Carcinoma of the penis pathophysiology: Difference between revisions

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*'''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 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 2:''' all [[tumors]] not fitting into criteria for grade 1 or 3
*'''Grade 3:''' any [[Anaplasia|anaplastic]] cells
*'''Grade 3:''' any [[Anaplasia|anaplastic]] [[Cell (biology)|cells]]


==Gross & Microscopic Pathology==
==Gross & Microscopic Pathology==
'''HPV-related Penile Carcinoma'''
'''HPV-related Penile Carcinoma'''
*'''Basaloid SCC'''
*'''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>
**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 masses, which are deeply invasive and sometimes necrotic
**Flat [[Ulcerated lesion|ulcerated]] [[Mass|masses]], which are deeply [[Invasive (medical)|invasive]] and sometimes [[necrotic]]
**Metastasis is seen in about 50% of cases; lymph nodes most common
**[[Metastasis]] is seen in about 50% of cases; [[Lymph node|lymph nodes]] most common
**Closely packed small basophilic cells; mitosis is frequent with central keratinization
**Closely packed small [[basophilic]] [[Cell (biology)|cells]]; [[mitosis]] is frequent with central [[keratinization]]
**“Starry sky” like features; displays close features to neuroendocrine tumors
**“Starry sky” like features; displays close features to [[neuroendocrine]] [[Tumor|tumors]]
**p16 positive
**p16 positive
**Hyalinization of the stroma is frequent
**[[Hyaline|Hyalinization]] of the [[stroma]] is frequent
**Local recurrence is high; mortality is high, depends on the extension at time of treatment
**[[Local]] recurrence is high; [[mortality]] is high, depends on the extension at time of treatment


*'''Papillary basaloid carcinoma'''
*'''Papillary basaloid carcinoma'''
**Rare and affect the glans
**Rare and affect the [[glans]]
**Hyperparakeratosis and kondylomatous 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>
**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
**p16 positive
**Resemble urothelial carcinomas
**Resemble [[Urothelial carcinoma|urothelial]] [[Urothelial carcinoma|carcinomas]]


*'''Warty carcinoma'''
*'''Warty carcinoma'''
**Look like condylomas  
**Look like [[Condyloma|condylomas]]
**Account for 5–10% of the penile carcinomas
**Account for 5–10% of the [[Penis|penile]] [[Carcinoma|carcinomas]]
**Macronodular cauliflower-like appearance
**Macronodular cauliflower-like [[appearance]]
**Papillae have a dark fibrovascular core that the tumor surrounds with a whitish aspect
**[[Papillae]] have a dark fibrovascular [[Core (anatomy)|core]] that the [[tumor]] surrounds with a whitish aspect
**Pleomorphic koilocytes, hyper and parakeratosis, nuclear pleomorphism, and cellular clarification
**[[Pleomorphic]] [[Koilocyte|koilocytes]], hyper and parakeratosis, [[nuclear]] [[pleomorphism]], and [[cellular]] clarification
**Individual cell necrosis
**Individual [[cell]] [[necrosis]]
**Carcinomas invading corpus cavernosum and dartos, usually do not display intravascular or perineural invasion
**[[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%
**Nodal [[metastasis]] is seen in <20%
**The mortality rate is low
**The [[Mortality rate|mortality]] [[rate]] is low


*'''Warty–basaloid carcinoma'''
*'''Warty–basaloid carcinoma'''
**Shows both warty and basaloid features
**Shows both warty and basaloid features
**Present as voluminous masses growing from the glans and foreskin
**Present as voluminous [[Mass|masses]] growing from the [[glans]] and [[foreskin]]
**Histologically, these tumors are mixed with a papillomatous warty-like surface and a solid basaloid invasive component
**[[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
**p16 is strongly expressed
**Invasion into deeper structures is frequent, vascular and perineural invasions are frequent
**[[Invasive (medical)|Invasion]] into deeper structures is frequent, [[vascular]] and perineural [[Invasion|invasions]] are frequent
**More aggressive than their warty counterpart
**More aggressive than their warty counterpart
**Around 50% will develop lymph node metastasis; 30% will die of disease  
**Around 50% will develop [[lymph node]] [[metastasis]]; 30% will die of [[disease]]


*'''Clear-cell carcinoma'''
*'''Clear-cell carcinoma'''
**Aggressive
**Aggressive
**Occurs as a large mass of the glans and foreskin
**Occurs as a large [[mass]] of the [[glans]] and [[foreskin]]
**Tumor develops in sheets
**[[Tumor]] develops in sheets
**Necrosis is frequent
**[[Necrosis]] is frequent
**Staining of the clear cells is positive for p16
**[[Staining]] of the [[Clear cell|clear cells]] is positive for p16
**Vascular and perineural invasion is frequent
**[[Vascular]] and perineural [[Invasive (medical)|invasion]] is frequent
**Tumor-related mortality is around 20%
**[[Tumor]]-related mortality is around 20%


