This disease entry was made possible due to the generosity of the Kathleen Keany Memorial Foundation, 8502 East Chapman Avenue, Suite 195, Orange, CA 92869, (714) 538-6920.
Adenoid cystic carcinoma (ACC) is a relatively rare form of cancer that most commonly develops in the salivary glands or other regions of the head and neck. In some cases, ACC may arise in other primary sites, such as the skin; the breast; the neck of the uterus (cervix) in females, the prostate gland in males; or other areas.
The term "cancer" refers to a group of diseases characterized by abnormal, uncontrolled cellular growth that invades surrounding tissues and may spread (metastasize) to distant bodily tissues or organs via the bloodstream, the lymphatic system, or other means. Different forms of cancer, including adenoid cystic carcinoma, may be classified based upon the cell type involved, the specific nature of the malignancy, the tissues or organs affected, and the disease's clinical course.
ACC tumors are characterized by a distinctive pattern in which abnormal "nests" or cords of certain cells (epithelial cells) surround and/or infiltrate ducts or glandular structures within the affected organ. These structures are typically filled with a mucous-like material or contain abnormal fibrous membranes (hyaline membranes). Such characteristics are apparent during microscopic evaluation of the tumor cells. ACC is considered a low-grade malignancy that has a history of slow growth, but tends to be aggressively invasive and to infiltrate nearby lymph nodes as well as the "sheaths" or coatings surrounding nerve fibers (perineural spaces). This form of cancer may have a tendency to recur later at the site where it first developed (local recurrence) and to spread to distant bodily sites, particularly the lungs, potentially resulting in life-threatening complications.
Adenoid cystic carcinoma (ACC) primarily occurs during adulthood, although some forms of the disease (e.g., ACC of the lacrimal glands) have been reported among children and adolescents. The average age at symptom onset is variable, depending upon the specific form of ACC present and other factors. (For more information, please see the “Affected Populations” section of this report below.)
In individuals with cancer, including ACC, cells in a particular area of the body may revert to a more primitive form (anaplasia), resulting in uncontrolled cellular growth, local invasion of surrounding tissues, and possible spread to distant bodily tissues or organs (metastasis). ACC has a tendency to spread to nearby lymph nodes and along the coatings on certain nerve fibers (perineural spaces). Lymph nodes have several functions, including trapping and destroying invading microorganisms and other foreign bodies before they are able to enter the bloodstream. Although invasion of regional lymph nodes is a characteristic associated with many cancers, tumor invasion of perineural spaces is a feature that is not often seen.
ACC most commonly arises in the salivary glands or other areas within the head and neck region. The salivary glands release saliva via ducts into the mouth (oral cavity). ACC may develop within large or small (major or minor) salivary glands. There are three pairs of major salivary glands, including those that secrete saliva onto the floor of the mouth (sublingual glands); those located toward the back of the mouth (submandibular glands); and the largest salivary glands (parotid glands), which are located below the ears at the angles of the jaws. There are also numerous minor salivary glands in various areas of the oral cavity, including in the tongue, cheeks, lips, and roof of the mouth (palate), as well as the nasal cavities and sinuses. ACC most commonly develops in minor salivary glands. However, many cases of primary ACC affecting the parotid or submandibular glands have been reported in the medical literature.
Individuals with benign (noncancerous) tumors of the major or minor salivary glands often develop swelling in the affected area with no associated symptoms (asymptomatic). The occurrence of unusual neurologic symptoms may suggest the presence of a malignant growth. Depending upon the specific salivary gland and nerve(s) affected by the malignancy, as well as the tumor’s size, such symptoms may include numbness of the lower lip and/or other facial areas; nerve impairment causing weakness of certain facial muscles; ongoing pain; and/or other associated abnormalities.
In individuals with ACC of the salivary glands, recurrences at the primary site of tumor development are not uncommon months or years after treatment. In addition, approximately 40 percent or more of affected individuals may experience metastasis to distant bodily sites, particularly the lungs. According to reports in the literature, those with primary tumors of the submandibular salivary gland may be up to twice as likely to experience distant metastases as those with ACC of the parotid gland.
