Salivary Gland Cancer

  • Dana-Farber/Brigham and Women's Cancer Care

    Salivary gland cancer is a rare cancer that forms in tissues of the gland in the mouth that makes saliva. Most salivary gland cancers occur in older people. Learn about salivary gland cancer and find information on how we support and care for adults with salivary gland cancer before, during, and after treatment.

Treatment 

The Head and Neck Oncology Program is dedicated exclusively to treating patients with head and neck cancers, which include cancers of the throat, larynx, nose, sinuses, and mouth.

Our specialists evaluate and treat all types and stages, from early lesions to the rarest and most challenging cases.  We also specialize in the treatment of all forms and stages of salivary gland and thyroid cancer.

As a patient, you will be seen by highly experienced clinicians from numerous specialties, including head and neck surgery, medical and radiation oncology, dentistry, oral surgery, reconstructive surgery, nutrition services, social work, speech, voice, and swallowing therapy.

Beginning with the initial consultation, your team of specialists will work with you to create a comprehensive treatment plan tailored to your type of cancer, as well as your lifestyle and personal needs, to achieve the best possible outcome.

Providers meet regularly to discuss new developments in clinical and basic research. The close relationships between world-class researchers and medical clinicians ensure that the latest research findings are translated into new, effective treatment approaches as quickly as possible.

Learn more about treatment and support for patients with head and neck cancers 

Our clinicians are experts in treating all types of head and neck cancers, including: 

  • Hypopharyngeal cancer
  • Laryngeal cancer
  • Nasopharyngeal cancer
  • Oral cancer
  • Oral cavity cancer
  • Oropharyngeal cancer
  • Paranasal sinus and nasal cavity cancer
  • Pharyngeal cancer
  • Laryngeal cancer
  • Lip cancer
  • Ear and Temporal Bone cancer
  • Skull Base cancer
  • Head and Neck Sarcomas
  • Mandible and jaw cancer
  • Adult craniopharyngioma
  • Unknown primary cancer
  • Merkel cell carcinoma
  • Head and Neck Melanoma
  • Salivary gland cancer
  • Parotid gland cancer
  • Acinic cell cancer
  • Adenoidcystic carcinoma
  • Mucoepidermoid cancer
  • Adenocarcinoma cancer
  • Papillary thyroid cancer
  • Follicular thyroid cancer
  • Anaplastic thyroid cancer
  • Medullary thyroid cancer
  • Hurthle cell cancer

Contact us 

New patients 

If you have never been seen before at Dana-Farber/Brigham and Women’s Cancer Center, please call 877-442-3324 or use this online form to make an appointment.

For all other inquiries, please call 617-632-3090

Referring physicians: 617-632-6869

Fax: 617-632-4448

Mailing address
Head and Neck Oncology Center
Dana-Farber Cancer Institute
450 Brookline Ave.
Boston, MA 02115-5450

Information for: Patients | Healthcare Professionals

General Information About Salivary Gland Cancer

Salivary gland cancer is a rare disease in which malignant (cancer) cells form in the tissues of the salivary glands.

The salivary glands make saliva and release it into the mouth. Saliva has enzymes that help digest food and antibodies that help protect against infections of the mouth and throat. There are 3 pairs of major salivary glands:

  • Parotid glands: These are the largest salivary glands and are found in front of and just below each ear. Most major salivary gland tumors begin in this gland.
  • Sublingual glands: These glands are found under the tongue in the floor of the mouth.
  • Submandibular glands: These glands are found below the jawbone.
Anatomy of the salivary glands; drawing shows a cross section of the head  and the three main pairs of  salivary glands. The parotid glands  are in front of and just below each ear; the sublingual glands are under the tongue in the floor of the mouth; the submandibular glands are below each side of the jawbone. The tongue and lymph nodes are also shown.
Anatomy of the salivary glands. The three main pairs of salivary glands are the parotid glands, the sublingual glands, and the submandibular glands.

There are also hundreds of small (minor) salivary glands lining parts of the mouth, nose, and larynx that can be seen only with a microscope. Most small salivary gland tumors begin in the palate (roof of the mouth).

More than half of all salivary gland tumors are benign (not cancerous) and do not spread to other tissues.

Salivary gland cancer is a type of head and neck cancer.

Being exposed to certain types of radiation may increase the risk of salivary cancer.

Anything that increases the chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Although the cause of most salivary gland cancers is not known, risk factors include the following:

  • Older age.
  • Treatment with radiation therapy to the head and neck.
  • Being exposed to certain substances at work.

Possible signs of salivary gland cancer include a lump or trouble swallowing.

Salivary gland cancer may not cause any symptoms. It is sometimes found during a regular dental check-up or physical exam. Symptoms caused by salivary gland cancer also may be caused by other conditions. Check with your doctor if you have any of the following problems:

  • A lump (usually painless) in the area of the ear, cheek, jaw, lip, or inside the mouth.
  • Fluid draining from the ear.
  • Trouble swallowing or opening the mouth widely.
  • Numbness or weakness in the face.
  • Pain in the face that does not go away.

Tests that examine the head, neck, and the inside of the mouth are used to detect (find) and diagnose salivary gland cancer.

The following procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health. The head, neck, mouth, and throat will be checked for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
  • Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. For salivary gland cancer, an endoscope is inserted into the mouth to look at the mouth, throat, and larynx. An endoscope is a thin, tube-like instrument with a light and a lens for viewing.
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
    • Fine needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle. An FNA is the most common type of biopsy used for salivary gland cancer.
    • Incisional biopsy: The removal of part of a lump or a sample of tissue that doesn’t look normal.
    • Surgery: If cancer cannot be diagnosed from the sample of tissue removed during an FNA biopsy or an incisional biopsy, the mass may be removed and checked for signs of cancer.

Because salivary gland cancer can be hard to diagnose, patients should ask to have the tissue samples checked by a pathologist who has experience in diagnosing salivary gland cancer.

Certain factors affect treatment options and prognosis (chance of recovery).

The treatment options and prognosis (chance of recovery) depend on the following:

  • The stage of the cancer (especially the size of the tumor).
  • The type of salivary gland the cancer is in.
  • The type of cancer cells (how they look under a microscope).
  • The patient's age and general health.

Stages of Salivary Gland Cancer

After salivary gland cancer has been diagnosed, tests are done to find out if cancer cells have spread within the salivary gland or to other parts of the body.

The process used to find out if cancer has spread within the salivary glands or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following procedures may be used in the staging process:

  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if salivary gland cancer spreads to the lung, the cancer cells in the lung are actually salivary gland cancer cells. The disease is metastatic salivary gland cancer, not lung cancer.

The following stages are used for major salivary gland cancers:

Tumor size compared to everyday objects; shows various measurements of a tumor compared to a pea, peanut, walnut, and lime
Pea, peanut, walnut, and lime show tumor sizes.

Stage I

In stage I, the tumor is in the salivary gland only and is 2 centimeters or smaller.

Stage II

In stage II, the tumor is in the salivary gland only and is larger than 2 centimeters but not larger than 4 centimeters.

Stage III

In stage III, one of the following is true:

  • The tumor is not larger than 4 centimeters and has spread to a single lymph node on the same side as the tumor and the lymph node is 3 centimeters or smaller.
  • The tumor is larger than 4 centimeters and/or has spread to soft tissue around the affected gland. Cancer may have spread to a single lymph node on the same side as the tumor and the lymph node is 3 centimeters or smaller.

Stage IV

Stage IV is divided into stages IVA, IVB, and IVC as follows:

  • Stage IVA:
    • The tumor may be any size and may have spread to soft tissue around the affected gland. Cancer has spread to a single lymph node on the same side as the tumor and the lymph node is larger than 3 centimeters but not larger than 6 centimeters, or has spread to more than one lymph node on either or both sides of the body and the lymph nodes are not larger than 6 centimeters; or
    • Cancer has spread to the skin, jawbone, ear canal, and/or facial nerve, and may have spread to one or more lymph nodes on either or both sides of the body. The lymph nodes are not larger than 6 centimeters.
  • Stage IVB:
    • The tumor may be any size and may have spread to soft tissue around the affected gland. Cancer has spread to a lymph node larger than 6 centimeters; or
    • Cancer has spread to the base of the skull and/or the carotid artery, and may have spread to one or more lymph nodes of any size on either or both sides of the body.
  • Stage IVC:
    • The tumor may be any size and may have spread to soft tissue around the affected gland, to the skin, jawbone, ear canal, facial nerve, base of the skull, or carotid artery, or to one or more lymph nodes on either or both sides of the body. Cancer has spread to distant parts of the body.

Salivary gland cancers are also grouped by grade. The grade of a tumor tells how fast the cancer cells are growing, based on how the cells look under a microscope. Low-grade cancers grow more slowly than high-grade cancers.

Minor salivary gland cancers are staged according to where they were first found in the body.

Recurrent Salivary Gland Cancer

Recurrentsalivary gland cancer is cancer that has recurred (come back) after it has been treated. Recurrent salivary gland cancer may come back in the salivary glands or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with salivary gland cancer.

Different types of treatment are available for patients with salivary gland cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Patients with salivary gland cancer should have their treatment planned by a team of doctors who are experts in treating head and neck cancer.

