Adenoid cystic carcinoma (AdCC) is a rare form of adenocarcinoma, which is a broad term covering any cancer arising from glandular tissues. AdCC is found mainly in the head and neck, but can occasionally occur in the uterus or other sites in the body. It most commonly occurs in the salivary glands, which consist of clusters of secretory cells scattered throughout the upper aerodigestive tract. Therefore, tumors may arise in areas such as the palate, nasopharynx, tongue base, or mucosal lining of the mouth, larynx, or trachea. It may also occur in the major salivary glands (parotid, submandibular, or sublingual).

Regardless of where it originates, AdCC has the same basic biologic behavior. AdCC tends to spread along nerves (perineural invasion) or through the bloodstream. It only spreads to the lymph nodes in about 5% to 10% of cases. The most common place of metastases (spreading) is the lung.

There are many other terms that are used to describe AdCC, which mostly refer to histologic (how cells look under a microscope) variations of the tumor, including cylindroma, cribiform, and solid AdCC. AdCC may be grouped with other tumors of the minor salivary gland, even though it may begin at other sites. AdCC is known for having long periods of indolence (no growth), followed by growth spurts. However, AdCC may behave aggressively in some people, making the course of the AdCC unpredictable.

Statistics

AdCC is most often diagnosed in people in their 40s to 60s, but there are documented cases of pediatric AdCC. Women are slightly more likely to be diagnosed with AdCC than men (the female to male ratio is approximately 3 to 2).

The five-year relative survival rate (the percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases)for AdCC is approximately 89%. The 15-year relative survival rate (the percentage of patients who survive at least 15 years after the cancer is detected, excluding those who die from other diseases) for AdCC is approximately 40%. Tumor progression for AdCC is often slow and patients may live a long time with metastatic disease; however, a late relapse of AdCC is common, and can occur many years after initial treatment.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer in the United States each year, but the actual risk for a particular individual may differ. It is not possible to tell a person how long he or she will live with AdCC. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not represent advances made in the treatment or diagnosis of this cancer.

Sources: University of Virginia Health System

To learn about the cancer terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: Basic Oncology Terms.

A risk factor is anything that increases a person's chance of developing a disease, including cancer. There are risk factors that can be controlled, such as smoking, and risk factors that cannot be controlled, such as age and family history. Although risk factors can influence disease, for many risk factors it is not known whether they actually cause the disease directly. Some people with several risk factors never develop the disease, while others with no known risk factors do. However, knowing your risk factors and communicating them to your doctor may help you make more informed lifestyle and health-care choices.

The cause of AdCC is unknown at this time. There is some evidence that the p53 tumor suppressor gene (a gene that limits cell growth by monitoring the rate at which cells divide) is inactivated in advanced and aggressive forms of AdCC.

People with AdCC may experience the following symptoms. Sometimes, people with AdCC do not show any of these symptoms. Or, these symptoms may be similar to symptoms of other medical conditions. If you are concerned about a symptom on this list, please talk with your doctor.

The initial symptoms of AdCC depend on the location of the tumor. Early lesions of the salivary glands may become apparent as painless, usually slow-growing, masses of the mouth or face. Because there are many salivary glands under the mucosal lining of the mouth, throat, and sinuses, lumps in these locations could be from this type of tumor. Other symptoms may include:

• Difficulties in swallowing



• Hoarseness



• Dull pain



• A bump or nodule in front of the ear or underneath the jaw



• Paralysis of a facial nerve



• Numbness of the face or tongue



• A lump under the tongue or on the palate (roof of the mouth)

Staging is a way of describing a cancer, such as where it is located, if or where it has spread, and if it is affecting the functions of other organs in the body. Doctors use diagnostic tests such as x-rays to determine the cancer’s stage. Sometimes, when an unusual or suspicious area is identified on an x-ray, a biopsy may be needed to confirm whether the suspicious area is a cancerous tumor, so staging may not be complete until the doctor performs a biopsy. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient’s prognosis (chance of recovery). There are different stage descriptions for different types of cancer.

There is no uniform staging system used for AdCC, but often the staging system for major salivary gland tumors is used.

One tool that doctors use to describe the stage is the TNM system. This system uses three criteria to judge the stage of the cancer: the size of the tumor itself, whether or not the tumor has spread to the lymph nodes around the tumor, and if the tumor has spread to the rest of the body (usually through the blood stream). The results are combined to determine the stage of cancer for each person. There are five stages: stage 0 (zero) and stages I through IV (one through four). The stage provides a common way of describing the cancer so doctors can work together to plan the best treatments.

