Vulval & Vaginal Malignancies
Obstetrics & Gynaecology · Gynae-oncology · lean revision notes
Vulval & Vaginal Malignancies
Vulval and vaginal cancers are uncommon gynaecological malignancies but are disproportionately tested in NEET PG because of a handful of crisp, examinable facts: the dual HPV vs non-HPV pathway, the lymphatic drainage of the vulva, DES-associated clear cell adenocarcinoma of the vagina, and the FIGO staging that hinges on lymph nodes. This note builds the topic from histology up to surgical lymphadenectomy, with emphasis on the points that recur in MCQs.
Vulval cancer — overview & epidemiology
The vulva accounts for roughly 4% of female genital tract malignancies. It is predominantly a disease of the elderly (mean age 65–70 years), though the HPV-driven subset occurs in younger women. The most common site is the labia majora, followed by the labia minora; the clitoris and posterior fourchette are less common primary sites.
High-yield: ~90% of vulval cancers are squamous cell carcinoma (SCC). The next commonest is melanoma (the second most common vulval malignancy), followed by basal cell carcinoma, Bartholin gland adenocarcinoma, verrucous carcinoma, and sarcoma.
Two distinct pathways of vulval SCC
This dichotomy is the single most tested concept in vulval cancer.
| Feature | HPV-associated (basaloid/warty) | Non-HPV (keratinising) |
|---|---|---|
| Proportion | ~20–25% | ~70–75% (commonest) |
| Age | Younger (40s–50s) | Older (>70 yr) |
| HPV type | 16 (also 18, 33) | HPV-negative |
| Precursor | Usual-type VIN (uVIN / HSIL) | Differentiated VIN (dVIN) |
| Background lesion | Multifocal, condyloma, smoking-related | Lichen sclerosus, chronic dermatosis |
| p53 | Wild-type | Mutated p53 (overexpression) |
| p16 immunostain | Positive (block positivity) | Negative |
| Histology | Basaloid / warty | Keratinising SCC |
| Behaviour | Better prognosis | More aggressive, higher recurrence |
High-yield: dVIN (differentiated VIN) arises on a background of lichen sclerosus, is p53-mutated, p16-negative, has the highest malignant potential of the VIN lesions, and progresses fastest to invasive keratinising SCC. uVIN (HSIL) is HPV/p16-positive and progresses more slowly.
VIN (Vulval Intraepithelial Neoplasia)
The terminology was revised. The old VIN 1/2/3 grading is obsolete. Current ISSVD/WHO classification:
- Low-grade squamous intraepithelial lesion (LSIL) — flat condyloma / HPV effect, low risk.
- High-grade squamous intraepithelial lesion (HSIL) = usual-type VIN (uVIN) — HPV-driven.
- Differentiated VIN (dVIN) — HPV-independent, lichen sclerosus-related, p53-mutated.
Clinical features: pruritus is the dominant symptom; lesions may be white, red, pigmented, or raised/warty. Diagnosis is by biopsy (Keyes punch biopsy) with colposcopy/acetic acid to delineate.
Treatment of HSIL/uVIN: wide local excision, laser ablation, or topical imiquimod (immunomodulator) for multifocal disease. dVIN should be excised because of high progression risk.
Etiology & risk factors (vulval SCC)
→ Lichen sclerosus → dVIN → keratinising SCC is the classic non-HPV cascade. → HPV 16 → uVIN/HSIL → basaloid/warty SCC is the HPV cascade.
Other risks: smoking (synergistic with HPV), immunosuppression (HIV, transplant), prior cervical/vaginal neoplasia (field effect), and chronic granulomatous disease. Lichen sclerosus carries a ~4–5% lifetime risk of vulval SCC and warrants surveillance.
Clinical features of invasive vulval cancer
- Long-standing pruritus (most common symptom).
- A lump, ulcer or plaque, often on the labium majus.
- Bleeding, discharge, pain, dysuria with advanced disease.
- Palpable inguinal lymphadenopathy in advanced cases.
Patients frequently present late owing to embarrassment and misattribution to benign dermatoses — delayed diagnosis is a recurring theme.
Lymphatic drainage — the examiner's favourite
Understanding drainage is essential to staging and surgical management.
