Malignant Parotid Tumors 

Updated: May 18, 2017
  • Author: Bardia Amirlak, MD; Chief Editor: Deepak Narayan, MD, FRCS  more...
  • Print

Introduction and Anatomy

The parotid glands are the largest salivary glands in humans and are frequently involved in disease processes. Approximately 25% of parotid masses are nonneoplastic; the remaining 75% are neoplastic.

Nonneoplastic causes of parotid enlargement include cysts, parotitis, lymphoepithelial lesions associated with AIDS, collagen vascular diseases, and benign hypertrophy. Benign hypertrophy is encountered in patients with bulimia, sarcoidosis, sialosis, actinomycosis infections, and mycobacterial infections. The vast majority (approximately 80%) of parotid neoplasms are benign; these are discussed in detail in the Medscape Drugs & Diseases article Benign Parotid Tumors.

The paired parotid glands are formed as epithelial invaginations into the embryological mesoderm and first appear at approximately 6 weeks gestation. The glands are roughly pyramidal in shape, with the main body overlying the masseter muscle.

The glands extend to the zygomatic process and mastoid tip of the temporal bone and curve around the angle of the mandible to extend to the retromandibular and parapharyngeal spaces. The parotid duct exits the gland medially, crosses the superficial border of the masseter, pierces the buccinator, and enters the oral cavity through the buccal mucosa opposite the second maxillary molar.

The gland is divided into a superficial and deep portion by the facial nerve, which passes through the gland. While not truly anatomically discrete, these "lobes" are important surgically, as neoplasms involving the deep lobe require sometimes significant manipulation of the facial nerve to allow excision. The superficial lobe is the larger of the two and thereby the location of the majority of parotid tumors.

The facial nerve exits the cranium via the stylomastoid foramen and courses through the substance of the parotid gland. The superficial lobe of the parotid lies superficial or lateral to the facial nerve, whereas the deep lobe is deep or medial to the facial nerve. The facial nerve branches within the substance of the parotid gland, and the branching pattern can be highly variable. The main trunk typically bifurcates in to the zygomaticotemporal branch and the cervicofacial branch at the pes anserinus, also known as the goose’s foot (see images below), and thereafter into the temporal, zygomatic, buccal, marginal, and cervical branches. Pes is about 1.3 cm from the stylomastoid foramen. Extensive anastomoses are usually present between branches of the zygomatic and buccal branches of the nerve.

The (Z) zygomaticotemporal branch and the (C) cerv The (Z) zygomaticotemporal branch and the (C) cervicofacial branch of the facial nerve are dissected out during resection of a parotid tumor. The pes (goose's foot) is visible in this photograph.
The surgical anatomy and landmarks of the facial n The surgical anatomy and landmarks of the facial nerve.

Numerous lymph nodes also are present within the parotid gland itself, subsequently draining to preauricular, infra-auricular, and deep upper jugular nodes.

Next:

Diagnosis

Evaluation of a patient with a suspected parotid gland malignancy must begin with a thorough medical history and physical examination.

The most common presentation is a painless, asymptomatic mass; >80% of patients present because of a mass in the posterior cheek region. Approximately 30% of patients describe pain associated with the mass, though most parotid malignancies are painless. Pain most likely indicates perineural invasion, which greatly increases the likelihood of malignancy in a patient with a parotid mass.

Of patients with malignant parotid tumors, 7-20% present with facial nerve weakness or paralysis, which almost never accompanies benign lesions and indicates a poor prognosis. Approximately 80% of patients with facial nerve paralysis have nodal metastasis at the time of diagnosis. These patients have an average survival of 2.7 years and a 10-year survival of 14-26%.

Other important aspects of the history include length of time the mass has been present and history of prior cutaneous lesion or parotid lesion excision. Slow-growing masses of long-standing duration tend to be benign. A history of prior squamous cell carcinoma, malignant melanoma, or malignant fibrous histiocytoma suggests intraglandular metastasis or metastasis to parotid lymph nodes. Prior parotid tumor most likely indicates a recurrence because of inadequate initial resection.

Trismus often indicates advanced disease with extension into the masticatory muscles or, less commonly, invasion of the temporomandibular joint. Dysphagia or a sensation of a foreign body in the oropharynx indicates a tumor of the deep lobe of the gland. A report of ear pain may indicate extension of the tumor into the auditory canal. The presence of numbness in the distribution of the second or third divisions of the trigeminal nerve often indicates neural invasion.

