Skip to main content
SpringerLink
Log in
Book cover

Pathology of Testicular and Penile Neoplasms pp 229–273Cite as

Tumors of the Penis and Scrotum

  • Chapter
  • First Online:

  • 1213 Accesses

Abstract

Squamous cell carcinoma (SCC) is the most frequent penile tumor, occurring as usual-type SCC in almost 50 % of cases. It presents most frequently in the sixth to seventh decades of life [1], while it is uncommon in young adults. The different rates among countries and regional differences in prevalence even in the same country are not fully understood; the comparison of subtypes of penile cancer reported from high- and low-incidence regions showed no geographical differences between histologic subtypes and in the frequency of HPV-related tumors [2]. For instance, a similar distribution of penile cancer subtypes was observed in Paraguay and the USA, supporting the notion that previously reported geographical variations may have been the result of staging variation at clinical presentation, probably because lesions tend to be diagnosed early (i.e., in precancerous or in situ stages) in developed countries [2, 3]. The presence of human papillomavirus (HPV) was found to be a risk factor for penile SCC [4]: depending on the population examined, the technique used, and tumor morphology, the HPV detection rate has been estimated to range from 30 to 83 % of cases, while the prevalence is thought to be around 50 % [5]. In a recent immunohistochemical and HPV in situ hybridization (HPV ISH) study in a North American population, a low percentage (27 %) of high-risk HPV-positive cases of penile cancer was found [6]. In the majority of these cases, high-risk HPV subtypes (HPV-16 and HPV-18) were integrated into the genome with a characteristic nuclear ISH reactivity; the same integrated subtype was observed in both primary and metastatic tumors. HPV is most frequently associated with basaloid or warty carcinoma variants, where it has been reported in 75–100 % of cases, while the majority of usual/keratinizing and verrucous carcinomas are not HPV related [1, 2, 6–9].

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Cubilla AL, Reuter V, Velazquez E, Piris A, Saito S, Young RH. Histologic classification of penile carcinoma and its relation to outcome in 61 patients with primary resection. Int J Surg Pathol. 2001;9:111–20.

    Article  CAS  PubMed  Google Scholar 

  2. Chaux A, Lezcano C, Cubilla AL, Tamboli P, Ro J, Ayala A. Comparison of subtypes of penile squamous cell carcinoma from high and low incidence geographical regions. Int J Surg Pathol. 2010;18:268–77.

    Article  PubMed  Google Scholar 

  3. Chaux A, Velazquez EF, Amin A, Soskin A, Pfannl R, Rodríguez IM, Barreto JE, Lezcano C, Ayala G, Netto GJ, Cubilla AL. Distribution and characterization of subtypes of penile intraepithelial neoplasia and their association with invasive carcinomas: a pathological study of 139 lesions in 121 patients. Hum Pathol. 2012;43:1020–7.

    Article  PubMed  Google Scholar 

  4. Gregoire L, Cubilla AL, Reuter VE, Haas GP, Lancaster WD. Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma. J Natl Cancer Inst. 1995;87:1705–9.

    Article  CAS  PubMed  Google Scholar 

  5. Miralles-Guri C, Bruni L, Cubilla AL, Castellsagué X, Bosch FX, de Sanjosé S. Human papillomavirus prevalence and type distribution in penile carcinoma. J Clin Pathol. 2009;62:870–8.

    Article  CAS  PubMed  Google Scholar 

  6. Mentrikoski MJ, Stelow EB, Culp S, Frierson Jr HF, Cathro HP. Histologic and immunohistochemical assessment of penile carcinomas in a North American population. Am J Surg Pathol. 2014;38:1340–8.

    Article  PubMed  Google Scholar 

  7. Chaux A, Cubilla AL. The role of human papillomavirus infection in the pathogenesis of penile squamous cell carcinomas. Semin Diagn Pathol. 2012;29:67–71.

    Article  PubMed  Google Scholar 

  8. Chaux A, Velazquez EF, Algaba F, Ayala G, Cubilla AL. Developments in the pathology of penile squamous cell carcinomas. Urology. 2010;76:S7–14.

    Article  PubMed  Google Scholar 

  9. Epstein JH, Cubilla AL, Humphrey PA. Tumors of the prostate gland, seminal vesicles, penis and scrotum. Washington, DC: American Registry of Pathology AFIP Atlas of tumor pathology 3rd series, 2011. Fascicle 14, p. 405–612.

    Google Scholar 

  10. Longpre MJ, Lange PH, Kwon JS, Black PC. Penile carcinoma: lessons learned from vulvar carcinoma. J Urol. 2013;189:17–24.

    Article  PubMed  Google Scholar 

  11. Velazquez EF, Amin MB, Cubilla AL. Penis and scrotum. Chapter 14. In: Amin MB, Eble JN, Grignon DJ, Srigley JR, editors. Urologic pathology. Philadelphia: Lippincott Williams and Wilkins; 2014.

    Google Scholar 

  12. Velazquez EF, Cubilla AL. Lichen sclerosus in 68 patients with squamous cell carcinoma of the penis: frequent atypias and correlation with special carcinoma variants suggests a precancerous role. Am J Surg Pathol. 2003;27:1448–53.

    Article  PubMed  Google Scholar 

  13. Oertell J, Duarte S, Ayala J, Chaux A, Velazquez EF, Cubilla AL. Squamous cell carcinoma (SCC) exclusive of the foreskin: distinctive association with low grade variants, multicentricity and lichen sclerosus. Mod Pathol. 2002;15:175A.