ACC may also arise in other sites within the head and neck region, such as the glands that produce tears (lacrimal glands). Lacrimal gland ACC may be associated with regional invasion of the bony cavity that contains the eyeball and possible tumor extension within the skull. Although lacrimal gland ACC appears to occur predominantly during adulthood, there have been some reports of the disease in children and adolescents. Some researchers indicate that this form of ACC assumes a somewhat less aggressive course when it occurs among the young.
In rare cases, ACC may also arise in certain skin regions (primary cutaneous ACC). Such malignancies primarily develop on the external ear canal, potentially resulting in pain, discharge of pus and/or blood, and/or other symptoms. ACC of the skin is typically characterized by the development of isolated or multiple reddish (erythematous) nodules or plaques that may vary in size. Such malignancies tend to invade local soft tissue and bone aggressively. Other primary sites of tumor development have been reported, including the scalp, arms or legs, and trunk. Although associated symptoms may vary, findings may include pain, increased sensitivity, or perceiving pain from stimuli not normally associated with pain. In addition, individuals with involvement of the scalp may experience hair loss (alopecia) in the area of tumor growth. ACC of the skin may be associated with infiltration of nerves and, in rare cases, result in distant metastases. In addition, in many affected individuals, local recurrences may develop months or years after surgical removal of the initial lesion.
ACC may also arise within certain organs of the lower or upper respiratory tract, breast, esophagus, neck of the uterus (cervix) in females, prostate gland in males, or other areas.
ACC of the lower respiratory tract most frequently develops in mucous glands of the windpipe (trachea), particularly the upper third of the trachea. (Most primary tracheal cancers tend to develop in the lower third of the windpipe.) The trachea, a tube-like structure, is composed of involuntary muscle, rings of cartilage, and fibrous and elastic tissue. It is lined with mucous membranes. In individuals with tracheal ACC, tumor growth gradually causes obstruction of the windpipe, resulting in difficult or labored breathing; hoarseness; and/or a high-pitched, respiratory sound upon the intake of breath (stridor). Additional symptoms may include a general feeling of ill health (malaise), weight loss, pain, recurrent inflammation of the lungs (pneumonitis), and/or the coughing up of blood.
In ACC of the lower respiratory tract, the malignancy tends to infiltrate regional lymph nodes and may spread along nerves to bone, particularly the spine (vertebrae). More rarely, sites of metastases may include the lungs, liver, brain, kidneys, or other regions.
In some individuals, ACC may also arise in mucous glands of the voice box (larynx), which lies between the throat (pharynx) and the trachea. The larynx is composed of fibrous connective tissue and is lined with mucous membranes. ACC of the larynx most commonly arises in the region beneath the glottis (subglottic region), which is the slit-like opening between the vocal cords. In addition, these tumors may regionally invade the vocal cords. Tumor growth in the subglottic region gradually results in difficulty breathing upon exertion, shortness of breath, and eventual airway obstruction. When the malignancy develops above the opening; between the vocal cords (supraglottic region), it may eventually result in persistent hoarseness, difficulty swallowing, and soreness of the throat. In some individuals with ACC of the larynx, a mass may be seen in the neck area. Because this malignancy tends to infiltrate nerves, some affected individuals may also experience associated pain or discomfort. Laryngeal ACC may spread through the bloodstream, as well as via the nerves. Metastatic disease most typically occurs in the lungs; however, other sites may include bone or the brain.