Your treatment will be overseen by a medical oncologist, a doctor who specializes in treating people with cancer. Because the salivary glands help in eating and digesting food, patients may need special help adjusting to the side effects of the cancer and its treatment. The medical oncologist may refer you to other doctors who have experience and expertise in treating patients with head and neck cancer and who specialize in certain areas of medicine. These include the following:

  • Head and neck surgeon.
  • Radiation oncologist.
  • Dentist.
  • Speech therapist.
  • Dietitian.
  • Psychologist.
  • Rehabilitation specialist.
  • Plastic surgeon.

Three types of standard treatment are used:

Surgery

Surgery (removing the cancer in an operation) is a common treatment for salivary gland cancer. A doctor may remove the cancer and some of the healthy tissue around the cancer. In some cases, a lymphadenectomy (surgery in which lymph nodes are removed) will also be done.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given radiation therapy after surgery to kill any cancer cells that are left. Treatment given after surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Special types of radiation may be used to treat some salivary gland tumors. These include:

  • Fast neutron radiation therapy: Fast neutron radiation therapy is a type of high-energy external radiation therapy. A radiation therapy machine aims tiny, invisible particles, called neutrons, at the cancer cells to kill them. Fast neutron radiation therapy uses a higher-energy radiation than the x-ray type of radiation therapy. This allows the radiation therapy to be given in fewer treatments.
  • Photon-beam radiation therapy: A type of radiation therapy that reaches deep tumors with high-energy x-rays made by a machine called a linear accelerator. This can be delivered as hyperfractionated radiation therapy, in which the total dose of radiation is divided into small doses and the treatments are given more than once a day.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Head and Neck Cancer for more information. (Salivary gland cancer is a type of head and neck cancer.)

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Radiosensitizers

Radiosensitizers are drugs that make tumor cells more sensitive to radiation therapy. Combining radiation therapy with radiosensitizers may kill more tumor cells.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

Stage I Salivary Gland Cancer

Treatment for stage I salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

  • Surgery with or without radiation therapy.
  • Fast neutron radiation therapy.

If the cancer is high-grade, treatment may include the following:

  • Surgery with or without radiation therapy.
  • A clinical trial of chemotherapy.
  • A clinical trial of a new local therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I salivary gland cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage II Salivary Gland Cancer

Treatment for stage II salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

  • Surgery with or without radiation therapy.
  • Radiation therapy.
  • Chemotherapy.

If the cancer is high-grade, treatment may include the following:

  • Surgery with or without radiation therapy.
  • Fast neutron or photon-beam radiation therapy.
  • A clinical trial of radiation therapy and/or radiosensitizers.
  • A clinical trial of chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II salivary gland cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage III Salivary Gland Cancer

Treatment for stage III salivary gland cancer depends on whether the cancer is low-grade (slow growing) or high-grade (fast growing).

If the cancer is low-grade, treatment may include the following:

  • Surgery with or without lymphadenectomy. Radiation therapy may also be given after surgery.
  • Radiation therapy.
  • Fast neutron radiation therapy to lymph nodes with cancer.
  • Chemotherapy.
  • A clinical trial of fast neutron radiation therapy to the tumor.
  • A clinical trial of chemotherapy.

If the cancer is high-grade, treatment may include the following:

  • Surgery with or without lymphadenectomy. Radiation therapy may also be given after surgery.
  • Fast neutron radiation therapy.
  • Radiation therapy as palliative therapy to relieve symptoms and improve quality of life.
  • A clinical trial of radiation therapy and/or radiosensitizers.
  • A clinical trial of chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III salivary gland cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IV Salivary Gland Cancer

Treatment of stage IV salivary gland cancer may include the following:

  • Fast neutron or photon-beam radiation therapy.
  • A clinical trial of chemotherapy with or without radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV salivary gland cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Salivary Gland Cancer

Treatment of recurrentsalivary gland cancer may include the following:

  • Radiation therapy.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent salivary gland cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Salivary Gland Cancer

For more information from the National Cancer Institute about salivary gland cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on December 26, 2013.


General Information About Salivary Gland Cancer

Related Summaries

Note: Other PDQ summaries containing information related to salivary gland cancer include the following:

  • Hypopharyngeal Cancer Treatment
  • Laryngeal Cancer Treatment
  • Lip and Oral Cavity Cancer Treatment
  • Nasopharyngeal Cancer Treatment
  • Paranasal Sinus and Nasal Cavity Cancer Treatment

Salivary gland tumors are a morphologically and clinically diverse group of neoplasms, which may present significant diagnostic and management challenges. These tumors are rare, with an overall incidence in the Western world of approximately 2.5 cases to 3.0 cases per 100,000 per year.[1] Malignant salivary gland neoplasms account for more than 0.5% of all malignancies and approximately 3% to 5% of all head and neck cancers.[1][2] Most patients with malignant salivary gland tumors are in the sixth or seventh decade of life.[3][4] Although exposure to ionizing radiation has been implicated as a cause of salivary gland cancer, the etiology of most salivary gland cancers cannot be determined.[2][3][5][6] Occupations associated with an increased risk for salivary gland cancers include rubber products manufacturing, asbestos mining, plumbing, and some types of woodworking.[3]

Tumors of the salivary glands comprise those in the major glands (e.g., parotid, submandibular, and sublingual) and the minor glands (e.g., oral mucosa, palate, uvula, floor of mouth, posterior tongue, retromolar area and peritonsillar area, pharynx, larynx, and paranasal sinuses).[2][7] Minor salivary gland lesions are most frequently seen in the oral cavity.[2]

Of salivary gland neoplasms, more than 50% are benign, and approximately 70% to 80% of all salivary gland neoplasms originate in the parotid gland.[1][2][8] The palate is the most common site of minor salivary gland tumors. The frequency of malignant lesions varies by site. Approximately 20% to 25% of parotid tumors, 35% to 40% of submandibular tumors, 50% of palate tumors, and more than 90% of sublingual gland tumors are malignant.[1][9]

Histologically, salivary gland tumors represent the most heterogenous group of tumors of any tissue in the body.[10] Although almost 40 histologic types of epithelial tumors of the salivary glands exist, some are exceedingly rare and may be the subject of only a few case reports.[1][11] The most common benign major and minor salivary gland tumor is the pleomorphic adenoma, which comprises about 50% of all salivary gland tumors and 65% of parotid gland tumors.[1] The most common malignant major and minor salivary gland tumor is the mucoepidermoid carcinoma, which comprises about 10% of all salivary gland neoplasms and approximately 35% of malignant salivary gland neoplasms.[1][12] This neoplasm occurs most often in the parotid gland.[2][12][13] This type and other histologic types of salivary gland neoplasms are reviewed in detail in the Cellular Classification of Salivary Gland Treatment section of this summary.

Most patients with benign tumors of the major or minor salivary glands present with painless swelling of the parotid, submandibular, or the sublingual glands. Neurological signs, such as numbness or weakness caused by nerve involvement, typically indicate a malignancy.[2] Facial nerve weakness that is associated with a parotid or submandibular tumor is an ominous sign. Persistent facial pain is highly suggestive of malignancy; approximately 10% to 15% of malignant parotid neoplasms present with pain.[8][14] (Refer to the PDQ summary on Pain for more information.) The majority of parotid tumors, both benign and malignant, however, present as an asymptomatic mass in the gland.[2][8]

Early-stage low-grade malignant salivary gland tumors are usually curable by adequate surgical resection alone. The prognosis is more favorable when the tumor is in a major salivary gland; the parotid gland is most favorable, then the submandibular gland; the least favorable primary sites are the sublingual and minor salivary glands. Large bulky tumors or high-grade tumors carry a poorer prognosis and may best be treated by surgical resection combined with postoperative radiation therapy.[15] The prognosis also depends on the following:[16][17]

  • Gland in which they arise.
  • Histology.
  • Grade (i.e., degree of malignancy).
  • Extent of primary tumor (i.e., the stage).
  • Whether the tumor involves the facial nerve, has fixation to the skin or deep structures, or has spread to lymph nodes or distant sites.

Overall, clinical stage, particularly tumor size, may be the crucial factor to determine the outcome of salivary gland cancer and may be more important than histologic grade.[18]

Perineural invasion can also occur, particularly in high-grade adenoid cystic carcinoma, and should be specifically identified and treated.[19] Radiation therapy may increase the chance of local control and increase the survival of patients when adequate margins cannot be achieved.[20][Level of evidence: 3iiiDii] Unresectable or recurrent tumors may respond to chemotherapy.[21][22][23] Fast neutron-beam radiation therapy or accelerated hyperfractionated photon-beam schedules have been shown to be effective in the treatment of inoperable, unresectable, and recurrent tumors.[24][25][26]

Complications of surgical treatment for parotid neoplasms include facial nerve dysfunction and Frey syndrome also known as gustatory flushing and sweating and the auriculotemporal syndrome.[8] Frey syndrome has been successfully treated with injections of botulinum toxin A.[27][28][29]

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  19. Gormley WB, Sekhar LN, Wright DC, et al.: Management and long-term outcome of adenoid cystic carcinoma with intracranial extension: a neurosurgical perspective. Neurosurgery 38 (6): 1105-12; discussion 1112-3, 1996.

