Melanoma Flashcards by Alex Martin

What is melanoma?

Tumor derived from melanocytes

Can arise in other organs

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How common is melanoma?

4th most common cancer in Australia
1/14 males
1/23

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What is survival chance of 5 years if caught early?

96%

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What is % chance of 5 yr survival if local spread?

63%

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What is % chance of 5 yr survival if metastatic spread?

34%

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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

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What is the model for the development of melanoma?

Benign Nevus
Dysplastic Nevus
Radial-Growth Phase
Vertical - Growth Phase = Tumour
Metastatic Melanoma

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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

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What type of Naevus are there?

Spitz Naevus - histo looks cancer, and found in chidlren

Blue Naevus

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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

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What are the histological characteristics of Dysplastic Naevus?

Less symmetrical
More single cell growth
Some larger, darker nuclei
Fibrosis in upper dermis

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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. changing

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What 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

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What does the Radial growth phase refer to?

Growth within the epidermis along with microinvasion into superficial dermis

Lacks metastatic potential

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What does the vertical growth phase refer to?

Invasive melanoma in the dermis
Mitotic figures
Large dermal nests
Capacity for metastatic spread

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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