Your pathology report for paraganglioma

by Ashley Flaman MD and Bibianna Purgina MD FRCPC
December 19, 2025

Paraganglioma is a rare tumour that arises from paraganglion cells, specialized cells of the autonomic nervous system. These cells normally help regulate functions such as blood pressure, heart rate, and the body’s response to stress. Paragangliomas are neuroendocrine tumours, meaning they arise from cells that release hormones or hormone-like substances in response to nerve signals.

Paragangliomas can arise in many different parts of the body. Historically, they have been divided into parasympathetic paragangliomas (most often in the head and neck) and sympathetic paragangliomas (most often in the chest, abdomen, or pelvis). In practice, these tumours share many features, and on MyPathologyReport, they are described together under the single diagnosis of paraganglioma.

Paragangliomas are not classified as benign or malignant at the time of diagnosis. Instead, all paragangliomas are considered to have metastatic potential, so long-term follow-up is essential.

Where is a paraganglioma found?

Paragangliomas can arise anywhere paraganglion cells are present.

In the head and neck, common locations include:

• The carotid body near the carotid artery.

• The middle ear (jugulotympanic region).

• Along the vagus nerve.

• Less commonly, along the cervical sympathetic chain or in sites such as the larynx, thyroid region, parotid gland, nasal cavity, orbit, or skull base.

These are often referred to as head-and-neck paragangliomas.

Outside the head and neck, paragangliomas most often occur in the abdomen, retroperitoneum, pelvis, or chest, where they arise from paraganglia associated with the sympathetic nervous system. These are sometimes called extra-adrenal paragangliomas.

Some people develop multiple tumours, either at the same time or over many years. Tumours can also occur on both sides of the body.

What symptoms can a paraganglioma cause?

Symptoms depend on the location of the tumour and whether it produces hormones.

Many head and neck paragangliomas do not produce hormones and may present as a slow-growing, painless mass. Middle ear tumours often cause pulsatile tinnitus (a rhythmic whooshing sound), hearing changes, or a feeling of fullness in the ear. Larger tumours or those near nerves may cause hoarseness, difficulty swallowing, tongue weakness, or other cranial nerve symptoms.

Paragangliomas arising from the sympathetic nervous system are more likely to produce hormones such as norepinephrine or dopamine. When functional, these tumours can cause symptoms related to excess catecholamines, including high blood pressure, headaches, palpitations, sweating, anxiety, and tremors. However, some sympathetic paragangliomas—especially those associated with specific genetic mutations—may be biochemically silent.

Increasingly, paragangliomas are discovered through genetic screening in families with known inherited predisposition syndromes, sometimes before symptoms develop.

How common is paraganglioma?

Paragangliomas are rare. Tumours in the head and neck account for less than 0.5% of all head and neck tumours. They can occur at any age but are most often diagnosed in adults in their 40s to 60s. Head and neck paragangliomas show a female predominance.

Paragangliomas in the chest, abdomen, and pelvis are less common overall but occur across a wide age range, including children. In children and adolescents, paragangliomas are more likely to be associated with inherited genetic mutations.

What causes a paraganglioma?

A major cause of paraganglioma is genetic predisposition. At least 40% of paragangliomas, and possibly more, are associated with inherited mutations. In children, a hereditary cause is especially likely.

The most common genes involved encode subunits of succinate dehydrogenase (SDH), including SDHD, SDHB, SDHC, SDHA, and SDHAF2. Mutations in these genes affect how cells handle oxygen and energy, leading to abnormal cell growth.

• SDHD mutations are most often associated with head and neck paragangliomas, usually multiple.

• SDHB mutations are more often associated with abdominal paragangliomas and a higher risk of metastasis.

Less commonly, paragangliomas are associated with other inherited conditions involving genes such as VHL, RET, or NF1. Rare non-inherited mechanisms affecting SDH function have also been described.

Environmental factors such as chronic low oxygen levels, including living at high altitude or having congenital heart disease, may increase the risk in genetically susceptible individuals.

How is the diagnosis made?

The diagnosis of paraganglioma is based on a combination of clinical findings, imaging, laboratory tests, and pathology.

Imaging and biochemical testing

Imaging studies such as CT, MRI, or PET-CT are used to locate the tumour and assess for multifocal disease. PET-CT using tracers that bind somatostatin receptors (such as Ga-68 DOTATATE) is especially sensitive and can also help guide treatment options.

Blood or urine tests may be performed to measure catecholamines and their metabolites, including metanephrines and 3-methoxytyramine, even if the tumour is thought to be non-functioning.

Microscopic features

When examined under the microscope, paragangliomas show a characteristic nested growth pattern called a Zellballen pattern. The nests are made of chief cells, which have moderate amounts of pink or pale cytoplasm and round to oval nuclei with finely stippled (“salt and pepper”) chromatin. These nests are surrounded by delicate blood vessels and supporting cells called sustentacular cells.

Mitotic figures are usually rare, and the microscopic appearance alone cannot determine whether a paraganglioma will behave aggressively.

Immunohistochemistry

Immunohistochemical stains help confirm the diagnosis. Chief cells express neuroendocrine markers such as synaptophysin, chromogranin A, and INSM1, as well as nuclear GATA3. Sustentacular cells are highlighted with S100 or SOX10.

Staining for SDHB is especially important. Loss of SDHB staining suggests an underlying SDH gene mutation and identifies patients who may have a hereditary syndrome and a higher risk of aggressive behaviour.

Are molecular tests needed?

Routine molecular testing of the tumour is not required for diagnosis. However, genetic testing of the patient is strongly recommended for most people diagnosed with paraganglioma, regardless of age or tumour location, because of the high rate of inherited mutations.

What is the prognosis for a person with paraganglioma?

Most paragangliomas grow slowly. Head and neck paragangliomas have a relatively low risk of metastasis, whereas paragangliomas in the abdomen and retroperitoneum have a higher risk.

The most important predictors of aggressive behaviour include:

• Tumour location outside the head and neck.

• Underlying SDHB mutation.

• Tumour size and local invasion.

Metastases can occur many years after the initial diagnosis, which is why lifelong follow-up is recommended, especially for patients with hereditary disease.

Questions to ask your doctor

• Where is my paraganglioma located?
• Does my tumour produce hormones?
• Do I need genetic testing, and should my family members be tested?
• Was SDHB testing performed on my tumour?
• What imaging or blood tests will I need for follow-up?
• What is my risk of developing additional paragangliomas?
• How often will I need long-term surveillance?