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Adrenocortical carcinoma, also known as adrenal cortical carcinoma (ACC), is a rare and aggressive cancer that originates in the outer layer of the adrenal gland. Adrenocortical carcinoma is remarkable for the many hormonal syndromes which can occur in patients as a result of hormone-producing ("functional") tumors.
For a rare and aggressive disease such as ACC, experience matters. At Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) we have a team of experienced ACC specialists that works together to provide necessary compassionate and comprehensive care for patients. We are passionately committed to providing every patient with the best and most personalized treatment options available, taking advantage of the full range of resources and services of a top-ranked cancer hospital and research center.
Exceptional Care for Patients with Adrenocortical Carcinoma
Multidisciplinary team approach including medical oncology, surgical oncology, endocrinology, pathology, radiation oncology, interventional radiology, and genetic counseling based on each patient’s unique situation.
Deep expertise in diagnosing and aggressively treating even the most complicated cases.
Genetic evaluation for patients who have a personal or family history that suggests an inherited predisposition to develop cancer.
One of the few multidisciplinary ACC teams in the nation with experienced specialists working together on every case.
Treatment tailored to you with a clear plan that rapidly engages all of our resources.
Timely diagnosis and treatment — appointments within three business days.
The very latest therapies, including clinical trials.
Aggressive symptom management to help you feel better.
Comprehensive support services for you and your family.
The full expertise of two world-class medical centers — Brigham and Women's Hospital and Dana-Farber Cancer Institute.
To schedule a consultation or second opinion, contact our New Patient Coordinators at 617-632-2682 to make an appointment with Rana McKay, MD. For further questions, please reach Dr. McKay's office at 617-632-3237.
There are two adrenal glands. The adrenal glands are small and shaped like a triangle. One adrenal gland sits on top of each kidney. Each adrenal gland has two parts. The outer layer of the adrenal gland is the adrenal cortex. The center of the adrenal gland is the adrenal medulla.
The adrenal cortex makes important hormones that:
Adrenocortical carcinoma is also called cancer of the adrenal cortex. A tumor of the adrenal cortex may be functioning (makes more hormones than normal) or nonfunctioning (does not make hormones). Most adrenocortical tumors are functioning. The hormones made by functioning tumors may cause certain signs or symptoms of disease.
The adrenal medulla makes hormones that help the body react to stress. Cancer that forms in the adrenal medulla is called pheochromocytoma and is not discussed in this summary. See the PDQ summary on Pheochromocytoma and Paraganglioma for more information.
Adrenocortical carcinoma and pheochromocytoma can occur in both adults and children. Treatment for children, however, is different than treatment for adults. (See the sections on Cancer of Adrenal Cortex and Pheochromocytoma and Paraganglioma in the PDQ summary on Unusual Cancers of Childhood Treatment for more information.)
Anything that increases your risk 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.
Risk factors for adrenocortical carcinoma include having the following hereditary diseases:
These and other signs and symptoms may be caused by adrenocortical carcinoma:
A nonfunctioning adrenocortical tumor may not cause signs or symptoms in the early stages.
A functioning adrenocortical tumor makes too much of one of the following hormones:
Too much cortisol may cause:
Too much aldosterone may cause:
Too much testosterone (in women) may cause:
Men who make too much testosterone do not usually have signs or symptoms.
Too much estrogen (in women) may cause:
Too much estrogen (in men) may cause:
These and other signs and symptoms may be caused by adrenocortical carcinoma or by other conditions. Check with your doctor if you have any of these problems.
The tests and procedures used to diagnose adrenocortical carcinoma depend on the patient's signs and symptoms. The following tests and procedures may be used:
The prognosis (chance of recovery) and treatment options depend on the following:
Adrenocortical carcinoma may be cured if treated at an early stage.
The process used to find out if cancer has spread within the adrenal gland 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 tests and procedures may be used in the staging process:
Cancer can spread through tissue, the lymph system, and the blood:
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.
