by Jason Wasserman MD PhD FRCPC
November 28, 2024
This article is designed to help you understand your pathology report for secretory carcinoma of the head and neck. Each section explains a specific aspect of the diagnosis and what it means for you.
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 genes. 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. Similar tumours can be found in the breast and the skin.
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.
In the context of a salivary gland tumour such as secretory 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 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 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.
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.
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.
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.
The tumour stage describes the size of the tumour in the salivary gland and whether it has spread into nearby tissues.
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.