Carcinoma of the penis pathophysiology: Difference between revisions

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{{Carcinoma of the penis}}
{{Carcinoma of the penis}}


'''Editor(s)-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:mgibson@perfuse.org] Phone:617-632-7753; Joel Gelman, M.D. [mailto:jgelman@uci.edu], ''Director of the Center for Reconstructive Urology and Associate Clinical Professor in the Department of Urology at the University of    California,Irvine''
'''Editor(s)-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com] Phone:617-632-7753; {{Swathi}}


==Overview==
==Overview==
On [[Gross pathology|gross]] [[pathology]], the [[glans]] and the [[foreskin]] are the most common locations to find scaly patches, [[nodules]], [[palpable]] painless [[lump]], [[erythematous]], [[ulceration]], concurrent [[phimosis]] may conceal the [[lesion]], [[Surface anatomy|surface]] of the [[lesion]] may be exophytic, flat, or [[Ulcerated lesion|ulcerated]], [[Chronic (medical)|chronic]] [[Penis|penile]] [[rash]] or subtle [[Burning sensation when urinating|burning]] [[Burning sensation when urinating|sensation]] and [[Swelling|swollen]] [[inguinal lymph nodes]] as characteristic findings of [[carcinoma]] of [[penis]].  On [[microscopic]] [[histopathological]] [[analysis]], [[keratinization]] and intercellular bridges are characteristic findings of [[carcinoma]] of the [[penis]].
==Pathogenesis==
*[[Penis|Penile]] [[Cancer|cancers]] traditionally begin as small [[Lesion|lesions]], most commonly on the [[glans]] or [[prepuce]] <ref name="doi10.3322/caac.21354">{{cite book | last = Spiess | first = Philippe | title = Penile cancer : diagnosis and treatment | publisher = Humana Press | location = New York | year = 2013 | isbn = 978-1-4939-6679-0 }} </ref>
* About 95% of [[penile cancer]]s develop from flat, scale-like [[Cell (biology)|cells]] called [[squamous]] [[Cells (biology)|cells]]. [[squamous cell carcinoma]] ([[Squamous cell carcinoma|SCC]]) can develop anywhere on the [[penis]], but most develop on the [[foreskin]] (in uncircumcised men) or the [[glans]]. This type of [[cancer]] is typically slow growing. When found early, it is often curable
* [[Penis|Penile]] [[cancer]] arises from [[precursor]] [[Lesion|lesions]], which generally progress from low-grade to high-grade [[Lesion|lesions]]
[[Gross|Grossly]] noted [[growth]] [[Pattern|patterns]] include:
#'''Superficial spreading''': [[tumors]] are limited to [[Lamina propria|lamina]] [[Lamina propria|propria]] or [[superficial]] [[Corpus spongiosum penis|corpus spongiosum]]. 
##Usually [[extend]] horizontally through multiple [[anatomical]] [[compartments]]
#'''Vertical growth''': [[tumors]] invade deep [[anatomical]] levels, [[Surface anatomy|surface]] is non-verruciform and frequently [[Ulcerated lesion|ulcerated]]
#'''Verruciform''': [[tumors]] are exophytic and [[Papillomatosis|papillomatous]] with a cauliflower-like aspect.
##May be limited to [[Surface area|surface]] ([[Verrucous carcinoma|verrucous]]) or invade deep [[anatomical]] levels (cuniculatum) 
#'''Mixed patterns''': observed in 10 - 15% of all cases
On [[microscopic]] [[histopathological]] [[analysis]], characteristic findings of [[carcinoma]] of the [[penis]] include:
*[[keratinization]]
*intercellular bridges
*Most [[histologic]] subtypes resemble those in [[vulva]], [[anus]] or [[Buccal mucosa|buccal]] [[mucosa]]
*48 - 65% are [[squamous cell carcinoma]]
