Neoplastic Disease of the Vulva and Vagina

• Preinvasive neoplastic disease of the vulva

  Divided into two categories: squamous (vulvar intraepithelial neoplasia; VIN) and nonsquamous intraepithelial neoplasias (Paget disease, melanoma in situ)
• Vulvar intraepithelial neoplasia (VIN)


  Cellular atypia contained within the epithelium, characterized by loss of epithelial cell maturation, cellular crowding, nuclear hyperchromatosis, and abnormal mitosis
• VIN classification


  • VIN I (mild dysplasia)
  • VIN II (moderate dysplasia)
  • VIN III (severe dysplasia)
• Revised VIN classification (2004)


  • Koilocytic atypia
  • VIN, usual type
  • VIN, differentiated type
• 20% of patients with VIN will have a coexistent invasive carcinoma
• VIN


  • Correlated with human papillomavirus (HPV) infection
  • 80-90% of VIN lesions have HPV DNA fragments
  • 60% of women with VIN have cervical neoplasia as well
  • Additional risk factors include cigarette smoking and immunocompromised state
• Two distinct forms of VIN

  • Younger premenopausal women: more aggressive multifocal lesions, rapidly become invasive, associated with HPV 75-100% of the time
  • Older postmenopausal women: more likely to involve focal lesions, slow to become invasive, not typically associated with HPV
• Incidence of VIN has nearly doubled in the past few decades
• Majority of VIN cases occur in premenopausal women (75%), median age is 40 years
• Incidence of HPV-associated VIN decreases as age increases
• There is no racial predisposition to VIN
• Symptoms of VIN


  • Vulvar pruritus or irritation
  • Palpable abnormality
  • Perineal or perianal burning
  • Dysuria
• Physical examination findings of VIN

  • Discrete, often multifocal lesions that may appear white, red, or pigmented, and may be raised or flat
  • Acetowhite lesions with or without punctations
  • Associated vascular abnormalities more commonly associated with invasive disease
• Treatment of VIN


  • Wide local excision
  • Laser vaporization
  • Superficial skinning vulvectomy with or without split-thickness skin grafting
  • Topical 5-fluorouracil (5-FU) and imiquimod (Aldara) in younger patients
• Recurrence rates for VIN treatment range from 18% to 55%
• Close follow-up is recommended due to high likelihood of recurrence
• Paget disease of the vulva

  • Uncommon apocrine gland neoplasia most often affecting the anogenital areas
  • Typically presents between ages 50-80 in Caucasian women
  • Commonly an intraepithelial disease that tends to recur locally with minimal propensity to invade
• Only about 20% of patients with Paget disease will have coexistent adenocarcinoma
• Diagnosis of Paget disease

  • Lesions are consistent with chronic inflammatory changes: hyperemic, sharply demarcated, thickened with areas of excoriation and induration
  • Diagnosis made by vulvar biopsy
• Treatment of Paget disease

  • Wide local excision of the circumscribed lesion
  • Important to rule out underlying adenocarcinoma
• Paget disease has a high recurrence rate and may require multiple local excisions
• Vulvar cancer


  • Most common type is squamous cell carcinoma (87%)
  • Other types include malignant melanoma (6%), Bartholin's adenocarcinoma (4%), basal cell carcinoma (<2%), and soft tissue sarcomas (<1%)
  • Lesions can appear anywhere on the vulva, most commonly on the labia majora
• Vulvar cancer accounts for only 5% of gynecologic malignancies
• Rate of vulvar carcinoma has remained relatively stable despite increase in VIN, likely due to early detection and treatment
• Risk factors for vulvar cancer

  • Menopausal status
  • Cigarette smoking
  • VIN
  • CIN
  • HPV
  • Immunosuppression
  • History of cervical cancer
• Diagnosis of vulvar cancer

  • Patients often present with long histories of vulvar pruritus, pain, and bleeding
  • Focal lesions tend to be inflamed and erythematous in early cancers, heaped up or ulcerated in later stages
  • Final diagnosis made by pathologic examination of biopsy specimen
• Staging of vulvar cancer

  • Based on FIGO criteria: tumor size, level of invasion, nodal involvement, and distant metastases
  • Inguinal lymph node dissection required for definitive staging
• Treatment of vulvar cancer

  • Wide radical local excision with inguinal lymph node dissection for stage I disease
  • Modified radical vulvectomy and separate inguinal incisions for lymph node resection for stage II disease
  • Radical vulvectomy, pelvic lymphadenectomy, and/or radiation therapy for stage III and IV disease
• Treatment for vulvar cancer

  1. Complete pelvic examination including palpation of inguinal nodes, collection of cervical cytology, and colposcopy of the cervical vagina, vulva, and perianal areas

  2. Wide radical local excision with inguinal lymph node dissection for stage I disease

  3. Modified radical vulvectomy and separate inguinal incisions for resection of lymph nodes for most stage II disease

  4. Radical vulvectomy, bilateral inguino-femoral lymph node dissection, and pelvic exenteration for stage III and IV disease

  5. Preoperative radiation therapy and chemoradiation to avoid morbidity and mortality associated with pelvic exenteration
• Lymphadenectomy


  If reveals metastatic disease, pelvic radiation is used as adjunct therapy
• Treatment for recurrence of vulvar cancer

  1. Secondary excision

  2. Chemoradiation therapy
• Melanoma of the vulva


  • Occurs predominantly in postmenopausal Caucasians
  • Can be treated similarly to SCC, except that lymphadenectomy is rarely performed
  • Depth of invasion is the key prognostic factor
  • Once metastasized, mortality rate is near 100%
• Basal cell carcinoma of the vulva


  • Can be treated with wide local excision
  • Rarely metastasize to the lymph nodes, thus lymphadenectomy is not required
• The 5-year survival rate for all patients after surgical treatment of invasive SCC is approximately 75%
• Prognostic factor for vulvar cancer

  • Number of positive inguinal lymph nodes
  • 90-95% 5-year survival for one positive lymph node
  • 50-80% 5-year survival for two positive lymph nodes
  • Less than 15% 5-year survival for three or more positive lymph nodes
• Vaginal intraepithelial neoplasia (VAIN)

  • Premalignant lesion similar to VIN and CIN
  • VAIN I and II encompass the lower one-third and two-thirds of the epithelium respectively
  • VAIN III involves greater than two-thirds of the epithelium as well as full thickness abnormalities (carcinoma in situ)
• VAIN occurs most commonly as multifocal lesions in the vaginal apex
• At least 50% to 90% of patients with VAIN will have coexistent or prior neoplasia, or cancer of the vulva or cervix
• Diagnosis of VAIN


  1. Thorough colposcopy of the cervix (if present) and upper vagina using both acetic acid and Lugol's solution

  2. Identified lesions should then be biopsied to give a final pathologic diagnosis and rule out invasive disease
• Treatment of VAIN


  1. Local excision or laser ablation for focal lesions

  2. Hysterectomy if lesions are found on the cervix and extend into the upper third of the vagina

  3. Laser vaporization if invasive disease has been ruled out

  4. Intravaginal 5-fluorouracil (5-FU) for multifocal lesions and immunosuppression