Clinical features

Pigmented or amelanotic plaque, nodule, ulcer or bleeding lesion of the vulva.
Map the exact anatomical origin: hair-bearing labia majora / vulval skin behaves as cutaneous melanoma, while labia minora, vestibular, clitoral, urethral or vaginal mucosal disease is managed as mucosal vulval melanoma.
Median age 65–75; female by definition.
Frequently late presentation due to anatomical site and patient under-recognition.
Examine entire anogenital mucosa — multifocal disease and synchronous vaginal / urethral lesions occur.
Differential — atypical melanotic macule of the vulva (benign), pigmented VIN, traumatic ecchymosis, naevus, EMPD with pigmentation.

Biology

BRAF V600 mutations uncommon (5–10%) — contrast with cutaneous melanoma (~ 50%).
KIT mutations / amplifications in 10–30% — particularly exons 11, 13, 17; potential for imatinib / nilotinib in advanced disease.
NRAS mutations in 10–30%.
Higher tumour mutational burden than other mucosal melanomas but lower than UV-driven cutaneous melanoma — variable ICI response.
SF3B1 mutations recognised in mucosal melanoma series.

Hair-bearing vulval skin melanoma — stage as cutaneous melanoma (AJCC 8: Breslow thickness, ulceration, nodal and metastatic status) and manage through the cutaneous melanoma pathway.
True mucosal vulval / vaginal melanoma — do not force into the head-and-neck AJCC mucosal melanoma T3/T4 schema. Record Breslow thickness / depth, ulceration, mitotic rate, LVI, margins, nodal status and distant disease; MDTs may also record FIGO / gynae-oncology anatomical extent for local planning.
N — regional inguinofemoral nodal metastasis; M — distant metastasis.
Stage-for-stage prognosis for mucosal disease is worse than for cutaneous melanoma.
Workup for suspected mucosal disease — examination under anaesthetic with biopsy mapping, MRI pelvis, CT NCAP, brain MRI, FDG-PET; gynae and melanoma MDTs.

Hair-bearing vulval skin melanoma — manage as cutaneous melanoma: excision margins, SLNB discussion, BRAF testing, adjuvant therapy and surveillance per cutaneous melanoma pathway, with anatomical/function modification by the MDT.
True mucosal vulval melanoma — radical local excision with a clear margin where achievable; balance against urinary, sexual and reconstructive function. Vulvectomy is occasionally required for extensive disease.
SLNB in mucosal vulval melanoma remains debated — yield positive in 25–40%; it may inform staging and adjuvant decisions but has no proven survival benefit.
Inguinofemoral lymphadenectomy for clinically positive nodes.
Adjuvant therapy — anti-PD-1 (nivolumab, pembrolizumab) considered for resected high-risk disease at MDT.
Advanced / metastatic — first-line anti-PD-1 ± ipilimumab; KIT-mutant disease may respond to imatinib; BRAF-mutant disease is uncommon but should follow the melanoma MDT pathway if present.
Adjuvant radiotherapy — for positive margins, close margins or extensive locoregional disease; improves local control without proven survival benefit.

5-year overall survival 30–50% — substantially worse than cutaneous melanoma of equivalent thickness.
Adverse features — depth of invasion, ulceration, mitotic rate, lymphovascular invasion, positive nodes, distant metastases.
Prognosis driven by both biology (less BRAF, more KIT / NRAS) and late presentation at anatomically obscure site.
Outcomes are improving with modern systemic therapy; long-term follow-up remains essential.