Parapharyngeal Space Tumors

Updated: Jan 03, 2023

Author: Neerav Goyal, MD, MPH, FACS; Chief Editor: Arlen D Meyers, MD, MBA

Overview

Practice Essentials

Tumors of the parapharyngeal space (PPS), a potential space lateral to the upper pharynx, are uncommon, making up less than 1% of all head and neck neoplasms. Both benign and malignant tumors may arise from any of the structures contained in this space. Of PPS tumors, 70-80% are benign, and 20-30% are malignant.[1, 2, 3, 4, 5, 6] Most PPS tumors are of salivary or neurogenic origin, although metastatic lesions, lymphoreticular lesions, and a variety of uncommon, miscellaneous lesions or masses may arise in this location.[1, 3, 4] Radiologic studies are essential in the evaluation of a patient with a suspected PPS mass.[4, 7, 8, 9, 10] Surgery is the mainstay of treatment for these lesions.

A literature review by Riffat et al that included 1143 PPS tumors found that these lesions most frequently presented as a cervical or intraoral mass (50% and 47%, respectively). Pleomorphic adenomas were the most common primary lesion (34%).[2]

Workup of parapharyngeal space tumors

Performing radiologic studies before considering biopsy is important because, given the differential diagnosis of a PPS lesion, one can often make a diagnosis on the basis of imaging assessments without the need for fine-needle aspiration biopsy or open biopsy.

The differential diagnosis of a PPS mass can be greatly narrowed by determining whether the mass arises from the deep lobe of the parotid and whether the mass originates in the prestyloid or poststyloid space.[11] Computed tomography (CT) scanning and magnetic resonance imaging (MRI) have equal efficacy in localizing the lesion to these spaces.

Angiography is recommended in the workup of most vascular lesions.[4] It is useful in the evaluation of poststyloid lesions to demonstrate their relationship to the great vessels and to distinguish between neurogenic and vascular lesions; however, this distinction can usually be made with MRI.[12]

Other means of assessing PPS tumors include the balloon occlusion test, nuclear scanning, and a metastatic workup.

Under most circumstances, a presumptive diagnosis can be made on the basis of the findings of imaging studies. Do not consider a biopsy of a PPS prior to obtaining results from the radiologic studies, to ensure that the mass is not a vascular lesion.

Management of parapharyngeal space tumors

Complete surgical excision is the mainstay of treatment for PPS tumors. The choice of surgical approach is dictated by the size of the tumor, its location, its relationship to the great vessels, and the suspicion of malignancy. Such approaches include the following:

Transoral approach
Transcervical approach
Transcervical-transparotid approach
Transcervical-transmandibular approach
Infratemporal fossa approach

Etiology

Salivary gland neoplasms

Neoplasms of salivary gland origin are located in the prestyloid parapharyngeal space (PPS) and account for 40-50% of PPS lesions.[2, 13, 10] Salivary neoplasms may arise from the deep lobe of the parotid gland, ectopic salivary rests, or minor salivary glands of the lateral pharyngeal wall.[10] The prevalence of neoplasms that arise within the deep lobe of the parotid gland is identical to that of those that arise in the superficial lobe. The most common prestyloid PPS lesion is pleomorphic adenoma, which represents 45-64% of salivary neoplasms in the PPS.[1, 2, 3, 4, 5, 14] Common benign neoplasms include pleomorphic adenomas, monomorphic adenomas, Warthin tumors, and oncocytomas. Malignant neoplasms include adenoid cystic carcinomas, mucoepidermoid carcinomas, adenocarcinomas, and acinic cell carcinomas. Approximately 20% of all salivary lesions in the PPS are malignant, with carcinoma ex pleomorphic adenoma and adenoid cystic carcinoma being the most frequently reported.[2, 14, 5]

Neurogenic lesions

Neurogenic lesions are the most common tumors of the poststyloid PPS and account for 14-41% of PPS lesions.[2, 10] Benign neurogenic lesions include neurilemmomas (schwannomas), paragangliomas, neurofibromas, and ganglioneuromas. Malignant neurogenic lesions include malignant paragangliomas, neurofibrosarcomas, schwannosarcomas, and sympathicoblastomas. Neurilemmomas are the most commonly encountered lesions, followed in frequency by paragangliomas and neurofibromas.[2]

Neurilemmomas

Neurilemmomas, or schwannomas, arise from any nerve surrounded by Schwann cells. They grow slowly and rarely cause palsy of the nerve of origin. In the PPS, the most common sites of origin are the vagus nerve and the sympathetic chain.[8] Neurilemmomas are encapsulated and histologically distinct from the nerve itself. Treatment is by enucleation, and preservation of the nerve of origin is usually possible; however, every patient should be cautioned about the possibility of postoperative paralysis.[7]

Neurofibromas

Neurofibromas, in contrast, are unencapsulated and intimately involved with the nerve of origin. These tumors most commonly arise from the vagus nerve; however, there have been rare reports of a hypoglossal nerve origin.[15] Neurofibromas are often multiple. They may occur as a manifestation of the neurofibromatosis-1 (NF-1) syndrome, a disease in which the incidence of malignant transformation is increased. The nerve of origin is usually sacrificed during excision to ensure complete removal of the neoplasm.

Paragangliomas

Paragangliomas are benign vascular neoplasms that arise from the paraganglia or extra-adrenal neural crest tissue.[16] Paraganglia function as chemoreceptors and are associated with the carotid body, the jugular bulb, and the vagus nerve in the poststyloid PPS. Carotid body tumors, glomus jugulare, and glomus vagale are slow-growing paragangliomas that may not produce symptoms or may cause cranial nerve (CN) deficits, bone erosion, or intracranial extension as they increase in size.[16, 7]

Approximately 2% of head and neck paragangliomas secrete catecholamines and may cause paroxysmal symptoms of catecholamine excess.[2] Ten percent of paragangliomas are multiple and associated with paraganglioma at other locations.[16] Ten percent of paragangliomas are hereditary, associated with a familial paraganglioma syndrome.[17, 18] In patients with hereditary paraganglioma, the prevalence of multicentricity is greater than 35%.[18]

Hypertension and flushing are suggestive of either a secreting paraganglioma or an associated pheochromocytoma.[19] If these symptoms are present, obtain urinary catecholamine levels.[19] If the level of catecholamines is elevated, rule out a concomitant pheochromocytoma. Malignant paragangliomas occur in less than 5-13.5% of patients and are associated with rapid growth and development of metastatic disease.[20, 21, 22]

Lymphoreticular lesions

Lymphoreticular lesions make up 10-15% of PPS lesions.[3, 23] The lymphatics of the PPS may be involved primarily or secondarily by carcinoma, or they may be involved by infectious or inflammatory processes. Lymphoma is the most common malignant lymphoid process, but metastases from thyroid cancer, osteogenic sarcoma, squamous cell carcinoma, renal cell carcinoma, hypernephroma, and meningioma may also appear as PPS masses. The most common lymphoreticular lesions are lymphomas and metastases.[3]

Miscellaneous lesions

These include the following:

Aneurysm
Ameloblastoma
Amyloid tumor
Angiofibroma[24]
Arteriovenous malformation
Branchial cleft cyst
Chondroma
Chondrosarcoma
Chordoma
Choroid plexus tumor
Dermoid
Desmoid
Ectomesenchymoma
Ectopic parathyroid adenoma[25]
Fibrosarcoma
Fibrous histiocytoma
Granular cell myoblastoma
Hemangioendothelioma
Hibernoma
Inflammatory pseudotumor
Leiomyoma
Liposarcoma
Malignant meningioma
Malignant teratoma
Meningioma
Rhabdomyoma
Rhabdomyosarcoma
Sarcoma
Teratoma
Venous angioma

A variety of more unusual lesions may occur in the PPS, and these lesions make up 10-15% of PPS masses.[2, 23] While the pathologist usually makes the final determination and diagnosis in such cases, recognizing that vascular lesions, such as hemangiomas, arteriovenous malformations, and internal carotid artery aneurysms, may occur in the PPS is important. Imaging studies of this region must be performed before attempting to obtain a biopsy or to excise the lesion.

