Adrenocortical Carcinoma

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

    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.

Treatment

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.

Contact us

To schedule a consultation or second opinion with our multidisciplinary team, contact Aymen Elfiky, MD, at 617-632-5456 or aymen_elfiky@dfci.harvard.edu.

Information for: Patients | Healthcare Professionals

General Information About Adrenocortical Carcinoma

Adrenocortical carcinoma is a rare disease in which malignant (cancer) cells form in the outer layer of the adrenal gland.

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.

Anatomy of the adrenal gland; drawing of the abdomen showing the left and right adrenal glands, the left and right kidneys, and major blood vessels. A cross section of an adrenal gland is in an inset showing the adrenal cortex and the adrenal medulla. 
Anatomy of the adrenal gland. There are two adrenal glands, one on top of each kidney. The outer part of each gland is the adrenal cortex; the inner part is the adrenal medulla.

 

The adrenal cortex makes important hormones that:

  • Balance the water and salt in the body.
  • Help keep blood pressure normal.
  • Help control the body's use of protein, fat, and carbohydrates.
  • Cause the body to have masculine or feminine characteristics.

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.)

Having certain genetic conditions increases the risk of adrenocortical carcinoma.

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:

  • Li-Fraumeni syndrome.
  • Beckwith-Wiedemann syndrome.
  • Carney complex.

Symptoms of adrenocortical carcinoma include pain in the abdomen.

These and other signs and symptoms may be caused by adrenocortical carcinoma:

  • A lump in the abdomen.
  • Pain the abdomen or back.
  • A feeling of fullness in the abdomen.

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:

  • Cortisol.
  • Aldosterone.
  • Testosterone.
  • Estrogen.

Too much cortisol may cause:  

  • Weight gain in the face, neck, and trunk of the body and thin arms and legs.
  • Growth of fine hair on the face, upper back, or arms.
  • A round, red, full face.
  • A lump of fat on the back of the neck.
  • A deepening of the voice and swelling of the sex organs or breasts in both males and females.
  • Muscle weakness.
  • High blood sugar.
  • High blood pressure.

Too much aldosterone may cause:  

  • High blood pressure.
  • Muscle weakness or cramps.
  • Frequent urination.
  • Feeling thirsty.

Too much testosterone (in women) may cause:  

  • Growth of fine hair on the face, upper back, or arms.
  • Acne.
  • Balding.
  • A deepening of the voice.
  • No menstrual periods.

Men who make too much testosterone do not usually have signs or symptoms.

Too much estrogen (in women) may cause:  

  • Irregular menstrual periods in women who have not gone through menopause.
  • Vaginal bleeding in women who have gone through menopause.
  • Weight gain.

Too much estrogen (in men) may cause:  

  • Growth of breast tissue.
  • Lower sex drive.
  • Impotence.

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.

Imaging studies and tests that examine the blood and urine are used to detect (find) and diagnose adrenocortical carcinoma.

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:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of cortisol or 17-ketosteroids. A higher than normal amount of these in the urine may be a sign of disease in the adrenal cortex.
  • Low-dosedexamethasone suppression test: A test in which one or more small doses of dexamethasone is given. The level of cortisol is checked from a sample of blood or from urine that is collected for three days.
  • High-dose dexamethasone suppression test: A test in which one or more high doses of dexamethasone is given. The level of cortisol is checked from a sample of blood or from urine that is collected for three days.
  • Blood chemistry study: A procedure in which a blood sample is checked to measure the amounts of certain substances, such as potassium or sodium, released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). An MRI of the abdomen is done to diagnose adrenocortical carcinoma.
  • Adrenal angiography: A procedure to look at the arteries and the flow of blood near the adrenal glands. A contrast dye is injected into the adrenal arteries. As the dye moves through the arteries, a series of x-rays are taken to see if any arteries are blocked.
  • Adrenal venography: A procedure to look at the adrenal veins and the flow of blood near the adrenal glands. A contrast dye is injected into an adrenal vein. As the contrast dye moves through the veins, a series of x-rays are taken to see if any veins are blocked. A catheter (very thin tube) may be inserted into the vein to take a blood sample, which is checked for abnormal hormone levels.
  • PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
  • MIBG scan: A very small amount of radioactive material called MIBG is injected into a vein and travels through the bloodstream. Adrenal gland cells take up the radioactive material and are detected by a device that measures radiation. This scan is done to tell the difference between adrenocortical carcinoma and pheochromocytoma.
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. The sample may be taken using a thin needle, called a fine-needle aspiration (FNA) biopsy or a wider needle, called a core biopsy.