    Google Scholar 

  14. Fukunaga M, Yokoi K, Miyazawa Y, Harada T, Ushigome S. Penile verrucous carcinoma with anaplastic transformation following radiotherapy. A case report with human papillomavirus typing and flow cytometric DNA studies. Am J Surg Pathol. 1994;18:501–5.

    Article  CAS  PubMed  Google Scholar 

  15. Sanchez DF, Canete S, Fernandez-Nestosa MJ, Lezcano C, Rodriguez I, Barreto J, Alvarado-Cabreo I, Cubilla AL. HPV- and non-HPV-related subtypes of penile squamous cell carcinoma (SCC): morphological features and differential diagnosis according to the new WHO classification (2015). Semin Diagn Pathol. 2015;32:198–221.

    Article  PubMed  Google Scholar 

  16. Chaux A, Velazquez EF, Barreto JE, Ayala E, Cubilla AL. New pathologic entities in penile carcinomas: an update of the 2004 World Health Organization classification. Semin Diagn Pathol. 2012;29:59–66.

    Article  PubMed  Google Scholar 

  17. Velazquez EF, Barreto JE, Rodriguez I, Piris A, Cubilla AL. Limitations in the interpretation of biopsies in patients with penile squamous cell carcinoma. Int J Surg Pathol. 2004;12:139–46.

    Article  PubMed  Google Scholar 

  18. Guimarães GC, Cunha IW, Soares FA, Lopes A, Torres J, Chaux A, Velazquez EF, Ayala G, Cubilla AL. Penile squamous cell carcinoma clinicopathological features, nodal metastasis and outcome in 333 cases. J Urol. 2009;182:528–34.

    Article  PubMed  Google Scholar 

  19. Kurman RJ, Toki T, Schiffman MH. Basaloid and warty carcinomas of the vulva. Distinctive types of squamous cell carcinoma frequently associated with human papillomaviruses. Am J Surg Pathol. 1993;17:133–45.

    Article  CAS  PubMed  Google Scholar 

  20. Davies SW. Giant condyloma acuminata: incidence among cases diagnosed as carcinoma of the penis. J Clin Pathol. 1965;18:142–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cubilla AL, Velazques EF, Reuter VE, Oliva E, Mihm Jr MC, Young RH. Warty (condylomatous) squamous cell carcinoma of the penis: a report of 11 cases and proposed classification of ‘verruciform’ penile tumors. Am J Surg Pathol. 2000;24:505–12.

    Article  CAS  PubMed  Google Scholar 

  22. Epstein JI, Netto GJ. Differential diagnosis in surgical pathology: genitourinary system. Chapter 5: penis/scrotum. Philadelphia: Lippincott Williams and Wilkins; 2014.

    Google Scholar 

  23. Bezerra AL, Lopes A, Landman G, Alencar GN, Torloni H, Villa LL. Clinicopathologic features and human papillomavirus dna prevalence of warty and squamous cell carcinoma of the penis. Am J Surg Pathol. 2001;25:673–8.

    Article  CAS  PubMed  Google Scholar 

  24. Cubilla AL, Lloveras B, Alejo M, Clavero O, Chaux A, Kasamatsu E, Monfulleda N, Tous S, Alemany L, Klaustermeier J, Muñoz N, Quint W, de Sanjose S, Bosch FX. Value of p16(INK)4(a) in the pathology of invasive penile squamous cell carcinomas: A report of 202 cases. Am J Surg Pathol. 2011;35:253–61.

    Article  PubMed  Google Scholar 

  25. Chan KW, Lam KY, Chan AC, Lau P, Srivastava G. Prevalence of human papillomavirus types 16 and 18 in penile carcinoma: a study of 41 cases using PCR. J Clin Pathol. 1994;47:823–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Johnson DE, Lo RK, Srigley J, Ayala AG. Verrucous carcinoma of the penis. J Urol. 1985;133:216–8.

    CAS  PubMed  Google Scholar 

  27. Stankiewicz E, Kudahetti SC, Prowse DM, Ktori E, Cuzick J, Ambroisine L, Zhang X, Watkin N, Corbishley C, Berney DM. HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis. Mod Pathol. 2009;22:1160–8.

    Article  CAS  PubMed  Google Scholar 

  28. Masih AS, Stoler MH, Farrow GM, Wooldridge TN, Johansson SL. Penile verrucous carcinoma: a clinicopathologic, human papillomavirus typing and flow cytometric analysis. Mod Pathol. 1992;5:48–55.

    CAS  PubMed  Google Scholar 

  29. Mukai S, Nakahara K, Nagai T, Kamibeppu T, Sugie S, Tsukino H, Kamimura T, Wakeda H, Kamoto T. Pure verrucous carcinoma of the penis: two cases. Med Surg Urol. 2014;3:125–7.

    Google Scholar 

  30. Chaux A, Soares F, Rodríguez I, Barreto J, Lezcano C, Torres J, Velazquez EF, Cubilla AL. Papillary squamous cell carcinoma, not otherwise specified (NOS) of the penis: clinicopathologic features, differential diagnosis, and outcome of 35 cases. Am J Surg Pathol. 2010;34:223–30.

    Article  PubMed  Google Scholar 

  31. Cubilla AL, Lloveras B, Alejo M, Clavero O, Chaux A, Kasamatsu E, Velazquez EF, Lezcano C, Monfulleda N, Tous S, Alemany L, Klaustermeier J, Muñoz N, Quint W, de Sanjose S, Bosch FX. The basaloid cell is the best tissue marker for human papillomavirus in invasive penile squamous cell carcinoma: a study of 202 cases from Paraguay. Am J Surg Pathol. 2010;34:104–14.

