Carotid body tumor

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Maria Fernanda Villarreal, M.D. [3]

Carotid body tumor, also known as carotid body paraganglioma, is a neuroendocrine neoplasm originating from carotid body. It is located at the carotid bifurcation with characteristic splaying of the internal carotid artery and external carotid artery.

Carotid body was first described by Von Haller in 1743. From 1930, it has been accepted that monitoring of arterial blood oxygen is its main function. Carotid body tumor was first described by Bungeler in 1952. The familial form of the carotid body tumor was first described by Chase in 1993. In 1889, The first surgical excision of the tumor without complication was done by Dr. Albert.

Carotid body tumor is classified into sporadic, familial and hyper-plastic form. According to Shamblin surgical classification, carotid body tumor divided into three subtypes which includes: class I that localized with minimal vascular attachment, class II that partially surrounds carotids and class III which encases carotids as well.

The carotid body is an ellipsoid-like structure located in the adventitia or periadventitial tissue of the bifurcation of the common carotid artery. This organ is a chemo-receptor and its function is the monitoring of arterial blood oxygen and carbon dioxide levels. The exact pathogenesis of carotid body tumor is not fully understood. however, the overgrowth of chemoreceptor paraganglioma cells in the carotid body leads to the formation of carotid body tumor. Recent litreture has suggested the role of several germline mutations in the pathogenesis of this tumor. Also, the hyperplastic form of the tumor has been associated with conditions that causes chronic hypoxia.

Carotid body tumor may be caused by familial syndromes, germline mutation of several genes, or chronic hypoxia.

Carotid body tumor must be differentiated from other diseases that cause neck mass including schwannomas and lymphadenopathy.

The incidence of carotid body tumor is less than 3 in 100,000 individuals. It is the most common paraganaglioma of the head and neck and comprises approximately 65% of paragangliomas. The prevalence of head and neck paraganglioma is 3% of all paraganglioma. This tumor is more commonly observed in the adults and particularly in their fifth decade of life. It affects both gender equally.

Common risk factors in the development of carotid body tumor include genetic mutation and chronic hypoxia.

There is insufficient evidence to recommend routine screening for the carotid body tumor. However, patients who manifested the symptoms before the age of 50 years old, those with a positive family history and those with multiple paragangliomas has been recommended to undergo additional testing.

If left untreated, patients with carotid body tumor may progress to develop cranial nerve dysfunction, airway obstruction, and malignant transformation of the tumor. Prognosis is generally good, and the 10-year survival rate of patients is approximately 50%.

The carotid body tumor is diagnosed primarily by history and physical examination. However, imaging studies are necessary to make the final diagnosis. Color Doppler ultrasound has been recommended as a method of screening for the diagnosis of carotid body tumor. It is also suggested that CT angiography is more accurate than color Doppler ultrasound for the diagnosis of larger lesions. CT imaging combined with color Doppler ultrasound has been suggested as the optimal detection modality for the assessment and management of the tumor. It should be mentioned that, traditionally, digital subtraction angiography (DSA) has been the gold standard for the diagnosis of carotid body tumor.

The most common symptoms of carotid body tumor include neck mass, neck pain or headache. Other symptoms may also be present depending on the invasion of tumor to the neighboring structures.

Patients with carotid body tumor usually appear normal. Physical examination of patients with carotid body tumor is usually remarkable for a palpable, painless, rubbery mass at the lateral side of the neck.

There are no diagnostic laboratory findings associated with carotid body tumor. However, since these tumors originate from extra-adrenal chromaffin tissue of the autonomic nervous system, they may be capable of catecholamine productions.

There are no ECG findings associated with carotid body tumor.

There are no x-ray findings associated with carotid body tumor.

The combination of B mode ultrasound imaging and color-Doppler sonography has been observed to be diagnostic for carotid body tumor.

Cervical CT scan may be helpful in the diagnosis of the carotid body tumor. Findings on CT scan suggestive of/diagnostic of carotid body tumor include a well-defined, hypervascular mass which will show homogeneous and intense enhancement after intravenous administration of contrast dye.

MRI may be helpful in the diagnosis of carotid body tumor. Findings on MRI suggestive of/diagnostic of carotid body tumor is salt and pepper appearance on the T2 weighted images. On T1 weighted images, the tumor has the same intensity as the muscle.

