Carotid Body Tumors 

Carotid body tumors (CBTs) are rare neoplasms, although they represent about 65% of head and neck paragangliomas.^[1] These tumors develop within the adventitia of the medial aspect of the carotid bifurcation.

The carotid body, which originates in the neural crest, is important in the body's acute adaptation to fluctuating concentrations of oxygen, carbon dioxide, and pH. The carotid body protects the organs from hypoxic damage by releasing neurotransmitters that increase the ventilatory rate when stimulated.

See the image below.

The following 3 different types of carotid body tumors (CBTs) have been described in the literature:

• Familial
• Sporadic
• Hyperplastic

The sporadic form is the most common type, representing approximately 85% of carotid body tumors (CBTs). The familial type (10-50%) is more common in younger patients. The hyperplastic form is very common in patients with chronic hypoxia, which includes those patients living at a high altitude (> 5000 feet above sea level), like those patients living in New Mexico, Peru, and Colorado.^[2] The hyperplastic form is also seen in patients who have chronic obstructive pulmonary disease (COPD) or cyanotic heart disease.

Descriptions of surgery for carotid body tumors have existed for over 100 years. The early reports described significant complications, particularly mortalities secondary to intraoperative bleeding.^{[3, 4, 5]}

In the United States, the earliest successful carotid body tumor resection was performed by Scudder in 1903.^[3]

Even into the middle of the 20th century, resecting these tumors remained a problem because of the complications; Hayes Martin, in his textbook of head and neck tumors, recommended against resection of any tumor that is now considered a Shamblin type III (see Staging).^[6]

Modern imaging and current surgical and vascular techniques have significantly improved the safety and success of this operation.

Frequency

Parasympathetic paragangliomas are rare, with a prevalence of 1-2 per 100,000 population.^[7] Carotid body tumors (CBTs) constitute about 65% of head and neck paragangliomas.

Carotid body tumors (CBTs) can occur in children; however, carotid body tumors (CBTs) are considered to be a disease of middle age. The mean age of onset is reported to be 45 years.^[8] Paragangliomas are inherited in 10-50% of cases. Age of onset in the hereditary group is typically younger, in the second to fourth decade.^[9]

About 5% of carotid body tumors (CBTs) are bilateral and 5-10% are malignant, but these rates are much higher in patients with inherited disease.^{[10, 11, 12]} Familial tumors are found to be 5.8 times more common among patients who have carotid body tumors as compared with patients who have paragangliomas at other sites.

Interestingly, the male-to-female ratio differs in patients dwelling at high altitudes above 2,000 meters (1:8.3) than those patients dwelling at sea level (1:1.0-1.4).^[13]

The only known risk factors are the presence of chronic hypoxic stimulation and the genetic predisposition.

Carotid body tumors (CBTs) are classified into sporadic, familial, and hyperplastic forms. The familial paraganglioma form is a genetically heterogenous entity; currently, 4 genes are identified. The first 3 genes encode the subunits of the enzyme succinate dehydrogenase complex, which is part of the Kreb's cycle. Paraganglioma (PG) syndrome 1, 3, and 4 occur because of mutations of the corresponding genes of the subunits D, C, and B.^[14] PG syndrome 2 gene mutations are yet to be identified.

Defective succinate dehydrogenase has been postulated to cause an increase in the intracellular concentration of molecular hypoxia mediators and the vascular endothelial growth factor (VEGF) thus resulting in hyperplasia, angiogenesis, and neoplasia.^[7]

In patients who lack a positive family history, germline mutations in the PGL susceptibility genes are still possible via multiple causes, including genomic imprinting, reduced penetrance, or de novo mutations in the genes of the parental gametes.^[14]

Chronic hypoxic conditions, such as patients living at high altitudes or those who have chronic obstructive pulmonary disease (COPD) or cyanotic heart problems, can overburden the carotid bodies and subsequently lead to hypertrophy, hyperplasia, and neoplasia of the chief cells.^[14] This condition is seen in the hyperplastic type of carotid body tumors (CBTs). However, the mechanism by which reduced oxygen concentrations can lead to CB hyperplasia is unclear.

Finally, carotid body tumors (CBTs) can be occasionally coupled with nonparaganglonic tumors in syndromes including MEN type II, von Hippel-Lindau syndrome, and neurofibromatosis type 1.

Carotid body tumors (CBTs) present most commonly as an asymptomatic palpable neck mass in the anterior triangle of the neck. They are slow-growing tumors that can remain asymptomatic for many years. The doubling time (T_D) of carotid body tumors (CBTs), as estimated by Jansen et al using sequential imaging, was 7.13 years with a median growth rate of 0.83 mm/year.^[15]

On examination, the mass is typically vertically fixed because of its attachment to the bifurcation of the common carotid (Fontaine sign). A bruit can be felt; however, the absence of a bruit does not rule out a carotid body tumor (CBT). Vagal body tumors are more cranially located and sometimes project into the lateral pharynx as a pulsatile mass.

Approximately 10% of the cases present with cranial nerve palsy with paralysis of the hypoglossal, glossopharyngeal, recurrent laryngeal, or spinal accessory nerve, or involvement of the sympathetic chain.^[16] Carotid body tumors (CBTs) may, therefore, be associated with pain, hoarseness, dysphagia, Horner syndrome, or shoulder drop.

As the tumor enlarges and compresses the carotid artery and the surrounding nerves, other symptoms may also be present, such as pain, tongue paresis, hoarseness, Horner syndrome, and dysphagia.

Fever is an uncommon sign of carotid body tumor (CBT), although the literature has reported it as one of the causes of fever of unknown origin.^[17] In cases of functional carotid body tumors (CBTs), symptoms similar to those of pheochromocytoma, such as paroxysmal hypertension, palpitations, and diaphoresis, are seen.

The carotid body is a small, reddish-brown, oval structure, located in the posteromedial aspect of the carotid artery bifurcation. The healthy gland measures 3-5 mm in diameter and weighs less than 15 mg on average.^[18] The vast majority of the literature states that the gland is located in the adventitia near the carotid artery bifurcation. However, according to Maxwell et al, most surgeons experienced with carotid body dissection maintain that it is more peripherally located, within periadventitial tissue. This distinction is critical, as dissections in the deeper planes of the carotid artery are associated with higher risk for complications from vessel injury.^[19]

The gland is highly vascular and receives its blood supply from feeder vessels running through the Mayer ligaments, primarily from the external carotid artery, typically the ascending pharyngeal artery. It is innervated by the Hering nerve, originating from the glossopharyngeal nerve about 1.5 cm distal to the jugular foramen.^[20]