ACC may also arise in the breast. However, the disease course may be markedly different from primary ACC in other regions of the body. For example, ACC of the breast is considered a less aggressive malignancy that is not as likely to invade regional lymph nodes, metastasize, or locally recur. Researchers attribute such characteristics to several possible factors, such as slower overall tumor growth, relatively small tumor size, and an increased ability to remove all traces of such malignancies surgically, as opposed to ACC in other primary sites. However, this malignancy may invade adjacent tissue and infiltrate nerves. In addition, although considered extremely rare, local recurrences may develop and metastatic disease may occur months or years after surgical removal of the primary tumor. The most common site of metastatic disease is the lung. Other, more rarely reported areas of metastasis include lymph nodes, soft tissue, bone, the brain, and the kidneys. These rare cases of local recurrence and metastasis have been attributed to incomplete removal of the primary tumor.
According to reports in the medical literature, only one breast is affected. To date, no cases have been reported in which both breasts developed ACC. ACC of the breast is characterized by the development of a slowly enlarging, moveable mass that may cause tenderness or pain, unlike some other forms of breast cancer. Tumors tend to develop in the region of the nipple or areola, the pigmented, circular area of skin surrounding the nipple. Findings that may be associated with other malignancies in this region, such as bloody discharge, indentation of the nipple, and/or tumor invasion of the chest muscle, appear to be uncommon in association with ACC.
Other rare primary sites of ACC may include the esophagus, the neck of the uterus (cervix) in females, and the prostate gland in males. The esophagus, which is the muscular tube that transports food from the throat to the stomach, is also lined with mucous membranes. The term “adenoid cystic carcinoma” has been used to describe two quite different, rare forms of esophageal cancer. The more common of the two is mistakenly identified as ACC; instead, it is more accurately identified as “basaloid squamous carcinoma.” This malignancy aggressively invades nearby tissues and typically metastasizes late in the disease’s course, predominantly to the lungs. Other metastatic sites may include soft tissues, the liver, or the brain. “True” ACC of the esophagus, which is extremely rare, has the same cellular structure and composition as ACC of the salivary glands and other areas of the body. As with ACC of the salivary gland, true esophageal ACC is a slow-growing malignancy that may be prone to perineural invasion, local recurrences, and distant metastases. Initially, affected individuals may have problems swallowing solids. With increasing tumor growth, they may have difficulties swallowing soft foods as well as liquids, including even saliva in some cases. This typically results in regurgitation of food and liquids, with associated weight loss.
Rarely, ACC may arise in the cervix, particularly in females after menopause. The cervix is a relatively small organ that forms the lower region and neck of the uterus. Initial symptoms may include a watery or blood-stained discharge or vaginal bleeding in association with a relatively large cervical mass. This form of ACC may also tend to recur and may spread to distant sites.
In some males, ACC may arise in the prostate gland, an organ that is part of the male reproductive system. This rare form of ACC is considered a subtype of prostate adenocarcinoma, a common form of prostate cancer. Symptoms may include poor flow of urine, increased frequency of urination, and/or difficulties beginning urination due to enlargement of the prostate gland and associated obstruction of the urinary tract.
Rarely, ACC may arise in other regions of the body. The specific symptoms and clinical course may vary from case to case, depending upon the primary tumor site, size, nature, progression, and other factors.
As discussed above, most forms of ACC may tend to recur locally and to spread to distant bodily sites. Many researchers attribute local recurrences to incomplete surgical removal of microscopic traces of the malignancy. In addition, local recurrences may more commonly occur if the primary tumor is advanced when first detected. Some studies suggest that most local recurrences tend to occur by about three to three and a half years after initial therapy. In addition, the average time between initial treatment for ACC and metastasis is thought to be approximately eight years. However, depending upon the primary site and other factors, infiltration of surrounding tissues and distant metastases may also be relatively common at diagnosis, occurring in up to approximately one-third of individuals with ACC. Due to the slow-growing nature of ACC, survival may be long-term, even in those with advanced tumor involvement, local recurrences, and/or distant metastases. However, it is important to note that overall clinical course may vary greatly from case to case.
The exact underlying cause of adenoid cystic carcinoma is unknown. Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., exposure to ultraviolet rays, certain chemicals, ionizing radiation), diet, stress, and/or other factors may play contributing roles in causing specific types of cancer. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer.
