by Jason Wasserman MD PhD FRCPC
November 4, 2024
Secretory carcinoma is a relatively uncommon type of salivary gland cancer. It is characterized by a genetic change involving the genes ETV6, RET, or NTRK3. This change results in a combination or fusion of two of the three genes. Similar tumours can be found in the breast and the skin.
Secretory carcinoma can develop in any of the salivary glands, but it is most commonly found in the parotid gland, minor salivary glands of the oral cavity, and submandibular gland.
The most common symptom of secretory carcinoma is a painless, slow-growing mass.
Secretory carcinoma is caused by a genetic change called a fusion. A fusion is a combination of two genes that results in the production of an abnormal protein. The most common fusions found in secretory carcinoma of the salivary glands involve the genes ETV6 and NTRK3 or ETV6 and RET. These fusions allow the tumour cells to grow and divide faster than normal cells. The reason why some people develop this genetic change is still unknown.
A pathologist can diagnose secretory carcinoma of the salivary glands by examining tissue from the tumour under the microscope.
When examined under the microscope, secretory carcinoma of the salivary glands comprises large eosinophilic (pink) cells with round centrally located nuclei. Most cells also contain a prominent nucleolus (clump of genetic material) in the centre of the nucleus. The tumour cells often connect to form round structures called tubules or glands, large open spaces called cysts, and finger-like projections that pathologists describe as papillary or micropapillary. Mitotic figures (cells dividing to create new cells) are often found, but the number of mitotic figures is usually relatively low.
Other tests, including immunohistochemistry (IHC) and next-generation sequencing (NGS), may be performed to confirm the diagnosis and rule out other conditions that can look very similar to secretory carcinoma under the microscope.
When immunohistochemistry is performed the tumour cells are typically positive for cytokeratin-7 (CK7), S100, SOX10, and mammaglobin and negative for p63, p40, and DOG1. However, not all of these markers will be ordered for every case.
Next-generation sequencing (NGS) may be ordered to look for one of the genetic changes or fusions commonly seen in secretory carcinoma of the salivary glands. The results will describe any fusions or other genetic changes identified.
High grade transformation in secretory carcinoma means that the tumour has started to change, resulting in more aggressive behaviour. When examined under the microscope, tumours with high grade transformation have lost some of the features typically seen in secretory carcinoma. In particular, the cells in a tumour with high grade transformation may be described as atypical or pleomorphic. In addition, these tumours typically contain more mitotic figures (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.
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.
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.
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.
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.