    Article  PubMed  Google Scholar 

  32. Cubilla AL, Velazquez EF, Ayala GE, Chaux A, Torres J, Reuter V. Identification of prognostic pathologic parameters in squamous cell carcinoma of the penis: significance and difficulties. Pathol Case Rev. 2005;10:3–13.

    Article  Google Scholar 

  33. Barreto JE, Velazquez EF, Ayala E, Torres J, Cubilla AL. Carcinoma cuniculatum: a distinctive variant of penile squamous cell carcinoma: report of 7 cases. Am J Surg Pathol. 2007;31:71–5.

    Article  PubMed  Google Scholar 

  34. Seehafer JR, Rahman D, Soderstrom CW. Epithelioma cuniculatum: verrucous carcinoma of the foot. Cutis. 1979;23:287–90.

    CAS  PubMed  Google Scholar 

  35. Kathuria S, Rieker J, Jablokow VR, Van den Broek H. Plantar verrucous carcinoma (epithelioma cuniculatum): case report with review of the literature. J Surg Oncol. 1986;31:71–5.

    Article  CAS  PubMed  Google Scholar 

  36. Reuter VE. Sarcomatoid lesions of the urogenital tract. Semin Diagn Pathol. 1993;10:188–201.

    CAS  PubMed  Google Scholar 

  37. Velazquez EF, Soskin A, Bock A, Codas R, Barreto JE, Cubilla AL. Positive resection margins in partial penectomies: sites of involvement and proposal of local routes of spread of penile squamous cell carcinoma. Am J Surg Pathol. 2004;28:384–9.

    Article  PubMed  Google Scholar 

  38. Velazquez EF, Melamed J, Barreto JE, Aguero F, Cubilla AL. Sarcomatoid carcinoma of the penis: a clinicopathologic study of 15 cases. Am J Surg Pathol. 2005;29:1152–8.

    Article  PubMed  Google Scholar 

  39. Cubilla AL, Reuter VE, Gregoire L, Ayala G, Ocampos S, Lancaster WD, Fair W. Basaloid squamous cell carcinoma: a distinctive human papilloma virus-related penile neoplasm: a report of 20 cases. Am J Surg Pathol. 1998;22:755–61.

    Article  CAS  PubMed  Google Scholar 

  40. Soskin A, Vieillefond A, Carlotti A, Plantier F, Chaux A, Ayala G, Velazquez EF, Cubilla AL. Warty/basaloid penile intraepithelial neoplasia is more prevalent than differentiated penile intraepithelial neoplasia in nonendemic regions for penile cancer when compared with endemic areas: a comparative study between pathologic series from Paris and Paraguay. Hum Pathol. 2012;43:190–6.

    Article  PubMed  Google Scholar 

  41. Winters R, Trotman W, Adamson CS, Rajendran V, Tang A, Elhosseiny A, Evans MF. Screening for human papillomavirus in basaloid squamous carcinoma: utility of p16(INK4a), CISH, and PCR. Int J Surg Pathol. 2011;19:309–14.

    Article  PubMed  Google Scholar 

  42. Cubilla AL, Lloveras B, Alemany L, Alejo M, Vidal A, Kasamatsu E, Clavero O, Alvarado-Cabrero I, Lynch C, Velasco-Alonso J, Ferrera A, Chaux A, Klaustermeier J, Quint W, de Sanjosé S, Muñoz N, Bosch FX. Basaloid squamous cell carcinoma of the penis with papillary features: a clinicopathologic study of 12 cases. Am J Surg Pathol. 2012;36:869–75.

    Article  PubMed  Google Scholar 

  43. Rubin MA, Kleter B, Zhou M, Ayala G, Cubilla AL, Quint WG, Pirog EC. Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol. 2001;159:1211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cubilla AL, Velazquez EF, Young RH. Pseudohyperplastic squamous cell carcinoma of the penis associated with lichen sclerosus. An extremely well-differentiated, nonverruciform neoplasm that preferentially affects the foreskin and is frequently misdiagnosed: a report of 10 cases of a distinctive clinicopathologic entity. Am J Surg Pathol. 2004;28:895–900.

    Article  PubMed  Google Scholar 

  45. Cunha IW, Guimaraes GC, Soares F, Velazquez E, Torres JJ, Chaux A, Ayala G, Cubilla AL. Pseudoglandular (adenoid, acantholytic) penile squamous cell carcinoma: a clinicopathologic and outcome study of 7 patients. Am J Surg Pathol. 2009;33:551–5.

    Article  PubMed  Google Scholar 

  46. Colecchia M, Insabato L. Pseudoglandular (adenoid, acantholytic) penile squamous cell carcinoma. Am J Surg Pathol. 2009;33:1421–2.

    Article  PubMed  Google Scholar 

  47. Cubilla AL, Ayala MT, Barreto JE, Bellasai JG, Nöel JC. Surface adenosquamous carcinoma of the penis. A report of three cases. Am J Surg Pathol. 1996;20:156–60.

    Article  CAS  PubMed  Google Scholar 

  48. Masera A, Ovcak Z, Volavsek M, Bracko M. Adenosquamous carcinoma of the penis. J Urol. 1997;157:2261.

    Article  CAS  PubMed  Google Scholar 

  49. Chaux A, Tamboli P, Ayala A, Soares F, Rodríguez I, Barreto J, Cubilla AL. Warty-basaloid carcinoma: clinicopathological features of a distinctive penile neoplasm. Report of 45 cases. Mod Pathol. 2010;23:896–904.

