Glomus Tumours (Paragangliomas)

Definition and epidemiology

Paragangliomas (PGLs) are neuroendocrine tumours that arise from paraganglion tissue of the autonomic nervous system. Head and neck paragangliomas are rare, mostly benign and slow-growing, but their growth and course are hard to predict in an individual patient (Taïeb et al., 2014). Two main types occur in the temporal bone. Glomus tympanicum arises from paraganglia along the tympanic branch of the glossopharyngeal nerve (Jacobson’s nerve) on the promontory of the medial middle ear wall. Glomus jugulare arises from the wall of the jugular bulb and grows within the jugular foramen, from where it can extend into the middle ear, the skull base and the cranial cavity. Tumours involving both regions are also called tympanojugular paragangliomas.

The Fisch classification groups tumours by extent into four classes: A, confined to the middle ear (tympanic); B, tympanomastoid; C, extending below the labyrinth to the jugular bulb and carotid canal (infralabyrinthine); and D, with intracranial extension (Oldring and Fisch, 1979). The Glasscock-Jackson classification defines four separate grades for tympanicum and jugulare tumours (Jackson et al., 1982) and is summarised in the table below.

About 5% of head and neck paragangliomas secrete catecholamines; the great majority are hormonally silent. Overall, about 35-40% of all paragangliomas and phaeochromocytomas are associated with a hereditary predisposition (Else et al., 2023).

Symptoms and signs

The commonest complaints are tinnitus in time with the heartbeat (pulsatile tinnitus), hearing loss and a mass seen in the ear. In a classic surgical series of 23 patients from Zurich, 15 had significant hearing loss and 10 had cranial nerve involvement, most often of the facial and vagus nerves (Oldring and Fisch, 1979). Aural fullness and blockage are also common. Pulsatile tinnitus is often most noticeable in quiet surroundings and at night.

Otoscopy shows a red or purple retrotympanic mass behind the eardrum, sometimes pulsating. If the upper margin of the mass can be seen behind the drum, the tumour is small; if it cannot, wider extension is likely. Blanching of the mass when pressure is applied with a pneumatic otoscope (Brown’s sign) supports the diagnosis. Advanced tumours can appear as a bleeding, polyp-like mass in the ear canal.

As glomus jugulare enlarges it can affect the glossopharyngeal, vagus and accessory nerves passing through the jugular foramen, and the hypoglossal nerve, causing difficulty swallowing, hoarseness, shoulder weakness and tongue weakness. Facial nerve involvement causes facial palsy, and labyrinthine involvement causes sensorineural hearing loss and vertigo. Catecholamine-secreting tumours can produce episodes of palpitations, sweating, headache and high blood pressure.

Causes and risk factors

A substantial proportion of head and neck paragangliomas are hereditary. Germline pathogenic variants in the genes encoding subunits of the succinate dehydrogenase enzyme (SDHx: SDHA, SDHB, SDHC, SDHD, SDHAF2) are the commonest cause. SDHD variants account for 40-50% of head and neck paragangliomas while SDHB variants are found in 12-20% of people with head and neck paragangliomas. SDHD and SDHAF2 variants cause disease almost exclusively when inherited from the father; maternal transmission usually carries little risk, although exceptions occur. About 75% of SDHD carriers develop tumours at more than one site, whereas SDHB variants are associated with a higher risk of metastasis (Else et al., 2023).

Three guidelines, including that of the Endocrine Society, therefore recommend that everyone diagnosed with a paraganglioma or phaeochromocytoma be referred for genetic assessment (Else et al., 2023). Diagnosis at a young age (under 45), multiple tumours and a family history particularly suggest a hereditary syndrome. Because patients with an SDHD variant can also develop tumours outside the head and neck, they need whole-body assessment and care from an expert multidisciplinary team (Taïeb et al., 2023). In non-hereditary (sporadic) cases the exact cause is usually unknown.

Audiological and clinical assessment

The combination of pulsatile tinnitus and a red retrotympanic mass suggests a glomus tumour; the diagnosis is made by imaging. This highly vascular mass should not be biopsied in clinic because it can bleed heavily. Audiological assessment documents hearing, informs the treatment plan and provides a baseline for comparison after treatment.

