Laryngeal cancer pathophysiology: Difference between revisions

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__NOTOC__
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{{Laryngeal cancer}}
{{Laryngeal cancer}}
{{CMG}} {{AE}}{{Faizan}}
{{CMG}} {{AE}} {{OK}}, {{Faizan}}
==Overview==
==Overview==
Laryngeal cancer arises from [[squamous cell]]s, which are cells that are normally involved in protection of upper respiratory airways. Genes involved in the pathogenesis of laryngeal cancer include ''[[P16 (gene)|p16]]'', ''[[NOTCH1]]'', ''[[cyclin D1]]'', and ''[[TP53]]''. On gross pathology, flattened plaques, mucosal ulceration, and raised margins of the lesion are characteristic findings of laryngeal cancer. On microscopic histopathological analysis, [[spindle cell]]s, basaloid cells, and nuclear atypia are characteristic findings of laryngeal cancer.
[[Laryngeal cancer]] arises from [[squamous cell]]s, which are [[cells]] that are normally involved in protection of upper respiratory airway. [[Genes]] involved in the [[pathogenesis]] of [[laryngeal cancer]] include ''[[P16 (gene)|p16]]'', ''[[NOTCH1]]'', ''[[cyclin D1]]'', and ''[[TP53]]''. On gross [[pathology]], flattened plaques, mucosal [[ulceration]], and raised margins of the [[lesion]] are characteristic findings of [[laryngeal cancer]]. On microscopic [[histopathological]] analysis, [[spindle cell]]s, basaloid cells, and [[nuclear]] [[atypia]] are characteristic findings of [[laryngeal cancer]].


==Pathophysiology==
==Pathophysiology==
Laryngeal cancer arises from [[squamous cell]]s, which are cells that are normally involved in protection of upper respiratory airways.
[[Laryngeal cancer]] arises from [[squamous cell]]s, which are [[cells]] that are normally involved in protection of upper respiratory airways.<ref name="pmid8995133">{{cite journal |vauthors=Koufman JA, Burke AJ |title=The etiology and pathogenesis of laryngeal carcinoma |journal=Otolaryngol. Clin. North Am. |volume=30 |issue=1 |pages=1–19 |date=February 1997 |pmid=8995133 |doi= |url=}}</ref>


==Genetics==
===Genetics===
Development of laryngeal cancer is the result of multiple genetic mutations. These mutations lead to activation of oncogenes and inactivation of tumor suppression genes which ultimately result in deregulated cellular proliferation. Genes involved in the pathogenesis of laryngeal cancer include:
Development of [[laryngeal cancer]] is the result of multiple [[genetic mutations]]. These [[mutations]] lead to activation of [[oncogenes]] and inactivation of [[tumor]] suppression [[genes]] which ultimately result in deregulated [[cellular]] [[proliferation]]. [[Genes]] involved in the [[pathogenesis]] of [[laryngeal cancer]] include:<ref name="pmid26940775">{{cite journal |vauthors=de Miguel-Luken MJ, Chaves-Conde M, Carnero A |title=A genetic view of laryngeal cancer heterogeneity |journal=Cell Cycle |volume=15 |issue=9 |pages=1202–12 |date=May 2016 |pmid=26940775 |pmc=4894505 |doi=10.1080/15384101.2016.1156275 |url=}}</ref>
*''[[P16 (gene)|p16]]''
*''[[P16 (gene)|p16]]''
*''[[NOTCH1]]''
*''[[NOTCH1]]''
Line 15: Line 15:
*''[[TP53]]''
*''[[TP53]]''


==Gross Pathology==
===Gross Pathology===
On gross pathology, laryngeal cancer is characterized by:
On [[gross pathology]], [[laryngeal cancer]] is characterized by:<ref name="pmid933673">{{cite journal |vauthors=Sessions DG |title=Surgical pathology of cancer of the larynx and hypopharynx |journal=Laryngoscope |volume=86 |issue=6 |pages=814–39 |date=June 1976 |pmid=933673 |doi=10.1288/00005537-197606000-00009 |url=}}</ref><ref name="urljournals.sagepub.com">{{cite web |url=http://journals.sagepub.com/doi/pdf/10.1177/0194599816662631 |title=journals.sagepub.com |format= |work= |accessdate=}}</ref>
*Flattened plaques
*Flattened [[plaques]]
*Raised margins of the lesion
*Raised margins of the [[lesion]]
*Mucosal ulceration
*[[Mucosal]] ulceration


