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Salivary Gland Cancer

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What is salivary gland cancer?

Salivary gland cancer is a cancer that starts in one of the salivary glands. It is not a single disease. There are actually several different salivary glands found inside and near your mouth. Several types of cancer and benign (non-cancerous) tumors can develop in these glands.

About the salivary glands

Salivary glands produce saliva -- the lubricating fluid found in the mouth and throat. Saliva contains enzymes that begin the process of digesting food. It also contains antibodies and other substances that help prevent infections of the mouth and throat.

There are 3 major salivary glands, which occur in pairs:

The parotid glands, the largest salivary glands, are found on each side of the face, just in front of the ears. About 7 out of 10 salivary gland tumors start here. Most of these tumors are benign (non-cancerous), but the parotid gland is still where most malignant (cancerous) salivary gland tumors start.

The submandibular glands are smaller and are found at the back of the jaw. They secrete saliva under the tongue area. About 1 or 2 out of 10 tumors start in these glands, and about half of these tumors are benign.

The sublingual glands, which are the smallest, are found under the floor of the mouth and below either side of the tongue. Tumors starting in these glands are rare.

In addition, there are several hundred minor salivary glands that are too small to see without a microscope. These glands are located beneath the lining of the lips, tongue, hard and soft palate, and inside the cheeks, nose, sinuses, and larynx (voice box). Tumors in these glands are uncommon, but they are more often malignant than benign. Cancers of the minor salivary glands most often occur in the roof of the mouth (hard and soft palate).

Benign salivary gland tumors

Most salivary gland tumors are benign -- that is, they are not cancerous and do not spread from the salivary gland to other parts of the body. They are almost never life threatening.

There are several types of benign salivary gland tumors, with names such as adenomas, oncocytomas, Warthin tumors, and benign mixed tumors (also known as pleomorphic adenomas).

Benign tumors are almost always cured by surgery. Very rarely, they may become malignant (cancerous) if left untreated for a long time or if they are not completely removed and recur (grow back) several times. How benign tumors become cancers is poorly understood.

Only malignant tumors of the salivary glands will be discussed further in this document.

Salivary gland cancers (malignant salivary gland tumors)

There are many types of salivary gland cancers. Normal salivary glands are made up of several different types of cells, and tumors can start in any of these cell types. Salivary gland tumors are named according to which of these cell types they most look like when viewed under a microscope. The main types of cancers are described below.

There is also a wide range in how quickly salivary gland cancers may grow and spread, with some types tending to grow faster than others. Doctors usually give these cancers a grade (from 1 to 3, or from low to high), based on how abnormal the cancers look under a microscope. The grade gives a rough idea of how quickly the cancer is likely to grow and spread.

Grade 1 cancers (also called low grade or well differentiated) look very much like normal salivary gland cells. They tend to grow slowly and have a good outcome.

Grade 2 cancers (also called intermediate grade or moderately differentiated) have an appearance and outlook that is between grade 1 and grade 3 cancers.

Grade 3 cancers (also called high grade or poorly differentiated) look quite different from normal cells and often grow and/or spread quickly. The outlook (prognosis) for these cancers is usually not as good as for lower grade cancers.

Mucoepidermoid carcinoma : Mucoepidermoid carcinomas are the most common type of salivary gland cancer. Most start in the parotid glands. They develop less often in the submandibular glands or in minor salivary glands inside the mouth. These cancers are usually low grade, but they can also be intermediate or high grade. Low-grade mucoepidermoid tumors have a much better prognosis than high-grade ones.

Adenoid cystic carcinoma : Adenoid cystic carcinoma is usually slow growing and often appears to be low-grade when looked at under the microscope. Still, it is very hard to completely get rid of because it tends to spread along nerves. Adenoid cystic carcinomas tend to come back after treatment (generally surgery and radiation), sometimes many years later. The outlook for patients is better for smaller tumors.

Adenocarcinomas : Adenocarcinoma is a term used to describe cancers that start in gland cells (cells that normally secrete a substance). There are many types of salivary gland adenocarcinomas.

Acinic cell carcinoma: Most acinic cell carcinomas start in the parotid gland. They tend to be slow growing and tend to occur at a younger age than most salivary gland cancers. They are usually low grade, but how far they have grown into nearby tissue is probably a better predictor of a patient's prognosis (outlook).

Polymorphous low-grade adenocarcinoma (PLGA): These tend to start in the minor salivary glands. These are usually low grade (as the name states) and are mostly curable.

Adenocarcinoma, not otherwise specified (NOS): When viewed under a microscope, these cancers have enough features to tell that they are adenocarcinomas, but not enough detail to classify them further. They are most common in the parotid glands and the minor salivary glands. These tumors can be of any grade.

