Benign Tumors of Major Salivary Glands 

Updated: Sep 04, 2019
Author: Michael J Eliason, MD; Chief Editor: John Geibel, MD, DSc, MSc, AGAF 

Overview

Practice Essentials

Salivary gland tumors (SGTs) are uncommon and represent 2-4% of head and neck neoplasms. In 2017, the World Health Organization reclassified tumors of salivary glands into five broad categories, as follows[1] :

  • Benign tumors
  • Malignant tumors
  • Nonneoplastic epithelial lesions
  • Benign soft-tissue lesions
  • Hematolymphoid tumors

The salivary glands exist as larger, named “major” glands and also as many widely dispersed “minor” glands that exist throughout the upper aerodigestive submucosa (ie, palate, lip, pharynx, nasopharynx, larynx, and parapharyngeal space). The paired major salivary glands include the following:

  • Parotid
  • Submandibular
  • Sublingual

Approximately 80% of SGTs originate in the parotid gland; the remaining SGTs arise in the submandibular, sublingual, and minor salivary glands.  A good rule of thumb is that the likelihood of an SGT being malignant is inversely proportional to the size of the gland from which it originates.  Specifically, the odds of malignancy in the parotid, submandibular, and minor salivary glands are 20%, 50%, and 80%, respectively.

The approach to a suspected SGT begins with a thorough history and a meticulous physical examination. SGTs usually manifest as an enlargement or growth of the affected gland. Depending on the location of the gland, they can present with nerve compression symptoms when patients are seen later in the course with larger tumors. Clinicians may investigate and exclude a history of weight loss, underlying infectious processes (eg, fever, elevated white blood cell [WBC] count, and concomitant lymphadenopathy), and clinical indications of lymphoma type B symptoms (eg, night sweats, fever, and chills).

Additionally, clinical workup should aim to exclude malignant neoplasms originating from the salivary tissue or malignancies that originate in the mucosal or cutaneous lining of the head and neck region but may exhibit contiguous or metastatic involvement of salivary tissue. Features such as pain, rapid growth, cranial neuropathies, fixation to soft tissue or bone, and associated adenopathy should alert the clinician to the possibility of a malignant diagnosis.

Radiographic imaging (eg, ultrasonography [US], computed tomography [CT], and magnetic resonance imaging [MRI]) often provide useful information before definitive surgical therapy. Cytopathologic evaluation using fine-needle aspiration (FNA) may be performed in selected cases and may help dictate the extent of surgical management. However, in most cases presenting with salivary masses, the decision to intervene surgically is largely based on clinical assessment and imaging findings.[2, 3, 4, 5]

From 1650 to 1750, salivary gland surgery was limited to the treatment of ranulas and oral calculi. The concept of surgical excision of a parotid tumor has been attributed to Bertrandi in 1802. The initial applications of this surgery included an extensive approach, causing serious disfiguration and disability.

By approximately 1850, the focus shifted toward dissection and the intimate relation between the facial nerve and the parotid gland. Attempts were made to perform the surgery with nerve preservation. John C Warren, MD, was the first to use ether inhalation anesthesia during his resection of a parotid tumor in Boston in 1846. In 1892, Codreanu (a Romanian native) performed the first total parotidectomy with facial nerve preservation. Grafting of the facial nerve after resection was attempted in the early 1950s.

In 1958, Beahrs and Adson eloquently described the relevant anatomy and surgical technique of current parotid gland surgery.[6]  They stressed surgical landmarks for avoiding injury to the main trunk and branches of the facial nerve and advocated complete removal of the superficial portion of the parotid gland for noninvasive lesions confined to that portion of the gland.[6]

For patient education resources, see the Cancer Center, as well as Cancer of the Mouth and Throat.

Anatomy

The parotid gland is situated in the musculoskeletal recess formed by portions of the temporal bone, atlas, and mandible, along with their related muscles. The gland is divided into superficial and deep lobes on the basis of the plane in which the extratemporal portion of the facial nerve runs. The deep lobe can extend in the parapharyngeal space via the stylomandibular tunnel. The superficial layer of the deep cervical fascia surrounds the parotid gland. This fascia has an anteroinferior portion that becomes the stylomandibular ligament, separating the parotid gland from the submandibular gland.