  20. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999.

  21. Borthne A, Kjellevold K, Kaalhus O, et al.: Salivary gland malignant neoplasms: treatment and prognosis. Int J Radiat Oncol Biol Phys 12 (5): 747-54, 1986.

  22. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb.

  23. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996.

  24. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991.

  25. Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992.

  26. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996.

  27. Naumann M, Zellner M, Toyka KV, et al.: Treatment of gustatory sweating with botulinum toxin. Ann Neurol 42 (6): 973-5, 1997.

  28. Arad-Cohen A, Blitzer A: Botulinum toxin treatment for symptomatic Frey's syndrome. Otolaryngol Head Neck Surg 122 (2): 237-40, 2000.

  29. von Lindern JJ, Niederhagen B, Bergé S, et al.: Frey syndrome: treatment with type A botulinum toxin. Cancer 89 (8): 1659-63, 2000.

Cellular Classification of Salivary Gland Cancer

Salivary gland neoplasms are remarkable for their histologic diversity. These neoplasms include benign and malignant tumors of epithelial, mesenchymal, and lymphoid origin. Salivary gland tumors pose a particular challenge to the surgical pathologist. Differentiating benign from malignant tumors may be difficult, primarily because of the complexity of the classification and the rarity of several entities, which may exhibit a broad spectrum of morphologic diversity in individual lesions.[1] In some cases, hybrid lesions may be seen.[2] The key guiding principle to establish the malignant nature of a salivary gland tumor is the demonstration of an infiltrative margin.[1]

The following cellular classification scheme draws heavily from a scheme published by the Armed Forces Institute of Pathology (AFIP).[3] Malignant nonepithelial neoplasms are included in the scheme because these neoplasms comprise a significant proportion of salivary gland neoplasms seen in the clinical setting. For completeness, malignant secondary tumors are also included in the scheme.

Where AFIP statistics regarding the incidence, or relative frequency, of particular histopathologies are cited, some bias may exist because of the AFIP methods of case accrual as a pathology reference service. When possible, other sources are cited for incidence data. Notwithstanding the AFIP data, the incidence of a particular histopathology has been found to vary considerably depending upon the study cited. This variability in reporting may be partially caused by the rare incidence of many salivary gland neoplasms.

Epithelial Neoplasms

The clinician should be aware that several benign epithelial salivary gland neoplasms have malignant counterparts, which are shown below:[3]

  • Pleomorphic adenoma (i.e., mixed tumor) (see carcinoma ex pleomorphic adenoma).
  • Warthin tumor, also known as papillary cystadenoma lymphomatosum.
  • Monomorphic adenomas:
    • Basal cell adenoma (see basal cell adenocarcinoma).
    • Canalicular adenoma.
    • Oncocytoma (see oncocytic carcinoma).
    • Sebaceous adenoma.
    • Sebaceous lymphadenoma (see sebaceous lymphadenocarcinoma).
  • Myoepithelioma (see myoepithelial carcinoma).
  • Cystadenoma (see cystadenocarcinoma).
  • Ductal papillomas.
  • Sialoblastoma.

Histologic grading of salivary gland carcinomas is important to determine the proper treatment approach, though it is not an independent indicator of the clinical course and must be considered in the context of the clinical stage. Clinical stage, particularly tumor size, may be the critical factor to determine the outcome of salivary gland cancer and may be more important than histologic grade.[1] For example, stage I intermediate-grade or high-grade mucoepidermoid carcinomas can be successfully treated, whereas low-grade mucoepidermoid carcinomas that present as stage III disease may have a very aggressive clinical course.[4]

Grading is used primarily for mucoepidermoid carcinomas, adenocarcinomas, not otherwise specified (NOS), adenoid cystic carcinomas, and squamous cell carcinomas.[1][3] Various other salivary gland carcinomas can also be categorized according to histologic grade as follows:[3][5][6][7][8]

Low grade

  • Acinic cell carcinoma.
  • Basal cell adenocarcinoma.
  • Clear cell carcinoma.
  • Cystadenocarcinoma.
  • Epithelial-myoepithelial carcinoma.
  • Mucinous adenocarcinoma.
  • Polymorphous low-grade adenocarcinoma (PLGA).

Low grade, intermediate grade, and high grade

  • Adenocarcinoma, NOS.
  • Mucoepidermoid carcinoma.*
  • Squamous cell carcinoma.

Intermediate grade and high grade

  • Myoepithelial carcinoma.

High grade

  • Anaplastic small cell carcinoma.
  • Carcinosarcoma.
  • Large cell undifferentiated carcinoma.
  • Small cell undifferentiated carcinoma.
  • Salivary duct carcinoma.

*Some investigators consider mucoepidermoid carcinoma to be of only two grades: low grade and high grade.[5]

Salivary gland carcinomas and mixed tumors

  1. Mucoepidermoid carcinoma.
  2. Adenoid cystic carcinoma.
  3. Adenocarcinomas.
    1. Acinic cell carcinoma.
    2. PLGA.
    3. Adenocarcinoma, NOS.
    4. Rare adenocarcinomas.
      1. Basal cell adenocarcinoma.
      2. Clear cell carcinoma.
      3. Cystadenocarcinoma.
      4. Sebaceous adenocarcinoma.
      5. Sebaceous lymphadenocarcinoma.
      6. Oncocytic carcinoma.
      7. Salivary duct carcinoma.
      8. Mucinous adenocarcinoma.
  4. Malignant mixed tumors.
    1. Carcinoma ex pleomorphic adenoma.
    2. Carcinosarcoma.
    3. Metastasizing mixed tumor.
  5. Rare carcinomas.
    1. Primary squamous cell carcinoma.
    2. Epithelial-myoepithelial carcinoma.
    3. Anaplastic small cell carcinoma.
    4. Undifferentiated carcinomas.
      1. Small cell undifferentiated carcinoma.
      2. Large cell undifferentiated carcinoma.
      3. Lymphoepithelial carcinoma.
    5. Myoepithelial carcinoma.
    6. Adenosquamous carcinoma.

Mucoepidermoid carcinoma

Mucoepidermoid carcinoma is a malignant epithelial tumor that is composed of various proportions of mucous, epidermoid (e.g., squamous), intermediate, columnar, and clear cells and often demonstrates prominent cystic growth. It is the most common malignant neoplasm observed in the major and minor salivary glands.[1][9] Mucoepidermoid carcinoma represents 29% to 34% of malignant tumors originating in both major and minor salivary glands.[3][5][10][11] In two large retrospective series, 84% to 93% of cases originated in the parotid gland.[12][13] With regard to malignant tumors of the minor salivary glands, mucoepidermoid carcinoma shows a strong predilection for the lower lip.[3][14] In an AFIP review of civilian cases, the mean age of patients was 47 years, with an age range of 8 years to 92 years.[3] Prior exposure to ionizing radiation appears to substantially increase the risk of developing malignant neoplasms of the major salivary glands, particularly mucoepidermoid carcinoma.[3][13]

Most patients are asymptomatic and present with solitary, painless masses. Symptoms include pain, drainage from the ipsilateral ear, dysphagia, trismus, and facial paralysis.[3] (Refer to the PDQ summary on Pain for more information.)

Microscopic grading of mucoepidermoid carcinoma is important to determine the prognosis.[1][12][15] Mucoepidermoid carcinomas are graded as low grade, intermediate grade, and high grade. Grading parameters with point values include the following:

  • Intracystic component (+2).
  • Neural invasion present (+2).
  • Necrosis present (+3).
  • Mitosis (≥4 per 10 high-power field [+3]).
  • Anaplasia present (+4).

Total point scores are 0 to 4 for low grade, 5 to 6 for intermediate grade, and 7 to 14 for high grade.