Rare adenocarcinomas: Several types of adenocarcinoma are quite rare. Many of these tumor types tend to be low grade and usually have a very good outcome:

Basal cell adenocarcinoma

Clear cell carcinoma

Cystadenocarcinoma

Sebaceous adenocarcinoma

Sebaceous lymphadenocarcinoma

Mucinous adenocarcinoma

Other rare adenocarcinomas are more likely to be high grade and may have a less favorable outcome:

Oncocytic carcinoma

Salivary duct carcinoma

Malignant mixed tumors :  There are 3 types of malignant mixed tumors, carcinoma ex pleomorphic adenoma, carcinosarcomas, andmetastasizing mixed tumor. Carcinoma ex pleomorphic adenoma accounts for the vast majority of these cancers. The other 2 are very, very rare. Carcinoma ex pleomorphic adenoma is a cancer that develops from a benign mixed tumor (also known as a pleomorphic adenoma). This tumor occurs mainly in the major salivary glands. Both the grade of the cancer and how far it has spread (stage) are important in predicting the outcome of this tumor.

Other rare salivary gland cancers

Several other cancer types can develop in the salivary glands.

Squamous cell carcinoma: This cancer occurs mainly in older men. It can develop after radiation therapy for other cancers in the area. This type of cancer tends to have a poorer outlook.

Epithelial-myoepithelial carcinoma: This is a rare tumor. It tends to be low grade, but it can come back after treatment or spread to other parts of the body.

Anaplastic small cell carcinoma: The cells in these tumors have nerve-like features. These tumors are most often found in minor salivary glands and tend to grow quickly.

Undifferentiated carcinomas: This group of cancers includes small cell undifferentiated carcinoma, large cell undifferentiated carcinoma and lymphoepithelial carcinoma. These are high-grade cancers that often spread. Overall, the survival outlook tends to be poor. Lymphoepithelial carcinoma, which is much more common in Eskimo and Inuit people, has a slightly better outcome.

Other cancers that can affect the salivary glands

Non-Hodgkin lymphoma: Most non-Hodgkin lymphomas start in lymph nodes. Rarely, these cancers start in immune system cells within the salivary glands. They behave and are treated differently than other types of cancer in the salivary glands. Most lymphomas that start in the salivary glands affect people with Sjögren's syndrome (a disorder that causes immune system to attack salivary gland cells). For more information on lymphomas, see our document called Non-Hodgkin Lymphoma.

Sarcomas: The salivary glands contain blood vessels, muscle cells, and cells that make connective tissue. Cancers that start in these types of cells are called sarcomas. These rarely occur in the salivary gland. For more information on sarcomas, 

Secondary salivary gland cancers: Cancers that start elsewhere and spread to the salivary glands are called secondary salivary gland cancers. These cancers are not true salivary gland cancers, and are treated based on where the cancer started.

What are the risk factors for salivary gland cancer?

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for cancers of the lung, larynx (voice box), mouth, throat, esophagus (tube that carries food to the stomach), kidneys, bladder, and several other organs.

But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you will definitely get the disease. And many people who get the disease may not have had any known risk factors. Even if a person has one or more risk factors, it is not possible to know for sure how much that risk factor contributed to causing the cancer.

Scientists have found few risk factors that make a person more likely to develop salivary gland cancer.

Radiation exposure :  Radiation treatment to the head and neck area for other medical reasons increases your risk of salivary gland cancer. Workplace exposure to certain radioactive substances may also increase the risk of salivary gland cancer.

Family history : Very rarely, members of some families seem to have a higher than usual risk of developing salivary gland cancers.

Other possible risk factors

Certain workplace exposures : Some studies have suggested that working with certain metals (nickel alloy dust) or minerals (silica dust) may increase the risk for salivary gland cancer, but these links are not certain. The rarity of these cancers makes this a difficult area to study.

Tobacco and alcohol use : Tobacco and alcohol can increase the risk for several cancers of the head and neck area, but they have not been strongly linked to salivary gland cancers in most studies.

Diet : Some studies have found that a diet low in vegetables and high in animal fat may increase the risk of salivary gland cancer, but more research is needed to confirm this possible link.

Cell phones :  One study suggested an increased risk of parotid gland tumors among heavy cell phone users. In this study, most of the tumors seen were benign (not cancer). Other studies looking at this issue have not found such a link. Research in this area is still in progress. If there is any excess risk, it could be decreased by using corded or cordless earpieces that move the device away from the user's head and decrease the amount of radiation that reaches the body.