The metastatic tumor is the same type of cancer as the primary tumor. For example, if adrenocortical carcinoma spreads to the lung, the cancer cells in the lung are actually adrenocortical carcinoma cells. The disease is metastatic adrenocortical carcinoma, not lung cancer.
In stage I, the tumor is 5 centimeters or smaller and is found in the adrenal gland only.
In stage II, the tumor is larger than 5 centimeters and is found in the adrenal gland only.
In stage III, the tumor can be any size and has spread:
In stage IV, the tumor can be any size and has spread:
Recurrentadrenocortical carcinoma is cancer that has recurred (come back) after it has been treated. The cancer may come back in the adrenal cortex or in other parts of the body.
Different types of treatments are available for patients with adrenocortical carcinoma. 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.
Surgery to remove the adrenal gland (adrenalectomy) is often used to treat adrenocortical carcinoma. Sometimes surgery is done to remove the nearby lymph nodes and other tissue where the cancer has spread.
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.
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). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type and stage of the cancer being treated.
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.
Biologic therapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.
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.
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.
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 of stage I adrenocortical carcinoma may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I adrenocortical carcinoma. 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 of stage II adrenocortical carcinoma may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II adrenocortical carcinoma. 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 of stage III adrenocortical carcinoma may include the following:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III adrenocortical carcinoma. 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 of stage IV adrenocortical carcinoma may include the following as palliative therapy to relieve symptoms and improve the quality of life:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV adrenocortical carcinoma. 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 of recurrentadrenocortical carcinoma may include the following as palliative therapy to relieve symptoms and improve the quality of life:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adrenocortical carcinoma. 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.
For more information from the National Cancer Institute about adrenocortical carcinoma, see the Adrenocortical Carcinoma Home Page.
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 June 10, 2014.
Adrenocortical carcinoma (ACC) is a rare tumor that affects only 0.72 persons per
one million population. Although it mainly occurs in adults, children can be affected, too. The median age at
diagnosis is 46 years. Historically, only about 30%
of these malignancies are confined to the adrenal gland at the time of
diagnosis. However, recently, more ACCs have been diagnosed at early states, most likely due to the widespread use of high-quality imaging techniques.
Retrospective studies have identified the following three important
Patients who have low-grade tumors without evidence of invasion into local tissues or spread to lymph nodes have an improved prognosis. The role of other prognostic indicators is controversial.
In approximately 60% of patients, symptoms related to excessive hormone secretion are the main reasons for seeking medical attention. Biochemical hormone testing reveals that up to 80% of tumors are functioning. The second most common symptoms at time of initial presentation are unspecific abdominal symptoms, such as abdominal pain or fullness. A small percentage of ACCs is incidentally discovered by imaging studies conducted for reasons other than potential adrenal disease.
Initial evaluation should include careful endocrine studies to reveal any excessive hormone production by the tumor, which can serve as a tumor marker during therapy. Staging should include imaging of the primary site by computed tomography (CT) and/or magnetic resonance imaging of the abdomen. In addition, a CT of the chest is necessary to assess potential lung metastasis. Although the use of positron emission tomography may be effective in identifying unsuspected sites of metastases, its role as a staging tool is unclear. The detection of metastatic lesions may allow effective palliation of both functioning and nonfunctioning lesions.
The most common sites of metastases are the lung, liver, peritoneum, and less commonly, the bones and major veins. Palliation of metastatic functioning tumors may be achieved by resection of both the primary tumor and metastatic lesions. Unresectable or widely disseminated tumors may be palliated by adrenolytic therapy with mitotane antihormonal drugs (i.e., ketoconazole and metyrapone), systemic chemotherapy, and/or radiation therapy. However, 5-year survival for patients with stage IV tumors is usually less than 20%.
Although several studies have shown partial or even complete remission, there is no convincing evidence to date that systemic therapy will improve the survival duration of patients with adrenal cancer. Radical
open surgical excision is the treatment of choice for patients with localized malignancies and
remains the only method by which long-term disease-free survival may be
achieved. Overall 5-year survival is
approximately 38% to 46%.
