17 - Melanoma Flashcards
Melanoma
A malignant tumour derived from melanocytes (cells responsible for melanin production)
How common is melanoma
4th most common cancer in aus
Strongest risk factors for melanoma
- Family history
- Large numbers of benign or atypical naevi
- Previous melanoma
Other risk factors for melanoma
- Immunosuppression
- Sun sensitivity
- Exposure to UV radiation
Clinical features of benign naevus
Small, well circumscribed, even colour
Histological features of benign naevus
- Symmetrical
- Round to oval, even nuclei
- Cells predominantly in nests
- “maturation” as the cells get deeper
Melanoma features
- Asymmetrical
- Border irregularity
- Colour variability
- Diameter
- Evolving
Types of extension n into the upper levels of the epidermis seen in a melanoma
Pagetoid spread and “buckshot” scatter
Radial growth phase
- Refers to growth within the epidermis (“melanoma in situ”) as well as “microinvasion” into the superficial dermis
- Microinvasive component is limited to single cells and
small nests - Lacks metastatic potential
Vertical growth phase
- Invasive melanoma within the dermis
- Larger than the epidermal nests
- Mitotic figures
- Implies a capacity for metastatic spread
Prognostic indicators of melanoma
- Tumour thickness
- Level of invasion
- Ulceration
- Mitotic rate
- Lymphovascular or perineural invasion
- Satellite lesions
Regression
Destruction of the melanoma cells by the body’s immune system
Spitz Naevus
A BENIGN LESION WHICH CAN BE MISTAKEN FOR MELANOMA MICROSCOPICALLY
Dysplastic naevus
- Larger than benign naevi
- Irregular borders
- Variable colouration
- Some patients develop large numbers of dysplastic naevi (dysplastic naevus syndrome)
Gene that is commonly mutated in melanoma
BRAF
BRAF
- Serine-threonine kinase
- Most mutations found in the kinase domain
- Caused by point mutation glutamate –> Valine
Important and early event in melanocytic neoplasia
- Mutation of BRAF and activation of the MAPK pathway
- Not sufficient for the development of melanoma (other mutations are required)
Why do we test for BRAF mutations
Specific BRAF inhibiting drugs have been developed
which are selective for the V600E mutation.
Downside of targeting BRAF mutation
- Darwinian selective pressure
- If tumour is BRAF mutated, some clones may not be reliant on BRAF mutation
- If all cells with BRAF mutation are killed, the ones with other mutation will come back
Common skin cancers besides melanoma
- Basal Cell Carcinoma
- Actinic Keratosis
- Intraepidermal squamous cell carcinoma
- Invasive squamous cell carcinoma
Basal cell carcinoma
- 70% of skin cancer
- High probability subsequent lesions
- Rare genetic predispositions (Gorlin’s syndrome)
- Locally aggressive
Actinic keratosis
- Dysplastic proliferation of keratinocytes
- Occurs on sun exposed sites, fair skin, elderly
Intraepidermal squamous cell carcinoma (bowen’s disease)
- Erythematous plaque
- Sun-exposed or sun-protected skin
- Cytological atypia
Squamous cell carcinoma
- Sun damaged skin
- Tenderness, “thickness” on palpation
- Low risk of metastasis
Risk factors of SCC
- Perineural invasion
- poorly differentiated grading
Keratoacanthoma
- Type of SCC
- Rapidly growing
crateriform lesion - Usually involutes
