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🩺 VULVAR & VAGINAL CANCER — COMPLETE ANSWER PAPER

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PART 1: PRE-INVASIVE LESIONS OF THE VULVA

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Q1. Describe Vulval Intraepithelial Neoplasia (VIN) and its Management / ISSVD Classification

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EVOLUTION OF ISSVD CLASSIFICATION

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2015 ISSVD CLASSIFICATION (Current Standard)

VULVAR SQUAMOUS INTRAEPITHELIAL LESIONS
├── LSIL of the Vulva (Vulvar LSIL)
│   = Flat condyloma / HPV effect (old VIN 1)
│   - NOT a cancer precursor
│   - HPV 6, 11
│   - No VIN grading used
│
├── HSIL of the Vulva (Vulvar HSIL) = "Usual VIN"
│   = Old VIN 2 + VIN 3 (warty/basaloid types)
│   - HPV-related (HPV 16 >80%)
│   - Young/middle-aged women
│   - 2-4% risk of invasion if untreated
│   - 5-8% risk in immunosuppressed
│
└── dVIN (Differentiated VIN)
    = HPV-independent pathway
    - Associated with lichen sclerosus, TP53 mutation
    - Older women, postmenopausal
    - HIGH malignant potential (up to 33% → invasion)
    - Often missed / underdiagnosed

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PATHOGENESIS — TWO PATHWAYS

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DIAGNOSIS

DIAGNOSTIC ALGORITHM FOR VIN
↓
Symptoms: Pruritus, burning, dysuria, visible lesion
↓
Examination under colposcopy + 5% acetic acid
↓
Toluidine blue test (nuclear staining)
↓
BIOPSY (mandatory) — punch or excisional
   ↓             ↓
Confirms    Rules out
VIN         Invasive Ca
↓
Histopathology grading:
- Koilocytes → LSIL
- Full-thickness dysplasia → HSIL
- Basal atypia, paradoxical maturation → dVIN
↓
HPV typing (if available)

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MANAGEMENT OF VIN

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MANAGEMENT FLOWCHART (ESGO/ACOG 2022/2024 Reaffirmed)

VIN DIAGNOSIS ON BIOPSY
        ↓
   ┌────────────────────────────────┐
   │    Is invasion excluded?       │
   └────────────────────────────────┘
        ↓ Yes                ↓ No
  Classify VIN           → Proceed to
                            vulvar cancer
                            management
        ↓
  ┌─────────────────────────────────────────┐
  │ LSIL    │  HSIL (usual)  │     dVIN     │
  └─────────────────────────────────────────┘
      ↓           ↓                 ↓
  Treat if   Size/location?     ALWAYS WLE
  symptomatic  ↓       ↓
           <3 lesions  ≥3 or large
               ↓           ↓
          Imiquimod    WLE or CO₂
          5% cream     laser
          3x/week      (with biopsy
          16 weeks     of any
                       suspicious
                       area)
        ↓
   FOLLOW-UP:
   Every 6 months for 2 years
   Then annually
   (lifetime — dVIN has high recurrence risk)

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MEDICAL TREATMENT — IMIQUIMOD

• Dose: 5% cream, 3x/week for 16-20 weeks
• Mechanism: TLR-7 agonist → innate + adaptive immune activation
• Complete Response: ~35-60%
• Side effects: Local inflammation, erosion (sign of activity)
• ESGO/ISSVD 2022 Consensus: Imiquimod as first-line for vulvar HSIL ≤3 lesions (Systematic Review, Silvestri 2025, PMID 40576260)

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Q2. Differential Diagnosis of Pruritus Vulvae

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Q3. Management of Vaginal and Vulval Intraepithelial Lesions (VaIN & VIN)

VaIN Classification (ISSVD)

VaIN Management

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PART 2: VULVAR CANCER

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Q4. Staging of Vulvar Cancer — FIGO 2021 (Current)

2021 FIGO STAGING — KEY CHANGES from 2009

First FIGO staging based on NCDB data analysis (2010-2017). Imaging now incorporated.

