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Female Reproductive System

Vulvar cancer

Rare and aggressive gynecological malignancy of external female genital tract.

Rare and aggressive gynecological malignancy of external female genital tract.

  • #4 M/C gynecologic cancer and contains 5% of all malignancies of the female genital tract (after cancer of the uterine corpus, ovary, and cervix)

Etiology

Risk factors:

The risk of developing vulvar carcinoma is related to different behavioral, reproductive, hormonal, and genetic aspects.
  • Other genital cancers
  • Chronic inflammatory diseases of the vulva
  • Smoking
  • History of genital warts
  • Vulvar intraepithelial neoplasia

Anatomy

Vulva

The vulva is comprised of the female external genitalia, which include the labia majora and minora, clitoris, vestibule, vaginal introitus, and urethral meatus. The vulva serves to direct urine flow, prevent foreign bodies from entering the urogenital tract, as well as being a sensory organ for sexual arousal. The internal pudendal artery and, to a lesser extent, the external pudendal artery are responsible for the blood supply. The ilioinguinal and genitofemoral nerve innervates the anterior part of the vulva, whereas the posterior part is innervated by the perineal branch of the posterior cutaneous nerve.
  • Labia majora (50%)
  • Labia minora
  • Clitoris
  • Bartholin gland
Vulvar anatomy and mapping of lesions
Vulvar anatomy and mapping of lesions. Vulvar anatomy (a). Vulva‐mapping, biopsy sites should be reported using the exact position on the clock‐face with distance from midline and vaginal introitus as well as describing the anatomic location (b). | Wohlmuth, C., & Wohlmuth-Wieser, I. (2019). Vulvar malignancies: an interdisciplinary perspective. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, 17(12), 1257–1276. https://doi.org/10.1111/ddg.13995

Lymph drainage:

The majority of the vulva is drained by lymphatics that pass laterally to the superficial inguinal lymph nodes. The clitoris and anterior labia minora may also drain directly to the deep inguinal or internal iliac lymph nodes
  • Tumors along the midline in the clitoral or urethral areas may spread to either groin. From the inguinal-femoral nodes, lymphatic spread continues to the deep pelvic iliac and obturator nodes.
Lymphatic drainage of the vulva
Lymphatic drainage of the vulva. | Rotmensch J, Yamada SD. Cancer of the Vulva. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from: https://www.ncbi.nlm.nih.gov/books/NBK13760/

Pathophysiology

Histological subtypes:

Relative frequency of histologic subtypes of vulvar malignancies
Relative frequency of histologic subtypes of vulvar malignancies. | Abbr.: Adeno‐Ca, Adenocarcinoma; BCC, basal cell carcinoma; SCC, squamous cell carcinoma. | Surveillance, Epidemiology, and End Results (SEER) Program (http://www.seer.cancer.gov) SEER*Stat Database: Incidence – SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2018 Sub (1975–2016 varying).

Squamous cell carcinoma (95% cases):

2 distinct histological patterns of vulvar carcinomas, with 2 different risk factor profiles:
  1. HPV‐dependent usual type VIN (uVIN) | Basaloid/warty lesions (common in young women):
    • Associated with HPV simulating risk factor profile of cervical cancer.
  2. HPV‐independent differentiated VIN (dVIN) | Keratinizing vulvar carcinomas (common variety, >60% and seen in older women):
    • Associated with chronic dermatoses: Lichen sclerosus et atrophicans and lichen planus
Pathophysiology of usual‐type and differentiated VIN and its progression to SCC
Pathophysiology of usual‐type and differentiated VIN and its progression to SCC. Suggested progression of usual‐type (uVIN) and differentiated vulvar intraepithelial neoplasia (dVIN) to squamous cell carcinoma (SCC). | uVIN: HPV‐protein E6 degrades the tumor suppressor p53; HPV‐protein E7 inactivates the tumor suppressor RB and releases E2F resulting in hyperproliferation. On IHC p16 is typically positive and p53 negative. | dVIN: chronic dermatoses, especially Lichen sclerosus and Lichen planus, can progress to dVIN and SCC. On IHC p16 is typically negative and p53 positive. | Abbr.: HPV, human papilloma virus; IHC, immunohistochemistry; SCC, squamous cell carcinoma; VIN, vulvar intraepithelial neoplasia. | van de Nieuwenhof HP, Massuger LFAG, van der Avoort IAM et al. Vulvar squamous cell carcinoma development after diagnosis of VIN increases with age. Eur J Cancer 2009; 45: 851–6.

Other less common histological subtypes:

  • Melanoma, basal cell
  • Bartholin gland adenocarcinoma
  • Sarcoma
  • Paget’s disease of the vulva (rare)
Macroscopic, dermoscopic and histopathologic features of vulvar malignancies
Macroscopic, dermoscopic and histopathologic features of vulvar malignancies: Vulvar SCC (a–c). Vulvar melanoma (d–f). Extramammary Paget’s disease (g–i). Basal cell carcinoma (j–l). | Wohlmuth, C., & Wohlmuth-Wieser, I. (2019). Vulvar malignancies: an interdisciplinary perspective. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, 17(12), 1257–1276. https://doi.org/10.1111/ddg.13995

Diagnosis

Physical examination: Suspicious vulvar lesion

Pruritic, keratinized or pigmented, possibly bleeding vulvar mass in postmenopausal women.
  • 4 P’s :
    • Papule (raised lesion ± bleeding)
    • Pruritic
    • Patriotic (Red, white, blue in colour)
    • Perakeratosis

Tissue biopsy:

  • Punch biopsy
    • Indications:
      • Pigmented lesion or genital wart in immunocompromised or postmenopausal woman
      • Persistent genital warts despite topical therapy
      • Evolving lesion
    • Obtained via:
      • Vulvoscopy
Elastica van Giesson stained
Elastica van Giesson stained (5× magnification) pT1G2 vulvar carcinoma. | Alkatout, I., Schubert, M., Garbrecht, N., Weigel, M. T., Jonat, W., Mundhenke, C., & Günther, V. (2015). Vulvar cancer: epidemiology, clinical presentation, and management options. International journal of women’s health, 7, 305–313. https://doi.org/10.2147/IJWH.S68979

International Federation of Gynecology and Obstetrics (FIGO)

Staging vulvar cancer: TNM & FIGO
Staging vulvar cancer (TNM and International Federation of Gynecology and Obstetrics, FIGO) | Alkatout I, Günther V, Schubert M, Weigel M, Garbrecht N, Jonat W, et al. Vulvar cancer: epidemiology, clinical presentation, and management options. Int J Womens Health [Internet]. 2015 Mar [cited 2017 Mar 24];Volume 7:305. Available from: http://www.dovepress.com/vulvar-cancer-epidemiology-clinical-presentation-and-management-option-peer-reviewed-article-IJWH
Survival of patients with carcinoma of the vulva
Survival of patients with carcinoma of the vulva. | 20th Report on end results of therapy of gynecologic malignancies. Stockholm: International Federation of Gynecology and Obstetrics, 1988.

Management

Surgical management:

gold standard for even a small invasive carcinoma of the vulva was historically radical vulvectomy with removal of the tumor with a wide margin followed by an en bloc resection of the inguinal and often the pelvic lymph nodes.
Incisions made in a vulvectom
Diagram of the incisions made in a vulvectomy, a treatment for vulvar cancer | By Cancer Research UK – Original email from CRUK, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=34332660
Gross vulvectomy specimen showing a vulvar carcinoma
Gross vulvectomy specimen showing a vulvar carcinoma. | Rotmensch J, Yamada SD. Cancer of the Vulva. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from: https://www.ncbi.nlm.nih.gov/books/NBK13760/

Adjuvant chemo/radiotherapy:

Also used as a primary treatment option for patients who were not eligible for surgery or who refused surgery and also a treatment option for patients with recurrence after surgery.
  • External beam radiation therapy (EBRT) with/without concurrent chemotherapy
  • Completion of inguinofemoral node dissection followed by EBRT with or without concurrent chemotherapy (especially if ≥ 2 positive nodes or 1 positive node with > 2 mm metastasis) is recommended
Treatment of squamous cell carcinomas of the vulva
Treatment of squamous cell carcinomas of the vulva. | Rotmensch J, Yamada SD. Cancer of the Vulva. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from: https://www.ncbi.nlm.nih.gov/books/NBK13760/

Summary

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