Malignant melanoma

A melanoma is a malignant tumour of pigment producing cells of the skin, melanocytes (1).

• compared to non melanoma skin cancers (NMSC), malignant melanomas (MM) are far less common (around 10% of skin cancers) although it is responsible for the majority of deaths due to skin cancer (2)
• it accounts for less than 1% of all cancers
• it may arise in a pre-existing naevus (mole) or develop de novo on the skin (1)
• the incidence of MM continues to rise faster than any other form of cancer throughout the world (1)
• is more common in people with non-pigmented skin who have been exposed to excessive sunlight, especially if sunburn ensues
  • age standardised melanoma incidence rates are highest in countries where populations with predominantly fair, sun sensitive skin types are exposed to high ambient solar UV radiation levels, such as in Australia and New Zealand (7)
    • note though that melanoma rates are also high in some regions with relatively low solar UV radiation levels, such as in northern Europe, where cultural norms support intense and episodic exposure, for example during vacations or from sunbeds
      • this is evidenced as Danish women under 40 have higher melanoma rates than similar aged women in Australia and New Zealand
• MM is the third most common skin cancer in the UK. It accounts for more cancer deaths than all other skin cancers combined. In 2011 there were 13,348 new cases of melanoma and 2209 deaths from melanoma (5)
• almost all (98.2%) of people diagnosed with melanoma skin cancer in England survive their disease for one year or more (2013-2017) (6)
• around 9 in 10 (91.3%) of people diagnosed with melanoma skin cancer in England survive their disease for five years or more (2013-2017) (6)
• predicted that almost 9 in 10 (87.4%) of people diagnosed with melanoma skin cancer in England survive their disease for ten years or more (2013-2017) (6)
• 95% of people in England diagnosed with melanoma skin cancer aged 15-39 survive their disease for five years or more, compared with more than 8 in 10 people diagnosed aged 80 and over (2009-2013) (6)

Melanoma is not restricted to the skin (although 95% are skin cancers). It may occur in primary extracutaneous sites such as the eye, mucosa, gastrointestinal or genitourinary tract, CNS and lymph nodes (melanoma of unknown primary cancer) (3).

Spread occurs via superficial lymphatics to give satellite lesions, to regional lymph nodes via deep lymphatics, and via haematogenous spread to the lung, liver and brain. Haematogenous spread usually follows lymphatic.

Different clinico-pathologic types are recognised. The lesions may exhibit a range of colours and uniformity, and often may bleed and ulcerate. Some malignant melanomas are amelanotic (upto 10% of melanomas) (4). It may cause pigmented lesions in the mouth.

With respect to vitamin D and MM (5)

• measure vitamin D levels at diagnosis in secondary care in all people with melanoma
  • give people whose vitamin D levels are thought to be suboptimal advice on vitamin D supplementation

Prognosis (8):

• improvements in melanoma mortality over the last decade are attributed to the advent of multiple effective therapies including:
  • immune checkpoint blockade with anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibodies (ipilimumab),
  • anti–programmed cell death protein 1 (PD-1) antibodies (nivolumab, pembrolizumab),
  • anti–lymphocyte activation gene 3 protein (LAG-3) antibodies (relatlimab),
  • oral combination targeted therapy with B-Raf protein (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors (eg, encorafenib + binimetinib, vemurafenib + cobimetinib, dabrafenib + trametinib)
• in 2024, a trial that included patients with unresectable stage III or stage IV melanoma, reported a 10-year overall survival rate of 43% for those treated with nivolumab + ipilimumab vs 37% with nivolumab and 19% with ipilimumab

Reference:

• (1) Bristow IR et al. Clinical guidelines for the recognition of melanoma of the foot and nail unit. J Foot Ankle Res. 2010;3:25
• (2) NICE 2006. Guidance on cancer services. Improving Outcomes for People with Skin Tumours including Melanoma. The manual
• (3) Markovic SN et al. Malignant melanoma in the 21st century, part 1: epidemiology, risk factors, screening, prevention, and diagnosis. Mayo Clin Proc. 2007;82(3):364-80
• (4) Scottish Intercollegiate Guidelines Network (SIGN) 2003. Cutaneous melanoma. A National Clinical Guideline
• (5) NICE (July 2022).Melanoma: assessment and management
• (6) CRUK. Melanoma skin cancer statistics (accessed 12/9/21)
• (7) Nicholson A, Abbott R, Wright C Y, Kamali P, Sinclair C. Skin cancer prevention and sunscreensBMJ 2025; 390 :e085121
• (8) Joshi UM, Kashani-Sabet M, Kirkwood JM. Cutaneous Melanoma: A Review. JAMA. Published online August 25, 2025