TNM is an abbreviation for tumor (T), node (N), and metastasis (M). Doctors look at these three factors to determine the stage of cancer:

• How large is the primary tumor and where is it located? (Tumor, T)
• Has the tumor spread to the lymph nodes? (Node, N)
• Has the cancer metastasized to other parts of the body? (Metastasis, M)

Tumor. Using the TNM system, the "T" plus a letter or number (0 to 4) is used to describe the size and location of the tumor.

TX: Indicates the primary tumor cannot be evaluated.

T0: No evidence of a tumor is found.

T1: Describes a small noninvasive tumor that is 2 centimeters (cm) at its greatest dimension.

T2: Describes a larger noninvasive tumor, between 2 cm to 4 cm.

T3: Describes a tumor that is larger than 4 cm, but not larger than 6 cm that has spread beyond the salivary gland. However, the tumor does not affect the seventh nerve, the facial nerve that controls expression such as smiles or frowns.

T4a: The tumor invades the skin, jawbone, ear canal, and/or facial nerve.

T4b: The tumor invades the skull base and/or the nearby bones and/or encases the arteries.

Node. The "N" in the TNM staging system is for lymph nodes, the tiny, bean-shaped organs that help fight infection. For AdCC, lymph nodes near the head and neck are called regional lymph nodes. Lymph nodes in other parts of the body are called distant lymph nodes.

NX: Indicates the regional lymph nodes cannot be evaluated.

N0: There is no evidence of cancer in the regional nodes.

N1: Indicates that cancer has spread to a single node on the same side as the primary tumor and the cancer found in the node is 3 cm or smaller.

N2: Describes any of these conditions:

N2a: Cancer has spread to a single lymph node on the same side as the primary tumor, and is larger than 3 cm, but not larger than 6 cm.

N2b: Cancer has spread to more than one lymph node on the same side as the primary tumor, and no tumor measures larger than 6 cm.

N2c: Cancer has spread to more than one lymph node on either side of the body, and no tumor measures larger than 6 cm.

N3: Cancer found in lymph nodes is larger than 6 cm.

Distant metastasis. The "M" in the TNM system describes cancer that has spread to other parts of the body.

MX: Indicates distant metastasis cannot be evaluated.

M0: Indicates the cancer has not spread to other parts of the body.

M1: Describes cancer that has spread to other parts of the body.

Cancer stage grouping

Doctors assign the stage of the cancer by combining the T, N, and M classifications.

Stage I: Describes noninvasive tumors (T1, T2) with no spread to lymph nodes (N0) and no distant metastasis (M0).

Stage II: Describes an invasive tumor (T3) with no spread to lymph nodes (N0) or distant metastasis (M0).

Stage III: Describes smaller tumors (T1, T2) that have spread to regional lymph nodes (N1), but have no sign of metastasis (M0).

Stage IVA: Describes any invasive tumor (T4a) with either no lymph node involvement (N0) or spread to only a single, same-sided lymph node (N1), but no metastasis (M0). It is also used for a T3 tumor with one-sided nodal involvement (N1), but no metastasis (M0), or any tumor (T) with extensive nodal involvement (N2).

Stage IVB: Describes any cancer (T) with more extensive spread to lymph nodes (N2, N3) and no metastasis (M0).

Stage IVC: Describes any cancer with distant metastasis (M1).

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth Edition (2002) published by Springer-Verlag New York, www.springer-ny.com.

The treatment of AdCC depends on the size and location of the tumor, whether the cancer has spread, and the person's overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.

Surgery

Surgical removal of the tumor is the primary treatment for AdCC. During surgery, the surgeon will remove the tumor and an area of tissue surrounding it. The presence of clean margins, meaning a minimum of 2 millimeters (mm) of tissue that is cancer-free surrounding the tumor, signals total tumor removal and gives the best chance for good local (at the site of origin) control of the cancer. Side effects from surgery vary depending upon the surgical site. A concern with all surgeries of the parotid gland is that the surgery may damage or sever facial nerves, which can cause the muscles in the face to droop. Sometimes, a facial nerve graft may be used to restore function of the facial muscles after surgery to remove the tumor. The extent of surgery will vary by the site of the tumor and the structures that are involved.