Since paragangliomas including carotid body tumor are of neuroendocrine origin, they may have somatostatin surface receptor which can be detected as an area of intense radio-tracer uptake by the Indium-111 octreotide scan. This modality may be helpful in the diagnosis of multicentric or metastatic disease. It also may be used after the surgery to look for a residual tumor.

There are no other diagnostic studies associated with carotid body tumor.

There is no treatment for carotid body tumor; the mainstay of therapy is surgery.

Traditionally, surgery is considered the mainstay of treatment for the carotid body tumor. However, there is a growing amount of studies observing that radiotherapy can be used as an alternative treatment with equal efficacy and lower complications.

There are no established measures for the primary prevention of carotid body tumor.

There is insufficient evidence to recommend routine screening for the carotid body tumor. However, patients who manifested the symptoms before the age of 50 years old, those with a positive family history and those with multiple paragangliomas has been recommended to undergo additional testing.

​

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Maria Fernanda Villarreal, M.D. [3]

Carotid body was first described by Von Haller in 1743. From 1930, it has been accepted that monitoring of arterial blood oxygen is its main function. Carotid body tumor was first described by Bungeler in 1952. The familial form of the carotid body tumor was first described by Chase in 1993. In 1889, The first surgical excision of the tumor without complication was done by Dr. Albert.

• Carotid body was first described by Von Haller in 1743.^[1]
• The exact mechanism of action of the carotid body is still needed to be discovered, however, from 1930, it has been accepted that monitoring of arterial blood oxygen is its main function.^[2]
• The familial form of the carotid body tumor was first described by Chase in 1993.^[1]
• Carotid body tumor was first described by Bungeler in 1952.^[3]
• The tumor is also called chemodectema, first suggested by Mulligan in 1951.^[4]
• In 1971, Dr. Shamblin established a classification system for carotid body tumor according to tumor size and involvement of the carotid vessels.^[5]

• In 1880, The first surgical excision of the tumor was done by Dr. Reigner, which resulted in the death of the patient shortly after the surgery.^[6]
• In 1886, The first successful surgical excision of the tumor was done by Dr. Maydl but again resulted in neurological complications in the patient.^[7]
• In 1889, The first surgical excision of the tumor without complication was done by Dr. Albert.^[8]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Maria Fernanda Villarreal, M.D. [3]

Carotid body tumor is classified into sporadic, familial and hyper-plastic form. According to Shamblin surgical classification, carotid body tumor divided into three subtypes which includes: class I that localized with minimal vascular attachment, class II that partially surrounds carotids and class III which encases carotids as well.

• Carotid body tumor is classified into 3 categories:^[1]

• Familial carotid body tumor
• Sporadic carotid body tumor
• Hyperplastic carotid body tumor

• Carotid body tumor is sub-classified into 2 categories:

• Single
• Bilateral

• Carotid body tumor may also be classified according to Shamblin surgical classification into 3 subtypes: I, II, and III.^[2]

• Class I: localized tumor, splaying the carotid bifurcation and with minimal vascular attachment
• Class II: partially surrounds carotid vessels
• Class III: encases carotids.

• The purpose of this classification is to make a estimate of the possible complications of surgical removal of the tumor.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Maria Fernanda Villarreal, M.D. [3]

The carotid body is an ellipsoid-like structure located in the adventitia or periadventitial tissue of the bifurcation of the common carotid artery. This organ is a chemo-receptor and its function is the monitoring of arterial blood oxygen and carbon dioxide levels. The exact pathogenesis of carotid body tumor is not fully understood. however, the overgrowth of chemoreceptor paraganglioma cells in the carotid body leads to the formation of carotid body tumor. Recent litreture has suggested the role of several germline mutations in the pathogenesis of this tumor. Also, the hyperplastic form of the tumor has been associated with conditions that causes chronic hypoxia.

• The carotid body is an ellipsoid-like structure located in the adventitia or periadventitial tissue of the bifurcation of the common carotid artery.^[1]
• The normal carotid body weighs less than 15 mg and measures between 3 to 5 mm.
• This structure innervated by the hearing branch of the glossopharyngeal nerve, however, the carotid body is in close proximity of a majority of important nerves.
• The blood supply to the carotid body is provided by ascending pharyngeal artery, which is the branch of the external carotid artery.

