Parapharyngeal Space Tumors Treatment & Management

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]

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]

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]

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.

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.

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.

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.

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]

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.