*Verruciform [[tumors]] are [[Verrucous carcinoma|verrucous]], warty, [[papillary]] or cuniculatum [[Carcinoma|carcinomas]]
*Basaloid and sarcomatoid [[Carcinoma|carcinomas]] usually have a vertical [[growth]] [[pattern]]
* [[Penis|Penile]] [[malignant]] [[lesions]] and [[tumors]], can be divided into [[Human papillomavirus|HPV]]-related and non–[[Human papillomavirus|HPV]]-related groups<ref name="SpiessDhillon2016">{{cite journal|last1=Spiess|first1=Philippe E.|last2=Dhillon|first2=Jasreman|last3=Baumgarten|first3=Adam S.|last4=Johnstone|first4=Peter A.|last5=Giuliano|first5=Anna R.|title=Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies|journal=CA: A Cancer Journal for Clinicians|volume=66|issue=6|year=2016|pages=481–495|issn=00079235|doi=10.3322/caac.21354}}</ref>
* For [[HPV]] related [[Penis|penile]] [[cancers]] this sequence is as follows:<ref name="pmid18607597">{{cite journal| author=Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ| title=Penile cancer: epidemiology, pathogenesis and prevention. | journal=World J Urol | year= 2009 | volume= 27 | issue= 2 | pages= 141-50 | pmid=18607597 | doi=10.1007/s00345-008-0302-z | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18607597  }} </ref>
:* [[Squamous]] [[hyperplasia]]
:* Low-grade [[Penis|penile]] intraepithelial [[neoplasia]] (PIN)
:* High-grade PIN (carcinoma [[in situ]]—[[Bowen's disease]], [[erythroplasia of Queyrat]] and [[bowenoid papulosis]] ([[Bowenoid papulosis|BP]]))
:* [[Invasive (medical)|Invasive]] [[carcinoma]] of the [[penis]]
* Non-[[Human papillomavirus|HPV]] related [[Penis|penile]] [[Squamous cell carcinoma|squamous cell cancers]] include:
:*[[Squamous cell carcinoma|SCC]] usual type/Not Otherwise Specified (NOS)
:*Pseudohyperplastic [[carcinoma]]
:*Pseudoglandular [[carcinoma]]
:*[[Verrucous carcinoma]]
:*[[Carcinoma cuniculatum]]
:*[[Papillary|Papillary carcinoma]] NOS
:*[[Adenosquamous carcinoma]]
:*Sarcomatoid [[carcinoma]]
*[[Tumors]] with [[Basal (medicine)|basal]] and/or warty [[morphology]] display [[Human papillomavirus|HPV]] more frequently
'''Grading:'''
*'''Grade 1:''' well [[Differentiate|differentiated]] [[cells]], almost undistinguishable from normal [[Squamous epithelium|squamous]] [[cells]] except for the presence of minimal [[Basal (medicine)|basal]] / [[Parabasalid|parabasal]] [[Cell (biology)|cell]] [[atypia]]
*'''Grade 2:''' all [[tumors]] not fitting into criteria for grade 1 or 3
*'''Grade 3:''' any [[Anaplasia|anaplastic]] [[Cell (biology)|cells]]
==Gross & Microscopic Pathology==
'''HPV-related Penile Carcinoma'''
*'''Basaloid SCC'''
**Occurs most frequently the [[glans]] or the [[foreskin]] <ref name="pmid18766352">{{cite journal| author=Cubilla AL| title=The role of pathologic prognostic factors in squamous cell carcinoma of the penis. | journal=World J Urol | year= 2009 | volume= 27 | issue= 2 | pages= 169-77 | pmid=18766352 | doi=10.1007/s00345-008-0315-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18766352  }} </ref> <ref name="pmid29763105">{{cite journal| author=| title=StatPearls | journal= | year= 2019 | volume=  | issue=  | pages=  | pmid=29763105 | doi= | pmc= | url= }} </ref>
**Flat [[Ulcerated lesion|ulcerated]] [[Mass|masses]], which are deeply [[Invasive (medical)|invasive]] and sometimes [[necrotic]]
**[[Metastasis]] is seen in about 50% of cases; [[Lymph node|lymph nodes]] most common
**Closely packed small [[basophilic]] [[Cell (biology)|cells]]; [[mitosis]] is frequent with central [[keratinization]]
**“Starry sky” like features; displays close features to [[neuroendocrine]] [[Tumor|tumors]]
**p16 positive
**[[Hyaline|Hyalinization]] of the [[stroma]] is frequent
**[[Local]] recurrence is high; [[mortality]] is high, depends on the extension at time of treatment
*'''Papillary basaloid carcinoma'''