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Prognostic Impact of Nodes

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Q5. Surgical Techniques in Management of Vulvar Cancer

PRINCIPLES — MODERN APPROACH

OLD (Radical En Bloc):          NEW (Triple Incision Technique):
"Butterfly Incision"              3 separate incisions
- En bloc radical vulvectomy   - Wide local excision (WLE)
- Bilateral groin dissection   - Bilateral/unilateral groin
- High morbidity (60-80%)        dissection via separate incision
                               - Lower morbidity (<30%)
                               - Equivalent oncologic outcomes

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SURGICAL DECISION TREE

VULVAR CANCER — SURGICAL PLANNING
            ↓
   Tumor confined to vulva?
   ↓ Yes                ↓ No (Stage II+)
   ↓                   Multi-disciplinary planning
   ↓                   Consider CRT → surgery
   Size?
   ↓ <2cm + invasion <1mm     ↓ >1mm invasion or >2cm
   Stage IA                    Stage IB or greater
   WLE (1cm margin)            WLE or radical partial vulvectomy
   NO groin dissection         + groin node evaluation
                               ↓
                   ┌───────────────────────────────┐
                   │     Node Evaluation            │
                   │  SLN if eligible:              │
                   │  - Unifocal tumor              │
                   │  - <4 cm                       │
                   │  - Clinically N0               │
                   │  - No prior groin surgery      │
                   │              ↓                 │
                   │   SLN negative → No IFLD       │
                   │   SLN micromet (≤2mm) → RT     │
                   │   SLN macromet (>2mm) → IFLD   │
                   └───────────────────────────────┘

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SURGICAL MARGINS

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INGUINOFEMORAL LYMPHADENECTOMY (IFLD)

1. Incision parallel to and 2 cm below inguinal ligament
2. Limits: inguinal ligament (superior), sartorius (lateral), adductor longus (medial)
3. Preserve great saphenous vein → reduces lymphedema
4. Cribriform fascia opened → deep femoral nodes removed
5. Drain placement + primary closure

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Q6. Sentinel Lymph Node (SLN) Mapping in Vulvar Cancer

INDICATIONS (GROINSS-V criteria — widely adopted)

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TECHNIQUE — DUAL TRACER METHOD (Gold Standard)

SLN PROCEDURE
        ↓
Preoperatively:
Intradermal injection of 99mTc-nanocolloid
(4 sites perilesionally) → Lymphoscintigraphy / SPECT-CT
        ↓
Intraoperatively:
Intradermal injection of patent blue V or isosulfan blue dye
        ↓
Handheld gamma probe guidance
        ↓
Excise hot (>10x background) and/or blue nodes
        ↓
Ultrastaging with step-serial sections + immunohistochemistry
        ↓
   ┌─────────────────────────────────┐
   │ SLN negative:                  │
   │ No further groin surgery       │
   │ (97-98% NPV)                   │
   ├─────────────────────────────────┤
   │ SLN micrometastasis (≤2mm):    │
   │ Inguinofemoral RT only         │
   │ (GROINSS-V II — 1.6% recurrence)│
   ├─────────────────────────────────┤
   │ SLN macrometastasis (>2mm):    │
   │ Complete bilateral IFLD        │
   │ ± adjuvant RT                  │
   ├─────────────────────────────────┤
   │ SLN not identified:            │
   │ Complete ipsilateral IFLD      │
   └─────────────────────────────────┘

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NEW TRACERS (2024-2025)

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Q7. GROINSS-V and GROINSS-V II Trials

GROINSS-V (Groningen International Study on Sentinel Nodes in Vulvar Cancer)

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GROINSS-V II (GOG-270) — Key Trial

Key conclusion: RT is safe ONLY for micrometastases (≤2mm); macrometastases require complete IFLD.

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GROINSS-V III (NRG-GY024) — Ongoing Trial

• Testing dose-escalated RT for patients with SLN-positive disease (including macrometastases)
• Uses ICG/NIR fluorescence for SLN detection
• Aims to further reduce need for IFLD

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GROIN-SS (GROINSS-V I Follow-up Analysis)

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Q8. Management — Positive Groin Node in Vulvar Cancer

