Head and neck -
Adenoid cystic carcinoma
This article was last reviewed and updated on May 1, 2019
by Simon Kirby, MD FRCSC FRCPC
Adenoid cystic carcinoma is a type of cancer that commonly starts in a salivary gland.
The salivary glands are small organs found in the head and neck, especially around the mouth.
Your pathology report for adenoid cystic carcinoma will include important information including the tumour grade and margin status.
Adenoid cystic carcinoma can also develop in the lung and skin. This article focuses on tumours developing in the head and neck.
The normal salivary glands
When we chew food our body releases a fluid into the mouth called saliva. Saliva is important because it contains chemicals that aid in digestion. Saliva is produced by organs called salivary glands which are located throughout the head and neck.
Most people have three major salivary glands and numerous minor salivary glands. The major salivary glands are called the parotid gland, submandibular gland, and sublingual gland. The minor salivary glands are very small and there are so many of them that they are not given their own names. Most of the minor salivary glands are found inside the mouth.
The parotid gland is the largest salivary gland and it can be found on the side of the face just in front of the ear. The submandibular gland can be found just below the lower jaw near the top of the neck. The sublingual gland is the smallest of the major glands and it can be found below the tongue.
The salivary glands are made up of small groups of cells called glands which are connected to the inside of the mouth by long thin channels called ducts. The glands make the chemicals in the saliva which travels down the ducts into the mouth.
What is adenoid cystic carcinoma?
Adenoid cystic carcinoma (ACC) is a cancer that develops from the cells normally found in the salivary glands. Approximately 75 % arise in minor salivary glands (palate most common) and 25 % in major salivary glands (parotid gland most common).
Most adenoid cystic carcinomas are small tumours (typically less than 5 cm) that grow slowly over time. However, groups of tumour cells commonly surround nerves (perineural invasion) and use the nerves to spread into the surrounding tissues. Because of this the tumour is often difficult to remove completely by surgery alone. Unfortunately, the overall prognosis is poor as many patients experience late local recurrences and distant metastasis.
Depending on the location of the tumour, the symptoms of an adenoid cystic carcinoma may include an ulcer in the roof of the mouth, a slow-growing lump in the face or neck, pain, or inability to move some of the muscles on one side of the face. The last two symptoms suggest that the tumour cells have surrounded a large nerve in the face called the facial nerve (cranial nerve VII).
If your doctor suspects that you have an adenoid cystic carcinoma, they will refer you to an ears, nose, and throat (ENT) surgeon for diagnosis and management. Following a history and physical examination, your surgeon will perform a biopsy and order imaging tests (most often a CT scan).
Most adenoid cystic carcinomas are first diagnosed after a small tissue sample is removed in a procedure called a biopsy. A larger surgical procedure will then be performed to remove the entire tumour.
This is the size of the tumour measured in centimeters after it has been removed fully from your body. Your pathologist will measure it in three dimensions although only the largest dimension is typically included in your report. For example, if the tumour measures 5.0 cm by 3.2 cm by 1.1 cm, the report may describe the tumour size as 5.0 cm in greatest dimension.
Why is this important? Larger tumours are associated with worse prognosis and the tumour size is used to determine the tumour stage (see Pathologic stage below).
Grade is a word pathologists use to describe the difference between the cancer cells and the cells normally found in the salivary glands. Higher grade tumours are more abnormal and look less like normal tissue.
Adenoid cystic carcinoma is graded on a scale of 1 to 3 (or low, intermediate, and high) based on the amount of tumour cells that are growing in very large groups which pathologists call solid growth.
Grade 1 (low) - No solid growth is seen.
Grade 2 (intermediate) - Some solid growth is seen but it is less than 30 % of the tumour.
Grade 3 (high) - More than 30% of the tumour shows solid growth.
Why is this important? Grade is important because it provides your doctor with important prognostic information and higher grade tumours (grades 2 and 3) are associated with worse prognosis.
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.
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 margin is considered positive when there are cancer cells at the very 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 millimeters.
Margins will only be described in your report after the entire tumour has been removed.
Why is this important? A positive margin is associated with a higher risk that the tumour will grow back in the same site after treatment (local recurrence).
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 cancer cells were seen attached to a nerve.
Perineural invasion is almost always seen in an adenoid cystic carcinoma. If perineural invasion is not seen after the entire tumour has been removed, the diagnosis should be questioned. Perineural invasion may not be seen on a biopsy as this tissue is very small and may be show all the features of the tumour.
Why is this important? Perineural invasion is important because cancer cells that have attached to a nerve can use the nerve to travel into tissue outside of the original tumour. Perineural invasion is also associated with a higher risk that the tumour will come back in the same area of the body (local recurrence) after treatment.
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.
Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.
Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion.
The tumour cells in an adenoid cystic carcinoma almost never invade lymphatics. However, late in the course of the disease, tumour cells in an adenoid cystic carcinoma may be seen invading blood vessels.
Why is this important? Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.
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 a 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.
Why is this important? 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.
The pathologic stage for adenoid cystic carcinoma 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 worse prognosis.
The pathologic stage is usually only included in your report after the entire tumour has been removed. It is not included in the report after a small sample of tissue has been removed in a biopsy or fine needle aspiration.
Tumour stage (pT) for adenoid cystic carcinoma:
Adenoid cystic carcinoma is given a tumour stage from 1 to 4 based on the size of the tumour and the distance that the cancer cells have traveled outside of the salivary gland (extraparenchymal extension).
T1 - The tumour is less than 2 cm in size and still found entirely within the salivary gland.
T2 - The tumour is between 2 cm and 4 cm in size and is still found entirely within the salivary gland.
T3 - The tumour is larger than 4 cm in size AND/OR the cancer cells have traveled 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:
Adenoid cystic carcinoma is given a nodal stage from 0-3. 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.
Extracapsular 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 extracapsular extension. Extracapsular 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 increases the nodal stage.
Location of positive lymph nodes - Cancer cells found in a lymph node on the same side of the tumour are called ipsilateral. Cancer cells found in a lymph node on the opposite side of the tumour are called contralateral. Cancer cells found in a contralateral lymph node increases the nodal stage.
Metastatic stage (pM) for adenoid cystic carcinoma:
Adenoid cystic carcinoma is given a metastatic stage between 0 and 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.
Adenoid cystic carcinomas are commonly composed of two main cell types: ductal and myoepithelial cells. Pathologists occasionally perform a test called immunohistochemistry on these tumours which helps your pathologist clearly see the cell types.