Over 50% of salivary gland neoplasms are benign, and approximately 70% to 80% of all salivary gland neoplasms originate in the parotid gland. The palate is the most common site of minor salivary gland tumors. The frequency of malignant lesions varies by site. Approximately 20% to 25% of parotid tumors, 35% to 40% of submandibular tumors, 50% of palate tumors, and over 90% of sublingual gland tumors are malignant.

Histologically, salivary gland tumors represent the most heterogeneous group of tumors of any tissue in the body. Although there are almost 40 histologic types of epithelial tumors of the salivary glands, some are exceedingly rare and may be the subject of only a few case reports. The most common benign major and minor salivary gland tumor is the pleomorphic adenoma, which comprises about half of all salivary gland tumors and 65% of parotid gland tumors. The most common malignant major and minor salivary gland tumor is the mucoepidermoid carcinoma, which comprises about 10% of all salivary gland neoplasms and approximately 35% of malignant salivary gland neoplasms. This neoplasm occurs most often in the parotid gland.

Cellular Classification

Salivary gland neoplasms are remarkable for their histologic diversity. These neoplasms include benign and malignant tumors of epithelial, mesenchymal, and lymphoid origin. Salivary gland tumors pose a particular challenge to the surgical pathologist primarily because of the complexity of the classification and the rarity of several entities, which may exhibit a broad spectrum of morphologic diversity in individual lesions, thus making differentiating benign from malignant tumors difficult. In some cases, hybrid lesions may be seen. The key guiding principle in establishing the malignant nature of a salivary gland tumor is the demonstration of an infiltrative margin.

The following cellular classification scheme draws heavily from a scheme published by the Armed Forces Institute of Pathology (AFIP). Malignant nonepithelial neoplasms are included because these neoplasms comprise a significant proportion of salivary gland neoplasms seen in the clinic. For completeness, malignant secondary tumors are also included.

It should be noted that where AFIP statistics regarding the incidence (or relative frequency) of particular histopathologies are cited, some bias may exist due to the AFIP’s methods of case accrual as a pathology reference service. When possible, other sources are cited for incidence data. However, notwithstanding the AFIP data, the incidence of a particular histopathology has been found to vary considerably depending upon the study cited. This variability in reporting may be due in part to the rare incidence of many salivary gland neoplasms.

Epithelial neoplasms

The clinician should be aware that several benign epithelial salivary gland neoplasms have malignant counterparts, shown below:

• Pleomorphic adenoma (mixed tumor) (see carcinoma ex pleomorphic adenoma).
• Warthin’s tumor (papillary cystadenoma lymphomatosum).
• Monomorphic adenomas:
  • Basal cell adenoma (see basal cell adenocarcinoma).
  • Canalicular adenoma.
  • Oncocytoma (see oncocytic carcinoma).
  • Sebaceous adenoma.
  • Sebaceous lymphadenoma (see sebaceous lymphadenocarcinoma).
• Myoepithelioma (see myoepithelial carcinoma).
• Cystadenoma (see cystadenocarcinoma).
• Ductal papillomas.
• Sialoblastoma.

Histologic grading of salivary gland carcinomas is important in determining the proper treatment approach, although it is not an independent indicator of the clinical course and must be considered in the context of the clinical stage. Clinical stage, particularly tumor size, may be the critical factor in determining the outcome of salivary gland cancer, and may be more important than histologic grade. For example, stage I intermediate- or high-grade mucoepidermoid carcinomas can be successfully treated, whereas low-grade mucoepidermoid carcinomas that present as stage III disease may have a very aggressive clinical course.

Grading is used primarily for mucoepidermoid carcinoma, adenocarcinoma, not otherwise specified (NOS), adenoid cystic carcinoma, and squamous cell carcinoma.Various other salivary gland carcinomas can also be categorized according to histologic grade as follows:

Low-grade

• Acinic cell carcinoma.
• Basal cell adenocarcinoma.
• Clear cell carcinoma.
• Cystadenocarcinoma.
• Epithelial-myoepithelial carcinoma.
• Mucinous adenocarcinoma.
• Polymorphous low-grade adenocarcinoma.

Low-grade, intermediate-grade, and high-grade

• Adenocarcinoma, NOS.
• Mucoepidermoid carcinoma*.
• Squamous cell carcinoma.

Intermediate-grade and high-grade

• Myoepithelial carcinoma.

High-grade

• Anaplastic small cell carcinoma.
• Carcinosarcoma.
• Large cell undifferentiated carcinoma.
• Small cell undifferentiated carcinoma.
• Salivary duct carcinoma.

* [Note: Some investigators consider mucoepidermoid carcinoma to be of only 2 grades: low-grade and high-grade.]