Glomus Jugulare Tumour

Glomus jugulare tumour is a benign, highly vascular paraganglioma arising from the paraganglionic tissue in the adventitia of the jugular bulb (in the jugular foramen). The glomus bodies are associated with the Arnold nerve (the auricular branch of the vagus) and the Jacobson nerve. It accounts for about 0.6 percent of head and neck tumours and is the commonest primary tumour of the jugular foramen.

The incidence is about 1 in 1.3 million, with a peak age of 40 to 60 years and a female predominance (about 3 to 6:1).

Most are sporadic. About 10 to 30 percent have germline mutations in the SDHx family:

• SDHD, with the highest risk of multiple tumours
• SDHB, with a higher risk of malignancy
• SDHC, SDHA, SDHAF2

Multiple paragangliomas are present in up to 10 percent of sporadic and 25 to 50 percent of hereditary cases. About 1 to 4 percent are catecholamine secreting. About 4 to 10 percent (SDHB mutation, up to 30 percent) are malignant with nodal or distant metastases.

The tumour grows slowly (doubling time of about 4 years, up to 10 years). It invades along the path of least resistance via the jugular bulb and venous channels, the hypotympanum and middle ear, the carotid canal, the lower cranial nerves, the posterior fossa, and the neck.

In the Fisch classification, class C is infralabyrinthine involvement of the temporal bone with extension to the petrous apex (C1 to C4: carotid canal). Class D is intracranial extension (De1 and De2 extradural, Di1 to Di3 intradural). The Glasscock-Jackson classification divides glomus jugulare tumours into types I to IV by the size and extent.

• Pulsatile tinnitus (about 60 to 80 percent), hearing loss (conductive from middle ear involvement, or sensorineural if the inner ear is invaded, in about 60 to 70 percent), and aural fullness.
• Lower cranial nerve palsies (IX to XII, in about 10 to 30 percent at diagnosis: dysphagia, hoarseness from vocal cord paralysis, aspiration, tongue deviation and atrophy, shoulder weakness, and loss of the gag reflex, the Collet-Sicard and Vernet syndromes).
• Facial nerve weakness, vertigo, otalgia, headache, ear bleeding or a polypoid mass in the ear canal, and a retrotympanic red mass on otoscopy (rising sun sign).
• Neck mass (extension to the carotid space), and signs of intracranial extension (headache, ataxia, brainstem compression and raised intracranial pressure).
• Catecholamine excess in secretory tumours: paroxysmal hypertension, palpitations, flushing, headache, and sweating.
• Horner syndrome (carotid canal extension), and a "salt and pepper" appearance on MRI.

• Otoscopic and neurological examinations (cranial nerves); do not biopsy a vascular retrotympanic mass.
• Audiometry; laryngoscopy for vocal cord paralysis; swallowing assessment.
• CT of the temporal bone (bone window): moth eaten erosion of the jugular foramen and the jugular spine, with a destructive mass in the jugular fossa extending into the middle ear, with erosion of the carotid canal and the hypotympanum.
• MRI with gadolinium and MR angiography: a heterogeneously enhancing mass with "salt and pepper" appearance on T1 and T2 (flow voids), and the tumour extent and relationships with the carotid artery, jugular vein and cranial nerves; MR venography for venous sinus patency (collateral circulation) and tumour thrombus.
• Digital subtraction angiography is used for embolisation and balloon occlusion tests of the internal carotid artery if the carotid is involved: shows a hypervascular tumour fed by the ascending pharyngeal artery, and sometimes the occipital and internal carotid branches.
• Functional imaging: 68Ga-DOTATATE PET-CT (high sensitivity and specificity for paraganglioma) or 123I-MIBG for multifocal or metastatic disease.
• Biochemical testing: plasma free metanephrines or 24-hour urinary fractionated metanephrines before any intervention to exclude catecholamine secretion.
• Genetic testing of SDHx genes and counselling.

Treatment options are surgery, radiotherapy and observation, tailored to the age and general condition of the patient, the tumour extent, the cranial nerve function, the growth rate, and the risks of treatment related morbidity.

• Observation (wait and scan): for elderly patients or those with small, asymptomatic or minimally symptomatic tumours, or in whom the risk of treatment (new cranial neuropathies) outweighs benefit. Serial MRI at 6 months and then yearly. About 40 to 60 percent grow over several years, and intervention is considered for growth above 2 mm per year, or new neurological deficits.
• Radiotherapy: stereotactic radiosurgery (gamma knife or CyberKnife; 12 to 15 Gy to the margin in a single fraction, or hypofractionated 18 to 25 Gy in 3 to 5 fractions) or fractionated radiotherapy (45 to 50 Gy in 25 fractions). Tumour control is 90 to 95 percent (tumours shrink in a minority, but stop growing in most).
• Radiotherapy is the first line option for many patients with extensive disease, those with high surgical risk, older patients, residual and recurrent disease, and preservation of lower cranial nerve function. Risks include radiation induced hearing loss, osteoradionecrosis, and a small risk of secondary malignancy.
• Surgery: complete excision is curative, but carries a risk of lower cranial nerve injury (which may be permanent and cause aspiration), facial nerve injury, hearing loss, cerebrospinal fluid leak, and bleeding.
• Surgical approaches: infratemporal fossa approach type A of Fisch, with anterior transposition of the facial nerve, or transmastoid neck approach for lesions confined to the jugular foramen. Use the combined neurosurgical approach for the intradural extension. Preoperative embolisation (24 to 72 hours before) lowers blood loss.
• Surgery is indicated for young patients with small to medium tumours, secretory tumours, tumours causing brainstem compression, and cases of failed radiation. Use staged surgery for large tumours. Subtotal resection with postoperative radiosurgery can reduce cranial nerve deficits.
• Secretory tumours: preoperative alpha adrenergic blockade (phenoxybenzamine 10 mg twice daily, increased to 20 to 100 mg daily, or doxazosin 2 to 16 mg daily, for 10 to 14 days) before beta blockade. Control blood pressure, and use an anaesthetist experienced in catecholamine tumours.
• Malignant or metastatic paraganglioma (SDHB-related): surgical resection of accessible disease, radiotherapy, 131I-MIBG therapy or peptide receptor radionuclide therapy with 177Lu-DOTATATE (7.4 GBq every 8 weeks, 4 cycles), chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD), temozolomide, and tyrosine kinase inhibitors (sunitinib 37.5 to 50 mg daily).
• Rehabilitation of lower cranial nerve palsies: speech and swallowing therapy, vocal cord medialisation (injection laryngoplasty or thyroplasty), tracheostomy or gastrostomy in severe aspiration, and shoulder physiotherapy; hearing aids; facial nerve rehabilitation.
• Genetic counselling and screening for SDHx mutation carriers and relatives (annual biochemical tests and whole body MRI every 1 to 2 years).
• Follow up: MRI and clinical review at 6 to 12 months after treatment, then annually for life (recurrence in 5 to 15 percent, and late recurrences after radiation).
• Prognosis: normal life expectancy with benign disease; local control in over 90 percent.