Vulvar and vaginal cancer

Epidemiology & Risk Factors

• Vulvar Cancer:
  • Most common histology: Squamous cell carcinoma (SCC) (~90%).
  • HPV-dependent pathway (~60%): High-risk HPV 16, 18, 31; younger pts (40–50 yrs), association w/ smoking, multiple sexual partners, immunosuppression (HIV); precursor is high-grade VIN (Vulvar Intraepithelial Neoplasia).
  • HPV-independent pathway (~40%): Older postmenopausal pts (60–80 yrs); precursor is differentiated VIN arising on chronic inflammatory vulvar dermatoses, primarily Lichen sclerosus.
  • Non-SCC etiologies: Melanoma (2nd most common vulvar malignancy), Extramammary Paget Disease.
• Vaginal Cancer:
  • Rare primary malignancy (<2% GYN cancers); most vaginal tumors are metastatic (from cervix, endometrium, vulva).
  • SCC: Most common primary (>80%); HPV-associated; typically affects postmenopausal women in the upper 1/3 of posterior vaginal wall.
  • Clear Cell Adenocarcinoma: Strongly linked to in utero exposure to Diethylstilbestrol (DES); presents in young females (mean age ~19 yrs); affects anterior upper 1/3 of vagina.
  • Sarcoma botryoides (embryonal rhabdomyosarcoma): Rare pediatric neoplasm (<4 yrs old); arises from immature skeletal muscle cells.

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Clinical Features

• Vulvar Cancer:
  • Vulvar pruritus (most common presenting symptom, often chronic).
  • Unhealing vulvar plaque, nodule, or ulcerative lesion (most commonly on labia majora).
  • Vulvar bleeding, pain, or dyspareunia.
  • Inguinal lymphadenopathy (palpable firm nodes in advanced disease).
• Vaginal Cancer:
  • Painless abnormal vaginal bleeding (postmenopausal or postcoital bleeding).
  • Malodorous vaginal discharge or watery leukorrhea.
  • Palpable mass or ulcerated lesion on vaginal wall.
  • Advanced disease: Pelvic pain, hematuria, tenesmus, constipation (secondary to local invasion).
  • Sarcoma botryoides: Polypoid, polypoid-like “cluster of grapes” mass protruding from the vagina in infant/child.

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Diagnosis

• Vulvar Cancer:
  • Initial & Confirmatory Test: Punch biopsy or excisional biopsy of the lesion edge (includes dermis/stroma to evaluate depth of invasion).
  • Staging: Surgical staging (FIGO) via Wide local excision (WLE) w/ Sentinel lymph node biopsy (SLNB) or inguinofemoral lymphadenectomy.
  • Imaging: CT/PET or pelvic MRI for regional/distant metastasis assessment in advanced disease.
• Vaginal Cancer:
  • Initial & Confirmatory Test: Biopsy of vaginal lesion (guided by colposcopy w/ acetic acid if subtle).
  • Exclusion Requirement: Must rule out primary cervical or vulvar carcinoma via comprehensive exam and Pap/biopsy before diagnosing primary vaginal cancer.
  • Staging: Clinical staging (FIGO) using pelvic exam under anesthesia, cystoscopy, proctosigmoidoscopy, and pelvic MRI/CT.

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Differential Diagnostics

• Lichen Sclerosus:
  • Differentiating features: “Porcelain-white” atrophic plaques, figure-of-eight perianal distribution, loss of vulvar architecture (phimosis of clitoris), no exophytic mass.
  • Biopsy: Epidermal thinning w/ dermal hyalinization. Precursor to HPV-independent SCC.
• Extramammary Paget Disease:
  • Differentiating features: Pruritic, erythematous, eczematous, velvety vulvar plaque.
  • Key labs/stains: Intraepithelial adenocarcinoma cells; PAS (+), CEA (+), Cytokeratin 7 (+). High association w/ underlying internal malignancy (GI/GU).
• Vulvar Melanoma:
  • Differentiating features: Hyperpigmented, dark, asymmetric lesion w/ irregular borders on labia majora/clitoris; S100 (+), HMB-45 (+).
• Condyloma Acuminata:
  • Differentiating features: Low-risk HPV (6, 11); warty, fleshy, pedunculated cauliflower-like lesions; non-invasive. Biopsy shows koilocytes without nuclear atypia/stromal invasion.
• Cervical Cancer Extraterritorial Extension:
  • Differentiating features: Lesion involving both cervix and upper vagina is managed/staged as Cervical Cancer, not Vaginal Cancer.

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Management

• Vulvar Cancer:
  • Stage I/II (Early/Localized):
    1. Wide Local Excision (WLE) or radical partial vulvectomy w/ 1 cm clear margins.
    2. Inguinofemoral lymph node evaluation: SLNB for unifocal lesions <2 cm; ipsilateral/bilateral inguinofemoral lymphadenectomy for larger lesions.
  • Stage III/IV (Advanced):
    1. Chemoradiation: Cisplatin-based concurrent chemoradiotherapy (primary tx to shrink tumor prior to surgery or as definitive tx).
    2. Adjuvant RT/chemoradiation if positive nodes, close margins, or deep invasion.
• Vaginal Cancer:
  • Stage I (Upper 1/3 Vagina):
    1. Radical hysterectomy + upper vaginectomy + pelvic lymphadenectomy OR primary Radiation Therapy (RT).
  • Stage II–IV / Lower 2/3 Vagina:
    1. Definitive Chemoradiation (External beam RT + Brachytherapy + concurrent Cisplatin). Surgical intervention avoided due to high morbidity and exenterative requirements.
• Sarcoma Botryoides:
  • Complete surgical resection (multimodal conservative surgery) + adjuvant chemotherapy (Vincristine, Dactinomycin, Cyclophosphamide [VAC]).

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Complications

• Treatment-Related:
  • Lower extremity lymphedema (high incidence following inguinofemoral/pelvic lymph node dissection).
  • Wound breakdown and breakdown of groin incisions.
  • Vaginal stenosis, loss of elasticity, and severe dyspareunia (post-RT).
  • Radiation cystitis, proctitis, or vesicovaginal/rectovaginal fistula formation.
• Disease-Related:
  • Locoregional recurrence (inguinal nodes, pelvic soft tissue).
  • Distant hematogenous dissemination (lungs, liver, bones).
  • Lower extremity deep vein thrombosis (DVT) and venous thromboembolism (VTE).