Gynecology Topic 20. Malignant tumors of the vulva and the vagina

I. Vulvar Tumors

Vulvar Intraepithelial Neoplasia (VIN)

• VIN: vulvar squamous precancer / SCC in situ.
• Types: LSIL = low-grade HPV effect; HSIL = HPV-related true precancer; differentiated VIN = HPV-independent, linked to lichen sclerosus and higher SCC risk.
• Risk factors: high-risk HPV 16/18, smoking, immunosuppression, previous lower-genital-tract dysplasia.
• Mechanism: HPV E6/E7 → p53/Rb inhibition → squamous dysplasia → VIN → invasive SCC.
• Symptoms/lesion: pruritus, burning pain, dyspareunia; hyperkeratotic, red/white or pigmented plaque/papule on labia, perineum or clitoris.
• Diagnosis: vulvoscopy with acetic acid → acetowhite areas; biopsy is mandatory to rule out invasion.
• Treatment: local excision/wide local excision or laser ablation if invasion excluded; vulvectomy/skinning vulvectomy for extensive disease; imiquimod in selected cases.
• Follow-up: recurrence is common → long-term vulvar inspection.

Paget Disease of the Vulva

• Paget disease: intraepithelial adenocarcinoma of vulvar skin; usually postmenopausal.
• May be associated with underlying adenocarcinoma: Bartholin gland, sweat gland, urethra, bladder/rectum in selected cases.
• Clinical features: itching/pain; red well-demarcated eczematous plaque with white scales, erosion or ulceration.
• Diagnosis: biopsy; Paget cells = large pale mucin-rich cells.
• Treatment: wide local excision with clear margins; topical 5-FU/imiquimod for selected recurrent/non-surgical lesions.

Invasive Vulvar Cancer

• Epidemiology: about 5% of gynecologic malignancies; peak 60-70 years.
• Histology: SCC 85-90%; malignant melanoma 5-10%.
• Etiology: HPV/VIN pathway or lichen-sclerosus/differentiated-VIN pathway; smoking and immunosuppression increase risk.
• Symptoms/lesion: chronic pruritus/irritation, burning pain, bleeding/discharge; nodule, ulcer, warty lesion or pigmented lesion.
• Spread: local to vagina/urethra/anus; lymphatic superficial/deep inguinal → femoral/pelvic nodes; distant spread late.
• Diagnosis: inspection + palpation including inguinofemoral nodes; vulvoscopy/colposcopy of lower genital tract; biopsy definitive; MRI/CT/PET-CT if nodal/advanced disease suspected.

1. Stage I: confined to vulva/perineum.
2. Stage II: extension to adjacent lower vagina/urethra or anus.
3. Stage III: inguinal/inguinofemoral lymph node metastasis.
4. Stage IV: upper urethra/vagina, bladder/rectum, fixed nodes or distant metastasis.

• Treatment: wide/radical local excision or radical vulvectomy with sentinel node/groin node assessment or inguinofemoral lymphadenectomy.
• Adjuvant radiotherapy +/- chemotherapy: positive nodes, close/positive margins or advanced risk factors.
• Stage IV/metastatic: palliative chemoradiotherapy and symptom control.
• Vulvar melanoma: wide excision and melanoma-style staging by Breslow depth.

II. Vaginal Tumors

Vaginal Intraepithelial Neoplasia (VAIN)

• VAIN: squamous dysplasia of vaginal epithelium; much rarer than CIN/VIN.
• Risk factors: high-risk HPV 16/18, smoking, immunosuppression, previous cervical/vulvar cancer or CIN/VIN.
• Mechanism: HPV E6/E7 → p53/Rb inhibition → VAIN → possible invasive SCC.
• Clinical features: often asymptomatic; postcoital/postmenopausal bleeding or discharge; flat/pigmented/acetowhite plaque, often posterior vaginal wall.

1. VAIN 1: mild dysplasia, lower 1/3 epithelium → low-grade.
2. VAIN 2: moderate dysplasia, up to lower 2/3 → high-grade.
3. VAIN 3: severe dysplasia / carcinoma in situ → high-grade.

• Diagnosis: Pap/vaginal cytology + HPV DNA test; colposcopy/vaginoscopy with acetic acid/Lugol; biopsy for grading.
• Treatment: VAIN 1 observation; VAIN 2-3 laser ablation, local excision or topical imiquimod/5-FU; recurrent/extensive disease → selected vaginectomy.

Invasive Vaginal Cancer

• Rare: 1-3% of gynecologic malignancies; peak 55-60 years.
• Most vaginal tumors are secondary from cervix, vulva, endometrium, bladder or rectum; primary vaginal cancer requires exclusion of these sites.
• Histology: SCC 85-90%; adenocarcinoma/clear cell carcinoma 5-10%, classically linked to in utero DES exposure.
• Symptoms/lesion: postcoital/intermenstrual/postmenopausal bleeding, watery/bloody discharge, pelvic pain/dyspareunia; ulcer or mass, often upper posterior wall.
• Spread: local to cervix/vulva/bladder/urethra/rectum; upper 1/3 drains to pelvic nodes, lower 1/3 to inguinal nodes; lung/liver/bone late.
• Diagnosis: speculum examination + biopsy; evaluate cervix/vulva/endometrium and adjacent organs; MRI/CT for staging.

1. Stage I: confined to vaginal wall.
2. Stage II: subvaginal tissue involvement, no pelvic wall involvement.
3. Stage III: pelvic wall involvement.
4. Stage IVA: bladder/rectal mucosa or beyond true pelvis.
5. Stage IVB: distant metastasis.

• Treatment: mainly radiotherapy, usually external beam + brachytherapy.
• Stage I: radiotherapy or selected surgical excision.
• Stage II-III: external radiotherapy + intracavitary/brachytherapy; chemoradiotherapy may be used.
• Stage IV: palliative chemoradiotherapy and symptom control.