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

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

  • The stage of the cancer (the size of the tumor and whether it is in the adrenal gland only or has spread to other places in the body).
  • Whether the tumor can be completely removed in surgery.
  • Whether the cancer has been treated in the past.
  • The patient's general health.
  • The grade of the tumor (how the tumor cells look under a microscope).

Adrenocortical carcinoma may be cured if treated at an early stage.

Stages of Adrenocortical Carcinoma

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

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:

  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the abdomen or chest, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium may be injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • PET scan (positron emission tomography scan): A procedure to find malignanttumor cells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
  • Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs, such as the vena cava, and make echoes. The echoes form a picture of body tissues called a sonogram.
  • Adrenalectomy: A procedure to remove the affected adrenal gland. A tissue sample is viewed under a microscope by a pathologist to check for signs of cancer.

There are three ways that cancer spreads in the body.

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

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

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

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

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

The metastatic tumor is the same type of cancer as the primary tumor. For example, if 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.

The following stages are used for adrenocortical carcinoma:

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

Stage I

In stage I, the tumor is 5 centimeters or smaller and is found in the adrenal gland only.

Stage II

In stage II, the tumor is larger than 5 centimeters and is found in the adrenal gland only.

Stage III

In stage III, the tumor can be any size and has spread:

  • to fat or lymph nodes near the adrenal gland; or
  • to nearby tissues, but not to the organs near the adrenal gland.

Stage IV

In stage IV, the tumor can be any size and has spread:

  • to nearby tissues and to fat and lymph nodes near the adrenal gland; or
  • to organs near the adrenal gland and may have spread to nearby lymph nodes; or
  • to other parts of the body, such as the liver or lung.

Recurrent Adrenocortical Carcinoma

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.

Treatment Option Overview

There are different types of treatment for patients with adrenocortical carcinoma.

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.

Three types of standard treatment are used:

Surgery

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

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

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.

New types of treatment are being tested in clinical trials.

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

Biologic therapy

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

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

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

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

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

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

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

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

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

Follow-up tests may be needed.

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

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

Treatment Options by Stage

Stage I Adrenocortical Carcinoma

Treatment of stage I adrenocortical carcinoma may include the following:

  • Surgery (adrenalectomy). Nearby lymph nodes may also be removed if they are larger than normal.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with 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.

Stage II Adrenocortical Carcinoma

Treatment of stage II adrenocortical carcinoma may include the following:

  • Surgery (adrenalectomy). Nearby lymph nodes may also be removed if they are larger than normal.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with 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.

Stage III Adrenocortical Carcinoma

Treatment of stage III adrenocortical carcinoma may include the following:

  • Surgery (adrenalectomy). Nearby lymph nodes may also be removed if they are larger than normal.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with 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.

Stage IV Adrenocortical Carcinoma

Treatment of stage IV adrenocortical carcinoma may include the following as palliative therapy to relieve symptoms and improve the quality of life:

  • Chemotherapy or combination chemotherapy.
  • Radiation therapy to bones or other sites where cancer has spread.
  • Surgery to remove cancer that has spread to tissues near the adrenal cortex.
  • A clinical trial of chemotherapy, biologic therapy, or targeted therapy.

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 Options for Recurrent Adrenocortical Carcinoma

Treatment of recurrentadrenocortical carcinoma may include the following as palliative therapy to relieve symptoms and improve the quality of life:

  • Surgery.
  • Radiation therapy.
  • A clinical trial of chemotherapy or biologic therapy.