<gallery>
===Microscopic Pathology===
Image:Larynx cancer 01.jpg |Gross pathology specimen of laryngeal cancer<ref name=GrossLC1>Media in category Laryngeal cancer. Wikimedia Commons 2015. https://commons.wikimedia.org/wiki/Category:Laryngeal_cancer. Accessed on October 29, 2015</ref>
On microscopic histopathological analysis, laryngeal carcinoma is characterized by:<ref name="pmid22180291">{{cite journal |vauthors=Hilly O, Raz R, Vaisbuch Y, Strenov Y, Segal K, Koren R, Shvero J |title=Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics |journal=Head Neck |volume=34 |issue=11 |pages=1586–90 |date=November 2012 |pmid=22180291 |doi=10.1002/hed.21972 |url=}}</ref><ref name="pmid21719209">{{cite journal |vauthors=Caldas-Magalhaes J, Kasperts N, Kooij N, van den Berg CA, Terhaard CH, Raaijmakers CP, Philippens ME |title=Validation of imaging with pathology in laryngeal cancer: accuracy of the registration methodology |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=82 |issue=2 |pages=e289–98 |date=February 2012 |pmid=21719209 |doi=10.1016/j.ijrobp.2011.05.004 |url=}}</ref><ref name="pmid20286025">{{cite journal |vauthors=MUSTAKALLIO S |title=Relation of microscopic structure of laryngeal cancer to radiocurability |journal=Acta radiol |volume=27 |issue=5 |pages=473–80 |date=August 1946 |pmid=20286025 |doi= |url=}}</ref><ref name="pmid7453440">{{cite journal |vauthors=Franz B, Wetzel M |title=[Cytology of the early invasive laryngeal cancer (author's transl)] |language=German |journal=Laryngol Rhinol Otol (Stuttg) |volume=59 |issue=7 |pages=401–5 |date=July 1980 |pmid=7453440 |doi= |url=}}</ref>
 
</gallery>
 
==Microscopic Pathology==
On microscopic histopathological analysis, laryngeal carcinoma is characterized by:<ref name=abc>Protocol applies to all invasive carcinomas of the larynx, including supraglottis, glottis, and subglottis.http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf. Accessed on: October 28, 2015.</ref>
*[[Spindle cell]]s
*[[Spindle cell]]s
*Basaloid cells
*Basaloid cells
*Nuclear atypia
*[[Nuclear]] [[atypia]]
*Abundant chromatin
*Abundant [[chromatin]]


Squamous cell carcinoma is subdivided histopathologically by the World Health Organization into:<ref name=abc>Protocol applies to all invasive carcinomas of the larynx, including supraglottis, glottis, and subglottis.http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf. Accessed on: October 28, 2015.</ref>
[[Squamous cell carcinoma]] is subdivided histopathologically:<ref name="pmid22180291">{{cite journal |vauthors=Hilly O, Raz R, Vaisbuch Y, Strenov Y, Segal K, Koren R, Shvero J |title=Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics |journal=Head Neck |volume=34 |issue=11 |pages=1586–90 |date=November 2012 |pmid=22180291 |doi=10.1002/hed.21972 |url=}}</ref><ref name="pmid21719209">{{cite journal |vauthors=Caldas-Magalhaes J, Kasperts N, Kooij N, van den Berg CA, Terhaard CH, Raaijmakers CP, Philippens ME |title=Validation of imaging with pathology in laryngeal cancer: accuracy of the registration methodology |journal=Int. J. Radiat. Oncol. Biol. Phys. |volume=82 |issue=2 |pages=e289–98 |date=February 2012 |pmid=21719209 |doi=10.1016/j.ijrobp.2011.05.004 |url=}}</ref><ref name="pmid21165725">{{cite journal |vauthors=Lewis JS |title=Not your usual cancer case: variants of laryngeal squamous cell carcinoma |journal=Head Neck Pathol |volume=5 |issue=1 |pages=23–30 |date=March 2011 |pmid=21165725 |pmc=3037456 |doi=10.1007/s12105-010-0232-0 |url=}}</ref>
*Keratinizing type:  
*Keratinizing type:  
**Keratinization & intercellular bridges through-out most of the malignant lesion
**[[Keratinization]] & intercellular bridges through-out most of the [[malignant]] [[lesion]]
*Undifferentiated type:
*[[Undifferentiated]] type:
**Non-distinct borders/syncytial pattern
**Non-distinct borders/syncytial pattern
**[[Nucleoli]]
**[[Nucleoli]]
*Non keratinizing type:
*Non keratinizing type:
**Well-defined cell borders
**Well-defined [[cell]] borders
**[[Eosinophilia]]
**[[Eosinophilia]]
**Extra large nuclei/bizarre nuclei
**Extra large [[nuclei]]/bizarre [[nuclei]]
**[[Inflammation]] (lymphocytes, plasma cells)
**[[Inflammation]] ([[lymphocytes]], [[plasma cells]])
**Long rete ridges
**Long [[rete]] ridges
**Numerous beeds/blobs of [[epithelial cells]] that seem unlikely to be rete ridges
**Numerous beeds/blobs of [[epithelial cells]] that seem unlikely to be [[rete]] ridges
'''Squamous Cell Carcinoma Subtypes'''