High-yield: The vulva drains first to the superficial inguinal nodes → then deep inguinal (femoral) nodes → then pelvic (external iliac) nodes. The most medial deep femoral node is the node of Cloquet (Rosenmüller) — the sentinel gateway to the pelvic nodes.
Key drainage rules tested in MCQs:
- Lateral lesions (>1–2 cm from the midline) drain to the ipsilateral groin first.
- Midline structures (clitoris, perineum, anterior labial commissure) may drain bilaterally, hence require bilateral groin assessment.
- Clitoral and Bartholin gland lesions can drain directly to deep pelvic nodes, occasionally bypassing the superficial groin.
- Lymph node status is the single most important prognostic factor in vulval cancer.
| Drainage step | Nodes |
|---|---|
| 1st (superficial) | Superficial inguinal nodes |
| 2nd (deep) | Deep inguinal / femoral nodes (incl. node of Cloquet) |
| 3rd (pelvic) | External iliac → obturator → common iliac |
FIGO staging (vulval carcinoma, 2021)
Staging is surgical. The depth-of-invasion cut-off and nodal involvement dominate questions.
| Stage | Key feature |
|---|---|
| IA | Tumour ≤2 cm confined to vulva/perineum, stromal invasion ≤1 mm |
| IB | Tumour >2 cm OR stromal invasion >1 mm, confined to vulva/perineum |
| II | Tumour of any size extending to lower urethra/vagina/anus, nodes negative |
| III | Extension to upper structures and/or inguinofemoral node involvement |
| IVA | Invades upper urethra/bladder/rectal mucosa, fixed to pelvic bone, or fixed/ulcerated nodes |
| IVB | Distant metastases (incl. pelvic nodes) |
High-yield: Stage IA = lesion ≤2 cm with depth of invasion ≤1 mm. This is the threshold below which groin lymphadenectomy can be omitted, because the risk of nodal metastasis is negligible.
Diagnosis & investigation of choice
- Investigation/diagnosis of choice: wedge/incisional biopsy including the lesion edge with adjacent normal skin and underlying stroma (depth needed to measure invasion). Excisional biopsy for small lesions.
- Colposcopy of vulva/vagina/cervix to map field disease.
- Sentinel lymph node biopsy (SLNB) for early disease: tumour <4 cm, unifocal, clinically negative groins — uses technetium-99m and/or blue dye. A negative sentinel node avoids full lymphadenectomy and its morbidity.
- Imaging: MRI pelvis for local extent; CT/PET for nodal and distant disease in advanced cases.
Management — surgery is the mainstay
The modern principle is individualised, conservative surgery to reduce the morbidity of the historical radical en-bloc "butterfly" vulvectomy.
Stepwise approach:
- Microinvasive (Stage IA, ≤1 mm invasion): wide local excision alone; no groin node dissection.
- Early invasive (>1 mm, unilateral, lateral lesion): radical wide local excision (1 cm tumour-free margin) + ipsilateral inguinofemoral lymphadenectomy (or SLNB if eligible).
- Midline / large lesions: radical excision + bilateral inguinofemoral lymphadenectomy (separate "triple-incision" technique now preferred over en-bloc).
- Node-positive / advanced: surgery followed by adjuvant radiotherapy ± concurrent chemoradiation (cisplatin); chemoradiation also used as primary therapy to preserve sphincters when surgery would be mutilating.
High-yield: A surgical/pathological margin <8 mm (which corresponds to a ~1 cm fresh margin before fixation shrinkage) predicts local recurrence — aim for at least a 1 cm clinical margin.
High-yield: The triple-incision technique (separate vulval and bilateral groin incisions) replaced the classic en-bloc radical (butterfly) vulvectomy to dramatically reduce wound breakdown and lymphoedema while maintaining oncological outcomes.
Indications for adjuvant radiotherapy: ≥2 positive groin nodes, any node with extracapsular spread, or close/positive surgical margins.
Complications of treatment
- Wound breakdown / infection (commonest early complication of groin dissection).
- Chronic lymphoedema of lower limbs (commonest long-term morbidity).
- Lymphocyst / lymphocele formation.
- Femoral nerve injury, DVT, sexual dysfunction, psychological morbidity.
