Oral cancer pathophysiology: Difference between revisions
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{{Oral cancer}} | {{Oral cancer}} | ||
{{CMG}};{{AE}}{{SSW}};{{ | {{CMG}}; {{AE}} {{SSW}}, {{Simrat}}; {{GRR}} {{Nat}} | ||
==Overview== | ==Overview== | ||
It is understood that oral cancers occur as a the result of [[carcinogen]]-[[Metabolize|metabolizing]] [[enzymes]], [[alcohol]], [[tobacco]] and [[Genetics|genetic factors]]. [[Cytotoxicity|Cytotoxic]] [[enzymes]] such as [[alcohol dehydrogenase]] result in the production of [[free radicals]] and [[hydroxylation]] of [[DNA]] base units. [[Alcohol dehydrogenase]] oxidizes [[ethanol]] to [[acetaldehyde]] which is [[Cytotoxicity|cytotoxic]] in nature. 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]].The development of oral cancer is the result of multiple [[genetic mutations]]. These [[mutations]] occur in [[Tumor suppressor genes|tumor suppressor genes (TSGs)]] and [[Oncogene|oncogenes]]. [[Squamous cell carcinoma]] is the most common [[malignancy]] of the oral cavity. It typically has three gross morphological growth patterns, which are exophytic, [[Ulcerated lesion|ulcerative]], and infiltrative. [[Microscopic|Microscopically]], oral cancers are broadly based and invasive through [[papillary]] fronds. Oral cancer consists of highly [[Differentiate|differentiated]] [[Squamous cell|squamous cells]] lacking frank [[Cytological|cytologic]] criteria of [[malignancy]] with rare [[Mitosis|mitoses]].The surface of the lesion is covered with compressed invaginating folds of [[keratin]] layers. A stroma-like [[Inflammatory response|inflammatory reaction]] and a blunt pushing margin may be seen. | |||
==Pathophysiology== | ==Pathophysiology== | ||
It is understood that oral cancer occurs as a the result of [[carcinogen]]-[[Metabolize|metabolizing]] [[enzymes]], [[alcohol]], [[tobacco]] and [[Genetics|genetic factors]]. | |||
===Carcinogen-metabolizing enzymes=== | ===Carcinogen-metabolizing enzymes=== | ||
*Carcinogen-metabolizing enzymes are known to cause cancer in some patients. | *[[Carcinogen]]-[[Metabolize|metabolizing]] [[enzymes]] are known to cause [[cancer]] in some patients. | ||
*Cytotoxic enzymes such as alcohol dehydrogenase result in the production of: | *[[Cytotoxicity|Cytotoxic]] [[enzymes]] such as [[alcohol dehydrogenase]] result in the production of: | ||
**Free | **[[Free radicals]] | ||
**DNA hydroxylated bases | **[[DNA]] hydroxylated [[Base (chemistry)|bases]] | ||
*These cytotoxic enzymes | *These [[cytotoxic]] [[enzymes]] dominantly play a key role in the development of oral squamous cell carcinoma. | ||
===Alcohol=== | ===Alcohol=== | ||
*Alcohol dehydrogenase oxidizes ethanol to acetaldehyde which is cytotoxic in nature. | *[[Alcohol dehydrogenase]] oxidizes [[ethanol]] to [[acetaldehyde]], which is [[cytotoxic]] in nature. | ||
* | *[[CYP2E1|Cytochrome P450 IIEI]] ([[CYP2E1]]) also [[Metabolize|metabolizes]] [[ethanol]] to [[acetaldehyde]]. | ||
*Alcohol dehydrogenase type 3 genotype predisposes to oral squamous cell carcinoma. | *[[Alcohol dehydrogenase]] type 3 genotype predisposes to oral squamous cell carcinoma. | ||
*Carcinogenic potential increases when combined with tobacco use. | *[[Carcinogen|Carcinogenic]] potential increases when combined with [[tobacco]] use. | ||
===Tobacco=== | ===Tobacco=== | ||
*Cigarette smoke has various carcinogens which can lead to oral cancers. | *[[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. | *Low reactive [[free radicals]] in [[cigarette smoke]] interact with [[redox]]-active metals in [[saliva]]. | ||
* | *[[saliva]] then looses its [[antioxidant]] potential and becomes a potent pro-oxidant milieu.<ref name="pmid17344667">{{cite journal |vauthors=Nagler R, Dayan D |title=The dual role of saliva in oral carcinogenesis |journal=Oncology |volume=71 |issue=1-2 |pages=10–7 |year=2006 |pmid=17344667 |doi=10.1159/000100445 |url=}}</ref> | ||
==='''Pathology of classical or conventional squamous cell carcinoma'''=== | ==='''Pathology of classical or conventional squamous cell carcinoma'''=== | ||
* Most cancers of the oral cavity are 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 | * This type of SCC starts in the [[squamous epithelium]], which lines the [[oral cavity]] and occurs most often on the [[lower lip]], [[tongue]] and floor of the mouth. | ||
* The microscopic features of classical SCC | * The [[microscopic]] features of classical SCC involve | ||
** | ** Keratin pearls | ||
*** These are circular layers of squamous cells | *** These are circular layers of [[Squamous cell|squamous cells]] that surround [[keratin]] (a tough fibrous [[protein]]). | ||
* | *Cancer starts in the [[Squamous cell|squamous cells]] of the [[epithelium]], and then invades the deeper layers of the [[oral cavity]]. | ||
==='''Pathology | ==='''Pathology of squamous cell carcinoma variants'''=== | ||
* | * The following [[squamous cell carcinomas]] have distinct [[microscopic]] features that make them look and behave differently from classical SCC: | ||
*Verrucous carcinoma | *'''Verrucous carcinoma''' | ||
