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{{Vulvar cancer}}
{{Vulvar cancer}}
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==Overview==
==Overview==
Development of vulvar cancer is the result of multiple genetic mutations.  
Development of vulvar cancer is the result of multiple genetic mutations.  
==Pathogenesis==
==Pathogenesis==
* [[HPV|Human papillomaviruses]] subtypes 16 and 18 (High risk) play an essential role in the pathogenesis of  vulvar cancer. Once [[HPV]] enters an epithelial cell, the virus begins to make the proteins it encodes.  
* [[HPV|Human papillomaviruses]] subtypes 16 and 18 (High risk) play an essential role in the [[pathogenesis]] of  vulvar cancer. Once [[HPV]] enters an epithelial cell, the virus begins to make the proteins it encodes.  
* Two of the proteins made by high-risk HPVs (E6 and E7) interfere with cell functions that normally prevent excessive growth, helping the cell to grow in an uncontrolled manner and to avoid cell death.
* Two of the proteins made by high-risk [[HPV]]<nowiki/>s (E6 and E7) interfere with cell functions that normally prevent excessive growth, helping the cell to grow in an uncontrolled manner and to avoid cell death.
*Many times these infected cells are recognized by the immune system and eliminated. Sometimes, however, these infected cells are not destroyed, and a persistent infection results.  
*Many times these infected cells are recognized by the immune system and eliminated. Sometimes, however, these infected cells are not destroyed, and a persistent infection results.  
*Persistently infected cells continue to grow, they may develop mutations in cellular genes that promote even more abnormal cell growth.
*Persistently infected cells continue to grow, they may develop mutations in cellular genes that promote even more abnormal cell growth.
* HPV- related vulvar carcinoma is most commonly seen in younger women. [[ Vulvar intraepithelial neoplasia]] (VIN), related to HPV infection, subsequently leads to  invasive  vulvar cancer.<ref> The Histopathology of Vulvar Neoplasia. Glown. http://www.glowm.com/section_view/heading/The%2520Histopathology%2520of%2520Vulvar%2520Neoplasia/item/256#13421  URL Accessed on September 30, 2015</ref>
* HPV- related vulvar carcinoma is most commonly seen in younger women. [[ Vulvar intraepithelial neoplasia]] (VIN), related to HPV infection, subsequently leads to  invasive  vulvar cancer.<ref>The Histopathology of Vulvar Neoplasia. Glown. http://www.glowm.com/section_view/heading/The%2520Histopathology%2520of%2520Vulvar%2520Neoplasia/item/256#13421  URL Accessed on September 30, 2015</ref>
*The development of both vulvar low-grade squamous intraepithelial lesions (LSIL) and vulvar high-grade squamous intraepithelial lesions (HSIL; formerly VIN usual type) is associated with human papillomavirus (HPV) infection, as is the corresponding vulvar cancer of the warty and basaloid subtypes.
*The development of both vulvar low-grade squamous intraepithelial lesions (LSIL) and vulvar high-grade squamous intraepithelial lesions (HSIL; formerly VIN usual type) is associated with [[human papillomavirus]] ([[HPV]]) infection, as is the corresponding vulvar cancer of the warty and basaloid subtypes.
*Multifocal vulvar HSIL and multicentric vulvar HSIL are most often associated with high-oncogenic-risk HPV subtypes 16, 18, and 31 and should be considered premalignant lesions<ref name="pmid8290182">{{cite journal |vauthors=Ogunbiyi OA, Scholefield JH, Robertson G, Smith JH, Sharp F, Rogers K |title=Anal human papillomavirus infection and squamous neoplasia in patients with invasive vulvar cancer |journal=Obstet Gynecol |volume=83 |issue=2 |pages=212–6 |date=February 1994 |pmid=8290182 |doi= |url=}}</ref>. By contrast, vulvar condylomata acuminata are usually associated with low-oncogenic-risk HPV subtypes 6 and 11<ref name="pmid7896198">{{cite journal |vauthors=Hørding U, Junge J, Poulsen H, Lundvall F |title=Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential |journal=Gynecol. Oncol. |volume=56 |issue=2 |pages=276–9 |date=February 1995 |pmid=7896198 |doi=10.1006/gyno.1995.1046 |url=}}</ref>.
*Multifocal vulvar HSIL and multicentric vulvar HSIL are most often associated with high-oncogenic-risk HPV subtypes 16, 18, and 31 and should be considered premalignant lesions<ref name="pmid8290182">{{cite journal |vauthors=Ogunbiyi OA, Scholefield JH, Robertson G, Smith JH, Sharp F, Rogers K |title=Anal human papillomavirus infection and squamous neoplasia in patients with invasive vulvar cancer |journal=Obstet Gynecol |volume=83 |issue=2 |pages=212–6 |date=February 1994 |pmid=8290182 |doi= |url=}}</ref>. By contrast, vulvar [[condylomata acuminata]] are usually associated with low-oncogenic-risk [[HPV]] subtypes 6 and 11<ref name="pmid7896198">{{cite journal |vauthors=Hørding U, Junge J, Poulsen H, Lundvall F |title=Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential |journal=Gynecol. Oncol. |volume=56 |issue=2 |pages=276–9 |date=February 1995 |pmid=7896198 |doi=10.1006/gyno.1995.1046 |url=}}</ref>.
*The anogenital epithelium is derived from the embryonic cloaca and includes the cervix, vagina, vulva, anus, and lower three centimeters of rectal mucosa up to the dentate line.  
*The anogenital [[epithelium]] is derived from the embryonic cloaca and includes the [[cervix]], [[vagina]], [[vulva]], anus, and lower three centimeters of rectal mucosa up to the dentate line.  
*Since the entire region shares the same embryological origin and is susceptible to similar exogenous agents (eg, HPV infection), squamous intraepithelial lesions in this area are often both multifocal (multiple foci of disease within the same organ) and multicentric (foci of disease involving more than one organ).  
*Since the entire region shares the same embryological origin and is susceptible to similar exogenous agents (eg, [[HPV infection]]), squamous intraepithelial lesions in this area are often both multifocal (multiple foci of disease within the same organ) and multicentric (foci of disease involving more than one organ).  
*Women with VIN may have synchronous or metachronous squamous neoplasia of other lower genital tract sites (cervix, vagina, anus). *There is evidence that some cases of high-grade VIN and vaginal intraepithelial neoplasia represent a monoclonal lesion derived from high-grade or malignant cervical neoplasia<ref name="pmid16368943">{{cite journal |vauthors=Vinokurova S, Wentzensen N, Einenkel J, Klaes R, Ziegert C, Melsheimer P, Sartor H, Horn LC, Höckel M, von Knebel Doeberitz M |title=Clonal history of papillomavirus-induced dysplasia in the female lower genital tract |journal=J. Natl. Cancer Inst. |volume=97 |issue=24 |pages=1816–21 |date=December 2005 |pmid=16368943 |doi=10.1093/jnci/dji428 |url=}}</ref>.
*Women with VIN may have synchronous or metachronous [[squamous]] [[neoplasia]] of other lower genital tract sites ([[cervix]], [[Vaginal|vagina]], anus). There is evidence that some cases of high-grade VIN and vaginal intraepithelial [[neoplasia]] represent a monoclonal lesion derived from high-grade or [[malignant]] cervical [[Neoplasia|neoplasia.]]<ref name="pmid16368943">{{cite journal |vauthors=Vinokurova S, Wentzensen N, Einenkel J, Klaes R, Ziegert C, Melsheimer P, Sartor H, Horn LC, Höckel M, von Knebel Doeberitz M |title=Clonal history of papillomavirus-induced dysplasia in the female lower genital tract |journal=J. Natl. Cancer Inst. |volume=97 |issue=24 |pages=1816–21 |date=December 2005 |pmid=16368943 |doi=10.1093/jnci/dji428 |url=}}</ref>
*The pathogenesis of differentiated VIN is less well understood than vulvar LSIL or HSIL.  
*The [[pathogenesis]] of differentiated VIN is less well understood than vulvar LSIL or HSIL.  
*It is typically associated with lichen sclerosus. The risk of vulvar squamous cell carcinoma in women with lichen sclerosus is approximately 5 percent<ref name="pmid20854400">{{cite journal |vauthors=Neill SM, Lewis FM, Tatnall FM, Cox NH |title=British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010 |journal=Br. J. Dermatol. |volume=163 |issue=4 |pages=672–82 |date=October 2010 |pmid=20854400 |doi=10.1111/j.1365-2133.2010.09997.x |url=}}</ref>.  
*It is typically associated with [[lichen sclerosus]]. The risk of vulvar squamous cell carcinoma in women with lichen sclerosus is approximately 5 percent<ref name="pmid20854400">{{cite journal |vauthors=Neill SM, Lewis FM, Tatnall FM, Cox NH |title=British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010 |journal=Br. J. Dermatol. |volume=163 |issue=4 |pages=672–82 |date=October 2010 |pmid=20854400 |doi=10.1111/j.1365-2133.2010.09997.x |url=}}</ref>.  
*Differentiated VIN is found adjacent to 80 percent of vulvar squamous cell carcinomas. The diagnosis of solitary differentiated VIN is very challenging and appears to be associated with rapid progression to squamous cell carcinoma.  
*Differentiated VIN is found adjacent to 80 percent of vulvar [[squamous cell carcinomas]]. The diagnosis of solitary differentiated VIN is very challenging and appears to be associated with rapid progression to [[squamous cell carcinoma]].  
*Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia, and/or basal cellular atypia tend to have the highest risk of progression to squamous cell carcinoma. There are no known biomarkers to reliably identify the patients at highest risk<ref name="pmid21057461">{{cite journal |vauthors=van de Nieuwenhof HP, Bulten J, Hollema H, Dommerholt RG, Massuger LF, van der Zee AG, de Hullu JA, van Kempen LC |title=Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma |journal=Mod. Pathol. |volume=24 |issue=2 |pages=297–305 |date=February 2011 |pmid=21057461 |doi=10.1038/modpathol.2010.192 |url=}}</ref>.
*Patients with [[lichen sclerosus]] with dyskeratosis and parakeratosis, [[hyperplasia]], and/or basal cellular [[atypia]] tend to have the highest risk of progression to [[squamous cell carcinoma]]. There are no known biomarkers to reliably identify the patients at highest risk<ref name="pmid21057461">{{cite journal |vauthors=van de Nieuwenhof HP, Bulten J, Hollema H, Dommerholt RG, Massuger LF, van der Zee AG, de Hullu JA, van Kempen LC |title=Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma |journal=Mod. Pathol. |volume=24 |issue=2 |pages=297–305 |date=February 2011 |pmid=21057461 |doi=10.1038/modpathol.2010.192 |url=}}</ref>.


==Gross Patholgy==
==Gross Patholgy==
{| {{table}}
{| style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;" cellspacing="0" {{table}} cellpadding="4"
| align="center" style="background: #4479BA;" | {{fontcolor|#FFF|''' Vulvar Carcinomas Subtype'''}}
| style="background: #4479BA;" align="center" | {{fontcolor|#FFF|''' Vulvar Carcinomas Subtype'''}}
| align="center" style="background: #4479BA;" | {{fontcolor|#FFF|'''Features on Gross Pathology'''}}
| style="background: #4479BA;" align="center" | {{fontcolor|#FFF|'''Features on Gross Pathology'''}}
|-
|-
| Squamous cell carcinoma of vulva||
| Squamous cell carcinoma of vulva||
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==Microscopic Pathology==
==Microscopic Pathology==


Histologic subtypes of vulvar cancer include:<ref>{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727 }}</ref><ref> Malignant melanoma. Libre pathology. http://librepathology.org/wiki/index.php/Malignant_melanoma. URL Accessed on September 30, 2015</ref><ref> Basal cell carcinoma
[[Histologic]] subtypes of vulvar cancer include:<ref>{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727 }}</ref><ref>Malignant melanoma. Libre pathology. http://librepathology.org/wiki/index.php/Malignant_melanoma. URL Accessed on September 30, 2015</ref><ref>Basal cell carcinoma
. Libre pathology. http://librepathology.org/wiki/index.php/Basal_cell_carcinoma. URL Accessed on September 30, 2015</ref><ref> Squamous cell carcinoma. Libre pathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma. URL Accessed on September 30, 2015</ref>
. Libre pathology. http://librepathology.org/wiki/index.php/Basal_cell_carcinoma. URL Accessed on September 30, 2015</ref><ref>Squamous cell carcinoma. Libre pathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma. URL Accessed on September 30, 2015</ref>
*Vulvar carcinomas
*Vulvar carcinomas
:* [[Squamous cell carcinoma]]
:* [[Squamous cell carcinoma]]
:* [[Basal cell carcinoma]]
:* [[Basal cell carcinoma]]
:* Vulvar [[Paget disease]]
:* Vulvar [[Paget disease]]
:* Adenocarcinoma
:* [[Adenocarcinoma]]
:* Transitional cell carcinoma
:* [[Transitional cell carcinoma]]
:* Verrucous carcinoma
:* [[Verrucous carcinoma]]
:* Merkel cell tumors
:* Merkel cell tumors
*Vulvar [[malignant melanoma]]
*Vulvar [[malignant melanoma]]
*Vulvar [[sarcoma]]
*Vulvar [[sarcoma]]
:* [[Leiomyosarcoma]]
:* [[Leiomyosarcoma]]
:* Malignant fibrous histiocytoma
:* [[Malignant fibrous histiocytoma]]
:* Epithelial sarcoma
:* Epithelial [[sarcoma]]
{| {{table}}
{| style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;" cellspacing="0" {{table}} cellpadding="4"
| align="center" style="background: #4479BA;" | {{fontcolor|#FFF|''' Vulvar Carcinomas Subtype'''}}
| style="background: #4479BA;" align="center" | {{fontcolor|#FFF|''' Vulvar Carcinomas Subtype'''}}
| align="center" style="background: #4479BA;" | {{fontcolor|#FFF|'''Features on Histopathological Microscopic Analysis'''}}
| style="background: #4479BA;" align="center" | {{fontcolor|#FFF|'''Features on Histopathological Microscopic Analysis'''}}
| align="center" style="background: #4479BA;" | {{fontcolor|#FFF|'''Image'''}}
| style="background: #4479BA;" align="center" | {{fontcolor|#FFF|'''Image'''}}
|-
|-
|-
|-
| Squamous cell carcinoma of vulva||
| Squamous cell carcinoma of vulva||
* 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
| [[File:Scc.jpg|thumb|none|300px|Squamous cell carcinoma of vulva]]
|


|-
|-
|Basal cell carcinoma of vulva||
|Basal cell carcinoma of vulva||
* Basaloid cells - similar in appearance to basal cells
* Basaloid cells - similar in appearance to basal cells
* Moderate blue/grey cytoplasm.
* Moderate blue/grey [[cytoplasm]]
* Dark ovoid/ellipsoid nucleus with uniform chromatin
* Dark ovoid/ellipsoid [[nucleus]] with uniform chromatin
* Palisading of cells at the edge of the cell nests
* Palisading of cells at the edge of the cell nests
* Artefactual separation of cells (forming the nests) from the underlying stroma - key feature
* Artefactual separation of cells (forming the nests) from the underlying stroma - key feature
* Surrounded by blue (myxoid) stroma - key feature
* Surrounded by blue (myxoid) stroma - key feature
| [[File:BCC.jpg|thumb|none|300px|Basal cell carcinoma of vulva]]
|


|-
|-
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* Presence of intraepidermal lateral spread (most characteristic feature)
* Presence of intraepidermal lateral spread (most characteristic feature)
* Dermal invasion
* Dermal invasion
* Desmoplasia
* [[Desmoplasia]]
* Epidermal hyperplasia
* [[Epidermal]] [[hyperplasia]]
*Appearance of epithelioid cells with occasional spindle cells
*Appearance of epithelioid cells with occasional [[spindle cells]]
| [[File:Melanoma.JPG |thumb|none|300px| Vulvar melanoma]]
|
|-
|-
|}
|}

Latest revision as of 22:30, 24 May 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2] Syed Musadiq Ali M.B.B.S.[3]

Overview

Development of vulvar cancer is the result of multiple genetic mutations.

Pathogenesis

  • Human papillomaviruses subtypes 16 and 18 (High risk) play an essential role in the pathogenesis of vulvar cancer. Once HPV enters an epithelial cell, the virus begins to make the proteins it encodes.
  • Two of the proteins made by high-risk HPVs (E6 and E7) interfere with cell functions that normally prevent excessive growth, helping the cell to grow in an uncontrolled manner and to avoid cell death.
  • Many times these infected cells are recognized by the immune system and eliminated. Sometimes, however, these infected cells are not destroyed, and a persistent infection results.
  • Persistently infected cells continue to grow, they may develop mutations in cellular genes that promote even more abnormal cell growth.
  • HPV- related vulvar carcinoma is most commonly seen in younger women. Vulvar intraepithelial neoplasia (VIN), related to HPV infection, subsequently leads to invasive vulvar cancer.[1]
  • The development of both vulvar low-grade squamous intraepithelial lesions (LSIL) and vulvar high-grade squamous intraepithelial lesions (HSIL; formerly VIN usual type) is associated with human papillomavirus (HPV) infection, as is the corresponding vulvar cancer of the warty and basaloid subtypes.
  • Multifocal vulvar HSIL and multicentric vulvar HSIL are most often associated with high-oncogenic-risk HPV subtypes 16, 18, and 31 and should be considered premalignant lesions[2]. By contrast, vulvar condylomata acuminata are usually associated with low-oncogenic-risk HPV subtypes 6 and 11[3].
  • The anogenital epithelium is derived from the embryonic cloaca and includes the cervix, vagina, vulva, anus, and lower three centimeters of rectal mucosa up to the dentate line.
  • Since the entire region shares the same embryological origin and is susceptible to similar exogenous agents (eg, HPV infection), squamous intraepithelial lesions in this area are often both multifocal (multiple foci of disease within the same organ) and multicentric (foci of disease involving more than one organ).
  • Women with VIN may have synchronous or metachronous squamous neoplasia of other lower genital tract sites (cervix, vagina, anus). There is evidence that some cases of high-grade VIN and vaginal intraepithelial neoplasia represent a monoclonal lesion derived from high-grade or malignant cervical neoplasia.[4]
  • The pathogenesis of differentiated VIN is less well understood than vulvar LSIL or HSIL.
  • It is typically associated with lichen sclerosus. The risk of vulvar squamous cell carcinoma in women with lichen sclerosus is approximately 5 percent[5].
  • Differentiated VIN is found adjacent to 80 percent of vulvar squamous cell carcinomas. The diagnosis of solitary differentiated VIN is very challenging and appears to be associated with rapid progression to squamous cell carcinoma.
  • Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia, and/or basal cellular atypia tend to have the highest risk of progression to squamous cell carcinoma. There are no known biomarkers to reliably identify the patients at highest risk[6].

Gross Patholgy

Vulvar Carcinomas Subtype Features on Gross Pathology
Squamous cell carcinoma of vulva
Basal cell carcinoma of vulva
  • Pearly nodule with telangiectasias
Vulvar melanoma
  • Superficial spreading is the most common type
  • Brown/black color, but may include reddish brown or white
  • Hyperkeratotic, diffused borders with no distinct demarcation
  • Irregular and elevated

Microscopic Pathology

Histologic subtypes of vulvar cancer include:[7][8][9][10]

  • Vulvar carcinomas
Vulvar Carcinomas Subtype Features on Histopathological Microscopic Analysis Image
Squamous cell carcinoma of vulva
  • 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
Basal cell carcinoma of vulva
  • Basaloid cells - similar in appearance to basal cells
  • Moderate blue/grey cytoplasm
  • Dark ovoid/ellipsoid nucleus with uniform chromatin
  • Palisading of cells at the edge of the cell nests
  • Artefactual separation of cells (forming the nests) from the underlying stroma - key feature
  • Surrounded by blue (myxoid) stroma - key feature
Vulvar melanoma

References

  1. ↑ The Histopathology of Vulvar Neoplasia. Glown. http://www.glowm.com/section_view/heading/The%2520Histopathology%2520of%2520Vulvar%2520Neoplasia/item/256#13421 URL Accessed on September 30, 2015
  2. ↑ Ogunbiyi OA, Scholefield JH, Robertson G, Smith JH, Sharp F, Rogers K (February 1994). "Anal human papillomavirus infection and squamous neoplasia in patients with invasive vulvar cancer". Obstet Gynecol. 83 (2): 212–6. PMID 8290182.
  3. ↑ Hørding U, Junge J, Poulsen H, Lundvall F (February 1995). "Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential". Gynecol. Oncol. 56 (2): 276–9. doi:10.1006/gyno.1995.1046. PMID 7896198.
  4. ↑ Vinokurova S, Wentzensen N, Einenkel J, Klaes R, Ziegert C, Melsheimer P, Sartor H, Horn LC, Höckel M, von Knebel Doeberitz M (December 2005). "Clonal history of papillomavirus-induced dysplasia in the female lower genital tract". J. Natl. Cancer Inst. 97 (24): 1816–21. doi:10.1093/jnci/dji428. PMID 16368943.
  5. ↑ Neill SM, Lewis FM, Tatnall FM, Cox NH (October 2010). "British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010". Br. J. Dermatol. 163 (4): 672–82. doi:10.1111/j.1365-2133.2010.09997.x. PMID 20854400.
  6. ↑ van de Nieuwenhof HP, Bulten J, Hollema H, Dommerholt RG, Massuger LF, van der Zee AG, de Hullu JA, van Kempen LC (February 2011). "Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma". Mod. Pathol. 24 (2): 297–305. doi:10.1038/modpathol.2010.192. PMID 21057461.
  7. ↑ Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
  8. ↑ Malignant melanoma. Libre pathology. http://librepathology.org/wiki/index.php/Malignant_melanoma. URL Accessed on September 30, 2015
  9. ↑ Basal cell carcinoma . Libre pathology. http://librepathology.org/wiki/index.php/Basal_cell_carcinoma. URL Accessed on September 30, 2015
  10. ↑ Squamous cell carcinoma. Libre pathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma. URL Accessed on September 30, 2015
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