    Article  PubMed  Google Scholar 

  50. Chaux A, Pfannl R, Lloveras B, Alejo M, Clavero O, Lezcano C, Muñoz N, de Sanjosé S, Bosch X, Hernández-Pérez M, Velazquez EF, Cubilla AL. Distinctive association of p16INK4a overexpression with penile intraepithelial neoplasia depicting warty and/or basaloid features: a study of 141 cases evaluating a new nomenclature. Am J Surg Pathol. 2010;34:385–92.

    Article  PubMed  Google Scholar 

  51. Kato N, Onozuka T, Yasukawa K, Kimura K, Sasaki K. Penile hybrid verrucous-squamous carcinoma associated with a superficial inguinal lymph node metastasis. Am J Dermatopathol. 2000;22:339–43.

    Article  CAS  PubMed  Google Scholar 

  52. Velazquez EF, Ayala G, Liu H, Chaux A, Zanotti M, Torres J, Cho SI, Barreto JE, Soares F, Cubilla AL. Histologic grade and perineural invasion are more important than tumor thickness as predictor of nodal metastasis in penile squamous cell carcinoma invading 5 to 10 mm. Am J Surg Pathol. 2008;32:974–9.

    Article  PubMed  Google Scholar 

  53. IARC Monograph Working Group. A review of human carcinogens-Part B: biological agents. Lancet Oncol. 2009;10:321–2.

    Article  Google Scholar 

  54. Lont AP, Kroon BK, Horenblas S, Gallee MP, Berkhof J, Meijer CJ, Snijders PJ. Presence of high-risk human papillomavirus DNA in penile carcinoma predicts favorable outcome in survival. Int J Cancer. 2006;119:1078–81.

    Article  CAS  PubMed  Google Scholar 

  55. Ferreux E, Lont AP, Horenblas S, Gallee MP, Raaphorst FM, von Knebel Doeberitz M, Meijer CJ, Snijders PJ. Evidence for at least three alternative mechanisms targeting the p16INK4A/cyclin D/Rb pathway in penile carcinoma, one of which is mediated by high-risk human papillomavirus. J Pathol. 2003;201:109–18.

    Article  CAS  PubMed  Google Scholar 

  56. Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T. Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions. Am J Pathol. 1998;153:1741–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chaux A, Cubilla AL, Haffner MC, Lecksell KL, Sharma R, Burnett AL, Netto GJ. Combining routine morphology, p16(INK4a) immunohistochemistry, and in situ hybridization for the detection of human papillomavirus infection in penile carcinomas: a tissue microarray study using classifier performance analyses. Urol Oncol. 2014;32:171–7.

    Article  CAS  PubMed  Google Scholar 

  58. Bezerra AL, Lopes A, Santiago GH, Ribeiro KC, Latorre MR, Villa LL. Human papillomavirus as a prognostic factor in carcinoma of the penis: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. Cancer. 2001;91:2315–21.

    Article  CAS  PubMed  Google Scholar 

  59. Gunia S, Erbersdobler A, Hakenberg OW, Koch S, May M. p16(INK4a) is a marker of good prognosis for primary invasive penile squamous cell carcinoma: a multi-institutional study. J Urol. 2012;187:899–907.

    Article  CAS  PubMed  Google Scholar 

  60. Djajadiningrat RS, Jordanova ES, Kroon BK, van Werkhoven E, de Jong J, Pronk DT, Snijders PJ, Horenblas S, Heideman DA. Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome. J Urol. 2015;193:526–31.

    Article  PubMed  Google Scholar 

  61. Bezerra SM, Chaux A, Ball MW, Faraj SF, Munari E, Gonzalez-Roibon N, Sharma R, Bivalacqua TJ, Burnett AL, Netto GJ. Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas. Hum Pathol. 2015;46:532–40.

    Article  CAS  PubMed  Google Scholar 

  62. Stankiewicz E, Prowse DM, Ng M, Cuzick J, Mesher D, Hiscock F, Lu YJ, Watkin N, Corbishley C, Lam W, Berney DM. Alternative HER/PTEN/Akt pathway activation in HPV positive and negative penile carcinomas. PLoS One. 2011;6:e17517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Necchi A, Nicolai N, Colecchia M, Catanzaro M, Torelli T, Piva L, Salvioni R. Proof of activity of anti-epidermal growth factor receptor-targeted therapy for relapsed squamous cell carcinoma of the penis. J Clin Oncol. 2011;29:e650–2.

    Article  PubMed  Google Scholar 

  64. Lam KY, Chan KW. Molecular pathology and clinicopathologic features of penile tumors: with special reference to analyses of p21 and p53 expression and unusual histologic features. Arch Pathol Lab Med. 1999;123:895–904.

    CAS  PubMed  Google Scholar 

  65. Lopes A, Bezerra AL, Pinto CA, Serrano SV, de MellO CA, Villa LL. p53 as a new prognostic factor for lymph node metastasis in penile carcinoma: analysis of 82 patients treated with amputation and bilateral lymphadenectomy. J Urol. 2002;168:81–6.

    Article  PubMed  Google Scholar 

  66. Chaux A, Munari E, Cubilla AL, Hicks J, Lecksell K, Burnett AL, Netto GJ. Immunohistochemical expression of the mammalian target of rapamycin pathway in penile squamous cell carcinomas: a tissue microarray study of 112 cases. Histopathology. 2014;64:863–71.

    Article  PubMed  Google Scholar 

  67. Alves G, Heller A, Fiedler W, Campos MM, Claussen U, Ornellas AA, Liehr T. Genetic imbalances in 26 cases of penile squamous cell carcinoma. Genes Chromosomes Cancer. 2001;31:48–53.

