Paragangliomas are 35-40 percent malignant, i.e. they spread/metastasize in approx. 35-40 percent of cases. They can form in various places, for example at the base of the skull or in the middle ear, in the neck at the carotid artery, in the chest and abdomen and at the aorta. The exact place of origin also determines the symptoms. However, most people affected do not notice a paraganglioma for a long time. Only when the tumor grows and becomes larger can symptoms occur.
We usually treat a paraganglioma by means of surgery. Every operation should be preceded by a so-called “alpha blockade” with the drug Dibenzyran for at least ten days in order to prevent severe blood pressure derailments due to hormone release during the operation. In the event of possible nerve damage due to surgery or difficult surgical accessibility, so-called “watch and wait”, i.e. regular monitoring of the tumor without therapy, can also be an alternative to surgery for slow-growing paragangliomas in the head and neck area. In some patients, these findings remain stable for years. Systemic therapies such as radionuclide therapies (radioreceptor therapy or MIBG therapy), chemotherapies or molecular-targeted therapies are used for metastatic tumors.
Every patient with paraganglioma should be linked to a specialized center, such as ours, and all decisions on the best possible diagnosis, treatment and aftercare should be made in an interdisciplinary (neuro)endocrine tumour board.
What is a paraganglioma?
Paraganglioma is a very rare tumor that is benign in most cases, but metastasizes in approx. 35-40 percent of cases and thus meets the definition of a malignant tumor. This tumor originates in the paraganglia of the sympathetic or, more rarely, parasympathetic nervous system. Paragangliomas of the sympathetic nervous system often produce the hormones noradrenaline and sometimes dopamine; this hormone production can be detected by a blood test for free plasma metanephrines. The rare parasympathetic paragangliomas usually do not produce hormones, as do some sympathetic paragangliomas. These tumors can then only be detected by imaging.
Paraganglioma – differentiation depending on the site of origin
Paragangliomas can develop in various parts of the body, for example:
- In the middle ear (glomus tympanicum, paraganglioma tympanicum): The origin lies in a ganglion in the middle ear – the glomus tympanicum. This glomus tumor has many vessels and is usually benign – but its growth can destroy the surrounding tissue.
- In the jugular fossa (glomus jugulare, paraganglioma jugulare): This paraganglioma forms in the area of the lateral base of the skull.
- At the carotid bifurcation (glomus caroticum, paraganglioma caroticum): This is the point in the carotid triangle where the carotid artery (arteria carotis communis) branches into the external carotid artery (arteria carotis externa) and the internal carotid artery (arteria carotis interna). This paraganglioma is usually benign, but often occurs together with malignant paragangliomas in the abdominal area – especially in the so-called familial paraganglioma syndrome type 4 with germline mutations in the SDHB
- On the vagus nerve – the tenth cranial nerve (glomus vagale, paraganglioma vagale): This is part of the parasympathetic nervous system, which controls many functions, such as breathing, digestion and heart rate.
- On the aorta – the main artery (paraganglioma aorticum): This is where it usually grows quickly and can become very dangerous without treatment.
Paragangliomas usually develop as single tumors, rarely they are localized in several places. In these cases, there are usually genetic causes or a familial clustering. Most people don’t notice their tumor at first. It usually grows slowly and does not cause any pain. Only when it has reached a certain size does it become noticeable.
The symptoms depend on where the paraganglioma has formed. A paraganglioma in the middle ear can cause a pulse-synchronous ringing in the ear, hearing loss or dizziness. Dysphagia and hoarseness, on the other hand, may indicate a paraganglioma at the carotid bifurcation in the neck or at the base of the skull. Paragangliomas in the chest/abdominal area stand out due to pain or symptoms associated with hormone secretion (see below).