**Rare and affect the [[glans]]
**Hyperparakeratosis and [[Condylomata acuminata|kondylomatous]] [[Features (pattern recognition)|features]] are frequent <ref name="pmid20115951">{{cite journal| author=Renaud-Vilmer C, Cavelier-Balloy B, Verola O, Morel P, Servant JM, Desgrandchamps F et al.| title=Analysis of alterations adjacent to invasive squamous cell carcinoma of the penis and their relationship with associated carcinoma. | journal=J Am Acad Dermatol | year= 2010 | volume= 62 | issue= 2 | pages= 284-90 | pmid=20115951 | doi=10.1016/j.jaad.2009.06.087 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20115951  }} </ref>
**p16 positive
**Resemble [[Urothelial carcinoma|urothelial]] [[Urothelial carcinoma|carcinomas]]
*'''Warty carcinoma'''
**Look like [[Condyloma|condylomas]]
**Account for 5–10% of the [[Penis|penile]] [[Carcinoma|carcinomas]]
**Macronodular cauliflower-like [[appearance]]
**[[Papillae]] have a dark fibrovascular [[Core (anatomy)|core]] that the [[tumor]] surrounds with a whitish aspect
**[[Pleomorphic]] [[Koilocyte|koilocytes]], hyper and parakeratosis, [[nuclear]] [[pleomorphism]], and [[cellular]] clarification
**Individual [[cell]] [[necrosis]]
**[[Carcinoma|Carcinomas]] invading [[Corpus cavernosum|corpus]] [[Corpus cavernosum penis|cavernosum]] and [[dartos]], usually do not display [[intravascular]] or perineural invasion
**Nodal [[metastasis]] is seen in <20%
**The [[Mortality rate|mortality]] [[rate]] is low
*'''Warty–basaloid carcinoma'''
**Shows both warty and basaloid features
**Present as voluminous [[Mass|masses]] growing from the [[glans]] and [[foreskin]]
**[[Histologically]], these [[tumors]] are mixed with a [[Papillomatosis|papillomatous]] warty-like [[Surface anatomy|surface]] and a solid basaloid [[Invasive (medical)|invasive]] component
**p16 is strongly expressed
**[[Invasive (medical)|Invasion]] into deeper structures is frequent, [[vascular]] and perineural [[Invasion|invasions]] are frequent
**More aggressive than their warty counterpart
**Around 50% will develop [[lymph node]] [[metastasis]]; 30% will die of [[disease]]
*'''Clear-cell carcinoma'''
**Aggressive
**Occurs as a large [[mass]] of the [[glans]] and [[foreskin]]
**[[Tumor]] develops in sheets
**[[Necrosis]] is frequent
**[[Staining]] of the [[Clear cell|clear cells]] is positive for p16
**[[Vascular]] and perineural [[Invasive (medical)|invasion]] is frequent
**[[Tumor]]-related mortality is around 20%
*'''Lymphoepithelioma-like carcinoma'''
**Poorly [[Differentiate|differentiated]]
**[[Tumor]] [[growth]] starts most of the time at the [[glans]] and extends to the [[foreskin]]
**More or less circumscribed; sheets with [[lymphocytic]] or plasmacytic [[Cells (biology)|cells]] mixed with [[tumor]] [[Cells (biology)|cells]] are common
**p63 and p16 positive
**[[Prognosis]] is adverse; only few cases have been described
'''Non-HPV related Penile Carcinoma'''
*'''SCC usual type/not otherwise specified'''
**Exophytic [[gross]] [[appearance]]
**Endophytic [[Ulcerated lesion|ulcerated]] cases
**A tendency to [[Invasive (medical)|invade]] deeply into the [[Penis|penile]] [[tissue]] deeply
**Two-thirds of [[patients]] present [[inguinal]] [[metastasis]], and the [[mortality]] is about 30%
**The number of positive [[lymph nodes]] is an important [[Prognosis|prognosticator]]
*'''Pseudohyperplastic carcinoma'''
**[[Tumor]] is an extremely [[Differentiate|differentiated]] [[Squamous cell carcinoma|SCC]]
**Mostly associated with [[Lichen sclerosus|lichen]] [[Lichen sclerosus|sclerosis]], and occurs on the [[foreskin]] of older [[patients]]
**An association with other [[histological]] types is frequent
**[[Gross]] aspects are flat or slightly elevated; multifocality is common
**Sharp [[Border cells|borders]], [[Cells (biology)|cells]] are very well [[Differentiate|differentiated]], and peritumoral [[stroma]] is absent or minimal
**No [[vascular]] or perineural [[invasion]] or [[metastasis]]
*'''Pseudoglandular carcinoma'''
**This variant is aggressive with acantholysis and pseudoglandular spaces
**[[Patients]] are younger, around 50 yr of [[age]]
**[[Distal]], irregular, firm, whitish, [[Ulcerated lesion|ulcerated]] [[mass]]
**[[Histologically]], honeycomb aspects present
**Filled with [[necrotic]] debris.
**Poorly [[Differentiate|differentiated]] and high-grade [[tumors]]
**[[Lymph node]] [[Metastasis|metastases]] occur in more than two-thirds and the [[mortality rate]] is high
*'''Verrucous carcinoma'''
**Accounts for 2-3% of all [[Penis|penile]] [[carcinomas]]
**Extremely well [[Differentiate|differentiated]] with [[Papillomatosis|papillomatous]] aspects;
**[[Tumor]] [[base]] is broad and the [[tumor]] has borders pushing into the [[stroma]]
**Has a slow evolution and is seen in [[Old age|older]] [[patients]]
**Frequently associated with [[lichen sclerosus]]
**[[Gross|Grossly]], the aspect is exophytic, [[Papillomatosis|papillomatous]] is white to [[gray]], and the interface between [[tumor]] and [[stroma]] is sharply delineated
**Shows [[hyperkeratosis]], [[Acanthosis nigricans|acanthosis]], and [[Papillomatosis|papillomatous]] aspects
**[[Tumor]] does not directly invade the [[lamina propria]], but pushes the [[Border cells|borders]] into deeper [[tissue]], known as [[Invasive (medical)|invasion]]
**[[Prognosis]] is good
**Slowly growing [[tumor]] recur in a third of cases, mostly because of underestimation in [[histology]] as a [[benign]] [[neoplasm]] or because of insufficient [[surgery]]
*'''Carcinoma cuniculatum'''
**A variant of the [[verrucous carcinoma]] and a low-grade [[carcinoma]]
**Men between the [[age]] of 70 and 80 yr
**Most frequently the [[lesions]] grow from the [[glans]] into the deeper layers to the erectile corpora
**[[Tumor]] is whitish and [[Gray|grey]], and deep [[Invagination|invaginations]] are common
**[[Histologically]] well [[Differentiate|differentiated]]; no [[Koilocyte|koilocytes]] are seen
**No [[vascular]] or perineural [[invasion]]
**The [[invasion]] is with broad pushing [[Border cells|borders]]; no [[metastasis]] can be found
*'''Papillary carcinoma NOS'''
**[[carcinoma]] is [[Papillomatosis|papillomatous]] and [[Verrucae|verruciform]]
**No [[Koilocyte|koilocytes]]
**[[Tumor]] accounts for about 5–8% of [[Penis|penile]] [[carcinomas]] and is usually associated with [[lichen sclerosus]]
**[[Tumor]] has a cauliflower-like, whitish aspect that is badly limited
**[[Histologically]], we see well-[[Differentiate|differentiated]] hyperkeratotic [[lesions]]
**[[Tumors]] can recur, but [[mortality]] and [[metastasis]] are [[rare]]
*'''Adenosquamous carcinoma'''
**[[Squamous cell carcinoma|SCCs]] with [[mucinous]] features
**Also called [[Mucoepidermoid carcinoma|mucoepidermoid]] [[Mucoepidermoid carcinoma|carcinomas]]
**Recurrence and [[lymph node]] [[metastasis]] is seen in up to 50%, but [[mortality]] remains low
**[[Rare]]
*'''Sarcomatoid SCC'''
**The most aggressive [[neoplasm]] of [[penis]]
**Focal [[squamous]] [[differentiation]] is seen
**[[Spindle cells|Spindle cell]] component should be present in at least 30%
**[[Mass|Masses]] are slowly [[Growth|growing]] and frequently [[Ulcerated lesion|ulcerated]]
**Recurrence and regional or [[systemic]] [[Metastasis|metastases]] are possible
**[[Necrosis]] and [[hemorrhage]] are frequent.
**[[Atypia]], [[mitosis]], [[pleomorphism]], and sarcomatoid aspects
**In 80%, local recurrence exists with [[Inguinal|inguina]]<nowiki/>l [[metastases]]
**[[Mortality]] is high (up to 75%), and most [[patients]] die within a [[year]]
*'''Mixed SCC'''
**Contain at least two variants of [[Squamous cell carcinoma|SCCs]]
**[[Patients]] are [[Old age|older]], mostly in their 7th decade
**Located on the [[glans]]
**Present as a white, exophytic, [[Gray|grayish]] [[mass]] replacing the [[distal]] [[penis]], invading deeply the [[erectile tissue]]
**Most frequent is the combination of [[Wart|warty]] and basaloid [[carcinomas]]
**Possible to have [[Human papillomavirus|HPV]]- and non–[[Human papillomavirus|HPV]]-related features in the same [[tumors]]
**[[Mortality]] is [[rare]] (<5%)
**Less aggressive
==Microscopic Pathology ==
* On [[microscopic]] [[histopathological]] [[analysis]], [[keratinization]] and intercellular bridges are characteristic findings of [[carcinoma]] of the [[penis]].<ref>{{Cite web | title =Squamous cell carcinoma of the penis.Libre Pathology 2015| url =http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma_of_the_penis}}</ref>
===Grades of penile cancer===
* [[Grading (tumors)|Grading]] is a way of classifying [[Penis|penile]] [[cancer]] [[Cell (biology)|cells]] based on their [[appearance]] and [[behaviour]] when viewed under a [[Microscopes|microscope]].<ref>{{Cite web | title =Grades of penile cancer.Canadian Cancer Society 2015| url =http://www.cancer.ca/en/cancer-information/cancer-type/penile/grading/?region=ab}}</ref>
* The grade of [[penile cancer]] is based on the degree of [[differentiation]] of [[Cells (biology)|cells]] and their [[rate]] of [[growth]].
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align="center"
| valign="top" |
|+
! style="background: #4479BA; width: 50px;" | {{fontcolor|#FFF|Grade}}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Definition}}
|-
| style="padding: 5px 5px; background: #DCDCDC;" |GX
| style="padding: 5px 5px; background: #F5F5F5;" |Grade of differentiation cannot be assessed
|-
| style="padding: 5px 5px; background: #DCDCDC;" |G1
| style="padding: 5px 5px; background: #F5F5F5;" |Well differentiated or low grade
|-
| style="padding: 5px 5px; background: #DCDCDC;" |G2
| style="padding: 5px 5px; background: #F5F5F5;" |Moderately well differentiated or moderate grade
|-
| style="padding: 5px 5px; background: #DCDCDC;" |G3
| style="padding: 5px 5px; background: #F5F5F5;" |Poorly differentiated or high grade
|-
| style="padding: 5px 5px; background: #DCDCDC;" |G4
| style="padding: 5px 5px; background: #F5F5F5;" |Undifferentiated or high grade
|}