Presentation

Clinical presentations may include the following:

Neck mass
Oropharyngeal mass
Unilateral eustachian tube dysfunction
Dysphagia
Dyspnea
Obstructive sleep apnea
CN deficits
Horner syndrome (ptosis, miosis, anhidrosis)
Pain
Trismus
Symptoms of catecholamine excess

Patients with tumors of the parapharyngeal space (PPS) most commonly present with a neck or oropharyngeal mass that does not cause symptoms detectable on physical examination, because only the inferior and medial boundaries of the PPS are distensible.

Tumors are usually at least 2 cm in size before the bulge or abnormality is palpable. Often, a PPS lesion is discovered incidentally on routine physical examination.[4] Unilateral eustachian tube dysfunction may result from significant medial extension, causing soft palate and nasopharyngeal swelling. Oropharyngeal bulging from an underlying PPS mass may cause significant displacement of the ipsilateral tonsil and may create the appearance of a primary tonsillar lesion. An ill-fitting denture may be the first symptom of a benign prestyloid lesion.

Symptoms of dysphagia, dyspnea, and obstructive sleep apnea may result from distortion of the lateral pharyngeal wall by a massive PPS lesion.[4, 10] In such cases, tracheostomy has been recommended for relief of airway obstruction.

There are a few reports of parapharyngeal space lesions syncope syndrome, but a trigger for syncope is not known.[26]

Cranial neuropathies may result from enlargement of PPS lesions, with compression of CNs IX, X, XI, or XII, resulting in symptoms of hoarseness, dysarthria, and dysphagia.[4] Horner syndrome (ie, ptosis, miosis, anhidrosis) has been described as resulting from pressure on the cervical sympathetic chain.[27] With the exception of glomus vagale tumors, which have been associated in the literature with a high frequency of vagal paresis, most benign lesions of the PPS do not result in cranial nerve dysfunction.[16] Pain is unusual with benign lesions and may be due to compression or hemorrhage into the lesion; however, pain and neurologic dysfunction are more often indicative of malignancy with infiltration of the skull base.[4] Under these circumstances, CN VII may be involved. Trismus results from malignant invasion of the pterygoid musculature or involvement of the coronoid process of the mandible.[10]

Physical examination findings may suggest the origin and nature of the tumor. The most common physical finding is a painless oropharyngeal or neck mass. Pay careful attention to the oropharynx, tonsillar area, pharynx, and neck. Lesions arising from the deep lobe of the parotid may often be localized using bimanual palpation. Perform a full cranial nerve evaluation, including laryngoscopy, to test the motor and sensory innervation of the larynx.[4] The vagus nerve is the most commonly involved cranial nerve, and vagal palsy is suggestive of either a paraganglioma or a malignancy.

A neck mass that is pulsatile or has a thrill to auscultation suggests a vascular tumor, although carotid pulsations may be transmitted through an overlying mass and may be misleading.[4] Paragangliomas are typically mobile in an anteroposterior direction but not in a vertical direction.[7] Any patient with aural symptoms should undergo thorough audiologic evaluation as well as careful examination of the nasopharynx.[23]

Indications

Complete surgical excision is the mainstay of treatment and is recommended for both diagnostic and therapeutic purposes. The choice of surgical approach is dictated by the size of the tumor, its location, its relationship to the great vessels, and the suspicion of malignancy (see Surgical therapy). However, when surgery is contraindicated, alternatives to surgical therapy consist of observation or radiation therapy.

Relevant Anatomy

The parapharyngeal space (PPS) is a potential space lateral to the upper pharynx. The PPS is shaped like an inverted pyramid, extending from the skull base superiorly to the greater cornu of the hyoid bone inferiorly.

The superior border of the PPS comprises a small area of the temporal and sphenoid bones, including the carotid canal, jugular foramen, and hypoglossal foramen. The PPS is limited anteriorly by the pterygomandibular raphe and pterygoid fascia and posteriorly by the cervical vertebrae and prevertebral muscles. The medial border of the PPS is the pharynx, and the lateral border is comprised of the ramus of the mandible, the medial pterygoid muscle, and the deep lobe of the parotid gland. Below the level of the mandible, the lateral boundary consists of the fascia overlying the posterior belly of the digastric muscle.

The fascia from the styloid process to the tensor veli palatini divides the PPS into an anteromedial compartment (ie, prestyloid) and a posterolateral (ie, poststyloid) compartment. The prestyloid compartment contains the retromandibular portion of the deep lobe of the parotid gland, adipose tissue, and lymph nodes associated with the parotid gland. The poststyloid compartment contains the internal carotid artery, the internal jugular vein, CNs IX-XII, the sympathetic chain, and lymph nodes.

These lymphatics receive afferent drainage from the oral cavity, oropharynx, paranasal sinuses, and thyroid. The distinction between the prestyloid and poststyloid space is more than just semantic because imaging studies can delineate between the two compartments and can assist in reaching the correct diagnosis preoperatively.

Contraindications

Surgery may be contraindicated and nonoperative management of parapharyngeal space (PPS) lesions considered for patients who are poor surgical candidates because of comorbid disease; those who are elderly; those in whom balloon occlusion fails; those who have unresectable lesions; and those who have benign, slow-growing tumors that would carry a significant risk of sacrifice of multiple cranial nerves if resected. The risks and benefits of surgery must be weighed in every case.

Workup

Laboratory Studies

Note the following:

Twenty-four–hour urine collection for catecholamines: Although functioning tumors are rare, if a secreting paraganglioma is suspected, obtain a 24-hour urine collection for catecholamines to screen for a secreting lesion.[4, 19, 23] If catecholamine level results are positive, perform a metaiodobenzylguanidine (MIBG) scan (see MIBG scanning).[16]
Vanillylmandelic acid (VMA), or 4-hydroxy-3-methoxymandelic acid[19]
Metanephrine[19]
Consider routine preoperative blood work such as a complete blood count (CBC) and basic metabolic panel

Imaging Studies

Radiologic studies are essential in the evaluation of a patient with a suspected parapharyngeal space (PPS) mass.[4, 7, 8, 9, 10] Performing these studies before considering biopsy is important because, given the differential diagnosis of a PPS lesion, one can often make a diagnosis on the basis of imaging studies without the need for fine-needle aspiration biopsy or open biopsy.

Imaging studies should answer the following questions:

Is the mass prestyloid or poststyloid?
What is the relationship to the parotid gland?
What is the relationship to the great vessels?
What are the soft tissue characteristics of the tumor?