Do we know what causes salivary gland cancer?

We know very little about the actual causes of most salivary gland cancers. Researchers have found that some salivary gland cancers have DNA abnormalities.

DNA is the chemical in each of our cells that makes up our genes -- the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look. It also can influence our risk for developing certain diseases, such as some kinds of cancer.

Some genes contain instructions for controlling when cells grow and divide. Genes that promote cell division are calledoncogenes. Genes that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

Exposure to radiation or certain carcinogens (cancer-causing chemicals) may result in these DNA changes, but in most cases of salivary gland cancer their cause is not known.

Can salivary gland cancer be prevented?

Because we do not know what causes most salivary gland cancers, it is not yet possible to prevent all of them. Avoiding certain risk factors (tobacco, excessive alcohol use, unhealthy diets) may slightly lower the likelihood of developing salivary gland cancer, but this is not certain. However, avoiding these factors is known to reduce the risk of other, more common cancers, as well as many other diseases.

People who work with radioactive substances, silica dust, and nickel alloy dust should take precautions to protect themselves against exposure to these materials.

These precautions may lower a person's risk of developing salivary gland cancer.

Can salivary gland cancer be found early?

Salivary gland cancer is uncommon, so doctors do not recommend testing for it unless someone has symptoms. Still, because of its location, in many cases salivary gland cancer can be found early. Often patients, their dentists, or their doctors notice a mass or lump within one of the salivary glands (usually on the sides of the face or in the mouth). Checking the salivary glands for lumps is often a routine part of general medical and dental checkups.

Being alert to certain symptoms and not ignoring them might help find salivary gland cancers early, when treatment is likely to be most effective.

How is salivary gland cancer diagnosed?

Salivary gland cancer is most often diagnosed when a patient goes to a doctor because of symptoms.

Signs and symptoms of salivary gland cancer

The major salivary glands are located on the sides of the face and below the tongue. Several important nerves and other structures run through or near salivary glands and can be affected by salivary tumors. Possible signs and symptoms of salivary gland cancer include:

A mass or lump in your face, neck, or mouth

Ongoing pain in one place in your face, neck, or mouth

A newly noticed difference between the size and/or shape of the left and right sides of your face or neck

Numbness in part of your face

New weakness of the muscles on one side of your face

Trouble swallowing

These are symptoms and signs of salivary gland cancer, but they may also be caused by other conditions. Still, if you have any of these problems, it's important to see your doctor right away so the cause can be found and treated, if needed.

Medical history and physical exam

If you have any signs or symptoms that suggest you might have a salivary gland tumor, your doctor will want to take a complete medical history to check for symptoms and risk factors, including your family history.

Medical history :  The first step is to take your complete medical history, in which the doctor asks you questions about risk factors and symptoms that might suggest salivary gland cancer. You will also be asked about your general health.

Physical exam :  A physical exam provides information about your general health, possible signs of salivary gland cancer, and other health problems. During your physical exam, your doctor will carefully examine your mouth and the areas on the sides of your face and around your jaw, and will look for enlarged lymph nodes in your neck area since these could be signs of cancer spread.

The doctor will also examine you for numbness or muscle weakness in part of your face (which can happen when cancer spreads into nerves) and any other related problem that you may be having.

If the results of this exam are abnormal, your doctor may order imaging tests or refer you to an otolaryngologist (a doctor specializing in ear, nose, and throat problems).

Imaging tests : Imaging tests use x-rays, magnetic fields, sound waves, or radioactive particles to create pictures of the inside of your body. Imaging tests may be done for a number of reasons, including to help find a suspicious area that might be cancerous, to learn how far cancer may have spread, and to help find out if treatment has been effective.

X-rays :  If you have a mass near the jaw, your doctor may order x-rays of the jaws and teeth to look for a tumor.

If you have been diagnosed with cancer, an x-ray of your chest may be done to see if the cancer has spread to your lungs. It also provides other information about your heart and lungs that might be useful if surgery is planned.

Computed tomography (CT or CAT) scan

A CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these into images of slices of the part of your body that is being studied. CT scans provide better detail about soft tissues than standard x-rays and can often detect tumors.

Before any pictures are taken, you may be asked to drink 1 to 2 pints of a liquid called oral contrast. This helps outline the intestine so that certain areas are not mistaken for tumors. This is most often needed for CT scans of the abdomen or pelvis. You may also receive an IV (intravenous) line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures in your body.

The injection can cause some flushing (redness and warm feeling). Some people are allergic and get hives or, rarely, more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.

You need to lie still on a table while the scan is being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in while the pictures are being taken.

