Adenoid cystic carcinoma

by Jason Wasserman MD PhD FRCPC
June 24, 2022

What is adenoid cystic carcinoma?

Adenoid cystic carcinoma (ACC) is a type of cancer that commonly starts in one of the major or minor salivary glands found throughout the head and neck. Other parts of the body including the skin, lungs, breasts, and prostate gland can also be involved. ACC is a slow-growing cancer that often spreads into organs surrounding the tumour. Unlike other types of cancer, ACC does not typically spread to lymph nodes. Approximately half of all tumours have a genetic alteration involving the genes MYB, MYBL1, or NFIB.

How does adenoid cystic carcinoma spread?

ACC is a slow-growing cancer. However, it can spread widely into tissues and organs surrounding the tumour. Unlike other types of cancer, ACC does not typically spread to lymph nodes unless it undergoes high grade transformation (see What is high grade transformation below).

What are the symptoms of adenoid cystic carcinoma?

The symptoms of ACC depend on where the tumour starts and the size of the tumour. Symptoms associated with tumours in the head and neck include pain, numbness, and tingling in the area of the tumour. In the skin or breast, the tumour may appear as a painless lump or nodule. Tumours in the lung may cause shortness of breath, coughing, or wheezing.

What does adenoid cystic carcinoma look like under the microscope?

When examined under the microscope, ACC is made up of two types of cells: ductal cells and myoepithelial cells. As a result, ACC is sometimes described as a biphasic salivary gland tumour. The tumour cells in ACC commonly show two patterns of growth: tubular and cribriform. In the tubular pattern, the tumour cells connect together to create a ring-shaped structure with a hole in the centre. In the cribriform pattern, the tumour cells connect together to form makes small spaces called microcysts. These microcysts are often filled with blue or pink-coloured material.

This picture shows the typical microscopic appearance of adenoid cystic carcinoma.

What does high grade transformation mean?

High grade transformation in adenoid cystic 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 an ACC. In particular, the tumour cells often stick together to create large groups of cells without the microcysts typically seen in ACC. Pathologists use the term solid to describe this pattern of growth. Tumours with high grade transformation often have more mitotic figures (tumour 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 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).

What is perineural invasion?

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. Perineural invasion is almost always seen in an ACC. If perineural invasion is not seen after the entire tumour has been removed, the diagnosis should be questioned.

What is lymphovascular invasion?

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. The tumour cells in an ACC very rarely invade lymphatics. However, late in the course of the disease, tumour cells in an ACC may be seen invading blood vessels.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs located throughout the body. Cancer 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 cancer 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.

Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells. 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 all lymph nodes for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative.

Finding cancer cells in a lymph node is important because it is associated with a higher risk that the cancer cells will be found in other lymph nodes or in a distant organ such as the lungs. However, unlike other types of cancer, the cancer cells in an adenoid cystic carcinoma are very rarely found in a lymph node.

What is a tumour deposit?

A group of cancer cells inside of a lymph node is called a tumour deposit. If a tumour deposit is found, your pathologist will measure the deposit and the largest tumour deposit found will be described in your report. Larger tumour deposits are associated with a worse prognosis. The size of the largest tumour deposit is also used to determine the nodal stage (see Pathologic stage below).

What does extranodal extension (ENE) mean?

All lymph nodes are surrounded by a capsule. Extranodal extension (ENE) means that cancer cells have broken through the capsule and into the tissue that surrounds the lymph node. Extranodal extension is also associated with a higher risk of new tumours developing in the neck and is often used by your doctors to guide your treatment. Extranodal extension is also used to determine the nodal stage (see Pathologic stage below).

How is adenoid cystic carcinoma staged?

​The pathologic stage for ACC is based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and a worse prognosis.

Tumour stage (pT) for adenoid cystic carcinoma

ACC is given a tumour stage from 1 to 4 based on the size of the tumour and the distance that the cancer cells have travelled outside of the salivary gland (extraparenchymal extension).

• T1 – The tumour is less than 2 cm in size and is found entirely within the salivary gland.
• T2 – The tumour is between 2 cm and 4 cm in size and is found entirely within the salivary gland.
• T3 – The tumour is larger than 4 cm in size AND/OR the cancer cells have travelled outside of the salivary gland into the tissue that normally surrounds the gland.
• T4 – The cancer cells have entered any of the organs that normally surround the salivary gland. These organs include large blood vessels, bones, skin, or the ear.

Nodal stage (pN) for adenoid cystic carcinoma

ACC is given a nodal stage from 0 to 3. If no cancer cells are seen in any of the lymph nodes examined, the nodal stage is N0. If cancer cells are seen in a lymph node, your pathologist will look for the following features to determine the nodal stage:

• Size  – The group of cancer cells in the lymph node will be measured. A size greater than 3 cm or 6 cm increases the nodal stage.
• Extranodal extension – All lymph nodes are surrounded by a thin layer of tissue called a capsule. If cancer cells break through the capsule and enter the tissue surrounding the lymph node it is called extranodal extension. Extranodal extension increases the nodal stage.
• Number of positive lymph nodes – Your pathologist will count the number of lymph nodes that contain cancer cells. Cancer cells found in more than one lymph node increase the nodal stage.
• Location of positive lymph nodes – Lymph nodes on the same side of the tumour are called ipsilateral. Lymph nodes on the opposite side of the tumour are called contralateral. Cancer cells found in a contralateral lymph node increase the nodal stage.​

Metastatic stage (pM) for adenoid cystic carcinoma

ACC is given a metastatic stage of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is sent for pathological examination. Because this tissue is rarely sent, the metastatic stage cannot be determined and is listed as MX.