**These | **These [[tumors]] make up less than 5% of all oral cavity tumors. | ||
**They have a wart-like appearance and develop most often on the gums (gingiva), lining of the cheeks (buccal mucosa) and larynx. | **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. | **Verrucous carcinomas are low grade, slow-growing and rarely spread. | ||
**They are associated with the chronic use of snuff or chewing tobacco. | **They are associated with the chronic use of snuff or chewing [[tobacco]]. | ||
*Basaloid SCC | *'''Basaloid SCC''' | ||
**This is a rare but aggressive | **This is a rare but aggressive sub-type of squamous cell carcinoma. | ||
**It is more common in men older than 60 years. | **It is more common in men older than 60 years old. | ||
*Papillary SCC | *'''Papillary SCC''' | ||
**This is a rare | **This is a rare sub-type of squamous cell carcinoma that grows outward from the surface of the [[epithelium]] (exophytic). | ||
**HPV | **[[Human papillomavirus|HPV]] infections may have a role in the development of this type of cancer. | ||
*Spindle cell carcinoma (SpCC) | *'''Spindle cell carcinoma (SpCC)''' | ||
**This is an aggressive, rare variant of squamous cell carcinoma. | **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. | **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. | **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 | *'''Acantholytic SCC''' | ||
**This results in microscopic spaces in the | **This is a rare variant of SCC in which the connections between the [[malignant]] [[Squamous cell|squamous cells]] are broken down. | ||
*Adenosquamous carcinoma | **This results in [[microscopic]] spaces in the tumor tissue, which appear like [[glands]] or [[vascular]] spaces. | ||
*'''Adenosquamous carcinoma''' | |||
**This is a very rare, aggressive type of squamous cell carcinoma. | **This is a very rare, aggressive type of squamous cell carcinoma. | ||
**It looks like classical squamous cell carcinoma | **It looks like classical squamous cell carcinoma but also has [[mucus]]-producing [[gland]] cells. | ||
*Lymphoepithelial carcinoma | *'''Lymphoepithelial carcinoma''' | ||
**This is a rare | **This is a rare sub-type of squamous cell carcinoma. | ||
**The microscopic appearance is similar to undifferentiated nasopharyngeal carcinoma. | **The [[microscopic]] appearance is similar to undifferentiated [[nasopharyngeal carcinoma]]. | ||
**It is also | **It is also known as [[undifferentiated]] carcinoma. | ||
== Genetics == | |||
* The development of oral cancer is the result of multiple [[genetic mutations]]. | |||
* These [[mutations]] include: | |||
** [[Tumor suppressor genes]] (TSGs) | |||
** [[Oncogenes]] | |||
===Gross | ====Tumor suppressor genes (TSGs)==== | ||
* [[Squamous cell carcinoma]] is | *Oral cavity cancer may be the result of an [[Allele|allelic]] imbalance, which is caused by [[chromosomal]] changes- particularly in [[chromosome]] 3, 9, 11 and 17. | ||
* It typically has three gross | *These changes lead to [[mutation]] in [[tumor suppressor genes]] ([[Tumor suppressor genes|TSGs]]). | ||
* The infiltrative and [[Ulceral|ulcerative]] are the | *In non-cancerous situations, [[Tumor suppressor genes|TSGs]] modulate normal growth. | ||
* The macroscopic appearance of | *Mutation of these [[Tumor suppressor genes|TSGs]] lead to dysfunctional growth control. | ||
*Mutation most commonly occurs in one of the following: | |||
**Short arm of [[Chromosome 3 (human)|chromosome 3]] | |||
**TSG termed ''[[P16 (gene)|P16]]'' on [[chromosome 9]] | |||
**TSG termed ''[[TP53]]'' on [[chromosome 17]] | |||
*The [[Cytochrome P450]] [[genotype]] is related to [[mutations]] in some [[Tumor suppressor genes|TSGs]] and leads to oral squamous cell carcinoma. | |||
*In western countries (eg. United Kingdom, United States, or Australia), ''[[TP53]]'' [[Mutation|mutations]] are the most common molecular change that leads to oral [[squamous cell carcinoma]]. | |||
====Oncogenes==== | |||
*Cancer may also occur if there is mutation in other [[genes]] that control [[cell growth]], typically [[oncogenes]]. | |||
*[[Oncogenes]] most commonly involved are: | |||
**[[Chromosome 11]] (''PRAD1)'' | |||
**[[Chromosome 17]] (Harvey ras [H-''ras'']) | |||
*In eastern countries (eg. India or Southeast Asia), ''[[Ras gene|ras]]'' [[oncogenes]] is a more common cause of oral squamous cell carcinoma. | |||
==Gross Pathology== | |||
* [[Squamous cell carcinoma]] is the most common [[Bone or cartilage mass|malignancy]] of the oral cavity. | |||
* It typically has three gross morphological growth patterns, which are exophytic, [[Ulcerated lesion|ulcerative]], and infiltrative. | |||
* The infiltrative and [[Ulceral|ulcerative]] are the growth patterns most commonly observed in the oral cavity. | |||
* The [[macroscopic]] appearance of oral cancer depends on the following: | |||
**Duration of the [[lesion]] | **Duration of the [[lesion]] | ||
**The amount of [[keratinization]] | **The amount of [[keratinization]] | ||
**The changes in the adjoining [[Mucosal|mucosa]] | **The changes in the adjoining [[Mucosal|mucosa]] | ||
**A fully developed | **A fully developed oral cavity 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== | |||
*[[Microscopic|Microscopically]], oral cancers are broadly based and invasive through [[papillary]] fronds. | |||
