Epithelial-myoepithelial carcinoma

by Jason Wasserman MD PhD FRCPC
November 5, 2024

Epithelial-myoepithelial carcinoma (EMC) is a type of salivary gland cancer. The tumour is described as a biphasic salivary gland neoplasm because it comprises two populations of cells: ductal (luminal) and myoepithelial (abluminal) cells. The most common location for epithelial-myoepithelial carcinoma is the parotid gland. However, the tumour can be found in any salivary glands, including the minor salivary glands in the oral cavity. Rarely, this tumour can be in the large airways of the lungs.

What are the symptoms of epithelial-myoepithelial carcinoma?

Most epithelial-myoepithelial carcinomas present as a slow-growing, painless mass.

What causes epithelial-myoepithelial carcinoma?

The cause of epithelial-myoepithelial carcinoma is currently unknown, and there are no genetic syndromes associated with this type of cancer.

What does epithelial-myoepithelial carcinoma ex pleomorphic adenoma mean?

Epithelial-myoepithelial carcinoma ex pleomorphic adenoma means that the malignant (cancerous) epithelial-myoepithelial carcinoma developed from within a previously benign (noncancerous) tumour called pleomorphic adenoma.

How is this diagnosis made?

To diagnose epithelial-myoepithelial carcinoma, your doctor will typically start with an imaging test, such as an ultrasound, CT scan, or MRI, to assess the size and location of the tumour. If a suspicious area is found, a biopsy will be performed to take a small tissue sample. A pathologist will then examine this sample under a microscope to confirm the diagnosis. Sometimes, additional tests are done to help confirm that the tumour is epithelial-myoepithelial carcinoma and to rule out other types of salivary gland cancers.

Microscopic features of epithelial-myoepithelial carcinoma

When a pathologist examines epithelial-myoepithelial carcinoma under a microscope, they look for specific patterns in the tumour. One of the key features of epithelial-myoepithelial carcinoma is its “biphasic” arrangement, meaning it has two different cell types arranged in layers. The inner layer, called luminal cells, are ductal cells with pinkish (eosinophilic) colouring, while the outer layer, known as myoepithelial cells, often appear clear. This layered structure can vary in thickness, from a single layer to several layers, and can even look solid in some areas.

The tumour can display various patterns, such as cribriform (with small, sieve-like spaces), basaloid (small, densely packed cells), and double-clear cell layers. In some cases, cells may also look like sebaceous (oil-producing) or squamous (flat) cells. The cells show only mild to moderate abnormalities in their nuclei (the central part of the cell). This mix of patterns and cell types helps pathologists identify epithelial-myoepithelial carcinoma and distinguish it from other salivary gland tumours.

What other tests may be performed to confirm the diagnosis?

Other tests, including immunohistochemistry (IHC), may be performed to confirm the diagnosis and rule out other conditions that look very similar to epithelial-myoepithelial carcinoma under the microscope. When immunohistochemistry is performed, the ductal cells are typically positive for pan-cytokeratin and cytokeratin 7 (CK7), while the myoepithelial cells are generally positive for S100, SOX10, p63, p40, smooth muscle actin, and muscle-specific actin. However, not all of these markers will be ordered for every case.

High grade transformation

High grade transformation in epithelial-myoepithelial carcinoma means that the tumour has started to change, resulting in more aggressive behaviour. When examined under the microscope, tumours with high grade transformations have lost some of the features typically seen in an epithelial-myoepithelial carcinoma. In particular, the tumour cells will no longer look like normal ductal or myoepithelial cells. The cells in a tumour showing high grade transformation may be described as being atypical or pleomorphic. In addition, tumours with high grade transformation often have more mitotic figures (tumour cells dividing to create new tumour cells) and a type of cell death called necrosis may also be seen. High grade transformation is important because these tumours are more likely to metastasize (spread) to lymph nodes and the lungs.

Extraparenchymal extension

In the context of a salivary gland tumour such as epithelial-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 refers explicitly 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. 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 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.

Lymph nodes​

Lymph nodes are small immune organs 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 epithelial-myoepithelial 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.

• 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.

What pathologic factors are associated with prognosis?

Several factors in the pathology report can help predict epithelial-myoepithelial carcinoma’s outcome or prognosis. Key factors include tumour size, the extent of spread to nearby tissues, and lymph node involvement. Smaller tumours confined to the salivary gland tend to have a better prognosis, while larger tumours or those that have spread to surrounding areas may require additional treatment. Epithelial-myoepithelial carcinoma is often a slow-growing cancer, but the prognosis depends on the tumour’s size, location, and whether it has spread at the time of diagnosis. Tumours that show high grade transformation are associated with worse prognosis and are more likely to spread to lymph nodes and other body sites.