Hyalinizing clear cell carcinoma

by Jason Wasserman MD PhD FRCPC
June 24, 2022

What is hyalinizing clear cell carcinoma?

Hyalinizing clear cell carcinoma (HCCC) is a slow-growing type of head and neck cancer. A genetic alteration involving the EWSR1 gene is found in most HCCCs.

Where is hyalinizing clear cell carcinoma normally found?

Most HCCCs tumours arise from minor salivary glands which are normally found in the lip, tongue, buccal mucosa (inner cheeks), gingiva (gums), hard and soft palate (the roof of the mouth), floor of the mouth, or oropharynx (tonsils and base of tongue). Less common sites include the nasal cavity, paranasal sinuses, parotid gland, and larynx.

How do pathologists make the diagnosis of hyalinizing clear cell carcinoma?

The diagnosis of HCCC is usually made after a small sample of the tumour is removed in a procedure called a biopsy. The tissue sample is then sent to a pathologist for examination under the microscope.

What does hyalinizing clear cell carcinoma look like under the microscope?

When examined under the microscope, HCCC is made up of tumour cells that connect together to form small groups called nests and longer groups called cords or trabeculae. The cytoplasm (the material inside the body of the cell) can appear clear or eosinophilic (pink). Mitotic figures (dividing tumour cells) are present but the number is usually small. Other features commonly seen in cancerous tumours such as necrosis (cell death) and lymphovascular invasion are usually absent. The tumour cells are often surrounded by bright pink connective tissue which pathologists describe as hyalinized.

What other tests may be performed to confirm the diagnosis?

Most HCCCs harbour a genetic alteration involving the EWSR1 gene and your pathologist may order a test such as fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) to look for this genetic change.

A test called immunohistochemistry may also be performed. By immunohistochemistry, the tumour cells are usually positive (or reactive) for the markers CK5, p40, p63, and CK7. The tumour cells are usually negative (or non-reactive) for the markers S100 and SOX-10. Other immunohistochemical markers may also be ordered although they are not required to make the diagnosis.

What does perineural invasion mean?

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 a term pathologists use to describe tumour cells attached to a nerve. Perineural invasion is important because the tumour cells can use the nerve to spread into surrounding tissues. This increases the risk that the tumour will re-grow after treatment.

What does lymphovascular invasion mean?​

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through specialized vessels called lymphatics. The term lymphovascular invasion is used to describe tumour cells that are found inside a blood or lymphatic vessel. Lymphovascular invasion is important because these cells are able to metastasize (spread) to other parts of the body such as lymph nodes or the lungs.

What does extraparenchymal extension mean and why is it important?

The term extraparenchymal extension describes a tumour that has grown beyond the normal salivary gland and into surrounding organs or tissue. Extraparenchymal extension is important because tumours that show extraparenchymal extension are more likely to spread to other parts of the body such as lymph nodes. Extraparenchymal extension is also used to determine the pathologic tumour stage (pT).

What is a margin?

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed. Most reports will only describe margins after the entire tumour has been removed.

Your pathologist will carefully examine all the margins in your tissue sample to see how close the cancer cells are to the edge of the cut tissue. A negative margin means there were no cancer cells at the very edge of the cut tissue. If all the margins are negative, most pathology reports will usually say how far the closest cancer cells were to a margin. The distance is usually described in millimetres. A positive margin means there were cancer cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will grow back in the same site after treatment (local recurrence).

Were lymph nodes removed and did any contain tumour cells?

Lymph nodes are small immune organs located throughout the body. Tumour cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of tumour cells from the tumour to a lymph node is called metastasis.

Lymph nodes from the neck are sometimes removed at the same time as the main tumour in a procedure called a neck dissection. The lymph nodes removed usually come from different areas of the neck and each area is called a level. The levels in the neck include 1, 2, 3, 4, and 5. Your pathology report will often describe how many lymph nodes were seen in each level sent for examination. Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.

Your pathologist will carefully examine each lymph node for tumour cells. Lymph nodes that contain tumour cells are often called positive while those that do not contain any tumour cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain tumour cells.