Melanoma Flashcards
What is melanoma?
Tumor derived from melanocytes
Can arise in other organs
How common is melanoma?
4th most common cancer in Australia
1/14 males
1/23
What is survival chance of 5 years if caught early?
96%
What is % chance of 5 yr survival if local spread?
63%
What is % chance of 5 yr survival if metastatic spread?
34%
What are some risk factors for melanoma?
Strongest
- Family hist
- Large number of moles/birth marks (naevi)
- Previous melanoma
Others
- Immunosuppression
- Sun sensitivity
- Exposure to ultraviolet radiation
What is the model for the development of melanoma?
Benign Nevus Dysplastic Nevus Radial-Growth Phase Vertical - Growth Phase = Tumour Metastatic Melanoma
What are the characteristics of the Benign Naevus?
Clinically
- Small
- Well circumscribed
- Even coloration
Histologically
- Symmetrical
- Cells predominantly in nests
- Round to oval, even nuclei
- “Maturation” as cells get deeper
What type of Naevus are there?
Spitz Naevus - histo looks cancer, and found in chidlren
Blue Naevus
What are Dysplastic Naevus?
>6mm - larger than benign naevi Irregular borders Variable colouration Can develop large numbers - Dysplastic naevus syndrome Increased risk of developing melanoma
What are the histological characteristics of Dysplastic Naevus?
Less symmetrical
More single cell growth
Some larger, darker nuclei
Fibrosis in upper dermis
What are the ABCDE’s of melanoma detection?
A = Asymmetrical
B = Border Irregularity
C = Color variability
D = Diameter
- > 6mm as a guide
E = Evolving
- i.e. changingWhat are the microscopic features of Melanoma?
Assymetrical Poorly circumscribed Single cells predominate over nests Growth in continuity from one rete ridge to another Extension into upper levels of epidermis - Pagetoid spread - "Buckshot" scatter
Cytological atypia
- Nuclear enlargement
- Hyperchromasia
- Irregularity
- Prominent nucleoli
What does the Radial growth phase refer to?
Growth within the epidermis along with microinvasion into superficial dermis
Lacks metastatic potential
What does the vertical growth phase refer to?
Invasive melanoma in the dermis
Mitotic figures
Large dermal nests
Capacity for metastatic spread
What are some prognostic indicators?
Men do worse than women
Old do worse than young
Back, upper arm, neck and scalp do worse than other sites
What are some microscopic prognostics indicators of melanoma?
Tumour thickness
- Breslow thickness
Level of invasion
- Clark level
Ulceration
Mitotic rate
Lymphovascular or perineural invasion
Satellite lesions
What types of melanoma are there?
Superficial spreading melanoma (buckshot pattern)
Nodular melanoma (Minimal epidermal component)
Lentigo Maligna Melanoma (Sun damaged skin, elderly)
- single cell growth pattern
Acral Lentiginous Melanoma
- Acral sites, feet hands etc
- Most common in dark skinned
Can melanomas regress and is this good or bad?
Yes they can
Immune system destroys melanoma cells
Indicates worse prognosis
Can find metastatic melanoma but no primary tumour
Do different chromasomal aberrations exist for different subtypes of melanoma?
Yes
What chromosomal aberrations are more common in acral melanomas?
Amplifications
Copy number increases in regions of cyclin D1, CDK4 and PDGFR
What gene is commonly mutated in melanoma?
BRAF V600E (glutamate - valine) 66% of melanomas Point mutations Kinase domain
What happens due to BRAF mutation?
Activation of kinase activity
Are BRAF mutations common in naevi?
yes
Are other mutations needed for development of melanoma other than BRAF?
Yes
Are there drugs that target V600E positive cells?
Yes
On what what body part do BRAF mutant melanomas arise on?
Trunk, intermittently rather than chronically exposed to sun
What histo features do BRAF mutant melanomas exhibit?
Upward scatter of intraepidermal cells
Nested Pattern
Heavy pigmentation
How often are NRAS mutations found in melanomas?
15%
HRAS + KRAS rare
In what kind of melanomas are KIT mutations found?
Glabrous skin (skin with no hair)
Nail
Mucosa
Skin with chronic sun exposure
Is BRAF mutation common in KIT mutations?
No relatively uncommon
What features do KIT mutations express?
Increasing incidence with age
Lentiginous growth pattern
Poorly circumscribed margins
Overall what kind of mutations are associated with melanoma?
BRAF mutations
NRAS
KIT
G protein mutations
What does G protein mutation lead to?
Constitutive activation
In what melanomas have G-protein mutations been found in?
Blue Naevis
Uveal melanomas
What is the divergent pathway hypothesis for melanoma?
Those with tendency to develop lots of naevi may initiate melanoma after only modest sun exposure
Those with less tendency for naevi development require repeated exposure
What are the two emerging subtypes of melanoma?
Chronic sun damage melanomas
- Arise after 5th decade
- Lentiginous, mutations in KIT, NRAS, BRAF less common
Non-chronic sun damage melanomas
- Peaks 5th decade
- Intermittently exposed sites
- Associated with naeivi
- Nested growth
- High frequency BRAf
Melanomas arising from epithelial melanocytes
- Acral melanomas
- Uv not causative
Unusual degree of genomic instability
Melanomas arising from non-epithelial melanocytes
- Intradermal - blue naevi
- Uveal melanomas
- G-protein mutations