Radiation therapy

In radiation therapy, high-energy x-rays are directed at the site of the tumor to kill cancer cells. It is particularly effective as an adjuvant therapy (therapy given in addition to the primary treatment) to surgery by helping to eliminate any microscopic cancer cells leftover after surgery. Radiation therapy is not used pre-operatively (before surgery) for this disease, as many surgeons feel that the surgical wound heals better if radiation therapy is not given prior to surgery. Since radiation therapy is targeted to a specific area, as opposed to being systemic like chemotherapy, the side effects will depend on where the radiation therapy was given. Generally, during head and neck treatments, people may experience a sore mouth and/or throat that can cause pain and difficulty in swallowing. They may also have a skin reaction or burn that causes some pain. Long-term side effects of radiation therapy vary with the sites involved, but they may include permanent loss of saliva causing dryness of the mouth and deterioration of the teeth. In some cases, a drug to stimulate the parotid saliva gland and increase or restore saliva levels may be given. Currently, amifostine (Ethyol), a drug to protect tissues during radiation therapy is being studied. Scarring or fibrosis (hardening or thickening) of the skin and muscles may develop several months to years after radiation therapy and lead to problems with wound healing, neck stiffness, and trouble swallowing. Other long-term effects that can develop include accelerated narrowing of the carotid arteries (the arteries that supply the head and neck with blood) and hypothyroidism (underactive thyroid disease).

Consultation with a qualified speech pathologist prior to radiation therapy is important, so appropriate exercises can be performed to maintain the strength and flexibility of the muscles used during speech and swallowing.

Neutron and proton therapy

Neutron therapy is a different form of radiation therapy. Compared with conventional radiation therapy, neutrons can deliver 20 times to 100 times more energy along their path length, causing much greater damage to the cancer cells. Neutron radiation therapy has been tested on many different types of tumors, with salivary gland tumors and, in particular, AdCC showing the greatest benefit. In certain instances, it may be the treatment of choice for AdCC, particularly in areas of the body where it is difficult to perform surgery. However, neutron therapy carries more severe side effects than conventional radiation therapy, such as severe sore mouth and/or throat and difficulty swallowing, and is therefore generally used more often with people with inoperable or recurrent disease. Again, medication to help increase saliva production and protect tissues may be given. Neutrons cannot be used to treat large areas of the body for metastatic disease, but they can be used to treat isolated metastases that are causing problems, such as pain, blocking part of the lung, or pressing on the spinal cord.

A new type of radiation is proton therapy. Proton therapy acts similarly to traditional radiation therapy to kill cancer cells. The advantage of proton therapy is the ability to better control where the radiation is delivered, greatly reducing the damage to normal healthy tissues that surround the tumor. Proton therapy has not been extensively investigated for use in AdCC.

Neither neutron nor proton therapy is widely available. Consult your doctor for information about availability of these treatments.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy is generally not used for AdCC, as this type of cancer appears to be less responsive to chemotherapy than other cancers. Various combinations of chemotherapy have been used to treat AdCC, with minimal success. The combination of chemotherapy and radiation therapy is considered experimental.

Because AdCC is a rare disease, and, in general, the available chemotherapy drugs are of limited benefit, it is recommended that people with AdCC ask about clinical trials to treat this disease. A second opinion at a cancer center may also be beneficial.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications you've been prescribed, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: During Treatment.

Doctors and scientists are always looking for better ways to treat patients with AdCC. A clinical trial is a way to test a new treatment in order to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments, such as new chemotherapy drugs, before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that this is the only way to make progress in treating AdCC, such as finding new drugs. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with AdCC.

In order to join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different than the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.

Cancer and cancer treatment can cause a variety of side effects; some are easily controlled and others require specialized care. Below are some of the side effects that are more common to AdCC and its treatments. For more detailed information on managing these and other side effects of cancer and cancer treatment, visit the Cancer.Net Managing Side Effects section.

Difficulty chewing. Difficulty chewing can result from pain in the mouth, stiffness or pain in the jaw muscles, or problems with the teeth. Difficulty chewing can be a result of physical changes to the mouth, jaw, or tongue caused by the cancer itself, especially oral and oropharyngeal cancers, or it can be a side effect of cancer treatment, especially from radiation therapy and surgery. For patients who wear dentures, pain or swelling in the mouth or gums may make it temporarily impossible to wear dentures for chewing. Difficulty chewing meats, fruits, and vegetables can make it difficult to eat a nutritious diet.

Difficulty swallowing (dysphagia). Dysphagia occurs when a patient has trouble getting food or liquid to pass down the throat. Some patients may gag, cough, or choke when trying to swallow, while others experience pain or feel like food is stuck in the throat. Difficulty swallowing is a relatively common side effect of some cancer treatments. Potential side effects of cancer treatment that can cause swallowing difficulties include soreness, pain, or inflammation in the throat, esophagus, or mouth (mucositis); dry mouth from radiation treatment or chemotherapy; infections of the mouth or esophagus from radiation treatment or chemotherapy; swelling or constriction of the throat or esophagus from radiation treatment or surgery; and physical changes to the mouth, jaw, throat, or esophagus as a result of surgery.