The differential diagnosis of a PPS mass can be greatly narrowed by determining whether the mass arises from the deep lobe of the parotid and whether the mass originates in the prestyloid or poststyloid space.[11] The parapharyngeal fat pad is located in the prestyloid space. Prestyloid lesions cause medial displacement of the parapharyngeal fat pad and are located anterior to the great vessels.[13, 10] Poststyloid lesions displace the parapharyngeal fat pad anteriorly and laterally, between the mass and the pterygoid muscles.[13, 10]

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) have equal efficacy in localizing the lesion to the prestyloid or poststyloid space. Both studies have advantages and disadvantages when compared to each other.[4, 11] CT scanning or MRI is used as a starting point in the evaluation of a PPS mass, and, sometimes, only one test may be needed. Angiography is reserved for enhancing lesions.[10] Ultrasonography does not provide adequate resolution of the PPS and is not indicated in the workup of PPS lesions.[28]

CT scanning

CT scanning can localize a PPS mass to the prestyloid or poststyloid space. It may also demonstrate whether the mass arises from the deep lobe of the parotid; a fat plane between the parotid and the mass suggests an extraparotid origin.[10]

CT scanning is superior to MRI in demonstrating the presence of calcifications and bony involvement.[9]

With contrast infusion, the relationship of the mass to the great vessels may be appreciated, although enhanced poststyloid lesions may be difficult to separate from the carotid artery.[10]

CT scanning is inferior to MRI in delineating soft tissue characteristics of the tumor, particularly in large lesions in which the tumor margin may be difficult to distinguish from the fascia of adjacent musculature.[11] CT scanning also carries the risk of exposure to ionizing radiation and intravenous contrast.[4] Nevertheless, CT scanning remains widely used because of its wide availability and lower cost. CT scanning may be the only study required because most PPS masses are prestyloid lesions arising from the parotid gland. Because of its superior soft tissue and vascular resolution, a subsequent MRI is recommended to further evaluate all poststyloid masses or, if malignancy is suspected, to evaluate the extent of malignancy and to rule out intracranial extension.[11]

Magnetic resonance imaging

MRI is superior to CT scanning in its ability to ascertain the soft tissue characteristics of parapharyngeal space (PPS) tumors.[4, 11] MRI can be used to differentiate between tumor and muscle, and it has greater resolution in defining the great vessels and their relationship to tumor.[4, 11] Intracranial extension is better delineated on MRI.

The diagnosis can often be made on the basis of characteristic MRI findings. Paragangliomas have been described as having a "salt-and-pepper" appearance on MRI because of numerous flow voids within the lesion.[7] Schwannomas show greater enhancement on T2-weighted images, enhance with gadolinium, and lack flow voids.[12]

MRI scanning is probably the screening test of choice to evaluate a PPS lesion because of the greater soft tissue resolution and vascular information obtained.[23] However, its cost is significantly greater, the ability to determine bone involvement is poor, and it may be contraindicated in certain patients (eg, those with pacemakers, those with certain hardware, those who are claustrophobic).

The information obtained from both CT scanning and MRI is complementary, and both studies should be performed in the evaluation of extensive lesions or when malignancy is suspected.

Angiography

Angiography is recommended in the workup of most vascular lesions.[4] Angiography is also used if malignancy is suspected and if carotid sacrifice is possible during resection.[23] If carotid resection is considered, angiography is combined with balloon occlusion testing to measure cerebral blood flow (see Balloon occlusion test in Other Tests).

Angiography is useful in the evaluation of poststyloid lesions to demonstrate their relationship to the great vessels and to distinguish between neurogenic and vascular lesions; however, this distinction can usually be made with MRI.[12]

Findings on angiography may be diagnostic of neurogenic lesions. Carotid body tumors are usually located at the bifurcation and cause splaying of the carotid bifurcation, called the lyre sign.[12]

Glomus vagale tumors, because of their association with the vagus nerve, lie laterally and posteriorly to the carotid system, displacing this anteriorly and medially.[16]

Schwannomas appear as avascular masses displacing the carotid system anteriorly.[12] Metastases (eg, renal cell carcinoma) often appear quite vascular if they take their blood supply from the external carotid. Most vascular lesions should be evaluated with angiography to delineate their extent and blood supply; feeding vessels may be identified and may be embolized preoperatively to facilitate resection.

CT angiography and magnetic resonance angiography are emerging as alternatives to conventional arteriography. These tests are becoming more widely used, but they may relegate conventional arteriography to those instances in which the blood supply remains in question, balloon occlusion is required, or embolization is being considered.

Other Tests

Balloon occlusion test

The balloon occlusion test measures the effect of internal carotid artery occlusion on cerebral blood flow (CBF) and the adequacy of the contralateral circulation. It is indicated when findings on imaging studies suggest carotid involvement or when resection of the lesion carries a high risk of intraoperative carotid artery injury.[4, 12, 6]

Angiography is performed, and the internal carotid artery is occluded for 10-15 minutes using a balloon-tipped catheter. In patients who develop neurologic symptoms, the test is abandoned, and no further evaluation is performed. These patients are considered at high risk for stroke and should undergo nonoperative therapy, subtotal resection with carotid preservation, or revascularization prior to resection. In some settings, blood flow can be quantitated using substances such as xenon.[4]

In patients without neurologic symptoms during balloon occlusion, xenon-enhanced CT scanning is performed to quantitate CBF. CBF is evaluated both before and after balloon occlusion; xenon gas is inhaled, it diffuses rapidly into the bloodstream, and it causes perfused areas of the brain to become radiopaque. Patients with diminished perfusion on xenon-enhanced CT scanning (approximately 25% of patients) are considered at mild-to-moderate risk of stroke with prolonged carotid occlusion. Interposition grafting of the internal carotid artery is recommended if the artery is to be sacrificed.

A 4% risk of neurologic sequelae exists from the balloon occlusion test itself, so the procedure is reserved only for cases in which the carotid is suspected to be involved or at risk.

Nuclear scanning

If screening for a functional paraganglioma by urinary VMA and metanephrine levels is positive, obtain a metaiodobenzylguanidine (MIBG) scan. The radioisotope MIBG has a molecular structure similar to that of norepinephrine and is used to trace catecholamine uptake and storage. Alternatively, an octreotide scan can be used to identify paragangliomas and metastasis, with the tracer binding to somatostatin receptors two and five (SSTR2, SSTR5).[29]

Metastatic workup

If a metastatic lesion is suspected, the primary tumor should be sought by performing a full clinical evaluation, panendoscopy, and a full metastatic workup as directed by the clinical examination findings.

Diagnostic Procedures

Biopsy

Under most circumstances, a presumptive diagnosis can be made on the basis of the findings of the imaging studies described above. Do not consider a biopsy of a parapharyngeal space (PPS) prior to obtaining results from the radiologic studies, to ensure that the mass is not a vascular lesion. Complete surgical excision is the mainstay of treatment and is recommended for both diagnostic and therapeutic purposes.

Fine-needle aspiration biopsy (FNAB) may be a useful adjunct when the mass is readily accessible, either transcervically or transorally, and may provide useful information if a diagnosis of malignancy is suspected. However, if imaging studies suggest a vascular lesion, FNAB provides little if any useable information and is not indicated.

Incisional biopsy should be considered only if the patient is not an operative candidate and FNAB findings are inconclusive and if a diagnosis of malignancy or lymphoma is strongly suspected.

Transoral open biopsy has been described but carries a significant risk of hemorrhage and of contamination of the pharyngeal mucosa by tumor, which requires excision of that site during subsequent definitive resection. Most surgeons do not support this practice.