    Article  CAS  PubMed  Google Scholar 

  68. Berney D. Molecular aspects of carcinoma of the penis. The science. Abstract SC-03-002 26 European Congress of Pathology. London, 2014.

    Google Scholar 

  69. Campos RS, Lopes A, Guimarães GC, Carvalho AL, Soares FA. E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: analysis of 125 patients. Urology. 2006;67:797–802.

    Article  PubMed  Google Scholar 

  70. Graafland NM, Lam W, Leijte JA, Yap T, Gallee MP, Corbishley C, van Werkhoven E, Watkin N, Horenblas S. Prognostic factors for occult inguinal lymph node involvement in penile carcinoma and assessment of the high-risk EAU subgroup: a two-institution analysis of 342 clinically node-negative patients. Eur Urol. 2010;58:742–7.

    Article  PubMed  Google Scholar 

  71. Novara G, Galfano A, De Marco V, Artibani W, Ficarra V. Prognostic factors in squamous cell carcinoma of the penis. Nat Clin Pract Urol. 2007;4:140–6.

    Article  PubMed  Google Scholar 

  72. Lont AP, Kroon BK, Gallee MP, van Tinteren H, Moonen LM, Horenblas S. Pelvic lymph node dissection for penile carcinoma: extent of inguinal lymph node involvement as an indicator for pelvic lymph node involvement and survival. J Urol. 2007;177:947–52.

    Article  PubMed  Google Scholar 

  73. Johnson TV, Hsiao W, Delman KA, Jani AB, Brawley OW, Master VA. Extensive inguinal lymphadenectomy improves overall 5-year survival in penile cancer patients: results from the Surveillance, Epidemiology, and End Results program. Cancer. 2010;116:2960–6.

    Article  PubMed  Google Scholar 

  74. Lughezzani G, Catanzaro M, Torelli T, Piva L, Biasoni D, Stagni S, Crestani A, Guttilla A, Raggi D, Giannatempo P, Necchi A, Pizzocaro G, Colecchia M, Salvioni R, Nicolai N. The relationship between characteristics of inguinal lymph nodes and pelvic lymph node involvement in penile squamous cell carcinoma: a single institution experience. J Urol. 2014;191:977–82.

    Article  PubMed  Google Scholar 

  75. Horenblas S, van Tinteren H. Squamous cell carcinoma of the penis. IV. Prognostic factors of survival: analysis of tumor, nodes and metastasis classification system. J Urol. 1994;151:1239–43.

    CAS  PubMed  Google Scholar 

  76. Chaux A, Torres J, Pfannl R, Barreto J, Rodriguez I, Velazquez EF, Cubilla AL. Histologic grade in penile squamous cell carcinoma: visual estimation versus digital measurement of proportions of grades, adverse prognosis with any proportion of grade 3 and correlation of a Gleason-like system with nodal metastasis. Am J Surg Pathol. 2009;33:1042–8.

    Article  PubMed  Google Scholar 

  77. Emerson RE, Ulbright TM, Eble JN, Geary WA, Eckert GJ, Cheng L. Predicting cancer progression in patients with penile squamous cell carcinoma: the importance of depth of invasion and vascular invasion. Mod Pathol. 2001;14:963–8.

    Article  CAS  PubMed  Google Scholar 

  78. Cubilla AL. The role of pathologic prognostic factors in squamous cell carcinoma of the penis. World J Urol. 2009;27:169–77.

    Article  PubMed  Google Scholar 

  79. Cubilla AL, Piris A, Pfannl R, Rodriguez I, Agüero F, Young RH. Anatomic levels: important landmarks in penectomy specimens: a detailed anatomic and histologic study based on examination of 44 cases. Am J Surg Pathol. 2001;25:1091–4.

    Article  CAS  PubMed  Google Scholar 

  80. Chaux A, Caballero C, Soares F, Guimarães GC, Cunha IW, Reuter V, Barreto J, Rodríguez I, Cubilla AL. The prognostic index: a useful pathologic guide for prediction of nodal metastases and survival in penile squamous cell carcinoma. Am J Surg Pathol. 2009;33:1049–57.

    Article  PubMed  Google Scholar 

  81. Slaton JW, Morgenstern N, Levy DA, Santos Jr MW, Tamboli P, Ro JY, Ayala AG, Pettaway CA. Tumor stage, vascular invasion and the percentage of poorly differentiated cancer: independent prognosticators for inguinal lymph node metastasis in penile squamous cancer. J Urol. 2001;165:1138–42.

    Article  CAS  PubMed  Google Scholar 

  82. Ficarra V, Zattoni F, Cunico SC, Galetti TP, Luciani L, Fandella A, Guazzieri S, Maruzzi D, Sava T, Siracusano S, Pilloni S, Tasca A, Martignoni G, Gardiman M, Tardanico R, Zambolin T, Cisternino A, Artibani W, Gruppo Uro-Oncologico del Nord Est (Northeast Uro-Oncological Group) Penile Cancer Project. Lymphatic and vascular embolizations are independent predictive variables of inguinal lymph node involvement in patients with squamous cell carcinoma of the penis: Gruppo Uro-Oncologico del Nord Est (Northeast Uro-Oncological Group) Penile Cancer data base data. Cancer. 2005;103:2507–16.

    Article  PubMed  Google Scholar 

  83. Guimarães GC, Lopes A, Campos RS, Zequi Sde C, Leal ML, Carvalho AL, da Cunha IW, Soares FA. Front pattern of invasion in squamous cell carcinoma of the penis: new prognostic factor for predicting risk of lymph node metastases. Urology. 2006;68:148–53.

