Malignant Melanoma Flashcards
What is melanoma?
Melanoma = malignant, most serious skin cancer
=> uncontrolled growth of melanocytes (pigment cells)
Normal melanocytes are found in basal layer of the epidermis (outer layer of skin)
Melanocytes produce a protein called melanin => this protects skin cells by absorbing UV radiation
Equal numbers of melanocytes in black & white skin, but melanocytes in black skin produce much more melanin.
=> People with dark brown / black skin less likely to be damaged by UV radiation than white skin
Non-cancerous growth of melanocytes:
=> moles (aka called benign melanocytic naevi)
=> freckles (ephelides and lentigines)
Cancerous growth of melanocytes = melanoma
Melanoma is described as:
=> In situ if tumour is confined to the epidermis
=> Invasive if a tumour has spread into the dermis
=> Metastatic if a tumour has spread to other tissues
Who is at risk of melanoma?
=> Men > Women
=> Incidence increased in last 20yrs
=> ~4% of cases with 80% mortality
=> 75% melanomas de novo from normal skin ; remainder from existing naves
Risk factors:
=> UV exposure
=> Sunburn
=> Fair complexion
=> Multiple atypical/dysplastic moles
=> Strong family hx i.e. 1st degree relative
=> Old age
=> 66% related to BRAF V600 protein kinase mutations
=> Previous melanoma / BCC / SCC
What causes melanoma?
Uncontrolled proliferation of melanocytic stem cells that have undergone a genetic transformation
Superficial forms of melanoma spread out within the epidermis (in situ).
Further genetic changes promote the tumour to invade through basement membrane into the surrounding dermis (horizontal growth phase) => invasive melanoma
Nodular melanoma has a vertical growth phase, (potentially more dangerous than the horizontal growth phase)
Once the melanoma cells have reached the dermis, they cn spread to other tissues via lymphatic system to the local lymph nodes or via the circulation to other organs i.e. lungs or brain.
=> metastatic disease
- 75% Melanoma arise from normal appearing skin
- Melanomas also arise from within a mole or freckle, which starts to grow larger and change in appearance.
What are the pre-cursor lesions of melanoma?
Precursor lesions include:
- Benign melanocytic naevus (normal mole)
- Atypical or dysplastic naevus (funny-looking mole)
- Atypical lentiginous naevus (flat naevus in heavily sun damaged skin) or atypical solar lentigo
- Large or giant-sized congenital melanocytic naevus (brown birthmark).
What are the clinical features of melanoma?
=> 1st sign = unusual looking freckle or mole
=> Variety of colours including tan, dark brown, black, blue, red and, light grey
=> Melanomas lacking pigment = amelanotic melanoma
=> During its horizontal phase of growth, melanoma is normally flat.
=> As the vertical phase develops, the melanoma becomes thickened and raised.
=> Can be itchy or tender
=> More advanced lesions can bleed easily or crust over.
Most melanomas have characteristics described by the Glasgow 7-point checklist or by the ABCDE criteria of melanoma.
Most melanomas characteristics described by the Glasgow 7-point checklist or by the ABCDE criteria of melanoma.
Describe the Glasgow 7-point system and the ABCDE criteria.
- Glasgow 7-point checklist
Major features
=> Change in size
=> Irregular shape
=> Irregular colour
Minor features
=> Diameter >7 mm
=> Inflammation
=> Oozing
=> Change in sensation
- The ABCDEs of Melanoma
=> A : Asymmetry
=> B : Border irregularity
=> C : Colour variation
=> D : Diameter over 6 mm
=> E : Evolving (enlarging, changing)
What are the subtypes of a melanoma?
Four clinical types of Melanoma:
- Lentigo maligna melanoma
=> invasive tumour that develops within pre-existing lentigo maligna
=> apparent as a new nodule
- Superficial spreading malignant melanoma
=> large, flat, irregularly pigmented lesion that grows laterally before vertical invasion
- Nodular malignant melanoma:
=> most aggressive type
=> presents as a rapidly growing pigmented nodule which bleeds or ulcerates
=> rarely can be amelanotic (non-pigmented) and can mimic pyogenic granuloma
- Acral lentigious malignant melanomas
=> pigmented lesions on the palm, soles or under the nails
=> presents late
=> may not be related to sun exposure
How is melanoma diagnosed?
Clinical signs using ABCDE criteria or Glasgow 7-point checklist
Dermatoscopy
Biopsy (suspected lesion surgically removed)
=> pathology report with macro and microscopic lesions
What is Breslow thickness?
The Breslow thickness is reported for invasive melanomas.
=> measured vertically in millimetres from the top of the granular layer (or base of superficial ulceration) to the deepest point of tumour involvement.
=> strong predictor of outcome; the thicker the melanoma, the more likely it is to metastasise
How do you manage / treat melanomas?
Wide local excision of the melanoma = usually curative
Suspicious lesions (growing, changing, pigmented) should be completely excised with 2mm margin
Treatment for metastatic melanoma (stage 3 & 4) => targeted therapy with oral tyrosine kinase inhibitors and MEK inhibitor targeting BRAF mutation
What is the prognosis of melanoma?
Prognosis depends on excision completeness and tumour depth
=> Breslow thickness is a major prognostic sign
=> Sentinel node mets ≈ poorer prognosis.
What is the staging for melanoma?
Cutaneous melanoma staging guidelines
Stage 0: In situ melanoma
Stage 1: Thin melanoma <2mm in thickness
Stage 2: Thick melanoma >2mm in thickness or >1mm thickness with ulceration
Stage 3: Melanoma spread to involve local lymph nodes
Stage 4: Distant metastases detected
UV exposure:
- UVA (long-wave) and UVB (medium-wave) = mutagenic and carcinogenic especially in fair skinned people
=> UVC (short-wave) filtered out - UV light causes sunburn (mainly UVB), premature ageing or photo damage (mainly UVA)
=> A for ageing and B for burns - UV radiation has immunosuppression effects => skin cancer
Photo-protection advice:
- Sunscreen protect against UVA and UVB irradiation
- Important to wear protective clothing + restrict exposure
- Sunscreen works by:
=> absorbing or filtering UV radiation e.g. benzophenones, cinnamates, salicylates
OR
=> reflecting UV radiation e.g. zinc/titanium dioxides
- SPF (sun protection factor) is a measure of UVB protection
* many cases sunscreen not applied in adequate amounts so do not provide the said protection
* UV-absorbing chemicals can cause allergic contact-dermatitis
*sunlight = main source of vitamin D => necessary in those with darker skin living in temperate climates
=> advice about sun protection needs to take into account individual skin type