Treatment

Medical Therapy

Nonoperative management of parapharyngeal space (PPS) lesions may be considered for patients who are poor surgical candidates because of comorbid disease; those who are elderly; those who fail balloon occlusion; those who have unresectable lesions; and those who have benign, slow-growing tumors that would carry a significant risk of sacrifice of multiple cranial nerves if resected.[2] The risks and benefits of surgery must be weighed in every case. The risk of neurovascular complications, including cranial nerve injury and stroke, is increased in patients with paragangliomas and malignancies.[20, 30] Alternatives to surgical therapy consist of observation or radiation therapy.[31, 30]

The risks of observation of benign tumors of the PPS are continued growth and malignant degeneration. Most prestyloid lesions can be removed with minimal morbidity. Observation is an acceptable alternative in patients in whom the risks of surgery are greater than not operating.[31] This group consists of patients who are poor surgical candidates and patients who are elderly who have paragangliomas that do not produce symptoms.[31] Paragangliomas typically do not grow or have a slow growth rate (estimated to be as high as 2 mm per year).[31]

In young patients who are asymptomatic, resection is recommended to avoid future loss of cranial nerve function as the tumor enlarges and to attempt to preserve the nerve of origin, which is far more likely to be successful with a small tumor than a larger one. Patients with partial cranial nerve deficits may initially be observed for 6-12 months to allow compensation to occur because functional compensation to a gradual loss of function is greater than sudden loss of function.[32]

Observation may be appropriate in patients with multiple paragangliomas who have preexisting contralateral cranial nerve deficits resulting from resection of a contralateral paraganglioma.[31] Patients who are elderly do not fare as well following loss of CN function, and the natural course of a paraganglioma that is not producing symptoms may be associated with less morbidity than the morbidity associated with surgical resection.[32]

Radiation therapy can be used as a primary treatment modality in patients with paragangliomas who are poor surgical candidates and in the treatment of malignancies of the PPS.[32] Radiation is not used for cure in the management of paragangliomas because the chief cells of paragangliomas are not radiosensitive, but it may be used to arrest or slow the growth of these lesions by causing endarteritis and fibrosis.[30] Radiation therapy may be considered in those patients who are poor surgical candidates but who require treatment.[2] These include symptomatic patients who are elderly, patients with internal carotid artery involvement in whom balloon occlusion fails, and patients with contralateral cranial nerve deficits in whom resection would result in a significant reduction in quality of life.[30] Radiation therapy is used as an adjunct to surgery in patients with high-grade malignancies and when an oncologic or adequate resection margin cannot be obtained.[4]

Surgical Therapy

Surgery is the mainstay of treatment for tumors of the parapharyngeal space (PPS). The choice of surgical approach is dictated by the size of the tumor, its location, its relationship to the great vessels, and the suspicion of malignancy.

In the aforementioned literature review by Riffat et al of PPS tumor studies (1143 tumors total), the investigators found that 95% of patients underwent surgery, with the cervical approach being the most frequently used technique (48%). The most common complication, vagus nerve injury, occurred in 14% of cases.[2]

A retrospective study by Prasad et al indicated that benign PPS tumors can be effectively managed with a lateral skull base approach, which, according to the investigators, offers excellent exposure and reduced morbidity. Transcervical, transcervical-transparotid, transcervical-transmastoid, and infratemporal fossa approaches were used, with 46 of 48 tumors (96%) undergoing total radical removal.[33]

A cadaver study by Ferrari et al indicated that in parapharyngeal space (PPS) surgery, the upper PPS can be exposed via the transnasal approach (medial, lateral), providing limited volume to work, while exposure of the middle PPS, allowing minimization of the neurovascular structures crossed, can be achieved with the transoral approach (transpharyngeal, transvestibular, transmandibular), and the entire PPS can be exposed through the transcervical (transcervical, transparotid, transmandibular, transmastoid) approach.[34]

Preoperative Details

Surgical morbidity can be minimized, or at least anticipated, with careful attention to preoperative evaluation so that both the surgeon and the patient are adequately prepared.

The relationship of the tumor to the great vessels should be clearly delineated by preoperative imaging prior to planning resection, and patients should be counseled accordingly.[4, 32] Injury to the great vessels may result in uncontrollable bleeding, stroke, or death. Consult a vascular surgeon if a possibility of carotid resection requiring interposition grafting exists. Consulting a neurosurgeon may be appropriate for lesions involving the skull base.

Counsel patients preoperatively about the possibility of loss of cranial nerve (CN) function and the effects on speech and swallowing.[4, 32] Injury or sacrifice of the vagus nerve alone may initially be managed expectantly to determine the effect on function and the final position of the vocal cord; this is done before proceeding with vocal cord medialization at a subsequent date, because many patients compensate for an isolated deficit to a significant degree.[32] Injury to both the vagus and the hypoglossal nerves can be expected to significantly impair swallowing function. If a patient has multicentric tumors, such as are found in familial paraganglioma syndromes, staging of surgical resection should be performed to reduce the risk of bilateral CN injury.

If multiple CN deficits are anticipated, plans may be made for gastrostomy tube placement concomitant with resection if the patient's underlying status suggests that swallowing rehabilitation will be prolonged. Parotidectomy or mandibulotomy may need to be performed intraoperatively for improved exposure; this, as well as the possibility of tracheostomy if mandibulotomy is required, should be discussed with the patient.

Preoperative embolization of vascular lesions may decrease intraoperative blood loss and may facilitate dissection of tumors at the skull base by causing retraction.[32] Embolization is recommended for vascular lesions greater than 3 cm in which obvious feeding vessels can be identified on angiography.[32] The use of embolization of paragangliomas is more controversial.[7, 32] Glomus vagale tumors rarely have a single blood supply, and resection is not associated with excessive blood loss.[16] Carotid body tumors are supplied by the adventitia of the carotid rather than an obvious dominant feeding vessel.[7] Embolization of a carotid body tumor may cause an inflammatory response that may obscure the subadventitial plane in which the tumor is dissected, increasing the risk of inadvertent carotid injury during resection. Embolization carries a risk of possible disruption of the blood supply to cranial nerves. If embolization is performed, it is performed within 24-48 hours prior to resection.

Functioning tumors must be identified prior to resection because manipulation of a catecholamine-secreting tumor may cause intraoperative cardiac arrhythmias and hypertensive crisis. Preoperatively, institute alpha- and beta-adrenergic blockade with phenoxybenzamine and propranolol.[19] Patients with multiple paragangliomas should undergo preoperative CT scanning of the adrenal glands to search for an associated pheochromocytoma.

Feng et al suggested the use of a simplified classification based on intraoral growth patterns to improve the preoperative diagnostic accuracy of radiologic findings and to assist in surgical planning. This classification consists of pattern 1, which is when the tumor bulges submucosally "into the oropharynx from the soft palate, with the center convexity above the uvula," and pattern 2, which is when the tumor bulges submucosally into the oropharynx from the lateral wall, "with the center convexity below the uvula." Such a distinction can help to determine when implementing a transoral approach would be most appropriate.[35]

Intraoperative Details

Transoral approach

The transoral approach has been described for the removal of small benign neoplasms that originate in the prestyloid parapharyngeal space (PPS) and manifest as an oropharyngeal mass. The limitations of this approach are limited exposure, inability to visualize the great vessels, and an increased risk of facial nerve injury and tumor rupture. The transoral approach is best suited for small benign salivary tumors arising from minor salivary glands of the lateral pharyngeal wall. Although most lesions of the PPS are resected via other approaches, well-selected tumors are amenable to transoral surgery.[36]

Benefits of the transoral approach include elimination of a neck scar, reduced risk of first bite syndrome, shortened postoperative hospitalization, and lower incidence of complications.[37]

Several studies have suggested the feasibility of transoral robotic surgery (TORS) for the resection of appropriately selected parapharyngeal tumors.[38] Favorable characteristics for TORS resection include benign pathology, lack of poststyloid extension, and close proximity to the constrictor muscles and oral mucosa.[39]

Transcervical approach

Most authors prefer the transcervical approach as the method for removal of most poststyloid PPS tumors.[40, 5] A transverse incision at the level of the hyoid bone, two fingerbreadths below the mandible, is performed, and the carotid artery and internal jugular vein are identified. The digastric and stylohyoid muscles are retracted to allow access to the PPS. The submandibular gland can be retracted anteriorly for exposure, or it can be removed if necessary.

