Paragangliomas are rare neuroendocrine tumors that arise from specialized nerve cells called paraganglia. These cells are found in clusters throughout the body, playing a role in regulating various bodily functions.
What Paragangliomas Are
Paragangliomas originate from paraganglia, small groups of neuroendocrine cells distributed along the autonomic nervous system. These cell clusters produce and release hormones, particularly catecholamines like adrenaline and noradrenaline, which are important for the body’s stress response. Paragangliomas are broadly categorized into two types: functional and non-functional. Functional paragangliomas actively secrete these hormones, leading to a range of symptoms, while non-functional ones do not produce significant amounts of hormones and may only cause symptoms by their physical presence.
Most paragangliomas are benign, meaning they are non-cancerous and do not spread, but some can be malignant. Malignant paragangliomas can spread to other parts of the body, such as lymph nodes, lungs, liver, and bones. The distinction between a paraganglioma and a pheochromocytoma is based on location; tumors within the adrenal glands are pheochromocytomas, while those outside are paragangliomas. Paragangliomas can occur anywhere paraganglia are found, from the head and neck down to the pelvis, with an estimated incidence of about 1 in 300,000 people.
How Paragangliomas Affect the Body
The effects of paragangliomas vary widely depending on their location and whether they are functional (hormone-secreting). They can develop in various sites, including the head and neck, chest, abdomen, and pelvis. Head and neck paragangliomas, while often non-functional, can cause symptoms by pressing on nearby nerves and structures as they grow. For instance, a paraganglioma in the neck might present as a painless mass. Tumors in this region can also lead to symptoms such as hearing loss, ringing in the ears (tinnitus), difficulty swallowing, hoarseness, or vision changes due to pressure on surrounding tissues or nerves.
Functional paragangliomas, regardless of their location, release excess catecholamines, leading to systemic symptoms. These symptoms often include high blood pressure (hypertension), which can be persistent or episodic, a fast or pounding heartbeat (palpitations), excessive sweating, and headaches. Abdominal paragangliomas, for example, are more likely to be functional and cause these hormone-related symptoms.
Identifying and Treating Paragangliomas
Identifying paragangliomas involves a combination of diagnostic methods. Imaging studies are used to locate the tumor and assess its size and extent. Common techniques include magnetic resonance imaging (MRI) and computed tomography (CT) scans, which provide detailed anatomical views. Specialized nuclear medicine scans, such as MIBG (metaiodobenzylguanidine) and PET (positron emission tomography) scans, detect paragangliomas based on their metabolic activity or specific receptor uptake. These functional imaging methods help distinguish paragangliomas from other growths and identify if the tumor is producing hormones.
Biochemical tests are performed, especially when a functional tumor is suspected. These tests measure levels of catecholamines and their breakdown products (metanephrines) in blood plasma or 24-hour urine collections. Elevated levels indicate a hormone-secreting paraganglioma. A biopsy may be performed to confirm the diagnosis, though distinguishing between benign and malignant paragangliomas can be challenging even with tissue analysis.
Surgical removal is often the primary treatment for paragangliomas, aiming to excise the tumor completely. Before surgery for functional tumors, medications are administered to control blood pressure and heart rate, preventing complications. For tumors that cannot be fully removed or have spread, other treatments may be considered. Radiation therapy can stop tumor growth or shrink tumors, particularly for head and neck paragangliomas or when surgery is risky due to proximity to sensitive structures. Systemic therapies, such as chemotherapy or targeted therapy, are options for more complex or metastatic cases, aiming to control disease progression.
Understanding the Genetic Link and Future Outlook
A significant proportion of paragangliomas have a hereditary component, linked to specific gene mutations inherited from parents. Genetic mutations in genes such as SDHA, SDHB, SDHC, SDHD (collectively known as SDHx genes), as well as VHL, NF1, and MEN2, are associated with an increased risk of developing paragangliomas. Approximately 40% of paragangliomas and related tumors arise from these inherited genetic variants. This genetic predisposition highlights genetic testing for individuals diagnosed with paraganglioma and their family members, which helps assess risks and guide surveillance strategies.
The long-term outlook for individuals with paragangliomas varies depending on factors such as tumor location, whether it is functional, and if it has spread. While many paragangliomas are slow-growing and benign, long-term follow-up and monitoring are needed due to the potential for recurrence or, in some cases, metastasis. Multidisciplinary care, involving a team of specialists such as endocrinologists, surgeons, oncologists, and genetic counselors, aids in managing the condition comprehensively. Even with metastatic disease, individuals can live for extended periods with good quality of life due to available treatments and ongoing management.