==References==
==References==
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Types of cancer]]
[[Category:Oncology]]
[[Category:Andrology]]
[[Category:Andrology]]
[[Category:Penis]]
[[Category:Penis]]

Latest revision as of 10:36, 3 April 2019

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Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-632-7753; Swathi Venkatesan, M.B.B.S.[2]

Overview

On gross pathology, the glans and the foreskin are the most common locations to find scaly patches, nodules, palpable painless lump, erythematous, ulceration, concurrent phimosis may conceal the lesion, surface of the lesion may be exophytic, flat, or ulcerated, chronic penile rash or subtle burning sensation and swollen inguinal lymph nodes as characteristic findings of carcinoma of penis. On microscopic histopathological analysis, keratinization and intercellular bridges are characteristic findings of carcinoma of the penis.

Pathogenesis

Grossly noted growth patterns include:

  1. Superficial spreading: tumors are limited to lamina propria or superficial corpus spongiosum.
    1. Usually extend horizontally through multiple anatomical compartments
  2. Vertical growth: tumors invade deep anatomical levels, surface is non-verruciform and frequently ulcerated
  3. Verruciform: tumors are exophytic and papillomatous with a cauliflower-like aspect.
    1. May be limited to surface (verrucous) or invade deep anatomical levels (cuniculatum)
  4. Mixed patterns: observed in 10 - 15% of all cases

On microscopic histopathological analysis, characteristic findings of carcinoma of the penis include:

Grading:

Gross & Microscopic Pathology

HPV-related Penile Carcinoma

Non-HPV related Penile Carcinoma

Microscopic Pathology

Grades of penile cancer
Grade Definition
GX Grade of differentiation cannot be assessed
G1 Well differentiated or low grade
G2 Moderately well differentiated or moderate grade
G3 Poorly differentiated or high grade
G4 Undifferentiated or high grade

References

  1. ↑ Spiess, Philippe (2013). Penile cancer : diagnosis and treatment. New York: Humana Press. ISBN 978-1-4939-6679-0.
  2. ↑ Spiess, Philippe E.; Dhillon, Jasreman; Baumgarten, Adam S.; Johnstone, Peter A.; Giuliano, Anna R. (2016). "Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies". CA: A Cancer Journal for Clinicians. 66 (6): 481–495. doi:10.3322/caac.21354. ISSN 0007-9235.
  3. ↑ Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ (2009). "Penile cancer: epidemiology, pathogenesis and prevention". World J Urol. 27 (2): 141–50. doi:10.1007/s00345-008-0302-z. PMID 18607597.
  4. ↑ Cubilla AL (2009). "The role of pathologic prognostic factors in squamous cell carcinoma of the penis". World J Urol. 27 (2): 169–77. doi:10.1007/s00345-008-0315-7. PMID 18766352.
  5. ↑ "StatPearls". 2019. PMID 29763105.
  6. ↑ Renaud-Vilmer C, Cavelier-Balloy B, Verola O, Morel P, Servant JM, Desgrandchamps F; et al. (2010). "Analysis of alterations adjacent to invasive squamous cell carcinoma of the penis and their relationship with associated carcinoma". J Am Acad Dermatol. 62 (2): 284–90. doi:10.1016/j.jaad.2009.06.087. PMID 20115951.
  7. ↑ "Squamous cell carcinoma of the penis.Libre Pathology 2015".
  8. ↑ "Grades of penile cancer.Canadian Cancer Society 2015".


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