Paraganglioma

A paraganglioma — also called a “para,” or a PGL — is a type of neuroendocrine tumor that forms near clusters of nerve cells called ganglia. Many paragangliomas involve nerve calls called chromaffin cells — the same cells that can give rise to a related tumor called a pheochromocytoma. There are differences between the two types of chromaffin-related tumors, though:

• Paragangliomas can occur in any area where there are ganglia or nerve endings for the sympathetic or parasympathetic (more common) nervous systems. They’re usually found in the abdomen, pelvis, or head and neck (head and neck PGLs). Parasympathetic paras are much less likely to secret (release) hormones than sympathetic tumors.
• Pheochromocytomas are found in the adrenal gland. Pheochromocytomas arise from sympathetic ganglia and usually release hormones related to the fight or flight response.

Other paragangliomas form in related cells called glomus cells, part of the parasympathetic nervous system. These tumors grow in the chest, neck and at the bottom of the skull.

Most paragangliomas are slow growing, and most are benign (noncancerous). But some have a higher risk of turning malignant (cancerous), including tumors that may run in families.

Even benign paragangliomas can pose a risk. If the tumors release hormones, for example, blood pressure can rise and heart health can be threatened.

Paragangliomas in the head and neck can push on nerves and other structures, causing a wide variety of potential symptoms. Symptoms depend on the location and may include:

• Hearing loss
• Pain
• Swallowing issues
• Ringing in the ears

Elsewhere in the body, symptoms vary. Sometimes, they’re subtle. But many of these tumors cause a noticeable, characteristic set of signs that may come and go. Episodes typically last less than an hour, but may continue for several days. The experience may happen a couple of times a week or just a few times a month.

These classic signs are:

• Anxiety, nervousness or panic attacks
• Headaches
• Heart palpitations, marked by the heart pounding, fluttering or beating rapidly
• Hypertension (high blood pressure), though levels may rise and fall and sometimes even drop too low
• Sweating

These symptoms overlap with other conditions, but when they occur together, they can indicate paraganglioma or pheochromocytoma. Paragangliomas cause these symptoms by boosting the production and release of hormones called catecholamines. Catecholamines, which include epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine, are neurotransmitters. They bring instructions from nerves to other parts of the body.

Less commonly, paragangliomas can cause:

• Dizziness
• Dyspnea, or difficulty breathing
• Fatigue
• Flushing of the skin
• Hyperglycemia (high blood sugar)
• Nausea
• Pain in the back or belly
• Pale appearance
• Vomiting

Up to 40 percent of paragangliomas and pheochromocytomas come from genetic mutations, or variants, inherited from parents. In each case, there’s a change in one of the following genes:

• SDHA, SDHAF2, SDHB, SDHC and SDHD, a group of related genes tied to the protein succinate dehydrogenase (SDH)
• MDH2
• FH
• EPAS1, also called HIF2A

If either of your parents carries one of the genetic variants, you have a 50-50 chance of inheriting it. But even if you inherit a known variant, you don’t always develop paraganglioma. The chances vary depending on the specific variant and other factors.

For example, people with a SDHA variant have a less than 10 percent chance of developing the disease. The risk is 40 percent for SDHB and SDHD variants. With SDHD and SDHAF2, you’re only at risk of developing disease if the variant comes from your father. You can still pass on the variant to your children, regardless of which parent you got it from.

We offer genetic testing for neuroendocrine tumors and genetic counseling for families with a history of paraganglioma. Identifying risk helps us create individualized screening plans to find the disease early and make successful treatment more likely.

Sometimes, paraganglioma is found during a scan given for another reason. At other times, people come to us because of symptoms or known genetic variants in their families. (We may also confirm earlier diagnoses.) Most people are diagnosed with paraganglioma between the ages of 20 and 50.

If our team suspects paraganglioma, we recommend genetic testing to identify which variants (if any) may be involved. Results help us determine which scans and treatments to recommend.

In addition to genetic testing, our evaluation typically includes:

• Family history: We ask whether relatives have had a paraganglioma or a related tumor or are known to carry a connected genetic variant. For example, those tied to the SDH protein can cause particular tumors in the kidneys and gastrointestinal tract. A RET mutation can be related to the condition of multiple endocrine neoplasia type 2 (MEN2) and tumors on the parathyroid and thyroid glands. And EPAS1 mutations are tied to a pancreatic tumor called a somatostatinoma. If you or a family member has one of these tumors, it’s another indication pointing toward paraganglioma.
• Blood or urine testing: We look for markers in blood and urine left from high levels of catecholamines. These markers can provide vital information, though they may miss paragangliomas (such as in the head and neck) that don’t release hormones. They can also fail to detect small tumors.
• Imaging: Scans help us determine the number of tumors, the location and the size. We start with either CT — X-rays from multiple angles — or MRI involving radio waves and a computer. If there’s a chance of multiple tumors or cancer that has metastasized (spread), we also use a special scanning approach called functional imaging. This nuclear medicine tool shows tumors’ behavior and uses molecules with low radiation.

Can paragangliomas metastasize?

At the time they’re found, most paragangliomas are benign and confined to one spot. But up to 25 percent of paragangliomas eventually spread (metastasize).

When paragangliomas do metastasize, they typically spread to the lymph nodes, lungs, liver and bones. The metastatic lesions can be painful.

Metastatic paraganglioma is often less aggressive than other metastatic cancers. Treatments are available to manage the tumor and control symptoms. People can live for decades with metastatic paraganglioma with a good quality of life.

Paragangliomas and pheochromocytomas can be challenging, so you need a team of experts with experience diagnosing and treating these tumors. We run a focused program within Penn’s Neuroendocrine Tumor Program, caring for more than 200 people with these rare tumors each year.

When you come to our program, you’ll find:

• Coordination: Our clinicians represent a range of specialties working closely together. Many serve on a weekly neuroendocrine tumor board. For paragangliomas in the head and neck, they’re joined by specialized oncologists, ENT surgeons and neurosurgeons. Learn more about the tumor board at our Neuroendocrine Tumor Program.
• Expertise: All of our specialists have deep experience with paragangliomas. Many of our providers publish leading papers and give national talks, including for genetics, nuclear medicine and symptom control.
• Innovation: We offer clinical trials to improve care and develop new treatments. We also run a research effort to secure and analyze tumor samples to answer questions about paragangliomas and find new treatments. Learn more about neuroendocrine tumor research and clinical trials.
• Center of Excellence: We hold a Center of Excellence designation from the Pheo Para Alliance, the leading advocacy and research organization for paragangliomas and pheochromocytomas. It recognizes our personalized care, range of specialists and research projects. We’re one of only nine such centers in the world, seven in the U.S. and the only program east of the Appalachians.
• Support: We try to make your experience as easy and stress-free as possible. A nurse coordinator oversees records, scheduling and many other needs. Throughout your treatment, we offer a range of additional support for neuroendocrine tumors.