Oral cancer pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2];Simrat Sarai, M.D. [3]
Overview
Pathophysiology
Carcinogen-metabolizing enzymes
- Carcinogen-metabolizing enzymes are known to cause cancer in some patients.
- Cytotoxic enzymes such as alcohol dehydrogenase result in the production of:
- Free radicles
- DNA hydroxylated bases
- These cytotoxic enzymes especially predispose oral squamous cell carcinoma.
Alcohol
- Alcohol dehydrogenase oxidizes ethanol to acetaldehyde which is cytotoxic in nature.
- cytochrome P450 IIEI (CYP2E1) also metabolizes ethanol to acetaldehyde.
- Alcohol dehydrogenase type 3 genotype predisposes to oral squamous cell carcinoma.
- Carcinogenic potential increases when combined with tobacco use.
Tobacco
- Cigarette smoke has various carcinogens which can lead to oral cancers.
- Low reactive free radicals in cigarette smoke interact with redox-active metals in saliva.
- This makes saliva to loose its antioxidant potential and become a potent pro-oxidant milieu.[1]
Pathology of classical or conventional squamous cell carcinoma
- 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.
- Epithelial pearls
- The cancer starts in the squamous cells of the epithelium and invades the deeper layers of the oral cavity.
Pathology of variants of squamous cell carcinoma
- 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.
Genetics
- It is understood that oral cavity carcinoma is the result of dysfunction of either :
Tumor suppressor genes (TSGs)
- Oral cavity cancer may be the result of allelic imbalance which is caused by chromosomal changes particularly in chromosome 3,9,11 and 17.
- These changes lead to mutation in tumor suppressor genes (TSGs).
- Normally TSGs modulate normal growth.
- Mutation of these TSGs leads to dysfunctional growth control.
- Mutation most commonly occurs in either of the following:
- Short arm of chromosome 3
- TSG termed P16 on chromosome 9
- TSG termed TP53 on chromosome 17
- Cytochrome P450 genotypes is related to mutations in some TSGs and lead to oral squamous cell carcinoma.
- In western countries (eg, United Kingdom, United States, Australia) TP53 mutations are the most common molecular change that leads to oral squamous cell carcinoma.
Oncogenes
- Cancer may also occur if there is mutation to other genes that control cell growth, mainly oncogenes.
- Oncogenes most commonly involved are:
- Chromosome 11 (PRAD1)
- Chromosome 17 (Harvey ras [H-ras])
- In eastern countries (eg, India, Southeast Asia), ras oncogenes is a more common cause of oral squamous cell carcinoma.
Gross Pathology
- Squamous cell carcinoma is the most common malignancy of the oral cavity.
- It typically has three gross morphologic growth patterns: exophytic, ulcerative, and infiltrative.
- The infiltrative and ulcerative are the types most commonly observed on the tongue.
- The macroscopic appearance of tongue cancer depends on the following:
- Duration of the lesion
- The amount of keratinization
- The changes in the adjoining mucosa
- A fully developed tongue lesion appears as an exophytic bulky lesion that is gray to grayish-red and has a rough, shaggy, or papillomatous surface.
Microscopic Pathology
- Microscopically, oral cancers are broadly based and invasive through papillary fronds.
- Oral cancer constitutes of highly differentiated squamous cells lacking frank cytologic criteria of malignancy with rare mitoses.
- The surface of the lesion is covered with compressed invaginating folds of keratin layers. A stroma-like inflammatory reaction and a blunt pushing margin may be seen.
- SCC is subdivided by the WHO into:[2]
- Keratinizing type: Worst prognosis.
- Undifferentiated type: Intermediate prognosis, EBV association.[3]
- Nonkeratinizing type: Good prognosis, EBV association.
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References
- ↑ Nagler R, Dayan D (2006). "The dual role of saliva in oral carcinogenesis". Oncology. 71 (1–2): 10–7. doi:10.1159/000100445. PMID 17344667.
- ↑ Peterson BR, Nelson BL (2013). "Nonkeratinizing undifferentiated nasopharyngeal carcinoma". Head Neck Pathol. 7 (1): 73–5. doi:10.1007/s12105-012-0401-4. PMC 3597164. PMID 23015393.
- ↑ Pathmanathan R, Prasad U, Chandrika G, Sadler R, Flynn K, Raab-Traub N (1995). "Undifferentiated, nonkeratinizing, and squamous cell carcinoma of the nasopharynx. Variants of Epstein-Barr virus-infected neoplasia". Am J Pathol. 146 (6): 1355–67. PMC 1870892. PMID 7778675.