A paraganglioma is a rare neuroendocrineneoplasm that may develop at various body sites. They are rare tumors, with an overall estimated incidence of 1/300 000. Unlike other types of cancer, there is no test that determines benign from malignant tumors; long-term followup is therefore recommended for all individuals with paraganglioma. The five-year survival in the setting of metastatic disease is 90% to 100%.
Signs and symptoms
Most paragangliomas are either asymptomatic or present as a painless mass. While all contain neurosecretory granules, only in 1–3% of cases is secretion of hormones such as catecholamines abundant enough to be clinically significant; in that case manifestations often resemble those of pheochromocytomas.
Genetics
About 75% of paragangliomas are sporadic; the remaining 25% are hereditary. Mutations of the genes for the succinate dehydrogenase, SDHD, SDHA, SDHC and SDHB have been identified as causing familial head and neck paragangliomas. Mutations of SDHB play an important role in familial adrenal pheochromocytoma and extra-adrenal paraganglioma, although there is considerable overlap in the types of tumors associated with SDHB and SDHD gene mutations. Paragangliomas may also occur in MEN type 2A and 2B. Other genes related to familial paraganglioma are SDHAF2, VHL, NF1, TMEM127, MAX and SLC25A11.
About 85% of paragangliomas develop in the abdomen; only 12% develop in the chest and 3% in the head and neck region. While most are single, rare multiple cases occur. Paragangliomas are described by their site of origin and are often given special names:
Head and neck paraganglioma : There are various types of head and neck paraganglioma; they may have specialized names depending on the precise location.
* Glomus tympanicum and Glomus jugulare, also known as jugulotympanic paraganglioma: Both commonly present as a middle ear mass resulting in tinnitus and hearing loss. The cranial nerves of the jugular foramen may be compressed, resulting swallowing difficulty, or ipsilateral weakness of the upper trapezius and sternocleiodomastoid muscles. These patients present with a reddish bulge behind an intact ear drum. This condition is also known as the "Red drum". On application of pressure to the external ear canal with the help of a pneumatic ear speculum the mass could be seen to blanch. This sign is known as "Brown's sign". A deficient bony plate along the tympanic portion of the internal carotid artery is a normal variant and can be mistaken with glomus jugulare.
Organ of Zuckerkandl: A collection of paraganglia near the bifurcation of the aorta, comprising a small mass of neural crest-derived chromaffin cells. Serves as a common origin of abdominal paragangliomas.
Vagal paraganglioma: These are the least common of the head and neck paragangliomas. They usually present as a painless neck mass, but may result in dysphagia and hoarseness.
Pulmonary paraganglioma: These occur in the lung and may be either single or multiple.
Other sites: Rare sites of involvement are the larynx, nasal cavity, paranasal sinuses, thyroid gland, and the thoracic inlet, as well as the bladder in extremely rare cases.
Diagnosis
Classification
Paragangliomas originate from paraganglia in chromaffin-negative glomus cells derived from the embryonic neural crest, functioning as part of the sympathetic nervous system. These cells normally act as special chemoreceptors located along blood vessels, particularly in the carotid bodies and in aortic bodies. Accordingly, paragangliomas are categorised as originating from a neural cell line in the World Health Organization classification of neuroendocrine tumors. In the categorization proposed by Wick, paragangliomas belong to group II. Given the fact that they originate from cells of the orthosympathetic system, paragangliomas are closely related to pheochromocytomas, which however are chromaffin-positive.