*Oral cancer constitutes of highly-[[Differentiate|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 and [[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> | |||
**Non-keratinizing type: Good [[prognosis]] and [[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== | ||
Latest revision as of 12:49, 11 April 2019
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Oral cancer Microchapters |
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Oral cancer pathophysiology On the Web |
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Risk calculators and risk factors for Oral cancer pathophysiology |
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]; Grammar Reviewer: Natalie Harpenau, B.S.[4]
Overview
It is understood that oral cancers occur as a the result of carcinogen-metabolizing enzymes, alcohol, tobacco and genetic factors. Cytotoxic enzymes such as alcohol dehydrogenase result in the production of free radicals and hydroxylation of DNA base units. Alcohol dehydrogenase oxidizes ethanol to acetaldehyde which is cytotoxic in nature. 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.The development of oral cancer is the result of multiple genetic mutations. These mutations occur in tumor suppressor genes (TSGs) and oncogenes. Squamous cell carcinoma is the most common malignancy of the oral cavity. It typically has three gross morphological growth patterns, which are exophytic, ulcerative, and infiltrative. Microscopically, oral cancers are broadly based and invasive through papillary fronds. Oral cancer consists 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.
Pathophysiology
It is understood that oral cancer occurs as a the result of carcinogen-metabolizing enzymes, alcohol, tobacco and genetic factors.
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 radicals
- DNA hydroxylated bases
- These cytotoxic enzymes dominantly play a key role in the development of 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.
- saliva then looses its antioxidant potential and becomes 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, which lines the oral cavity and occurs most often on the lower lip, tongue and floor of the mouth.
- The microscopic features of classical SCC involve
- Keratin pearls
- These are circular layers of squamous cells that surround keratin (a tough fibrous protein).
- Keratin pearls
- Cancer starts in the squamous cells of the epithelium, and then invades the deeper layers of the oral cavity.
Pathology of squamous cell carcinoma variants
- The following squamous cell carcinomas have distinct microscopic features that make them look and behave differently from classical SCC:
- Verrucous carcinoma
- These tumors make up less than 5% of all oral cavity tumors.
- 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 sub-type of squamous cell carcinoma.
- It is more common in men older than 60 years old.
- Papillary SCC
- This is a rare sub-type of squamous cell carcinoma that grows outward from the surface of the epithelium (exophytic).
- HPV infections 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 are broken down.
- This results in microscopic spaces in the tumor tissue, which appear like glands or vascular spaces.
- Adenosquamous carcinoma
- Lymphoepithelial carcinoma
- This is a rare sub-type of squamous cell carcinoma.
- The microscopic appearance is similar to undifferentiated nasopharyngeal carcinoma.
- It is also known as undifferentiated carcinoma.
Genetics
- The development of oral cancer is the result of multiple genetic mutations.
- These mutations include:
- Tumor suppressor genes (TSGs)
- Oncogenes
Tumor suppressor genes (TSGs)
- Oral cavity cancer may be the result of an 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).
- In non-cancerous situations, TSGs modulate normal growth.
- Mutation of these TSGs lead to dysfunctional growth control.
- Mutation most commonly occurs in one of the following:
- Short arm of chromosome 3
- TSG termed P16 on chromosome 9
- TSG termed TP53 on chromosome 17
- The Cytochrome P450 genotype is related to mutations in some TSGs and leads to oral squamous cell carcinoma.
- In western countries (eg. United Kingdom, United States, or 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 in other genes that control cell growth, typically oncogenes.
- Oncogenes most commonly involved are:
- Chromosome 11 (PRAD1)
- Chromosome 17 (Harvey ras [H-ras])
- In eastern countries (eg. India or 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 morphological growth patterns, which are exophytic, ulcerative, and infiltrative.
- The infiltrative and ulcerative are the growth patterns most commonly observed in the oral cavity.
- The macroscopic appearance of oral cancer depends on the following:
- Duration of the lesion
- The amount of keratinization
- The changes in the adjoining mucosa
- A fully developed oral cavity 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]
_squamous_cell_carcinoma_histopathology.jpg)
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.