Adenoid Cystic Carcinoma

Adenoid cystic carcinoma (AdCC) is a rare form of adenocarcinoma, which is a broad term describing any cancer arising from glandular tissues. AdCC is found mainly in the head and neck, but it can occasionally occur in a woman’s uterus or other sites in the body. It most commonly occurs in the salivary glands, which consist of clusters of cells that secrete saliva scattered throughout the upper aerodig  estive tract (the organs and tissues of the upper respiratory tract, including the lips, mouth, tongue, nose, throat, vocal cords, and part of the esophagus and windpipe). A tumor may begin in the:

• Minor salivary glands
• Palate (roof of the mouth)
• Nasopharynx (air passageway at the upper part of the throat and behind the nose)
• Tongue base (the back third of the tongue)
• Mucosal lining of the mouth (inner lining of the mouth; glands located here produce mucus)
• Larynx (voicebox)
• Trachea (windpipe)
• Major salivary glands
• Parotid (largest salivary gland found on either side of the face in front of the ears)
• Submandibular (found under the jawbone)
• Sublingual glands (in the bottom of the mouth under the tongue)

Regardless of where it starts, AdCC tends to spread along nerves (perineural invasion) or through the bloodstream. It spreads to the lymph nodes in only about 5% to 10% of cases. The most common place of metastases (spreading) is the lung. AdCC is known for having long periods of indolence (no growth) followed by growth spurts. However, AdCC can behave aggressively in some people, making the course of the AdCC unpredictable.

Besides being classified based on where the cancer begins, AdCC is also described based on the histologic (how cells look under a microscope) variations of the tumor, including cylindroma, cribiform, and solid AdCC. AdCC is sometimes classified as a disease of the minor salivary gland, even though it may begin at other sites.

AdCC is rare. AdCC is most often diagnosed in people in their 40s to 60s, but there are known cases of pediatric (childhood) AdCC. Each year, approximately 1,200 people are diagnosed with AdCC in the United States, and about 60% are women. The five-year survival rate (the percentage of people who survive at least five years after the cancer is detected, excluding those who die from other diseases) for people with AdCC is approximately 89%. The 15-year survival rate of people with AdCC is approximately 40%. Tumor growth for AdCC is often slow, and people may live a long time with metastatic disease; however, a late recurrence (cancer that comes back after treatment) 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 people with this type of cancer in the United States, 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 survival statistics are often measured in multi-year intervals, they may not represent advances made in the treatment or diagnosis of this cancer.

The cause of AdCC is unknown at this time, and risk factors for this type of cancer have not been proven consistently with scientific research. 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 somehow inactivated in advanced and aggressive forms of AdCC.

Symptoms And Signs

People with AdCC may experience the following symptoms or signs. Sometimes, people with AdCC do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom or sign 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 appear as painless, usually slow-growing masses underneath the normal lining of the mouth or skin of the 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:

• A lump on the palate, under the tongue, or in the bottom of the mouth
• An abnormal area on the lining of the mouth
• Numbness of the upper jaw, palate, face, or tongue
• Difficulty swallowing
• Hoarseness
• Dull pain
• A bump or nodule in front of the ear or underneath the jaw
• Paralysis of a facial nerve

Diagnosis

Doctors use many tests to diagnose cancer and find out if it has metastasized (spread). Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

• Age and medical condition
• Type of cancer suspected
• Severity of symptoms
• Previous test results

In addition to a physical examination, the following tests may be used to diagnose AdCC:

Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only a biopsy can make a definite diagnosis. The sample removed from a biopsy is analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease). The pathology of the salivary gland may be complicated even among experienced pathologists so it is important that the tissue is examined by a head and neck pathologist who is experienced in diagnosing salivary disease.

The biopsy can be performed by using a fine needle biopsy or by surgical removal of part or all of the tumor. A fine needle biopsy is also called fine needle aspiration or FNA. This procedure uses a thin needle to remove fluid and cells. An AdCC tumor is characterized by a distinctive pattern in which bundles of epithelial cells surround and/or infiltrate ducts or glandular structures within the organ. Frequently, diagnosis of AdCC is made after the surgical removal of a tumor first thought to be benign.

Imaging tests. Imaging techniques, primarily magnetic resonance imaging (MRI) or computed tomography (CT) scan, are useful to help doctors see the extent of the tumor before any surgery. A positron emission tomography (PET) scan may also be used to determine if the tumor has spread to other parts of the body.

• An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A contrast medium (a special dye) may be injected into a patient’s vein to create a clearer picture. An MRI is very useful for identifying perineural spread (growth of the tumor along nerve branches) of AdCC.
• A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. Sometimes, a contrast medium is injected into a patient’s vein to provide better detail.
• A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body. This substance is absorbed mainly by organs and tissues that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body.

Stages

Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting the functions of other organs in the body. Doctors use diagnostic tests to determine the cancer’s stage, so staging may not be complete until all of the tests are finished. 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 standard staging system used for AdCC, but often the staging system for a major salivary gland tumor is used.

One tool that doctors use to describe the stage is the TNM system. This system judges three factors: the size of the tumor itself, whether the tumor has spread to the lymph nodes around the tumor, and if the tumor has spread to other parts of the body. 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. Some stages are divided into smaller groups that help describe the tumor in even more detail. Specific tumor stage information is listed below.

TX: The primary tumor cannot be evaluated.

T0: No evidence of a tumor is found.

T1: The tumor is small, 2 centimeters (cm) at its widest dimension, and noninvasive.

T2: The tumor is larger, between 2 cm and 4 cm, but noninvasive.

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

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

T4b: The tumor has invaded 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: The neck has undergone an intervention that prevents the status of lymph nodes from being evaluated.

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

N1: The 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: The 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: The 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: The cancer has spread to more than one lymph node on either side of the body, and no tumor measures larger than 6 cm.

N3: The cancer found in the 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: Distant metastasis cannot be evaluated.

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

M1: The cancer 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: This stage describes a noninvasive tumor (T1, T2) with no spread to lymph nodes (N0) and no distant metastasis (M0).

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

Stage III: This stage describes a smaller tumor (T1, T2) that has spread to regional lymph nodes (N1) but shows no sign of metastasis (M0).

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

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

Stage IVC: This stage describes any cancer (any T, any N) with distant metastasis (M1).

Recurrent: Recurrent cancer is cancer that comes back after treatment. If there is a recurrence, the cancer may need to be staged again (called re-staging) using the system above.