Review of precancerous vulvar lesions

Česká verzia

Authors: P. Škapa ¹; H. Robová ² ; Lukáš Rob ² ; J. Zámečník ¹
Authors place of work: Ústav patologie a molekulární medicíny UK 2. LF a FN Motol, Praha, Česká republika ¹; Gynekologicko-porodnická klinika UK 2. LF a FN Motol, Praha, Česká republika ²
Published in the journal: Čes.-slov. Patol., 48, 2012, No. 1, p. 15-21
Category: Přehledový článek

Summary

Classification of squamous vulvar precancerous lesions is based on the concept of vulvar intraepithelial neoplasia (VIN) and incorporates a three grade evaluation of the intensity of dysplastic changes (VIN I, II and III). On the basis of histological features, VIN has been subdivided into the usual VIN (u-VIN) and differentiated VIN (d-VIN), which represent the two basic pathways of the pathogenesis of vulvar squamous cell carcinoma. Although u-VIN is etiologically associated with the human papillomavirus (HPV) infection and histologically corresponds to cervical intraepithelial neoplasia, d-VIN represents the HPV-negative sequence of vulvar carcinogenesis, which is linked to lichen sclerosus (LS) and lichen simplex chronicus (LSC). u-VIN preferentially occurs in relatively young women with a history of cervical, vaginal or vulvar premalignant lesions. On the other hand, d-VIN usually affects postmenopausal women without anamnestic data of other dysplastic lesions of the lower female genital tract. d-VIN is characterized by a higher tendency of stromal invasion than u-VIN and its malignant potential is analogous to carcinoma in situ (VIN III). The histological appearance of d-VIN is subtle with basal atypia and a well-preserved differentiation of the superficial parts of the squamous epithelium, therefore it is frequently misdiagnosed for u-VIN I, LS or LSC in vulvar biopsies. Primarily because of the low diagnostic reproducibility of the u-VIN I category and the doubts about its precancerous potential as well as due to the questionable differentiation between u-VIN II and III, a revised VIN classification was proposed in 2004. The grading of vulvar precancerous lesions was abandoned, the u-VIN I category was discontinued and u-VIN II and III were merged. In the revised terminology, the term u-VIN represents HPV-associated high grade precancerous vulvar lesions (formerly u-VIN II and III) and d-VIN encompasses HPV-negative high grade dysplasias.

Keywords:
vulvar intraepithelial neoplasia – VIN of the usual type – VIN of the differentiated type – lichen sclerosus – lichen simplex chronicus – HPV

Zdroje

1. Munoz N, Castellsague X, de Gonzales AB, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine 2006; 24 Suppl 3: S1–10.

2. van Beurden M, ten Kate FW, Tjong AHSP, et al. Human papillomavirus DNA in multicentric vulvar intraepithelial neoplasia. Int J Gynecol Pathol 1998; 17: 12–16.

3. Hampl M, Sarajuuri H, Wentzensen N, Bender HG, Kueppers V. Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer. Obstet Gynecol 2006; 108: 1361–1368.

4. van der Avoort IA, Shirango H, Hoevenaars BM, et al. Vulvar squamous cell carcinoma is a multifactorial disease following two separate and independent pathways. Int J Gynecol Pathol 2006; 25: 22–29.

5. Hoevenaars BM, van der Avoort IA, de Wilde PC, et al. A panel of p16(INK4A), MIB1 and p53 proteins can distinguish between the 2 pathways leading to vulvar squamous cell carcinoma. Int J Cancer 2008; 123: 2767–2773.

6. Toki T, Kurman RJ, Park JS, et al. Probable nonpapillomavirus etiology of squamous cell carcinoma of the vulva in older women: a clinicopathologic study using in situ hybridization and polymerase chain reaction. Int J Gynecol Pathol 1991; 10: 107–125.

7. Wilkinson EJ, Teixeira MR. Epithelial tumours of the vulva. In: Tavassoli FA, Devilee P, eds. Pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press; 2003: 316–325.

8. Wilkinson EJ, Kneale B, Lynch PJ. Report of the ISSVD terminology committee. J Reprod Med 1986; 31: 973.

9. Hart WR. Vulvar intraepithelial neoplasia: historical aspects and current status. Int J Gynecol Pathol 2001; 20: 16–30.

10. Škapa P, Zámečník J, Hamšíková E, et al. Human papillomavirus (HPV) profiles of vulvar lesions: possible implications for the classification of vulvar squamous cell carcinoma precursors and for the efficacy of prophylactic HPV vaccination. Am J Surg Pathol 2007; 31: 1834–1843.

11. Srodon M, Stoler MH, Baber GB, Kurman RJ. The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN). Am J Surg Pathol 2006; 30: 1513–1518.

12. van de Nieuwenhof HP, van der Avoort IA, de Hullu JA. Review of squamous premalignant vulvar lesions. Crit Rev Oncol Hematol 2008; 68: 131–156.

13. Preti M, Mezzetti M, Robertson C, Sideri M. Inter-observer variation in histopathological diagnosis and grading of vulvar intraepithelial neoplasia: results of an European collaborative study. Br J Obstet Gynaecol 2000; 107: 594–599.

14. Santos M, Montagut C, Mellado B, et al. Immunohistochemical staining for p16 and p53 in premalignant and malignant epithelial lesions of the vulva. Int J Gynecol Pathol 2004; 23: 206–214.

15. Yang B, Hart WR. Vulvar intraepithelial neoplasia of the simplex (differentiated) type: a clinicopathologic study including analysis of HPV and p53 expression. Am J Surg Pathol 2000; 24: 429–441.

16. Scurry J. Does lichen sclerosus play a central role in the pathogenesis of human papillomavirus negative vulvar squamous cell carcinoma? The itch-scratch-lichen sclerosus hypothesis. Int J Gynecol Cancer 1999; 9: 89–97.

17. Ambros RA, Malfetano JH, Carlson JA, Mihm MC, Jr. Non-neoplastic epithelial alterations of the vulva: recognition assessment and comparisons of terminologies used among the various specialties. Mod Pathol 1997; 10: 401–408.

18. Pinto AP, Miron A, Yassin Y, et al. Differentiated vulvar intraepithelial neoplasia contains Tp53 mutations and is genetically linked to vulvar squamous cell carcinoma. Mod Pathol 2010; 23: 404–412.

19. Chiesa-Vottero A, Dvoretsky PM, Hart WR. Histopathologic study of thin vulvar squamous cell carcinomas and associated cutaneous lesions: a correlative study of 48 tumors in 44 patients with analysis of adjacent vulvar intraepithelial neoplasia types and lichen sclerosus. Am J Surg Pathol 2006; 30: 310–318.

20. 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 24: 297–305.

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: 268–274.

22. Choschzick M, Hantaredja W, Tennstedt P, et al. Role of TP53 Mutations in Vulvar Carcinomas. Int J Gynecol Pathol 2011; 30: 497–504.

23. Poulsen H, Junge J, Vyberg M, Horn T, Lundvall F. Small vulvar squamous cell carcinomas and adjacent tissues. A morphologic study. APMIS 2003; 111: 835–842.

24. Roma AA, Hart WR. Progression of simplex (differentiated) vulvar intraepithelial neoplasia to invasive squamous cell carcinoma: a prospective case study confirming its precursor role in the pathogenesis of vulvar cancer. Int J Gynecol Pathol 2007; 26: 248–253.

25. Mulvany NJ, Allen DG. Differentiated intraepithelial neoplasia of the vulva. Int J Gynecol Pathol 2008; 27: 125–135.

26. Micheletti L, Barbero M, Preti M, et al. Vulvar intraepithelial neoplasia of low grade: a challenging diagnosis. Eur J Gynaecol Oncol 1994; 15: 70–74.

27. Sideri M, Jones RW, Wilkinson EJ, et al. Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee. J Reprod Med 2005; 50: 807–810.

28. Wilkinson EJ. Premalignant and malignant tumors of the vulva. In: Kurman RJ, Ellenson LH, Ronnett BM, eds. Blaustein’s pathology of the female genital tract (6th ed). New York, NY: Springer; 2011: 55–103.

29. Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol 2009; 113: 18–25.

30. Wright TC, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 2007; 197: 340–345.

31. Medeiros F, Nascimento AF, Crum CP. Early vulvar squamous neoplasia: advances in classification, diagnosis, and differential diagnosis. Adv Anat Pathol 2005; 12: 20–26.