Paraganglioma

What is a paraganglioma?

A paraganglioma (also known as an extra-adrenal pheochromocytoma) is a rare neuroendocrine tumor (NET) that forms near your carotid artery (the major blood vessels in your neck), along nerve pathways in your head and neck and in other parts of your body. The tumor is made of a certain type of cell called chromaffin cells, which produce and release certain hormones known as catecholamines.

Your adrenal glands, the two glands that are on top of each kidney, make several hormones. Among these are hormones called catecholamines that help control the following important bodily functions:

• Heart rate.
• Blood pressure.
• Blood sugar (blood glucose).
• The way your body responds to stress.

The primary catecholamines include:

• Dopamine.
• Epinephrine (adrenaline).
• Norepinephrine (noradrenaline).

Even though paragangliomas don’t form in your adrenal glands, they’re made of tissue that’s found in your adrenal glands. Paragangliomas may release extra catecholamines into your blood, causing certain signs and symptoms.

What is the difference between paraganglioma and pheochromocytoma?

Paraganglioma and pheochromocytoma are both rare tumors that form from the same type of cells known as chromaffin cells. The difference is where they form in your body.

Pheochromocytomas form in the center of your adrenal gland (adrenal medulla), and paragangliomas form outside your adrenal gland, usually along the arteries or nerves in your neck. Paragangliomas are also called extra-adrenal pheochromocytomas.

Is paraganglioma cancer?

Paragangliomas can be benign (not cancer) or malignant (cancer). Approximately 20% of paragangliomas are malignant.

It can be very challenging for healthcare providers to tell if a paraganglioma is cancerous or not — even after they’ve looked at the tumor tissue under a microscope after it’s been removed. Because of this, a paraganglioma is often considered cancer if it has:

• Spread to nearby tissues (regional spread of paraganglioma).
• Spread to distant areas like your lungs or bone (metastasized).
• Come back after initial treatment (recurred).

There’s no standard staging system for paraganglioma if it’s cancerous. Instead, it’s described as the following:

• Localized paraganglioma: The tumor is in one area only.
• Regional paraganglioma: Cancer has spread to lymph nodes or other tissues near its original location.
• Metastatic paraganglioma: Cancer has spread to other parts of your body, such as your liver, lungs, bone or distant lymph nodes. Approximately 35% to 50% of malignant paragangliomas may spread to other parts of your body (metastasize).
• Recurrent paraganglioma: Cancer has recurred (come back) after it has been treated. It may come back in the same place or in another part of your body.

How fast does a paraganglioma grow?

Paragangliomas usually grow very slowly. But this could vary from case to case.

Who does paraganglioma affect?

Anyone at any age can get a paraganglioma, but they occur most often in people between 30 and 50 years of age. Approximately 10% of cases occur in children.

How common is paraganglioma?

Paraganglioma is a rare tumor. It’s estimated that only 2 out of every 1 million people have paraganglioma.

What are the symptoms of paraganglioma?

Signs and symptoms of paraganglioma happen when the tumor releases too much adrenaline or noradrenaline into your blood. However, some paraganglioma tumors don’t make extra adrenaline or noradrenaline and don’t cause symptoms (are asymptomatic). Common symptoms of paraganglioma include episodes of:

• High blood pressure (hypertension).
• Headaches.
• Excessive sweating for no known reason.
• A pounding, fast or irregular heartbeat.
• Feeling shaky.

Less common symptoms of pheochromocytoma include:

• Being much paler than you usually are.
• Nausea and/or vomiting.
• Diarrhea.
• Constipation.
• Elevated blood glucose levels (hyperglycemia).
• An extreme drop in blood pressure upon standing suddenly (orthostatic hypotension).
• Unexplained weight loss.

Some people who have a paraganglioma may experience symptoms infrequently or in bursts.

What causes paraganglioma?

In most cases of paraganglioma, the exact cause is unknown, and it occurs randomly. Approximately 25% to 35% of people who have paraganglioma have a hereditary condition (passed through the family) that’s linked to paraganglioma, including:

• Multiple endocrine neoplasia 2 syndrome, types A and B (MEN2A and MEN2B).
• Von Hippel-Lindau (VHL) disease.
• Neurofibromatosis type 1 (NF1).
• Hereditary paraganglioma syndrome.
• Carney-Stratakis dyad (paraganglioma and gastrointestinal stromal tumor [GIST]).
• Carney triad (paraganglioma, GIST, and pulmonary chondroma).

How is paraganglioma diagnosed?

Since paraganglioma is a rare tumor and is sometimes asymptomatic, it can be difficult to diagnose. Healthcare providers sometimes find paragangliomas when they order a test or procedure for another reason.