• The carotid body is a chemo-receptor and its function is the monitoring of arterial blood oxygen and carbon dioxide levels.^[2][3]
• This organ is sensitive to the reduction of oxygen partial pressure in the blood which results in reflexive activation of the autonomic nervous system and the resultant increase in the

ventilation rate.

• Carotid body tumor is a neuroendocrine neoplasm originating from carotid body.^[4]
  • Carotid body is a component of the autonomic nervous system derived from neural crest cells of the embryonic third branchial arch.^[1]
• The overgrowth of chemoreceptor paraganglioma cells in the carotid body leads to the formation of carotid body tumor.
• Carotid body tumors are normally located in the medial aspect adventitia of the carotid bifurcation.
• Carotid body tumor occurs sporadicly in 85% to 90% of the cases.^[1][5]
• Recent litreture has suggested the role of several germline mutations in the pathogenesis of this tumor.^[6]
• It has been explained that the hyperplastic form of the tumor is associated with chronic hypoxia due to such as:^[1][7]
  • Chronic obstructive pulmonary disease
  • Cyanotic heart disease
• The tumor may be bilateral in fewer than 5% of the sporadic cases.
• The tumor may be familial in the rest 10% to 15%.
  • In familial cases, it may be bilateral in 30% to 40% of the cases.

• The familial form of the tumor is associated with a mutation in a gene located on 11q23.^[8]
• The disease inheritance is through autosomal dominance.^[9]
• The following genes has been linked to an increased incidence of paraganglioma including carotid body tumor:^[10][6]
  • Succinate dehydrogenase (SDH) complex subunits B, C, and D.
  • RET
  • Von Hippel-Lindau (VHL)
  • Neurofibromatosis type I (NF1)

Conditions associated with carotid body tumor include:^[6]

• Von Hippel-Lindau syndrome
• Neurofibromatosis type I (von Recklinghausen disease)
• MEN 2A
• MEN 2B
• Carney’s triad which consists of:^[11]
  • Gastric leiomyosarcoma
  • Pulmonary chondroma
  • Extraadrenal paraganglioma

|Characteristic findings of carotid body tumor, include:^[6]

• • Well-circumscribed with psudocapsule
  • The size of the tumor varies greatly and it may be as large as 10 cm
  • The cutting surface is solid with a smooth, rubbery texture

• On microscopic histopathological analysis, carotid body tumor composed of:
  • The chief or paraganglionic cells composing the predominant part of the tumor and contain eosinophilic granular materials and oval or round nuclei.^[12]
  • The supporting or sustentacular cells responsible for the chemoreceptor activity of the carotid body
• The characteristic finding of this tumor is:

• Chief cells Arranged in distinctive pattern called cell balls (zellballen)
• Separated by fibrovascular stroma and surrounded by sustentacular cells
• The cytoplasm is pale and diffuse with occasional presence of the eosinophilic granules.^[13]
• The nuclei are round to spindle shape.

• The tumor is highly vascular.
• Although there is no well-accepted histologic criteria for the diagnosis of malignant tumors, worrisome histologic features include:^[6]
  • Necrosis
  • Extensive vascular or capsular invasion
  • Increased mitotic activity
  • Atypical mitotic figures

• Type 1 cells, sustentacular cells, are stained by:^[14]
  • S-100
• Type 2 cells, cheif cell, are stained by:
  • Chromogranins
  • Synaptophysisn
• The tumor cells may also be positive for other markers of neuroendocrine differentiation such as:^[6]
  • CD56
  • Neuron specific enolase

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Maria Fernanda Villarreal, M.D. [3]

Carotid body tumor may be caused by familial syndromes, germline mutation of several genes, or chronic hypoxia.

