Mucoepidermoid carcinoma

by Jason Wasserman MD PhD FRCPC
November 29, 2024


Mucoepidermoid carcinoma is a type of salivary gland cancer. The salivary glands are small saliva-producing organs located in the head and neck.  Although less common, this type of cancer can also be found in the nasal cavity and lungs.

Mucoepidermoid carcinoma comprises three types of cells: mucus-producing cells, epidermoid (squamous-like) cells, and intermediate cells that share features of the other two cell types. It can range from low-grade, which grows slowly and is less aggressive, to high-grade, which grows more quickly and is more likely to spread to other body parts.

Major salivary glands

What are the symptoms of mucoepidermoid carcinoma?

The symptoms of mucoepidermoid carcinoma can vary depending on the size and location of the tumour.

Common symptoms include:

  • A painless lump or swelling in the face, neck, or mouth.
  • Pain or discomfort in the area of the tumour.
  • Difficulty swallowing or opening the mouth.
  • Numbness or weakness in part of the face if the tumour is pressing on nerves.

What causes mucoepidermoid carcinoma?

The exact cause of mucoepidermoid carcinoma is not always known. However, like many cancers, it is thought to develop due to changes in the DNA of cells that cause them to grow uncontrollably. These genetic changes may occur randomly, due to environmental factors, or due to inherited genetic predispositions.

What genetic changes are found in mucoepidermoid carcinoma?

A common genetic change found in mucoepidermoid carcinoma is a rearrangement (fusion) of two genes, MAML2 and CRTC1 or CRTC3. This genetic fusion creates an abnormal protein that plays a role in the growth and survival of cancer cells. This fusion is particularly common in low- and intermediate-grade tumours and is often used to help confirm the diagnosis.

How is this diagnosis made?

The diagnosis of mucoepidermoid carcinoma is made by examining a tissue sample from the tumour under a microscope. Pathologists look for the characteristic mixture of mucus-producing, epidermoid, and intermediate cells.

Microscopic features of this tumour

When examined under the microscope, mucoepidermoid carcinoma is typically made up of three types of cells: mucous, intermediate, and epidermoid. 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 often more challenging to see. In some tumours, the intermediate cells are larger, and the cell’s body appears clear. Finally, the epidermoid cells often appear pink and may be described using terms such as eosinophilic or squamoid.

Tumour cells often connect to form open spaces called cysts, which are frequently lined by mucus (goblet) cells. The intermediate and epidermoid cells are more likely to be arranged in groups described as nests or solid sheets.

mucoepidermoid carcinoma
Mucoepidermoid carcinoma. This picture shows a typical mucoepidermoid carcinoma with large mucus cells forming a cyst (top left) and intermediate and epidermoid cells in a solid nest (right).

Grade

Pathologists divide mucoepidermoid carcinoma into three grades—low, intermediate, and high. The grade is important because it helps 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 initially 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.

Brandwein later developed an alternative system, and some pathologists now use a modified or hybrid system that combines some of the features of the AFIP system with those of 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 invasionPerineural invasion means that cancer cells are seen attached to a nerve. A mucoepidermoid carcinoma with perineural invasion is given 2 points.
  • AnaplasiaAnaplasia 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.

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

Additional features used to determine the Brandwein grade

  • Pattern of growth: The pattern of growth describes how the tumour cells 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: Pathologists use the term lymphovascular invasion 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 can 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.

Molecular tests

Pathologists may use molecular tests to confirm the diagnosis of mucoepidermoid carcinoma and identify genetic changes like the MAML2 fusion. Next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) are two commonly used techniques.

  • Next-generation sequencing (NGS): NGS is a highly advanced technology that analyzes the genetic material (DNA or RNA) from the tumour. For mucoepidermoid carcinoma, NGS can detect the presence of the MAML2 fusion and other genetic changes.
  • Fluorescence in situ hybridization (FISH): FISH is a laboratory test that uses fluorescent probes to identify specific genetic changes in the tumour cells. For mucoepidermoid carcinoma, FISH can confirm the presence of the MAML2 gene rearrangement.

The results of these tests help support the diagnosis and may provide additional information about the tumour’s behaviour and prognosis.

Extraparenchymal extension

In the context of a salivary gland tumour such as mucoepidermoid carcinoma, extraparenchymal extension (EPE) is the spread of the tumour beyond the salivary gland into the surrounding tissues. This condition is often associated with a more aggressive form of cancer, indicating that the tumour can invade beyond its original site. The presence of extraparenchymal extension is associated with more aggressive tumours and a worse prognosis.

Extraparenchyma, extension impacts the pathologic stage but only for tumours arising from one of the major salivary glands (parotid, submandibular, and sublingual). Tumours with extraparenchymal extension are generally classified at a higher stage, reflecting their advanced nature and the associated challenges in treatment and management.

Lymphovascular invasion​

Lymphovascular invasion occurs when cancer cells invade a blood vessel or lymphatic vessel. Blood vessels are thin tubes that carry blood throughout the body, unlike lymphatic vessels, which carry a fluid called lymph instead of blood. These lymphatic vessels connect to small immune organs known as lymph nodes scattered throughout the body. Lymphovascular invasion is important because it spreads cancer cells to other body parts, including lymph nodes or the liver, via the blood or lymphatic vessels.