The facial nerve exits the stylomastoid foramen just posterior to the base of the styloid, gives off small branches to the postauricular and posterior belly of the digastric muscles, and then turns anterolaterally. The main trunk then becomes embedded in parotid tissue and divides into temporofacial and cervicofacial branches just superficial to the retromandibular vein. Beyond this point, the nerve anatomy varies. In general, however, there are five peripheral nerve branches, as follows:

  • Temporal or frontal
  • Zygomatic
  • Buccal
  • Marginal mandibular
  • Cervical

Multiple landmarks are used to identify the main trunk of the facial nerve during surgery. (See the image below.)

Facial nerve (white arrow) and its divisions (gree Facial nerve (white arrow) and its divisions (green arrows) are shown. Retromandibular vein is visible (blue arrow).

The submandibular gland encompasses most of the submandibular or digastric triangle. Like the parotid gland, the submandibular gland can be divided into superficial and deep lobes on the basis of the relationship with the mylohyoid muscle. The marginal mandibular branch of the facial nerve courses between the deep surface of the platysma and the investing fascia that lies over the submandibular gland. The facial artery and vein are located just deep to this nerve, and ligation and superior traction of these vascular structures can prevent nerve injury during surgery.

Located along the posterior border of the mylohyoid are the lingual nerve, submandibular ganglion, and submandibular duct (Wharton duct). The hypoglossal nerve courses deep to the tendon of the digastric and thus lies medial to the superficial layer of the deep cervical fascia.

The sublingual gland is located between the mylohyoid and hyoglossus muscles. The gland is rather superficial and is covered by only a thin layer of oral mucosa; thus, it can often be palpated in the floor of the mouth.

The minor salivary glands are widely dispersed throughout the upper respiratory tract, including the palate, lip, pharynx, nasopharynx, larynx, and parapharyngeal space. The greatest densities of glands are located in the hard (250 glands) and soft (150 glands) palates.

Pathophysiology

The histogenesis of SGTs is based on the salivary gland unit (see the image below). According to the multicellular theory of SGTs, pleomorphic adenomas originate from the intercalated duct cells and myoepithelial cells; oncocytic tumors originate from the striated duct cells; acinic cell tumors originate from the acinar cells; and mucoepidermoid and squamous cell tumors originate from the excretory duct cells.

Histology of salivary gland unit. Histology of salivary gland unit.

Etiology

Although the etiology of SGTs is unknown, associations with environmental or genetic factors have been suggested.[7]

Smoking has been closely associated with Warthin tumors. Radiation exposure has been linked to the development of the benign Warthin tumor and to the malignant mucoepidermoid carcinoma. Epstein-Barr virus may be a factor in the development of lymphoepithelial tumors of the salivary glands. Genetic alterations (eg, allelic loss, monosomy and polysomy, and structural rearrangement) have been studied as factors in the development of SGTs.

Epidemiology

SGTs represent 2-3% of head and neck neoplasms and are more common in women than in men. The peak incidence is in the third and fourth decades of life. Pleomorphic adenomas are the most common benign SGTs, followed by Warthin tumors (papillary cystadenoma lymphomatosum; see the image below).

Heterogeneous, predominantly low-density mass in t Heterogeneous, predominantly low-density mass in tail of right parotid gland with minimal thin peripheral enhancement consistent with Warthin tumor.

Prognosis

Whereas surgical excision of benign SGTs can have specific consequences or complications, given the unique anatomic locations of these lesions, the overall outcome after removal is excellent.

Pleomorphic adenomas, in particular, have a very low rate of recurrence, which is presumed to be the result of incomplete surgical excision due to pseudopod extension of the tumor. If untreated, benign pleomorphic adenoma may, in rare cases, undergo transition to a malignant variant called carcinoma ex pleomorphic adenoma; the rate of such transformation is estimated at 10% over 10-15 years.

