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) tumors 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 tumor.
• Non-keratinized SCC has very little or no keratin in the tumor.
• 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 tumors 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 tumor and Lane tumor.

• 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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