B6-030 CBCL Skin Cancers Flashcards

1
Q

brown/black melanin

A

eumelanin

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2
Q

yellow/orange melanin

A

pheomelanin

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3
Q

[…] skin color is impacted by solar radiation, UVR, and endocrine system

A

facultative

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4
Q

are differences constitutive skin color due to the number of melanocytes?

A

no

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5
Q

what amino acid is necessary for pheomelanin synthesis?

A

cysteine

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6
Q

TRP1 and DCT contribute to the synthesis of […] melanin

A

eumelanin

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7
Q

the expression of […] is a major determinant for blue/brown eye color

A

OCA2

**tyrosinase trafficking/processing enzymes

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8
Q

lower MC1R signaling results in

A

more pheomelanin and lighter skin

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9
Q

higher MC1R signaling results in

A

relatively more eumelanin and darker skin

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10
Q

loss/significantly reduced function of MC1R is associated with

A

red hair phenotype

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11
Q

induces MITF, which activates expression of melanin synthesizing enzymes

A

a-MSH

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12
Q

MC1R agonist [2]

A

a-MSH
ACTH

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13
Q

MC1R antagonist

A

Asip

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14
Q

inhibits eumelanin and promotes expression of genes for pheomelanin

A

Asip

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15
Q

activates DNA repair signaling

A

MC1R

**deficits increase risk of skin cancer

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16
Q

how do deficits in MC1R signaling cause an increased risk of skin cancer? [2]

A
  1. decreased production of protective eumelanin
  2. less activation of DNA repair pathways
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17
Q

sunburn is mostly caused by UV[…]

A

UVB

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18
Q

UVB results in lesions of […] in DNA

A

pyrimidine dimers

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19
Q

delayed tanning (sunburn) damages keratinocytes and causes the secretion of […], which stimulate eumelanin production

A

cytokines and chemokines

**mediated by a-MSH and ACTH

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20
Q

does sunscreen protect from UVA or UVB?

A

UVB

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21
Q

at high SPF values, protection [does/does not] increase proportionally

A

does not

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22
Q

are current recommendations promoting UV protection for melanoma prevention in skin of color supported by current research?

A

no, there is little evidence to support this

**however, AAD recommends everyone use sunscreen regardless of skin tone

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23
Q

[keratinocytes or melanocytes]
tend to be in stratum basale or even below stratum basale

A

melanocytes

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24
Q

[keratinocytes or melanocytes]
small, dark nucleus
light, fluffy cytoplasm

A

melanocytes

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25
Q

[keratinocytes or melanocytes]
cleft goes all the way around, or partly around nucleus with no intervening cytoplasm

A

keratinocyte

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26
Q

[keratinocytes or melanocytes]
found in stratum spinosum

A

keratinocytes

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27
Q

melanocytic tumors [3]

A

benign nevi
dysplastic nevus
malignant melanoma

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28
Q

melanocytic nevi located where the dermis and epidermis meet

A

junctional nevus

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29
Q

melanocytic nevi located in epidermis and dermis

A

compound nevus

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30
Q

melanocytic nevi located in dermis

A

dermal nevus

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31
Q

what is this?

A

dysplastic nevus

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32
Q

what is this?

A

malignant melanoma

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33
Q

keratinocytic tumors [5]

A

lentigo
seborrheic keratosis
actinic keratosis
squamous cell carcinoma
basal cell carcinoma

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34
Q

looks like “socks dipped in chocolate”

A

solar lentigo

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35
Q

white pores

A

seborrheic keratosis

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36
Q

feels like sandpaper
precursor to squamous cell carcinoma

A

actinic keratosis

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37
Q

spiky contours

A

squamous cell carcinoma

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38
Q

[…] carcinoma is pink

A

squamous cell

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39
Q

[…] carcinoma is blue

A

basal cell

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40
Q

dense red keratin with preserved nuclei

A

squamous cell carcinoma

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41
Q
A

basal cell carcinoma

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42
Q

occur due to mutations in the Hedgehog signaling pathway, most commonly PTCH1 or also P53

A

basal cell carcinoma

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43
Q

raised, rolled edges

A

basal cell carcinoma

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44
Q

therapy for metastatic or inoperable basal cell carcinoma [2]

A

anti- PD1 inhibitor
vismodegib, sonidegib (inhibit Hedgehog pathway)