 

Presentation

History and Physical Examination

The classic presentation of a benign salivary gland tumor (SGT) is a painless, slow-growing mass on the face (parotid; see the first image below), the angle of the mandible (parotid tail, submandibular gland), the neck (submandibular gland; see the second and third images below), or the floor of the mouth (sublingual gland). One may also appreciate medialization of the palatine tonsil in cases of tumor originating in the deep lobe of parotid and extending into the parapharyngeal space.

Parotidectomy. Left parotid mass; preoperative mar Parotidectomy. Left parotid mass; preoperative marking of modified Blair incision on skin.
Right submandibular benign salivary gland tumor in Right submandibular benign salivary gland tumor in 42-year-old woman.
Pictures before (above, left) and after (above, ri Pictures before (above, left) and after (above, right) treatment for benign mandibular gland tumor. Specimen picture of gland (below).

A sudden increase in size may be indicative of infection, cystic degeneration, hemorrhage inside the mass, or malignant degeneration. In contrast to malignant SGTs, benign neoplasms are slow-growing, are almost always freely mobile and not fixed to the skin, and generally do not cause neural palsies (facial nerve dysfunction, pain, hoarseness, etc).[8]

Tumor Classification

Tumors of the salivary glands are classified on the basis of their cytologic, architectural, and biologic characteristics. The 2017 World Health Organization (WHO) classification of head and neck tumors groups SGTs into the following five categories[1] :

  • Malignant tumors (including various carcinomas, adenocarcinomas, and sarcomas) (see Salivary Gland Neoplasms and Malignant Parotid Tumors)
  • Benign tumors (see below)
  • Nonneoplastic epithelial lesions (sclerosing polycystic adenosis, oncocytic hyperplasia, lymphoepithelial sialadenitis, intercalated duct hyperplasia)
  • Benign soft-tissue lesions (hemangioma, lipoma, nodular fasciitis)
  • Hematolymphoid tumors (mucosa-associated lymphoid tissue [MALT] lymphoma)

The 2017 WHO classification of benign SGTs is detailed in Table 1 below.[1]

Table 1. World Health Organization Classification of Benign Salivary Gland Tumors (Open Table in a new window)

Pleomorphic adenoma

Warthin tumor

Oncocytoma

Basal cell adenoma

Myoepithelioma

Lymphadenoma

Cystadenoma

Sialadenoma papilliferum

Ductal papillomas

Sebaceous adenoma

Canalicular adenoma and other ductal adenomas

Pleomorphic adenoma

Pleomorphic adenomas (benign mixed tumors) are the most common tumors of the salivary gland and are most often located in the tail of the parotid gland. When they are found in the minor salivary glands, the hard palate is the site most frequently involved, followed by the upper lip. (See the images below.)

Note 12-mm right parotid, smoothly marginated, mul Note 12-mm right parotid, smoothly marginated, multilobulated, solid lesion, without focal calcification or necrosis. This was proven to be pleomorphic adenoma.
Note 2- × 1.5-cm uniformly enhancing, smoothly mar Note 2- × 1.5-cm uniformly enhancing, smoothly marginated mass in superficial right parotid gland without necrosis or calcification, which is consistent with epithelial neoplasm such as pleomorphic adenoma.

These tumors were termed pleomorphic because of the epithelial and connective tissue components that compose them in varying degrees. Their gross appearance is a round, smooth mass with a thin, delicate, incomplete capsule. Notably, pleomorphic adenomas that arise in the minor salivary glands usually lack a capsule.

These tumors grow slowly, though they may become larger than other SGTs. The thin, delicate capsule may have pseudopod projections into the surrounding parotid tissue. This is of particular clinical significance because obtaining clean margins and avoiding spillage are mandatory to minimize recurrence.

Microscopically, benign mixed tumors are characterized by variable and diverse structural histologic patterns. Frequently, they have growth patterns of sheets, strands, or islands of spindle and stellate cells, with a myxoid configuration occasionally predominating. Treatment of benign neoplasms involves the complete surgical excision of the affected gland. If the parotid gland is involved, superficial parotidectomy with standard facial nerve dissection and preservation is the procedure of choice. Enucleation is contraindicated because of the tendency toward tumor spillage and recurrence.

