by Jason Wasserman MD PhD FRCPC
August 6, 2024

Epithelial-myoepithelial carcinoma (EMC) is a type of salivary gland cancer. The tumour is described as a biphasic salivary gland neoplasm because it is made up of two populations of cells: ductal (luminal) cells and myoepithelial (abluminal) cells. The most common location for epithelial-myoepithelial carcinoma is the parotid gland, although the tumour can be found in any of the 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?

The diagnosis of epithelial-myoepithelial carcinoma is typically only made after the entire tumour has been removed and sent to a pathologist for examination under the microscope. This is because it can be very difficult to distinguish between epithelial-myoepithelial carcinoma and the similar appearing pleomorphic adenoma in a small tissue sample such as a biopsy or fine needle aspiration.

Microscopic features of epithelial-myoepithelial carcinoma

When examined under the microscope, the tumour cells in epithelial-myoepithelial carcinoma are typically arranged in large groups called nodules that infiltrate (spread) through the salivary gland tissue. The tumour is made up of two types of cells: ductal cells and myoepithelial cells. The ductal cells usually form round structures called glands, ducts, or tubules. The ductal cells are surrounded by myoepithelial cells, which often appear clear. Some tumours are made up primarily of myoepithelial cells. Mitotic figures (cells dividing to create new cells) may be seen, but the mitotic rate is usually low.

What other tests may be performed to confirm the diagnosis?

Other tests including immunohistochemistry (IHC) may be performed to confirm the diagnosis and to rule out other conditions that can 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 typically 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 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.

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​

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 that have been 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.

Pictures of epithelial-myoepithelial carcinoma

Atlas of pathology