A paraganglioma is a rare neuroendocrine tumor that develops from specialized nerve cells called paraganglia. These growths are typically slow-growing and are most frequently benign, but they can occasionally become malignant and spread to other parts of the body. Paragangliomas are closely related to pheochromocytomas, which are tumors arising from the same cell type but located specifically within the adrenal glands.
Cellular Origin and Primary Locations
Paragangliomas originate from the paraganglia system, which consists of small clusters of neuroendocrine cells derived from the embryonic neural crest. These cells are distributed throughout the body and are associated with the autonomic nervous system, which controls involuntary body functions. The function of the tumor is determined by whether it arises from the sympathetic or parasympathetic division of this system.
Paragangliomas are broadly divided into two groups: those found in the head and neck, and those found in the trunk (chest, abdomen, and pelvis). Tumors arising in the head and neck, such as those near the carotid artery or in the middle ear, are typically associated with the parasympathetic nervous system. These tumors are often non-functional, meaning they do not secrete hormones.
Conversely, paragangliomas located in the trunk, particularly in the abdomen along the aorta, are associated with the sympathetic nervous system. These are generally functional tumors that produce and release excessive amounts of catecholamines, such as norepinephrine and epinephrine.
Recognizing the Symptoms
Symptoms of a paraganglioma are highly variable and depend primarily on whether the tumor is functional (hormone-producing) or non-functional (biochemically silent). Non-functional tumors typically cause symptoms due to a phenomenon known as the mass effect, where the physical size of the tumor presses on nearby structures. For instance, a paraganglioma in the neck may present as a palpable, slow-growing, and often painless mass.
Tumors in the head and neck often cause symptoms related to their proximity to cranial nerves and blood vessels. Patients may experience pulsatile tinnitus, which is a rhythmic whooshing or pulsing sound heard in the ear. Other localizing symptoms can include hearing loss, hoarseness, or difficulty swallowing due to the tumor compressing adjacent nerves.
Functional tumors cause a distinct set of symptoms due to the excessive and erratic release of catecholamines into the bloodstream. These powerful hormones trigger the body’s “fight-or-flight” response, leading to episodes that can be paroxysmal, or sudden and severe.
The classic combination of symptoms for a catecholamine-secreting tumor is often described as the triad of severe headaches, profuse sweating (diaphoresis), and a pounding heart sensation (palpitations). The surge of catecholamines also causes episodes of sustained or paroxysmal high blood pressure (hypertension), which can be difficult to control with standard medication. Other effects of this hormonal excess include anxiety, panic attacks, tremors, paleness, and occasionally nausea or vomiting.
Diagnostic Testing and Treatment Options
The initial diagnostic process for a suspected paraganglioma begins with biochemical tests to check for hormonal activity. This involves measuring the levels of fractionated metanephrines and catecholamines, typically in a 24-hour urine collection or a blood plasma sample. Metanephrines are breakdown products of catecholamines that are released continuously by the tumor, making their measurement a highly sensitive indicator of a functional paraganglioma.
Once biochemical evidence suggests a functional tumor, or if a mass is found incidentally, imaging studies are used to pinpoint the location and extent of the tumor. Cross-sectional imaging, such as Computed Tomography (CT) scans or Magnetic Resonance Imaging (MRI), provide detailed anatomical information. Functional imaging techniques are often used to confirm the diagnosis and check for multiple tumors or metastasis.
Specialized nuclear medicine scans like MIBG scintigraphy or the more modern 68-Gallium (Ga)-DOTATATE PET/CT are used because they target specific receptors on the tumor cells. Ga-DOTATATE PET/CT is often considered superior to MIBG.
Surgical resection is the primary and curative treatment approach for most localized paragangliomas. For patients with functional tumors, a careful period of pre-operative medical management is necessary to prevent dangerous fluctuations in blood pressure during surgery.
This preparation involves administering alpha-adrenergic receptor blockers, such as phenoxybenzamine or doxazosin, for seven to fourteen days before the operation. Alpha-blockade works to normalize the patient’s blood pressure by preventing the excessive catecholamines from causing severe vasoconstriction and hypertension during tumor manipulation. Beta-blockers are usually only added a few days before surgery, and only after adequate alpha-blockade has been established, to control heart rate. For tumors that are inoperable, metastatic, or carry a high risk of surgical complication, alternative treatments such as radiation therapy or systemic therapies may be considered.