A provider may suspect a diagnosis of paraganglioma after reviewing the following factors:

• A detailed medical history, including previous pheochromocytoma or paraganglioma cases in your family.
• A thorough physical and medical evaluation.
• Certain symptom characteristics, such as high blood pressure that’s unresponsive to standard treatment.

What tests are used to diagnose paraganglioma?

Your healthcare provider may use the following tests and procedures to diagnose paraganglioma:

• Physical exam: Your provider will perform a physical exam of your body to check general signs of health, such as your blood pressure. They will also ask you about your medical history, including your family’s medical history as it relates to endocrine issues.
• 24-hour urine test: This type of urine (pee) test involves collecting samples of your urine for 24 hours to measure the amounts of adrenal hormones called catecholamines in your urine. Substances that result from the breakdown of these hormones are also measured. Higher-than-normal amounts of certain catecholamines in your urine may be a sign of paraganglioma.
• Blood catecholamine tests: These tests measure the level of catecholamines in your blood. Substances that result from the breakdown of these hormones are also measured. Higher-than-normal amounts of certain catecholamines in your blood may be a sign of paraganglioma.
• PET scan (positron emission tomography scan): A positron emission tomography (PET) scan uses a safe injectable radioactive chemical called a radiotracer and a device called a PET scanner to produce images of your organs and tissues. The scanner detects metabolically active cells and tumors that absorb large amounts of the radiotracer, which indicates a potential health problem. This imaging test is particularly good for determining the location of paragangliomas.
• CT scan (computer tomography scan): A CT scan is an imaging procedure that takes a series of X-ray images from different angles to provide detailed pictures of areas inside your body. Your provider may recommend a CT scan so that they can determine where the tumor is (most commonly in the neck area).
• MRI (magnetic resonance imaging): An MRI is an imaging procedure that uses a magnet, radio waves and a computer to make a series of detailed pictures of areas inside your body. Your provider may recommend an MRI so that they can look at the region of your body where the tumor is located.

After your provider has diagnosed you with paraganglioma, they’ll likely perform additional tests to see if it has spread to other parts of your body.

Is there genetic testing for paraganglioma?

If you’re diagnosed with paraganglioma, your provider will likely recommend genetic counseling to find out your risk for having an inherited syndrome and associated cancers.

Your healthcare provider may recommend genetic testing if any of the following situations apply to you:

• You have a personal or family history of traits linked with inherited pheochromocytoma or paraganglioma syndrome.
• You have signs or symptoms of higher-than-normal catecholamine levels in your blood or cancerous paraganglioma.
• You’ve been diagnosed with paraganglioma before age 40.

If your genetic counselor finds certain gene changes in your testing results, they will likely recommend that your family members who are at risk but don't have signs or symptoms be tested as well.

How is paraganglioma treated?

Treatment options for paraganglioma depend on several factors, including:

• The size of the tumor.
• If the tumor is benign (not cancer) or malignant (cancer).
• If you have symptoms caused by higher-than-normal levels of catecholamines.
• If the tumor is in one area only or has spread to other places in your body (metastasized).
• If the tumor has been diagnosed for the first time or has come back (recurred).

If you have a paraganglioma that causes symptoms due to excess adrenal hormones, your healthcare provider will likely recommend medication to manage the symptoms. Medications may include:

• Medication that keeps your blood pressure regulated, such as alpha-blockers.
• Medication that keeps your heart rate normal, such as beta-blockers.
• Medication that blocks the effect of the excess hormones released by your adrenal gland(s).

Treatment options for paraganglioma include:

• Surgery and tumor removal.
• Radiation therapy.
• Chemotherapy.
• Ablation therapy.
• Targeted therapy.

Together, you and your healthcare team will determine a treatment plan that works best for you and your situation.

Surgery and tumor removal

Surgery is the main form of treatment for paragangliomas. During the surgery to remove the tumor, your surgeon will check the surrounding tissue and lymph nodes to see if the tumor has spread. If it has, your surgeon will remove the affected tissue(s) as well, if possible.

Most paragangliomas can be removed using minimally invasive techniques such as laparoscopic surgery, which involves making a few small incisions in your skin and removing the tumor with special instruments. However, traditional open surgery may be needed for large tumors.

After surgery, your provider will check your catecholamine levels in your blood or urine. Normal catecholamine levels are a sign that all the paraganglioma cells were removed.

Radiation therapy

Radiation therapy is a cancer treatment that focuses strong beams of energy to destroy cancer cells or keep them from growing while sparing as much surrounding healthy tissue as possible.

There are two types of radiation therapy:

• External radiation therapy: This therapy uses a machine outside your body to send radiation toward cancer.
• Internal radiation therapy: This therapy uses a radioactive substance sealed in needles, seeds, wires or catheters that a healthcare provider places directly into or near cancer.

