L11 – Skin Pathology: Melanoma and the Impact of BRAF Mutation Flashcards
What are the three primary layers of the skin?
The skin is composed of the epidermis, dermis, and hypodermis.
What is the role of the epidermis in skin protection?
The epidermis provides a barrier against UV radiation, pathogens, and environmental insults, with melanocytes producing melanin for UV protection.
Which structures are considered adnexal elements in the skin?
Adnexal structures include sweat glands, hair follicles with associated sebaceous glands, and the arrector pili muscle.
How does the process of keratinisation occur in the epidermis?
Keratinocytes divide in the basal layer, then differentiate as they migrate upwards, eventually forming the keratinised, protective stratum corneum.
What is the ABCD rule used for in melanoma screening?
The ABCD rule (Asymmetry, Border, Colour, Dimension) helps identify suspicious pigmented lesions that may represent melanoma.
What additional criteria are suggested for recognising nodular melanoma?
The EFG rule (Elevation, Firmness, Growth) is used to assess lesions that may lack traditional ABCD features.
What percentage of melanomas arise de novo?
Approximately 70% of melanomas develop de novo rather than from pre-existing pigmented lesions.
Why is early detection critical in melanoma prognosis?
Early detection, when the lesion is in situ, allows for surgical excision with excellent survival outcomes.
Describe the progression from a nevus to invasive melanoma.
Progression follows stages: benign nevus formation, dysplastic nevus, radial growth phase (intraepidermal proliferation), vertical growth phase (basement membrane invasion), and finally metastatic melanoma.
What histological features indicate melanoma in situ?
Features include junctional activity with pagetoid spread, prominent melanin, large atypical cells, and preserved dermoepidermal architecture.
How is invasive melanoma identified histologically?
Invasive melanoma shows dermal involvement with atypical melanocytes lacking maturation and often demonstrates features like ulceration and mitotic figures.
What are some helpful microscopic features used to differentiate melanoma from benign lesions?
Asymmetry, cellular atypia, lack of maturation in the dermal component, and the presence of mitotic figures are key indicators.
Which molecular pathways are commonly altered in melanoma?
The key altered pathways include the RAS-RAF-MEK-ERK pathway, p16(INK4A)-CDK4-RB, and ARF-p53 pathways.
What is the significance of BRAF mutations in melanoma?
BRAF mutations, present in about 50% of melanomas, play an early role in oncogenesis and have led to the development of targeted therapies that improve prognosis.
How does the presence of a BRAF mutation influence treatment options?
Detection of BRAF mutations enables the use of BRAF inhibitors (e.g. vemurafenib, dabrafenib), often in combination with MEK inhibitors, to target the altered signalling pathway.
Why is molecular testing important in the management of melanoma?
Molecular testing guides targeted therapy decisions, helps predict response to treatment, and provides prognostic information regarding tumour behaviour.
How do NRAS mutations influence melanoma progression?
NRAS mutations activate the MAPK pathway, contributing to cell proliferation and potential resistance to targeted therapies.
What histopathological features are characteristic of acral lentiginous melanoma?
It typically occurs on palms, soles, or nail beds and displays a lentiginous growth pattern with irregular, variegated pigmentation.
How is melanoma thickness (Breslow depth) used in prognostication?
Greater Breslow depth is directly correlated with a higher risk of metastasis and poorer survival outcomes.
How does the tumour microenvironment affect melanoma progression?
Factors such as immune cell infiltration, angiogenesis, and stromal interactions can influence tumour growth and metastatic potential.
What is the clinical relevance of detecting microsatellites in melanoma lesions?
Their presence suggests lymphatic spread and is associated with an increased risk of recurrence.
How are emerging biomarkers, like PD-L1, utilised in melanoma management?
They guide immunotherapy decisions by indicating which tumours are more likely to respond to checkpoint inhibitors.
Why is combination targeted therapy advantageous in melanoma treatment?
Combining BRAF inhibitors with MEK inhibitors has been shown to improve response rates and delay the development of resistance.
What are the primary locations where melanocytic tumors can develop?
Melanocytic tumors primarily develop on the skin but can also arise in mucosal tissues and the meninges.
How does the thickness of the skin vary across different body regions?
The thickness of the skin varies from 0.5 mm around the eyes to several millimeters on the soles of the feet.
What are the major histological components of the epidermis?
The epidermis consists of multiple layers, including the stratum corneum, which is composed of dead, tightly bound cells.
Where are melanocytes primarily located within the epidermis?
Melanocytes are primarily located in the basal layer of the epidermis, where they produce pigment.
How does melanin production affect skin coloration and UV protection?
Melanin production influences skin coloration, with darker skin providing better UV protection than lighter skin.
Why is UV radiation a major risk factor for melanoma?
UV radiation damages DNA and contributes to melanoma development, particularly in fair-skinned individuals.
Which populations are at the highest risk of melanoma due to UV exposure?
Populations with high sun exposure, such as those in Australia, are at the greatest risk of developing melanoma.
What clinical criteria help distinguish malignant melanocytic lesions?
The ABCD rule (Asymmetry, Border irregularity, Color variation, and Diameter) helps identify suspicious melanocytic lesions.
What percentage of melanomas arise de novo rather than from pre-existing nevi?
Approximately 70% of melanomas arise de novo rather than from pre-existing pigmented lesions.
What are key risk factors for melanoma development?
Risk factors for melanoma include fair skin, family history, UV exposure, and prior dysplastic nevi.
How do benign nevi differ clinically from dysplastic nevi?
Benign nevi are typically symmetric, uniform in color, and stable in size, whereas dysplastic nevi exhibit atypical features.
What are the typical phases of melanoma progression?
Melanoma progresses from localized epidermal changes to dermal invasion and eventual metastasis.
Which genetic mutations are most commonly associated with melanocytic lesions?
BRAF mutations are commonly found in melanocytic lesions and play a role in oncogenesis.
How do BRAF mutations contribute to melanoma oncogenesis?
BRAF mutations lead to increased cellular proliferation, but additional mutations are required for melanoma progression.
What additional genetic alterations are necessary for melanoma progression?
Genetic alterations in the P16INK4A and PTEN pathways contribute to melanoma development.
How has the understanding of genetic mutations influenced melanoma treatment?
Targeting genetic mutations in melanoma has led to the development of effective, personalized treatments.
What impact have BRAF and MEK inhibitors had on melanoma prognosis?
BRAF and MEK inhibitors have significantly improved survival rates for patients with metastatic melanoma.
How have recent therapeutic advancements changed survival outcomes for melanoma patients?
Recent advancements in targeted therapy have transformed melanoma from a fatal disease to a treatable condition.
Why is ongoing research into melanoma genetics crucial for future treatments?
Ongoing research into melanoma genetics is essential for developing more effective and durable treatments.