SLNB exists precisely to avoid these — its biggest advantage is reduced lymphoedema.
Vulval melanoma & other histologies (quick facts)
- Melanoma = 2nd most common vulval cancer; staged by Breslow thickness / Clark levels (not FIGO). Poor prognosis.
- Verrucous carcinoma — large warty/cauliflower lesion, locally invasive, rarely metastasises; radiotherapy contraindicated (may induce anaplastic transformation) — treat by wide excision.
- Bartholin gland carcinoma — suspect in a Bartholin "cyst/abscess" in a postmenopausal woman; can be SCC or adenocarcinoma.
- Extramammary Paget's disease of the vulva — see below.
- Basal cell carcinoma — locally invasive, rarely metastasises.
Extramammary Paget's disease of the vulva
An intraepithelial adenocarcinoma of the vulva presenting as an eczematous, red, "velvety" plaque with white islands, intensely pruritic, in an elderly woman.
High-yield: Vulval Paget's shows large pale Paget cells that are PAS-positive, CEA-positive, CK7-positive, and CK20/S-100 negative (CK20 positivity suggests underlying anorectal/urothelial adenocarcinoma). ~10–20% have an underlying invasive adnexal adenocarcinoma; always exclude a synchronous breast, GI, or GU malignancy.
Treatment: wide local excision (margins often positive, recurrence common).
Vaginal cancer
Primary vaginal cancer is rare (~1–2% of gynaecological malignancies). A lesion in the vagina is far more often a metastasis (from cervix, endometrium, vulva, choriocarcinoma) — so a tumour involving both the cervix and vagina is classified as cervical cancer, and one involving the vulva is classified as vulval cancer. The commonest site of a primary vaginal cancer is the upper third of the posterior wall.
High-yield: ~85–90% of primary vaginal cancers are squamous cell carcinoma, HPV-related, occurring in older women, preceded by VaIN (vaginal intraepithelial neoplasia). SCC is overwhelmingly the most common histology.
Clear cell adenocarcinoma & the DES story
This is the classic high-difficulty NEET PG association.
High-yield: Diethylstilbestrol (DES) taken by a mother during pregnancy (used 1940s–1971 for threatened abortion) causes clear cell adenocarcinoma of the vagina/cervix in the female offspring, typically presenting in adolescence/young adulthood (mean ~19 years). The associated benign change is vaginal adenosis (glandular epithelium in the vagina).
DES-exposed daughters classically show:
- Vaginal adenosis (most common finding).
- Clear cell adenocarcinoma (the malignancy).
- Cervical ectropion / "cockscomb" cervix, transverse vaginal/cervical ridges, T-shaped uterus (Müllerian/structural anomalies → infertility, preterm birth, ectopic pregnancy).
Sons of DES-exposed mothers: epididymal cysts, cryptorchidism.
| Vaginal cancer type | Key association | Age |
|---|---|---|
| SCC (commonest) | HPV, VaIN, prior cervical CA | Older (60s) |
| Clear cell adenocarcinoma | DES exposure in utero | Young (~15–25) |
| Embryonal rhabdomyosarcoma (sarcoma botryoides) | — | Infants <5 yr |
| Endodermal sinus (yolk sac) tumour | AFP-secreting | Infants |
| Melanoma | Lower vagina, pigmented | Elderly |
High-yield: Sarcoma botryoides (embryonal rhabdomyosarcoma) presents as a "bunch of grapes" polypoid mass protruding from the vagina in a child under 5 years; histology shows the subepithelial cambium layer of Nicholson and desmin/myogenin-positive rhabdomyoblasts.
Vaginal cancer — clinical features, diagnosis, staging
- Painless vaginal bleeding (postmenopausal or postcoital) is the commonest symptom; discharge, mass, urinary/rectal symptoms in advanced disease.
- Diagnosis: speculum exam + biopsy; colposcopy with Lugol's iodine to detect VaIN.
- FIGO staging is clinical (like cervical cancer): Stage I confined to vagina; II to subvaginal tissue (not pelvic wall); III to pelvic wall; IVA bladder/rectal mucosa; IVB distant.
