L11 – Skin Pathology: Melanoma and the Impact of BRAF Mutation

Question 1

What are the three primary layers of the skin?

Answer 1

The skin is composed of the epidermis, dermis, and hypodermis.

Question 2

What is the role of the epidermis in skin protection?

Answer 2

The epidermis provides a barrier against UV radiation, pathogens, and environmental insults, with melanocytes producing melanin for UV protection.

Question 3

Which structures are considered adnexal elements in the skin?

Answer 3

Adnexal structures include sweat glands, hair follicles with associated sebaceous glands, and the arrector pili muscle.

Question 4

How does the process of keratinisation occur in the epidermis?

Answer 4

Keratinocytes divide in the basal layer, then differentiate as they migrate upwards, eventually forming the keratinised, protective stratum corneum.

Question 5

What is the ABCD rule used for in melanoma screening?

Answer 5

The ABCD rule (Asymmetry, Border, Colour, Dimension) helps identify suspicious pigmented lesions that may represent melanoma.

Question 6

What additional criteria are suggested for recognising nodular melanoma?

Answer 6

The EFG rule (Elevation, Firmness, Growth) is used to assess lesions that may lack traditional ABCD features.

Question 7

What percentage of melanomas arise de novo?

Answer 7

Approximately 70% of melanomas develop de novo rather than from pre-existing pigmented lesions.

Question 8

Why is early detection critical in melanoma prognosis?

Answer 8

Early detection, when the lesion is in situ, allows for surgical excision with excellent survival outcomes.

Question 9

Describe the progression from a nevus to invasive melanoma.

Answer 9

Progression follows stages: benign nevus formation, dysplastic nevus, radial growth phase (intraepidermal proliferation), vertical growth phase (basement membrane invasion), and finally metastatic melanoma.

Question 10

What histological features indicate melanoma in situ?

Answer 10

Features include junctional activity with pagetoid spread, prominent melanin, large atypical cells, and preserved dermoepidermal architecture.

Question 11

How is invasive melanoma identified histologically?

Answer 11

Invasive melanoma shows dermal involvement with atypical melanocytes lacking maturation and often demonstrates features like ulceration and mitotic figures.

Question 12

What are some helpful microscopic features used to differentiate melanoma from benign lesions?

Answer 12

Asymmetry, cellular atypia, lack of maturation in the dermal component, and the presence of mitotic figures are key indicators.

Question 13

Which molecular pathways are commonly altered in melanoma?

Answer 13

The key altered pathways include the RAS-RAF-MEK-ERK pathway, p16(INK4A)-CDK4-RB, and ARF-p53 pathways.

Question 14

What is the significance of BRAF mutations in melanoma?

Answer 14

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.

Question 15

How does the presence of a BRAF mutation influence treatment options?

Answer 15

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.

Question 16

Why is molecular testing important in the management of melanoma?

Answer 16

Molecular testing guides targeted therapy decisions, helps predict response to treatment, and provides prognostic information regarding tumour behaviour.

Question 17

How do NRAS mutations influence melanoma progression?

Answer 17

NRAS mutations activate the MAPK pathway, contributing to cell proliferation and potential resistance to targeted therapies.

Question 18

What histopathological features are characteristic of acral lentiginous melanoma?

Answer 18

It typically occurs on palms, soles, or nail beds and displays a lentiginous growth pattern with irregular, variegated pigmentation.

Question 19

How is melanoma thickness (Breslow depth) used in prognostication?

Answer 19

Greater Breslow depth is directly correlated with a higher risk of metastasis and poorer survival outcomes.

Question 20

How does the tumour microenvironment affect melanoma progression?

Answer 20

Factors such as immune cell infiltration, angiogenesis, and stromal interactions can influence tumour growth and metastatic potential.

Question 21

What is the clinical relevance of detecting microsatellites in melanoma lesions?

Answer 21

Their presence suggests lymphatic spread and is associated with an increased risk of recurrence.

Question 22

How are emerging biomarkers, like PD-L1, utilised in melanoma management?

Answer 22

They guide immunotherapy decisions by indicating which tumours are more likely to respond to checkpoint inhibitors.

Question 23

Why is combination targeted therapy advantageous in melanoma treatment?

Answer 23

Combining BRAF inhibitors with MEK inhibitors has been shown to improve response rates and delay the development of resistance.

Question 24

What are the primary locations where melanocytic tumors can develop?

Answer 24

Melanocytic tumors primarily develop on the skin but can also arise in mucosal tissues and the meninges.

Question 25

How does the thickness of the skin vary across different body regions?

Answer 25

The thickness of the skin varies from 0.5 mm around the eyes to several millimeters on the soles of the feet.

Question 26

What are the major histological components of the epidermis?

Answer 26

The epidermis consists of multiple layers, including the stratum corneum, which is composed of dead, tightly bound cells.

Question 27

Where are melanocytes primarily located within the epidermis?

Answer 27

Melanocytes are primarily located in the basal layer of the epidermis, where they produce pigment.

Question 28

How does melanin production affect skin coloration and UV protection?

Answer 28

Melanin production influences skin coloration, with darker skin providing better UV protection than lighter skin.

Question 29

Why is UV radiation a major risk factor for melanoma?

Answer 29

UV radiation damages DNA and contributes to melanoma development, particularly in fair-skinned individuals.

Question 30

Which populations are at the highest risk of melanoma due to UV exposure?

Answer 30

Populations with high sun exposure, such as those in Australia, are at the greatest risk of developing melanoma.

Question 31

What clinical criteria help distinguish malignant melanocytic lesions?

Answer 31

The ABCD rule (Asymmetry, Border irregularity, Color variation, and Diameter) helps identify suspicious melanocytic lesions.