    Article  PubMed  Google Scholar 

  84. Guimarães GC, Leal ML, Campos RS, Zequi Sde C, da Fonseca FP, da Cunha IW, Soares FA, Lopes A. Do proliferating cell nuclear antigen and MIB-1/Ki-67 have prognostic value in penile squamous cell carcinoma? Urology. 2007;70:137–42.

    Article  PubMed  Google Scholar 

  85. Kroon BK, Leijte JA, van Boven H, Wessels LF, Velds A, Horenblas S, van’t Veer LJ. Microarray gene-expression profiling to predict lymph node metastasis in penile carcinoma. BJU Int. 2008;102:510–5.

    Article  CAS  PubMed  Google Scholar 

  86. Ficarra V, Zattoni F, Artibani W, Fandella A, Martignoni G, Novara G, Galetti TP, Zambolin T, Kattan MW, G.U.O.N.E. Penile Cancer Project Members. Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis. J Urol. 2006;175:1700–4.

    Article  PubMed  Google Scholar 

  87. Kattan MW, Ficarra V, Artibani W, Cunico SC, Fandella A, Martignoni G, Fandella A, Novara G, Galetti TP, Zattoni F, GUONE Penile Cancer Project Members. Nomogram predictive of cancer specific survival in patients undergoing partial or total amputation for squamous cell carcinoma of the penis. J Urol. 2006;175:2103–8.

    Article  PubMed  Google Scholar 

  88. UICC. TNM classification of malignant tumours. 7th ed. New York: Wiley & Sons; 2009.

    Google Scholar 

  89. Protzel C, Knoedel J, Zimmermann U, Woenckhaus C, Poetsch M, Giebel J. Expression of proliferation marker Ki67 correlates to occurrence of metastasis and prognosis, histological subtypes and HPV DNA detection in penile carcinomas. Histol Histopathol. 2007;22:1197–204.

    CAS  PubMed  Google Scholar 

  90. Zhu Y, Zhou XY, Yao XD, Dai B, Ye DW. The prognostic significance of p53, Ki-67, epithelial cadherin and matrix metalloproteinase-9 in penile squamous cell carcinoma treated with surgery. BJU Int. 2007;100:204–8.

    Article  CAS  PubMed  Google Scholar 

  91. Van Poppel H, Watkin NA, Osanto S, Moonen L, Horwich A, Kataja V, ESMO Guidelines Working Group. Penile cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:vi115–24.

    PubMed  Google Scholar 

  92. Protzel C, Kakies C, Kleist B, Poetsch M, Giebel J. Down-regulation of the metastasis suppressor protein KAI1/CD82 correlates with occurrence of metastasis, prognosis and presence of HPV DNA in human penile squamous cell carcinoma. Virchows Arch. 2008;452:369–75.

    Article  CAS  PubMed  Google Scholar 

  93. Termini L, Fregnani JH, Boccardo E, da Costa WH, Longatto-Filho A, Andreoli MA, Costa MC, Lopes A, da Cunha IW, Soares FA, Villa LL, Guimarães GC. SOD2 immunoexpression predicts lymph node metastasis in penile cancer. BMC Clin Pathol. 2015;15:3–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Alves G, Fiedler W, Guenther E, Nascimento P, Campos MM, Ornellas AA. Determination of telomerase activity in squamous cell carcinoma of the penis. Int J Oncol. 2001;18:67–70.

    CAS  PubMed  Google Scholar 

  95. Hungerhuber E, Schlenker B, Schneede P, Stief CG, Karl A. Squamous cell carcinoma antigen correlates with tumor burden but lacks prognostic potential for occult lymph node metastases in penile cancer. Urology. 2007;70:975–9.

    Article  PubMed  Google Scholar 

  96. Golijanin D, Tan JY, Kazior A, Cohen EG, Russo P, Dalbagni G, Auborn KJ, Subbaramaiah K, Dannenberg AJ. Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis. Clin Cancer Res. 2004;10:1024–31.

    Article  CAS  PubMed  Google Scholar 

  97. Muneer A, Kayes O, Ahmed HU, Arya M, Minhas S. Molecular prognostic factors in penile cancer. World J Urol. 2009;27:161–7.

    Article  CAS  PubMed  Google Scholar 

  98. Amin A, Griffith RC, Chaux A. Penile intraepithelial neoplasia with pagetoid features: report of an unusual variant mimicking Paget disease. Hum Pathol. 2014;45:889–92.

    Article  PubMed  Google Scholar 

  99. Leijte JA, Kroon BK, Valdés Olmos RA, Nieweg OE, Horenblas S. Reliability and safety of current dynamic sentinel node biopsy for penile carcinoma. Eur Urol. 2007;52:170–7.

    Article  PubMed  Google Scholar 

  100. Leijte JA, Hughes B, Graafland NM, Kroon BK, Olmos RA, Nieweg OE, Corbishley C, Heenan S, Watkin N, Horenblas S. Two-center evaluation of dynamic sentinel node biopsy for squamous cell carcinoma of the penis. J Clin Oncol. 2009;27:3325–9.

    Article  PubMed  Google Scholar 

  101. Chaux A, Reuter V, Lezcano C, Velazquez EF, Torres J, Cubilla AL. Comparison of morphologic features and outcome of resected recurrent and nonrecurrent squamous cell carcinoma of the penis: a study of 81 cases. Am J Surg Pathol. 2009;33:1299–306.

    Article  PubMed  Google Scholar 

  102. Lont AP, Gallee MP, Meinhardt W, van Tinteren H, Horenblas S. Penis conserving treatment for T1 and T2 penile carcinoma: clinical implications of a local recurrence. J Urol. 2006;176:575–80.

