Update in carotid chemodectomas.
Chemodectoma is one of possible non atherosclerotic pathologies of the neck that include vessel thromboembolism, dissecting aneurysms, fibromuscular dysplasia, Takayasu's arteritis, pseudoaneurysms and arteriovenous fistulae. The prevalence of nonatherosclerotic pathologies was calculated as 0.65% in a previous study of Labropoulos done in 11480 ultrasound tests held from 1997 to 2003. 91)
Carotid chemodectomas are called paragangliomas or carotid body tumors (Fig 1). Carotid body was first described in 1743. Kohn first used the term paraganglion to describe the carotid body. (2) Paragangliomas are highly vascular and slow growing tumors (5 mm annually) deriving from the paraganglia, which are specialized tissue of the extra-adrenal neuroendocrine system. (2) They are formed by cells divided by vascular channels and fibrosis matrix (Fig 2). Usually they are localized in the neck anterior to the sternocleidomastoid muscle at the level of the hyoid bone. Glennes and Grimley (3) proposed a classification of these tumors based on location, innervation and microscopic appearance, and helped distinguish the adrenal paragangliomas from the extra-adrenal paragangliomas (Table 1).
Paragangliomas are uncommon: they have an incidence of 0.6% of head and neck tumors and 0.03% of all tumors, can be bilateral in 10% of cases, familial in 30% with autosomal dominant hereditary transmission. Malignancy is more common in the non-familial than in the hereditary form. Paragangliomas can be seen in adult 30-60 years old, generally women. (4)
Carotid body tumors are composed by two cells types: the type I cells are the chief or paraganglionic cells; the type II cells are the sustentacular cells. Chief cells are arranged in a characteristic pesudoalveolar pattern described as Zellballen (which means cells balls). These cells contain eosinophilic cytoplasmatic granules and predominate in case of paraganglioma. (5) These tumors are functionally active only in 1-3% of cases. Usually sporadic and unilateral, they can be familiar in 10% of cases with autosomic dominant transmission: the latter is bilateral up to 30%. Generally benign, malignant transformation may occur in up to 10% of the cases. Metastases are found in less than 5% and multiple tumors in 5%.6 Malignancy is usually more common in the sporadic form and it is not related with tumor size. The malignant type of chemodectoma cannot be predicted by the initial clinical presentation or by the histologic appearance. Nuclear pleomorphism, atypia or mitotic activity are not considered signs of malignancy. The presence of metastasis to the cervical lymph nodes or other sites (such as lung, bone, breast, liver) is the most important criterion for the diagnosis of malignancy. (7)
Around 80% of paragangliomas are carotid body or jugulotympanic glomus tumors. There is not agreement about which site of clinical appearance is the most common. The local distribution of paraganglioma was recently reported as: 47% jugulotympanic, 43% carotid, 10% vagal tumors. (2) The tumor location is variable, posterior to the bifurcation of the common carotid artery or partially wedged in between the internal and external carotids.
The pathogenesis of paragangliomas remains unknown. Some authors have indicated that the histologic category of the tumor, the hyperplastic type, is very common in patients with chronic hypoxia, like people living at high altitudes and patients with obstructive chronic pulmonary disease, or patients with congenital cyanotic heart disease. (8) Probably that kind of tumor is the result of over-response to change in body homeostasis. It is demonstrated that chronic exposure to hypoxia is responsible of a compensatory hypertrophy of carotid body and some studies have shown that long exposure to high altitudes appears to be correlated with a 10-fold higher incidence of carotid body tumors but no increase in the incidence of paragangliomas located in other sites has been reported. (8)
The clinical presentation of the tumor depends on the site and the size of the tumor. Symptoms are related to tumor dimension after 3-10 years of tumor enlarging with nearest structures compression or to cathecolamine production. The typical form of presentation is a painless slow-growing mass, that can bulge into pharynx or extend into parapharyngeal space and can splay internal and external carotid artery ("lyre" sign, Fig. 3). A bruit may be auscultated over the mass. Sometimes the symptoms like dysphagia, odynophagia, dysphonia, are related to compression of cranial nerves 9 to 12 due to a great mass.