The type of radiation therapy your provider may recommend depends on whether your cancer is localized, regional, metastatic or recurrent. Providers most often use external radiation therapy and/or 131I-MIBG therapy to treat malignant paraganglioma. The treatment 131I-MIBG is a radioactive substance infusion that collects in certain kinds of tumor cells, killing them with the radiation that it gives off.

Chemotherapy

Chemotherapy is the standard therapy for treating metastatic paraganglioma. It’s a cancer treatment that uses drugs to stop the growth of cancer cells by killing the cells or by preventing them from dividing and multiplying. Chemotherapy is usually given through a vein (intravenously). It’s usually an effective treatment, but it can cause side effects.

Ablation therapy

Ablation therapy is a minimally invasive treatment option that uses very high or very low temperatures to destroy tumors. Ablation therapies that can help kill cancer cells and abnormal cells include:

• Radiofrequency ablation: This is a therapy that uses radio waves to heat and destroy cancer cells and abnormal cells. The radio waves travel through electrodes (small devices that carry electricity).
• Cryoablation: This therapy uses liquid nitrogen or liquid carbon dioxide to freeze and destroy cancer cells and abnormal cells.

Targeted therapy

Targeted therapy is a treatment option that uses medications or other substances to attack specific cancer cells without harming healthy cells. Healthcare providers use targeted therapies to treat metastatic and recurrent paraganglioma.

Researchers are currently studying sunitinib, a type of tyrosine kinase inhibitor, for treatment for metastatic paraganglioma. Tyrosine kinase inhibitor therapy is a type of targeted therapy that prevents tumors from growing.

Can I prevent paraganglioma?

Unfortunately, you can’t prevent developing a paraganglioma. However, if you’re at risk for developing a paraganglioma due to certain inherited syndromes and genes, genetic counseling can help screen for paraganglioma and potentially catch it in its early phases.

Talk to your healthcare provider if you have any first-degree relatives (siblings and parents) that have been diagnosed with paraganglioma or pheochromocytoma and/or any of the following genetic conditions:

• Multiple endocrine neoplasia 2 syndrome.
• Von Hippel-Lindau (VHL) disease.
• Neurofibromatosis type 1.
• Hereditary paraganglioma syndrome.
• Carney-Stratakis dyad.
• Carney triad.

What is the prognosis (outlook) for paraganglioma?

The prognosis (outlook) for paraganglioma varies depending on certain factors, including:

• Where the tumor is in your body and how big it is.
• If it’s cancer and has spread to other parts of your body.
• If the tumor was able to be surgically removed and if so, how much of the tumor was removed during surgery.

People who have a small paraganglioma that has not spread to other parts of their body (has not metastasized) have a five-year survival rate of about 95%. People who have paraganglioma that has come back after initial treatment (recurred) or spread to other parts of their body (metastasized) have a five-year survival rate between 34% and 60%.

There are also cases of aggressive paraganglioma tumors that haven’t metastasized but have invaded local tissue to the point where surgery can’t fully remove it. In these cases, the excess release of adrenaline and noradrenaline can be dangerous and difficult to treat.

If paragangliomas are left untreated, whether benign or malignant, they can potentially cause serious, life-threatening complications due to the excess amounts of adrenaline and noradrenaline they can secrete. Complications can include:

• Heart muscle disease (cardiomyopathy).
• Inflammation of your heart muscle (myocarditis).
• Uncontrolled bleeding in your brain (cerebral hemorrhaging).
• Accumulation of fluid in your lungs (pulmonary edema).
• Heart attack (myocardial infarction).
• Stroke.
• Coma.
• Death.

When should I see my healthcare provider about paraganglioma?

If you’ve been diagnosed with paraganglioma and experience concerning symptoms, contact your healthcare provider.

If you’re experiencing symptoms of paraganglioma, such as high blood pressure and headaches, talk to your provider. Even though paraganglioma is rare and the likelihood of having it is low, it’s important to treat high blood pressure regardless.

If you’ve recently found out that one of your first-degree relatives (siblings and parents) has a genetic syndrome, such as multiple endocrine neoplasia 2 syndrome or von Hippel-Lindau (VHL) disease, that puts you at a higher risk of developing a paraganglioma, ask your provider about genetic testing.

What questions should I ask my doctor?

If you’ve been diagnosed with a paraganglioma, it may be helpful to ask your healthcare provider the following questions:

• What caused my paraganglioma?
• Could my children and/or relatives develop a paraganglioma?
• What are my treatment options?
• What are the side effects of different treatment therapies?
• How can I manage my symptoms?

A note from Cleveland Clinic

While most paraganglioma cases have an unknown cause, there’s a significant link to certain inherited conditions. If you or one of your first-degree relatives have been diagnosed with paraganglioma or pheochromocytoma, it’s important to go through genetic testing to make sure you don’t have a genetic condition that could potentially cause other medical issues. If you have any questions about your risk of developing a paraganglioma, talk to your healthcare provider. They’re there to help you.