*'''Lymphoepithelioma-like carcinoma'''
*'''Lymphoepithelioma-like carcinoma'''
**Poorly differentiated
**Poorly [[Differentiate|differentiated]]
**Tumor growth starts most of the time at the glans and extends to the foreskin
**[[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 mixed with tumor cells are common
**More or less circumscribed; sheets with [[lymphocytic]] or plasmacytic [[Cells (biology)|cells]] mixed with [[tumor]] [[Cells (biology)|cells]] are common
**p63 and p16 positive
**p63 and p16 positive
**Prognosis is adverse; only few cases have been described
**[[Prognosis]] is adverse; only few cases have been described


'''Non-HPV related Penile Carcinoma'''
'''Non-HPV related Penile Carcinoma'''
*'''SCC usual type/not otherwise specified'''
*'''SCC usual type/not otherwise specified'''
**Exophytic gross appearance
**Exophytic [[gross]] [[appearance]]
**Endophytic ulcerated cases
**Endophytic [[Ulcerated lesion|ulcerated]] cases
**A tendency to invade deeply into the penile tissue deeply  
**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%
**Two-thirds of [[patients]] present [[inguinal]] [[metastasis]], and the [[mortality]] is about 30%
**The number of positive lymph nodes is an important prognosticator
**The number of positive [[lymph nodes]] is an important [[Prognosis|prognosticator]]


*'''Pseudohyperplastic carcinoma'''
*'''Pseudohyperplastic carcinoma'''
**Tumor is an extremely differentiated SCC
**[[Tumor]] is an extremely [[Differentiate|differentiated]] [[Squamous cell carcinoma|SCC]]
**Mostly associated with lichen sclerosis, and occurs on the foreskin of older patients
**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
**An association with other [[histological]] types is frequent
**Gross aspects are flat or slightly elevated; multifocality is common
**[[Gross]] aspects are flat or slightly elevated; multifocality is common
**Sharp borders, cells are very well differentiated, and peritumoral stroma is absent or minimal
**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  
**No [[vascular]] or perineural [[invasion]] or [[metastasis]]


*'''Pseudoglandular carcinoma'''
*'''Pseudoglandular carcinoma'''
**This variant is aggressive with acantholysis and pseudoglandular spaces
**This variant is aggressive with acantholysis and pseudoglandular spaces
**Patients are younger, around 50 yr of age
**[[Patients]] are younger, around 50 yr of [[age]]
**Distal, irregular, firm, whitish, ulcerated mass
**[[Distal]], irregular, firm, whitish, [[Ulcerated lesion|ulcerated]] [[mass]]
**Histologically, honeycomb aspects present
**[[Histologically]], honeycomb aspects present
**Filled with necrotic debris.
**Filled with [[necrotic]] debris.
**Poorly differentiated and high-grade tumors
**Poorly [[Differentiate|differentiated]] and high-grade [[tumors]]
**Lymph node metastases occur in more than two-thirds and the mortality rate is high
**[[Lymph node]] [[Metastasis|metastases]] occur in more than two-thirds and the [[mortality rate]] is high


*'''Verrucous carcinoma'''
*'''Verrucous carcinoma'''
**Accounts for 2-3% of all penile carcinomas
**Accounts for 2-3% of all [[Penis|penile]] [[carcinomas]]
**Extremely well differentiated with papillomatous aspects;
**Extremely well [[Differentiate|differentiated]] with [[Papillomatosis|papillomatous]] aspects;
**Tumor base is broad and the tumor has borders pushing into the stroma  
**[[Tumor]] [[base]] is broad and the [[tumor]] has borders pushing into the [[stroma]]
**Has a slow evolution and is seen in older patients
**Has a slow evolution and is seen in [[Old age|older]] [[patients]]
**Frequently associated with lichen sclerosus
**Frequently associated with [[lichen sclerosus]]
**Grossly, the aspect is exophytic, papillomatous is white to gray, and the interface between tumor and stroma is sharply delineated
**[[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, and papillomatous aspects
**Shows [[hyperkeratosis]], [[Acanthosis nigricans|acanthosis]], and [[Papillomatosis|papillomatous]] aspects
**Tumor does not directly invade the lamina propria, but pushes the borders into deeper tissue, known as invasion
**[[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
**[[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
**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'''
*'''Carcinoma cuniculatum'''
**A variant of the verrucous carcinoma and a low-grade carcinoma
**A variant of the [[verrucous carcinoma]] and a low-grade [[carcinoma]]
**Men between the age of 70 and 80 yr  
**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
**Most frequently the [[lesions]] grow from the [[glans]] into the deeper layers to the erectile corpora
**Tumor is whitish and grey, and deep invaginations are common
**[[Tumor]] is whitish and [[Gray|grey]], and deep [[Invagination|invaginations]] are common
**Histologically well differentiated; no koilocytes are seen
**[[Histologically]] well [[Differentiate|differentiated]]; no [[Koilocyte|koilocytes]] are seen
**No vascular or perineural invasion
**No [[vascular]] or perineural [[invasion]]
**The invasion is with broad pushing borders; no metastasis can be found
**The [[invasion]] is with broad pushing [[Border cells|borders]]; no [[metastasis]] can be found


