Vulvar cancer pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2] Syed Musadiq Ali M.B.B.S.[3]
Overview
Development of vulvar cancer is the result of multiple genetic mutations.
Pathogenesis
- Human papillomaviruses subtypes 16 and 18 (High risk) play an essential role in the pathogenesis of vulvar cancer. Once HPV enters an epithelial cell, the virus begins to make the proteins it encodes.
- Two of the proteins made by high-risk HPVs (E6 and E7) interfere with cell functions that normally prevent excessive growth, helping the cell to grow in an uncontrolled manner and to avoid cell death.
- Many times these infected cells are recognized by the immune system and eliminated. Sometimes, however, these infected cells are not destroyed, and a persistent infection results.
- Persistently infected cells continue to grow, they may develop mutations in cellular genes that promote even more abnormal cell growth.
- HPV- related vulvar carcinoma is most commonly seen in younger women. Vulvar intraepithelial neoplasia (VIN), related to HPV infection, subsequently leads to invasive vulvar cancer.[1]
- The development of both vulvar low-grade squamous intraepithelial lesions (LSIL) and vulvar high-grade squamous intraepithelial lesions (HSIL; formerly VIN usual type) is associated with human papillomavirus (HPV) infection, as is the corresponding vulvar cancer of the warty and basaloid subtypes.
- Multifocal vulvar HSIL and multicentric vulvar HSIL are most often associated with high-oncogenic-risk HPV subtypes 16, 18, and 31 and should be considered premalignant lesions[2]. By contrast, vulvar condylomata acuminata are usually associated with low-oncogenic-risk HPV subtypes 6 and 11[3].
- The anogenital epithelium is derived from the embryonic cloaca and includes the cervix, vagina, vulva, anus, and lower three centimeters of rectal mucosa up to the dentate line.
- Since the entire region shares the same embryological origin and is susceptible to similar exogenous agents (eg, HPV infection), squamous intraepithelial lesions in this area are often both multifocal (multiple foci of disease within the same organ) and multicentric (foci of disease involving more than one organ).
- Women with VIN may have synchronous or metachronous squamous neoplasia of other lower genital tract sites (cervix, vagina, anus). There is evidence that some cases of high-grade VIN and vaginal intraepithelial neoplasia represent a monoclonal lesion derived from high-grade or malignant cervical neoplasia.[4]
- The pathogenesis of differentiated VIN is less well understood than vulvar LSIL or HSIL.
- It is typically associated with lichen sclerosus. The risk of vulvar squamous cell carcinoma in women with lichen sclerosus is approximately 5 percent[5].
- Differentiated VIN is found adjacent to 80 percent of vulvar squamous cell carcinomas. The diagnosis of solitary differentiated VIN is very challenging and appears to be associated with rapid progression to squamous cell carcinoma.
- Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia, and/or basal cellular atypia tend to have the highest risk of progression to squamous cell carcinoma. There are no known biomarkers to reliably identify the patients at highest risk[6].
Gross Patholgy
| Vulvar Carcinomas Subtype | Features on Gross Pathology |
| Squamous cell carcinoma of vulva |
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| Basal cell carcinoma of vulva |
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| Vulvar melanoma |
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Microscopic Pathology
Histologic subtypes of vulvar cancer include:[7][8][9][10]
- Vulvar carcinomas
- Squamous cell carcinoma
- Basal cell carcinoma
- Vulvar Paget disease
- Adenocarcinoma
- Transitional cell carcinoma
- Verrucous carcinoma
- Merkel cell tumors
- Vulvar malignant melanoma
- Vulvar sarcoma
- Leiomyosarcoma
- Malignant fibrous histiocytoma
- Epithelial sarcoma
| Vulvar Carcinomas Subtype | Features on Histopathological Microscopic Analysis | Image |
| Squamous cell carcinoma of vulva |
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| Basal cell carcinoma of vulva |
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| Vulvar melanoma |
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References
- ↑ The Histopathology of Vulvar Neoplasia. Glown. http://www.glowm.com/section_view/heading/The%2520Histopathology%2520of%2520Vulvar%2520Neoplasia/item/256#13421 URL Accessed on September 30, 2015
- ↑ Ogunbiyi OA, Scholefield JH, Robertson G, Smith JH, Sharp F, Rogers K (February 1994). "Anal human papillomavirus infection and squamous neoplasia in patients with invasive vulvar cancer". Obstet Gynecol. 83 (2): 212–6. PMID 8290182.
- ↑ Hørding U, Junge J, Poulsen H, Lundvall F (February 1995). "Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential". Gynecol. Oncol. 56 (2): 276–9. doi:10.1006/gyno.1995.1046. PMID 7896198.
- ↑ Vinokurova S, Wentzensen N, Einenkel J, Klaes R, Ziegert C, Melsheimer P, Sartor H, Horn LC, Höckel M, von Knebel Doeberitz M (December 2005). "Clonal history of papillomavirus-induced dysplasia in the female lower genital tract". J. Natl. Cancer Inst. 97 (24): 1816–21. doi:10.1093/jnci/dji428. PMID 16368943.
- ↑ Neill SM, Lewis FM, Tatnall FM, Cox NH (October 2010). "British Association of Dermatologists' guidelines for the management of lichen sclerosus 2010". Br. J. Dermatol. 163 (4): 672–82. doi:10.1111/j.1365-2133.2010.09997.x. PMID 20854400.
- ↑ van de Nieuwenhof HP, Bulten J, Hollema H, Dommerholt RG, Massuger LF, van der Zee AG, de Hullu JA, van Kempen LC (February 2011). "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 (2): 297–305. doi:10.1038/modpathol.2010.192. PMID 21057461.
- ↑ Hoffman, Barbara (2012). Williams gynecology. New York: McGraw-Hill Medical. ISBN 9780071716727.
- ↑ Malignant melanoma. Libre pathology. http://librepathology.org/wiki/index.php/Malignant_melanoma. URL Accessed on September 30, 2015
- ↑ Basal cell carcinoma . Libre pathology. http://librepathology.org/wiki/index.php/Basal_cell_carcinoma. URL Accessed on September 30, 2015
- ↑ Squamous cell carcinoma. Libre pathology. http://librepathology.org/wiki/index.php/Squamous_cell_carcinoma. URL Accessed on September 30, 2015