Paragangliomas are also called “glomus” tumors, a commonly used but inaccurate name. These are usually benign, slow-growing but highly vascular tumors that cause symptoms by their 1) mass effect in small spaces such as the ear, 2) high blood flow, 3) invasion of adjacent structures, and 4) secretion of hormones, which is rare.
As they grow, their mass effect can block sound transmission in the middle ear, causing conductive hearing loss, and the high blood flow within them is usually perceived as a pulsating sound (a form of tinnitus). With larger tumors, structures in the temporal bone can be invaded, including the facial nerve, leading to facial paralysis, or the inner ear, causing sensorineural hearing loss or vertigo (the illusion of motion). Rarely, these tumors can produce hormones such as adrenaline, which can cause episodes of sweating, flushing, headache, and a rapid heartbeat.
A small paraganglioma limited to the middle ear is often called a “glomus tympanicum.” A larger tumor that originates from the bulb of the jugular vein and involves the base of the skull is called a “glomus jugulare.” “Glomus vagale” refers to a paraganglioma originating from the vagus nerve, an important cranial nerve which empowers the vocal cords and the muscles of swallowing. When arising from the main branchpoint of the carotid artery in the neck, a paraganglioma is termed a “carotid body tumor.” These tumors can occur in multiple other areas, including the eye socket, the larynx, or inside the chest or abdomen.
What causes paragangliomas (glomus tumors)?
Breakthrough research has identified at least four genetic mutations that lead to an inherited condition where the individual is at high risk for developing multiple paragangliomas. If there is no underlying inherited condition, then the tumor is considered “sporadic,” or random. Part of the difficulty in determining whether someone has an inherited or sporadic form of disease is that the mutations are subject to a process called imprinting, where the mutation is masked if inherited through one’s mother. Therefore, the disease may appear to skip a generation and then be expressed when someone inherits the mutation from his/her father.
These tumors are derived from specialized cells called paraganglia, which are modified nerve cells that are capable of sensing the oxygen and carbon dioxide content, as well as the pH, of the bloodstream. Living at altitude appears to be a risk factor for developing disease, since the lower oxygen content at elevation encourages the paraganglia cells to multiply. Prolonged living at altitude is a risk factor for developing multiple tumors, at least in the inherited or familial cases.
The natural course of these tumors is generally one of slow growth, since the vast majority of paragangliomas are benign. However, a small percentage are malignant, with the ability to metastasize or spread to nearby lymph nodes, or other sites such as the lungs, bones, or the liver. Some tumors behave very aggressively and invade the bone of the skull base. In the temporal bone, the malignancy rate is about 5%.
An important study from the Netherlands showed that, to some extent, patients could co-exist with their tumors and that usually the tumor did not threaten one’s life expectancy. This study should be interpreted with caution, since patients in this country all live at very low elevation. Depending on symptoms and whether the tumor is malignant, then, treatment of a paraganglioma is generally elective but sometimes more urgent.
How is a paraganglioma (glomus tumor) diagnosed?
Examination of the eardrum (otoscopy) typically reveals a vascular, reddish mass behind the eardrum. A glomus tympanicum appears as rounded mass entirely contained in the middle ear, while a glomus jugulare may appear as the “tip of the iceberg”, with the majority of the tumor hidden below the eardrum. There may be enlarged blood vessels running towards the tumor along the eardrum or the ear canal. In addition, air pressure applied through the otoscope may cause a blanching effect on the tumor, which is filled with blood.
When the question of a paraganglioma has been raised, CT and MRI scans are very useful. In the case of a glomus tympanicum, the CT scan usually demonstrates a rounded mass behind the eardrum with the same density as soft tissue. This must be distinguished from an abnormal carotid artery, which can have a similar appearance through the ear canal. For a glomus jugulare, the CT usually shows erosion of the bone over the bulb of the jugular vein at the skull base. MRI scans classically demonstrate a “salt-and-pepper” pattern, with voids or blank areas where the blood is flowing rapidly within the tumor. Before surgical removal, an angiogram is important for confirming the vascular nature of the tumor and determining which blood vessels are feeding it; this allows for embolization, a procedure where small pellets are deliberately fed into the tumor, to block the blood flow and reduce surgical blood loss.
Ultimate proof that a lesion is actually a paraganglioma requires analysis of a piece of the tumor by a pathologist. However, biopsies prior to surgery are rarely done since 1) the diagnosis is almost certain based on the characteristic appearance on otoscopy, plus CT and MRI scans, and 2) the surgery required to biopsy the lesion is similar to that required for removal. Once this presumptive diagnosis is made, a patient should seek the care of an otolaryngologist experienced in the management and surgery of these tumors, usually a subspecialist in otology / neurotology.
The microscopic appearance is classically termed “zellballen,” where tumor cells are clustered together and surrounded by connective tissue that is very rich in blood vessels. This rich vascularity is the basis for the tumors having a red coloration when seen during examination of the eardrum (otoscopy), and it likely results from their production of proteins which cause sprouting and development of new blood vessels (angiogenesis). This process leads to very high blood flow into the tumors, which has to be controlled during surgical removal.
How are paragangliomas (glomus tumors) treated?
Treatment options for paragnangliomas include 1) observation, or “watchful waiting,” where the patient has CT and/or MRI scans periodically to monitor the growth of the tumor, 2) radiation therapy, or 3) surgical removal. Each option has advantages and disadvantages, and the decision-making must account for a number of factors, including the severity of symptoms, the age and health of the patient, the size and location of the tumor, the presence of cranial nerve deficits such as hearing loss and facial paralysis, and of course the patient’s wishes.
Observation is often valid as the initial option, given the generally slow growth of these tumors. However, if symptoms are significant or if there is evidence of growth on serial CT or MRI scans, then the tumor should be treated. As yet, there is no medication or chemotherapy that is effective against these tumors.
Surgical removal can be relatively straightforward or complex, depending on the size and location of the tumor. For a small glomus tympanicum, the tumor can be removed through the ear canal, with low risk to hearing and no external scars. For larger glomus tympanic lesions, an incision behind the ear and a procedure called a mastoidectomy might be required. Even in this situation, the risks of hearing loss or facial nerve injury are quite low.
The risks significantly increase when removing a glomus jugulare, since the exposure requires working around or even moving the facial nerve, and the tumor must be removed from the bulb of the jugular vein, which causes bleeding. For this operation, the major blood vessels and the associated cranial nerves must be exposed in the neck, in order to protect them. In addition, the ear canal may need to be closed off, resulting in a significant blockage of sound transmission. Nonetheless, in experienced hands the surgery can be done safely.
Radiation therapy is an alternative treatment, but the goal is fundamentally different. While the goal of surgery is complete removal, the goal of radiation therapy is stopping growth. Radiation does not destroy the tumor but damages the blood vessels within and ultimately encases the tumor in scar tissue. However, as with surgery there are risks, including damage to the inner ear, facial paralysis, failure to stop tumor growth, and the very low risk of converting a benign tumor into a malignancy.