Salivary gland tumor pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

The pathophysiology of salivary gland tumors depends on the histological subtype.

Pathophysiology

Pathogenesis

The parotid gland is the most frequent site of salivary gland tumors which accounts for approximately 80 to 85 percent of these tumors. About 75 percent of parotid lesions are benign and approximately 25 percent are malignant. Less frequently, salivary gland tumors originate in the sublingual, submandibular, and minor salivary glands, which are located throughout the submucosa of the upper aerodigestive tract and mouth.

• In comparison to tumors arising in the parotid, 70 to 90 percent of sublingual gland tumors, 50 to 75 percent of minor salivary gland tumors, and 40 to 45 percent of submandibular gland tumors are malignant. Approximately 85% of salivary gland tumors occur in the parotid glands, followed by the minor salivary glands and submandibular, and approximately 1% occur in the sublingual glands. Overall approximately 80% of all parotid masses are benign.

Microscopic Pathology

• Histologically, pleomorphic adenoma is the most common type of benign salivary gland tumor, which comprises about half of all salivary tumors. Other rarer benign salivary gland tumors include basal cell adenoma, Warthin's tumor, and canalicular adenoma. The most common malignant salivary gland tumors are adenoid cystic carcinoma and mucoepidermoid carcinoma, which together constitute approximately one-half of all malignant salivary gland tumors.

Histological features of benign tumors

Tabular form - adapted from Libre Pathology

Entity	Architecture	Morphology	Cell borders	Cytoplasm	Nucleus	Other
Pleomorphic adenoma	Variable	Mixed proportion; must include: Myoepithelium Mesenchymal stroma Epithelium (ductal cells) or Chondromyxoid stroma	Variable	Variable	Plasmacytoid	Occasionally encapsulated, mixed proportion of glandular, myoepithelial and mesenchymal cells
Warthin tumor	Papillary, bilayer	Cuboid (basal), columnar (apical)	Clearly seen	Eosinophilic, abundant	Unremarkable	AKA papillary cystadenoma lymphomatosum
Basal cell adenoma	Variable, islands surrounded by hyaline bands, lesion encapsulated	Basaloid	Subtle	Scant, hyperchromatic	Granular
Canalicular adenoma	Chains of cells	Cuboid or columnar	Subtle	Scant, hyperchromatic	Granular	Exclusively oral cavity, 80% in upper lip; immunohistochemistry: p63-
Sialoblastoma	Variable, islands surrounded by loose fibrous stroma	Basaloid	Subtle	Scant, hyperchromatic	Granular	Basal cell adenocarcinoma

Histological features of malignant tumors

Tabular form - adapted from Libre Pathology

Entity	Architecture	Morphology	Cell borders	Cytoplasm	Nucleus	Other
Mucoepidermoid carcinoma	Cystic and solid	Epitheloid	Distinct	Fuffy, clear, abundant	Nuclei small	Immunohistochemistry: p63+
Adenoid cystic carcinoma (AdCC)	Pseudocysts, cribriform, solid, hyaline stroma	Epitheloid	Subtle	Scant, hyperchromatic	Small+/-"carrot-shaped"	Stains: PAS+ (pseudocyst material), CD117+, cyclin D1+
Acinic cell carcinoma (AcCC)	Sheets, acinar (islands)	Epithelioid	Clear	Granular abundant	Stippled, +/-occasional nucleoli	Stains: PAS +ve, PAS-D +ve; Immunohistochemistry: S-100 -ve, p63 -ve
Salivary duct carcinoma	Glandular, cribriform	Columnar	Subtle/clear	Hyperchromatic	Columnar	Similar to ductal breast carcinoma; male>female
Polymorphous low-grade adenocarcinoma	Variable, often small nests, may be targetoid	Epithelioid	Indistinct	Eosinophilic	Ovoid & small with small nucleoli	Minor salivary gland tumour, often in palate, cytologically monotonous; IHC: S-100+, CK+, vim.+, GFAP+/-, BCL2+/-
Epithelial-myoepithelial carcinoma	Nests (myoepithelial) with tubules (epithelial)	Epithelioid	Not distinct	Eosinophilic cytoplasm; epithelial: scant; myoepithelial: moderate	Focal clearing	Rare
Basal cell adenocarcinoma	Variable, islands surrounded by hyaline bands, lesion not encapsulated	Basaloid	Subtle	Scant, hyperchromatic	Granular	Rare, usually parotid gland, may arise from a basal cell adenoma

Tumor grades of salivary gland cancer

• Grading is a way of classifying salivary cancer cells based on their appearance and behavior when viewed under a microscope. To find out the grade of a tumor, the biopsy sample is examined under a microscope. A grade is given based on how the cancer cells look and behave compared with normal cells (differentiation). This can give the healthcare team an idea of how quickly the cancer may be growing and how likely it is to spread. The grade of salivary gland cancer is based on the degree of differentiation of cells and their rate of growth.

Grade	Description
low	Well differentiated – slow growing, less likely to spread
Intermediate	Moderately well-differentiated
High	poorly differentiated – tend to grow quickly, more likely to spread

• Grading for salivary gland cancers is used mainly for mucoepidermoid carcinomas, adenocarcinomas, adenocarcinoma NOS, squamous cell carcinomas and adenoid cystic carcinomas. Other salivary gland cancers can also be graded in the same way. Grading plays an important part in planning salivary gland cancer treatment and can also be used to help estimate the prognosis. However, the grade is not the only factor used to predict the future outcome.
• It must be considered together with staging information. Staging, in particular tumor size, is an important prognostic factor and may be more important than the grade in terms of successful treatment. For example, sometimes a stage I, intermediate or high-grade tumor can be treated with more success than a low-grade tumor that is a stage III.

Low grade	Low, intermediate or high grade	High grade
Acinic cell carcinoma	Adenocarcinoma not otherwise specified (NOS)	Adenoid cystic carcinoma*
Basal cell adenocarcinoma	Mucoepidermoid carcinoma	Anaplastic small cell carcinoma
Clear cell carcinoma	Squamous cell carcinoma	Carcinosarcoma
Cystadenocarcinoma		Small and large cell undifferentiated carcinoma
Epithelia-myoepithelial carcinoma		Salivary duct carcinoma
Mucinous adenocarcinoma		Carcinoma ex pleomorphic adenoma
Polymorphous low-grade adenocarcinoma (PLGA)

• *Some adenoid cystic carcinomas can also be intermediate grade.