MANAGEMENT ALGORITHM

POSITIVE GROIN NODE DETECTED
          ↓
   ┌──────────────────────────────────────────┐
   │ How was positive node found?              │
   └──────────────────────────────────────────┘
       ↓ Preoperative            ↓ Intraoperative SLN
       imaging (CT/MRI/PET)
       ↓                         ↓
   Suspicious                  SLN positive:
   unresectable nodes?         Micromet vs Macromet?
       ↓
   ┌──────────────────────────────────────────────────────┐
   │ PREOP APPROACH:                                       │
   │ - Neoadjuvant CRT (if bulky/fixed)                   │
   │ - Goal: convert to resectable                        │
   │ - Then: radical vulvectomy + bilateral IFLD          │
   └──────────────────────────────────────────────────────┘
       ↓ Resectable nodes
   COMPLETE BILATERAL INGUINOFEMORAL LND
       ↓
   POST-OP ASSESSMENT:
   ┌─────────────────────────────────────────┐
   │ # Positive Nodes  │ Recommendation       │
   ├──────────────────┼──────────────────────┤
   │ 1 node, no ECE   │ Bilateral groin RT   │
   │ ≥2 nodes or ECE  │ Groin + pelvic RT    │
   │ ≥2mm micromet    │ Groin RT (SLN path)  │
   │ <2mm micromet    │ Groin RT alone       │
   └─────────────────────────────────────────┘

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ADJUVANT TREATMENT AFTER POSITIVE NODES

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Q9. Management of Locally Advanced Vulvar Carcinoma

DEFINITION

• Tumor invading upper urethra, bladder, rectum, pelvic bone (Stage IVA) OR
• Fixed/ulcerated groin nodes (IIIC-IVA)

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TREATMENT APPROACH

LOCALLY ADVANCED VULVAR CANCER
           ↓
    ┌──────────────────────────────────────┐
    │ GOAL: Organ preservation + survival  │
    └──────────────────────────────────────┘
           ↓
   Primary exenterative surgery?
   → HIGH MORBIDITY, rarely done upfront
           ↓
   PREFERRED: Neoadjuvant CRT
           ↓
   Concurrent Cisplatin + RT
   (Weekly cisplatin 40mg/m²; 45Gy + boost)
           ↓
   Reassessment at 4-8 weeks
   CT/PET + clinical exam
           ↓
    ┌───────────────────────────────────┐
    │ Response?                          │
    │ CR/PR → WLE or radical vulvectomy  │
    │ No response → palliation           │
    └───────────────────────────────────┘
           ↓
   Adjuvant RT if margins positive

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CHEMOTHERAPY REGIMENS FOR VULVAR CANCER

GOG 279 shows highest CPR (73%) with cisplatin + gemcitabine + IMRT.

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ROLE OF RADIOTHERAPY

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Q10. Patient with Left Vulvar Carcinoma + Large Left Inguinal Nodes

CLINICAL SCENARIO MANAGEMENT

LEFT VULVAR CARCINOMA + LARGE LEFT INGUINAL NODES
              ↓
   Assess: Fixed? Ulcerated? Bilateral?
              ↓
   STAGING:
   CT chest-abdomen-pelvis / PET-CT
   MRI vulva/pelvis (for local extent)
   FNA/biopsy of inguinal node if doubt
              ↓
   ┌────────────────────────────────────────┐
   │ Are nodes resectable?                  │
   └────────────────────────────────────────┘
        ↓ YES                    ↓ NO (Fixed)
   Radical vulvectomy        Neoadjuvant CRT first
   + bilateral IFLD          (cisplatin + RT 45Gy)
   + post-op RT                     ↓
   to groin/pelvis           Reassess at 6-8 wks
                             → Resection if feasible
              ↓
   POST-OP ADJUVANT:
   • ≥2 positive nodes → bilateral groin + pelvic RT
   • ECE → CRT (cisplatin + 45-50 Gy)
   • Positive margins → boost RT to vulva
              ↓
   SURVEILLANCE: 3-monthly × 2 yrs → 6-monthly × 3 yrs

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Q11. Paget's Disease of the Vulva

DEFINITION & CLASSIFICATION

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PATHOLOGY

• Paget cells: Large cells with pale cytoplasm, prominent nuclei
• Staining: PAS+, Alcian blue+, mucicarmine+ (distinguish from melanoma)
• IHC: CK7+, CEA+, GCDFP-15+ (most cases)
• Key: Spreads BEYOND visible lesion margins → frequent positive margins

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CLINICAL FEATURES

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INVESTIGATION

• Vulvoscopy + Biopsy (multiple biopsies as lesion extent often underestimated)
• IHC panel to determine primary vs secondary Paget
• Cystoscopy + colonoscopy if secondary type suspected
• Mammography (associated breast cancer ~4%)
• CT/PET if invasion suspected

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TREATMENT

Key clinical point: Paget disease extends microscopically 2-3 cm beyond gross margins. Despite 2 cm margins, 30-50% recurrence rate is expected. Multiple recurrences are common and usually treated conservatively unless invasion develops.