===Squamous Cell Carcinoma Subtypes===
There are several [[histological]] subtypes of [[squamous cell carcinoma]] of [[larynx]] which include:
There are several histological subtypes of squamous cell carcinoma of larynx which include:<ref name=abc>Protocol applies to all invasive carcinomas of the larynx, including supraglottis, glottis, and subglottis.http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf. Accessed on: October 28, 2015.</ref>
*Basaloid
*Basaloid
*Warty (condylomatous)
*Warty (condylomatous)
*Verrucous
*[[Verrucous carcinoma|Verrucous]]
*Papillary
*[[Papillary]]
*Lymphoepithelial
*Lymphoepithelial
*[[Spindle cell]]
*[[Spindle cell]]


<gallery>
===Immunohistochemistry===
Image: 800px-Laryngeal_squamous_carcinoma_--_intermed_mag.jpg | Laryngeal squamous carcinoma (intermediate magnification)<ref name=aaa>Head and neck SCC Librepathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_head_and_neck Accessed on October 26, 2015</ref>
There are several [[immunohistochemistry]] markers of laryngeal carcinoma which include:<ref name="pmid24370715">{{cite journal |vauthors=Rodrigo JP, Martínez P, Allonca E, Alonso-Durán L, Suárez C, Astudillo A, García-Pedrero JM |title=Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas |journal=Clin. Exp. Metastasis |volume=31 |issue=3 |pages=317–25 |date=March 2014 |pmid=24370715 |doi=10.1007/s10585-013-9630-5 |url=}}</ref><ref name="pmid16683119">{{cite journal |vauthors=Wittekindt C, Sittel C, Kvasnicka HM, Eckel HE |title=Immunohistochemistry of whole-organ sections of advanced human laryngeal cancer |journal=Eur Arch Otorhinolaryngol |volume=263 |issue=8 |pages=741–6 |date=August 2006 |pmid=16683119 |doi=10.1007/s00405-006-0055-5 |url=}}</ref>
Image: 800px-Laryngeal_squamous_carcinoma_--_high_mag.jpg | Laryngeal squamous carcinoma (high magnification)<ref name=aaa>Head and neck SCC Librepathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_head_and_neck Accessed on October 26, 2015</ref>
Image: 800px-Laryngeal_squamous_carcinoma_--_very_high_mag.jpg | Laryngeal squamous carcinoma (very high magnification)<ref name=aaa> Head and neck SCC Librepathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_head_and_neck Accessed on October 26, 2015</ref>
</gallery>
 
==Immunohistochemistry==
There are several immunohistochemistry markers of laryngeal carcinoma which include:
*p63 positive
*p63 positive
*EBER negative
*EBER negative
*p16 negative
*[[p16]] negative
*BCL2 positive/negative<ref name=pmid20233885>{{cite journal |author=Nichols AC, Finkelstein DM, Faquin WC, ''et al.'' |title=Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer |journal=Clin. Cancer Res. |volume=16 |issue=7 |pages=2138–46 |year=2010 |month=April |pmid=20233885 |doi=10.1158/1078-0432.CCR-09-3185 |url=}}</ref>
*[[BCL2L2|BCL2]] positive/negative


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Types of cancer]]
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Otolaryngology]]

Latest revision as of 06:02, 18 March 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2], Faizan Sheraz, M.D. [3]

Overview

Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airway. Genes involved in the pathogenesis of laryngeal cancer include p16, NOTCH1, cyclin D1, and TP53. On gross pathology, flattened plaques, mucosal ulceration, and raised margins of the lesion are characteristic findings of laryngeal cancer. On microscopic histopathological analysis, spindle cells, basaloid cells, and nuclear atypia are characteristic findings of laryngeal cancer.

