Salivary Gland Tumors

Definition and Pathophysiology:

The salivary gland tumors are collections of cells that form a mass in different secretory organs that produce saliva, an electrolyte- and enzyme-rich fluid that has digestive and immune functions. The mass or neoplasm can be benign or malignant.

There are three pairs of major salivary glands: the parotid, submandibular, and sublingual glands. salivary_glands In addition, there are hundreds of minor salivary glands present in the mucosa of the oral cavity and oropharynx. Salivary glands are composed of secretory units, which comprise an acinus, a secretory duct, and a collecting duct. The acinus may produce serous, mucous, or mixed fluid, depending on the type of salivary gland.

photo of facial nerve trunk

main facial nerve trunk with upper and lower divisions

The parotid gland is the largest of the three major salivary glands and is situated anteroinferior to the external auditory canal, extending inferiorly to the angle of the mandible and slightly behind the ear lobe. They are responsible for up to a quarter of the saliva production during a day. The parotid is divided into superficial and deep lobes by the facial nerve, which has five major branches. The parotid duct (also known as Stensen’s duct) runs anteriorly from the superficial lobe, piercing the buccinator muscle and emptying into the oral cavity via a papilla in the buccal mucosa near the second maxillary molar.

The submandibular glands are located under the jaw, inferior to the angle of the mandible. They are composed of mixed acini and account for the majority of the body’s unstimulated resting saliva production. The submandibular duct (also known as Wharton’s duct) travels in the sublingual space in close association with the lingual and hypoglossal nerves before emptying into the oral cavity via papillae in the floor of the mouth.

photo of sublingual gland

Right sublingual duct (Wharton’s duct) with lingual nerve deep to duct

The sublingual glands are the smallest of the major salivary glands and are located under the tongue. They are composed of mucous acini. Their drainage is via multiple ducts of Rivinus that empty into the submandibular duct and floor of the mouth. ((Picture of sublingual gland))

The minor salivary glands number in the hundreds and are present throughout the mucosa of the upper airway, but are prominent in the lips and palate. Many inflammatory and neoplastic conditions can affect any of the salivary glands. This chapter will focus on benign and malignant salivary gland tumors, as these are the primary reasons for surgical intervention on the salivary glands. However, it should be noted that some inflammatory conditions, such as chronic sialadenitis, may also be treated with surgical methods.

Overall, salivary gland neoplasms account for 3% of all head and neck tumors. Eighty percent of salivary gland neoplasms occur in the superficial parotid gland, of which 80% are benign. The smaller salivary glands are more likely to harbor malignancies when they develop growths. For instance, 46% of minor salivary gland tumors and over 80% of sublingual gland tumors are malignant.



Benign Neoplasms

The most common salivary gland neoplasm is pleomorphic adenoma (also known as benign mixed tumor), which occurs predominantly in the parotid gland, and may account for up to 80% of all salivary gland tumors. Histologically, as the name suggests, pleomorphic adenomas are composed of multiple cell types. Although they are benign, a small percentage of these tumors undergo malignant transformation (carcinoma ex-pleomorphic adenoma), with the risk increasing over time.

Papillary cystadenoma lymphomatosum, more commonly referred to by the eponym Warthin tumor, is the second most common benign salivary gland growth. They most commonly occur in the parotid glands. Among salivary gland tumors, it has a relatively higher risk of bilaterality. Histologically, it has a cystic component and is characterized by the presence of eosinophilic cells called oncocytes. Other, less common benign salivary gland tumors include oncocytoma, myoepithelioma, basal cell adenoma, canalicular adenoma, and lipoma.

Malignant Neoplasms

The most common salivary gland malignancy is mucoepidermoid carcinoma, which is characterized by both mucoid and epidermoid cell types. The histological grade of the tumor depends on the ratio of the two cell types, with low grade tumors being mostly glandular and cystic, while high grade tumors consist predominantly of solid sheets of epidermoid cells. Adenoid cystic carcinoma is the second most common salivary gland malignancy overall, although it represents the most common malignancy of the submandibular, sublingual, and minor salivary glands. Behavior of the tumor depends on its histologic structure, which may be a combination of tubular, cribriform, and solid growth patterns. Adenoid cystic carcinoma is noted for its propensity for perineural invasion, as well as late distant metastasis. Acinic cell carcinoma and polymorphous low-grade adenocarcinoma (PLGA) are two low-grade malignancies that are predominantly found in the parotid gland. Other, less common salivary gland malignancies include squamous cell carcinoma, adenocarcinoma, carcinoma ex-pleomorphic adenoma, and salivary duct carcinoma. See Table 51.1 for a summary of the most commonly encountered salivary gland neoplasms.