In individuals with cancer, including ACC, malignancies may develop due to abnormal changes in the structure and orientation of certain cells. The specific cause of such changes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body’s genetic code, are the underlying basis of cellular malignant transformation. These abnormal genetic changes may occur spontaneously for unknown reasons or, more rarely, may be inherited.
In cells that have undergone malignant transformation, there is typically reversion to a less specialized, more primitive form (anaplasia or loss of “differentiation”), meaning that they are no longer capable of performing their “intended,” specialized functions within the tissue in question. Malignant cells pass their abnormal changes on to all their “daughter” cells and typically grow and divide at an unusually rapid, uncontrolled rate that cannot be contained by the body’s natural immune defenses. Eventually, such proliferation of abnormal cells may result in formation of a mass known as a tumor (neoplasm). Disease progression may be characterized by invasion of surrounding tissues, infiltration of regional lymph nodes, and spread of the malignancy via the bloodstream, the lymphatic circulation, or other means to other bodily tissues and organs.
Research is ongoing to isolate and characterize the specific genes in which abnormalities in or loss of their expression may play a role in ACC development or progression. Such information concerning the molecular changes in ACC may ultimately be helpful in improving the diagnosis and treatment of this cancer.
ACC primarily affects adults, although some forms have been reported during childhood and adolescence, such as ACC of the lacrimal glands. The average age at disease onset may vary from case to case, depending upon the form of ACC present and other factors. The ratio of males to females with the disease may also be variable, based upon the specific form of ACC in question.
ACC of the salivary glands, the most common form of the disease, is thought to account for approximately 25 percent of malignant salivary gland tumors. It typically develops from early to late adulthood. ACC of the lower respiratory tract accounts for less than one percent (0.1 to 0.2 percent) of all primary lung tumors. It appears to affect males and females relatively equally, and most commonly occurs during the fifth decade of life. ACC of the larynx has been reported in individuals ranging from approximately 25 to 75 years of age, with most cases occurring in the fifth to sixth decade of life. Males and females appear to be equally affected. Primary ACC of the breast is extremely rare, representing less than one percent of all breast cancers (0.1 percent). This form of ACC primarily occurs in females. In the few reported cases among males, disease presentation and course have been similar to that seen in affected females. This malignancy tends to become apparent during mid to late adulthood. In females, ACC of the cervix typically becomes apparent after menopause. However, there are a few reports of the disease in younger females. Prostate ACC also tends to develop during or after middle age.
As mentioned above, the term “adenoid cystic carcinoma of the esophagus” has been used to describe two different, rare forms of cancer. “True” ACC is extremely rare, with only a few cases reported in the medical literature. The more common of the two entities, which is more appropriately termed “basaloid squamous carcinoma,” has been reported in individuals who range in age from approximately 35 to 85 years. Although initial reports indicated that females were primarily affected, later descriptions have found a higher incidence in males.
The diagnosis of adenoid cystic carcinoma is based upon a thorough clinical evaluation, characteristic symptoms and physical findings, a detailed patient history, and a variety of specialized tests. Such testing includes microscopic evaluation of tumor cells.
In individuals with ACC of the salivary glands, physical examination may reveal the presence of a hard fixed mass, and certain neurologic symptoms, such as facial numbness, weakness, or pain due to involvement of particular nerves. In some cases, a diagnostic technique may be performed in which a thin, hollow needle is used to withdraw small samples of tissue from the salivary glands (fine-needle biopsy).
Specialized imaging techniques may be used to help evaluate the size, placement, and extension of the tumor and to serve as an aid for future surgical procedures, among individuals with ACC of the salivary glands or other regions of the head and neck. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. Laboratory tests and specialized imaging tests may also be conducted to determine possible infiltration of regional lymph nodes and the presence of distant metastases.
In addition, in some individuals, the diagnosis of ACC may be established through the surgical removal of a portion of an affected salivary gland and microscopic evaluation of tumor tissue. Similar clinical, biopsy, laboratory, and imaging techniques may be used to evaluate and confirm the diagnosis of other primary ACC tumors.
