Clinical overview
Melanoma of the female genital tract is rare but disproportionately lethal, and it is a tumour the FCOG(SA) registrar must be able to recognise pathologically because the diagnosis is so easily missed clinically. Mucosal melanoma of the vulva and vagina accounts for roughly 5–10% of all vulval malignancies and a smaller fraction of vaginal cancers, yet it is the second commonest vulval malignancy after squamous cell carcinoma. The vulva is the single most frequent site of female genital melanoma, with the labia minora, clitoris and the mucocutaneous junction of the introitus being characteristic locations; the vagina (most often the lower third and anterior wall) and, rarely, the cervix and urethra follow. The peak incidence is in postmenopausal women in the sixth to eighth decades, although it occurs at any age.
What makes this tumour dangerous is biology, not just rarity. Genital mucosal melanoma is fundamentally a different disease from cutaneous melanoma: it is not driven by ultraviolet radiation, it carries a lower mutational burden, a distinct molecular profile, and a markedly worse stage-for-stage prognosis — five-year survival figures of roughly 10–25% for vaginal and 25–50% for vulval primaries reflect both intrinsically aggressive behaviour and late presentation. Pigmented vulval lesions are frequently dismissed as benign naevi, seborrhoeic keratoses, angiokeratomas or simply attributed to physiological hyperpigmentation, and amelanotic melanomas masquerade as granulation tissue, polyps or even a Bartholin's cyst. For the South African registrar working in a high-HIV-prevalence, resource-variable setting, the practical message is that any new, changing, pigmented, ulcerated or bleeding vulvovaginal lesion warrants a biopsy with melanoma explicitly on the differential — this is a tumour where pattern recognition and a low threshold to biopsy save lives. This objective concerns the pathological features, so the weight below sits in Core knowledge: gross morphology, microscopic architecture and cytology, the immunohistochemical panel, and the molecular landscape that increasingly drives systemic therapy.
Core knowledge
Origin and the WHO framework
Melanocytes are neural-crest-derived dendritic cells that normally reside scattered along the basal layer of squamous epithelium. In the vulva they populate keratinised skin, the mucocutaneous transition zone and glabrous mucosa; in the vagina and cervix they are present in a minority of women as an embryological remnant, which is why primary vaginal and cervical melanomas can arise at all. Melanoma is the malignant proliferation of these melanocytes. The authoritative typing framework is the WHO Classification of Tumours of the Female Genital Tract, 5th edition (2020), which classifies genital melanocytic lesions and recognises the distinction between mucosal (mucocutaneous) melanoma and rarer purely cutaneous vulval melanoma, alongside the benign melanocytic differential (lentigo, melanosis, genital naevi including the histologically alarming atypical melanocytic naevus of the genital type, "AMNGT", which must not be over-diagnosed as melanoma).
Gross / macroscopic features
Figure D16.1 — Mucosal melanoma, easy to miss: arises from mucosal melanocytes, often amelanotic, the ABCDE warning features, and Breslow-thickness staging.
Macroscopic recognition is the first diagnostic gate, and it follows the same logic as the ABCDE rule adapted to mucosa:
- Asymmetry, irregular Borders, Colour variegation — true melanomas are typically asymmetrical with notched, ill-defined margins and a mottled mixture of black, brown, blue-grey, tan, pink and depigmented (white/regressed) zones. Uniform, symmetrical, evenly pigmented small lesions are more reassuring but never exempt from biopsy if changing.
- Diameter and Evolution — lesions are often >7 mm and, crucially, have changed (enlarged, darkened, become raised, ulcerated or begun to bleed).
- Pigmentation is variable: most are pigmented (brown-black macule, plaque, polypoid or nodular mass), but a clinically critical minority — perhaps a quarter of vulvovaginal melanomas — are amelanotic or hypomelanotic, appearing as flesh-coloured, pink, red or ulcerated nodules. Amelanotic melanoma is a notorious diagnostic trap and a frequent cause of delay.
- Surface and growth pattern: ranges from a flat spreading macule to an exophytic, polypoid or fungating ulcerated mass. Ulceration and bleeding are adverse features and correlate with advanced primary tumour thickness.
- Satellite lesions and multifocality can be present, reflecting radial intra-epithelial spread or in-transit metastasis.
Microscopic features — architecture
Histology is the diagnostic gold standard. Two architectural components are assessed: the intra-epithelial (in-situ / radial-growth) component and the dermal/stromal invasive (vertical-growth) component.