Bilimoria KY, Shen WT, Elaraj D, et al.: Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors. Cancer 113 (11): 3130-6, 2008.
Fassnacht M, Allolio B: Epidemiology of adrenocortical carcinoma. In: Hammer GD, Else T, eds.: Adrenocortical Carcinoma: Basic Science and Clinical Concepts. New York, Springer, 2010, pp 23-9.
Miller BS, Gauger PG, Hammer GD, et al.: Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade. Langenbecks Arch Surg 395 (7): 955-61, 2010.
Allolio B, Fassnacht M: Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 91 (6): 2027-37, 2006.
Adrenocortical carcinoma can be classified into functioning and nonfunctioning tumors by clinical and biochemical assessment. Approximately 60% of adrenocortical carcinomas produce hormones. The associated clinical syndromes include the following:
Biochemical assessment aims to detect increased levels of cortisol (24-hour urine, 1 mg dexamethasone suppression test, serum adrenocorticotropic hormone and cortisol), androgens (dehydroepiandrosterone sulfate, testosterone), estrogens (estradiol) and mineralocorticoids (renin, aldosterone).
Pathology can differentiate high-grade and low-grade tumors according to the mitotic activity of the tumor. The differentiation of benign and malignant adrenocortical tumors can be achieved by determination of the Weiss score, which scores several histopathological criteria, including the following:
Allolio B, Fassnacht M: Clinical presentation and initial diagnosis. In: Hammer GD, Else T, eds.: Adrenocortical Carcinoma: Basic Science and Clinical Concepts. New York, Springer, 2010, pp 31-47.
Weiss LM, Medeiros LJ, Vickery AL Jr: Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 13 (3): 202-6, 1989.
There are several staging systems in use. The American Joint Committee on Cancer (AJCC) staging system  is based on the following assessment:
The stage of adrenocortical carcinoma is determined by the size of the primary
tumor, the degree of local invasion, and whether it has spread to regional
lymph nodes or distant sites. Proper staging should include computed
tomography (CT) of the abdomen and chest. Magnetic resonance imaging (MRI) may add
specificity to CT evaluation of an adrenal mass. In-phase and out-of-phase
T1-weighted imaging may be the most effective noninvasive method to
differentiate benign from malignant adrenal masses. MRI may suggest evidence of extracapsular tumor invasion, extension into the
vena cava, or metastases. Patency of surrounding vessels can often be
demonstrated with gadolinium-enhanced sequences or flip-angle techniques.
In addition to the above-mentioned AJCC staging, the European Network for the Study of Adrenal Tumors (ENSAT) staging system is widely used internationally. The ENSAT staging system is essentially the same as the AJCC system, but reserves stage IV only for tumors with distant metastasis. Other staging systems include the classical Macfarlane system, modified by Sullivan, and the Union Internationale Contre le Cancer staging system, published by the World Health Organization.
The AJCC has designated staging by TNM to define adrenocortical carcinoma.
Primary tumor cannot be assessed.
No evidence of primary tumor.
Tumor ≤5 cm in greatest dimension, no extra-adrenal invasion.
Tumor >5 cm, no extra-adrenal invasion.
Tumor of any size with local invasion, but not invading adjacent organs.b
Tumor of any size with invasion of adjacent organs.b
aReprinted with permission from AJCC: Adrenal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 515-20.
bAdjacent organs include kidney, diaphragm, great vessels, pancreas, spleen, and liver.
Regional lymph nodes cannot be assessed.
No regional lymph node metastasis.
Metastases in regional lymph node(s).
No distant metastasis.
Adrenal. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 516-7.
Doppman JL, Reinig JW, Dwyer AJ, et al.: Differentiation of adrenal masses by magnetic resonance imaging. Surgery 102 (6): 1018-26, 1987.