Management of vaginal cancer
- VaIN: topical 5-fluorouracil/imiquimod, laser ablation, or excision.
- Invasive SCC: radiotherapy (external beam + brachytherapy) is the mainstay for most stages because of the proximity of bladder, rectum and urethra. Surgery (radical hysterectomy + upper vaginectomy + lymphadenectomy) is reserved for selected early upper-third lesions.
- Clear cell adenocarcinoma: surgery for early disease (fertility/vaginal function preservation considered), radiotherapy for advanced; combined modality often used.
Lymphatic drainage of the vagina: upper 2/3 → pelvic (iliac) nodes; lower 1/3 → inguinal nodes — mirroring its dual embryological origin. This determines the nodal fields irradiated.
Key differentials
- Vulval cancer vs benign dermatoses (lichen sclerosus, psoriasis, candidiasis) — any non-healing pruritic vulval lesion in an elderly woman warrants biopsy.
- Vulval Paget's vs candidal/eczematous dermatitis — Paget's is persistent, refractory to antifungals/steroids → biopsy.
- Bartholin carcinoma vs Bartholin cyst/abscess — solid or persistent mass after menopause is malignant until proven otherwise; biopsy/excise rather than just marsupialise.
- Vaginal SCC vs metastatic deposit (cervix/endometrium) — rule out a primary elsewhere before labelling it primary vaginal.
- Clear cell adenocarcinoma vs Arias-Stella reaction / microglandular hyperplasia in young women.
Recently asked / exam angle
- Most common vulval malignancy? → Squamous cell carcinoma. Second most common? → Melanoma.
- VIN with highest malignant potential / associated with lichen sclerosus? → Differentiated VIN (dVIN), p53-mutated, p16-negative.
- Most medial deep inguinal node / sentinel of pelvic spread? → Node of Cloquet (Rosenmüller).
- Depth of invasion at which groin dissection can be omitted in vulval cancer? → ≤1 mm (Stage IA).
- DES in utero exposure causes which vaginal tumour? → Clear cell adenocarcinoma; benign change = adenosis; structural lesion = cockscomb cervix / T-shaped uterus.
- "Bunch of grapes" vaginal mass in a child? → Sarcoma botryoides (embryonal rhabdomyosarcoma) with cambium layer.
- Commonest site of vaginal cancer? → Upper third, posterior wall.
- Treatment of choice for invasive vaginal SCC? → Radiotherapy (EBRT + brachytherapy).
- Single most important prognostic factor in vulval cancer? → Inguinal lymph node status.
- Immunohistochemistry of vulval Paget cells? → CK7+, CEA+, PAS+; CK20− (S-100−).
- Surgical technique replacing en-bloc radical vulvectomy? → Triple-incision technique.
Rapid revision
- Vulval cancer = elderly women; SCC 90%, melanoma 2nd; commonest site labia majora.
- HPV pathway → uVIN/HSIL → p16+ basaloid SCC (younger); non-HPV pathway → lichen sclerosus → dVIN → p53-mutated keratinising SCC (older, commonest, aggressive).
- dVIN has the highest malignant potential; p53-mutated, p16-negative.
- Vulval drainage: superficial inguinal → deep femoral (node of Cloquet) → pelvic; lateral lesions drain ipsilaterally, midline lesions bilaterally.
- Stage IA = ≤2 cm, ≤1 mm invasion → wide local excision, no groin dissection.
- Aim for ≥1 cm surgical margin; triple-incision surgery replaced butterfly vulvectomy; SLNB reduces lymphoedema.
- Adjuvant radiotherapy if ≥2 positive nodes / extracapsular spread / positive margins.
- Vulval Paget's: pruritic red velvety plaque; CK7+, CEA+, CK20−; exclude underlying adenocarcinoma.
- Verrucous carcinoma: warty, local; radiotherapy contraindicated.
- Vaginal cancer mostly metastatic; primary = SCC 90%, upper-third posterior wall; radiotherapy is treatment of choice.
- DES in utero → clear cell adenocarcinoma of vagina in young women; adenosis is the benign marker; cockscomb cervix/T-shaped uterus.
- Sarcoma botryoides = "bunch of grapes" in children <5 yr, cambium layer, desmin/myogenin positive.