As part of this dissection, there are several key structures that are relevant. The cranial nerves (CNs), including the hypoglossal, vagus, and spinal accessory nerves, should be identified and can usually be preserved. The inferior border of the mandible should be delineated and dissected away from the submandibular gland. Often, the distal facial artery and vein need to be ligated to increase the exposure. With this exposure, the carotid bifurcation is usually easily visualized and the external carotid artery can be traced. Additionally, a rigid structure, the stylomandibular ligament, can be palpated and visualized. Dividing this can improve the rotation of the mandible to expose the PPS.[5] Occasionally, the external carotid artery needs to be ligated to allow for increased exposure of the PPS. If necessary, the posterior belly of the digastric and the styloid musculature can be divided, though usually this division does not significantly increase exposure. A retractor placed under the border of the mandible can help to rotate it and increase visualization of the PPS.

Transcervical-transparotid approach

For tumors arising from the deep lobe of the parotid, the transcervical approach can be combined with a transparotid approach by extending the incision superiorly as for parotidectomy.[5, 41] The facial nerve is identified and dissected, superficial parotidectomy is performed, and the deep lobe portion of the tumor is identified. The cervical incision allows access to the PPS component of the tumor, with identification of the facial nerve. This surgical approach has been associated with longer operative times and increased blood loss compared with the transcervical approach alone.[42]

Transcervical-transmandibular approach

The transcervical approach may be combined with mandibulotomy when better exposure is required. Such situations include very large tumors, vascular tumors with superior PPS extension, malignancies in which better exposure facilitates oncologic resection, and cases in which distal control of the carotid at the skull base is required. Mandibulotomy may be lateral or anterior (midline); an osteotomy anterior to the mental foramen is preferred for preservation of inferior alveolar nerve function.[43] A lip-splitting incision is used to expose the mandible for midline osteotomy. After mandibulotomy, the incision is continued intraorally along the floor of the mouth back to the level of the tonsil pillar, and the mandible is retracted laterally. This will usually lead to significant floor-of-mouth and oral cavity swelling, often necessitating a tracheotomy or prolonged intubation. Additionally, there can be some subacute and chronic dysphagia secondary to the disruption of the oral cavity. There can also be malocclusion following mandibulotomy.

Lateral mandibulotomy involves a vertical cut through the ramus of the mandible. The masseter is separated from the ascending ramus and retracted superiorly, allowing access to the sigmoid (mandibular) notch. The mandibular osteotomy is made vertically between the central point of the sigmoid notch and the angle of the mandible in order to preserve the inferior alveolar nerve, which enters anterior to this osteotomy. The two segments of the mandible can then be swung away from each other to expose the PPS tumor.

However, the need for mandibulotomy can be decreased with adequate retraction and exposure, which can ultimately reduce associated patient morbidity.[44] In many surgeons' hands, a mandibulotomy is a rare occurrence in approaching the PPS.[45, 46]

Infratemporal fossa approach

A preauricular infratemporal fossa approach, as described by Fisch, can be used for malignant tumors involving the skull base or jugular foramen.[33] This approach can be combined with frontotemporal craniotomy for removal of tumors with significant intracranial extension. A parotidectomy incision with cervical extension, as described above, is extended superiorly into a hemicoronal scalp incision. The temporalis muscle is elevated to expose the glenoid fossa, which is removed laterally. The temporomandibular joint can be displaced inferiorly, or the mandible condyle can be transected for improved exposure. Orbitozygomatic osteotomies are performed, and the infratemporal skull base and distal carotid are exposed. The facial nerve and vascular structures in the neck are identified through the cervical and preauricular approaches.

A postauricular approach, also described by Fisch, can be employed to resect parapharyngeal tumors that affect the skull base and extend into the temporal bone or middle cranial fossa. The Fisch type A technique includes radical mastoidectomy, anterior transposition of the facial nerve, and exploration of the posterior infratemporal fossa. In conjunction with cervical dissection, the type A procedure allows access to the jugular bulb, vertical petrous carotid, and posterior infratemporal fossa. The Fisch type B technique allows access to the superior infratemporal fossa after middle meningeal artery and V3 transection. Removal of the eustachian tube permits access to the internal carotid artery up to the foramen lacerum.

Postoperative Details

Strongly consider tracheostomy in conjunction with a transmandibular approach, because significant upper airway edema may result from surgical manipulation of the oral cavity and oropharynx, causing obstruction.[45] Bleeding may also cause airway obstruction because of the proximity of the parapharyngeal space (PPS) to the pharynx. Pay careful attention to hemostasis, and closely monitor all patients in the immediate postoperative period.

All patients should be managed with closed suction drains because the dead space resulting from removal of PPS tumors may result in seroma formation. The risk of infection is greater if a transoral approach is used or combined with a cervical approach, and patients with oral contamination should be administered broad-spectrum perioperative antibiotics.

Injury to the facial nerve may be temporary, from traction injury, or permanent, if the nerve is inadvertently sacrificed or injured. Eye protection with artificial tears, a moisture chamber, and Lacri-Lube ointment is required in these cases in order to prevent corneal exposure and abrasion.

Cranial nerve (CN) palsies may result from removal of poststyloid PPS lesions. An isolated unilateral vagal injury is usually well tolerated in the otherwise healthy patient, but a high vagal injury or a vagal injury combined with injury to CN IX and XII may result in significant problems with swallowing and aspiration.[7] Patients should be carefully evaluated prior to the institution of oral feedings, and an alternate method of feeding (eg, nasogastric tube, gastric tube) should be instituted if necessary. Tracheostomy may be required for airway protection if multiple cranial nerve deficits result from resection. Glossopharyngeal and hypoglossal nerve injuries can also be identified; they are likely temporary and secondary to retraction unless the nerves were transected during the case.

Cerebrospinal fluid leaks may occur after removal of tumors with jugular foramen or intracranial extension and result in meningitis. Pay careful attention to the dural closure after tumor removal. Fascia, fat, or muscle can be used to reinforce the closure if necessary. Lumbar drainage is instituted for small leaks; large leaks or those leaks refractory to lumbar drainage require reoperation.

Follow-up

All patients with parapharyngeal space (PPS) masses should undergo routine follow-up, regardless of whether treatment is nonoperative or surgical. The frequency of follow-up examinations varies according to the tumor histology. Patients treated nonoperatively should be monitored for tumor growth and development or progression of symptoms. Following surgical excision, patients with benign histology are routinely monitored to rule out recurrence. Patients with malignancies require closer observation and monitoring. Adjunctive radiation therapy is appropriate for high-grade malignancies and in cases in which an adequate resection margin cannot be obtained.

Complications

In addition to the postoperative complications discussed above, injury to the lingual and hypoglossal nerves may result from the transcervical approach when the submandibular triangle is entered. Warn patients preoperatively that injury to any or all branches of the facial nerve may result from nerve resection or traction injury and also that the ramus mandibularis branch is at risk during cervical approaches. Intraoperative transection of the facial nerve is best managed by performing nerve grafting at the time of surgery. Eye protection (as mentioned above) is required in the postoperative period; insertion of a gold weight can be performed at surgery or postoperatively. Facial reanimation procedures may be required for unrecognized facial nerve injury that does not resolve.

