mucoepidermoid carcinoma into three grades based on the presence or absence of specific microscopic features (see list below). Points are assigned for each feature and the total score determines the grade.

An alternative system was later developed by Brandwein and some pathologists now use a modified or hybrid system that uses all of the features from the AFIP system with some from the Brandwein system.

Microscopic features used to determine the AFIP grade:

• Cysts: A cyst is a small open space lined by tumour cells. When examined under the microscope, most mucoepidermoid carcinomas are made up of cysts of various shapes and sizes. A mucoepidermoid carcinoma that is made up of less than 20% cysts is given 2 points.
• Necrosis: Necrosis is a type of cell death that is commonly seen in cancerous tumours. A mucoepidermoid carcinoma with necrosis is given 3 points.
• Perineural invasion – Perineural invasion means that cancer cells were seen attached to a nerve. A mucoepidermoid carcinoma with perineural invasion is given 2 points.
• Anaplasia – Anaplasia is a word pathologists use to describe very abnormal-looking cancer cells. A mucoepidermoid carcinoma with anaplastic tumour cells is given 4 points.
• Mitosis – Cancer cells divide in order to create new cancer cells. This process is called mitosis and a cell that is dividing is called a mitotic figure. A mucoepidermoid carcinoma with more than 4 mitotic figures in an area measuring 10 high-powered fields (viewed at high magnification) is given 3 points.

Additional features used to determine the Brandwein grade:

• Pattern of growth: The pattern of growth describes the way the cells in the tumour are attached together. A tumour that shows more nests or solid groups of cells is associated with more aggressive behaviour. For this reason, a mucoepidermoid carcinoma with large nests or solid groups of cells is given 2 points.
• Lymphovascular invasion: Lymphovascular invasion is a term pathologists use to describe tumour cells that are seen inside blood vessels or lymphatic vessels. Lymphovascular invasion is important because once tumour cells enter either of these types of vessels, they are able to spread to lymph nodes and other parts of the body. A mucoepidermoid carcinoma that shows lymphovascular invasion is given 3 points.
• Bone invasion: Bone invasion means that the tumour cells have spread into nearby bones. This is typically associated with a more aggressive tumour. For this reason, a mucoepidermoid carcinoma with bone invasion is given 3 points.

Final tumour grade according to the AFIP system:

• 0 to 4 points = Low grade
• 5 or 6 points = Intermediate grade
• 7 or more points = High grade

Tumour size​

Once the entire tumour has been removed it will be measured and the size will be included in your pathology report. The size of the tumour is typically given in centimetres. The tumour size is important because it is used to determine the pathologic tumour stage (pT).

Extraparenchymal extension

Parenchyma is a word used to describe the normal tissue found on the inside of an organ. Because mucoepidermoid carcinoma typically starts in a salivary gland, parenchyma is used to describe the normal salivary gland tissue. Extraparenchymal extension means that the tumour cells have grown beyond the normal salivary gland tissue and are seen in the surrounding tissue.

Extraparenchymal extension is important because tumours that have grown beyond the normal salivary gland tissue are more likely to spread to other parts of the body such as lymph nodes. Extraparenchymal extension is also used to determine the tumour stage (see Pathologic stage below).

Margins

Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed. A margin is a rim of normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery. The types of margins described in your report will depend on the location of the tumour.

Your pathologist will carefully examine all the margins in your tissue sample to see how close the cancer cells are to the edge of the cut tissue. A negative margin means that no cancer cells were seen at the cut edge of the tissue. In contrast, a positive margin means that cancer cells were seen at the cut edge of the tissue. A positive margin is associated with an increased risk that the tumour will grow back in the same location after treatment.

Perineural invasion

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 the tumour cells can use the nerve to spread into surrounding tissues. This increases the risk that the tumour will re-grow 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 specialized vessels called lymphatics. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood or lymphatic vessel. Lymphovascular invasion is important because these cells are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.

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.

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).

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 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

​The pathologic stage for mucoepidermoid 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 mucoepidermoid carcinoma

Mucoepidermoid carcinoma is given a tumour stage from 1 to 4 based on the size of the tumour and the distance that the cancer cells have spread outside of the salivary gland (extraparenchymal extension).

• T1 – The tumour is less than 2 cm in size and is found entirely within the salivary gland.
• T2 – The tumour is between 2 cm and 4 cm in size and is found entirely within the salivary gland.
• T3 – The tumour is larger than 4 cm in size AND/OR the cancer cells have spread outside of the salivary gland into the tissue that normally surrounds the gland.
• T4 – The cancer cells have entered any of the organs that normally surround the salivary gland. These organs include large blood vessels, bones, skin, or the ear.

Nodal stage (pN) for mucoepidermoid carcinoma

Mucoepidermoid carcinoma is given a nodal stage from 0 to 3. If no cancer cells are seen in any of the lymph nodes examined, the nodal stage is N0. If cancer cells are found in any of the lymph nodes examined, the nodal stage will be 1, 2, or 3. In order to determine the nodal stage, your pathologist will determine the number of lymph nodes with cancer cells, the size of the largest group of cancer cells in a lymph node, the location of the lymph nodes involved, and whether any extranodal extension is seen (see Extranodal extension above).

Metastatic stage (pM) for mucoepidermoid carcinoma

Mucoepidermoid carcinoma is given a metastatic stage of 0 or 1 based on the finding 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 submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.