Common Salivary Gland Neoplasms

Pleomorphic adenomaBenign75% of benign salivary gland tumors, 45% of all salivary gland neoplasms85% in parotid, can occur in any of the major or minor salivary glandsSmall chance of malignant
transformation, local recurrences can be very difficult to treat
Warthin tumorBenign21% of benign salivary gland tumors, 7% of all salivary gland neoplasmsAlmost exclusively in parotidAssociated with smoking;
often bilateral
Malignant; may be low-, intermediate-, or high-grade34% of malignant salivary gland tumors, 16% of all salivary gland neoplasms
Mostly in major salivary glands, can occur in minor salivary glandsHigh grade tumors have
more epidermoid/solid component
Adenoid cystic carcinomaMalignant22% of malignant salivary gland tumors; the most common malignancy in all non-parotid salivary glandsEven distribution across all salivary glandsHigh incidence of perineural invasion and late distant metastasis; grade depends on combination of tubular, cribriform, and solid patterns
Acinic cell carcinomaMalignant (low-grade)7-10% of malignant salivary gland tumors, 3% of all salivary gland neoplasmsOver 90% in parotid, also occurs in minor salivary glands and rarely submandibularSecond most common salivary gland malignancy in children
Polymorphous low-grade adenocarcinomaMalignant (low-grade)Second most common
minor salivary gland malignancy
Almost exclusively in
minor salivary glands, predominantly in palate
Associated with perineural
invasion; metastases are
very rare
Carcinoma ex-pleomorphic adenomaMalignantUp to 10% of malignant salivary gland tumorsMost common in parotid, can occur in any salivary glandBelongs to the malignant
mixed tumor (MMT) class of salivary gland neoplasms; histology may be any type of carcinoma




The incidence of salivary gland tumors is estimated to be approximately 1.5 cases per 100,000 individuals in the United States. Overall, salivary gland neoplasms are more common in patients over the age of 60 years, particularly malignant tumors. Salivary gland tumors are very rare in children (less than 5% occur in the pediatric population); however, salivary gland neoplasms that occur in children are more likely to be malignant. Typically, benign salivary gland tumors occur more frequently in females, while malignant tumors show no sex predilection. Warthin tumor is an exception, as it is more common in males.

Natural History:

The natural history of a salivary gland neoplasm depends on its type, although most salivary gland tumors tend to be slow-growing and relatively asymptomatic. As mentioned previously, pleomorphic adenoma carries a risk of malignant transformation that increases with time; the rate may be as high as 10% for untreated tumors at 15 years. The behavior of mucoepidermoid carcinoma depends on its histologic grade. In general, low-grade tumors very rarely metastasize or decrease survival, although low-grade mucoepidermoid tumors occurring in the submandibular glands have a higher rate of metastasis. High grade mucoepidermoid carcinoma is an aggressive malignancy, with a high rate of locoregional lymph node metastasis. Adenoid cystic carcinoma, while slow-growing and not prone to regional lymph node metastasis, is notable for its high rate of distant metastases (particularly to the lung), often occurring years after diagnosis and treatment of the primary.


photo of parotid mass

Right parotid mass

Salivary gland neoplasms typically present as slow-growing, painless masses. Only an estimated 10% of patients with salivary gland tumors have pain at the time of initial presentation. The presence of pain is more commonly associated with inflammatory conditions, although it may also be observed in malignancies. A small percentage of patients with parotid masses present with facial paralysis, which is a poor prognostic indicator. Perineural involvement can result in sensory or motor deficits of the tongue or lips. Extraglandular extension may result in trismus, dysfunction of other cranial nerves, and oropharyngeal obstruction due to mass effect (particularly in deep lobe parotid tumors, which expand into the parapharyngeal space).