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45
Q

premalignant cutaneous lesions that may progress to squamous cell carcinoma

A

actinic keratoses

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46
Q

[…] mutation is thought to occur early in the development of actinic keratosis

A

p53

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47
Q

treatment options for metastatic squamous cell carcinoma

A

chemotherapy
EGFR inhibitor (cetuximab)
anti PD1 (cemiplimab, prembolizumab)

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48
Q

constitutive activation of RAS or BRAF but growth arrest is mediated by CDK

A

benign nevi

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49
Q

nevi located in the dermo-epidermal junction

A

junctional nevi

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50
Q

nevi located partially in the dermis

A

compound

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51
Q

nevi located completely in the dermis

A

intradermal nevi

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52
Q

50% of patients with congenital […] will develop melanoma by age 60

A

dysplastic nevus syndrome

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53
Q

loss of CDKN2A is associated with [2]

A

dysplastic nevus syndrome
familial melanoma syndrome

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54
Q

activating mutations in NRAS/BRAF and inactivating mutations in CDKN2A/CDK4 [2]

A

dysplastic melanocytic nevus
melanoma

55
Q

activating mutations in FGFR3

A

seborrheic keratoses

56
Q

sudden appearance of several seborrheic keratoses
maybe due to TGF-a

A

Leser-Trelat sign

**commonly associated with GI adenocarcinomas

57
Q

multiple, small seborrheic keratoses occurring in people of color

A

dermatosis papulosa nigra

benign finding, can be removed for cosmetic reasons

58
Q

diagnostic steps for melanoma [3]

A

biopsy-depth of primary lesion
determine sentinel node involvement
staging studies

59
Q

treatment for stage III melanoma BRAF +

A

BRAF/MEK inhibitor or anti PD-1

60
Q

treatment for stage III melanoma BRAF -

A

one year anti PD-1 (pembrolizumab)

61
Q

constitutive skin tone is determined by [2]

A

number, size, distribution of pigment granules in skin

relative amount of eumelanin and pheomelanin in melanosomes

62
Q

solar UVR exposure contributes to […] skin tone

A

facultative

63
Q

MC1R signaling activates [2]

A

expression of pigment synthesizing enzymes

DNA repair enzymes

64
Q

[UVB or UVA]
most effective at producing erythema

A

UVB

65
Q

[UVB or UVA]
penetrates into dermis

A

UVA

66
Q

[UVB or UVA]
passes through glass

A

UVA

67
Q

[UVB or UVA]
production of pyrimidine dimers on DNA

A

UVB

68
Q

what causes sunburn at the cellular level?

A

release of inflammatory mediatiors

69
Q

DNA damage triggers […] that produces the warmth, pain, and erythema of sunburn

A

inflammatory mediators

70
Q

immediate pigment darkening in the hours following UVR exposure is caused by

A

redistribution and oxidation of melanin already present in melanosomes

71
Q

aspects of mechanism that induce delayed tanning [2]

A

DNA damage and subsequent MCR1 activation and signaling

increased expression of enzymes responsible for pigment synthesis

72
Q

what layer of skin are adipocytes found in?

A

hypodermis

73
Q

what layer of skin is collagen found in?

A

dermis

74
Q

what layer of skin are melanocytes found in?

A

epidermis-stratum basale

75
Q

what layer of skin are hair follicles found in?

A

dermis

76
Q

what layer of skin are keratinocytes found in?

A

epidermis

77
Q

melanocyte nests located only in the epidermis

A

junctional nevus

78
Q

melanocyte nests located in epidermis and dermis

A

compound nevus

79
Q

melanocytes nests located in the dermis

A

dermal nevi

80
Q

nevi that are lentiginous, broad, and mostly at the junction

A

dysplastic nevi

81
Q

elongated rete pegs
melanin pigment in dermis within macrophages
spread out (lentiginous)

A

dysplastic nevi

82
Q

asymmetric appearance with upward scatter of single melanocytes

A

melanoma

83
Q

hyperpigmented rete pegs
“socks dipped in chocolate”

A

solar lentigo

84
Q

solar lentigo are derived from

A

keratinocytes

85
Q

characteristic “sand paper” feel

A

actinic keratosis

86
Q

keratin pearls visible on histology

A

squamous cell carcinoma

87
Q

blue nodules with palisading of tumor cells

A

basal cell carcinoma

88
Q

has potential to progress to squamous cell carcinoma

A

actinic keratosis

89
Q

a history of immunosuppression leads to an increased risk for

A

squamous cell carcinoma

90
Q

edges that are shiny, slightly raised, rolled

A

basal cell carcinoma

91
Q

pigmented nevi often have mutations in

A

BRAF/RAS

92
Q

transcriptional silencing of […] is found in 1/5 of non-sun-exposed melanoma

A

PTEN

93
Q

are solar lentigines cancerous precursors?

