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 Reference 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 gooses 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)
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 nerve.
Numerous lymph nodes also are present within the parotid gland itself,
subsequently draining to preauricular, infra-auricular, and deep upper jugular
nodes.
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
priorsquamous cell carcinoma, malignant melanoma, or malignant fibrous
histiocytomasuggests 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. Dysphagiaor 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
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 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.
CT scan and 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.
For more information on imaging studies for malignant parotid tumors, see
Medscape Reference Radiology article Malignant Parotid Tumor Imaging.
Pathology
Many types of parotid malignancies exist, most arising from the epithelial
elements of the gland.
[3, 4, 5, 6, 7]
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.
[8, 9]

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.
[10]

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
andmyasthenia gravis.
[11]

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 expleomorphic 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.
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.
[12]

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 them 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.
[13]

Parotid metastasis from other sites
The parotid also may be the site of metastasis from cutaneous, renal, lung,
breast, prostate, or GI tract malignancies.
Operative Management
Generally, therapy for parotid malignancy is complete surgical resection followed,
when indicated, by radiation therapy.
[14]
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.
[15]
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.
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
theFlaps section of the Medscape Reference 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.
[16]
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.
[17]

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 Medscape Reference articles Facial Nerve
Paralysis,Dynamic Reconstruction for Facial Nerve Paralysis, and Static
Reconstruction for Facial Nerve Paralysis.
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.
[18]
EGFR-targeting agents have potential to be
used for therapy.
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.
[19, 20, 21, 22]

Although statements regarding survival are difficult to make because of the large
variety of histologic types, 20% of all patients will develop distant
metastases.
[23]
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.
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.