The CT scan can provide information about the size, shape, and position of a tumor and can help find enlarged lymph nodes that might contain cancer. If needed, CT scans can also be used to look for tumors in other parts of the body.

Magnetic resonance imaging (MRI) : Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into very detailed images of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan.

MRI scans provide detailed images of soft tissues, so they can be helpful in determining the exact location and extent of a tumor. Sometimes they can help a doctor tell a benign tumor from a malignant one.

MRI scans may be a little more uncomfortable than CT scans. They take longer -- often up to an hour. You may be placed inside a large cylindrical tube, which is confining and can upset people with a fear of enclosed spaces. Special open MRI machines can help with this if needed. The MRI machine makes buzzing and clicking noises that you may find disturbing. Some places will provide earplugs or headphones to help block this out.

Positron emission tomography (PET) scan : PET scans involve injecting glucose (a form of sugar) that contains a radioactive atom into the blood. The amount of radioactivity used is very low. Cancer cells in the body are growing rapidly, so they absorb large amounts of the radioactive sugar. A special camera can then be used to create a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it can provide helpful information about your whole body.

A PET scan can help give the doctor a better idea of whether an abnormal lump or a mass seen on another imaging test may be cancer. If you have been diagnosed with cancer, your doctor may use this test to see if the cancer has spread to lymph nodes. A PET scan can also be useful if your doctor thinks the cancer may have spread but doesn't know where.

Some machines are able to perform both a PET and CT scan at the same time (PET/CT scan). This allows the doctor to compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT.

Biopsy : Symptoms and the results of exams or imaging tests may strongly suggest that salivary gland cancer is present, but the actual diagnosis is made by removing cells from an abnormal area and looking at them under a microscope. This is known as a biopsy. Different types of biopsies may be done, depending on the situation.

Fine needle aspiration (FNA) biopsy : This type of biopsy can be done in a doctor's office or clinic. It is done with a hollow needle similar to those used for routine blood tests. Your doctor may first numb the area over the tumor with local anesthesia. The doctor then places the needle directly into the tumor mass for about 10 seconds and pulls cells and a few drops of fluid into a syringe. The cells are then viewed under a microscope by a specialist in diagnosing cancer (pathologist) to find out if they are malignant (cancerous).

Doctors may use FNA if they are not sure whether a mass is a salivary gland cancer. If the FNA shows the mass is due to an infection or is a kind of cancer that can be treated without surgery, then an unnecessary operation can sometimes be avoided.

An FNA biopsy is only helpful if enough representative cells are removed to be able to tell for certain what a mass is made of. But sometimes a biopsy is read as negative even when cancer is present. This most often occurs when the area biopsied is inflamed and full of immune system cells or when too few cells are removed to make a diagnosis.

Incisional biopsy : This type of biopsy may sometimes be done if the FNA does not get enough material to examine. In this procedure, the surgeon numbs the area over the tumor, makes a small incision and removes a tiny part of the tumor. The specimen is sent to the lab to be looked at by the pathologist. These types of biopsies are not done often for salivary gland tumors.

Surgery : As mentioned above, FNA biopsy of salivary gland cancers may not always provide an answer. If this is the case but the physical exam and imaging tests suggest that cancer may be present, the doctor may advise surgery to completely remove the mass. This can both provide enough of a sample for a diagnosis and treat the tumor at the same time. 

In some cases if the exams and tests suggest cancer is likely, the doctor may skip the FNA biopsy altogether and go directly to surgically removing the tumor. The specimen is then sent to the lab to confirm the diagnosis.

How is salivary gland cancer staged?

Staging is the process of finding out how far a cancer has spread. The stage of salivary gland cancer is one of the most important factors in selecting treatment options and estimating a patient's outlook for recovery (prognosis).

The stage of a cancer is determined from the results of physical exams, imaging tests (ultrasound, CT or MRI scan, etc.) and other tests, which are described in the section called “How is salivary gland cancer diagnosed?,” and by the results of surgery if it has been done.

The American Joint Committee on Cancer (AJCC) TNM system

A staging system is a standardized way for the cancer care team to summarize information about how far a cancer has spread. The most common system used to describe the stages of salivary gland cancers is the TNM system of the American Joint Committee on Cancer (AJCC). This system contains 3 key pieces of information:

T describes the size of the primary tumor and whether it has invaded into nearby organs or tissues.

N describes whether the cancer has spread to nearby (regional) lymph nodes (bean-sized collections of immune system cells located throughout the body).

M indicates whether the cancer has metastasized (spread) to other organs of the body (The most common site of distant salivary gland cancer spread is the lungs).

Numbers or letters appear after T, N, and M to provide more details about each of these factors:

The numbers 0 through 4 indicate increasing severity.