Physical examination of the head and neck must be thorough and complete. The entire head and neck must be examined for cutaneous lesions, which may represent malignancies that could metastasize to the parotid gland or parotid nodes.

  • Palpation of the mass should determine the degree of firmness. Even benign tumors are usually firm, but a rock-hard mass generally denotes malignancy.
  • Skin fixation, skin ulceration, or fixation to adjacent structures also indicates malignancy. The external auditory canal must be visualized for tumor extension.
  • All regional nodes must be carefully palpated to detect nodal metastasis. Examination of the oral cavity and oropharynx also may yield further evidence of metastasis or malignant nature of the lesion.
  • Blood or pus from the Stenson duct is a sign of malignancy but is infrequently encountered. More often, one may see bulging of the lateral pharyngeal wall or soft palate, indicating tumor in the deep lobe of the gland.
  • Bimanual palpation with one finger against the lateral pharyngeal wall and the other against the external neck may confirm extent into the tonsillar fossa and soft palate.

Once a thorough history and physical examination are complete, perform diagnostic procedures to confirm the diagnosis and extent of the disease process.

Fine needle aspiration

See the list below:

  • Fine needle aspiration of the mass or an enlarged lymph node may be performed to obtain a tissue diagnosis. [1] Most surgeons recommend excision of a parotid mass whether it is benign or malignant unless a patient's comorbidity precludes safe surgery. As such, many surgeons do not routinely perform cytology before proceeding with surgery.
  • The sensitivity of this procedure is greater than 95% in experienced hands. However, only a positive diagnosis should be accepted; negative results indicate the need for further attempts at obtaining a histologic diagnosis, including repeat fine needle aspiration.
  • The results of the fine needle aspiration provide a histologic diagnosis and assist in preoperative planning and patient counseling. It may not distinguish benign from malignant epithelial lesions because malignancy of parotid epithelial cells is related to the behavior of the tumor cells in relation to tissue planes and surrounding structures rather than cellular architecture, which may be rather normal even in malignancy. Therefore, nonepithelial lesions may be diagnosed with accuracy, but epithelial lesions may require further investigation.
  • If fine needle aspiration is unsuccessful in obtaining a diagnosis, an incisional biopsy should not be performed. This procedure has a high rate of local recurrence and places the facial nerve at risk for injury from inadequate visualization.
  • Some authors advocate large core needle biopsies, but this procedure is less popular because of potential facial nerve injury and the possibility of seeding the needle tract with tumor cells.
  • If a core biopsy is performed, the needle should be inserted so that the tract may be excised during the definitive operation. When all attempts at obtaining a histologic diagnosis have failed, operative exploration should proceed after appropriate imaging studies have been obtained.
  • Intraoperatively, a frozen section of the specimen should be submitted for diagnosis. The use of frozen sections has demonstrated greater than 93% accuracy in the diagnosis of parotid malignancy.

Imaging studies

Imaging studies may be helpful in staging and for surgical planning. Sialography may help to differentiate inflammatory versus neoplastic processes, but this test is infrequently performed and is of limited value in the evaluation of parotid masses. It is mentioned herein for historic interest only.

Sonography may be very useful. Benign lesions are of lower density and have smaller caliber blood vessels. However, determination of a cystic component may be misleading, because cystic degeneration may occur as a result of necrosis at the avascular center of a malignancy.

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) [2] can be valuable for evaluation of parotid malignancies. CT scanning provides better detail of the surrounding tissues, whereas MRI demonstrates the mass in greater contrast than a CT scan.

These imaging studies may identify regional lymph node involvement or extension of the tumor into the deep lobe or parapharyngeal space. CT scan criteria for lymph node metastasis include any lymph node larger than 1-1.5 cm in greatest diameter, multiple enlarged nodes, and nodes displaying central necrosis.

Lymph nodes harboring metastasis also may appear round rather than the normal kidney bean shape, and evidence of extracapsular extension may be identified.

A study by Mamlouk et al of pediatric patients with parotid neoplasms indicated that on MRI scans, the presence of a hypointense T2 signal, restricted diffusion, poorly defined borders, and focal necrosis are suggestive of malignancy, although not specific for it. The study involved 17 patients, including 11 with malignant tumors and six with benign neoplasms. [3]

For more information on imaging studies for malignant parotid tumors, see Medscape Drugs & Diseases article Malignant Parotid Tumor Imaging.

Previous
Next:

Pathology

Many types of parotid malignancies exist, most arising from the epithelial elements of the gland. [4, 5, 6, 7, 8] Classification of these tumors can be quite confusing. In addition, malignancy may develop in the secretory element of the gland or malignancy arising elsewhere may first be noticed as a metastasis to the gland.

Mucoepidermoid carcinoma

Mucoepidermoid carcinoma is the most common malignant tumor of the parotid gland, accounting for 30% of parotid malignancies. [9, 10]

Three cell types are found in varying proportions: mucous, intermediate, and epidermoid cells. High-grade tumors exhibit cytologic atypia, higher mitotic frequency, areas of necrosis and more epidermoid cells. High-grade tumors behave like a squamous cell carcinoma; low-grade tumors often behave similar to a benign lesion. [11]

Limited local invasiveness and low metastatic potential characterize this tumor, particularly when cytologically low-grade. If metastatic, it is most likely to metastasize to regional nodal basins rather than to distant locations.

For patients with low-grade tumors without nodal or distant metastasis, 5-year survival is 75-95%, whereas patients with high-grade tumors with lymph node metastasis at the time of diagnosis have a 5-year survival of only 5%. Overall 10-year survival is 50%.

Differential diagnosis includes chronic sialoadenitis, necrotizing sialometaplasia, and other carcinomas. An association has been reported between mucoepidermoid carcinoma and myasthenia gravis. [12]

Adenoid cystic carcinoma

The adenoid cystic carcinoma is characterized by its unpredictable behavior and propensity to spread along nerves. It possesses a highly invasive quality but may remain quiescent for a long time.

This tumor may be present for more than 10 years and demonstrate little change and then suddenly infiltrate the adjacent tissues extensively.

The tumor has an affinity for growth along perineural planes and may demonstrate skip lesions along involved nerves. Clear margins do not necessarily mean that the tumor has been eradicated.

Metastasis is more common to distant sites than to regional nodes; lung metastases are most frequent. This tumor has the highest incidence of distant metastasis, occurring in 30-50% of patients.

Three histologic types have been identified: cribrose, tubular, and solid. The solid form has the worst prognosis; the cribrose pattern possesses the most benign behavior and best prognosis. This tumor requires aggressive initial resection. Overall 5-year survival is 35%, and 10-year survival is approximately 20%.

Malignant mixed tumors

Malignant mixed tumors arise most commonly as a focus of malignant degeneration within a preexisting benign pleomorphic adenoma (carcinoma ex pleomorphic adenoma).

These tumors also may develop de novo (carcinosarcoma). The longer pleomorphic adenoma has been present, the greater the chance of carcinomatous degeneration.

Carcinosarcomas, true malignant mixed tumors, are rare. Overall 5-year survival is 56%, and 10-year survival is 31%.

Acinic cell carcinoma

Acinic cell carcinoma is an intermediate-grade malignancy with low malignant potential. This tumor may be bilateral or multicentric and is usually solid, rarely cystic.

Although this tumor rarely metastasizes, occasional late distant metastases have been observed. This tumor also may spread along perineural planes. Overall 5-year survival is 82%, and 10-year survival is 68%.

Adenocarcinoma

Adenocarcinoma of the parotid develops from the secretory element of the gland. This is an aggressive lesion with potential for both local lymphatic and distant metastases.

Approximately 33% of patients have nodal or distant metastasis present at the time of initial diagnosis. Overall 5-year survival is 19-75%, as it is highly variable and related to grade and stage at presentation.

A study by Zhan and Lentsch of basal cell adenocarcinoma of the major salivary glands (509 cases) found that 88% of tumors were in the parotid glands, with 11.2% in the submandibular glands and 0.8% being sublingual gland lesions. Overall 5- and 10-year survival rates were 79% and 62%, respectively, while regional and distant metastases occurred in just 11.9% and 1.8% of cases, respectively. Older age (65 years or older) and high primary tumor stage had a significant negative impact on survival; in patients with a high tumor stage, the survival rate was significantly better with a combination of surgery and radiation therapy than with surgery alone. [13]

Primary squamous cell carcinoma

Primary squamous cell carcinoma of the parotid is rare, and metastasis from other sites must be excluded. Overall 5-year survival is 21-55%, and 10-year survival is 10-15%.

Sebaceous carcinoma

Sebaceous carcinoma is a rare parotid malignancy that often presents as a painful mass. It commonly involves the overlying skin.

Salivary duct carcinoma

Salivary duct carcinoma is a rare and highly aggressive tumor. Small cell carcinoma exists as 2 types. The ductal cell origin type is mostly benign and rarely metastasizes. The neuroendocrine origin type is often aggressive and has higher metastatic potential.

Lymphoma

The parotid gland also may be the site of occurrence of lymphoma, most commonly in elderly males. This is also observed in approximately 5-10% of patients with Warthin tumor of the parotid gland, a benign neoplasm. [14]

The entire parotid is typically enlarged with a rubbery consistency on palpation. Often, regional nodes also are enlarged. Biopsy of enlarged regional nodes avoids unnecessary parotid surgery, as the definitive treatment consists of chemotherapy or radiation therapy.

Malignant fibrohistiocytoma

Malignant fibrohistiocytoma is very rare in the parotid gland. It presents as a slow growing and painless mass.

Fine needle aspiration and imaging could confuse this lesion with other kinds of parotid tumors; therefore, definite diagnosis should be based on immunohistochemical analysis of the resected tumor. The tumor should be completely resected. [15]

Parotid metastasis from other sites

The parotid also may be the site of metastasis from cutaneous, renal, lung, breast, prostate, or GI tract malignancies.

Previous
Next:

Operative Management

Generally, therapy for parotid malignancy is complete surgical resection followed, when indicated, by radiation therapy. [16] Conservative excisions are plagued by a high rate of local recurrence. The extent of resection is based on tumor histology, tumor size and location, invasion of local structures, and the status of regional nodal basins.

Most tumors of the parotid (approximately 90%) originate in the superficial lobe. Superficial parotid lobectomy is the minimum operation performed in this situation. This procedure is appropriate for malignancies confined to the superficial lobe, those that are low grade, those less than 4 cm in greatest diameter, tumors without local invasion, and those without evidence of regional node involvement.

Surgical resection procedure

The most important initial step is identification of the facial nerve and its course through the substance of the parotid gland. In order to preserve the facial nerve, it is important to try to determine the proximity of the nerve to the capsule of the tumor prior to surgery. Results of a retrospective review showed that malignant tumors were likely to have a positive facial nerve margin. [17] Virtually all surgeons avoid using paralytic agents, and, to assist finding the nerve, many surgeons use a nerve stimulator. Increasingly, surgeons are using intraoperative continuous facial nerve monitoring any time a parotidectomy is performed. This is not usually necessary in the primary setting, but recurrent resections may be very difficult and probably should be performed using this device.

  • Ideally, the dissection of the facial nerve should be performed without disturbing or violating the tumor. The facial nerve may be found exiting the stylomastoid foramen by reflecting the parotid gland anteriorly and the sternocleidomastoid muscle posteriorly. Landmarks include the digastric ridge and the tympanomastoid suture. Knowledge of the relationships among these structures allows more efficient and reproducible identification of the nerve.
  • The cartilaginous external auditory canal lies approximately 5 mm superior to the facial nerve in this region. The facial nerve is also anterior to the posterior belly of the digastric muscle and external to the styloid process.
  • A second technique for locating the facial nerve is to identify a distal branch of the nerve and to dissect retrograde toward the main trunk. This technique may be more difficult depending on the ease of identifying the branching pattern. To perform this maneuver, the buccal branch may be found just superior to the parotid duct, or the marginal mandibular branch may be found crossing over (superficial to) the facial vessels. These may then be traced back to the origins of the main facial nerve trunks.
  • A final way of identifying the nerve in particularly difficult situations is to drill the mastoid and to locate the nerve within the temporal bone. It may then be followed through the stylomastoid foramen antegrade towards the parotid.
  • Once these have been identified, the superficial lobe of the parotid gland may be removed en bloc and sent to the pathology laboratory.
  • If the immediate intraoperative pathologic examination reveals that the tumor is actually high-grade or >4 cm in greatest diameter, or lymph node metastasis is identified within the specimen, a complete total parotidectomy should be performed.
  • If the facial nerve or its branches are adherent to or directly involved by the tumor, they must be sacrificed. However, a pathologic diagnosis of malignancy must be confirmed intraoperatively prior to sacrificing facial nerve branches.
  • All involved local structures should be resected in continuity with the tumor. This may include skin, masseter, mandible, temporalis, zygomatic arch, or temporal bone.
  • Tumors of the deep lobe are treated by total parotidectomy. Identification of the facial nerves and branches is the first and most crucial step.
  • Total parotidectomy is then performed en bloc, and the fate of the facial nerve and surrounding local structures must be decided similar to superficial lobe tumors. The specimen should be sent to the pathology laboratory for immediate examination.
  • Neck dissection should be performed when malignancy is detected in the lymph nodes pre- or intraoperatively.
  • Other indications for functional neck dissection include tumors >4 cm in greatest diameter, tumors that are high-grade, tumors that have invaded local structures, recurrent tumors when no neck dissection was performed initially, and deep lobe tumors.
  • These recommendations are based on the higher likelihood of occult, clinically undetectable nodal disease present at the time of operation in patients whose tumors display the above characteristics.
Previous
Next:

Reconstruction

Following resection of the tumor specimen, most wounds can be closed primarily. However, the presence of extension of the tumor to the overlying skin or surrounding structures may require reconstructive procedures. The overall goal following tumor excision is to restore function and achieve the best possible aesthetic result.

Options for wound closure in the presence of a skin or soft tissue deficit include skin grafting, cervicofacial flap, trapezius flap, pectoralis flap, deltopectoral flap, and microvascular free flap. For information on various flap procedures, see the Flaps section of the Medscape Drugs & Diseases Plastic Surgery journal.

Sacrifice of the facial nerve or one of its branches also must be managed appropriately. If inadvertently severed during the operation, the facial nerve should be immediately repaired under the operating microscope. If intentionally resected with the tumor specimen, several options for reconstruction are available to the surgeon.

  • The ipsilateral or contralateral great auricular nerve may be used as an interposition graft, although this sacrifices sensation to the area normally supplied by this nerve.
  • Another option is to anastomose the facial nerve to the ipsilateral hypoglossal nerve. This anastomosis may be performed end-to-side to avoid interfering with normal hypoglossal nerve function.
  • During the period of waiting for facial nerve recovery, maintain corneal protection if the innervation to the orbicularis oculi has been interrupted.
  • Measures include taping the eye closed at night over ophthalmic ointment and frequent use of wetting drops during the day. Some authors recommend a moisture chamber.

If facial nerve recovery is not achieved, certain measures may be taken to improve form and function.

  • A gold weight (0.8-1.2 g) may be inserted in the upper eyelid to assist with closure. Dynamic slings of temporalis muscle to the upper and lower lids and corner of the mouth or masseter sling to the mouth have proven very successful in the reconstruction of these patients. Static slings also have been used and include fascia lata, tendon, and Mitek anchors.
  • Following parotidectomy, some patients develop gustatory sweating or Frey syndrome. [18] This denotes an aberrant connection of regenerating parasympathetic salivary fibers to the sweat glands in the overlying skin flap. Treatment of this condition has included irradiation, atropinelike creams, division of the auriculotemporal nerve (sensory), division of the glossopharyngeal nerve (parasympathetic), insertion of synthetic materials (AlloDerm), fascial grafts, or vascularized tissue flaps between the parotid bed and overlying skin flap. Intracutaneous injections of botulinum toxin A is also an attractive option which has showed some promise.

Finally, neurovascular free tissue transfer has been described for facial reanimation for treatment of established facial paralysis following ablative parotid surgery. [19]

  • Vascularized nerve grafts, such as sural nerve graft, have been described to reestablish facial nerve continuity.
  • Functional free muscle transfer with gracilis, pectoralis minor, or latissimus dorsi muscles are further options for reconstruction. The ipsilateral facial nerve stump may be used as the recipient nerve.
  • Alternatively, cross facial nerve grafting can be performed. This is typically performed as a 2-stage surgery, with anastomosis to a nerve graft as the first stage and free tissue transfer as the second stage.

For more information on facial nerve reconstruction and the treatment of facial nerve paralysis, see the Medscape Drugs & Diseases articles Facial Nerve Paralysis, Dynamic Reconstruction for Facial Nerve Paralysis, and Static Reconstruction for Facial Nerve Paralysis.

Previous
Next:

Adjunctive Therapy

Because of the many histologic subtypes of parotid malignancies, a general statement regarding the usefulness of adjunctive therapy cannot be made.

If resectable, surgery is the primary modality of treatment for most malignant tumors of the parotid gland. General indications for postsurgical radiation therapy include tumors >4 cm in greatest diameter, tumors of high grade, tumor invasion of local structures, lymphatic invasion, neural invasion, vascular invasion, tumor present very close to a nerve that was spared, tumors originating in or extending to the deep lobe, recurrent tumors following re-resection, positive margins on final pathology, and regional lymph node involvement. Postoperative radiation is, thus, usually indicated for all parotid malignancies with the exception of small low-grade tumors with no evidence of local invasion or nodal/distant spread. Radiation therapy is considered the cornerstone of adjunctive therapy.

No chemotherapy has been proven effective as single modality therapy. For certain histologic subtypes, some clinicians recommend combined modality chemotherapy and radiation. Presently, immunotherapy is in the clinical trial phase.

A recent study demonstrated that epidermal growth factor receptor (EGFR) is expressed strongly in the cell membranes of parotid mucoepidermoid carcinomas and of the lymph node metastases. [20] EGFR-targeting agents have potential to be used for therapy.

Previous
Next:

Prognosis

The major determinants of survival are histology and clinical stage. Poor prognostic factors include high grade, neural involvement, locally advanced disease, advanced age, associated pain, regional lymph node metastases, distant metastasis, and accumulation of p53 or c-erbB2 oncoproteins. [21, 22, 23, 24]

Although statements regarding survival are difficult to make because of the large variety of histologic types, 20% of all patients will develop distant metastases. [25] The presence of distant metastases heralds a poor prognosis, with a median survival of 4.3-7.3 months.

Overall 5-year survival for all stages and histologic types is approximately 62%. The overall 5-year survival for recurrent disease is approximately 37%. Because of the risk of recurrence, all patients who have had a histologically proven malignant salivary gland tumor should have lifelong follow-up.

A study by Kim et al of 126 patients treated for primary parotid cancer found the following disease-specific survival rates for the various tumor stages (mean follow-up period 29.7 months) [26] :

  • Stage I (97%)
  • Stage II (81%)
  • Stage III (56%)
  • Stage IV (15%)

Patients in the study underwent superficial, total, or radical parotidectomy, with 57 also undergoing postoperative radiotherapy. Fifteen patients (12%) experienced disease recurrence.

Previous
Next:

Surveillance

Surveillance must continue indefinitely, as local recurrence or distant metastases may become apparent many years after the initial treatment.

The patient should undergo a thorough physical examination every 3 months for 2 years, every 6 months for another 3 years, then annually thereafter. Liver function tests and chest radiograph should be obtained annually.

Previous
Next:

Guidelines

Published in 2016, national multidisciplinary guidelines from the United Kingdom on the management of salivary gland tumors include the following recommendations [27] :

  • Ultrasonographically guided fine-needle aspiration cytology is recommended for all salivary tumors; cytology should be reported by an expert histopathologist
  • Adjuvant radiotherapy following surgery is recommended for all malignant submandibular tumors except in cases of small low-grade tumors that have been completely excised
  • For benign parotid tumors, complete excision of the tumor should be performed and offers good cure rates
  • In the event of intraoperative tumor spillage, most cases need long-term follow-up for clinical observation only; the issue should be raised in the multidisciplinary team so that the merits of adjuvant radiotherapy can be discussed
  • As a general principle, if facial nerve function is normal preoperatively, then every attempt to preserve facial nerve function should be made during parotidectomy; if the facial nerve is divided intraoperatively, then immediate microsurgical repair (with an interposition nerve graft if required) should be considered
  • Neck dissection is recommended in all cases of malignant parotid tumors except for small low-grade tumors
  • Where malignant parotid tumors lie in close proximity to the facial nerve, there should be a low threshold for adjuvant radiotherapy
  • Adjuvant radiotherapy should be considered in high-grade or large tumors or in cases where there is an incomplete or close resection margin
  • Adjuvant radiotherapy should be prescribed on the basis of clinical factors—eg, stage, preoperative facial weakness, positive margins, perineural invasion, and extracapsular spread—in addition to histology and grade
Previous