Secretory carcinoma of the salivary glands

by Jason Wasserman MD PhD FRCPC
August 9, 2023

What is secretory carcinoma of the salivary glands?

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 genetic change results in a combination or fusion of two of the three genes. A similar tumour can be found in the breast and the skin.

Where is secretory carcinoma normally found?

Secretory carcinoma can develop in any of the salivary glands but it is most commonly found in the parotid gland, the minor salivary glands of the oral cavity, and the submandibular gland.

What are the symptoms of secretory carcinoma of the salivary glands?

The most common symptom of secretory carcinoma is a painless slow-growing mass.

What causes secretory carcinoma of the salivary glands?

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. Why some people develop this genetic change is still unknown.

How is this diagnosis made?

The diagnosis of secretory carcinoma of the salivary glands can be made after tissue from the tumour is examined under the microscope by a pathologist.

What does secretory carcinoma of the salivary glands look like under the microscope?

When examined under the microscope, secretory carcinoma of the salivary glands is made up of 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 together 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 quite low.

What other tests may be ordered to confirm the diagnosis?

Other tests including immunohistochemistry (IHC) and next-generation sequencing (NGS) may be performed to confirm the diagnosis and to 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. When NGS is ordered, the results will describe any fusions or other genetic changes identified.

What does it mean if secretory carcinoma of the salivary glands shows high grade transformation?

High grade transformation in secretory carcinoma means that the tumour has started to change in a way that results 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 being 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.

What is lymphovascular invasion and why is it important?

Lymphovascular invasion (LVI) means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs. If lymphovascular invasion is seen, it will be included in your report. However, it is rare for lymphovascular invasion to be found in secretory carcinoma.

What is perineural invasion and why is it important?

Perineural invasion (PNI) is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery. If perineural invasion is seen, it will be included in your report. However, it is rare for perineural invasion to be found in secretory carcinoma.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. The cancer cells in secretory carcinoma typically do not spread to lymph nodes and for this reason, lymph nodes are not always removed at the same time as the tumour. However, when lymph nodes are removed, they will be examined under a microscope and the results will be described in your report.

Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.

What does extranodal extension mean?

All lymph nodes are surrounded by a thin layer of tissue called a capsule. Extranodal extension means that cancer cells within the lymph node have broken through the capsule and have spread into the tissue outside of the lymph node. Extranodal extension is important because it increases the risk that the tumour will regrow in the same location after surgery. For some types of cancer, extranodal extension is also a reason to consider additional treatment such as chemotherapy or radiation therapy.

What is a margin?

In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) also depends on the type of tumour being removed and the location of the tumour.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin.