Oral cancer 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

Genes involved in the pathogenesis of oral cancer include tumor suppressor genes (TSGs), particularly in chromosomes 3, 9, 11, and 17.

Pathophysiology

The pathophysiology of oral cancer involves inactivated tumor suppressor genes, P16, and TP53 and overexpressed oncogenes, PRAD1.The molecular changes in oral squamous cell carcinoma in western countries (eg, United Kingdom, United States, Australia), are particularly TP53 mutations. These mutations are infrequent in eastern countries (eg, India, Southeast Asia), where the involvement of ras oncogenes is more common.

Pathology of squamous cell carcinoma of oral cavity

• Squamous cell carcinoma (SCC) tumours make up 95% of all oral cavity cancers. They are classified based on macroscopic or microscopic features.

Macroscopic features of squamous cell carcinoma are:

• Infiltrative – Cancer is growing into the deeper layers of the oral cavity.
• Exophytic – Cancer is growing outwards from the surface of the oral cavity.
• Verrucous – Cancer has a wart-like appearance.
• Ulcerated – Cancer appears as an open sore.
• Flat – Cancer appears as an abnormal area in the lining of the oral cavity.

• Microscopic features can be seen only with a microscope:

• Type of cells.
• Differentiation: The cancerous cells may be well differentiated (look like normal cells), moderately differentiated or poorly differentiated (do not look or act like normal cells).
• Keratinization: Keratin is a protein found in the hair, skin and some mucous membranes. It makes tissue tough.

• • Keratinized SCC has more keratin in the tumour.
  • Non-keratinized SCC has very little or no keratin in the tumour.
  • Well-differentiated SCC is usually keratinized, while poorly differentiated SCC is non-keratinized.
• Invasion of the cancer into deeper layers and tissues, such as fat and muscle.
• Based on their microscopic features, squamous cell carcinomas are divided into 2 types:

• Classical or conventional SCC
• Variants of SCC

Pathology of classical or conventional SCC

Most cancers of the oral cavity are classical or conventional squamous cell carcinoma. This type of SCC starts in the squamous epithelium that lines the oral cavity and occurs most often on the lower lip, tongue and floor of the mouth. The microscopic features of classical SCC include:

• Epithelial pearls
  • These are circular layers of squamous cells around a collection of keratin (a tough fibrous protein) in the centre.
• Spread of cancer into deeper layers of the oral cavity
  • The cancer starts in the squamous cells of the epithelium and invades the deeper layers of the oral cavity.

Pathology of variants of SCC

These squamous cell carcinomas have distinct microscopic features that make them look and behave differently from classical SCC.

• Verrucous carcinoma
  • These tumours make up less than 5% of all oral cavity tumours.
  • They have a wart-like appearance and develop most often on the gums (gingiva), lining of the cheeks (buccal mucosa) and larynx.
  • Verrucous carcinomas are low grade, slow growing and rarely spread.
  • They are associated with the chronic use of snuff or chewing tobacco.
• Basaloid SCC
  • This is a rare but aggressive subtype of squamous cell carcinoma.
  • It is more common in men older than 60 years.
• Papillary SCC
  • This is a rare subtype of squamous cell carcinoma that grows outward from the surface of the epithelium (exophytic).
  • HPV infection may have a role in the development of this type of cancer.
• Spindle cell carcinoma (SpCC)
  • This is an aggressive, rare variant of squamous cell carcinoma.
  • These tumours contain a mixture of conventional squamous cell carcinoma and spindle cells that resemble a sarcoma.

It is also known as sarcomatoid carcinoma, pseudosarcoma, carcinosarcoma, pleomorphic carcinoma, metaplastic carcinoma, collision tumour and Lane tumour.

• Acantholytic SCC
  • This is a rare variant of SCC in which the connections between the malignant squamous cells break down.
  • This results in microscopic spaces in the tumour tissue, which appear like glands or vascular spaces.
• Adenosquamous carcinoma
  • This is a very rare, aggressive type of squamous cell carcinoma.
  • It looks like classical squamous cell carcinoma, but also has mucus-containing gland cells.
• Lymphoepithelial carcinoma
  • This is a rare subtype of squamous cell carcinoma.
  • The microscopic appearance is similar to undifferentiated nasopharyngeal carcinoma.
  • It is also called undifferentiated carcinoma.

References

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