    Article  CAS  PubMed  Google Scholar 

  103. Hoffman MA, Renshaw AA, Loughlin KR. Squamous cell carcinoma of the penis and microscopic pathologic margins: how much margin is needed for local cure? Cancer. 1999;85:1565–8.

    Article  CAS  PubMed  Google Scholar 

  104. Leijte JA, Kirrander P, Antonini N, Windahl T, Horenblas S. Recurrence patterns of squamous cell carcinoma of the penis: recommendations for follow-up based on a two-centre analysis of 700 patients. Eur Urol. 2008;54:161–9.

    Article  PubMed  Google Scholar 

  105. Liegl B, Regauer S. Penile clear cell carcinoma: a report of 5 cases of a distinct entity. Am J Surg Pathol. 2004;28:1513–7.

    Article  PubMed  Google Scholar 

  106. Lopez-Beltran A, Menendez CL, Montironi R, Cheng L. Rare tumors and tumor-like conditions in urological pathology. Switzerland: Springer International Publishing; 2015. p. 410.

    Google Scholar 

  107. Smith KJ, Tuur S, Corvette D, Lupton GP, Skelton HG. Cytokeratin 7 staining in mammary and extramammary Paget’s disease. Mod Pathol. 1997;10:1069–74.

    CAS  PubMed  Google Scholar 

  108. Liegl B, Leibl S, Gogg-Kamerer M, Tessaro B, Horn LC, Moinfar F. Mammary and extramammary Paget’s disease: an immunohistochemical study of 83 cases. Histopathology. 2007;50:439–47.

    Article  CAS  PubMed  Google Scholar 

  109. Lee JY. Clear cell papulosis: a unique disorder in early childhood characterized by white macules in milk-line distribution. Pediatr Dermatol. 1998;15:328–9.

    Article  PubMed  Google Scholar 

  110. Sánchez-Ortiz R, Huang SF, Tamboli P, Prieto VG, Hester G, Pettaway CA. Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience. J Urol. 2005;173:1958–65.

    Article  PubMed  CAS  Google Scholar 

  111. van Geel AN, den Bakker MA, Kirkels W, Horenblas S, Kroon BB, de Wilt JH, Eggermont AM, Mooi WJ, van der Aa MN. Prognosis of primary mucosal penile melanoma: a series of 19 Dutch patients and 47 patients from the literature. Urology. 2007;70:143–7.

    Article  PubMed  Google Scholar 

  112. Zurrida S, Bartoli C, Clemente C, De Palo G. Malignant melanoma of the penis. A report of four cases. Tumori. 1990;76:599–602.

    CAS  PubMed  Google Scholar 

  113. Barnhill RL, Albert LS, Shama SK, Goldenhersh MA, Rhodes AR, Sober AJ. Genital lentiginosis: a clinical and histopathologic study. J Am Acad Dermatol. 1990;22:453–60.

    Article  CAS  PubMed  Google Scholar 

  114. Katona TM, Lopez-Beltran A, MacLennan GT, Cheng L, Montironi R, Cheng L. Soft tissue tumors of the penis: a review. Anal Quant Cytol Histol. 2006;28:193–206.

    PubMed  Google Scholar 

  115. Fetsch JF, Sesterhenn IA, Miettinen M, Davis Jr CJ. Epithelioid hemangioma of the penis: a clinicopathologic and immunohistochemical analysis of 19 cases, with special reference to exuberant examples often confused with epithelioid hemangioendothelioma and epithelioid angiosarcoma. Am J Surg Pathol. 2004;28:523–33.

    Article  PubMed  Google Scholar 

  116. Fetsch JF, Brinsko RW, Davis Jr CJ, Mostofi FK, Sesterhenn IA. A distinctive myointimal proliferation (‘myointimoma’) involving the corpus spongiosum of the glans penis: a clinicopathologic and immunohistochemical analysis of 10 cases. Am J Surg Pathol. 2000;24:1524–30.

    Article  CAS  PubMed  Google Scholar 

  117. McKenney JK, Collins MH, Carretero AP, Boyd TK, Redman JF, Parham DM. Penile myointimoma in children and adolescents: a clinicopathologic study of 5 cases supporting a distinct entity. Am J Surg Pathol. 2007;31:1622–6.

    Article  PubMed  Google Scholar 

  118. Lowe FC, Lattimer DG, Metroka CE. Kaposi’s sarcoma of the penis in patients with acquired immunodeficiency syndrome. J Urol. 1989;142:1475–7.

    CAS  PubMed  Google Scholar 

  119. Micali G, Nasca MR, De Pasquale R, Innocenzi D. Primary classic Kaposi’s sarcoma of the penis: report of a case and review. J Eur Acad Dermatol Venereol. 2003;17:320–3.

    Article  CAS  PubMed  Google Scholar 

  120. Dehner LP, Smith BH. Soft tissue tumors of the penis. A clinicopathologic study of 46 cases. Cancer. 1970;25:1431–47.

    Article  CAS  PubMed  Google Scholar 

  121. Fetsch JF, Davis Jr CJ, Miettinen M, Sesterhenn IA. Leiomyosarcoma of the penis: a clinicopathologic study of 14 cases with review of the literature and discussion of the differential diagnosis. Am J Surg Pathol. 2004;28:115–25.

    Article  PubMed  Google Scholar 

  122. Antunes AA, Nesrallah LJ, Goncalves PD, Ferreira YA, Campagnari JC, Srougi M. Deep-seated sarcomas of the penis. Int Braz J Urol. 2005;31:245–50.