In a retrospective review of 243 cases of mucoepidermoid carcinoma of the major salivary glands, a statistically significant correlation was shown between this point-based grading system and outcome for parotid tumors but not for submandibular tumors.[12] Another retrospective study that used this histologic grading system indicated that tumor grade correlated well with prognosis for mucoepidermoid carcinoma of the major salivary glands, excluding submandibular tumors, and minor salivary glands.[13] A modification of this grading system placed more emphasis on features of tumor invasion.[16] Nonetheless, though tumor grade may be useful, stage appears to be a better indicator of prognosis.[3][16]

Cytogenetically, mucoepidermoid carcinoma is characterized by a t(11;19)(q14–21;p12–13) translocation, which is occasionally the sole cytogenetic alteration.[17][18][19] This translocation creates a novel fusion product, MECT1-MAML2, which disrupts a Notch signaling pathway.[20] Notch signaling plays a key role in the normal development of many tissues and cell types, through diverse effects on cellular differentiation, survival, and/or proliferation, and may be involved in a wide variety of human neoplasms.[21]

Rarely, mucoepidermoid carcinoma may originate within the jaws. This tumor type is known as central mucoepidermoid carcinoma.[3] The mandibular to maxillary predilection is approximately 3:1.[22]

Adenoid cystic carcinoma

Adenoid cystic carcinoma, formerly known as cylindroma, is a slow growing but aggressive neoplasm with a remarkable capacity for recurrence.[23] Morphologically, three growth patterns have been described: cribriform, or classic pattern; tubular; and solid, or basaloid pattern. The tumors are categorized according to the predominant pattern.[3][23][24][25] The cribriform pattern shows epithelial cell nests that form cylindrical patterns. The lumina of these spaces contain periodic acid-Schiff (PAS)-positive mucopolysaccharide secretions. The tubular pattern reveals tubular structures that are lined by stratified cuboidal epithelium. The solid pattern shows solid groups of cuboidal cells. The cribriform pattern is the most common, and the solid pattern is the least common.[26] Solid adenoid cystic carcinoma is a high-grade lesion with reported recurrence rates of as much as 100% compared with 50% to 80% for the tubular and cribriform variants.[25]

In a review of its case files, the AFIP found adenoid cystic carcinoma to be the fifth most common malignant epithelial tumor of the salivary glands after mucoepidermoid carcinomas; adenocarcinomas, NOS; acinic cell carcinomas; and PLGA.[3] Other series, however, report adenoid cystic carcinoma to be the second most common malignant tumor with an incidence or relative frequency of approximately 20%.[1] In the AFIP data, this neoplasm constitutes approximately 7.5% of all epithelial malignancies and 4% of all benign and malignant epithelial salivary gland tumors. The peak incidence for this tumor is reported to be in the fourth through sixth decades of life.[3]

This neoplasm typically develops as a slow growing swelling in the preauricular or submandibular region. Pain and facial paralysis develop frequently during the course of the disease and are likely related to the associated high incidence of nerve invasion.[3] (Refer to the PDQ summary on Pain for more information.) Regardless of histologic grade, adenoid cystic carcinomas, with their unusually slow biologic growth, tend to have a protracted course and ultimately a poor outcome, with a 10-year survival reported to be less than 50% for all grades.[1][27] These carcinomas typically show frequent recurrences and late distant metastases.[1][28] Clinical stage may be a better prognostic indicator than histologic grade.[28][29] In a retrospective review of 92 cases, a tumor size larger than 4 cm was associated with an unfavorable clinical course in all cases.[30]

Adenocarcinomas

Acinic cell carcinoma

Acinic cell carcinoma, also known as acinic cell adenocarcinoma, is a malignant epithelial neoplasm in which the neoplastic cells express acinar differentiation. By conventional use, the term acinic cell carcinoma is defined by cytologic differentiation towards serous acinar cells, as opposed to mucous acinar cells, whose characteristic feature is cytoplasmic periodic acid-Schiff (PAS)-positive zymogen-type secretory granules.[3] In AFIP data of salivary gland neoplasms, acinic cell carcinoma is the third most common salivary gland epithelial neoplasm after mucoepidermoid carcinoma and adenocarcinoma, NOS.[3] In these data, acinic cell carcinoma comprised 17% of primary malignant salivary gland tumors or about 6% of all salivary gland neoplasms; more than 80% occur in the parotid gland; women were affected more than men; and the mean age was 44 years. Other studies have reported a relative frequency of acinic cell carcinoma from 0% to 19% of malignant salivary gland neoplasms.[3]

Clinically, patients typically present with a slowly enlarging mass in the parotid region. Pain is a symptom in more than 33% of patients. (Refer to the PDQ summary on Pain for more information.) For acinic cell carcinoma, staging is likely a better predictor of outcome than histologic grading.[3] In a retrospective review of 90 cases, poor prognostic features included pain or fixation; gross invasion; and microscopic features of desmoplasia, atypia, or increased mitotic activity. Neither morphologic pattern nor cell composition was a predictive feature.[31]

PLGA

PLGA is a malignant epithelial tumor that is essentially limited to occurrence in minor salivary gland sites and is characterized by bland, uniform nuclear features; diverse but characteristic architecture; infiltrative growth; and perineural infiltration.[3] In a series of 426 minor salivary gland tumors, PLGA represented 11% of all tumors and 26% of those that were malignant.[32] In minor gland sites, PLGA is twice as frequent as adenoid cystic carcinoma, and among all benign and malignant salivary gland neoplasms, only pleomorphic adenoma and mucoepidermoid carcinoma are more common.[3] In the AFIP case files, more than 60% of tumors occurred in the mucosa of either the soft or hard palates, approximately 16% occurred in the buccal mucosa, and 12% occurred in the upper lip. The average age of patients is reported to be 59 years, with 70% of patients between the ages of 50 and 79 years.[3] The female to male ratio is about 2:1, a proportion greater than for malignant salivary gland tumors in general.[3][33]

PLGA typically presents as a firm, nontender swelling involving the mucosa of the hard and soft palates (i.e., it is often found at their junction), the cheek, or the upper lip. Discomfort, bleeding, telangiectasia, or ulceration of the overlying mucosa may occasionally occur.[3] This salivary gland neoplasm typically runs a moderately indolent course. In a study of 40 cases with long-term follow-up, overall survival was 80% at 25 years.[34] Because of the unpredictable behavior of the tumor, some investigators consider the qualifying term, low grade, to be misleading and instead prefer the term, polymorphous adenocarcinoma.[1]

Adenocarcinoma, NOS

Adenocarcinoma, NOS, is a salivary gland carcinoma that shows glandular or ductal differentiation but lacks the prominence of any of the morphologic features that characterize the other, more specific carcinoma types. The diagnosis of adenocarcinoma, NOS, is essentially one of exclusion. In an AFIP review of cases, adenocarcinoma, NOS, was second only to mucoepidermoid carcinoma in frequency among malignant salivary gland neoplasms.[3] Other series have reported an incidence of 4% to 10%.[1] In AFIP files, the mean patient age was 58 years.[3] Approximately 40% and 60% of tumors occurred in the major and minor salivary glands, respectively. Among the major salivary gland tumors, 90% occurred in the parotid gland. Adenocarcinoma, NOS is graded in a similar way to extrasalivary lesions according to the degree of differentiation.[1] Tumor grades include low grade, intermediate grade, and high-grade categories.[3]

Patients with tumors in the major salivary glands typically present with solitary, painless masses.[35] Two retrospective studies indicate that survival is better for patients with tumors of the oral cavity than for those with tumors of the parotid and submandibular glands.[35][36] These studies differ regarding the prognostic significance of tumor grade.

Rare adenocarcinomas

Basal cell adenocarcinoma

Basal cell adenocarcinoma, also known as basaloid salivary carcinoma, carcinoma ex monomorphic adenoma, malignant basal cell adenoma, malignant basal cell tumor, and basal cell carcinoma, is an epithelial neoplasm that is cytologically similar to basal cell adenoma but is infiltrative and has a small potential for metastasis.[3] In AFIP case files spanning almost 11 years, basal cell carcinoma comprised 1.6% of all salivary gland neoplasms and 2.9% of salivary gland malignancies.[3] Nearly 90% of tumors occurred in the parotid gland.[3][37] The average age of patients is reported to be 60 years.[3]

Similar to most salivary gland neoplasms, swelling is typically the only sign or symptom experienced.[37] A sudden increase in size may occur in a few patients.[38] Basal cell carcinomas are low-grade carcinomas that are infiltrative, locally destructive, and tend to recur. The carcinomas occasionally metastasize. In a retrospective series that included 29 patients, there were recurrences in 7 patients and metastases in 3 patients.[37] In another retrospective review that included 72 patients, 37% of the patients experienced local recurrences.[38] The overall prognosis for patients with this tumor is good.[37][38]

Clear cell carcinoma

Clear cell carcinoma, also known as clear cell adenocarcinoma, is a very rare malignant epithelial neoplasm composed of a monomorphous population of cells that have optically clear cytoplasm with standard hematoxylin and eosin stains and lack features of other specific neoplasms. Because of inconsistencies in the methods of reporting salivary gland neoplasms, meaningful incidence rates for this tumor are difficult to derive from the literature.[3] Most cases involve the minor salivary glands.[1][3][39][40][41] In the AFIP case files, the mean age of patients is approximately 58 years.[3]

In most patients, swelling is the only symptom. Clear cell adenocarcinoma is a low-grade neoplasm. As of 1996, the AFIP reported that no patient is known to have died as a result of this tumor.[3]

Cystadenocarcinoma

Cystadenocarcinoma, also known as malignant papillary cystadenoma, mucus-producing adenopapillary, or nonepidermoid, carcinoma; low-grade papillary adenocarcinoma of the palate; and papillary adenocarcinoma, is a rare malignant epithelial tumor characterized histologically by prominent cystic and, frequently, papillary growth but lacking features that characterize cystic variants of several more common salivary gland neoplasms. Cystadenocarcinoma is the malignant counterpart of cystadenoma.[3]

In a review that included 57 patients, the AFIP found that men and women are affected equally; the average patient age was approximately 59 years; and approximately 65% of the tumors occurred in the major salivary glands, and primarily in the parotid.[3] Most patients present with a slowly growing asymptomatic mass. Clinically, this neoplasm is rarely associated with pain or facial paralysis. Cystadenocarcinoma is considered to be a low-grade neoplasm.[3]