A study by Bulut and colleagues found that in 48 patients with parapharyngeal space (PPS) tumors, the most frequent postoperative complication was cranial nerve (CN) palsy, either temporary (resolving within 6 mo) or permanent. It was also determined that 82.1% of the individuals with temporary CN palsy had benign neoplasms. In definitive palsy, 50% of tumors were malignant, and 50% were benign.[47] Another study found CN deficits to be significantly higher with neurogenic tumors than with other types of PPS tumors.[48]

In addition to injury to CNs IX, X, XI, and XII, damage to the cervical sympathetic chain may result from surgery to the PPS. The risk of postoperative CN deficits ranges from 11-57%, with higher frequencies observed in studies of patients with proportionately greater numbers of malignancies or neurogenic lesions.[2, 33, 7, 40, 12] An isolated nerve injury is usually well tolerated in an otherwise healthy patient.

Isolated injury to the hypoglossal nerve does not usually significantly impair swallowing or speech function. Injury to the vagus nerve results in vocal cord paralysis, and if injury occurs above the level of the nodose ganglion, laryngeal sensation is also affected. Thyroplasty or Teflon injection may be performed intraoperatively or at a later date. The advantage to delaying vocal cord medialization procedures is that patients will often compensate, and the extent of medialization required can be better assessed after this has occurred.

Surgery in the PPS, infratemporal fossa, and deep lobe of the parotid gland has been associated with a 10% incidence of first bite syndrome.[49] First bite syndrome is characterized by severe facial pain with the first bite of each meal, that diminishes with subsequent bites. Current theory holds that denervation of the sympathetic chain causes parasympathetic overactivity, leading to exaggerated myoepithelial cell contraction in the parotid gland and, subsequently, pain.[50]

Patients who are elderly or patients with multiple CN deficits are expected to have greater difficulty with swallowing. If swallowing rehabilitation is prolonged or unsuccessful, gastrostomy tube placement may be necessary. Patients with difficulty handling oral secretions may require tracheostomy for airway protection.

Injury to the spinal accessory nerve results in weakness of the trapezius muscle, winging of the scapula, and adhesive capsulitis from disuse. This can be managed postoperatively by an active range of motion physical therapy program. When recognized intraoperatively, transection of CN XI is best managed by nerve grafting to achieve some recovery of function. Horner syndrome may result from injury to the cervical sympathetic chain. The resulting anhidrosis is managed symptomatically.

Vascular complications are more common with removal of neurogenic or vascular lesions. The prevalence of intraoperative vascular injury and of perioperative stroke has been reported at 4% for poststyloid lesions. Morbidity may be reduced by avoidance of undue traction on the carotid artery, which may result in intimal tears. Primary repair or vein grafting should be performed for all vessel lacerations.

Complications of mandibulotomy include infection, temporomandibular joint dysfunction, nonunion, plate extrusion, and tooth loss.[45] When the osteotomy site is through dental sockets rather than between them, tooth loss is more common. Malocclusion may occur following mandibulectomy in dentate patients, but arch bars and intermaxillary fixation can control occlusion during and after rigid fixation.

Complications of radiation therapy, whether used primarily or as an adjunct to surgery, include xerostomia, tissue fibrosis, acceleration of dental caries, and osteoradionecrosis. Osteoradionecrosis is managed by debridement, antibiotics for secondary infection, and hyperbaric oxygen when it is available. Dental caries may be prevented by the use of fluoride trays. Teeth in poor condition should be extracted. Xerostomia is a life-long problem, but it can be alleviated by treatment with pilocarpine (Salagen, 5 mg PO tid) or artificial saliva applications.

Outcome and Prognosis

The recurrence rate of benign parapharyngeal space (PPS) neoplasms following surgical extirpation ranges from 0-9%. Paragangliomas recur in approximately 5% of cases, and because 10% are multicentric, the risk of developing a second tumor remains.[21] Up to 42% of patients with familial paraganglioma syndrome may have multicentric disease.[18] In addition, patients with paragangliomas who are being treated nonoperatively must be alerted to the risk of malignant degeneration, which is approximately 10% and usually associated with rapid growth. Thus, patients with paragangliomas require lifetime follow-up. Pleomorphic adenomas have a recurrence rate of less than 4%.[41, 51]

Malignant tumors of the PPS have a much higher rate of recurrence (25-77%), depending on histology, extent of resection, and duration of follow-up.[41] Postoperative radiation therapy for PPS malignancies is recommended to prevent recurrence; however, because of the relative scarcity of these lesions, no large series are available to demonstrate a survival benefit.[41]

Future and Controversies

In the future, genetic screening of patients at risk for hereditary paragangliomas should be possible. The gene responsible for transmission of hereditary paragangliomas, termed PGL, has been mapped to chromosome 11. In large pedigree analyses, loci at 11q23 (PGL1) have been shown to be most commonly associated with a mutant PGL gene, which is inherited from carrier fathers in an autosomal dominant fashion subject to maternal imprinting. No affected offspring from affected mothers are documented. Genetic manipulation of a mutant PGL gene may prevent or interrupt the development of these tumors.[17]

Several studies have suggested that transoral robotic surgery (TORS) is feasible for the resection of appropriately selected parapharyngeal tumors.[38] Favorable characteristics for TORS resection include benign pathology, lack of poststyloid extension, and close proximity to the constrictor muscles and oral mucosa.[39] Several authors have suggested that combining the transoral approach with a transcervical approach, as well as incorporating endoscopic techniques, can be useful in resecting tumors in the lateral and superior parapharyngeal space (PPS).[52, 53] Goldenberg et al reported introducing a surgical robot via a transcervical approach, with good outcomes.[54]

Arguments that favor a robotic approach include direct visualization and improved dexterity, as opposed to blind blunt finger dissection, which can lead to hemorrhage, tumor spillage, and cranial nerve (CN) injury. Arguments against TORS are similar to those against traditional transoral approaches to PPS tumors, namely higher rates of tumor spillage and recurrence. Recurrence of a tumor initially approached transorally may result in increased morbidity, as the resection will likely require resection of the pharyngeal mucosa, mandibulotomy, and possible free flap reconstruction.[46] Other arguments against robotic surgery include lack of haptic feedback and ease of violating the capsule with sharp instrumentation. Long-term follow-up studies are needed to determine the utility of this new technology in addressing PPS tumors.

Author

Neerav Goyal, MD, MPH, FACS Associate Professor of Otolaryngology-Head and Neck Surgery, Neurosurgery, Public Health Sciences, and Surgery, Chief, Division of Head and Neck Oncology and Surgery, Pennsylvania State University College of Medicine; Associate Director, Skull Base and Pituitary Center, Department of Otolaryngology-Head and Neck Surgery, Penn State Health, Milton S Hershey Medical Center, Penn State Cancer Institute

Neerav Goyal, MD, MPH, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, American Medical Association, Hobart Amory Hare Honor Society, North American Skull Base Society, Pennsylvania Academy of Otolaryngology-Head and Neck Surgery, Society of University Otolaryngologists-Head and Neck Surgeons

Disclosure: Received research grant from: Medrobotics, Inc; Synthes, Inc, LivaNova.

Coauthor(s)

Sarah Benyo, BS MD Candidate, Pennsylvania State University College of Medicine

Sarah Benyo, BS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Erik Kass, MD Chief, Department of Clinical Otolaryngology, Associates in Otolaryngology of Northern Virginia

Erik Kass, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Medical Association, American Association for Cancer Research, American Rhinologic Society

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Emeritus Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan; Neosoma; MI10;<br/>Received income in an amount equal to or greater than $250 from: Neosoma; Cyberionix (CYBX)<br/>Received ownership interest from Cerescan for consulting for: Neosoma, MI10 advisor.

