Polymorphous adenocarcinoma

by Jason Wasserman MD PhD FRCPC
August 30, 2023

What is polymorphous adenocarcinoma?

Polymorphous adenocarcinoma (PAC) is a type of salivary gland cancer. Pathologists divide polymorphous adenocarcinoma into two types: conventional and cribriform.

Where is polymorphous adenocarcinoma found in the body?

Polymorphous adenocarcinoma typically involves one of the minor salivary glands in the oral cavity, with the most common location being the palate.

Can the cells in polymorphous adenocarcinoma spread to other parts of the body?

Yes, the tumour cells in polymorphous adenocarcinoma can spread to other parts of the body with the most common site being a lymph node in the neck. However, the majority of tumours (85 – 90%) will not spread.

What are the symptoms of polymorphous adenocarcinoma?

Polymorphous adenocarcinoma commonly presents as a slow-growing, painless mass.

What causes polymorphous adenocarcinoma?

The cause of polymorphous is currently unknown and there are no genetic syndromes associated with this type of cancer.

Are there different types of polymorphous adenocarcinoma?

Yes. Pathologists divide polymorphous adenocarcinoma into two types – conventional and cribriform – based on the way the tumour looks when examined under the microscope. Both types of tumours are associated with genetic alterations involving members of the PRKD gene family (PRKD1, PRKD2, and PRKD3). However, the conventional type is more likely to contain a hotspot mutation involving the PRKD1 gene while the cribriform type may contain a mutation or translocation involving PRKD1, PRKD2, or PRKD3. Aside from the genetic differences, the tumour type is important because the cribriform type is more likely to metastasize (spread) to lymph nodes in the neck compared to the conventional type.

How is this diagnosis made?

The diagnosis of polymorphous adenocarcinoma can only be made after the tumour is examined under a microscope by a pathologist.

What does polymorphous adenocarcinoma look like under the microscope?

When examined under the microscope, the conventional type is made up of a uniform population of tumour cells arranged in a wide variety of patterns including single cells, tubular, trabecular, cystic, and solid. A small number of mitotic figures (cells dividing to create new cells) may be seen. The tumour cells in this type frequently surround nerves and blood vessels in a circular pattern that pathologists describe as targetoid or ‘eye of the storm’ because it resembles the eye of a hurricane.

The cribriform type of polymorphous adenocarcinoma shares many microscopic features with the conventional type. However, the tumour cells in the cribriform type are more likely to show cribriform or papillary patterns of growth. Distinctive round structures, characterized as glomeruloid because they resemble the glomerulus in the kidney are also often seen.

What other tests may be performed to confirm the diagnosis?

Other tests including immunohistochemistry (IHC) and next-generation sequencing (NGS) may be performed to confirm the diagnosis and to rule out other conditions that can look very similar to polymorphous adenocarcinoma under the microscope. When immunohistochemistry is performed the tumour cells are typically positive for cytokeratin 7 (CK7), S100, SOX10, and p63. Some tumours are positive for epithelial membrane antigen (EMA), smooth muscle actin (SMA) and muscle-specific actin (MSA). The tumour is also negative for p40. 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 polymorphous adenocarcinoma (PRKD mutations or translocations). When NGS is ordered, the results will describe any fusions or other genetic changes identified.

What does it mean if polymorphous adenocarcinoma is described as low grade?

Low grade means that the tumour did not have any microscopic features associated with more aggressive behaviour. These features include large numbers of mitotic figures (cells dividing to create new cells), cytologic atypia (cells that are abnormal looking in shape, size or colour), and necrosis (dead or dying tumour cells). Most polymorphous adenocarcinomas are low grade.

What does high grade transformation mean?

High grade transformation in polymorphous adenocarcinoma means that the tumour has started to change in a way that results in more aggressive behaviour. Tumours with high grade transformation often have more mitotic figures (tumour cells dividing to create new tumour cells), cytologic atypia (cells that are abnormal in shape, size, or colour), 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 does perineural invasion mean and why is it important?

Perineural invasion is a term pathologists use to describe cancer cells attached to a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. 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 important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery. Perineural invasion is almost always seen in polymorphous adenocarcinoma. Intraneural invasion is also common.

What does lymphovascular invasion mean and why is it important?

Lymphovascular invasion is a term used to describe cancer cells inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs.

What is a margin?

In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) depends on the type of tumour being removed and the location of the tumour.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved.

Were lymph nodes examined and did any contain cancer cells?

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body such as a lymph node is called a metastasis.

Cancer cells typically spread first to lymph nodes close to the tumour although lymph nodes far away from the tumour can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in the lymph node.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist and the results of this examination will be described in your report. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells. If cancer cells were seen in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) will also be included.

The examination of lymph nodes is important for two reasons. First, this information is used to determine the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment such as chemotherapy, radiation therapy, or immunotherapy is required.

What does it mean if a lymph node is described as positive?

Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.

What does it mean if a lymph node is described as negative?

Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.