Among individuals with ACC of the lower respiratory tract, such as tracheal ACC, diagnostic testing often includes the use of a flexible instrument (inserted through the mouth or nose) that produces an image of the trachea and the air passages of the lungs. During this procedure, biopsy samples are also obtained for microscopic evaluation. In addition, a series of procedures may be performed to evaluate the function of the lungs (pulmonary function tests), particularly among older individuals being considered as surgical candidates.
Diagnostic testing for ACC of the larynx may include direct visual examination with a flexible, tube-like instrument (direct laryngoscopy) or indirect observation of the larynx's interior with a mirror. Small samples of laryngeal tissue are also removed for microscopic examination.
In females with ACC of the breast, mammograms are typically performed. Fine-needle biopsy, microscopic evaluation of tumor tissue, and other laboratory techniques may then be performed to confirm ACC and to help characterize the nature of the malignancy. Some researchers suggest that the diagnosis and initial treatment of ACC of the breast should include surgical removal and microscopic evaluation of the malignancy. Unlike with many other forms of breast cancer, routine sampling of regional lymph nodes during initial surgery may be of questionable value, since involvement of regional lymph nodes is thought to be extremely rare with ACC of the breast.
In those with ACC of the esophagus, diagnostic testing may include barium x-ray procedures, during which a mixture containing water and a metallic chemical (barium) is swallowed. Because barium is impenetrable by x-rays, subsequent imaging of the digestive tract may help to reveal the nature and extent of the esophageal tumor. Diagnostic procedures may also include endoscopy, during which a flexible, tube-like instrument is used to visualize the esophagus and to obtain biopsy samples. Microscopic evaluation of biopsy samples may help to differentiate between “true ACC” and other forms of esophageal cancer.
In females with cervical ACC, diagnostic testing may include specialized tests to detect abnormal cellular changes in the cervix (cervical smear test), examination of the cervix with a magnifying instrument (colposcopy), and biopsy. In males with ACC of the prostate gland, clinical examination of the prostate (which may be felt through the rectum) may reveal the presence of a hard mass. Diagnostic testing may include blood studies, specialized imaging of the urinary tract (pyelography), the use of high-frequency sound waves to create an image of the prostate and other internal organs (ultrasonography), biopsies, and/or other tests.
The therapeutic management of individuals with ACC may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), specialists in the use of radiation to treat cancer (radiation oncologists), surgeons, oncology nurses, and other specialists (depending upon the primary tumor site).
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as primary tumor location, extent of the primary tumor (stage), and degree of malignancy (grade), whether the tumor has spread to lymph nodes or distant sites, individual's age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks; patient preference, and other appropriate factors.
In many individuals with ACC, standard therapy includes surgical removal of the malignancy and affected tissue. Depending upon the location of the primary tumor, surgical procedures may also include the use of certain reconstructive techniques (e.g., tracheal reconstruction in those with severe ACC involving the windpipe).
In addition, based upon primary tumor site, size, and other factors, recommended standard therapy may often include postoperative radiation to help treat known or possible residual disease. If initial surgery is not an option due to the specific location and/or progression of the malignancy, therapy may include radiation alone. Radiation therapy preferentially destroys or injures rapidly dividing cells, primarily cancerous cells. However, some healthy cells (e.g., hair follicles, bone marrow, etc.) may also be damaged, leading to certain side effects. Thus, during such therapy, the radiation is passed through diseased tissue in carefully calculated dosages to destroy cancer cells while minimizing exposure and damage to normal cells. Radiation therapy works to destroy cancer cells by depositing energy that damages their genetic material, preventing or slowing their growth and replication. Various types of radiation may be used–again, depending on cancer type, location, stage and grade, prior treatments, etc.–including conventional external radiotherapy (e.g., standard photon and/or electron treatments) and/or, in some selected cases, neutron radiation. (For more on neutron radiation, please see “Investigational Therapies” below.)