Additional Contributors

Christine G Gourin, MD, FACS Associate Professor, Director of Clinical Reasearch Program in Head and Neck Cancer, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine

Christine G Gourin, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, Phi Beta Kappa, Society of University Otolaryngologists-Head and Neck Surgeons, Association of Women Surgeons, Triological Society, American College of Surgeons Oncology Group

Disclosure: Nothing to disclose.

William M Lydiatt, MD, FACS Head and Neck Surgical Oncologist, Methodist Estabrook Cancer Center; Clinical Professor of Surgery, University of Nebraska; Professor, Department of Surgery, Creighton University School of Medicine; Faculty in Head and Neck Oncology, Department of Otolaryngology, Naval Medical Center Portsmouth

William M Lydiatt, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society

Disclosure: Nothing to disclose.

Jonas T Johnson, MD, FACS Emeritus Distinguished Service Professor, Department of Otolaryngology, University of Pittsburgh School of Medicine

Jonas T Johnson, MD, FACS is a member of the following medical societies: Allegheny County Medical Society, American Academy of Otolaryngology-Head and Neck Surgery, American Association for Cancer Research, American Bronchoesophagological Association, American College of Surgeons, American Head and Neck Society, American Laryngological Association, American Medical Association, American Rhinologic Society, American Society of Clinical Oncology, Pennsylvania Medical Society, Society of University Otolaryngologists-Head and Neck Surgeons, The Triological Society

Disclosure: Nothing to disclose.

Christopher D Pool, MD Resident Physician, Division of Otolaryngology-Head and Neck Surgery, Penn State Hershey Medical Center

Disclosure: Nothing to disclose.