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A carotid body tumor usually presents headache or neck pain in 35%, dizziness in 8%, hoarseness in 8% and dysphagia in 8% of patients. The involvement of the cranial nerves, especially the vagus and the hypoglossal, occurs in 10% of the cases. (9) Horner syndrome may result from cervical sympathetic chain invasion, and syncope can occur after carotid sinus compression. (4) Sometimes paragangliomas have an endocrine activity (up 3% of cases) and are responsible of systemic symptoms such as tachycardia, hypertension and tremors. The large majority of carotid paragangliomas are non-secreting but the patient must be questioned about any symptoms of excessive catecholamine secretion.
Diagnosis can be difficult due to the common absence of symptoms but if there is a typical neck mass diagnosis can be easy with palpation just lateral to tip of hyoid bone. The presence of a pulsatile neck mass located in the region of carotid triangle and generally present for several years should suggest the presence of a carotid body tumor. This mass has a positive Fontaine sign, which means that the mass is vertically fixed and laterally mobile because of the adherence of the carotid vessel. So the mass is mobile in anterior-posterior direction but not in the towards up and down. Sometimes a carotid bruit can be observed. (10) A high index of clinical suspicion for the presence of a carotid bifurcation related to paraganglioma is required to avoid an open or percutaneous biopsy, that can lead to significant hemorrhage. Differential diagnosis is very important because a variety of lesions can have the same clinical presentation such as lymphomas, cranial clefts cystis, neurilemomas, parotid gland tumors, thyroids masses, metastatic cervical lymphanedopathy, and tubercolosis. (4) After clinical examination, imaging studies are the most important step for evaluation of neck masses. (11)
Among imaging studies, the Color Flow Duplex Scanning (CFDS) is the first for the diagnosis of carotid body tumor and for differential diagnosis, with a high accuracy rate of about 94%. It is also a very helpful exam in the screening and follow-up of patient with a familial history of paragangliomas. (12)
CFDS is useful for diagnosis of bilateral or multicentric paragangliomas, especially when integrated with TC scan. A rapid and complete diagnosis is important for a surgical treatment, because this mass can be malignant. The histological appearance of a carotid body paraganglioma is not a reliable guide to its propensity for malignant behavior due to the poor correlation between histology and tumor behaviour. The majority of authors agree that the only proof of malignancy in paragangliomas is the presence of metastases.
CFDS (Fig 4) shows splaying of the carotid bifurcation because a well-defined, solid, hypoechoic mass is present; small vascular structures and channel are present too. The vessel must be studied with longitudinal and axial scan: in this way becomes apparent the relation of the tumor with the vessels. Axial scan shows the best delineation of the tumor mass within the carotid bifurcation. Usually the carotid bifurcation is enlarged; internal and external carotid arteries are surrounded by the mass. The imaging study must be complete, because sometimes the tumor is bilateral. Some authors (13) believe that the diagnosis of carotid body tumor with ultrasounds is practically made when a mass is present within the carotid bifurcation and there is demonstated that the mass is single or bilateral.
Color Doppler studies are necessary in order to produce state of the art tumor imaging. Color Doppler shows hypervascularity with a low-resistance flow pattern of intratumor vessels. If the intratumor vessels are large, a flow pattern resembling internal carotid artery can be observed, with the same or higher systolic velocities and diastolic velocities smaller than carotid internal diastolic velocities. The striking hypervascularity is one of most helpful data to discriminate paraganglioma from other lateral neck masses, and it is fundamental finding in cases of small tumors.
Spectral analysis with proton echo shows low-resistance blood flow from intratumor vessels and it is useful for a differential diagnosis from other solid and nonhypervascular neck masses, like inflammatory lymphonodes. Ultrasound tests can figure out the relationship between the mass and adjacent carotid arteries.
The limits of ultrasound evaluation is the diagnosis of chemodectoma arising from vagal glomus or in temporal bone and a precise vascular definition of the tumor vessel. Negative results of echo-imaging do not exclude the diagnosis of a vagal body tumor or the presence of multicentric paragangliomas in the skull base region.