A paraganglioma can be diagnosed by laboratory chemistry via hormone secretion or – in the absence of hormone secretion – with imaging procedures such as magnetic resonance imaging (MRI ) with contrast-enhanced vascular imaging in the head/neck and abdominal area and a CT scan of the thorax. The most sensitive functional imaging procedure is the so-called somatostatin receptor-guided radionuclide imaging (DOTA-TATE PET/CT) with a sensitivity of approx. 99% (sensitivity: probability of finding the tumor with the imaging). The treatment of choice is surgery and, if necessary, radiotherapy. We try to remove the paraganglioma as completely as possible. In the case of metastatic disease, there are various systemic treatment options (see below).
In any case, the diagnosis and treatment of this rare tumor should be discussed individually in an interdisciplinary (neuro)endocrine tumor board at a specialized center.
Paraganglioma – frequency and age
Paraganglioma is a very rare disease. There are no precise figures on the incidence of paraganglioma. It is also not possible to determine an exact age of onset. In principle, people of any age can develop paraganglioma – often between the ages of 40 and 60. In familial paraganglioma syndromes, paragangliomas often occur in childhood or early adulthood.
Paraganglioma of the carotid artery appears to affect women more frequently than men. Women also develop paraganglioma in the middle ear more often than men, usually around the age of 50. There also seems to be a tendency for paragangliomas on the vagus nerve to occur more frequently in women.
Paraganglioma: causes mostly unclear
The causes of a paraganglioma are still largely unknown. Paragangliomas are also very different and localized in different parts of the body. It is not possible to identify a single cause.
Paragangliomas are known to occur more frequently in the context of various familial syndromes/genetic diseases (germline mutations), particularly frequently in familial paraganglioma syndrome type 1(SDHD mutation), type 2(SDHAF2 mutation) and type 4(SDHB mutation) as well as in Pacak-Zhuang syndrome(EPAS1 mutation). In these cases, the tumors often occur in childhood or young adulthood.
In familial paraganglioma syndrome type 1(SDHD mutation) and type 2(SDHAF2 mutation), head and neck paragangliomas occur particularly frequently.
In familial paraganglioma syndrome type 4(SDHB mutation), malignant/metastatic paragangliomas often develop at various locations between the base of the skull and the pelvic floor, as well as so-called pheochromocytomas. Pheochromocytomas are tumors of the adrenal medulla that produce hormones such as noradrenaline or adrenaline.
Pacak-Zhuang syndrome(EPAS1 mutation) is mainly characterized by paragangliomas in the chest/abdominal area and pheochromocytomas.
Symptoms: Paragangliomas often without symptoms
A paraganglioma usually grows slowly and often causes no symptoms at first. Many patients therefore do not notice the paraganglioma for a long time. However, when the tumor reaches a certain size, it can cause local discomfort. The symptoms depend on where in the body it has formed. Some examples:
- Glomus tumor of the carotid bifurcation: (pulsating) swelling in the neck area, difficulty swallowing, hoarseness, drooping upper eyelid, ringing in the ears (synchronous with the pulse)
- Glomus tumor of the middle ear: dizziness, pulse-synchronous ringing in the ears (tinnitus), reduced hearing, in the worst case deafness
- Glomus tumor of the vagus nerve: hearing loss, tinnitus, facial paralysis, swallowing disorders or (rarely) high blood pressure that cannot be adjusted.
The symptoms also depend on whether the tumor secretes hormones. Hormones are usually secreted in larger quantities as the size of the tumor increases. In general, symptoms such as high blood pressure, severe hypertensive crises, tachycardia, sweating, headaches, anxiety, tremor, nausea, orthostatic hypotension, weakness, pallor, weight loss and diabetes mellitus can occur due to hormone secretion (mostly noradrenaline and dopamine).
Paraganglioma: Diagnosis with us
The diagnosis of a paraganglioma always begins with a discussion with us about the patient’s medical history (anamnesis). We ask you some questions, for example:
- What complaints are you experiencing exactly?
- When did they first appear?
- How pronounced are the symptoms?
- In which area are the symptoms localized?
- Have you improved again in the meantime or gotten continuously worse?
- Do you have any known diseases?
- Are there any diseases in your family?
The consultation is followed by a physical examination, during which we palpate the body for possible changes. A blood pressure measurement and a blood test, in particular for free plasma metanephrines and chromogranin A (another tumor marker for endocrine tumors), are also standard.