*'''Papillary carcinoma NOS'''
*'''Papillary carcinoma NOS'''
**carcinoma is papillomatous and verruciform
**[[carcinoma]] is [[Papillomatosis|papillomatous]] and [[Verrucae|verruciform]]
**No koilocytes  
**No [[Koilocyte|koilocytes]]
**Tumor accounts for about 5–8% of penile carcinomas and is usually associated with lichen sclerosus
**[[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
**[[Tumor]] has a cauliflower-like, whitish aspect that is badly limited
**Histologically, we see well-differentiated hyperkeratotic lesions
**[[Histologically]], we see well-[[Differentiate|differentiated]] hyperkeratotic [[lesions]]
**Tumors can recur, but mortality and metastasis are rare
**[[Tumors]] can recur, but [[mortality]] and [[metastasis]] are [[rare]]


*'''Adenosquamous carcinoma'''
*'''Adenosquamous carcinoma'''
**SCCs with mucinous features
**[[Squamous cell carcinoma|SCCs]] with [[mucinous]] features
**Also called mucoepidermoid carcinomas
**Also called [[Mucoepidermoid carcinoma|mucoepidermoid]] [[Mucoepidermoid carcinoma|carcinomas]]
**Recurrence and lymph node metastasis is seen in up to 50%, but mortality remains low  
**Recurrence and [[lymph node]] [[metastasis]] is seen in up to 50%, but [[mortality]] remains low  
**Rare
**[[Rare]]


*'''Sarcomatoid SCC'''
*'''Sarcomatoid SCC'''
**The most aggressive neoplasm of penis
**The most aggressive [[neoplasm]] of [[penis]]
**Focal squamous differentiation is seen
**Focal [[squamous]] [[differentiation]] is seen
**Spindle cell component should be present in at least 30%
**[[Spindle cells|Spindle cell]] component should be present in at least 30%
**Masses are slowly growing and frequently ulcerated
**[[Mass|Masses]] are slowly [[Growth|growing]] and frequently [[Ulcerated lesion|ulcerated]]
**Recurrence and regional or systemic metastases are possible
**Recurrence and regional or [[systemic]] [[Metastasis|metastases]] are possible
**Necrosis and hemorrhage are frequent.
**[[Necrosis]] and [[hemorrhage]] are frequent.
**Atypia, mitosis, pleomorphism, and sarcomatoid aspects
**[[Atypia]], [[mitosis]], [[pleomorphism]], and sarcomatoid aspects
**In 80%, local recurrence exists with inguinal metastases
**In 80%, local recurrence exists with [[Inguinal|inguina]]<nowiki/>l [[metastases]]
**Mortality is high (up to 75%), and most patients die within a year
**[[Mortality]] is high (up to 75%), and most [[patients]] die within a [[year]]


*'''Mixed SCC'''
*'''Mixed SCC'''
**Contain at least two variants of SCCs
**Contain at least two variants of [[Squamous cell carcinoma|SCCs]]
**Patients are older, mostly in their 7th decade
**[[Patients]] are [[Old age|older]], mostly in their 7th decade
**Located on the glans
**Located on the [[glans]]
**Present as a white, exophytic, grayish mass replacing the distal penis, invading deeply the erectile tissue
**Present as a white, exophytic, [[Gray|grayish]] [[mass]] replacing the [[distal]] [[penis]], invading deeply the [[erectile tissue]]
**Most frequent is the combination of warty and basaloid carcinomas
**Most frequent is the combination of [[Wart|warty]] and basaloid [[carcinomas]]
**Possible to have HPV- and non–HPV-related features in the same tumors
**Possible to have [[Human papillomavirus|HPV]]- and non–[[Human papillomavirus|HPV]]-related features in the same [[tumors]]
**Mortality is rare (<5%)
**[[Mortality]] is [[rare]] (<5%)
**Less aggressive
**Less aggressive


==Microscopic Pathology ==
==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>
* 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===
===Grades of penile cancer===
* Grading is a way of classifying penile cancer cells based on their appearance and behaviour when viewed under a 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>
* [[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 and their rate of growth.
* The grade of [[penile cancer]] is based on the degree of [[differentiation]] of [[Cells (biology)|cells]] and their [[rate]] of [[growth]].


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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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