Myoepithelial carcinoma of the salivary glands

by Jason Wasserman MD PhD FRCPC
November 29, 2024

Myoepithelial carcinoma is a rare cancer that starts in the salivary glands. It develops from myoepithelial cells, which are specialized cells normally found in the salivary gland. This tumour can arise on its own or from a pre-existing noncancerous tumour called pleomorphic adenoma. Myoepithelial carcinoma is typically a slow-growing type of cancer, but it can spread to other parts of the body over time.

What are the symptoms of myoepithelial carcinoma?

Symptoms of myoepithelial carcinoma often depend on the size and location of the tumour.

Common symptoms include:

• A lump or swelling in the face, neck, or mouth.
• Pain in the affected area.
• Difficulty opening the mouth or moving the jaw.
• Numbness or weakness in the face.

What causes myoepithelial carcinoma?

The exact cause of myoepithelial carcinoma is not fully understood. However, it often develops from changes in the DNA of myoepithelial cells. These changes can lead to uncontrolled cell growth and tumour formation. In some cases, myoepithelial carcinoma arises from a pre-existing benign tumour called pleomorphic adenoma, which undergoes further genetic changes to become cancerous.

What genetic changes are found in myoepithelial carcinoma?

Specific genetic changes are commonly found in myoepithelial carcinoma. Over half of these tumours show changes involving a gene called PLAG1. These changes happen when PLAG1 fuses with other genes, such as FGFR1 or TGFBR3, which can drive tumour growth. Other genetic changes, such as those involving the HMGA2 and EWSR1 genes, are less common. A specific type of myoepithelial carcinoma called “clear cell myoepithelial carcinoma” may show alterations in the EWSR1 gene without forming a fusion. These findings help pathologists understand and confirm the diagnosis.

How is this diagnosis made?

The diagnosis of myoepithelial carcinoma is made using a combination of clinical examination, imaging studies, and pathological evaluation. A biopsy of the tumour is typically performed to collect tissue for microscopic examination. Pathologists use specialized tests, including immunohistochemistry and genetic studies, to identify features specific to myoepithelial carcinoma and rule out other conditions.

Microscopic features of this tumour

Under the microscope, myoepithelial carcinoma can have a wide variety of appearances. It may develop on its own or from a pre-existing pleomorphic adenoma, making it the second most common type of cancer that arises from this benign tumour. The tumour cells can take on different shapes, including spindle, epithelioid (round), or clear.

The stroma surrounding the tumour cells can vary in appearance as well. It may look like a jelly-like substance (myxoid), cartilage (chondromyxoid), or dense scar tissue (hyalinized). One characteristic feature of myoepithelial carcinoma is how the tumour cells grow in nodules, with the outer areas of the tumour being more densely packed with cells than the inner areas. Sometimes, the tumour shows small duct-like structures or areas where the cells resemble squamous cells. Tumour necrosis, or areas where tumour cells have died, may also be present and is associated with a poorer outcome.

Immunohistochemistry

Immunohistochemistry is a special test that pathologists use to look for specific proteins in the tumour cells. This test helps confirm the diagnosis and provides additional information about the tumour’s characteristics. It applies antibodies to the tissue sample that bind to specific proteins, which can be visualized under the microscope.

In myoepithelial carcinoma, tumour cells often test positive for various proteins, including cytokeratins, SOX10, and S100. These proteins are markers commonly found in myoepithelial cells. Other markers, such as smooth muscle actin (SMA), calponin, and p63 or p40, may also be present, reflecting the myoepithelial origin of the tumour. These findings are important for distinguishing myoepithelial carcinoma from other salivary gland tumours.

Extraparenchymal extension

In the context of a salivary gland tumour such as myoepithelial 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.

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 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. 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.

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 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.

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.

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.