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[edit | edit source]

The pathophysiology of salivary gland tumors depends on the histological subtype.[1]

## Pathophysiology[edit | edit source]

### Pathogenesis[edit | edit source]

The parotid gland is the most frequent site of salivary gland tumors which accounts for approximately 80 to 85 percent of these tumors.[2][3] About 75 percent of parotid lesions are benign and approximately 25 percent are malignant.[4] 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.[5]

* 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.[6]

### Microscopic Pathology[edit | edit source]

* 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[edit | edit source]

Tabular form - adapted from Libre Pathology[1]

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[edit | edit source]

Tabular form - adapted from Libre Pathology[1]

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[edit | edit source]

* 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.[7] 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.

## References[edit | edit source]

1. ↑ 1.0 1.1 1.2 Salivary glands. Libre pathology(2015) http://librepathology.org/wiki/index.php/Salivary_glands Accessed on November 11, 2015
2. ↑ Barnes, Leon. Pathology and genetics of head and neck tumours. Lyon: IARC Press, 2005. Print.
3. ↑ Marco Guzzo, Laura D. Locati, Franz J. Prott, Gemma Gatta, Mark McGurk & Lisa Licitra (2010). "Major and minor salivary gland tumors". Critical reviews in oncology/hematology. 74 (2): 134–148. doi:10.1016/j.critrevonc.2009.10.004. PMID 019939701. Unknown parameter `|month=` ignored (help)CS1 maint: Multiple names: authors list (link)
4. ↑ R. H. Spiro (1986). "Salivary neoplasms: overview of a 35-year experience with 2,807 patients". Head & neck surgery. 8 (3): 177–184. PMID 03744850. Unknown parameter `|month=` ignored (help)
5. ↑ Marco Guzzo, Laura D. Locati, Franz J. Prott, Gemma Gatta, Mark McGurk & Lisa Licitra (2010). "Major and minor salivary gland tumors". Critical reviews in oncology/hematology. 74 (2): 134–148. doi:10.1016/j.critrevonc.2009.10.004. PMID 019939701. Unknown parameter `|month=` ignored (help)CS1 maint: Multiple names: authors list (link)
6. ↑ Salivary gland tumors. Radiopedia(2015) http://radiopaedia.org/articles/salivary-gland-tumours Accessed on November 8, 2015
7. ↑ Grades of salivary gland cancer. Canadian cancer society(2015) http://www.cancer.ca/en/cancer-information/cancer-type/salivary-gland/grading/?region=sk Accessed on November 8, 2015

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