• Pure-tone audiometry: a conductive loss is typical of a tympanic tumour that touches the eardrum and ossicles. If the labyrinth or internal auditory canal is involved, bone conduction thresholds rise and a mixed or sensorineural loss develops; this sign of spread should be reported to the surgeon.
• Tympanometry: small fluctuations in time with the heartbeat may be seen on the tympanogram, more clearly when recorded at high sensitivity and over a longer period. A large mass can flatten the trace. During acoustic reflex testing, vascular fluctuations can be mistaken for a reflex response.
• Assessing pulsatile tinnitus: whether the sound can be heard on auscultation of the ear or neck (objective tinnitus), whether it changes with pressure on the jugular vein in the neck, and tinnitus matching are recorded. The Tinnitus Handicap Inventory documents the impact on daily life.
• Computed tomography (CT): high-resolution temporal bone CT shows whether a tympanic tumour is confined to the promontory with an intact bony floor over the jugular bulb; a jugular tumour shows irregular bone erosion around the jugular foramen.
• Magnetic resonance imaging (MRI) and angiography: MRI shows extension into the skull base and cranial cavity; a ‘salt and pepper’ appearance from flow voids is typical of larger tumours. Angiography shows the feeding vessels and is used for preoperative embolisation when needed (Taïeb et al., 2014).
• Biochemistry, functional imaging and genetics: plasma or urinary metanephrines are measured to assess catecholamine secretion, and functional imaging such as somatostatin receptor PET is used to look for tumours at other sites (Taïeb et al., 2014). The patient is referred for genetic testing.

The differential diagnosis includes other red or blue masses behind the eardrum: an aberrant internal carotid artery, a high or dehiscent jugular bulb, cholesterol granuloma, facial nerve schwannoma, meningioma and middle ear adenoma. Because an aberrant carotid artery or exposed jugular bulb can bleed severely during surgery or myringotomy, the diagnosis must always be confirmed by imaging. Cholesteatoma is distinguished by its white colour.

Treatment and audiological rehabilitation

Treatment is decided by an experienced multidisciplinary team, taking into account the site and size of the tumour, its growth rate, cranial nerve function, the patient’s age and general health, and genetic findings. Some of these tumours grow very slowly: in a study following 48 head and neck paragangliomas, 60% increased in volume by more than 20%, and growing tumours had a median growth rate of 1.0 mm per year and a median volume doubling time of 4.2 years (Jansen et al., 2000). Observation with regular MRI (wait and scan) can therefore be a reasonable initial approach, especially for older patients and jugular tumours with preserved nerve function. The consensus guideline for patients with SDHD variants likewise often recommends a period of observation to understand how a tumour behaves before intervening (Taïeb et al., 2023).

Glomus tympanicum is usually treated surgically. In a series of 68 patients, all Fisch class A tumours were removed through the ear canal, and class B tumours through the mastoid or, for large tumours, by subtotal petrosectomy; complete removal was achieved in every patient and only one (1.4%) recurred, nine years later (Sanna et al., 2010). Options for glomus jugulare include skull base surgery, stereotactic radiosurgery, conventional radiotherapy or a combination; surgery carries a risk to the lower cranial nerves. A meta-analysis of 19 studies and 335 patients reported tumour control in 97% and clinical control in 95% after radiosurgery (Guss et al., 2011). The choice of treatment rests with the clinical team, and catecholamine-secreting tumours need medical preparation before surgery.

Audiological rehabilitation is part of the plan. After removal of a tympanic tumour, the conductive loss often improves and pulsatile tinnitus may disappear. For persistent conductive or mixed loss a hearing aid is considered, bone conduction implants after extensive surgery with closure of the ear canal, and a CROS system when no useful hearing remains in the ear (see Unilateral Hearing Loss). Counselling and sound enrichment are offered for persistent tinnitus. In hereditary cases follow-up is lifelong; carriers are advised to have whole-body MRI every 2-3 years and regular biochemical screening (Else et al., 2023).

Impact on quality of life and advice

The word ‘tumour’ understandably causes anxiety for patients and families. Knowing that most glomus tumours are benign and slow-growing, and that treatment options exist, helps to ease it. Pulsatile tinnitus can make it hard to fall asleep, and a soft background sound at night can help. For patients whose lower cranial nerves are affected, working with a speech and language therapist on swallowing and voice can improve quality of life considerably.

If a hereditary variant is found, genetic counselling and testing may be offered to your relatives; early diagnosis in relatives at risk matters particularly with paternally inherited SDHD variants. Keep your follow-up appointments and scans. Report new hoarseness, swallowing difficulty, facial weakness, a marked drop in hearing, or episodes of palpitations and sweating to your doctor without waiting for the next review. Have the affected ear tested regularly by an audiologist, as hearing may change after treatment.