Differential Diagnosis of Salivary Gland Masses

  • Benign Neoplasm
    • Pleomorphic adenoma (benign mixed tumor)
    • Warthin tumor (papillary cystadenoma lymphomatosum)
    • Basal cell adenoma
    • Canalicular cell adenoma
    • Oncocytoma
    • Oncocytic papillary cystadenoma
    • Myoepithelioma
    • Sialadenoma papilliferum
    • Inverted ductal papilloma
    • Lipoma
    • Hemangioma
    • Lymphangioma
    • Mucocele
    • Ranula
  • Malignant Neoplasm
    • Mucoepidermoid carcinoma
    • Adenoid cystic carcinoma
    • Acinic cell carcinoma
    • Polymorphous low-grade adenocarcinoma
    • Squamous cell carcinoma
    • Adenocarcinoma, not otherwise specified
    • Carcinoma ex-pleomorphic adenoma
    • Salivary duct carcinoma
    • Small cell carcinoma
    • Lymphoma
    • Metastasis from non-salivary gland primary
    • Myoepithelial carcinoma
  • Inflammatory/Infectious Conditions
    • Sialadenitis
    • Sialadenosis
    • Sialolithiasis
    • Parotitis (mumps)
    • HIV-associated lymphoepithelial cyst
    • Tuberculosis
    • Sjögren syndrome
    • Cat scratch disease (Bartonella henselae infection)



Important information to elicit when taking the patient history includes the rate of tumor growth, associated symptoms such as skin change, pain, facial paralysis, history of radiation exposure, and prior malignancy (e.g., of the facial skin or scalp, as these may metastasize to the parotid).

Physical Examination

The physical examination should note the size, consistency, location, depth, and mobility of the mass, as well as whether it is tender or inflamed. Benign tumors tend to be well-defined and mobile, whereas ulceration or fixation to over- or underlying structures is more suggestive of malignancy. Head and neck examination should include intraoral palpation to determine tumor extent. Patients should also be examined for cervical lymphadenopathy, sensory deficits of the head and neck, and cranial nerve dysfunction (particularly facial nerve paresis).


Malignancy must be ruled out in the case of any salivary gland mass. Fine needle aspiration biopsy (FNAB) is a safe, minimally invasive, and well-tolerated diagnostic tool with 85% sensitivity and almost 99% specificity rates. False negative results from FNAB are most common in cases of low-grade malignancy. Although FNAB can provide useful information about whether a tumor is benign or malignant, some tumor types cannot be definitively diagnosed based on needle aspiration alone. Additionally, surgical resection is indicated for almost all benign and malignant salivary gland tumors when possible; therefore, FNAB is most useful for operative planning (e.g., whether to consider a superficial or total parotidectomy, or neck dissection).

Imaging Studies

Radiographic imaging is also useful in determining the extent of tumor involvement, and thus the extent of planned resection. Magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET) can be used for radiographic staging depending on the pathology and initial clinical stage. MRI provides superior soft tissue detail and can reveal perineural spread, which may require a mastoidectomy to clear facial nerve margins.

CT scan of Left pleomorphic adenoma of parotid gland

Left pleomorphic adenoma of parotid gland




The American Joint Committee on Cancer (AJCC) has published the Tumor, Node, Metastasis or TNM staging system for major salivary glands. Below is the 7th edition published in the National Comprehensive Cancer Network Guidelines from February 2014.

AJCC TNM Staging System for Major Salivary Glands

Primary Tumor (T)Regional Lymph Nodes (N)Distant Metastasis (M) 
Tx: cannot assessNx: cannot assess
T0: No evidence of tumorN0: No regional lymph node metastasisM0: No distant metastasis
T1: ≤ 2 cm without extraparenchymal extensionN1: single, ipsilateral lymph node of ≤ 3 cmM1: Distant metastasis
T2: > 2 cm but ≤ 4 cm without extraparenchymal extensionN2a: single, ipsilateral lymph node > 3 cm but ≤ 6 cm
T3: > 4 cm and/or extraparenchymal extensionN2b: multiple, ipsilateral lymph nodes that are > 3 cm but ≤ 6 cm
T4a: Invades skin, mandible, ear canal, and/or facial nerveN2c: contralateral and/or bilateral lymph nodes that are > 3 cm but ≤ 6 cm
T4b: Invades skull base and/or pterygoid plates and/or encases carotid arteryN3: any lymph node > 6 cm
Stage IT1N0M0
Stage IIT2N0M0
Stage III≤ T3≤ N1M0
Stage IVA≤ T4a≤ N2M0
Stage IVBT4b or Any T≤ N3M0
Stage IVCAny TAny NM1


In the vast majority of cases, surgical resection is recommended for salivary gland neoplasms. Exceptions include lymphoma, pediatric hemangioma, and benign or less aggressive malignancies in elderly patients who may have difficulty tolerating general anesthesia. Benign parotid tumors are treated by complete excision with adequate margin. For small tumors of the superficial lobe of the parotid, a superficial parotidectomy may be performed. Tumors involving the deep lobe of the parotid require a total parotidectomy. See Chapter 57 for details regarding these procedures. Benign tumors of the submandibular glands are treated by submandibular gland excision. Enucleation of benign tumors should be avoided to reduce the risk of tumor recurrence. This is particularly true for pleomorphic adenoma. Recurrent pleomorphic adenoma after superficial parotidectomy is treated with total parotidectomy, although the risk to the facial nerve is greater with revision surgery.