Sebaceous adenocarcinoma

Sebaceous adenocarcinoma is a rare malignant epithelial tumor composed of islands and sheets of cells that have morphologically atypical nuclei, an infiltrative growth pattern, and focal sebaceous differentiation. This is a very rare tumor, as few cases have been reported in the literature.[3] Almost all cases occur in the parotid gland.[3] The average age of patients is reported to be 69 years.[42]

An equal number of patients present with a painless, slow-growing, asymptomatic swelling or pain. A few experience facial paralysis.[3] Most sebaceous adenocarcinomas are probably intermediate-grade malignancies. Tumor recurs in about 33% of cases.[43][44]

Sebaceous lymphadenocarcinoma

Sebaceous lymphadenocarcinoma is an extremely rare malignant tumor that represents carcinomatous transformation of sebaceous lymphadenoma. The carcinoma element may be sebaceous adenocarcinoma or some other specific or nonspecific form of salivary gland cancer.[3] Only three cases have been reported in the literature.[43][45] The three cases occurred in or around the parotid gland. All patients were in their seventh decade of life. Two of the three patients were asymptomatic. One had tenderness on palpation. Case reports suggest that this is a low-grade malignancy with a good prognosis.[44][45]

Oncocytic carcinoma

Oncocytic carcinoma, also known as oncocytic adenocarcinoma, is a rare, predominantly oncocytic neoplasm whose malignant nature is reflected both by its abnormal morphologic features and infiltrative growth. Oncocytic carcinoma represents less than 1% of almost 3,100 salivary gland tumors accessioned to the AFIP files during a 10-year period.[3] Most cases occur in the parotid gland. The average age of patients in the AFIP series was 63 years.[3]

Approximately 33% of the patients usually develop parotid masses that cause pain or paralysis.[46] Oncocytic carcinoma is a high-grade carcinoma. Tumors smaller than 2 cm have a better prognosis than larger tumors.[6]

Salivary duct carcinoma

Salivary duct carcinoma, also known as salivary duct adenocarcinoma, is a rare, typically high-grade malignant epithelial neoplasm composed of structures that resemble expanded salivary gland ducts. A low-grade variant exists.[47] Incidence rates vary depending upon the study cited.[3] In the AFIP files, salivary duct carcinomas represent only 0.2% of all epithelial salivary gland neoplasms. More than 85% of cases involve the parotid gland and approximately 75% of patients are men. The peak incidence is reported to be in the seventh and eighth decades of life.[3]

Clinically, parotid swelling is the most common sign. Facial nerve dysfunction or paralysis occur in more than 25% of patients and may be the initial manifestation.[3] The high-grade variant of this neoplasm is one of the most aggressive types of salivary gland carcinoma and is typified by local invasion, lymphatic and hematogenous spread, and poor prognosis.[3][7] In a retrospective review of 104 cases, 33% of patients developed local recurrence, and 46% of patients developed distant metastasis.[48]

Mucinous adenocarcinoma

Mucinous adenocarcinoma is a rare malignant neoplasm characterized by large amounts of extracellular epithelial mucin that contains cords, nests, and solitary epithelial cells. The incidence is unknown. Limited data indicate that most, if not all, occur in the major salivary glands with the submandibular gland as the predominant site.[3][49] These tumors may be associated with dull pain and tenderness.[3][49] This neoplasm may be considered to be low grade.[3]

Malignant mixed tumors

The classification of malignant mixed tumors, includes three distinct clinicopathologic entities: carcinoma ex pleomorphic adenoma, carcinosarcoma, and metastasizing mixed tumor. Carcinoma ex pleomorphic adenoma constitutes the vast majority of cases, whereas carcinosarcoma, a true malignant mixed tumor, and metastasizing mixed tumor are extremely rare.[3]

Carcinoma ex pleomorphic adenoma

Carcinoma ex pleomorphic adenoma, also known as carcinoma ex mixed tumor, is a carcinoma that shows histologic evidence of arising from or in a benign pleomorphic adenoma.[50] Diagnosis requires the identification of benign tumor in the tissue sample.[51] The incidence or relative frequency of this tumor varies considerably depending on the study cited.[1] A review of material at the AFIP showed carcinoma ex pleomorphic adenoma to comprise 8.8% of all mixed tumors and 4.6% of all malignant salivary gland tumors, ranking it as the sixth most common malignant salivary gland tumor after mucoepidermoid carcinoma; adenocarcinoma, NOS; acinic cell carcinoma; polymorphous low-grade adenocarcinoma; and adenoid cystic carcinoma.[3] The neoplasm occurs primarily in the major salivary glands.[52]

The most common clinical presentation is a painless mass.[3] Approximately 33% of patients may experience facial paralysis.[53] Depending on the series cited, survival times vary significantly: 25% to 65% at 5 years, 24% to 50% at 10 years, 10% to 35% at 15 years, and 0% to 38% at 20 years.[3] In addition to tumor stage, histologic grade and degree of invasion are important parameters to determine prognosis.[54]

Carcinosarcoma

Carcinosarcoma, also known as true malignant mixed tumor, is a rare malignant salivary gland neoplasm that contains both carcinoma and sarcoma components. Either or both components are expressed in metastatic foci. Some carcinosarcomas develop de novo while others develop in association with benign mixed tumor. This neoplasm is rare; only eight cases exist in the AFIP case files.[3] At one facility, only 11 cases were recorded over a 32-year period.[8] The majority of tumors occur in the major salivary glands.

Swelling, pain, nerve palsy, and ulceration have been frequent clinical findings. Carcinosarcoma is an aggressive, high-grade malignancy. In the largest series reported, which consisted of 12 cases, the average survival period was 3.6 years.[8]

Metastasizing mixed tumor

Metastasizing mixed tumor is a very rare histologically benign salivary gland neoplasm that inexplicably metastasizes. Often a long interval occurs between the diagnosis of the primary tumor and the metastases. The histologic features are within the spectrum of features that typify pleomorphic adenoma.[3] The majority occur in the major salivary glands. The primary neoplasm is typically a single, well-defined mass. Recurrences, which may be multiple, have been reported to occur for as many as 26 years after excision of the primary neoplasm.[55]

Rare carcinomas

Primary squamous cell carcinoma

Primary squamous cell carcinoma, also known as primary epidermoid carcinoma, is a malignant epithelial neoplasm of the major salivary glands that is composed of squamous (i.e., epidermoid) cells. Diagnosis requires the exclusion of primary disease located in some other head and neck site; indeed, most squamous cell carcinomas of the major salivary glands represent metastatic disease.[3] This diagnosis is not made in minor salivary glands because distinction from the more common mucosal squamous cell carcinoma is not possible.[3] Previous exposure to ionizing radiation appears to increase the risk for developing this neoplasm.[11][56][57] The median time between radiation therapy and diagnosis of the neoplasm is approximately 15.5 years.[11] The reported frequency of this tumor among all major salivary gland tumors has varied from 0.9% to 4.7%.[3][10] In AFIP major salivary gland accessions from 1985 to 1996, primary squamous cell carcinoma comprised 2.7% of all tumors; 5.4% of malignant tumors; and 2.5% and 2.8%, respectively, of all parotid and submandibular tumors.[3] The average age in the AFIP registry was 64 years.[3] This neoplasm occurs in the parotid gland almost nine times more often than in the submandibular gland.[3][57] There is a strong male predilection.[3][11][57][58][59] This tumor is graded in a similar way to extrasalivary lesions according to the degree of differentiation, namely, low grade, intermediate grade, and high grade.[1]

Most patients present with an asymptomatic mass in the parotid region. Other symptoms may include a painful mass and facial nerve palsy.[57] The prognosis for this neoplasm is poor. In a 30-year retrospective analysis of 50 cases of squamous cell carcinoma of the salivary glands, survival rates at 5 years and 10 years were 24% and 18%, respectively.[57]

Epithelial-myoepithelial carcinoma

Epithelial-myoepithelial carcinoma, also known as adenomyoepithelioma, clear cell adenoma, tubular solid adenoma, monomorphic clear cell tumor, glycogen-rich adenoma, glycogen-rich adenocarcinoma, clear cell carcinoma, and salivary duct carcinoma, is an uncommon, low-grade epithelial neoplasm composed of variable proportions of ductal and large, clear-staining, differentiated myoepithelial cells. The tumor comprises approximately 1% of all epithelial salivary gland neoplasms.[3][60] It is predominantly a tumor of the parotid gland. In the AFIP case files, the mean age of patients is about 60 years and about 60% of the patients are female.[3]

Localized swelling is commonly the only symptom, but occasionally patients experience facial weakness or pain.[61][62] Overall, epithelial-myoepithelial carcinoma is a low-grade carcinoma that recurs frequently, has a tendency to metastasize to periparotid and cervical lymph nodes, and occasionally results in distant metastasis and death.[60][62][63][64]

Anaplastic small cell carcinoma

Anaplastic small cell carcinoma of the salivary glands was first described in 1972.[65] Subsequent histochemical and electron microscopic studies have supported the neuroendocrine nature of this tumor.[66][67] Microscopically, the tumor cells have oval, hyperchromatic nuclei and scant amount of cytoplasm and are organized in sheets, strands, and nests. The mitotic rate is high. Neuroendocrine carcinomas are more frequently found in the minor salivary glands and have a better survival rate compared with small cell carcinomas of the lung.[68] The undifferentiated counterpart of this neoplasm is the small cell undifferentiated carcinoma.

