Melanoma Flashcards
Aetiology of Melanoma
UV exposure from UVA and UVB
Risk factors of Melanoma
>10 dysplastic naevi >100 common aquired naevi Fair skin Red hair High intermittent sun exposure Age
Prevention of Melanoma
Prevent skin exposure
Screening for skin cancer
Regular skin examination
Melanomas <0.76mm deep have 10yr survival >95%
Diagnosis of skin cancer
Asymmetry Border - uneven Colour - uneven Diameter >6mm Enlargement or evolution
Poor prognostic findings
Breslow depth
Bleeding and ulceration
Nodular melanoma
Melanoma subtypes
Superficial spreading
Lentigo malinga
Acral lentiginous
Nodular
Features of superficial spending melanoma
70% of melanomas
Intermittent sun exposure
Mid 40yrs
Trunk and limb location
Features of lentigo maligna melanoma
10-15% of melanomas
Cumulative sun exposure
Elderly
Face and neck
Long in-situ phase
Acral Lentiginous melanoma
2% of melanomas
Asian and dark skinned people
Palms, soles of feet under nails
Not caused by UV light
Nodular melanoma
10-15% of melanomas
50% of melanoma deaths
Vertical growth from outset - rapid growth
Symmetrical, dome shaped, firm amelanotic nodule
Not associated with high mole counts
Immunohistochem diagnosis of Melanoma
S100
Melan-A
Melanoma Staging
1 = small primary 2 = Large primary 3 = local disease in lymph nodes 4 = distant mets
Ulceration upstages disease
Poor prognostic factors by stage
Stage 1 and 2 = ulceration
Stage 3 = macroscopic disease, >2 lymph nodes, ulceration
Stage 4 = visceral mets except lung and high serum LDH
Staging Melanoma
For stage 3 and 4 Melanoma
MRI brain
CT chest, abdomen and pelvis
PET
Treatment of stage 1 disease
Local wide excision
Treatment of stage 2 disease
Local wide excision
Sentinel lymph node biopsy
MRI brain, CT CAP and PET
Treatment of stage 3 disease
Local wide excision
Total lymph node dissection
Nil other treatment currently recommended
Requires ongoing surveillence imaging
Treatment of stage 4 disease
Excision of primary
Curative if oligometastatic disease - 1-2 sites only
Common mets sites - skin, lung, brain and bone
Late relapses common
Treatment options:
- Chemo
- BRAF
- BRAF + MEK
- cKIT
- CTLA-4 inhibitors
- PD-1 inhibitors
BRAF inhibitors
BRAF = signal in the RAS-RAf pathway
Activating mutation of BRAF at V600
–> excessive cell proliferation and survival
50% of melanomas
Related to intermittent sun exposure
Drugs:
- Vemurafenib
- -> V600E mutation only
- -> No CNS activity
- Dabrafenib
- -> All V600 mutations
- -> CNS activity
Side effects:
- SCCs
- Arthralgias and fatigue
- Rash
- Photosensitivity
BRAF + MEK inhibitors
MEK is the downstream signal from BRAF in the RAS-AF pathway
Dabrafenib + Trametinib
Improves survival over BRAF alone
Reduces side effects of BRAF inhibition alone
cKIT inhibitors
KIT = extracellular part of the RAS-RAF pathway
cKIT mutations –> cell proliferation and survival
Acral melanomas
Drug = Imatinib
CTLA-4 Inhibition
CTLA-4 = a naturally occurring negative regulator of T cell function
Blocks co-stimulatory signalling of CD-28–> inhibits T cell activation and proliferation
Ipilimumab
Monoclonal antibody to CTLA-4 –> blocks CTLA-4 binding –> upregulation of T cell response
Causes psuedo-progression in the first 8 weeks –> regression which is often prolonged
Side effects of Ipilimumab
Rash Colitis Hepatitis Neuropathy Hypopituatarism Hypo and hyperthyroidism Adrenal crisis Pneumonitis
Surrogate for response to treatment