Lymphovascular invasion

Perineural invasion​

Pathologists use the term “perineural invasion” to describe a situation where cancer cells attach to or invade a nerve. “Intraneural invasion” is a related term that specifically refers to cancer cells found inside a nerve. Nerves, resembling long wires, consist of groups of cells known as neurons. These nerves, present throughout the body, transmit information such as temperature, pressure, and pain between the body and the brain. The presence of perineural invasion is important because it allows cancer cells to travel along the nerve into nearby organs and tissues, raising the risk of the tumour recurring after surgery.

Perineural invasion

Margins

In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure, like an excision or resection, that removes the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are present at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some cancer may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Margin

Lymph nodes​

Small immune organs, known as lymph nodes, are located throughout the body. Cancer cells can travel from a tumour to these lymph nodes via tiny lymphatic vessels. For this reason, doctors often remove and microscopically examine lymph nodes to look for cancer cells. This process, where cancer cells move from the original tumour to another body part, like a lymph node, is termed metastasis.

Cancer cells usually first migrate to lymph nodes near the tumour, although distant lymph nodes may also be affected. Consequently, surgeons typically remove lymph nodes closest to the tumour first. They might remove lymph nodes farther from the tumour if they are enlarged and there’s a strong suspicion they contain cancer cells.

Lymph node

Pathologists will examine any lymph nodes removed under a microscope, and the findings will be detailed in your report. A “positive” result indicates the presence of cancer cells in the lymph node, while a “negative” result means no cancer cells were found. If the report finds cancer cells in a lymph node, it might also specify the size of the largest cluster of these cells, often referred to as a “focus” or “deposit.” Extranodal extension occurs when tumour cells penetrate the lymph node’s outer capsule and spread into the adjacent tissue.

Examining lymph nodes is important for two reasons. First, it helps determine the pathologic nodal stage (pN). Second, discovering cancer cells in a lymph node suggests an increased risk of later finding cancer cells in other body parts. This information guides your doctor in deciding whether you need additional treatments, such as chemotherapy, radiation therapy, or immunotherapy.

Pathologic stage

Pathologic staging is a system doctors use to describe the size and spread of a tumour. This helps determine how advanced the cancer is and guides treatment decisions. The pathologic stage is usually determined after the tumour is removed and examined by a pathologist, who analyzes the tissue under a microscope. For acinic cell carcinoma, staging is based on the “TNM” system, where “T” stands for the size and extent of the primary tumour, “N” refers to lymph node involvement, and “M” indicates whether the cancer has spread to other parts of the body.

Tumour stage (pT)

The tumour stage describes the size of the tumour in the salivary gland and whether it has spread into nearby tissues.

  • T0 means there is no evidence of a primary tumour in the salivary gland.
  • Tis refers to carcinoma “in situ,” meaning the cancer cells are limited to where they started and have not invaded deeper tissues.
  • T1 means the tumour is 2 cm or smaller and has not spread beyond the salivary gland.
  • T2 refers to a tumour larger than 2 cm but not larger than 4 cm, still confined to the salivary gland.
  • T3 means the tumour is larger than 4 cm or has spread to nearby soft tissues.
  • T4 describes more advanced tumours. T4a means the tumour has spread to the skin, jawbone, ear canal, or facial nerve. T4b indicates very advanced cancer that has spread to the base of the skull, nearby bones, or major blood vessels.

Nodal stage (pN)

The nodal stage indicates whether the cancer has spread to the lymph nodes, which are small glands that help the body fight infection. Lymph node involvement can increase the risk of cancer spreading further.

  • Nx means that no lymph nodes were submitted for examination.
  • N0 means there is no spread to nearby lymph nodes.
  • N1 indicates the cancer has spread to a single lymph node on the same side of the neck, measuring 3 cm or smaller.
  • N2 describes more extensive lymph node involvement:
    • N2a: A single lymph node on the same side of the neck is affected, measuring up to 6 cm, or smaller nodes that show signs of cancer outside the node.
    • N2b: Multiple lymph nodes on the same side of the neck are affected, none larger than 6 cm.
    • N2c: Cancer has spread to lymph nodes on both sides of the neck or on the opposite side, none larger than 6 cm.
  • N3 indicates more advanced lymph node involvement. N3a means a node larger than 6 cm is affected. N3b involves multiple nodes or any nodes where cancer has spread outside the lymph node into nearby tissues.

Prognosis

The prognosis for mucoepidermoid carcinoma depends on several factors, including the tumour’s grade and size and whether it has spread to other parts of the body.

  • Low grade tumours generally have an excellent prognosis as they grow slowly and are less likely to spread.
  • Intermediate grade tumours have a moderately good prognosis, but they require close monitoring and sometimes more aggressive treatment.
  • High grade tumours tend to grow more quickly, spread to other tissues, and are associated with a poorer prognosis.

Treatment often includes surgery to remove the tumour, and in some cases, radiation therapy or chemotherapy may be recommended. Regular follow-up is important to monitor for any recurrence or spread of the cancer. Your doctor can provide a more detailed prognosis based on your specific situation.

About this article

Doctors wrote this article to help you read and understand your pathology report. Contact us if you have questions about this article or your pathology report. For a complete introduction to your pathology report, read this article.

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