Carotid Body Tumor: A Case Report and Review of Literature

Abstract

Carotid body tumour (CBT) is a rare hypervascular tumor in the head and neck region. It develops from neural crest origin paraganglionic tissue which is an arterial chemoreceptor. It presents as a slow growing mass at the carotid bifurcation. Its optimal evaluation and treatment requires involvement of multiple specialities. Because of the high rate of neurovascular complications, resection of this tumor is challenging for surgeons. Early tumor detection, meticulous evaluation and multidisciplinary approach are vital for successful management of these tumors. A case of CBT in a 50 year-old lady managed at our centre is being reported here along with a review of literature.

Introduction

Carotid body is a neural crest origin paraganglionic tissue which is an arterial chemoreceptor organ located at carotid bifurcation. It is responsible for detecting changes in arterial O₂, CO₂ and pH levels and stimulates respiratory centre in brainstem. CBT is a head and neck paraganglioma. There is a well-known association between hypoxia and these tumors, incidence increased proportionally with altitude, due to the chronic hypoxic stimulus that induces hyperplasia in the carotid body [1]. Only 3% of paragangliomas (PGs) occur in head and neck region and 85% in the abdomen. CBTs are the most common head and neck PGs, comprising 60% of them [2, 3]. Diagnosis of these tumors is often delayed because the clinical manifestations are very subtle and their growth pattern is very slow; hence, they can be present for decades before the patient seeks medical attention.

Due to rarity these cases are seldom encountered by surgeons. Comprehensive workup and multispeciality management are required for optimally managing these cases. Here we report a case of CBT with review of literature, discussion of which focuses on the diagnostic and surgical approaches.

Case Report

A 50 year old lady, known case of Type II diabetes mellitus and hypertension on injection insulin and oral antihypertensives, presented with complaints of gradually progressive swelling left lateral upper neck of 06 months duration. Neck examination revealed a firm, non-tender swelling measuring 04 × 04 cm, anterior extent 05 cm from midline, posteriorly 2.5 cm below the mastoid tip, inferiorly till the level of hyoid. Superior limit could not be palpated clearly as it was extending deep to mandible. There were no palpable lymph nodes. MRI Neck revealed a well-defined, large globular mass of size 04 × 04 × 3.7 cm, at the carotid bifurcation, causing marked splaying of the external carotid artery (ECA) and internal carotid artery (ICA). Left ICA and ECA were encased over half their circumference by the mass so the CBT was classified as Shamblin II (Fig. 1a). No lymph nodes were identified on MRI. Adequate vascular study was not available with MRI neck so a CT angiography of neck vessels was done to look at the status of ICA and ECA and to find out whether the CBT was receiving feeder vessels from ECA or ICA (Fig. 1b). CT angiography showed a large intensely enhancing lesion at the left carotid bifurcation consistent with CBT (Shamblin II) with multiple hypertrophied feeder vessels from ECA (from ascending pharyngeal and occipital arteries). ICA and ECA were normal in calibre and contrast opacification with no intraluminal filling defect. Gallium DOTA PET CT scan was done to look for multiple/metastatic lesions. A left carotid space mass was noted with intense somatostatin receptor expression compatible with the diagnosis of CBT, weakly metabolic on FDG PET CT (Fig. 2). No other such lesion anywhere in the body and no significant lymph nodes were identified with DOTA PET scan.

Fig. 3.

DSA, a CBT with feeders from ascending pharyngeal, occipital and carotid bulb including ICA, b tumor enhancement, c. Post embolization run showing reduced vascularity

Fig. 1.

Imaging, a CEMRI neck showing Left CBT with splaying of ICA and ECA (Shamblin II), b CT Angiography neck vessels axial section showing Left CBT, c CT Angiography coronal section showing left CBT

Fig. 2.

DOTA PET CT scan, a intense uptake on DOTA scan in left Carotid space lesion, b weak uptake on FDG PET in the same left carotid space lesion

FNAC was not done as radiology was fully diagnostic of CBT. Secretory paraganglioma workup with serum metanephrine was negative.