The suspected diagnosis of “paraganglioma” can be confirmed using imaging procedures in the case of clinical or laboratory suspicion. To be used:
- Ultrasound examination (sonography) – it works with ultrasound waves and can detect changes in organs and tissues
- Duplex sonography – a special ultrasound examination that can be used to visualize the blood vessels and the blood flow in the vessels
- Magnetic resonance imaging (MRI = magnetic resonance imaging) – a non-invasive method that allows good visualization of the paraganglioma and the feeding vessels. It provides a high soft tissue contrast. This imaging is particularly suitable for tumors in the head/neck/abdomen and pelvic area.
- Computer tomography – a procedure that works with X-rays and can, among other things, show the position of the tumor in relation to the adjacent bone structures. This imaging is particularly suitable for tumors in the breast area.
- Angiography – this allows the vessels to be visualized. Angiography can also be combined with MRI (MR angiography). Embolization, i.e. interventional closure of vessels, is also possible before an operation.
- Positron emission tomography (PET) – a nuclear medicine method that visualizes tumour tissue with certain characteristics in the body (e.g. increased somatostatin receptor expression). In the case of paragangliomas, low-level radioactive somatostatin analogs are used as part of the somatostatin receptor-guided(68Ga-DOTA-TATE) PET/CT examination (sensitivity approx. 99%).
- Otoscopy for suspected glomus tumors in the middle ear. An ear microscope is used. The tumor may appear reddish through the eardrum.
Glomus tumor: prevention, early detection, prognosis
You cannot prevent a paraganglioma because the causes are largely unclear. Commonly known carcinogens, such as smoking, are also considered a risk factor here.
Even if the paraganglioma occurs as part of a familial paraganglioma syndrome, you cannot prevent the tumor from developing in advance. However, in the case of familial paraganglioma syndromes, regular preventive examinations should be carried out when the syndrome/gene mutation becomes known – consisting of annual clinical and laboratory checks and imaging from the base of the skull to the pelvis every 2-3 years (PET/CT once when the gene mutation is first diagnosed/becomes known, usually MRI in the course of the disease).
Course and prognosis of a glomus tumor
The course and prognosis of a glomus tumor cannot be generally predicted. First of all, it plays a role whether the tumor is benign (approx. 60 percent) or malignant (approx. 40 percent). In the latter case, we must treat him quickly. Unfortunately, there are no reliable criteria for “malignant” behavior – even after postoperative histological examination. The WHO has thus defined “malignant” as “metastasized” in the case of paragangliomas/pheochromocytomas. It should be noted in this context that “benign”, i.e. non-metastatic tumors can also grow and destroy surrounding tissue, and that every “benign” tumor can theoretically metastasize at some point and become “malignant” by definition. Timely diagnosis, treatment and adequate follow-up care at a specialized center are of decisive importance for the prognosis.
Glomus tumor: Treatment
The treatment of choice for a paraganglioma is surgery. We try to remove the tumor as completely as possible. Surgical intervention is used for both benign and malignant paragangliomas and may be combined with embolization and/or (stereotactic) radiotherapy depending on the individual situation. If there are high surgical risks and the tumor grows slowly, which is often the case with head and neck tumors in particular, a “watch and wait” strategy, i.e. simply waiting while undergoing regular check-ups, may also make sense. Otherwise, local therapy can also be used directly, such as embolization or (stereotactic) radiotherapy/cyberknife.
Various systemic therapies are used for metastatic disease, such as somatostatin receptor-directed radionuclide therapy, MIBG therapy, chemotherapy, molecular-targeted therapy or immunotherapy.
With these rare tumors, it is particularly important that each individual patient case is discussed in an interdisciplinary tumor board – consisting of specialists in oncology, endocrinology (hormone specialists), radio-oncology, nuclear medicine, diagnostic and interventional radiology, surgery, gastroenterology, pathology and psycho-oncology – in order to provide the patient with the best possible therapy.