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.

To Learn More About Adrenocortical Carcinoma

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.


General Information About Adrenocortical Carcinoma

Incidence and Mortality

Adrenocortical carcinoma (ACC) is a rare tumor that affects only 0.72 persons per one million population.[1] 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.[2] However, recently, more ACCs have been diagnosed at early states, most likely due to the widespread use of high-quality imaging techniques.

Prognostic Factors

Retrospective studies have identified the following three important prognostic factors:[3]

  • Completeness of resection.
  • Stage of disease.
  • Pathological grade.

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.

Clinical Features

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.

Diagnosis

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.

Prognosis and Survival

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%.[2]

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.[4] Overall 5-year survival is approximately 38% to 46%.[1][2]

References:

  1. 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.

  2. 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.

  3. 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.

  4. Allolio B, Fassnacht M: Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 91 (6): 2027-37, 2006.

Cellular Classification of Adrenocortical Carcinoma

Adrenocortical carcinoma can be classified into functioning and nonfunctioning tumors by clinical and biochemical assessment. Approximately 60% of adrenocortical carcinomas produce hormones.[1] The associated clinical syndromes include the following:

  • Hypercortisolism (Cushing syndrome).
  • Hirsutism/virilization.
  • Feminization.
  • Precocious puberty.
  • Hyperaldosteronism.

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:[2]

  • Nuclear grade.
  • Number of mitoses.
  • Presence of atypical mitosis.
  • Percentage of clear cells.
  • Diffuse architecture.
  • Necrosis.
  • Venous invasion.
  • Sinusoidal invasion.
  • Capsular invasion.

References:

  1. 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.

  2. Weiss LM, Medeiros LJ, Vickery AL Jr: Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 13 (3): 202-6, 1989.

Stage Information for Adrenocortical Carcinoma

There are several staging systems in use. The American Joint Committee on Cancer (AJCC) staging system [1] 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.[2] 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.[3]

In addition to the above-mentioned AJCC staging, the European Network for the Study of Adrenal Tumors (ENSAT) staging system is widely used internationally.[4] 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.[5]

Definitions of TNM

The AJCC has designated staging by TNM to define adrenocortical carcinoma.[1]

Table 1. Primary Tumor (T)a

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

T1

Tumor ≤5 cm in greatest dimension, no extra-adrenal invasion.

T2

Tumor >5 cm, no extra-adrenal invasion.

T3

Tumor of any size with local invasion, but not invading adjacent organs.b 

T4

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.

Table 2. Regional Lymph Nodes (N)a

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1

Metastases in regional lymph node(s).

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.

Table 3. Distant Metastasis (M)a

M0

No distant metastasis.

M1

Distant metastasis.

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.

Table 4. Anatomic Stage/Prognostic Groupsa

Stage

T

N

M

I

T1

N0

M0

II

T2

N0

M0

III

T1

N1

M0

T2

N1

M0

T3

N0

M0

IV

T3

N1

M0

T4

N0

M0

T4

N1

M0

Any T

Any N

M1

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.

References:

  1. 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.

  2. Doppman JL, Reinig JW, Dwyer AJ, et al.: Differentiation of adrenal masses by magnetic resonance imaging. Surgery 102 (6): 1018-26, 1987.

  3. Brown ED, Semelka RC: Magnetic resonance imaging of the adrenal gland and kidney. Top Magn Reson Imaging 7 (2): 90-101, 1995 Spring.

  4. 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.

  5. Allolio B, Fassnacht M: Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 91 (6): 2027-37, 2006.

Stage I Adrenocortical Carcinoma

Standard treatment options:  

  • Complete surgical removal of the tumor is the treatment of choice for patients with stage I adrenocortical carcinomas. The long-term survival of patients with nonfunctioning tumors is comparable to that of patients with functioning tumors. The removal of regional lymph nodes that are not clinically enlarged is not indicated.

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.[1][2][3]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I 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.