Brown ED, Semelka RC: Magnetic resonance imaging of the adrenal gland and kidney. Top Magn Reson Imaging 7 (2): 90-101, 1995 Spring.
Fassnacht M, Johanssen S, Quinkler M, et al.: Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal for a Revised TNM Classification. Cancer 115 (2): 243-50, 2009.
Standard treatment options:
Treatment options under clinical evaluation:
Although adjuvant mitotane has shown some progression-free or disease-free survival advantage, there has been no overall survival advantage demonstrated thus far.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I adrenocortical carcinoma. 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.
Terzolo M, Angeli A, Fassnacht M, et al.: Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 356 (23): 2372-80, 2007.
Polat B, Fassnacht M, Pfreundner L, et al.: Radiotherapy in adrenocortical carcinoma. Cancer 115 (13): 2816-23, 2009.
Sabolch A, Feng M, Griffith K, et al.: Adjuvant and definitive radiotherapy for adrenocortical carcinoma. Int J Radiat Oncol Biol Phys 80 (5): 1477-84, 2011.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Two other cytotoxic chemotherapy regimens are suggested to be effective and have been compared in a phase III trial:
Furthermore, a substantial number of treated patients with functioning tumors will show diminution in hormone production. In cases of increased hormone production, antisteroidogenic drugs such as ketoconazole and metyrapone, and steroid receptor antagonists, such as spironolactone and mifepristone, should be considered.
The role of mitotane as adjuvant therapy after complete tumor resection is still a matter of debate but should be discussed with the patient. In the case of complete resection, the role for adjuvant mitotane and radiation therapy is the same as for stage I and stage II adrenocortical carcinoma.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Percarpio B, Knowlton AH: Radiation therapy of adrenal cortical carcinoma. Acta Radiol Ther Phys Biol 15 (4): 288-92, 1976.
Terzolo M, Ardito A, Zaggia B, et al.: Mitotane. In: Hammer GD, Else T, eds.: Adrenocortical Carcinoma: Basic Science and Clinical Concepts. New York, Springer, 2010, pp 369-82.
Temporary palliation of disseminated adrenocortical carcinomas can sometimes be achieved with the chemotherapeutic agent mitotane. Although measurable partial remissions are unusual and are reported in only 20% to 30% of cases, palliation of hormone symptoms is commonly observed. Prolonged treatment with mitotane, however, is often limited by gastrointestinal and neurologic toxicity. Local recurrences and selected sites of metastatic disease can sometimes be palliated surgically or with radiation therapy.
Two other cytotoxic chemotherapy regimens are suggested to be effective and have been compared in a phase III trial:
Furthermore, a substantial number of treated patients with functioning tumors will show diminution in hormone production. In cases of increased hormone production, antisteroidogenic drugs, such as ketoconazole and metyrapone, and steroid receptor antagonists, such as spironolactone and mifepristone, should be considered.
Clinical trials are appropriate and should be considered whenever possible because phase I and II trials evaluate newer chemotherapeutic and biologic agents.
Treatment options under clinical evaluation:
Several new agents are currently under investigation for unresectable adrenocortical cancer, including the following:
Trials of other chemotherapy regimens are also ongoing.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The question and selection of further treatment for patients with adrenocortical carcinoma
depends on many factors, including previous treatment and site of recurrence as
well as individual patient considerations. Local recurrence and selected sites
of metastatic disease can sometimes be palliated by surgery or radiation therapy. Although none of
these patients can be considered curable, palliation of hormonal symptoms and
occasional 5-year survivals can be achieved. Substantial morbidity,
however, is associated with resection of these recurrent tumors.
trials are appropriate and should be considered whenever possible because phase I and II trials evaluate newer chemotherapeutic and biological
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adrenocortical carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Jensen JC, Pass HI, Sindelar WF, et al.: Recurrent or metastatic disease in select patients with adrenocortical carcinoma. Aggressive resection vs chemotherapy. Arch Surg 126 (4): 457-61, 1991.
This information was last updated on November 15, 2012.
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