Pathophysiology

Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airways.[1]

Genetics

Development of laryngeal cancer is the result of multiple genetic mutations. These mutations lead to activation of oncogenes and inactivation of tumor suppression genes which ultimately result in deregulated cellular proliferation. Genes involved in the pathogenesis of laryngeal cancer include:[2]

Gross Pathology

On gross pathology, laryngeal cancer is characterized by:[3][4]

Microscopic Pathology

On microscopic histopathological analysis, laryngeal carcinoma is characterized by:[5][6][7][8]

Squamous cell carcinoma is subdivided histopathologically:[5][6][9]

Squamous Cell Carcinoma Subtypes

There are several histological subtypes of squamous cell carcinoma of larynx which include:

Immunohistochemistry

There are several immunohistochemistry markers of laryngeal carcinoma which include:[10][11]

  • p63 positive
  • EBER negative
  • p16 negative
  • BCL2 positive/negative

References

  1. ↑ Koufman JA, Burke AJ (February 1997). "The etiology and pathogenesis of laryngeal carcinoma". Otolaryngol. Clin. North Am. 30 (1): 1–19. PMID 8995133.
  2. ↑ de Miguel-Luken MJ, Chaves-Conde M, Carnero A (May 2016). "A genetic view of laryngeal cancer heterogeneity". Cell Cycle. 15 (9): 1202–12. doi:10.1080/15384101.2016.1156275. PMC 4894505. PMID 26940775.
  3. ↑ Sessions DG (June 1976). "Surgical pathology of cancer of the larynx and hypopharynx". Laryngoscope. 86 (6): 814–39. doi:10.1288/00005537-197606000-00009. PMID 933673.
  4. ↑ "journals.sagepub.com".
  5. ↑ 5.0 5.1 Hilly O, Raz R, Vaisbuch Y, Strenov Y, Segal K, Koren R, Shvero J (November 2012). "Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics". Head Neck. 34 (11): 1586–90. doi:10.1002/hed.21972. PMID 22180291.
  6. ↑ 6.0 6.1 Caldas-Magalhaes J, Kasperts N, Kooij N, van den Berg CA, Terhaard CH, Raaijmakers CP, Philippens ME (February 2012). "Validation of imaging with pathology in laryngeal cancer: accuracy of the registration methodology". Int. J. Radiat. Oncol. Biol. Phys. 82 (2): e289–98. doi:10.1016/j.ijrobp.2011.05.004. PMID 21719209.
  7. ↑ MUSTAKALLIO S (August 1946). "Relation of microscopic structure of laryngeal cancer to radiocurability". Acta radiol. 27 (5): 473–80. PMID 20286025.
  8. ↑ Franz B, Wetzel M (July 1980). "[Cytology of the early invasive laryngeal cancer (author's transl)]". Laryngol Rhinol Otol (Stuttg) (in German). 59 (7): 401–5. PMID 7453440.
  9. ↑ Lewis JS (March 2011). "Not your usual cancer case: variants of laryngeal squamous cell carcinoma". Head Neck Pathol. 5 (1): 23–30. doi:10.1007/s12105-010-0232-0. PMC 3037456. PMID 21165725.
  10. ↑ Rodrigo JP, Martínez P, Allonca E, Alonso-Durán L, Suárez C, Astudillo A, García-Pedrero JM (March 2014). "Immunohistochemical markers of distant metastasis in laryngeal and hypopharyngeal squamous cell carcinomas". Clin. Exp. Metastasis. 31 (3): 317–25. doi:10.1007/s10585-013-9630-5. PMID 24370715.
  11. ↑ Wittekindt C, Sittel C, Kvasnicka HM, Eckel HE (August 2006). "Immunohistochemistry of whole-organ sections of advanced human laryngeal cancer". Eur Arch Otorhinolaryngol. 263 (8): 741–6. doi:10.1007/s00405-006-0055-5. PMID 16683119.


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