A

no

94
Q

pearly white, skin colored nodule in light skinned people, more darkly pigmented in dark skin people
edges may be shiny, slightly raised, and rolled

A

basal cell carcinoma

95
Q

ulcerated, tender pink papule with central crust

A

squamous cell carcinoma

96
Q

precursor for squamous cell carcinoma

A

actinic keratosis

97
Q

gray elastosis on histology is a feature of [2]

A

solar lentigo
actinic keratosis

98
Q

keratin pearls on histology is a feature of

A

squamous cell carcinoma

99
Q

upward sweep of individual cancer cells on histology is a feature of

A

melanoma

100
Q

even when sunscreen is used properly, [….] can still result in sunburn

A

long enough exposure to sun

101
Q

number of melanocytes [does/does not] determine skin pigment production

A

does not

102
Q

MOA of PD-1 inhibitor (pembrolizumab)

A

killing of tumor cells by T cells

**normally PD-L1 binds to PD-1 on T cells inhibiting T cell mediated destruction of cancer cells
PD-1 inhibitors prevent the binding of PD-1L/PD-1, thus facillitating T cell mediated destruction of tumor cells

103
Q

though UVA is “less damaging” than UVB, it can generate

A

ROS which can damage DNA

104
Q

upward scatter of single melanocytes

A

melanoma

105
Q

“socks dipped in chocolate”

A

solar lentigo

106
Q

long rete pegs
singly spaced letiginous melanocytes
some melanin in dermis

A

dysplastic nevus

107
Q

architecturally disordered junctional nests and lentiginous spread extending well beyond the dermal component

A

dysplastic nevus

108
Q

describe the cell signaling pathway that promotes cell proliferation

A

RTK/RAS —> BRAF/MEK/ERK —> cyclin D1-CDK4/6

109
Q

BRAFV600E mutation results in

A

constitutive activation of BRAF, regardless of RAS signaling. Results in constitutive activation of cell proliferation pathway

110
Q

circular lamellae of keratin

A

SK (horn cysts)

111
Q

blue nodules in the dermis

A

basal cell carcinoma

112
Q

keratin pearls

A

squamous cell carcinoma

113
Q

inactivating mutations in […] can occur in dysplastic nevi

A

CDKN2A or CDK4

114
Q

congenital dysplastic nevi syndrome is associated with loss of […] gene

A

CDKN2A

115
Q

required to maintain the ends of chromosomes

A

telomerase

116
Q

overexpression of telomerase would result in

A

“replicative immortality”

telomerase maintains chromosome length. Usually once telomeres shorten to a certain length, the cell becomes senescent

117
Q

describe the cellular events leading to tanning/sunburn

A
  1. formation of pryrimidine dimers
  2. release of inflammatory mediatiors and secretion of ligands for MC1R
118
Q

SCC has […] risk of metastasis

A

low

119
Q

in what layer of skin are melanocytes found?

A

epidermis

120
Q

solar lentigines can develop into

A

SK

121
Q

BRAF signaling promotes

A

cellular proliferation

via activation of cyclin dependent kinases

122
Q

BCC has […] risk of metastasis

A

low

123
Q

commonly occurs above the upper lip

A

basal cell carcinoma

124
Q

commonly occurs below the lower lip

A

squamous cell carcinoma

125
Q

waxy pink pearly nodules
commonly with telangiectasias
rolled borders

A

BCC

126
Q

can appear as nonhealing ulcers with infiltrative growth/scaling plaque

A

BCC

127
Q

associated with immunosuppresion, chronic nonhealing wounds, and arsenic exposure

A

SCC

128
Q

commonly appears on face, lower lip, ears, hands

A

SCC

129
Q

melanoma has […] risk of metastasis

A

high

130
Q

S-100

A

melanoma

131
Q

in melanoma, […] of tumor corresponds with risk of metastasis

A

depth

**Breslow thickness

132
Q

often driven by activating mutation in BRAF kinase

A

melanoma

133
Q

BRAF inhibitor

A

vemurafenib