Common causes of carotid body tumor, include:^[1]

• Familial syndromes such as:
  • Multiple endocrine neoplasia (MEN) type 1 and 2
  • Neurofibromatosis type 1 (NF1)
  • Von Hippel-Lindau disease (VHL)
• Germline mutation in the following genes:
  • RET
  • SDH subunits SDHB, SDHC, and SDHD.
• Causes of chronic hypoxia such as:^[2][3]
  • Chronic obstructive pulmonary disease (COPD)
  • Cyanotic heart disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Maria Fernanda Villarreal, M.D. [3]

The incidence of carotid body tumor is less than 3 in 100,000 individuals. It is the most common paraganglioma of the head and neck and comprises approximately 65% of paragangliomas. The prevalence of head and neck paraganglioma is 3% of all paraganglioma. This tumor is more commonly observed in the adults and particularly in their fifth decade of life. It affects both gender equally.

• The incidence of this tumor is less than 3 in 100,000 individuals.^[1]
• The incidence of malignant case has been observed to be 10%.^[2]

• The prevalence of carotid body tumor is approximately 65% of head and neck paraganglioma.^[3]
• The prevalence of head and neck paraganglioma is 3% of all paraganglioma.
• The estimated prevalence of parasymapathetic paraganglioma is approximately 1-2 cases per 100,000 individuals worldwide.

• Carotid body tumor is more commonly observed in the adults and particularly in their fifth decade of life.^[4]
• In familial cases, the mean age of onset is younger, being the second or fourth decade of life.^[5]

• There is no gender preference in the incidence of this tumor according to the recent literature except in the high altitude where the tumor is more prevalent among women.^[5][6]

• There is no racial predilection to carotid body tumor.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Maria Fernanda Villarreal, M.D. [3]

Common risk factors in the development of carotid body tumor include genetic mutation and chronic hypoxia.

• Common risk factors in the development of carotid body tumor, include:^[1]

• Genetic mutations in the following genes:

• MEN 2A
• MEN 2B
• RET
• VHL
• NF1
• SDH subunits (SDHD, SDHB, and SDHC)

• Chronic hypoxia has been observed to be associated with hyperplastic form of carotid body tumor.^[2][3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2] Maria Fernanda Villarreal, M.D. [3]

If left untreated, patients with carotid body tumor may progress to develop cranial nerve dysfunction, airway obstruction, and malignant transformation of the tumor. Prognosis is generally good, and the 10-year survival rate of patients is approximately 50%.

• The symptoms of carotid body tumor usually develop in the fifth decade of life and start with symptoms such as asymptomatic mass in the anterior triangle of the neck.^[1]
  • In familial cases, it tends to manifest at a younger age.^[2]
• It may be clinically silent for years before presenting as a painless mass in the neck.^[3]
• The tumor can also present with a pulsating mass in the lateral side of the neck.
• This tumor is a slowly growing mass with the median growth rate of 1.0mm/year.^[2]
• The median time needed for the tumor to be doubled in 4.2 years.
• If left untreated, patients with carotid body tumor may progress to develop cranial nerve involvement, airway obstruction, and malignant transformation of the tumor.

• Carotid body tumor growth may cause local damage such as:^[4]
  • Cranial nerve dysfunction
  • Airway obstruction
• Carotid body tumor may result in neurovascular complications peri and postoperatively.^[5][6]
• These complications include cranial nerve damage as well as carotid vessel hemorrhage.
• Neurovascular complication rate differs according to the Shamblin subtype and the size of the tumor.
  • For type I and II, the peri and post-surgical complications are low and around 0% to 3% of the cases.
  • For Type III, it may be as high as 7% to 35% of the cases.
• Carotid body tumor may transform into malignant form in almost 10% of the cases.
  • There is no accepted guideline on the diagnosis of malignancy via histology of the tumor and it has been observed that pathological examination of the tumor is unable to differentiate between benign and malignant tumor. ^[7]
  • Malignant carotid body tumor is usually diagnosed by the presence of:
    • Local recurrence of the tumor
    • Regional lymph node involvement
    • Distant metastasis
    • Tumor may metastasizes locally or to the distant organs via lymphatics or vasculature.^[8]
      • The most common sites of distant metastasis are bone, liver and lungs.

• Prognosis is generally good after complete surgical removal of the tumor.^[9]
• In case of malignant metastasis, the follow-up must be done continuously, however, recurrence or metastasis may occur years later.
• The 10-year survival rate of patients with malignant paraganglioma is approximately 50%.