Contrast ultrasonography improved the quality of the standard color Duplex: this is a non-invasive method, easy to use and to repeat, and able to achieve high diagnostic accuracy. (14)
For these reasons the CFDS can be considered the initial diagnostic procedure of neck masses but must be integrated with others imaging studies such as contrast-enhanced computed tomography (CT), magnetic resonance (MR) or digital subtraction angiography (DSA). (15)
CT or MRI scanning is useful to study the relation of the tumor to adjacent structures, to determine cranial extension and to obtain information regarding the vasculature of the tumor and its feeding vessels. Another advantage of this technique is the diagnosis of other tumor sites.
On CT scan (Fig 5) paraganglioma appears as a mass with intensive enhance. It is very useful with bone windows to identify the tumor intracranial spread and the erosion of skull base. False positive findings are represented in most of cases by hypervascular lymph nodes, but usually in these cases there is a diagnosis of metastatic tumor.
MR shows paragangliomas as a mass with low-signal intensity in T1-weighted sequences and with an hyperintense signal in T2-weighted sequences. The classic salt and pepper picture, greater than 1 cm in diameter, is related to the slow flow vessels or hemorrhage, but also in this case the presence of hypervascular lymph nodes, or metastasis can due to a false positive image. MR is more sensitive than CT in the evaluation of skull base or intracranial spread of tumor and for the detection of paragangliomas smaller than 0.8 cm in diameter.
Carotid Digital Subtraction Angiography (DSA), with a percutaneous femoral approach, is the invaluable diagnostic exam when we have to define the exact vascular anatomy of the tumor. It shows a hypervascular mass with early, intense enhancement but also can identify an arterial map of the neoplasm. Both carotids should be studied to exclude multicentricity.
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DSA can also be used for performing an occlusion test to asses the circle of Willis supply in case of arterial exclusion. The identification of possible vascular anomalies and of intracranial perfusion is a corner step to evaluate the best treatment option. The diagnostic coincidence rates of ultrasound and angiography are 95% and 98% respectively. (17)
Other exams which are important in the general evaluation-phase of a carotid bulb paragangliomas are endocrine study and 123I-MIBG scan.
The endocrine studies (urinary metanephrine, vanillylmandelic acid, homovanillic acid and dopamine) are useful in patients with symptoms of cathacolamine-secreting tumors. A I-MIBG scan is useful in the setting of possible multicentric paragangliomas, especially in the context of a familial paraganglioma. (8)
To date there is not agreement about the best management of paragangliomas. If not treated, carotid body tumors may grow with conseguent neurovascular problems and mortality rate of about 8%.12 The treatment options are four: follow up, surgical resection, embolism and radiotherapy, alone or in combination. (14)
Follow-up is necessary after every treatment, because even if resected, carotid body tumors can produce metastases, like pulmonary. (18-19) The use of chemotherapy in metastatic paragangliomas has not been yet clearly established and although some results are optimistic, specially concerning the treatment of symptoms, an increase in survival rates has not been clearly proven.
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There are a lot of factors that could influence the treatment options such as age, symptoms, tumor size, multicentricity, growth rate, side of dominant hemisphere. Surgical mass resection and internal carotid artery reconstruction is the treatment of choice for carotid body tumors, especially when the tumor is small because decrease risk of neurological post-surgery complications. So is important the diagnosis when the mass is small. The surgical choice is related to Shamblin classification (20-21), made in 1971 and based up the degree of involvement of the carotid vessels in carotid body tumors, as appear with arteriographic or MRI study. Type I are small tumors with minimal arterial attachment; type II usually are larger tumors, exhibiting moderate arterial attachment and partially surrounding both carotid arteries; type III are characterized by encasement of the carotid bifurcation. This classification has implications for post-surgical morbidity and prognosis. So the worse prognosis is for Shamblin class III tumors. Surgical time and bleeding are directly related to the Shamblin as it reflects the size of tumors in relation to the blood vessels. The most important principle is to preserve the integrity of the internal carotid artery, eventually to repair defect with a graft.
Some authors suggest a multidisciplinary approach with co-operation of vascular surgeons, otolaryngologists and neuroradiologists, to treat these patients.
