Tumor lesions of penis and scrotum according to WHO classification 2022

Czech version

Authors: Květoslava Michalová ^1,2; Peter Beniač ³; Denisa Kacerovská ^1,2
Authors‘ workplace: Šiklův ústav patologie, Lékařská fakulta Univerzity Karlovy v Plzni a Fakultní nemocnice Plzeň ¹; Bioptická laboratoř s. r. o., Plzeň ²; Urologická klinika, Lékařská fakulta Univerzity Karlovy v Plzni a Fakultní nemocnice Plzeň ³
Published in: Čes.-slov. Patol., 58, 2022, No. 4, p. 192-197
Category: Reviews Article

Overview

Similarly to testicular tumors, key changes on penile and scrotal neoplasia were incorporated into WHO classification 2016. Therein, penile squamous cell carcinomas were divided into two groups based on the pathogenesis, namely HPV–associated and HPV–independent. This remains unchanged in WHO classification 2022. For those carcinomas where HPV status can not be determined, a category of squamous cell carcinoma NOS was added. Variants of squamous cell carcinoma, namely basaloid, papillary-basaloid, warty, warty-basaloid, clear cell and lymphoepithelioma-like carcinomas are not recognized as distinctive variants of HPV-associated group anymore. Similarly, squamous cell carcinoma, usual type, pseudohyperplastic, pseudoglandular, verrucous carcinoma, carcinoma cunniculatum, papillary, adenosquamous, sarcomatoid and mixed carcinoma are no more not recognized as distinctive variants of HPV–independent carcinomas. Instead, these variants are now called subtypes. Some previously distinct subtypes now belong to the morphological spectrum of other subtypes. Basaloid-papillary subtype belongs to basaloid squamous cell carcinoma and carcinoma cunniculatum is currently recognized as morphological variation of verrucous carcinoma. Pseudohyperplastic and mixed subtypes were removed from the classification. Adenosquamous carcinoma is currently termed adenosquamous and mucoepidermoid carcinoma and represents distinct entity.

Precursor lesions of squamous cell carcinoma underwent substantial modifications in the WHO classification 2016 as well, and remain unchanged in WHO classification 2022. Terminology for HPV – induced lesions have been unified to low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL). This classification applies to the whole anogenital area, including penis, anus, perianal region, vulva, vagina and uterine cervix. LSIL is further divided to condyloma accuminatum and (penile) intraepithelial neoplasia grade 1 (PeIN1), HSIL is divided to PeIN2 and PeIN3. Penile HPV-independent precursor lesions are named differrentiated penile intraepitelial neoplasia (dPeIN) and are identical to analogous lesions on vulva.

Keywords:

Penis – scrotum – tumors of the penis – WHO classification 2022

Sources

1. Canete-Portillo S, Velazquez EF, Kristiansen G, et al. Report from the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers V: Recommendations on the use of immunohistochemical and molecular biomarkers in penile cancer. Am J Surg Pathol 2020; 44(7): e80-e86.

2. WHO Classification of Tumours Editorial Board. Urinary and male genital tumours (5th ed). Lyon: International Agency for Research on Cancer; 2022.

3. Bezerra SM, Chaux A, Ball MW, et al. Human papillomavirus infection and immunohistochemical p16(INK4a) expression as predictors of outcome in penile squamous cell carcinomas. Hum Pathol 2015; 46(4): 532-540.

4. Hölters S, Khalmurzaev O, Pryalukhin A, et al. Challenging the prognostic impact of the new WHO and TNM classifications with special emphasis on HPV status in penile carcinoma. Virchows Arch 2019; 475(2): 211-221.

5. Yang EJ, Kong CS, Longacre TA. Vulvar and anal intraepithelial neoplasia: terminology, diagnosis, and ancillary studies. Adv Anat Pathol 2017; 24(3): 136-150.

6. Bhageerathy PS, Cecilia M, Sebastian A, et al. Human papilloma virus-16 causing giant condyloma acuminata. J Surg Case Rep 2014(1): rjt126.

7. Chrisofos M, Skolarikos A, Lazaris A, et al. HPV 16/18-associated condyloma acuminatum of the urinary bladder: first international report and review of literature. Int J STD AIDS 2004; 15(12): 836-838.

8. Cubilla AL, Velazquez EF, Amin MB, et al. The World Health Organisation 2016 classification of penile carcinomas: a review and update from the International Society of Urological Pathology expert-driven recommendations. Histopathology 2018; 72(6): 893-904.

9. Kacerovska D, Requena L, Carlson JA, et al. Pigmented squamous intraepithelial neoplasia of the anogenital area: a histopathological and immunohistochemical study of 64 specimens from 45 patients exploring the mechanisms of pigmentation. Am J Dermatopathol 2014; 36(6): 471-477.

10. Christodoulidou M, Sahdev V, Houssein S, et al. Epidemiology of penile cancer. Curr Probl Cancer 2015; 39(3): 126-136.

11. Velazquez EF, Chaux A, Cubilla AL. Histologic classification of penile intraepithelial neoplasia. Semin Diagn Pathol 2012; 29(2): 96-102.

12. Guerrero J, Trias I, Veloza L, et al. HPV-negative penile intraepithelial neoplasia (PeIN) with basaloid features. Am J Surg Pathol In press 2022.

13. Ordi J, Alejo M, Fusté V, et al. HPV-negative vulvar intraepithelial neoplasia (VIN) with basaloid histologic pattern: an unrecognized variant of simplex (differentiated) VIN. Am J Surg Pathol 2009; 33(11): 1659-1665.

14. Cañete-Portillo S, Sanchez DF, Fernández- Nestosa MJ, et al. Continuous spatial sequences of lichen sclerosus, penile intraepithelial neoplasia, and invasive carcinomas: a study of 109 cases. Int J Surg Pathol 2019; 27(5): 477-482.

15. Oertell J, Caballero C, Iglesias M, et al. Differentiated precursor lesions and low-grade variants of squamous cell carcinomas are frequent findings in foreskins of patients from a region of high penile cancer incidence. Histopathology 2011; 58(6): 925-933.

16. Chaux A, Netto GJ, Rodríguez IM, et al. Epidemiologic profile, sexual history, pathologic features, and human papillomavirus status of 103 patients with penile carcinoma. World J Urol 2013; 31(4): 861-867.

17. Piris A, Sanchez DF, Fernandez-Nestosa MJ, et al. Topographical evaluation of penile lichen sclerosus reveals a lymphocytic depleted variant, preferentially associated with neoplasia: a report of 200 cases. Int J Surg Pathol 2020; 28(5): 468-476.

18. van de Nieuwenhof HP, Bulten J, Hollema H, et al. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma. Mod Pathol 2011; 24(2): 297-305.

19. van den Einden LC, de Hullu JA, Massuger LF, et al. Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia. Mod Pathol 2013; 26(6): 874-880.

20. Chaux A, Pfannl R, Rodríguez IM, et al. Distinctive immunohistochemical profile of penile intraepithelial lesions: a study of 74 cases. Am J Surg Pathol 2011; 35(4): 553-562.

21. Liegl B, Regauer S. p53 immunostaining in lichen sclerosus is related to ischaemic stress and is not a marker of differentiated vulvar intraepithelial neoplasia (d-VIN). Histopathology 2006; 48(3): 268-274.

22. Eich ML, Del Carmen Rodriguez Pena M, Schwartz L, et al. Morphology, p16, HPV, and outcomes in squamous cell carcinoma of the penis: a multi-institutional study. Hum Pathol 2020; 96: 79-86.

23. Alemany L, Cubilla A, Halec G, et al. Role of human papillomavirus in penile carcinomas worldwide. Eur Urol 2016; 69(5): 953-961.

24. Vieira CB, Feitoza L, Pinho J, et al. Profile of patients with penile cancer in the region with the highest worldwide incidence. Sci Rep 2020; 10(1): 2965.

25. Cubilla AL, Reuter VE, Gregoire L, et al. Basaloid squamous cell carcinoma: a distinctive human papilloma virus-related penile neoplasm: a report of 20 cases. Am J Surg Pathol 1998; 22(6): 755-761.

26. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol 2016; 70(1): 93-105.

27. 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(4): 268-277.

28. Sanchez DF, Rodriguez IM, Piris A, et al. Clear cell carcinoma of the penis: an HPV-related variant of squamous cell carcinoma: a report of 3 cases. Am J Surg Pathol 2016; 40(7): 917-922.

29. Tilakarante WM, Chan JKC. Nasopharynx. In: WHO Classification of Tumours Editorial Board. Head and neck tumours (5th ed). Lyon (France): International Agency for Research on Cancer. In press 2022.

30. Mentrikoski MJ, Frierson HF, Jr., Stelow EB, Cathro P. Lymphoepithelioma-like carcinoma of the penis: association with human papilloma virus infection. Histopathology 2014; 64(2): 312-315.

31. Kashofer K, Winter E, Halbwedl I, et al. HPV-negative penile squamous cell carcinoma: disruptive mutations in the TP53 gene are common. Mod Pathol 2017; 30(7): 1013-1020.

32. 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(9): 1152- 1158.

33. Konstantinova AM, Spagnolo DV, Stewart CJR, et al. Spectrum of changes in anogenital mammary-like glands in primary extramammary (anogenital) Paget disease and their possible role in the pathogenesis of the disease. Am J Surg Pathol 2017; 41(8): 1053-1058.

34. Salamanca J, Benito A, García-Peñalver C, Azorín D, Ballestín C, Rodríguez-Peralto JL. Paget’s disease of the glans penis secondary to transitional cell carcinoma of the bladder: a report of two cases and review of the literature. J Cutan Pathol 2004; 31(4): 341-345.

35. Jonathan I. Epstein CM-G, Ming Zhou, and Antonio L. Cubilla. AFIP Atlas of Tumor and Non-Tumor Pathology: Tumors of the Prostate Gland, Seminal Vesicles, Penis, and Scrotum. Arlington, Virginia: American Registry of Pathology; 2020.

36. Nehal KS, Levine VJ, Ashinoff R. Basal cell carcinoma of the genitalia. Dermatol Surg 1998; 24(12): 1361-1363.

37. Nahass GT, Blauvelt A, Leonardi CL, Penneys NS. Basal cell carcinoma of the scrotum. Report of three cases and review of the literature. J Am Acad Dermatol 1992; 26(4): 574-578.

38. Gibson GE, Ahmed I. Perianal and genital basal cell carcinoma: A clinicopathologic review of 51 cases. J Am Acad Dermatol 2001; 45(1): 68-71.