Warthin tumor

Warthin tumor (papillary cystadenoma lymphomatosum or adenolymphoma) was first recognized by Albrecht in 1910 and later described by Warthin in 1929. In gross appearance, it is a smooth, soft, parotid mass. It is well encapsulated when located in the parotid gland and contains multiple cysts.

Histologically, the Warthin tumor has a heavy lymphoid stroma and aciniform epithelial cells that line the cystic areas with papillary projections. Malignant transformation is exceedingly rare, and surgical excision is typically curative, with an excellent prognosis. The Warthin tumor tends to be bilateral in 10% of cases and is usually found in the major glands.

Oxyphilic adenoma (oncocytoma)

Oxyphilic adenoma (oncocytoma) was first described by Duplay in 1875. Oncocytomas of the salivary glands are very uncommon. Such neoplasms occur more often in women than in men, with a female-to-male ratio of 2:1. Patients are older than 50 years, and the superficial lobe of the parotid gland is the most commonly reported location. Oncocytomas rarely, if ever, occur in the minor salivary glands. They manifest as small (< 5 cm in diameter), firm, slow-growing, spherical masses. Bilateral oncocytomas of the parotid glands have been described.

Histologically, oncocytomas are large and spherical and have a distinct capsule. Uniform cells are arranged in solid sheets. These tumors recur if excision is incomplete; with complete excision, the prognosis is excellent.[9]

Myoepithelioma

Myoepitheliomas are much less common benign tumors that originate as a monomorphic cell type. These tumors may display a spindle pattern of growth, a plasmacytoid pattern, or a combination of the two. Any recurrence after surgical excision is typically the result of incomplete resection, and the prognosis is generally very favorable.

Ductal papilloma

Ductal papilloma (DP) is a small, tan, fairly smooth lesion that is usually found in the submucosal layer. Microscopically, DP consists of a cystically dilated duct partially lined with a cuboidal epithelium with complex anastomosing papillary fronds of variable size filling the cystic area. DP of a minor salivary gland is a rare lesion that has been described only in various case reports.

Histologically, the differential diagnosis of DP includes papillary cystadenoma, which is commonly but erroneously diagnosed as DP. In papillary cystadenoma, intraductal hyperplasia occurs, and the dilated duct contains some papillary folds and projections. However, this occurs much less frequently than in DP.

Basal cell adenoma

Most basal cell adenomas arise in the major salivary glands and are composed of basaloid cells with scant cytoplasm. As with other benign monomorphic tumors of salivary gland origin, recurrence is uncommon after appropriate surgical excision, and malignant transformation is very rare.

Other benign salivary gland tumors

Additional benign SGTs include the following:

  • Lymphadenoma
  • Cystadenoma
  • Sialadenoma papilliferum
  • Sebaceous adenoma
  • Canalicular adenomas
 

Workup

Laboratory Studies

Perform a white blood cell (WBC) count to investigate for any evidence of leukocytosis and shift that might indicate a possible infectious process or lymphoproliferative disease.

Imaging Studies

Imaging studies are most helpful in the diagnostic evaluation of salivary gland tumors (SGTs).[2, 10]

Ultrasonography (US) is often the first-line modality for characterizing a neoplasm within the parotid or submandibular glands. In many cases, high-resolution US can adequately assess the size, evaluate the general morphology (cystic, solid, or complex), and define the type of borders (well-circumscribed vs poorly defined), thereby facilitating diagnosis and surgical management. Surgeon-performed US may serve as an extension of the physical examination or may be ordered as a separate standalone study, depending on institutional preferences.

Magnetic resonance imaging (MRI) and computed tomography (CT) may be used to further characterize larger tumors, those that extend beyond the depth that US can adequately assess, and those that raise concerns for malignant features on US or clinical assessment. (See the images below.) MRI is the most sensitive test for establishing the borders of soft-tissue tumor extension and perineural invasion or spread. 

