Laryngeal cancer pathophysiology: Difference between revisions

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{{CMG}} {{AE}}{{Faizan}}
{{CMG}} {{AE}}{{Faizan}}
==Overview==
==Overview==
Hypopharyngeal cancer arises from [[squamous cell]]s, which are cells that are normally involved in protection of aerodigestive tract. Genes involved in the pathogenesis of hypopharyngeal cancer include ''[[P16 (gene)|p16]]'', ''[[NOTCH1]]'', ''[[cyclin D1]]'', and ''[[TP53]]''. Hypopharyngeal cancer is associated with sideropenic dysphagia and Paterson Brown Kelly syndrome. On gross pathology, flattened plaques, mucosal ulceration, and raised margins of the lesion are characteristic findings of hypopharyngeal cancer. On microscopic histopathological analysis, [[spindle cell]]s, basaloid cells, and nuclear atypia are characteristic findings of hypopharyngeal cancer.<ref name="pmid12560383">{{cite journal| author=Helliwell TR| title=acp Best Practice No 169. Evidence based pathology: squamous carcinoma of the hypopharynx. | journal=J Clin Pathol | year= 2003 | volume= 56 | issue= 2 | pages= 81-5 | pmid=12560383 | doi= | pmc=PMC1769882 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12560383  }} </ref>
Laryngeal cancer arises from [[squamous cell]]s, which are cells that are normally involved in protection of 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==
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==Genetics==
==Genetics==
Genes involved in the pathogenesis of hypopharyngeal cancer include:
Genes involved in the pathogenesis of laryngeal cancer include:
*''[[P16 (gene)|p16]]''
*''[[P16 (gene)|p16]]''
*''[[NOTCH1]]''
*''[[NOTCH1]]''
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===Subclassification by site===
===Subclassification by site===
It is generally divided the following way:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf]. Accessed on: 2 May 2012.</ref>
It is generally divided the following way:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf]. Accessed on: October 28, 2015.</ref>


{{familytree/start}}
{{familytree/start}}
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{{familytree | | | | B01 | | | B02 | | | B03|B01=Supraglottis|B02=Glottis|B03=Subglottis }}
{{familytree | | | | B01 | | | B02 | | | B03|B01=Supraglottis|B02=Glottis|B03=Subglottis }}
{{familytree/end}}
{{familytree/end}}
Features:<ref name=Ref_WMSP24>{{Ref WMSP|24}}</ref><ref>URL: [http://www.health.am/cr/more/statistics-and-prognosis-for-cancer-of-the-larynx/ http://www.health.am/cr/more/statistics-and-prognosis-for-cancer-of-the-larynx/]. Accessed on: 2 May 2012.</ref>
*Prevalence - glottis > supraglottis > subglottis.
*Glottic carcinoma tends to present earlier (as it affects phonation) and, therefore, has a better prognosis.


SCC is subdivided by the WHO into:<ref name=Ref_Sternberg4_975>{{Ref Sternberg4|975}}</ref>
SCC is subdivided by the WHO into:<ref name=Ref_Sternberg4_975>{{Ref Sternberg4|975}}</ref>
*Keratinizing type (KT).
*Keratinizing type (KT).
**Worst prognosis.
*Undifferentiated type (UT).
*Undifferentiated type (UT).
**Intermediate prognosis.
**EBV association.
**EBV association.
*Nonkeratinizing type (NT).
*Nonkeratinizing type (NT).
**Good prognosis.
**EBV association.
**EBV association.


==Microscopic==
==Microscopic==
Features based on classification:<ref name=Ref_Sternberg4_975>{{Ref Sternberg4|975}}</ref>
Features based on classification:
*Keratinizing subtype:  
*Keratinizing subtype:  
**Keratinization & intercellular bridges through-out most of the malignant lesion
**Keratinization & intercellular bridges through-out most of the malignant lesion
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**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===
There are several subtypes:<ref>Squamous cell carcinoma subtypes. URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970297-2 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970297-2]. Accessed on: October 28, 2015.</ref>
*Basaloid
*Warty (Condylomatous)
*Verrucous
*Papillary
*Lymphoepithelial
*Spindle cell


===Images===
===Images===
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</gallery>
</gallery>


===Overview of subtypes===
 
There are several subtypes:<ref>URL: [http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970297-2 http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970297-2]. Accessed on: March 9, 2010.</ref>
*Basaloid
*Warty (Condylomatous)
*Verrucous
*Papillary
*Lymphoepithelial
*Spindle cell


====Verrucous squamous cell carcinoma====
====Verrucous squamous cell carcinoma====
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*"Glassy" appearance
*"Glassy" appearance
*Pushing border
*Pushing border
DDx: papilloma.


====Spindle cell squamous carcinoma====
====Spindle cell squamous carcinoma====
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*Typically keratin -ve.
*Typically keratin -ve.
*p63 +ve.
*p63 +ve.
DDx:
*Spindle cell [[melanoma]].
*Mesenchymal neoplasm.


