Oral cancer pathophysiology: Difference between revisions

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**A fully developed tongue lesion appears as an exophytic bulky lesion that is gray to grayish-red and has a rough, shaggy, or [[Papilloma|papillomatous]] surface.
**A fully developed tongue lesion appears as an exophytic bulky lesion that is gray to grayish-red and has a rough, shaggy, or [[Papilloma|papillomatous]] surface.
[[File:PLoS oral cancer.png|300px|center|thumb|Gross pathology of oral SCC, source: By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632]]
[[File:PLoS oral cancer.png|300px|center|thumb|Gross pathology of oral SCC, source: By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632]]
===Microscopic Pathology===
*Microscopically, tongue cancers are broadly based and invasive through [[papillary]] fronds.
*Tongue 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:<ref name="pmid23015393">{{cite journal| author=Peterson BR, Nelson BL| title=Nonkeratinizing undifferentiated nasopharyngeal carcinoma. | journal=Head Neck Pathol | year= 2013 | volume= 7 | issue= 1 | pages= 73-5 | pmid=23015393 | doi=10.1007/s12105-012-0401-4 | pmc=3597164 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23015393  }}</ref>
**[[Keratinized|Keratinizing]] type: Worst prognosis.
**Undifferentiated type: Intermediate prognosis, [[Epstein Barr virus|EBV]] association.<ref name="pmid7778675">{{cite journal| author=Pathmanathan R, Prasad U, Chandrika G, Sadler R, Flynn K, Raab-Traub N| title=Undifferentiated, nonkeratinizing, and squamous cell carcinoma of the nasopharynx. Variants of Epstein-Barr virus-infected neoplasia. | journal=Am J Pathol | year= 1995 | volume= 146 | issue= 6 | pages= 1355-67 | pmid=7778675 | doi= | pmc=1870892 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7778675  }}</ref>
**Nonkeratinizing type: Good prognosis, [[Epstein Barr virus|EBV]] association.
[[File:Oral cancer (1) squamous cell carcinoma histopathology.jpg|300px|center|thumb|Microscopic picture of oral SCC, source: By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=486166]]


==References==
==References==

Revision as of 22:21, 8 February 2018

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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

  • 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.

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.
  • 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.

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.
Gross pathology of oral SCC, source: By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632

Microscopic Pathology

  • Microscopically, tongue cancers are broadly based and invasive through papillary fronds.
  • Tongue 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.
Microscopic picture of oral SCC, source: By No machine-readable author provided. KGH assumed (based on copyright claims). - No machine-readable source provided. Own work assumed (based on copyright claims)., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=486166

References

  1. 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.
  2. 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.
  3. 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.


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