References:

  1. Terzolo M, Angeli A, Fassnacht M, et al.: Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 356 (23): 2372-80, 2007.

  2. Polat B, Fassnacht M, Pfreundner L, et al.: Radiotherapy in adrenocortical carcinoma. Cancer 115 (13): 2816-23, 2009.

  3. 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.

Stage II Adrenocortical Carcinoma

Standard treatment options:  

  • Complete surgical removal of the tumor is the treatment of choice for patients with stage II adrenocortical carcinomas. The long-term survival of patients with nonfunctioning tumors is comparable to that of patients with functioning tumors. The removal of regional lymph nodes that are not clinically enlarged is not indicated.

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.[1][2][3]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II 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.

References:

  1. Terzolo M, Angeli A, Fassnacht M, et al.: Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med 356 (23): 2372-80, 2007.

  2. Polat B, Fassnacht M, Pfreundner L, et al.: Radiotherapy in adrenocortical carcinoma. Cancer 115 (13): 2816-23, 2009.

  3. 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.

Stage III Adrenocortical Carcinoma

Standard treatment options:  

  • Complete surgical removal of the tumor, with or without regional lymph node dissection, is the treatment of choice for patients with stage III adrenocortical carcinomas. The treatment of patients who have tumors with local invasion, but without clinically enlarged regional lymph nodes, is complete surgical removal as for stage I and stage II tumors. For those with enlarged regional lymph nodes, a lymph node dissection should be included in the procedure. These patients are at a high risk of disease recurrence and should be considered for enrollment in a clinical trial.

Treatment options under clinical evaluation:  

  1. Clinical trials are appropriate for newly diagnosed patients when possible.
  2. Radiation therapy (approximately 50 to 70 Gy given over a period of 4 weeks) may be given to patients with localized but unresectable tumors.[1]
  3. For patients unable to undergo complete resection, mitotane in doses as high as 10 to 12 g per day to achieve a blood level of 14 to 20 mg/L should be considered. This adrenolytic drug produces useful clinical responses in about 20% to 30% of patients with measurable tumor burden.[2][3]

    Two other cytotoxic chemotherapy regimens are suggested to be effective and have been compared in a phase III trial:[2]

    • Streptozotocin plus mitotane.
    • Etoposide, doxorubicin, and cisplatin plus mitotane.

    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.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III 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.

References:

  1. Percarpio B, Knowlton AH: Radiation therapy of adrenal cortical carcinoma. Acta Radiol Ther Phys Biol 15 (4): 288-92, 1976.

  2. Allolio B, Fassnacht M: Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 91 (6): 2027-37, 2006.

  3. 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.

Stage IV Adrenocortical Carcinoma

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.[1][2]

Two other cytotoxic chemotherapy regimens are suggested to be effective and have been compared in a phase III trial:[1]

  • Streptozotocin plus mitotane.
  • Etoposide, doxorubicin, and cisplatin plus mitotane.

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.

Standard treatment options:  

  1. Chemotherapy with mitotane.
  2. Chemotherapy with mitotane plus streptozotocin or mitotane plus etoposide, doxorubicin, and cisplatin is used as part of the NCT00924144 phase III trial.
  3. Radiation therapy to bone metastases.
  4. Surgical removal of localized metastases, particularly those that are functioning.

Treatment options under clinical evaluation:  

Several new agents are currently under investigation for unresectable adrenocortical cancer, including the following:

  • Insulin-like growth factor 1 receptor–inhibitors.
  • Gossypol.

Trials of other chemotherapy regimens are also ongoing.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV 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.

References:

  1. Allolio B, Fassnacht M: Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 91 (6): 2027-37, 2006.

  2. 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.

Recurrent Adrenocortical Carcinoma

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.[1] Substantial morbidity, however, is associated with resection of these recurrent tumors.

Clinical trials are appropriate and should be considered whenever possible because phase I and II trials evaluate newer chemotherapeutic and biological agents.

Current Clinical Trials

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.

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

References:

  1. 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 is provided by the National Cancer Institute.

This information was last updated on November 15, 2012.

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