====Basaloid squamous cell carcinoma====
====Basaloid squamous cell carcinoma====
*May mimic ''[[adenoid cystic carcinoma]]''.
*May mimic ''[[adenoid cystic carcinoma]]''
*Classically base of tongue.<ref>URL: [http://www.biomedcentral.com/1471-2407/6/146 http://www.biomedcentral.com/1471-2407/6/146]. Accessed on: March 9, 2010.</ref>
*Typically poor prognosis.
 
Features:
*Need keratinization. (???)
 
DDx:
*Neuroendocrine tumour.


====Lymphoepithelial (squamous cell) carcinoma====
====Lymphoepithelial (squamous cell) carcinoma====
See ''[[nasopharyngeal carcinoma]]''.
*Lymphoid component


==IHC==
==IHC==
*p63 +ve.
Immunohistochemistry markers include:<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>
*EBER -ve.
*p63 positive
**Positive suggests [[nasopharyngeal carcinoma]].
*EBER negative
*p16 -ve.
*p16 negative
**Positive suggests [[HPV-associated head and neck squamous cell carcinoma]].
*BCL2 positive/negative
*Bcl2 +ve/-ve.
 
**Positive = poor prognosis.<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>
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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{{WikiDoc Sources}}
{{WikiDoc Sources}}


[[Category: Needs content]]
[[Category:Disease]]
[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Types of cancer]]

Revision as of 14:52, 28 October 2015

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

Overview

Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of 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 airway. 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 results in deregulated cellular proliferation.

Genetics

Genes involved in the pathogenesis of laryngeal cancer include:


Gross Pathology

On gross pathology, laryngeal cancer is characterized by:

  • Flattened plaques
  • Raised margins of the lesion
  • Mucosal ulceration
  • Gross pathology specimen of laryngeal cancer
    Gross pathology specimen of laryngeal cancer


Microscopic Pathology

On microscopic histopathological analysis, laryngeal carcinoma is characterized by:

Subclassification by site

It is generally divided the following way:[1]

 
 
 
 
 
 
 
 
Laryngeal cancer
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Supraglottis
 
 
Glottis
 
 
Subglottis

SCC is subdivided by the WHO into:[2]

  • Keratinizing type (KT).
  • Undifferentiated type (UT).
    • EBV association.
  • Nonkeratinizing type (NT).
    • EBV association.

Microscopic

Features based on classification:

  • Keratinizing subtype:
    • Keratinization & intercellular bridges through-out most of the malignant lesion
  • Undifferentiated type:
    • Non-distinct borders/syncytial pattern
    • Nucleoli
  • Non Keratinizing type:
    • Well-defined cell borders
    • Eosinophilia
    • Extra large nuclei/bizarre nuclei
    • Inflammation (lymphocytes, plasma cells)
    • Long rete ridges
    • Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges

Squamous cell carcinoma subtypes

There are several subtypes:[3]

  • Basaloid
  • Warty (Condylomatous)
  • Verrucous
  • Papillary
  • Lymphoepithelial
  • Spindle cell

Images

  • Laryngeal squamous carcinoma (Intermediate Magnification)[4]
    Laryngeal squamous carcinoma (Intermediate Magnification)[4]
  • Laryngeal squamous carcinoma (High Magnification)[4]
    Laryngeal squamous carcinoma (High Magnification)[4]
  • Laryngeal squamous carcinoma (Very High Magnification)[4]
    Laryngeal squamous carcinoma (Very High Magnification)[4]


Verrucous squamous cell carcinoma

Features:

  • Exophytic growth
  • Well-differentiated
  • "Glassy" appearance
  • Pushing border

Spindle cell squamous carcinoma

  • Key to diagnosis is finding a component of conventional squamous cell carcinoma

IHC:

  • Typically keratin -ve.
  • p63 +ve.

Basaloid squamous cell carcinoma

Lymphoepithelial (squamous cell) carcinoma

  • Lymphoid component

IHC

Immunohistochemistry markers include:[5]

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

References

  1. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Larynx_11protocol.pdf. Accessed on: October 28, 2015.
  2. ↑ Template:Ref Sternberg4
  3. ↑ Squamous cell carcinoma subtypes. URL: http://www.pathconsultddx.com/pathCon/diagnosis?pii=S1559-8675%2806%2970297-2. Accessed on: October 28, 2015.
  4. ↑ 4.0 4.1 4.2 Head and neck SCC Librepathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_head_and_neck Accessed on October 26, 2015
  5. ↑ Nichols AC, Finkelstein DM, Faquin WC; et al. (2010). "Bcl2 and human papilloma virus 16 as predictors of outcome following concurrent chemoradiation for advanced oropharyngeal cancer". Clin. Cancer Res. 16 (7): 2138–46. doi:10.1158/1078-0432.CCR-09-3185. PMID 20233885. Unknown parameter |month= ignored (help)


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