The letter X means "cannot be assessed" because the information is not available.

T groups for major salivary gland cancers

TX: The main (primary) tumor cannot be assessed; information not known.

T0: No evidence of a primary tumor.

T1: Tumor is 2 cm (about ¾ inch) across or smaller. It is not growing into nearby tissues.

T2: Tumor is larger than 2 cm but no larger than 4 cm (about 1½ inch) across. It is not growing into nearby tissues.

T3: Tumor is larger than 4 cm across and/or is growing into nearby soft tissues.

T4a: Tumor is any size and is growing into nearby structures such as the jaw bone, skin, ear canal, and/or facial nerve. This is known as moderately advanced disease.

T4b: Tumor is any size and is growing into nearby structures such as the base of the skull or other bones nearby, or it surrounds the carotid artery. This is known as very advanced disease.

N groups for major salivary gland cancers

NX: Nearby (regional) lymph nodes cannot be assessed; information not known.

N0: No spread to regional lymph nodes.

N1: The cancer has spread to 1 lymph node on the same side of the head or neck as the primary tumor. The lymph node is smaller than 3 cm (about 1¼ inch) across.

N2: This group includes 3 subgroups:

N2a: The cancer has spread to 1 lymph node on the same side as the primary tumor. The lymph node is larger than 3 cm but not larger than 6 cm (about 2½ inches) across.

N2b: The cancer has spread to more than 1 lymph node on the same side as the primary tumor, none of the lymph nodes are larger than 6 cm across.

N2c: The cancer has spread to 1 or more lymph nodes, none larger than 6 cm across, either on the side opposite the primary tumor or on both sides of the neck.

N3: The cancer has spread to a lymph node that is larger than 6 cm across.

M groups for major salivary gland cancers

M0: The cancer has not spread to tissues or organs far away from the salivary glands.

M1: The cancer has spread to tissues or organs far away from the salivary glands.

Stage grouping

Once the T, N, and M categories have been assigned, this information is combined in a process called stage grouping to assign an overall stage. The stage is expressed in Roman numerals from I (the least advanced) to IV (the most advanced). Some stages are subdivided with letters.

Stage I: T1, N0, M0: The tumor is no more than 2 cm (about ¾ inch) across and is not growing into nearby tissues (T1). It has not spread to nearby lymph nodes (N0) or distant sites (M0).

Stage II: T2, N0, M0: The tumor is larger than 2 cm but is no larger than 4 cm across and is not growing into nearby tissues (T2). It has not spread to nearby lymph nodes (N0) or distant sites (M0).

Stage III: Either of the following:

T3, N0, M0: The tumor is larger than 4 cm across and/or is growing into nearby soft tissues (T3). It has not spread to nearby lymph nodes (N0) or to distant sites (M0).

OR

T1 to T3, N1, M0: The tumor is any size and may have grown into nearby soft tissues (T1 to T3). The cancer has spread to one lymph node on the same side of the head or neck as the primary tumor, but the lymph node is no larger than 3 cm across (N1). The cancer has not spread to distant sites (M0).

Stage IVA: Either of the following:

T4a, N0 or N1, M0: The tumor is any size but invades nearby structures such as the jaw bone, skin, ear canal, and/or facial nerve (T4a). It may or may not have spread to one lymph node (no larger than 3 cm across) on the same side of the head or neck as the primary tumor (N0 or N1). The cancer has not spread to distant sites (M0).

OR

T1 to T4a, N2, M0: The tumor is any size and may or may not invade nearby soft tissues or structures such as the jaw bone, skin, ear canal, and/or facial nerve (T1 to T4a). The cancer has spread to more than one lymph node, to a lymph node larger than 3 cm across, or to lymph nodes on the other or both sides of the neck. None of the lymph nodes are larger than 6 cm across (N2). The cancer has not spread to distant sites (M0).

Stage IVB: Either of the following:

T4b, Any N, M0: The tumor is any size and invades nearby structures such as the base of the skull or other bones nearby, or it surrounds the carotid artery (T4b). The cancer may or may not have spread to nearby lymph nodes (any N). It has not spread to distant sites (M0).

OR

Any T, N3, M0: The tumor is any size and may or may not have invaded nearby soft tissues or other structures (any T). The cancer has spread to at least 1 lymph node that is larger than 6 cm across (N3). It has not spread to distant sites (M0).

Stage IVC: Any T, Any N, M1: The tumor is any size and may or may not have invaded nearby soft tissues or other structures (any T). The cancer may or may not have spread to nearby lymph nodes (any N). It has spread to distant sites (M1).

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