A decision was taken to surgically remove the tumor after preoperative embolization. A balloon occlusion test was asked however a digital subtraction angiography (DSA) with crossflow study was done by intervention radiologist and a good bilateral crossflow was ascertained.

The patient was then taken up for surgery 24 h after preoperative embolization. Embolization of feeder vessels from ECA (ascending pharyngeal, occipital and a branch of superior thyroid artery) was done using 250–350 microns polyvinyl alcohol particles. Operating team included a head and neck surgeon and a vascular surgeon. Tumor was approached by a vertical neck incision at the level of anterior border of sternocleidomastoid (SCM) from 02 cm below the mastoid tip to 01 cm below hyoid. Subplatysmal skin flaps were elevated anteriorly and posteriorly (Fig. 4). IJV was exposed after dissection at anterior border of SCM. Common facial vein, retromandibular vein and facial veins were identified and ligated. A level II lymph node in the field was dissected out and sent for histopathology (HPE). Common carotid artery was dissected and inferior control was taken by slinging it. Tumor was dissected caudocranially from carotid bifurcation along and off from the CCA, ICA and ECA (Fig. 4). Vagus, hypoglossal, glossopharyngeal and spinal accessory nerves plus the sympathetic trunk were preserved. Specimen was sent for HPE. Fascia over the SCM and anterior neck was approximated and wound was closed in layers over a suction drain. Post- operative period remained uneventful with no cranial nerve deficit. Final HPE with immunohistochemistry of the specimen was reported as paraganglioma and the lymph node was reported to be reactive.

Fig. 4.

Intraoperative pictures CBT excision, a CBT (yellow star) at the carotid bifurcation, b CBT dissected off ECA, ICA and the carotid bifurcation, c post excision tumor bed (green star), ICA (green arrow), ECA (white arrow)

Discussion

Swiss Albrecht von Haller first described carotid body in 1743 and first descriptions of surgical excision of CBT are attributed to Marchand in 1891 and Scudder in 1903 [4].

The carotid body is a small ovoid compact, pinkish tan tissue situated in the peri-adventitia along the medial aspect of the carotid bifurcation bilaterally. It is a chemoreceptor that protects organs from hypoxic damage by releasing neurotransmitters to stabilize concentrations of oxygen, carbon dioxide, and pH [5–7].

CBTs are rare neoplasms, with an incidence of 0.003% [8]; however, they represent 65% of head and neck paragangliomas (PGs) [9]. They occur at any age but the mean patient age is 30–40 years, with higher incidence in women [10].

The CBTs can be familial, sporadic and hyperplastic forms. Familial CBTs are mainly seen in younger patients and are more likely to be malignant. These hereditary tumors result from inactivating mutations in the genes SDHB, SDHD, SDHC and SDHAF2 [11]. SDH B, C and D genes code for subunits of enzyme succinate dehydrogenase while SDHAF2 codes for a protein which is required to make succinate dehydrogenase functional. The SDH enzyme links two important cellular pathways called the citric acid cycle (or Krebs cycle) and oxidative phosphorylation. As part of the citric acid cycle, the SDH enzyme converts succinate to fumarate. Succinate is an oxygen sensor in the cell and can switch on pathways that stimulate cells to grow in low oxygen hypoxic conditions [12]. Mutations in SDH gene cause reduced activity of SDH enzyme leading to its inability to convert succinate to fumarate. Thus succinate accumulates in cells and accumulated succinate triggers hypoxia pathways in normal oxygen conditions leading to abnormally excessive cell growth and formation of tumor.

The family history pertaining to PGs must be elicited. Approximately 50% of familial PGs are multicentric. They are prone to malignancy and are generally secretory. Symptoms of catecholamine secretion of the tumor should be sought carefully in these patients [13]. Catecholamine secretory work up should be done, along with appropriate imaging to rule out a concomitant adrenal pheochromocytoma and any other focus of PG.

The hyperplastic type is the most common type of CBT, seen in patients with chronic exposure to hypoxia such as high altitudes and conditions such as chronic obstructive pulmonary disease and congenital cyanotic heart disease [14].