Malignancies of the parotid gland are treated with total parotidectomy. Malignancies of the submandibular gland or sublingual gland are treated with excision (see Chapter 58 for details). The presence of clinically or radiographically detectable regional nodal metastasis warrants an ipsilateral modified radical neck dissection at the time of resection. Treatment of the N0 neck is controversial; the consensus view is that the neck should be addressed, either by neck dissection or with radiotherapy, if the tumor has a high propensity for regional metastasis. Occult nodal metastasis has been shown to be more common in non-parotid primaries, tumors larger than 4 cm, tumors with extraglandular extension, and tumors with high-grade histology (high-grade mucoepidermoid carcinoma, squamous cell carcinoma, adenocarcinoma, carcinoma ex-pleomorphic adenoma, salivary duct carcinoma, and undifferentiated carcinoma).

In addition to surgical resection, adjuvant radiotherapy is indicated with advanced stage, positive resection margins, perineural invasion, and high-grade histology. Because of its tendency toward delayed distant metastasis and perineural spread, adenoid cystic carcinoma may also be treated with adjuvant radiation, even though it is not considered a high-grade tumor.

Chemotherapy may also be added for certain advanced cancer or recurrent cancers.

Complications, Prognosis and Follow-Up:

The complications of parotidectomy include facial nerve injury, numbness in the distribution of the great auricular nerve, salivary fistula, seroma, hematoma, sialocele, wound breakdown and Frey’s syndrome. Various operative methods of facial nerve repair exist. If facial paralysis is present post-operatively, appropriate eye care measures must be taken to prevent corneal injury.

Frey’s syndrome, or gustatory sweating, may occur post-operatively in up to 60% of parotidectomy cases. However, only a small proportion of these patients are symptomatic. It is caused by the formation of aberrant connections between parasympathetic nerve fibers that innervated the parotid prior to surgery and sympathetic nerve fibers to sweat glands in the skin of the face. This results in sweat production by the facial skin with chewing.



The prognosis for benign salivary gland tumors is generally good. Pleomorphic adenomas have a low recurrence rate if adequately resected. When they do recur, they are often multifocal and difficult to eradicate; however, revision surgery or radiotherapy may achieve local control.

The prognosis of malignant salivary gland tumors depends on several factors, including the clinical stage of the tumor, the histologic grade of the tumor, presence of perineural invasion, and the age of the patient (age greater than 50 years portends a worse outcome). Overall, the 10-year disease-free survival rate for all salivary gland malignancies is between 50 and 75%. Low-grade tumor types may have a 5-year survival rate as high as 97%, while high-grade tumors have a 5-year survival rate of 25% or lower. Adenoid cystic carcinoma is a special case due to its high rate of delayed distant metastasis, resulting in a 5-year survival rate of 65% but a 15-year survival rate of only 12%. Recently, several molecular markers (e.g., Ki-67) have been found to correlate with poor survival and may be used to predict prognosis.

Key Points

  • The majority of salivary gland neoplasms occur in the superficial parotid gland and 85% of these are benign; tumors of the sublingual and minor salivary glands are more likely to be malignant.
  • Fine needle aspiration biopsy is a sensitive and specific diagnostic tool that aids in distinguishing between benign and malignant lesions.
  • Magnetic resonance imaging is the preferred imaging modality for determining extent of salivary gland tumors
  • Surgical resection is indicated for most salivary gland neoplasms (exceptions include lymphoma and hemangioma).
  • Simple enucleation or incisional biopsies are to be avoided, as recurrence risk is high; adequate surgical margins must be attained, even if the tumor is benign.
  • Adjuvant radiotherapy is indicated for advanced stage salivary malignancies, positive resection margins, presence of perineural or bony invasion, adenoid cystic carcinoma, and tumors with high-grade histology.