Heterogeneous, predominantly low-density mass in t Heterogeneous, predominantly low-density mass in tail of right parotid gland with minimal thin peripheral enhancement consistent with Warthin tumor.
Dense, small, solid lesions in parotid glands (mor Dense, small, solid lesions in parotid glands (more on left side than on right) in patient with lymphoma. This is representative of lymphomatous involvement of glands.
Ill-defined masses in parotid glands bilaterally, Ill-defined masses in parotid glands bilaterally, proven to be large B-cell lymphoma in this patient with known Sjögren disease.
Large B-cell lymphoma in patient with known Sjögre Large B-cell lymphoma in patient with known Sjögren disease.
Large B-cell lymphoma in patient with known Sjögre Large B-cell lymphoma in patient with known Sjögren disease.
Bilateral, solid, inhomogeneous parotid gland mass Bilateral, solid, inhomogeneous parotid gland masses that are larger on left side than on right, with minimal necrosis. These were caused by lymphoma.

In most circumstances, findings from CT and MRI cannot reliably be used to differentiate benign from malignant disease. In a study of 46 major SGTs, Aghaghazvini et al found that dynamic contrast-enhanced MRI had potential utility for differentiating SGTs preoperatively, specifically with regard to distinguishing between Warthin tumors and benign non-Warthin tumors.[11]

Biopsy

In selected cases, fine-needle aspiration (FNA) biopsy (FNAB) may facilitate the management of a mass in the salivary gland by helping to distinguish a tumor from certain nonneoplastic or inflammatory processes that may respond better to medical management. 

In most patients who present with a salivary mass, the decision to offer surgical management is likely to be determined by clinical and imaging characteristics, and FNA may be considered as part of the workup on the basis of specific considerations of the case. Most benign tumors and low-grade malignancies without lymphadenopathy are treated by surgical extirpation of the primary tumor alone. Patients with high-grade salivary malignancies may require removal of the primary tumor and lymphadenectomy at the same time.

The reliability of FNA in making the diagnosis and determining the grade of malignancy remains a controversial issue. Additionally, the utility of FNA in distinguishing high-grade malignancies from low-grade malignancies and benign tumors may be limited by the local availability of expertise. In the absence of the ability to differentiate the grade of malignancy, FNA may play a limited role in the decision to offer an operation; however, if the diagnosis of a high-grade salivary gland malignancy is made preoperatively, FNA may influence the extent of the operation.[5, 12]

 

Treatment

Approach Considerations

Experienced clinicians generally agree that surgical excision is indicated for all patients in whom a salivary gland mass develops, unless comorbid medical problems preclude such intervention. Ultimately, surgical excision permits definitive diagnosis and determines the need for any adjuvant therapy that may be indicated in malignant tumors.

Furthermore, surgery is recommended because given the location of these lesions in the head and neck, there are unique consequences that can arise from even a benign space-occupying mass or tumor, specifically related to loss of function, disfigurement, and the social isolation that may ensue from such issues.

Indications for more urgent surgical treatment of salivary gland tumors (SGTs) include the following:

  • Mass of the face, neck, and floor of the mouth
  • Presence of clinical signs of malignancy (eg, a rapid growth on a slow-growing tumor, bleeding, airway compromise due to larger tumors, and nerve dysfunction such as paresthesia)

Medical Therapy

Inflammatory infectious masses (eg, reactive or fungal) and lymphoma should be treated medically. When symptomatic, recurrent chronic gland infection (eg, parotitis) proves refractory to conservative medical or endoscopic (ie, sialoendoscopic) treatments, salivary gland excision is sometimes indicated.

Surgical Therapy

Management of benign SGTs includes complete removal of the neoplasm with an adequate margin of tissue to avoid recurrence. This usually involves either complete removal of the gland in which the tumor developed or extracapsular dissection of the tumor within the affected gland. Excision is performed with general anesthesia and without paralysis. The endotracheal tube is usually positioned in the corner of the mouth opposite to the surgical field.

