Malignant Melanoma

Proliferation of atypical melanocytes with potential for dermal invasion and widespread metastases

Aetiology

• Incidence increases with age, but may also affect young people

• Associated with intermittent intense sun exposure (sunbathing in particular) and sunburn in childhood

• Other risk factors include fair skin, multiple melanocytic naevi, a family history of melanoma and immunosuppression

• About 75% of cutaneous melanomas arise de novo from normal skin, the remainder arising from a pre-existing naevus

Genetic factors

• About 60% of melanomas have an activating BRAF mutation

• Some acral melanomas have c-kit mutations

• Rare associations - xeroderma pigmentosum, oculocutaneous albinism

Pathophysiology

Types of melaoma

• Large, flat, irregularly pigmented lesion

• Commonest in trunk and limbs

• Grows laterally before vertical invasion develops

• Arise as pigmented lesions on the palm or sole or under the nail, and usually present late

• Invasive tumour that develops within pre-existing lentigo maligna

• Occurs on sun damaged face/neck/scalp

• The most aggressive type

• Occurs on varied sites but often trunk

• Presents as a rapidly growing pigmented nodule, which bleeds or ulcerates

Spread and growth

• SSM, ALM and LMM all grow as macules, either entirely in situ or with dermal microinvasion - this is radial growth phase (RGP)

• Eventually the melanoma cells invade the dermis forming an expansile mass with mitosis - this is vertical growth phase (VGP)

• Only VGP melanomas can metastasise

• Nodular melanoma have no RGP which is why they are considered more aggressive

• Melanocytes are motile cells that move around - melanoma much more likely to metastasize than keratinocyte skin cancers
1. Local dermal lymphatics → satellite deposits
2. Regional lymph node metastases
3. Blood spread

Clinical presentation

• Can occur at any site but most common on sun-exposed sites - scalp, face, nack, arm, trunk, leg

• Rarely occur in eye, meninges, oesophagus, biliary tract and anus (anywhere there are melanocytes stuck in odd sites during migration in the embryo)

Suspect melanoma if:

• Change in shape

• Irregular pigmentation

• Bleeding

• Development of satellite nodules

• Ulceration

• New pigmented lesion develops in adulthood

• ABCD checklist - asymmetry, border, colour, diameter

Management

Excision

• Narrow complete exision first for confirmation of diagnosis and assessment of Breslow depth
• The Breslow depth is measured from the granular layer of the epidermis down to the deepest point of invasion
• Smaller the depth = better prognosis

• Staging will guide the margins of the subsequent wide local excision and assess the likely benefit from a sentinel lymph node biopsy to detect occult metastases in the adjacent lymph nodes

Advanced disease

• Treatment of advanced disease difficult; options include chemo, immunotherapy, genetic therapies

• Genetic therapies:
• Imatinib - c-kit mutations
• Debrafenib/vemurafenib - BRAF mutations, adding a MEK inbibitor can reduce resistance to BRAF inhibitors