Preoperative embolization has been used to lessen the morbidity in tumors that are larger than 2 cm in diameter. (22) Generally, embolization is performed with polyvinyl alcohol of varying participle diameters. These substances are delivered to the feeding artery through a superselective catheterization. The objective is directing the embolism material to selectively permeate only the vascularity of the paraganglioma without proximal occlusion of the feeding artery and certainly avoiding distal migration of emboli into the general systemic circulation, which would result inn possible central nervous system and pulmonary complications. The aim is to document at the postembolization angiography the absence of tumor blush and the patency of the external carotid system.
The decision for embolization depends on the tumor's location or extension and on the experience of surgeon and radiologist. (23) To obtain the best clinical results excision of tumor is to be performed within 48 hours to reduce the local edema and the antinflammatory response. The rate of major vascular complications dropped from 30% in the 1960s to less than 1% in the most recent reports. An important advance was the adoption of vascular reconstruction after internal carotid artery ligation, because it was associated with a risk of hemiplegia up to 20% in this series. (24-25) The risk of cranial nerve palsy in these patients ranges from 10% to 40%. The vagal, hypoglossal, glossopharyngeal, and sympathetic are the most commonly involved nerves. The rate of nerve complications is greater in patients with Shamblin II/III tumors. Saijd et al reported an incidence of cranial nerve deficit after CBT surgery that vain a review about data of many series of patients reported an incidence of cranial nerve deficit after CBT surgery that varies from 11% to 49%. Most of these injures are temporary. The incidence of permanent cranial nerve deficit has been reported as less than 1%. In the same review the incidence of TIA/stroke varies from 0 to 8%. Mortality is a rare complication and in international literature varies from 0-7.4%. (26)
The role of radiation therapy in this context is not definitively clear. Recently the radiotherapy is proposed for treatment of carotid body paragangliomas with extensive intracranial or skull base involvement, multiple or bilateral. It is also useful in older patients especially when there is a high risk of cranial nerve dysfunction or other complications. Radiotherapy is less invasive than surgery and with a favorable profile of treatment related complications and high rates of local control. In some series it is demonstrated that there is not any advantage of subtotal resection along with radiotherapy compared with radiotherapy alone.
Follow up examination is important to monitor the possibility of recurrence. It is consisted of CFDS and clinical examination in all patients annually. All first degree-relatives were also subjected to annual ultrasound evaluation of the cervical region for detection of familial tumors. (27)
In conclusion carotid body tumors are possible causes of lateral neck masses. CFDS can reveal the typical solid mass with many fine vascular channels and is useful for morphoplogical data, as size. According to current treatment trends, embolization before surgical resection is the treatment of choice. (28)
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Corresponding author: Costanza Goffredo, Via alvaro del portillo 200, 00128, Rome, Italy Phone number: +390622541-1165 E-mail: email@example.com
Costanza Goffredo , Pier Luigi Antignani , Francesco Gervasi , Elisabetta Ricottini 
 Department of Cardiology, Campus Bio-medico University, Rome, Italy
 Department of Angiology, S. Giovanni Hospital, Rome, Italy
 Department of Cardio-pulmonary diseases, Celio Military Hospital, Rome, Italy
Table 1. Classification of Paragangliomas (Grennes and Grimley) Group Description 1 Associated with the large vessels of the chest and neck (brachial origin) 2 Associated with the vagus nerve 3 Associated with the sympathetic chain in the thoracic-lumbar region, from the aortic arch to the bladder, including the organ of Zuckerland 4 Associated with viscerae Table 2. Ultrasound features of chemodectomas * Slowly enlarging mass * Color-Doppler shows splaying at the carotid bifurcation * Transmits the carotid pulsation * Highly vascular * Demonstrates pulsation * Mobile from side to side but not up and down. * Bilateral and multicentric tumors * Typical diastolic flow pattern
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|Title Annotation:||CME ARTICLE|
|Author:||Goffredo, Costanza; Antignani, Pier Luigi; Gervasi, Francesco; Ricottini, Elisabetta|
|Publication:||Archives: The International Journal of Medicine|
|Date:||Apr 1, 2009|
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