# Primary Clitoral Melanoma: Personalized Therapeutic Strategies Informed by Clinical Evidence and Systematic Review

**Authors:** Anna Pitsillidi, Laura Vona, Guglielmo Stabile, Günter Noé

PMC · DOI: 10.3390/jpm16020070 · 2026-01-31

## TL;DR

This paper reviews rare clitoral melanoma cases and emphasizes the need for personalized treatment strategies due to diagnostic and staging challenges.

## Contribution

The study provides a systematic review of primary clitoral melanoma cases, highlighting the lack of standardized protocols and the need for prospective research.

## Key findings

- Primary clitoral melanoma is rare, often diagnosed at advanced stages with poor prognosis.
- Most cases showed thick tumors and ulceration, with limited use of adjuvant therapies.
- Recurrence occurred in nearly one-third of cases, sometimes over a decade after initial treatment.

## Abstract

Introduction: Mucosal melanomas are rare, and vulvar melanoma is typically diagnosed at an advanced stage with aggressive behavior and poor prognosis. The clitoral region adds challenges due to its functional importance and lack of a dedicated staging system, requiring individualized management. This review evaluates current evidence on prognosis with emphasis on clitoral involvement and highlights diagnostic and therapeutic challenges, underscoring the need for personalized strategies and prospective multicentre studies. Materials and Methods: A systematic review, registered in PROSPERO (CRD420251151187), was conducted per PRISMA guidelines across PubMed, Scopus, Embase, and Web of Science, including English-language case reports and series of primary clitoral melanoma published until August 2025, with no historical limits. Results: 15 cases from 10 studies were identified. The mean patient age was 60 years, with most tumors presenting at advanced stages (median Breslow thickness of 8 mm, frequent ulceration). Immunohistochemical markers and gene mutations are rarely investigated in reported cases. All patients underwent surgery, with variable lymph node assessment; adjuvant therapy was rarely used. Recurrence occurred in nearly one-third of cases, sometimes more than 10 years after initial treatment. Conclusions: Primary clitoral melanoma is extremely rare and often diagnosed late, underscoring the need for heightened clinical awareness. Wide local excision with organ preservation is preferred, and bilateral sentinel lymph-node biopsy can improve staging. The absence of a dedicated staging system and limited systemic evidence highlight the need for standardized protocols. Emerging molecular and immunologic approaches are promising, but prospective multicentre studies are essential to guide management.

## Linked entities

- **Diseases:** melanoma (MONDO:0005105)

## Full-text entities

- **Genes:** S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, MLANA (melan-A) [NCBI Gene 2315] {aka MART-1, MART1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, SERPINE2 (serpin family E member 2) [NCBI Gene 5270] {aka GDN, GDNPF, PI-7, PI7, PN-1, PN1}, SOX10 (SRY-box transcription factor 10) [NCBI Gene 6663] {aka DOM, PCWH, SOX-10, WS2E, WS4, WS4C}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893] {aka ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6}
- **Diseases:** Ulceration (MESH:D014456), stage IV disease (MESH:D007676), Primary (MESH:D010538), dyspareunia (MESH:D004414), abdominal lesions (MESH:D000008), Tumour-Node-Metastasis (MESH:D009362), oncologic (MESH:D000072716), chronic gastritis (MESH:D005756), stage IIC (MESH:D062706), cutaneous melanoma (MESH:C562393), and neck (MESH:D006258), cardiac arrest (MESH:D006323), pigmented (MESH:D010859), Cancer (MESH:D009369), Mucosal melanomas (MESH:D008545), node (MESH:D012804), gastro-oesophageal reflux disease (MESH:D005764), injury to (MESH:D014947), struma (MESH:D050031), squamous cell carcinoma (MESH:D002294), dysuria (MESH:D053159), pruritus (MESH:D011537), melanomas of the female genital tract (MESH:D060737), multi-system organ failure (MESH:D009102), bleeding (MESH:D006470), lymphadenopathy (MESH:D008206), Vulvar tumours (MESH:D014846)
- **Chemicals:** pembrolizumab (MESH:C582435), Hematoxylin (MESH:D006416), H&amp;E (MESH:D006371), eosin (MESH:D004801), melanin (MESH:D008543), dacarbazine (MESH:D003606)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941946/full.md

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Source: https://tomesphere.com/paper/PMC12941946