25.2 Cutaneous Malignancy

4. Cutaneous Malignancies

Malignant Melanoma

Malignant melanoma originates from cutaneous melanocytes. Incidence is escalating rapidly in the UK, driven by intermittent intense ultraviolet radiation (sunburn) in fair-skinned individuals (Fitzpatrick skin types I–II).

• The Clinical ABCDE Criteria:
  • A — Asymmetry: One half of the lesion does not mirror the other.
  • B — Border Irregularity: Notched, scalloped, ragged, or poorly defined edges.
  • C — Colour Variegation: Multiple shades of brown, black, blue, red, or depigmented white.
  • D — Diameter: >6 mm (diameter of a pencil eraser; though melanomas can present smaller).
  • E — Evolving: Any change in size, shape, colour, elevation, bleeding, or pruritus (most sensitive clinical indicator).
• Diagnostic Biopsy: Suspicious pigmented lesions must undergo a complete excisional biopsy with a 2 mm margin of normal skin down to the subcutaneous fat. Incisional, punch, or shave biopsies are strictly contraindicated because they risk inaccurate histological staging.
• Breslow Thickness & Wide Local Excision Margins:
  • Breslow Thickness is the single most important independent prognostic factor for survival and metastatic risk. It measures the vertical microscopic depth in millimetres from the top of the epidermal granular layer to the deepest invasive malignant melanoma cell.

• Molecular Genetics & Systemic Therapy:
  • BRAF V600E Mutation: Present in ~50% of cutaneous melanomas; drives constitutive hyperactivation of the MAPK/ERK pathway. Targeted combination therapy: BRAF inhibitor (dabrafenib, vemurafenib) + MEK inhibitor (trametinib, cobimetinib).
  • Immune Checkpoint Inhibitors: First-line systemic therapy for advanced or metastatic melanoma: Anti-PD-1 antibodies (Nivolumab, Pembrolizumab) monotherapy or combined with Anti-CTLA-4 (Ipilimumab). Candidates must watch for immune-related adverse events (colitis, hypophysitis, hepatitis, thyroiditis, pneumonitis).

Non-Melanoma Skin Cancers: BCC vs SCC

Comparison of Non-Melanoma Skin Cancers
  │
  ├── BASAL CELL CARCINOMA (BCC) — Commonest Human Malignancy
  │     ├── Histogenesis: Basal layer of epidermis and follicular outer root sheath
  │     ├── Clinical Phenotype (Nodular BCC ~60%):
  │     │     ├── Pearly, translucent pink/flesh-coloured nodule with arborising telangiectasias
  │     │     └── Rolled, rounded borders with central depression or ulceration ("Rodent Ulcer")
  │     ├── Behaviour: Slow-growing, locally tissue-destructive; metastatic potential negligible (<0.01%)
  │     └── Management:
  │           ├── Surgical excision with 4–5 mm margin (curative in >95%)
  │           ├── Mohs Micrographic Surgery (for facial "H-zone", morpheaform, or recurrent lesions)
  │           └── Advanced/Metastatic BCC: Hedgehog pathway inhibitors (Vismodegib, Sonidegib)
  │
  └── SQUAMOUS CELL CARCINOMA (SCC) — Second Most Common Skin Malignancy
        ├── Histogenesis: Malignant proliferation of epidermal keratinocytes; UV-damaged skin
        ├── Precursor Lesions: Actinic keratosis (rough sandpapery macule); Bowen's disease (SCC in situ)
        ├── Clinical Phenotype: Indurated, firm, hyperkeratotic erythematous nodule with central ulcer/crust
        ├── Keratoacanthoma: Rapidly growing dome nodule with central keratin crater (well-differentiated SCC)
        ├── Immunosuppression Pearl:
        │     └── 65- to 250-fold increased incidence in solid organ transplant recipients (ciclosporin/azathioprine)
        ├── Metastatic Risk Factors: Size >2 cm, depth >4 mm, lip/ear location, perineural invasion, immunosuppression
        └── Management: Surgical excision with 4–6 mm margin (low-risk) or >=6–10 mm / Mohs surgery (high-risk)

Melanoma in Detail

Melanoma is the skin cancer that kills, and Part 1 questions revolve around recognition, prognosis and the referral pathway rather than surgical technique.

The ABCDE rule (Asymmetry, Border irregularity, Colour variegation, Diameter above 6 mm, Evolution) and the 7-point checklist used in UK primary care both feed the two-week-wait suspected cancer referral. Subungual melanoma presents as a pigmented longitudinal nail streak, and pigment spreading onto the proximal nail fold — Hutchinson sign — is the malignant clue.

Breslow thickness, measured in millimetres from the granular layer to the deepest tumour cell, is the dominant prognostic factor and sets the wide local excision margin. Sentinel lymph node biopsy is offered for staging in intermediate-thickness disease. Metastatic melanoma is now treated with BRAF and MEK inhibitors where a BRAF V600 mutation is present, or with immune checkpoint inhibitors such as ipilimumab, nivolumab and pembrolizumab — whose immune-related adverse effects (colitis, hepatitis, hypophysitis, thyroiditis, pneumonitis) are themselves examinable general medicine.

Premalignant Lesions and Non-Melanoma Skin Cancer

• Actinic (solar) keratosis: rough, scaly erythematous macules on sun-exposed skin; low individual risk of transformation, treated with cryotherapy, topical fluorouracil, imiquimod or diclofenac gel.
• Bowen disease: squamous cell carcinoma in situ, a well-demarcated scaly erythematous plaque, classically on the lower leg of older women.
• Keratoacanthoma: rapidly growing crateriform nodule with a keratin plug that may regress spontaneously, but is excised because it cannot be reliably distinguished from squamous cell carcinoma.

Risk Factors and Genodermatoses

Cumulative ultraviolet exposure, Fitzpatrick skin types I-II, immunosuppression, previous radiotherapy, chronic scarring (Marjolin ulcer) and arsenic exposure all raise risk. Organ transplant recipients have up to a 100-fold increase in squamous cell carcinoma, which behaves aggressively and warrants annual dermatological surveillance and, where possible, reduction or conversion of immunosuppression. Gorlin syndrome (naevoid basal cell carcinoma syndrome, PTCH1) causes multiple early basal cell carcinomas, odontogenic keratocysts and palmar pits, and xeroderma pigmentosum causes early multiple skin cancers through defective nucleotide excision repair.