Undifferentiated carcinomas

Undifferentiated carcinomas of salivary glands are a group of uncommon malignant epithelial neoplasms that lack the specific light-microscopic morphologic features of other types of salivary gland carcinomas. These carcinomas are histologically similar to undifferentiated carcinomas that arise in other organs and tissues. Accordingly, metastatic carcinoma is a primary concern in the differential diagnosis of these neoplasms.[3]

Small cell undifferentiated carcinoma

Small cell undifferentiated carcinoma, also known as extrapulmonary oat cell carcinoma, is a rare, primary malignant tumor that, with conventional light microscopy, is composed of undifferentiated cells and, with ultrastructural or immunohistochemical studies, does not demonstrate neuroendocrine differentiation. This is the undifferentiated counterpart of anaplastic small cell carcinoma (Refer to the anaplastic small cell carcinoma section of this summary.)

In an AFIP review of case files, small cell carcinoma represented 1.8% of all major salivary gland malignancies; the mean age of patients was 56 years.[3] In 50% of the cases, patients present with an asymptomatic parotid mass of 3 months' or less duration.[68][69][70] This is a high-grade neoplasm. In a retrospective review of 12 cases, a tumor size of more than 4 cm was found to be the most important predictor of behavior. In another small retrospective series, estimated survival rates at 2 and 5 years were 70% and 46%, respectively.[68]

Large cell undifferentiated carcinoma

Large cell undifferentiated carcinoma is a tumor in which features of acinar, ductal, epidermoid, or myoepithelial differentiation are absent under light microscopy, though occasionally, poorly formed duct–like structures are found. This neoplasm accounts for approximately 1% of all epithelial salivary gland neoplasms.[3][53][71][72] Most of these tumors occur in the parotid gland.[70][72] In AFIP data, the peak incidence is in the seventh to eighth decades of life.[3]

Rapid growth of a parotid swelling is a common clinical presentation.[59] This is a high-grade neoplasm that frequently metastasizes and has a poor prognosis. Neoplasms 4 cm or larger may have a particularly poor outcome.[70][72]

Lymphoepithelial carcinoma

Lymphoepithelial carcinoma, also known as undifferentiated carcinoma with lymphoid stroma and carcinoma ex lymphoepithelial lesion, is an undifferentiated tumor that is associated with a dense lymphoid stroma. An exceptionally high incidence of this tumor is found in the Eskimo and Inuit populations.[3][73] This neoplasm has been associated with Epstein-Barr virus infection.[74][75] Of the occurrences, 80% are in the parotid gland.[3]

In addition to the presence of a parotid or submandibular mass, pain is a frequent symptom, and facial nerve palsy occurs in as many as 20% of patients.[76] (Refer to the PDQ summary on Pain for more information.) Of the patients, more than 40% have metastases to cervical lymph nodes at initial presentation, 20% develop local recurrences or lymph node metastases, and 20% develop distant metastases within 3 years following therapy.[73][76][77][78]

Myoepithelial carcinoma

Myoepithelioma carcinoma is a rare, malignant salivary gland neoplasm in which the tumor cells almost exclusively manifest myoepithelial differentiation. This neoplasm represents the malignant counterpart of benign myoepithelioma.[3] To date, the largest series reported involves 25 cases.[79] Approximately 66% of the tumors occur in the parotid gland.[3][74] The mean age of patients is reported to be 55 years.[79]

The majority of patients present with the primary complaint of a painless mass.[79] This is an intermediate grade to high-grade carcinoma.[3][79] Histologic grade does not appear to correlate well with clinical behavior; tumors with a low-grade histologic appearance may behave aggressively.[79]

Adenosquamous carcinoma

Adenosquamous carcinoma is an extremely rare malignant neoplasm that simultaneously arises from surface mucosal epithelium and salivary gland ductal epithelium. The carcinoma shows histopathologic features of both squamous cell carcinoma and adenocarcinoma. Only a handful of reports have discussed this tumor.[3]

In addition to swelling, adenosquamous carcinoma produces visible changes in the mucosa including erythema, ulceration, and induration. Pain frequently accompanies ulceration. Limited data indicate that this is a highly aggressive neoplasm with a poor prognosis.[3]

Nonepithelial Neoplasms

Lymphomas and benign lymphoepithelial lesion

Lymphomas of the major salivary glands are characteristically of the non-Hodgkin type. In an AFIP review of case files, non-Hodgkin lymphoma accounted for 16.3% of all malignant tumors that occurred in the major salivary glands; disease in the parotid gland accounted for about 80% of all cases.[3]

Patients with benign lymphoepithelial lesion (e.g., Mikulicz disease), which is a manifestation of the autoimmune disease, Sjögren syndrome, are at an increased risk for development of non-Hodgkin lymphoma.[80][81][82][83][84] Benign lymphoepithelial lesion is clinically characterized by diffuse and bilateral enlargement of the salivary and lacrimal glands.[23] Morphologically, a salivary gland lesion is composed of prominent myoepithelial islands surrounded by a lymphocytic infiltrate. Germinal centers are often present in the lymphocytic infiltrate.[23] Immunophenotypically and genotypically, the lymphocytic infiltrate is composed of B-lymphocytes and T-lymphocytes, which are polyclonal. In some instances, the B-cell lymphocytic infiltrate can undergo clonal expansion and evolve into frank non-Hodgkin lymphoma. The vast majority of the non-Hodgkin lymphomas arising in a background of benign lymphoepithelial lesions are marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT).[81][82][83][84] MALT lymphomas of the salivary glands, like their counterparts in other anatomic sites, typically display relatively indolent clinical behavior.[3][85]

Primary non-MALT lymphomas of the salivary glands may also occur and appear to have a prognosis similar to those in patients who have histologically identical nodal lymphomas.[86][87] Unlike non-Hodgkin lymphoma, involvement of the major salivary glands by Hodgkin lymphoma is rare. Most tumors occur in the parotid gland.[3] The most common histologic types encountered are the nodular sclerosing and lymphocyte-predominant variants.[88][89]

Mesenchymal neoplasms

Mesenchymal neoplasms account for 1.9% to 5% of all neoplasms that occur within the major salivary glands.[90][91] These cellular classifications pertain to major salivary gland tumors. Because the minor salivary glands are small and embedded within fibrous connective tissue, fat, and skeletal muscle, the origin of a mesenchymal neoplasm from stroma cannot be determined.[3] The types of benign mesenchymal salivary gland neoplasms include hemangiomas, lipomas, and lymphangiomas.

Malignant mesenchymal salivary gland neoplasms include malignant schwannomas, hemangiopericytomas, malignant fibrous histiocytomas, rhabdomyosarcomas, and fibrosarcomas, among others; in the major salivary glands, these neoplasms represent approximately 0.5% of all benign and malignant salivary gland tumors and approximately 1.5% of all malignant tumors.[90][92][93] Of importance is to establish a primary salivary gland origin for these tumors by excluding the possibilities of metastasis and direct extension from other sites. In addition, the diagnosis of salivary gland carcinosarcoma should be excluded.[3] Primary salivary gland sarcomas behave like their soft tissue counterparts in which prognosis is related to sarcoma type, histologic grade, tumor size, and stage.[93][94] (Refer to the PDQ summary on Adult Soft Tissue Sarcoma Treatment for more information.) A comprehensive review of salivary gland mesenchymal neoplasms can be found elsewhere.[95]

Malignant Secondary Neoplasms

Malignant neoplasms whose origins lie outside the salivary glands may involve the major salivary glands by:[3]

  1. Direct invasion from cancers that lie adjacent to the salivary glands.
  2. Hematogenous metastases from distant primary tumors.
  3. Lymphatic metastases to lymph nodes within the salivary gland.

Direct invasion of nonsalivary gland tumors into the major salivary glands is principally from squamous cell and basal cell carcinomas of the overlying skin.

Approximately 80% of metastases to the major salivary glands may be from primary tumors elsewhere in the head and neck; the remaining 20% may be from infraclavicular sites.[96][97] The parotid gland is the site of 80% to 90% of the metastases, and the remainder involve the submandibular gland.[97][98] In a decade-long AFIP experience, metastatic tumors constituted approximately 10% of malignant neoplasms in the major salivary glands, exclusive of malignant lymphomas.[3] The majority of metastatic primary tumors to the major salivary glands are squamous cell carcinomas and melanomas from the head and neck that presumably reach the parotid gland via the lymphatic system; infraclavicular primary tumors, such as the lung, kidney, and breast, reach the salivary glands by a hematogenous route.[97][98][99] The peak incidence for metastatic tumors in the salivary glands is reported to be in the seventh decade of life.[3]

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Stage Information for Salivary Gland Cancer

In general, tumors of the major salivary glands are staged according to size, extraparenchymal extension, lymph node involvement (in parotid tumors, whether or not the facial nerve is involved), and presence of metastases.[1][2][3][4] Tumors arising in the minor salivary glands are staged according to the anatomic site of origin (e.g., oral cavity and sinuses).