    Article  PubMed  Google Scholar 

  123. Usta MF, Adams DM, Zhang JW, Davis R, Hellstrom WJ. Penile epithelioid sarcoma and the case for a histopathological diagnosis in Peyronie’s disease. BJU Int. 2003;91:519–21.

    Article  CAS  PubMed  Google Scholar 

  124. Rossi G, Ferrari G, Longo L, Trentini GP. Epithelioid sarcoma of the penis: a case report and review of the literature. Pathol Int. 2000;50:579–85.

    Article  CAS  PubMed  Google Scholar 

  125. Lowentritt B, Parsons JK, Argani P, Gearhart JP. Pediatric epithelioid sarcoma of the penis. J Urol. 2004;172:296–7.

    Article  PubMed  Google Scholar 

  126. Ponniah A, Brown CT, Taylor P. Priapism secondary to leukemia: effective management with prompt leukapheresis. Int J Urol. 2004;11:809–10.

    Article  PubMed  Google Scholar 

  127. Arena F, di Stefano C, Peracchia G, Barbieri A, Cortellini P. Primary lymphoma of the penis: diagnosis and treatment. Eur Urol. 2001;39:232–5.

    Article  CAS  PubMed  Google Scholar 

  128. Hizli F, Berkmen F. Penile metastasis from other malignancies. A study of ten cases and review of the literature. Urol Int. 2006;76:118–21.

    Article  PubMed  Google Scholar 

  129. Chaux A, Amin M, Cubilla AL, Young RH. Metastatic tumors to the penis: a report of 17 cases and review of the literature. Int J Surg Pathol. 2011;19:597–606.

    Article  PubMed  Google Scholar 

  130. Celma Doménech A, Planas Morin J, de Torres Ramírez I, Bestard Vallejo J, Mir Marisma C, Morote Robles J. Priapism secondary to penis infiltration of bladder cancer. Actas Urol Esp. 2008;32:749–51.

    Article  PubMed  Google Scholar 

  131. Gelbard MK, Dorey F, James K. The natural history of Peyronie’s disease. J Urol. 1990;144:1376–9.

    CAS  PubMed  Google Scholar 

  132. Leopardi O, Colombo F, Frigo B, Zucchi A, Patelli E, Colecchia M, Mantovani F, Naughten W, Pisani E. Immunohistochemical and quantitative study of mast cells in La Peyronie’s disease. Eur Urol. 2000;37:176–82.

    Article  CAS  PubMed  Google Scholar 

  133. Abdel-Hamid IA, Anis T. Peyronie’s disease: perspectives on therapeutic targets. Expert Opin Ther Targets. 2011;15:913–29.

    Article  CAS  PubMed  Google Scholar 

  134. Shen S, Truong LD, Ro JY. Frozen section library: genitourinary tract. Chapter 3. London/New York: Springer; 2009.

    Google Scholar 

  135. Cabanas RM. The concept of the sentinel lymph node. Recent Results Cancer Res. 2000;157:109–20.

    Article  CAS  PubMed  Google Scholar 

  136. Algaba F, Arce Y, López-Beltrán A, Montironi R, Mikuz G, Bono AV, European Society of Uropathology; Uropathology Working Group. Intraoperative frozen section diagnosis in urological oncology. Eur Urol. 2005;47:129–36.

    Article  CAS  PubMed  Google Scholar 

  137. Mukherjee S. The emperor of all maladies. A biography of cancer. New York: Simon and Shuster; 2010.

    Google Scholar 

  138. Crocker HR. Paget’s disease affecting the scrotum and penis. Trans Pathol Soc Lond. 1889;40:187–91.

    Google Scholar 

  139. Park S, Grossfeld GD, McAninch JW, Santucci R. Extramammary Paget’s disease of the penis and scrotum: excision, reconstruction and evaluation of occult malignancy. J Urol. 2001;166:2112–7.

    Article  CAS  PubMed  Google Scholar 

  140. Terada T, Kamo M, Sugiura M. Apocrine carcinoma of the scrotum with extramammary Paget’s disease. Int J Dermatol. 2013;52:504–6.

    Article  PubMed  Google Scholar 

  141. Wright JL, Morgan TM, Lin DW. Primary scrotal cancer: disease characteristics and increasing incidence. Urology. 2008;72:1139–43.

    Article  PubMed  Google Scholar 

  142. Froehner M, Koch R, Lossnitzer A, Schober RR, Schuler M, Wirth MP. Adult inguinoscrotal sarcomas: outcome analysis of 21 cases, systematic review of the literature and meta-analysis. World J Urol. 2014;32:445–51.

    Article  PubMed  Google Scholar 

  143. Johnson TV, Hsiao W, Delman KA, Canter DJ, Master VA. Scrotal cancer survival is influenced by histology: a SEER study. World J Urol. 2013;31:585–90.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Uropathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

    Maurizio Colecchia

  2. Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

    Alessia Bertolotti & Biagio Paolini

  3. Department of Urology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

    Roberto Salvioni

Authors
  1. Maurizio Colecchia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessia Bertolotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Biagio Paolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberto Salvioni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maurizio Colecchia .

Editor information

Editors and Affiliations

  1. Fondazione IRCCS, Istituto Nazionale Dei Tumori, Milan, Italy

    Maurizio Colecchia

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Colecchia, M., Bertolotti, A., Paolini, B., Salvioni, R. (2016). Tumors of the Penis and Scrotum. In: Colecchia, M. (eds) Pathology of Testicular and Penile Neoplasms. Springer, Cham. https://doi.org/10.1007/978-3-319-27617-5_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-27617-5_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-27615-1

  • Online ISBN: 978-3-319-27617-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation