Hyalinizing clear cell carcinoma

by Jason Wasserman MD PhD FRCPC
April 7, 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.

hyalinizing clear cell carcinoma

The microscopic appearance of hyalinizing clear cell carcinoma

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 send information (such as temperature, pressure, and pain) between your brain and your body. Perineural invasion means that tumour cells were seen attached to a nerve.

Tumour cells that have attached to a nerve can use the nerve to spread into tissue away from the original tumour. This increases the risk that the tumour will come back in the same area of the body (local recurrence) after treatment.

perineural invasion

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 lymphatic channels. Tumour cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of tumour cells from the tumour to another part of the body is called metastasis.

Before tumour cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion. Lymphovascular invasion increases the risk that tumour cells will be found in a lymph node or a distant part of the body such as the lungs.

lymphovascular invasion

What is a margin?

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. The types of margins described in your report will depend on the organ involved and the type of surgery performed. Margins will only be described in your report after the entire tumour has been removed.

A negative margin means that no tumour cells were seen at any of the cut edges of tissue. A margin is called positive when there are tumour cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will recur in the same site after treatment.

Margin

Lymph nodes

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.

Lymph node

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