Most CBT patients present with a slow growing painless compressible mass in the carotid cervical triangle for several months. Local neck discomfort, pharyngeal swelling, headache, dizziness, dysphagia, tinnitus, hearing loss, voice change and transient ischemic attack (rarely) are other presenting symptoms. Preoperative cranial nerve deficit is uncommon. They have been reported in 0–20% of cases and when present, Vagus nerve is the most common among the lower cranial nerves to be involved [15–17].

On examination, the neck mass is mobile from side to side but less mobile in craniocaudal direction due to adherence to carotid arteries (Fontaine’s sign). The mass is frequently pulsatile and a bruit can be auscultated over the mass. They are usually located at the anterior border of the sternocleidomastoid muscle just lateral to the tip of the hyoid bone. They may bulge into the pharynx or extend upward into the parapharyngeal space. The oral cavity should be carefully inspected as large PGs can fill the parapharyngeal space and displace the oropharyngeal wall medially. The involvement of cervical sympathetic chain can manifest as Horner’s syndrome. The features are ipsilateral miosis, ptosis, enophthalmos and anhidrosis. Facial muscle weakness, hoarseness, dysphagia or vocal cord paralysis may be manifested due to involvement of lower cranial nerves.

If the PG is secretory the most common finding is hypertension which can be paroxysmal (lasting minutes to days) or sustained. Patients who only experience hypertensive paroxysms can be overlooked by a casual blood pressure measurement that is normal. Hypertension is often accompanied by headache, palpitations, and sweating. Therefore careful history should be obtained from patients regarding any episodic symptoms, frequency, duration and any record of blood pressure and heart rate during the episodes.

Due to high cost of genetic screening, it is advised in only those cases where a genetic etiology is suspected such as multiple, metastatic, paediatric and syndromic PGs. In familial cases the results of genetic screening can be used for counselling the patients and their family members.

Catecholamine assays include 24 h urinary fractionated metanephrines or serum metanephrines. CBTs are bening tumors but rarely they can be malignant. There are no histology features of malignancy on fine needle aspiration cytology in PGs. The only means of diagnosing malignancy is by detecting metastasis to non-neuroendocrine tissues, which occur most commonly in cervical lymph nodes. Distant metastasis can occur to liver, lung, bone and skin.

The radiographic evaluation for a CBT can either be a contrast CT scan or a contrast MRI along with CT/MRI angiography to define the extent of tumor, to look for its feeder vessels and to look at the status of great neck vessels. The CBT has a typical salt and pepper appearance on contrast MRI where ‘salt’ denotes hyperintense areas of haemorrhage while ‘pepper’ denotes hypointense vascular flow voids. Splaying of ICA and ECA by tumor (Lyre sign) is characteristic of a CBT. Determining the feeder vessels with neck vessels CT/MRI angiography, whether they are arising from ICA or ECA, is important in planning for embolization preoperatively. If the feeder vessels are from ECA, they can be embolised however if they are primarily from ICA then they cannot be embolised due to risk of stroke [18–21].

Neuroendocrine tumors including PGs have marked overexpression of somatostatin receptors (SSTR) [22]. DOTATATE precursor has affinity specifically for SSTR-2 receptors. DOTA scan is a functional imaging of whole body where ⁶⁸ Ga-DOTATATE precursor is used and it can detect such tumors in any part of the body due to intense uptake of the precursor by SSTR on tumor. Therefore, this scan is important in detecting multiple/metastatic tumors. It is also useful in follow up of cases post treatment to detect any residual/recurrent/second tumor, and any metastasis. 18-FDG PET scan is generally combined with DOTATATE scan so as to identify tumors which have low SSTR expression which are generally more aggressive. DOTA scan is also useful for selecting patients for radionuclide therapy with ¹⁷⁷Lu/⁹⁰Y radiolabelled DOTATATE. Radionuclide therapy is generally offered in very advanced metastatic cases. This scan is also useful for checking treatment response and also surveillance of individuals with inherited mutations [23, 24].

There are currently two management options for patients with carotid PGs. These include surgery and radiotherapy. While selecting the treatment option, factors which need to be considered include size and extent of tumor, presence of other paragangliomas, bilateral CBTs, age and comorbidities of the patient and the patient's preference. Surgery is the mainstay of treatment for carotid PGs specially in younger patients.