Parotidectomy

The key to parotidectomy is safe localization of the facial nerve at the main trunk proximal to the gland. The possibility of total parotidectomy should be included in the preoperative plan. When a malignant diagnosis has not been ruled out, there should also be preoperative discussion of the potential need to sacrifice the facial nerve, with immediate grafting, cervical lymphadenectomy, and mandibulectomy.

Superficial parotidectomy remains the initial procedure of choice for benign parotid gland tumors. A modified Blair incision (see the image below) is often used. The incision usually starts just anterior to the ear helix, extends inferiorly below the ear lobe, and then continues onto the neck, paralleling—but staying at least 2 cm below—the body of the mandible. Other approaches, including a facelift incision, have been described.

Parotidectomy. Left parotid mass; preoperative mar Parotidectomy. Left parotid mass; preoperative marking of modified Blair incision on skin.

To avoid injury to the facial nerve, the surgical field is exposed broadly, with the sternocleidomastoid muscle and the posterior belly of the digastric muscle serving as anatomic landmarks (see the images below). Additionally, the cartilage of the external auditory canal is exposed, and the tragal pointer and the tympanomastoid suture line (a palpatory landmark) are used to direct careful dissection so that the main extratemporal trunk of the facial nerve can be visualized.

Parotidectomy. Wide plane maintaining thick vascul Parotidectomy. Wide plane maintaining thick vascularized skin flap is raised anteriorly. Note that greater auricular nerve is preserved, when possible, during this dissection.
Parotidectomy. With wide plane of dissection maint Parotidectomy. With wide plane of dissection maintained, sternocleidomastoid muscle and posterior belly of digastric muscle are exposed. Main trunk of facial nerve is starting to appear (white arrow).

Once the main trunk is exposed, dissection is performed to expose, while avoiding injury to, the individual branches of the nerve and, ultimately, to excise the tumor (see the image below).

Facial nerve (white arrow) and its divisions (gree Facial nerve (white arrow) and its divisions (green arrows) are shown. Retromandibular vein is visible (blue arrow).

An optional electromyographic (EMG) facial nerve monitor may be used to permit stimulation of the nerve for confirmation of integrity as needed during dissection. Although this is an exceedingly rare scenario with dissection for benign tumors, if the tumor necessitates resection of a portion of the facial nerve, the nerve should be immediately repaired or reconstructed to afford the best chance of maintaining tone in the muscle or muscles being innervated.

Another potential complication is sacrifice of the greater auricular nerve causing loss of sensation to the ear lobule and surrounding skin. To avoid this, careful dissection through the subcutaneous plane is performed to permit identification and preservation of the nerve as the anatomy allows.

The facial hollowing and loss of facial symmetry that may result from tumor and gland removal can sometimes be addressed at the time of surgery by placing cadaveric human dermal matrix or even by rotating a portion of the nearby sternocleidomastoid muscle into the deficit. Other approaches using avascular fat graft (harvested from the patient’s abdominal wall) have also been described.

Postoperative gustatory sweating (Frey syndrome) is rare but may occur with aberrant reinnervation of the parasympathetics after parotid surgery.  Use of thick skin flaps, placement of human dermal matrix, or both may mitigate this complication.

Recurrence of a benign tumor can be avoided with complete excision of the lesion. Enucleation should be avoided so as to minimize the chance of tumor spillage and seeding recurrence.

Submandibular gland surgery

Submandibular gland surgery is performed with the patient under general anesthesia with endotracheal intubation. Head rotation is to the opposite side of the tumor.

An incision at least 2 cm below the body of the mandible is made through the platysma to permit identification of the superficial layer of the deep cervical fascia. To avoid injury to the marginal mandibular branch of the facial nerve, a technique of dividing the facial vein and raising a fascial flap/plane may be employed to ensure that dissection is deep to the nerve. Other approaches include direct identification of the nerve to avoid injury during dissection.

Another potential complication during submandibular gland or tumor excision is injury to the hypoglossal nerve or the lingual nerve. Careful dissection with appropriate identification and preservation of these structures is recommended.