Clinical stage, particularly tumor size, may be the critical factor to determine the outcome of salivary gland cancer and may be more important than histologic grade.[5][6] Diagnostic imaging studies may be used in staging. With excellent spatial resolution and superior soft tissue contrast, magnetic resonance imaging (MRI) offers advantages over computed tomographic scanning in the detection and localization of head and neck tumors. Overall, MRI is the preferred modality for evaluation of suspected neoplasms of the salivary glands.[7]

Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define salivary gland cancer.[5]

Table 1. Primary Tumor (T)a

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

T1

Tumor ≤2 cm in greatest dimension without extraparenchymal extension.b

T2

Tumor >2 cm but ≤4 cm in greatest dimension without extraparenchymal extension.b

T3

Tumor >4 cm and/or tumor having extraparenchymal extension.b

T4a

Moderately advanced disease.

Tumor invades skin, mandible, ear canal, and/or facial nerve.

T4b

Very advanced disease.

Tumor invades skull base and/or pterygoid plates and/or encases carotid artery.

aReprinted with permission from AJCC: Major salivary glands (parotid, submandibular, and sublingual) . In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 79-86.

bExtraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes.

Table 2. Regional Lymph Nodes (N)a

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1

Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension.

N2

Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension.

Metastases in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension.

Metastases in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension.

N2a

Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension.

N2b

Metastases in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension.

N2c

Metastases in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension.

N3

Metastasis in a lymph node, > 6 cm in greatest dimension.

aReprinted with permission from AJCC: Major salivary glands (parotid, submandibular, and sublingual) . In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 79-86.

Table 3. Distant Metastasis (M)a

M0

No distant metastasis.

M1

Distant metastasis.

aReprinted with permission from AJCC: Major salivary glands (parotid, submandibular, and sublingual) . In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 79-86.

Table 4. Anatomic Stage/Prognostic Groupsa

Stage

T

N

M

I

T1

N0

M0

II

T2

N0

M0

III

T3

N0

M0

T1

N1

M0

T2

N1

M0

T3

N1

M0

IVA

T4a

N0

M0

T4a

N1

M0

T1

N2

M0

T2

N2

M0

T3

N2

M0

T4a

N2

M0

IVB

T4b

Any N

M0

Any T

N3

M0

IVC

Any T

Any N

M1

aReprinted with permission from AJCC: Major salivary glands (parotid, submandibular, and sublingual) . In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 79-86.

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  2. Fu KK, Leibel SA, Levine ML, et al.: Carcinoma of the major and minor salivary glands: analysis of treatment results and sites and causes of failures. Cancer 40 (6): 2882-90, 1977.

  3. Levitt SH, McHugh RB, Gómez-Marin O, et al.: Clinical staging system for cancer of the salivary gland: a retrospective study. Cancer 47 (11): 2712-24, 1981.

  4. Kuhel W, Goepfert H, Luna M, et al.: Adenoid cystic carcinoma of the palate. Arch Otolaryngol Head Neck Surg 118 (3): 243-7, 1992.

  5. Major salivary glands (parotid, submandibular, and sublingual). In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 79-82.

  6. Spiro RH: Factors affecting survival in salivary gland cancers. In: McGurk M, Renehan AG, eds.: Controversies in the Management of Salivary Gland Disease. Oxford, UK: Oxford University Press, 2001, pp 143-50.

  7. Shah GV: MR imaging of salivary glands. Magn Reson Imaging Clin N Am 10 (4): 631-62, 2002.

Treatment Option Overview

The minimum therapy for low-grade malignancies of the superficial portion of the parotid gland is a superficial parotidectomy. For all other lesions, a total parotidectomy is often indicated. The facial nerve or its branches should be resected if involved by tumor; repair can be done simultaneously. Growing evidence suggests that postoperative radiation therapy augments surgical resection, particularly for the high-grade neoplasms, when margins are close or involved, when tumors are large, or when histologic evidence of lymph node metastases is present.[1][2][3][4][5][6][7][8] Clinical trials, which have been completed in the United States and England, indicate that fast neutron-beam radiation therapy improves disease-free survival and overall survival in patients with unresectable tumors or for patients with recurrent neoplasms.[9][10][11][12] Facilities with fast neutron-beam radiation therapy are of limited availability in the United States. Accelerated hyperfractionated photon-beam radiation therapy has also resulted in high rates of long-term local regional controls.[13][14] The use of chemotherapy for malignant salivary gland tumors remains under evaluation.[15][16][17][18][19]

References:

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  10. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996.

  11. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999.

  12. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000.

  13. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991.

  14. Douglas JG, Koh WJ, Austin-Seymour M, et al.: Treatment of salivary gland neoplasms with fast neutron radiotherapy. Arch Otolaryngol Head Neck Surg 129 (9): 944-8, 2003.

  15. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986.

  16. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985.

  17. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb.

  18. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986.

  19. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996.

Stage I Major Salivary Gland Cancer

Low-grade stage I tumors of the salivary gland are curable with surgery alone.[1][2][3] Radiation therapy may be used for tumors for which resection involves a significant cosmetic or functional deficit or as an adjuvant to surgery when positive margins are present.[4] Neutron-beam therapy is effective in the treatment of poor-prognosis patients with malignant salivary gland tumors.[5][6][7]

High-grade stage I salivary gland tumors that are confined to the gland in which they arise may be cured by surgery alone, though adjuvant radiation therapy may be used, especially with the presence of positive margins.

Low-grade Tumors

Standard treatment options:

  1. Surgery alone.
  2. Postoperative radiation therapy should be considered when the resection margins are positive.

High-grade Tumors

Standard treatment options:

  1. Localized high-grade salivary gland tumors that are confined to the gland in which they arise may be cured by radical surgery alone.
  2. Postoperative radiation therapy may improve local control and increase survival rates for patients with high-grade tumors, positive surgical margins, or perineural invasion.[8][Level of evidence: 3iiiDii][9][10][11]

Treatment options under clinical evaluation:

  • Clinical trials exploring newer methods of local control are appropriate. The role of chemotherapy remains under evaluation, though data suggest that some salivary gland tumors may be responsive to chemotherapy.[12][13]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I salivary gland cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Byers RM, Jesse RH, Guillamondegui OM, et al.: Malignant tumors of the submaxillary gland. Am J Surg 126 (4): 458-63, 1973.

  2. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.

  3. Woods JE, Chong GC, Beahrs OH: Experience with 1,360 primary parotid tumors. Am J Surg 130 (4): 460-2, 1975.

  4. Guillamondegui OM, Byers RM, Luna MA, et al.: Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. Am J Roentgenol Radium Ther Nucl Med 123 (1): 49-54, 1975.

  5. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996.

  6. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999.

  7. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000.

  8. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999.

  9. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997.

  10. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005.

  11. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007.

  12. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986.

  13. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985.

Stage II Major Salivary Gland Cancer

Low-grade stage II tumors of the salivary gland may be cured with surgery alone.[1][2][3] Radiation therapy as primary treatment may be used for tumors for which resection involves a significant cosmetic or functional deficit or as an adjuvant to surgery when positive margins are present.[4]

High-grade stage II salivary gland tumors that are confined to the gland in which they arise may be cured by surgery alone, though adjuvant radiation therapy may be used, especially if positive margins are present. Primary radiation therapy may be given for tumors that are inoperable, unresectable, or recurrent. Fast neutron-beam radiation therapy has been shown to improve disease-free survival and overall survival in this clinical situation.[5][6][7]

Low-grade Tumors

Standard treatment options:

  1. Surgery alone or with postoperative radiation therapy, if indicated, is appropriate.[8][9]
  2. Chemotherapy should be considered in special circumstances, such as when radiation therapy or surgery is refused.

High-grade Tumors

Standard treatment options:

  1. Localized high-grade salivary gland tumors that are confined to the gland in which they arise may be cured by radical surgery alone.
  2. Postoperative radiation therapy may improve local control and increase survival rates for patients with high-grade tumors, positive surgical margins, or perineural invasion.[10][Level of evidence: 3iiiDii][11][12][13]
  3. Fast neutron-beam radiation therapy or accelerated hyperfractionated photon-beam schedules reportedly are more effective than conventional x-ray therapy in the treatment of patients with inoperable, unresectable, or recurrent malignant salivary gland tumors.[5][6][7][14]

Treatment options under clinical evaluation:

  • Clinical trials exploring ways to improve local control with radiation therapy and/or radiosensitizers are appropriate. The role of chemotherapy is also under study.[15][16]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II salivary gland cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Byers RM, Jesse RH, Guillamondegui OM, et al.: Malignant tumors of the submaxillary gland. Am J Surg 126 (4): 458-63, 1973.

  2. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.

  3. Woods JE, Chong GC, Beahrs OH: Experience with 1,360 primary parotid tumors. Am J Surg 130 (4): 460-2, 1975.

  4. Guillamondegui OM, Byers RM, Luna MA, et al.: Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. Am J Roentgenol Radium Ther Nucl Med 123 (1): 49-54, 1975.

  5. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996.

  6. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999.

  7. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000.

  8. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb.

  9. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986.