For some affected individuals, particularly those who have locally advanced, metastatic, or recurrent disease, therapy with certain anticancer drugs (chemotherapy) may also be recommended, possibly in combination with surgical procedures and/or radiation, physicians may recommend combination therapy with multiple chemotherapeutic drugs that have different modes of action in destroying tumor cells and/or preventing them from multiplying. In most cases, however, chemotherapy has had only limited success in slowing or stopping progression of ACC. The use of chemotherapy in the treatment of ACC remains under investigation. (Please see the “Investigational Therapies” section below.)
More specifically, depending upon the primary tumor site and other factors, particular surgical procedures and/or other therapies may be conducted.
Among individuals with ACC of the salivary glands, postoperative radiotherapy is playing an increasingly important, common role in treatment. In some cases, radiation therapy alone may be recommended, such as when the malignancy encases a nerve.
In individuals with ACC of the lacrimal glands, treatment may consist of surgical removal of the tumor, removal of the eye and associated tissues in case of local infiltration, and possible postoperative radiation therapy. Affected individuals may then undergo surgical reconstructive techniques and be fitted with an artificial ocular device. However, in other cases, such as among children who may tend to have a less malignant course, other measures may be considered appropriate.
In individuals with primary ACC of the skin, treatment typically includes surgical removal of affected skin areas and possible radiation therapy.
In those with ACC of the lower respiratory tract, standard treatment also includes surgical removal of all microscopic traces of the tumor. Depending upon the extent and location of tracheal ACC, reconstructive surgical measures may be required. In some individuals with ACC of the lower respiratory tract, therapy may also include postoperative radiation. More rarely, radiation therapy may be provided before surgery. In addition, radiation therapy alone may be provided if the tumor may not be surgically removed.
In individuals with ACC of the voice box (larynx), initial therapy may include partial or complete removal of the larynx (laryngectomy). In addition, with certain types of tumors, a portion of the esophagus may also need to be surgically removed. Distant metastases are commonly present at the time of diagnosis. In such cases, treatment may include radiotherapy and/or chemotherapy. Individuals who undergo surgical removal of all or a portion of the larynx typically learn new methods of producing speech.
As mentioned above, some researchers indicate that the initial treatment (and diagnosis) of ACC of the breast should include surgical removal of all microscopic traces of the malignancy. Routine sampling of regional lymph nodes during initial surgery is thought to be of questionable value. The effects of radiotherapy on local recurrence and disease course have not been determined. Local recurrences may be treated with repeat surgery.
In individuals with ACC of the esophagus, initial therapy typically includes surgical removal of all or a portion of the esophagus (esophagectomy). Some individuals may also receive radiation therapy.
Depending upon tumor stage, grade, progression, and other factors, females with ACC of the cervix may receive radiation alone or surgical removal of affected tissue, radiation, and/or chemotherapy.
In males with ACC of the prostate gland, treatment often includes surgical removal of the prostate gland, and of nearby tissues when they are infiltrated, and postsurgical radiation therapy.
Long-term follow-up is essential with ACC in ensuring the prompt detection and treatment of local recurrences and metastatic disease. Because the lungs are a common location of metastasis, physicians recommend regular CT scans of the lungs. Other standard therapies for individuals with ACC include symptomatic and supportive measures as required.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
On 30th of March 2009, the National Cancer Institute (NCI) granted approval and funding for a clinical trial of Dasatinib (also referred to by its brand name Sprycel) in patients with recurrent or metastatic malignant salivary gland cancers. The primary objective is to determine the drug’s efficacy in shrinking tumors (objective response) and keeping tumors from growing (progression-free survival) in ACC patients whose salivary gland tumors express c-kit (a gene associated with some cancers).
The following link provides additional information on the trial’s objectives, entry criteria, expected enrollment, sites and contact information:
For more information contact:
P.O. Box 442
Needham, MA 02494
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