Disorders of Pigmentation and Melanocytes Flashcards by Kolbie Chancellor

Most common pigmented lesion of childhood?

Freckle

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When does a Freckle arise?

AFTER sun exposure

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Can Freckles fade or darken, if so, when?

Yes, with season changes

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What spots are seen with Neurofibromatosis?

Cafe au lait spots

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Cafe au lait spots are seen with what condition?

Neurofibromatosis

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When do Cafe au lait spots arise?

INDEPENDENT of sun exposure

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How do Cafe au lait spots compare to Freckles?

Larger
Contain aggregated melanosomes (macromelanosomes) in the cytoplasm of melanocytes
Do not correlate with sun exposure

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Lentigo

Benign localized hyperplasia of melanocytes

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Benign localized hyperplasia of melanocytes

Lentigo

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When is Lentigo initiated?

Childhood but occurs at all ages

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How does Lentigo react when exposed to light?

(hyperplasia of melanocytes)

= Does NOT darken

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How does Lentigo look on histology?

Linear melanocytic hyperplasia

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Histologically, Lentigo is restricted to?

To cell layer immediately ABOVE basement membrane

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What is restricted to the cell layer immediately ABOVE the basement membrane?

Lentigo

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Linear melanocyte hyperplasia?

Lentigo

- Benign

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A Melanocytic Nevus is a?

Mole

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Mole

Melanocytic Nevus

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Melanocytic Nevi are acquired by mutations in components of what signaling pathways?

RAS and BRAF

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Melanocytic Nevi have activating mutations in RAS and BRAF that are only active for a limited time. What causes permanent growth arrest?

P16/INK4a cause permanent growth arrest

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How do Melanocytic Nevi usually look?

Usually small <6mm, well defined borders and one color

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Junctional Nevi

Nest at dermoepidermal junction

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Type of Nevi that nest at dermoepidermal junction

Junctional Nevi

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Compound Nevi

Nest in the epidermis and the dermis

Type of Nevi that nest in the epidermis and dermis

Compound Nevi

Intradermal Nevi

NO epidermal nests; usually older lesions

Type of nevi with NO epidermal nests

Intradermal Nevi - usually older

Describe how Melanocytic Nevi look from superficial to deeper tissues histologically

- Nests of large round cells - Smaller, single cells - Fusiform; fascicles resembling neural tissue

Superficial nests of large round cells that transitions into smaller cells and then into fascicles the deeper into the tissue suggests?

Melanocytic Nevi

Dysplastic Nevi have an increased risk of developing into?

Melanoma

Dysplastic Nevus Syndrome

> 50% chance to develop Melanoma by age 60 | - Autosomal Dominant

What genes are mutated with Dysplastic Nevus Syndrome?

CDKN2A or CDK4

Those with Dysplastic Nevus Syndrome will likely develop?

Multiple dysplastic nevi and melanoma

Dysplastic Nevi acquire activating mutations in what pathways?

NRAS and BRAF

Histo - Dysplastic Nevi are ____ than acquired Nevi

LARGER

Histo - How do Dysplastic Nevi look?

Irregular borders with varied pigmentation and nests may coalesce

Histo - what cells will infiltrate superficial dermis with Dysplastic Nevi?

Lymphocytes

Histo - With Dysplastic Nevi, what surrounds the epidermal rete ridges?

Fibrosis

What is Shouldering?

Extension of junctional component beyond the dermal nests of melanocytes - corresponds to the periphery of lesion

What is Atypia and what is it seen with?

Irregular nucleus with hyperchromasia | - Dysplastic Nevi

What is the most deadly skin cancer?

Melanoma

Melanoma is usually caused by?

DNA damage due to UV light exposure

There is an increased incidence of Melanoma and decreased death. Majority of Melanoma cases are ____. What is a risk factor?

Majority are sporadic | - Severe sunburns early in life increases risk

Males usually get Melanoma where?

Upper back

Females usually get Melanoma where?

Legs

Blacks and Asians usually get Melanoma where?

Soles/Palms, nail beds, mucosal membranes

For Melanoma, what mutations will activate pro-growth signaling pathways?

RAS BRAF P13K/AKT

What is the most commonly mutated gene in Melanoma and what does it activate?

TERT | - activates Telomerase

What are the 2 growth phases of Melanoma?

1. Radial growth | 2. Vertical growth

The Radial growth phase involves horizontal spread of melanoma in the epidermis. What does it lack?

Lacks capacity to metastasize

The Vertical growth phase of Melanoma involves tumor cells invading down into deeper layers. What will likely appear?

Nodule with metastatic potential

What is absent in the Vertical Growth phase of Melanoma?

Neurotization

Breslow thickness

Depth of invasion - correlates with metastasis

Breslow thickness measures between?

Epidermal granular layer Deepest tumor cell - Correlates with metastasis

5 favorable prognoses for Melanoma

1. Thinner tumor depth 2. NO mitosis 3. NO regression 4. Lack of ulceration 5. Brisk tumor infiltrating lymphocyte response

5 favorable prognoses for Melanoma

1. Thinner tumor depth 2. NO mitosis 3. NO regression 4. Lack of ulceration 5. Brisk tumor infiltrating lymphocyte response