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Q12. Myocutaneous Flaps in Vulvar Reconstruction

MATHES-NAHAI CLASSIFICATION (Based on Vascular Anatomy)

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FLAPS FOR VULVAR DEFECT RECONSTRUCTION

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CHOOSING A FLAP

VULVAR DEFECT → FLAP SELECTION
          ↓
   Defect size?
   ├── Small (<4cm) → Rhomboid / V-Y / Singapore
   ├── Medium → Gracilis / TFL
   └── Large (post-exenteration, irradiated) → VRAM / bilateral gracilis
          ↓
   Prior radiation?
   → Use flap bringing non-irradiated tissue
   → VRAM preferred (brings new blood supply)
          ↓
   Vaginal reconstruction needed?
   → Bilateral gracilis (neovagina)
   → Singapore flap
          ↓
   Anterior defect?
   → TFL flap
          ↓
   Posterior/perineal defect?
   → Gluteus maximus / VRAM

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Q13. Chemotherapy of Vulvar Cancer + Role of Radiotherapy

SYSTEMIC CHEMOTHERAPY

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CHEMORADIATION TRIALS SUMMARY

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RADIOTHERAPY TECHNIQUES

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PART 3: VAGINAL MALIGNANCIES

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Q14. Vaginal Carcinoma — Staging and Management

FIGO STAGING (2009 — still applicable for primary vaginal cancer)

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HISTOLOGY

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MANAGEMENT

PRIMARY VAGINAL CARCINOMA
          ↓
   Stage I (small, upper vagina):
   → Wide local excision + vaginectomy
   → OR intracavitary brachytherapy + EBRT
          ↓
   Stage II+:
   → Concurrent CRT (first-line)
   → Cisplatin 40 mg/m² weekly + EBRT 45Gy
   → Brachytherapy boost (HDR 4-6 Gy × 2-3 fractions)
          ↓
   Stage IVA:
   → CRT or pelvic exenteration
          ↓
   Stage IVB:
   → Palliative chemotherapy + RT for symptom control

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Q15. Vaginal Melanoma — Diagnosis and Management

EPIDEMIOLOGY & FEATURES

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DIAGNOSIS

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MANAGEMENT

VAGINAL MELANOMA
        ↓
  Staging work-up (MRI + CT + PET + mutation testing)
        ↓
  ┌──────────────────────────────────────────────────┐
  │             LOCALIZED DISEASE                    │
  └──────────────────────────────────────────────────┘
        ↓
  SURGERY (primary treatment):
  Wide local excision (WLE) — 1-2 cm margins
  vs
  Radical vaginectomy + vulvectomy (if large/central)
  → Equivalent survival; WLE preferred (less morbidity)
        ↓
  SLN biopsy — supported by systematic review 2023 (PMID 36696819)
        ↓
  Adjuvant:
  ┌──────────────────────────────────────┐
  │ BRAF V600E mutation → BRAF inhibitor │
  │ (dabrafenib + trametinib)            │
  │ c-KIT mutation → Imatinib           │
  │ Any mutation → Immunotherapy        │
  │ (pembrolizumab / nivolumab)         │
  └──────────────────────────────────────┘
        ↓
  ROLE OF RADIOTHERAPY:
  - NOT curative as sole treatment
  - Adjuvant RT: reduces local recurrence (controversial)
  - Palliative RT: bone/brain metastases
  - Synergy with immunotherapy: possible abscopal effect
  (PMID 37511755)

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SYSTEMIC TREATMENT — VAGINAL MELANOMA (2024/2025)

No routine established adjuvant role for chemotherapy (DTIC-based regimens have <15% response rate).

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PROGNOSIS — VAGINAL MELANOMA

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SUMMARY TABLE — ALL VULVAR CANCER KEY POINTS

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References: Berek & Novak's Gynecology; Sabiston Surgery; GROINSS-V (2008, 2021); FIGO 2021; GOG 101/205/279; ISSVD 2015; ESGO/ISSVD 2022 Consensus; ACOG CO 675 (reaffirmed 2024); Cancer of the Vulva 2025 Update (PMC12411818); PMID 34432481 (GROINSS-V II); PMID 40277771 (SLN limitations 2025); PMID 41812374 (Paget SLN 2026).