Cutaneous melanoma is a malignant tumor of melanocytes with high metastatic potential. Incidence has risen globally, though mortality has improved with earlier detection and effective systemic therapies. Subtypes include superficial spreading, nodular, lentigo maligna (melanoma in situ on chronically sun-damaged skin), acral lentiginous, and desmoplastic melanoma. Prognosis is primarily determined by Breslow thickness, ulceration, mitotic rate, nodal status, and stage. Management hinges on complete excision with appropriate margins, sentinel lymph node biopsy (SLNB) for staging when indicated, and adjuvant or metastatic systemic therapy with immune checkpoint inhibitors or targeted BRAF/MEK therapy.
Epidemiology and Risk Factors
- Risks: intermittent intense UV exposure, indoor tanning, fair skin/red hair (MC1R variants), numerous/atypical nevi, family history, prior melanoma, immunosuppression.
- Occurs in all skin types; in skin of color, acral and subungual sites are more common and diagnosed later.
Clinical Features and Early Detection
- ABCDE criteria: Asymmetry, Border irregularity, Color variegation, Diameter >6 mm (though smaller lesions occur), Evolution (most important).
- EFG for nodular melanoma: Elevated, Firm, Growing.
- Special sites: lentigo maligna on head/neck of elderly; acral lesions on palms/soles/nails (Hutchinson sign for subungual spread).
- Dermoscopy improves diagnostic accuracy (e.g., atypical pigment network, blue-white veil, irregular streaks).
Diagnosis
- Excisional biopsy with 1–3 mm margins preferred; saucerization deep shave acceptable if full thickness down to fat is obtained.
- Pathology report should include Breslow thickness, ulceration, mitotic rate, Clark level (historical), margins, microsatellitosis, lymphovascular/perineural invasion, and tumor-infiltrating lymphocytes.
Staging and Risk Stratification
- AJCC 8th edition staging: T (thickness/ulceration), N (nodal), M (metastasis, LDH).
- SLNB indicated for:
- T1b (≥0.8 mm with or without ulceration, or <0.8 mm with ulceration) and thicker tumors.
- Consider in T1a with high-risk features (high mitotic rate, lymphovascular invasion, regression with limited residual tumor, positive deep margin on biopsy) after multidisciplinary discussion.
- Imaging (US/CT/PET/MRI) for stage III/IV or symptoms; routine imaging not recommended for thin stage I.
Surgical Management
- Wide local excision margins (after diagnostic biopsy):
- Melanoma in situ: 0.5–1.0 cm (lentigo maligna often requires staged excision/Mohs with immunostains).
- ≤1.0 mm: 1 cm margin.
- 1.01–2.0 mm: 1–2 cm margin.
-
2.0 mm: 2 cm margin.
- SLNB performed concurrently with WLE when indicated.
- Desmoplastic melanoma often benefits from wider margins; pure desmoplastic has higher neurotropism—consider adjuvant RT if perineural spread.
Adjuvant and Systemic Therapy
- Stage III resected disease: adjuvant PD-1 inhibitors (nivolumab or pembrolizumab) reduce recurrence; BRAF V600-mutant: dabrafenib + trametinib option.
- Stage IIB/IIC (thick node-negative) adjuvant PD-1 therapy now standard in many regions.
- Unresectable/metastatic:
- Immunotherapy: PD-1 (pembrolizumab, nivolumab) ± CTLA-4 (ipilimumab) combinations; high durable response rates.
- Targeted therapy for BRAF V600 mutations: BRAF/MEK combinations (dabrafenib/trametinib, encorafenib/binimetinib, vemurafenib/cobimetinib).
- Brain metastases: combination immunotherapy has intracranial activity; stereotactic radiosurgery integration.
- Emerging: adoptive TIL therapy in refractory disease; novel checkpoints and combinations under study.
Surveillance and Survivorship
- Skin exams every 3–12 months based on stage for at least 5 years, then annually; nodal and scar checks, patient self-exams.
- Imaging/labs tailored to stage and symptoms (more frequent for stage IIB+ per local guidelines).
- Second primary melanoma and NMSC risk elevated; rigorous photoprotection and family screening.
Special Considerations
- Acral/subungual melanoma: often amelanotic or misdiagnosed; biopsy changing nail pigmentation or acral lesions with irregular patterns on dermoscopy.
- Lentigo maligna: staged excision/Mohs with MART-1/SOX10 immunostains; margins often >5 mm.
- Pregnancy: coordinate timing of surgery; immunotherapy typically avoided during pregnancy.
References (recent guidelines and key reviews)
- NCCN/ESMO/AAD melanoma guidelines, 2022–2024.
- Trials of adjuvant PD-1 in stage IIB/IIC and stage III, and metastatic ICI vs BRAF/MEK combinations, 2021–2024.
- Dermoscopy and early detection best practices, 2021–2024.