  10. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999.

  11. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997.

  12. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005.

  13. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007.

  14. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991.

  15. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982.

  16. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982.

Stage III Major Salivary Gland Cancer

Patients with low-grade stage III tumors of the salivary gland may be cured with surgery alone.[1][2][3] Radiation therapy as primary treatment is not often required but may be used for tumors for which resection involves a significant cosmetic or functional deficit, or as an adjuvant to surgery when positive margins are present.[4] Patients with low-grade tumors that have spread to lymph nodes may be cured with resection of the primary tumor and the involved lymph nodes, with or without radiation therapy. Neutron-beam therapy is effective in the treatment of patients with tumors that have spread to local lymph nodes.

Patients with high-grade stage III salivary gland tumors that are confined to the gland in which they arise may be cured by surgery alone, though adjuvant postoperative radiation therapy may be used, especially if positive margins are present. Primary conventional x-ray radiation therapy may provide palliation for patients with unresectable tumors. Fast neutron beams, however, have been reported to improve disease-free survival and overall survival in this clinical situation.[5][6][7] Patients with tumors that have spread to regional lymph nodes should have a regional lymphadenectomy as part of the initial surgical procedure. Adjuvant radiation therapy for these tumors may reduce the local recurrence rate.

Low-grade Tumors

Standard treatment options:

  1. Surgery alone or with postoperative radiation therapy, if indicated, is appropriate.
  2. Chemotherapy should be considered in special circumstances, such as when radiation or surgery is refused or when tumors are recurrent or nonresponsive.

Treatment options under clinical evaluation:

  • Data in which fast neutron-beam radiation therapy has been used have indicated superior results when compared with conventional radiation therapy using x-rays. The role of chemotherapy is under evaluation.[5][8][9][10]

High-grade Tumors

Standard treatment options:

  1. Patients with localized high-grade salivary gland tumors that are confined to the gland in which they arise may be cured by radical surgery alone.[11][12]
  2. Postoperative radiation therapy may improve local control and increase survival rates for patients with high-grade tumors, positive surgical margins, or perineural invasion.[13][Level of evidence: 3iiiDii][14][15][16]
  3. Fast neutron-beam radiation therapy or accelerated hyperfractionated photon-beam schedules have been reported to be more effective than conventional x-ray therapy in the treatment of patients with inoperable, unresectable, or recurrent malignant salivary gland tumors.[5][6][7][17]

Treatment options under clinical evaluation:

  • Clinical trials exploring ways to improve local control with radiation therapy and/or radiosensitizers and with chemotherapy are under evaluation.[8][9][10][18][19]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III salivary gland cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Byers RM, Jesse RH, Guillamondegui OM, et al.: Malignant tumors of the submaxillary gland. Am J Surg 126 (4): 458-63, 1973.

  2. Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.

  3. Woods JE, Chong GC, Beahrs OH: Experience with 1,360 primary parotid tumors. Am J Surg 130 (4): 460-2, 1975.

  4. Guillamondegui OM, Byers RM, Luna MA, et al.: Aggressive surgery in treatment for parotid cancer: the role of adjunctive postoperative radiotherapy. Am J Roentgenol Radium Ther Nucl Med 123 (1): 49-54, 1975.

  5. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996.

  6. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999.

  7. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000.

  8. Kaplan MJ, Johns ME, Cantrell RW: Chemotherapy for salivary gland cancer. Otolaryngol Head Neck Surg 95 (2): 165-70, 1986.

  9. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985.

  10. Catterall M, Errington RD: The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int J Radiat Oncol Biol Phys 13 (9): 1313-8, 1987.

  11. Spiro RH: Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg 8 (3): 177-84, 1986 Jan-Feb.

  12. Theriault C, Fitzpatrick PJ: Malignant parotid tumors. Prognostic factors and optimum treatment. Am J Clin Oncol 9 (6): 510-6, 1986.

  13. Hosokawa Y, Shirato H, Kagei K, et al.: Role of radiotherapy for mucoepidermoid carcinoma of salivary gland. Oral Oncol 35 (1): 105-11, 1999.

  14. Garden AS, el-Naggar AK, Morrison WH, et al.: Postoperative radiotherapy for malignant tumors of the parotid gland. Int J Radiat Oncol Biol Phys 37 (1): 79-85, 1997.

  15. Mendenhall WM, Morris CG, Amdur RJ, et al.: Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer 103 (12): 2544-50, 2005.

  16. Chen AM, Granchi PJ, Garcia J, et al.: Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys 67 (4): 982-7, 2007.

  17. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991.

  18. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982.

  19. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982.

Stage IV Major Salivary Gland Cancer

Standard therapy for patients with tumors that have spread to distant sites is not curative.

Standard treatment options:

  • Fast neutron-beam radiation therapy or accelerated hyperfractionated photon-beam schedules have been reported to be more effective than conventional x-ray therapy in the treatment of patients with inoperable, unresectable, or recurrent malignant salivary gland tumors.[1][2][3][4][5]

Treatment options under clinical evaluation:

  • Patients with stage IV salivary gland cancer should be considered candidates for clinical trials. Their cancer may be responsive to aggressive combinations of chemotherapy and radiation. Patients with any metastatic lesions could be considered for clinical trials. Chemotherapy using doxorubicin, cisplatin, cyclophosphamide, and fluorouracil as single agents or in various combinations is associated with modest response rates.[6][7][8][9][10][11][12][13][14]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV salivary gland cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Wang CC, Goodman M: Photon irradiation of unresectable carcinomas of salivary glands. Int J Radiat Oncol Biol Phys 21 (3): 569-76, 1991.

  2. Laramore GE, Krall JM, Griffin TW, et al.: Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council. Int J Radiat Oncol Biol Phys 27 (2): 235-40, 1993.

  3. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996.

  4. Douglas JG, Lee S, Laramore GE, et al.: Neutron radiotherapy for the treatment of locally advanced major salivary gland tumors. Head Neck 21 (3): 255-63, 1999.

  5. Douglas JG, Laramore GE, Austin-Seymour M, et al.: Treatment of locally advanced adenoid cystic carcinoma of the head and neck with neutron radiotherapy. Int J Radiat Oncol Biol Phys 46 (3): 551-7, 2000.

  6. Eisenberger MA: Supporting evidence for an active treatment program for advanced salivary gland carcinomas. Cancer Treat Rep 69 (3): 319-21, 1985.

  7. Venook AP, Tseng A Jr, Meyers FJ, et al.: Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group. J Clin Oncol 5 (6): 951-5, 1987.

  8. Rentschler R, Burgess MA, Byers R: Chemotherapy of malignant major salivary gland neoplasms: a 25-year review of M. D. Anderson Hospital experience. Cancer 40 (2): 619-24, 1977.

  9. Posner MR, Ervin TJ, Weichselbaum RR, et al.: Chemotherapy of advanced salivary gland neoplasms. Cancer 50 (11): 2261-4, 1982.

  10. Suen JY, Johns ME: Chemotherapy for salivary gland cancer. Laryngoscope 92 (3): 235-9, 1982.

  11. Catterall M, Errington RD: The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy. Int J Radiat Oncol Biol Phys 13 (9): 1313-8, 1987.

  12. Ono M, Watanabe A, Matsumoto Y, et al.: Methamphetamine modifies the photic entraining responses in the rodent suprachiasmatic nucleus via serotonin release. Neuroscience 72 (1): 213-24, 1996.

  13. Saroja KR, Mansell J, Hendrickson FR, et al.: An update on malignant salivary gland tumors treated with neutrons at Fermilab. Int J Radiat Oncol Biol Phys 13 (9): 1319-25, 1987.

  14. Licitra L, Cavina R, Grandi C, et al.: Cisplatin, doxorubicin and cyclophosphamide in advanced salivary gland carcinoma. A phase II trial of 22 patients. Ann Oncol 7 (6): 640-2, 1996.

Recurrent Major Salivary Gland Cancer

The prognosis for any treated cancer patient with progressing or relapsing disease is poor, regardless of cell type or stage. Selecting further treatment depends on many factors, including the specific cancer, prior treatment, site of recurrence, and individual patient considerations. Fast neutron-beam radiation therapy is superior to conventional radiation therapy using x-rays and may be curative in selected patients with recurrent disease.[1]

Disease-free survival and overall survival for patients with inoperable, unresectable, or recurrent malignant salivary gland tumors is superior in patients treated with fast neutron-beam radiation therapy as compared to those treated with conventional x-ray radiation therapy.[2][3][4][5] Clinical trials are appropriate and should be considered when possible.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent salivary gland cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Laramore GE, Krall JM, Griffin TW, et al.: Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council. Int J Radiat Oncol Biol Phys 27 (2): 235-40, 1993.

  2. Laramore GE: Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice? Int J Radiat Oncol Biol Phys 13 (9): 1421-3, 1987.

  3. Saroja KR, Mansell J, Hendrickson FR, et al.: An update on malignant salivary gland tumors treated with neutrons at Fermilab. Int J Radiat Oncol Biol Phys 13 (9): 1319-25, 1987.

  4. Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992.

  5. Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996.


This information is provided by the National Cancer Institute.

This information was last updated on July 20, 2012.

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