Size of the tumor has a great importance in defining the treatment strategy. Generally, tumors larger than 4–5 cm tend to have partial or complete encirclement of the carotid arteries [25]. The rate of complications correlates strongly with the size and anatomic location of tumor. Larger tumor sizes have been associated with higher risk of bleeding and cranial nerve injury complications with surgery. Pre-operative DSA and tumor embolization has been employed to decrease the vascularity of CBT thereby decreasing the intraoperative blood loss.

A preoperative balloon occlusion test (BOT) is useful to predict the neurological outcome in patients in whom carotid artery sacrifice is contemplated during surgery. The results of BOT may help surgeons to evaluate risks associated with carotid sacrifice, decide how aggressively the lesion is to be treated and to determine if revascularization procedure is to be done.

Shamblin classification system based on tumor size was proposed in 1971 [26]. According this classification, group I tumors are relatively small tumors minimally attached to carotid vessels; the surgical excision is not difficult. The group II tumors are large tumors with moderate attachment to the carotid vessels; these tumors are amenable to careful surgical excision. The group III tumors are very large tumors, encasing the carotid vessels and often require arterial resection and grafting. In a study by Luna-Ortiz et al. it was observed that 22% of tumors in their series of 50 CBTs were small tumors but infiltrating the carotid vessels to an extent requiring ICA sacrifice and reanastomosis with graft. They proposed a modification to the Shamblin classification suggesting CBT of any size, if intimately adherent to the vessels, should be classified as modified Shamblin class IIIb while class IIIa would be same as the previous Shamblin classification [27]. A study by S. Arya et al. has brought out that Shamblin classification can be predicted by the degree of contact of the tumor around the ICA as seen on MRI. According to it, tumor-ICA maximum degree of circumferential contact of less than or equal to 180° represents Shamblin I, more than 180° and less than 270° would represent Shamblin II and greater than or equal to 270° would represent Shamblin III [28].

Surgical approaches can be Trans- cervical, Transcervical with mandibulotomy and Trans-cervical with Trans-temporal—for extension to skull base, performed under GA. It is recommended to collaborate with a vascular surgeon in nearly all cases.

Excision of tumor needs adequate exposure, as well as proximal and distal vascular control. Associated cranial nerves should be identified away from the lesion and dissected free, when possible. It is easiest to approach through the periadventitial avascular space between the vessels of carotid system and the tumor [29]. The complication risk directly correlates to the size of the neoplasm, the cranial extent of resection, and the Shamblin classification.

Radiation therapy is employed in patients who are poor candidates for surgical excision, due to the extent of lesion, age or co-morbid conditions. A stable tumor size or regression after radiotherapy is considered controlled disease. The complications of radiotherapy include inflammation of the external auditory canal and middle ear, osteoradionecrosis, cranial nerve neuropathies, and direct injury to the brain tissue. Radiotherapy also makes subsequent head and neck surgeries highly challenging due to extensive fibrosis. Despite limited experience, radiotherapy for paragangliomas appears to be helpful in cases with unresectable lesions, in high-risk patients, and as an adjunct to surgery for incompletely excised tumors or metastases [30]. After surgery or after radiotherapy, PGs with sporadic and familial occurrence require follow-up [31]. The malignancy rate of carotid PGs is estimated to be between 2 and 10%. Malignancy and multifocality are more common in familial paragangliomas [32, 33].

PGs including CBTs are slow growing tumors with growth rates of 0.5 cm per year. So, there is a case for observation of small asymptomatic CBTs with wait and scan policy provided the patient is counselled about it and opts for this option [34, 35]. A summary of various CBTs reported in literature, their management and outcomes has been summarised and is presented here (Tables 1, 2).

Table 1.