Question 32

What percentage of melanomas arise de novo rather than from pre-existing nevi?

Answer 32

Approximately 70% of melanomas arise de novo rather than from pre-existing pigmented lesions.

Question 33

What are key risk factors for melanoma development?

Answer 33

Risk factors for melanoma include fair skin, family history, UV exposure, and prior dysplastic nevi.

Question 34

How do benign nevi differ clinically from dysplastic nevi?

Answer 34

Benign nevi are typically symmetric, uniform in color, and stable in size, whereas dysplastic nevi exhibit atypical features.

Question 35

What are the typical phases of melanoma progression?

Answer 35

Melanoma progresses from localized epidermal changes to dermal invasion and eventual metastasis.

Question 36

Which genetic mutations are most commonly associated with melanocytic lesions?

Answer 36

BRAF mutations are commonly found in melanocytic lesions and play a role in oncogenesis.

Question 37

How do BRAF mutations contribute to melanoma oncogenesis?

Answer 37

BRAF mutations lead to increased cellular proliferation, but additional mutations are required for melanoma progression.

Question 38

What additional genetic alterations are necessary for melanoma progression?

Answer 38

Genetic alterations in the P16INK4A and PTEN pathways contribute to melanoma development.

Question 39

How has the understanding of genetic mutations influenced melanoma treatment?

Answer 39

Targeting genetic mutations in melanoma has led to the development of effective, personalized treatments.

Question 40

What impact have BRAF and MEK inhibitors had on melanoma prognosis?

Answer 40

BRAF and MEK inhibitors have significantly improved survival rates for patients with metastatic melanoma.

Question 41

How have recent therapeutic advancements changed survival outcomes for melanoma patients?

Answer 41

Recent advancements in targeted therapy have transformed melanoma from a fatal disease to a treatable condition.

Question 42

Why is ongoing research into melanoma genetics crucial for future treatments?

Answer 42

Ongoing research into melanoma genetics is essential for developing more effective and durable treatments.

Question 43

What is the role of the adnexal structures in the skin?

Answer 43

Adnexal structures in the skin include sweat glands, hair follicles with associated sebaceous glands, and the arrector pili muscle, contributing to thermoregulation and sensation .

Question 44

How does the skin contribute to vitamin D synthesis?

Answer 44

The skin contributes to vitamin D synthesis by converting inactive forms of vitamin D to active forms upon exposure to sunlight, which is crucial for calcium absorption and bone health .

Question 45

What are the differences in skin cancer incidence between populations with different skin tones?

Answer 45

Populations with darker skin tones have lower incidences of melanoma but may develop it in less exposed areas and at more advanced stages compared to fair-skinned populations .

Question 46

How does UV radiation affect the skin and contribute to cancer risk?

Answer 46

UV radiation damages DNA and contributes to melanoma development, particularly in fair-skinned individuals, by causing mutations in skin cells .

Question 47

What are the clinical features that differentiate benign nevi from malignant melanocytic lesions?

Answer 47

Benign nevi are typically symmetric, uniform in colour, and stable in size, whereas malignant melanocytic lesions may show asymmetry, irregular borders, colour variation, and changes in size .

Question 48

What is the significance of the EFG rule in melanoma detection?

Answer 48

The EFG rule (Elevation, Firmness, Growth) is used to assess lesions that may lack traditional ABCD features, helping in the detection of nodular melanoma .

Question 49

How do genetic mutations influence the progression of melanocytic lesions?

Answer 49

Genetic mutations such as those in the BRAF, NRAS, and PTEN genes influence the progression of melanocytic lesions by affecting cell proliferation and survival pathways .

Question 50

What is the role of the tumour microenvironment in melanoma progression?

Answer 50

The tumour microenvironment, including immune cell infiltration and stromal interactions, affects melanoma growth and metastatic potential .

Question 51

How does the presence of microsatellites in melanoma lesions affect prognosis?

Answer 51

The presence of microsatellites in melanoma lesions suggests lymphatic spread and is associated with an increased risk of recurrence .

Question 52

What are the emerging biomarkers used in melanoma management?

Answer 52

Emerging biomarkers like PD-L1 are used in melanoma management to guide immunotherapy decisions and predict response to checkpoint inhibitors .

Question 53

How do combination therapies improve outcomes in melanoma treatment?

Answer 53

Combination therapies, such as BRAF inhibitors with MEK inhibitors, improve response rates and delay resistance development in melanoma treatment .

Question 54

What are the primary locations for melanocytic tumors outside the skin?

Answer 54

Melanocytic tumours primarily develop on the skin but can also arise in mucosal tissues and the meninges .

Question 55

How does skin thickness vary across different body regions?

Answer 55

Skin thickness varies from 0.5 mm around the eyes to several millimetres on the soles of the feet, reflecting functional adaptations .

Question 56

What are the major histological components of the epidermis?

Answer 56

The major histological components of the epidermis include multiple layers, with the stratum corneum composed of dead, tightly bound cells .

Question 57

Where are melanocytes primarily located within the epidermis?

Answer 57

Melanocytes are primarily located in the basal layer of the epidermis, where they produce pigment .

Question 58

How does melanin production affect skin coloration and UV protection?

Answer 58

Melanin production influences skin coloration, with darker skin providing better UV protection than lighter skin .

Question 59

Why is UV radiation a major risk factor for melanoma?

Answer 59

UV radiation is a major risk factor for melanoma as it damages DNA and contributes to melanoma development, particularly in fair-skinned individuals .

Question 60

Which populations are at the highest risk of melanoma due to UV exposure?

Answer 60

Populations with high sun exposure, such as those in Australia, are at the greatest risk of developing melanoma .