Dry mouth (xerostomia). Xerostomia occurs when the salivary glands do not make enough saliva (spit) to keep the mouth moist. Because saliva is needed for chewing, swallowing, tasting, and talking, these activities may be more difficult with a dry mouth. Dry mouth can be caused by chemotherapy or radiation treatment, which can damage the salivary glands. Dry mouth caused by chemotherapy is usually temporary and normally clears up about two to eight weeks after treatment ends. Radiation treatment to the head, face, or neck can cause dry mouth and is most common with radiation treatment to the oral cavity to treat head and neck cancer. It can take six months or longer for the salivary glands to start producing saliva again after the end of treatment.

Mouth sores (mucositis). Mucositis is an inflammation of the inside of the mouth and throat, leading to painful ulcers and mouth sores. It occurs in up to 40% of patients receiving chemotherapy treatments. Mucositis can be caused by a chemotherapeutic drug directly, the reduced immunity brought on by chemotherapy, or radiation treatment to the head and neck area.

Pain. Depending on the stage of disease, 30% to 75% of all patients experience pain from cancer. About 85% to 95% of cancer pain can be treated successfully. Pain can make other aspects of cancer seem worse, such as fatigue (tiredness), weakness, sleep disturbance, and confusion. Pain can come from the tumor itself or may be a result of cancer treatment. Pain from a tumor can be a result of the tumor growing and spreading to the bones or other organs and putting pressure on and damaging nerves. Pain from surgery is normal and may persist for months or years. Common procedures that cause pain afterward include mastectomy (removal of the breast and, occasionally, the surrounding tissue), chest surgery, neck surgery, and amputation of a limb (stump pain). Phantom pain is perceived pain in an organ or limb that has been removed. Pain may develop after radiation therapy and go away on its own. It can also develop months or years after treatment, especially after radiation therapy to the chest, breast, or spinal cord. Certain chemotherapeutic drugs can cause pain along with numbness in the fingers and toes. Usually this pain goes away when treatment is finished, but sometimes the damage can be permanent.

People treated with surgery may need rehabilitation to regain functioning and flexibility. The effects of radiation therapy on normal tissues, especially around the mouth and throat, require prophylactic (preventive) care by a dentist trained in oncology; sometimes, care may be given by a prosthodontist (a dental specialist with additional training and certification in the restoration and replacement of broken teeth with crowns, bridges, and removable prosthetics [dentures]) if major surgery to the mouth or jaw has taken place.

Intense treatments to the head and neck can affect swallowing, and patients may experience pain. These symptoms can be treated and, in most cases, subside some time after therapy.

Some people may experience depression following treatment, and this may require appropriate therapy as well. Most cancer centers have support groups that encourage people to become more informed about these issues.

Periodically, people need follow-up care with their doctor to monitor the effects of treatment and to check for relapses or distant metastases, which may occur even years after successful primary treatment. There is no known way to prevent relapse of AdCC. Secondary cancers are rare in AdCC.

People recovering from AdCC are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, eating a balanced diet, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. Moderate physical activity can help rebuild your strength and energy level. Your doctor can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about Healthy Living After Cancer.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: After Treatment.

Research for AdCC is ongoing. The following advancements may still be under investigation in clinical trials and may not be approved or available at this current time. Always discuss all diagnostic and treatment options with your doctor.

Antiangiogenesis research. Antiangiogenesis research, which explores how tumors develop their blood supplies and how agents disrupt these blood supplies that feed the tumors, may benefit people with AdCC.

Targeted therapies. New drugs called targeted therapies are designed to stop the growth of cancer cells at the level of genes and proteins. Currently, targeted therapies for cancer are being developed, and some of them may be useful in the treatment of AdCC.

Newer chemotherapy. Several clinical trials are examining the effects of relatively new chemotherapy drugs alone, or in combination with other drugs, in the control of metastatic or locally recurrent AdCC.

Regular communication with your doctor is important in making informed decisions about your health care. Consider asking the following questions of your doctor:

• Can you describe the stage of the cancer? Is it possible to predict its future behavior?



• What treatment options do I have?



• What clinical trials are open to me?



• What type of short-term and long-term side effects from treatment can I expect?



• Will there be cosmetic changes to my appearance?



• Will there be permanent issues relating to saliva production or eating?



• How can I keep myself as healthy as possible during treatment?



• What treatments are available if my cancer recurs?