Suarez-Fente V, Llorente-Pendas JL, Gomez-Martinez J, Garcia-Gonzalez LA, Lopez-Alvarez F, Suarez-Nieto C. [Primary tumours of the parapharyngeal space. Our experience in 51 patients.]. Acta Otorrinolaringol Esp. 2009 Jan. 60(1):19-24. [QxMD MEDLINE Link].
Riffat F, Dwivedi RC, Palme C, et al. A systematic review of 1143 parapharyngeal space tumors reported over 20 years. Oral Oncol. 2014 May. 50(5):421-30. [QxMD MEDLINE Link].
Batsakis JG, Sneige N. Parapharyngeal and retropharyngeal space diseases. Ann Otol Rhinol Laryngol. 1989 Apr. 98(4 Pt 1):320-1. [QxMD MEDLINE Link].
Carrau RL, Myers EN, Johnson JT. Management of tumors arising in the parapharyngeal space. Laryngoscope. 1990 Jun. 100(6):583-9. [QxMD MEDLINE Link].
Cohen SM, Burkey BB, Netterville JL. Surgical management of parapharyngeal space masses. Head Neck. 2005 Aug. 27(8):669-75. [QxMD MEDLINE Link].
Olsen KD. Tumors and surgery of the parapharyngeal space. Laryngoscope. 1994 May. 104(5 Pt 2 Suppl 63):1-28. [QxMD MEDLINE Link].
Leonetti JP, Donzelli JJ, Littooy FN, Farrell BP. Perioperative strategies in the management of carotid body tumors. Otolaryngol Head Neck Surg. 1997 Jul. 117(1):111-5. [QxMD MEDLINE Link].
Saito DM, Glastonbury CM, El-Sayed IH, Eisele DW. Parapharyngeal space schwannomas: preoperative imaging determination of the nerve of origin. Arch Otolaryngol Head Neck Surg. 2007 Jul. 133(7):662-7. [QxMD MEDLINE Link].
Som PM, Biller HF, Lawson W. Tumors of the parapharyngeal space: preoperative evaluation, diagnosis and surgical approaches. Ann Otol Rhinol Laryngol Suppl. 1981 Jan-Feb. 90(1 Pt 4):3-15. [QxMD MEDLINE Link].
Som PM, Biller HF, Lawson W, Sacher M, Lanzieri CF. Parapharyngeal space masses: an updated protocol based upon 104 cases. Radiology. 1984 Oct. 153 (1):149-56. [QxMD MEDLINE Link].
Som PM, Curtin HD. Lesions of the parapharyngeal space. Role of MR imaging. Otolaryngol Clin North Am. 1995 Jun. 28(3):515-42. [QxMD MEDLINE Link].
Hamza A, Fagan JJ, Weissman JL, Myers EN. Neurilemomas of the parapharyngeal space. Arch Otolaryngol Head Neck Surg. 1997 Jun. 123(6):622-6. [QxMD MEDLINE Link].
Curtin HD. Separation of the masticator space from the parapharyngeal space. Radiology. 1987 Apr. 163(1):195-204. [QxMD MEDLINE Link].
Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg. 1986 Jan-Feb. 8 (3):177-84. [QxMD MEDLINE Link].
Lum SG, Baki MM, Yunus MRM. A rare case of cervical hypoglossal nerve neurofibromas in a patient with type 1 neurofibromatosis. Braz J Otorhinolaryngol. 2022 Sep-Oct. 88 (5):812-6. [QxMD MEDLINE Link]. [Full Text].
Urquhart AC, Johnson JT, Myers EN, Schechter GL. Glomus vagale: paraganglioma of the vagus nerve. Laryngoscope. 1994 Apr. 104(4):440-5. [QxMD MEDLINE Link].
Baysal BE, Farr JE, Rubinstein WS, et al. Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23. Am J Hum Genet. 1997 Jan. 60(1):121-32. [QxMD MEDLINE Link].
McCaffrey TV, Meyer FB, Michels VV, Piepgras DG, Marion MS. Familial paragangliomas of the head and neck. Arch Otolaryngol Head Neck Surg. 1994 Nov. 120(11):1211-6. [QxMD MEDLINE Link].
Schwaber MK, Glasscock ME, Nissen AJ, Jackson CG, Smith PG. Diagnosis and management of catecholamine secreting glomus tumors. Laryngoscope. 1984 Aug. 94(8):1008-15. [QxMD MEDLINE Link].
Manolidis S, Shohet JA, Jackson CG, Glasscock ME 3rd. Malignant glomus tumors. Laryngoscope. 1999 Jan. 109 (1):30-4. [QxMD MEDLINE Link].
Lack EE, Cubilla AL, Woodruff JM, Farr HW. Paragangliomas of the head and neck region: a clinical study of 69 patients. Cancer. 1977 Feb. 39 (2):397-409. [QxMD MEDLINE Link]. [Full Text].
Gaylis H, Davidge-Pitts K, Pantanowitz D. Carotid body tumours. A review of 52 cases. S Afr Med J. 1987 Oct 3. 72 (7):493-6. [QxMD MEDLINE Link].
Pensak ML, Gluckman JL, Shumrick KA. Parapharyngeal space tumors: an algorithm for evaluation and management. Laryngoscope. 1994 Sep. 104(9):1170-3. [QxMD MEDLINE Link].
Panda NK, Patro SK, Behera S, Agarwal P, Das A. Parapharyngeal Space Angiofibroma: A Diagnostic Surprise. Iran J Otorhinolaryngol. 2021 Mar. 33 (115):107-11. [QxMD MEDLINE Link]. [Full Text].
Shonka DC Jr, Danan D. An Intravagal Parathyroid Adenoma in the Poststyloid Parapharyngeal Space. Laryngoscope. 2021 Feb. 131 (2):453-6. [QxMD MEDLINE Link].
Funabashi S, Yamagata K, Nishii T, Kusano K. Repeated loss of consciousness as the first symptom of recurrence of head and neck malignancy: a case report. Eur Heart J Case Rep. 2021 Jan. 5 (1):ytaa430. [QxMD MEDLINE Link]. [Full Text].
Langerman A, Rangarajan SV, Athavale SM, Pham MQ, Sinard RJ, Netterville JL. Tumors of the cervical sympathetic chain-Diagnosis and management. Head Neck. 2012 Sep 24. [QxMD MEDLINE Link].
Pitman KT, Weissman JL, Johnson JT. The parapharyngeal space: diagnosis and management of commonly encountered entities. Self-instructional package (SIPac). 3rd ed. Rochester, NY: The American Academy of Otolaryngology-Head and Neck Surgery Foundation; 1998. 1-66.
Maxwell JE, Howe JR. Imaging in neuroendocrine tumors: an update for the clinician. Int J Endocr Oncol. 2015. 2 (2):159-168. [QxMD MEDLINE Link]. [Full Text].
Hu K, Persky MS. The multidisciplinary management of paragangliomas of the head and neck, Part 2. Oncology (Williston Park). 2003 Aug. 17 (8):1143-53; discussion 1154, 1158, 1161. [QxMD MEDLINE Link].
Langerman A, Athavale SM, Rangarajan SV, Sinard RJ, Netterville JL. Natural history of cervical paragangliomas: outcomes of observation of 43 patients. Arch Otolaryngol Head Neck Surg. 2012 Apr. 138 (4):341-5. [QxMD MEDLINE Link].
Eisele DE, Netterville JL, Hoffman HT, Gantz BJ. Parapharyngeal space masses. Head Neck. 1999 Mar. 21(2):154-9. [QxMD MEDLINE Link].
Prasad SC, Piccirillo E, Chovanec M, et al. Lateral skull base approaches in the management of benign parapharyngeal space tumors. Auris Nasus Larynx. 2014 Sep 27. [QxMD MEDLINE Link].
Ferrari M, Schreiber A, Mattavelli D, et al. Surgical anatomy of the parapharyngeal space: multiperspective, quantification-based study. Head Neck. 2019 Mar. 41 (3):642-56. [QxMD MEDLINE Link].
Feng Y, Wang J, Li X, Meng L, Rao Y, Yang F. The intraoral growth patterns of parapharyngeal tumors: A proposed classification system. Ear Nose Throat J. 2021 Mar 9. 145561321997557. [QxMD MEDLINE Link]. [Full Text].
Yavuz H, Vural O. Transoral Approach to the Giant Deep Lobe Parotid Gland Pleomorphic Adenoma. J Craniofac Surg. 2021 Jul-Aug 01. 32 (5):e491-3. [QxMD MEDLINE Link].
Larson AR, Ryan WR. Transoral Excision of Parapharyngeal Space Tumors. Otolaryngol Clin North Am. 2021 Jun. 54 (3):531-41. [QxMD MEDLINE Link].
Chan JY, Tsang RK, Eisele DW, Richmon JD. Transoral robotic surgery of the parapharyngeal space: a case series and systematic review. Head Neck. 2015 Feb. 37 (2):293-8. [QxMD MEDLINE Link]. [Full Text].
O'Malley BW Jr, Quon H, Leonhardt FD, Chalian AA, Weinstein GS. Transoral robotic surgery for parapharyngeal space tumors. ORL J Otorhinolaryngol Relat Spec. 2010. 72 (6):332-6. [QxMD MEDLINE Link].
Chang SS, Goldenberg D, Koch WM. Transcervical approach to benign parapharyngeal space tumors. Ann Otol Rhinol Laryngol. 2012 Sep. 121(9):620-4. [QxMD MEDLINE Link].
Hughes KV 3rd, Olsen KD, McCaffrey TV. Parapharyngeal space neoplasms. Head Neck. 1995 Mar-Apr. 17(2):124-30. [QxMD MEDLINE Link].
Matsuki T, Okamoto I, Tada Y, et al. Resection of Parapharyngeal Space Tumors Located in the Prestyloid Compartment: Efficacy of the Cervical Approach. Ann Surg Oncol. 2021 Jun. 28 (6):3066-72. [QxMD MEDLINE Link].
Kumar L K S, S D, Mm J. Mandibular access osteotomy: Gate way to parapharyngeal space - A case report. Int J Surg Case Rep. 2021 Mar. 80:105683. [QxMD MEDLINE Link]. [Full Text].
Borras-Ferreres J, Armengot-Carceller M. Giant deep lobe parotid tumor removal via total parotidectomy without mandibulotomy. A simple and safe technique. J Clin Exp Dent. 2021 Mar. 13 (3):e313-7. [QxMD MEDLINE Link]. [Full Text].
Christopoulos E, Carrau R, Segas J, Johnson JT, Myers EN, Wagner RL. Transmandibular approaches to the oral cavity and oropharynx. A functional assessment. Arch Otolaryngol Head Neck Surg. 1992 Nov. 118(11):1164-7. [QxMD MEDLINE Link].
Cassoni A, Terenzi V, Della Monaca M, et al. Parapharyngeal space benign tumours: our experience. J Craniomaxillofac Surg. 2014 Mar. 42 (2):101-5. [QxMD MEDLINE Link].
Bulut OC, Giger R, Alwagdani A, et al. Primary neoplasms of the parapharyngeal space: diagnostic and therapeutic pearls and pitfalls. Eur Arch Otorhinolaryngol. 2021 Mar 19. [QxMD MEDLINE Link]. [Full Text].
Rzepakowska A, Osuch-Wojcikiewicz E, Zurek M, Durmaj A, Niemczyk K. Tumor, host and surgery related factors predisposing to cranial nerve deficits after surgical treatment of parapharyngeal space tumors. Eur Arch Otorhinolaryngol. 2021 Jun. 278 (6):1973-81. [QxMD MEDLINE Link]. [Full Text].
Linkov G, Morris LG, Shah JP, Kraus DH. First bite syndrome: incidence, risk factors, treatment, and outcomes. Laryngoscope. 2012 Aug. 122 (8):1773-8. [QxMD MEDLINE Link].
Chiu AG, Cohen JI, Burningham AR, Andersen PE, Davidson BJ. First bite syndrome: a complication of surgery involving the parapharyngeal space. Head Neck. 2002 Nov. 24 (11):996-9. [QxMD MEDLINE Link].
Witt RL. The significance of the margin in parotid surgery for pleomorphic adenoma. Laryngoscope. 2002 Dec. 112 (12):2141-54. [QxMD MEDLINE Link].
Duek I, Amit M, Sviri GE, Gil Z. Combined endoscopic transcervical-transoral robotic approach for resection of parapharyngeal space tumors. Head Neck. 2017 Apr. 39 (4):786-90. [QxMD MEDLINE Link].
Fan S, Lin SG, Zhang HQ, et al. A comparative study of the endoscopy-assisted transoral approach versus external approaches for the resection of large benign parapharyngeal space tumors. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Feb. 123 (2):157-62. [QxMD MEDLINE Link].
Goldenberg D, Ondik MP. DaVinci robot-assisted transcervical excision of a parapharyngeal space tumor. J Robot Surg. 2010 Sep. 4 (3):197-9. [QxMD MEDLINE Link].
Chen H, He Z, Li G, et al. Endoscopy-Assisted Transoral Approach to Resect Parapharyngeal Space Tumors: A Systematic Review and Meta-Analysis. Laryngoscope. 2021 Oct. 131 (10):2246-53. [QxMD MEDLINE Link].
Subramaniam N, Palme CE, Low TH. Combined approach for malignant tumours of the deep lobe of the parotid involving the stylomandibular tunnel and parapharyngeal space. Oral Oncol. 2021 Aug. 119:105283. [QxMD MEDLINE Link].