Description and management of cases of CBT reported in literature

Study	No of tumors	Males/females	Shamblin type	Focality of paraganglioma	Familial	Secretory/non-secretory	Management (Surgery/radiation/observation)
Gad et al. [8]	56 (54patients)	69.64%/30.36%	22-type I 26-type II 08-type III	Bilateral-02 (CBT) Unilateral-52	None	All were non-secretory	03-Pre-operative radiotherapy 56-Surgery 01-Post-operative radiotherapy
Georgiadis et al. [9]	01 (01patient)	nil/1	Type III	Unifocal	None	Non-secretory	Surgery
Farr et al. [33]	37 (37patients)	45.94%/54.05%	Not commented	Unifocal	01	Non-secretory	06-Pre-operative radiotherapy (failed attempts) 30-Surgery 07-Observation
Netterville et al. [5]	46 (30patients)	43.33%/56.66%	Not commented	Bilateral-16 (CBT) Unifocal-14	16	Not commented	30-Surgery 16-Observation
Chamorro Sanchez et al. [17]	01 (01patient)	1/nil	Type II-Left Type I-Right (As per our interpretation of tumor description in study)	Bilateral (CBT)	01	Not commented	Surgery
Kaman et al. [25]	03 (03patients)	66.66%/33.33%	All were type II	Unilateral	None	Non-secretory	Surgery
Shamblin et al. [26]	97 (90patients)	68.88%/31.11%	15-type I 27-type II 16-type III (Only 58 tumors were classified)	Bilateral-07 (CBT) Unilateral-83	Not commented	Non-secretory	74-Surgery 11-Radiation (post-operative) 03-Definitive Radiation (no surgery) 20-Observation (operated at another centre)
Ma et al. [36]	57 (53patients)	30.18%/69.81%	16-type I 30-type II 11-type III	Bilateral-04 (CBT) Unilateral-49	03	Not commented	55-Surgery 02-Radiation
Kotelis et al. [37]	17 [17patients]	35.29%/64.70%	02-type I 07-type II 08-type III	Multifocal-01 (second focus in retroperitoneal area) Unifocal-16	Not commented	Retroperitoneal paraganglioma was secretory	17-Surgery
Our case report	01	Female	Type II	Unifocal	Non-familial	Non-secretory	Surgery with preoperative embolization

Table 2.

Mortality and complications post surgery in cases of CBT reported in literature

Study	No of tumors	Mortality post treatment	Complications (injury to vessels and nerves)
Gad et al. [8]	56 (54patients)	None	Transient ischemic attack-2 Stroke-2 Hypoglossal nerve injury-6 Superior laryngeal nerve injury-1 Hematoma-1
Georgiadis et al. [9]	01 (01patient)	Nil	None
Farr et al. [33]	37 (37patients)	06 deaths (05due topostopstroke,01duetoaspirationpneumoniaayear aftersurgery)	Cranial nerve paralysis-14 Vagus nerve-12 Hypoglossal nerve-14 Sympathetic nerve-02
Netterville et al. [5]	46 (30patients)	02 deaths (01 due to metastatic disease, 01 died on 21 Postoperative day with disseminated fungal infection)	Superior laryngeal nerve-04 Vagus nerve-01 Hypoglossal nerve-01 Baroreceptor Failure-10
Chamorro Sanche et al. [17]	01 (01patient)	Nil	None
Kaman et al. [25]	03 (03patients)	None	Case3-Postoperatively the patient had weakness of ipsilateral 9th, 10th and 12th cranial nerves, which gradually improved
Shamblin et al. [26]	97 (90patients)	04 03 died following postoperative cerebrovascular accident 01 died of pneumonia secondary to aspiration postoperatively likely due to vagus palsy	Arterial injuries-29 patients Vagus nerve-15 Hypoglossal nerve-17 cerebrovascular accidents-16 aphasia-04
Ma et al. [36]	57 (53patients)	Nil	Post-operative Stroke-02
Kotelis et al. [37]	17 (17patients)	Nil	Recurrence (3 years post R1 resection)-01 The recurrent tumor in this patient extended intracranially causing occlusive hydrocephalus
Our case report	01	Nil	Nil

Conclusion

CBTs are rare neoplasms but are the most common head and neck paraganglioma. Their management requires detailed systematic evaluation by a multidisciplinary team. Treatment of CBTs must be individualized, taking into account the patient's age, comorbidities, tumour site and size, multiple occurrences, and pre-existing cranial nerve deficits.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

Not applicable as it involves one case report.

Informed Consent

Informed consent was obtained from the individual participating in the study.