Melanocytes, Nevi, and Melanoma Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

Melanocytes

A

found int he stratum basale

pale “halo” of cytoplasm

neural crest

produce melanin and pass it on to nearby keratinocytes

melanin covers nuclei of keratinocytes

skin color depends on activity of cells, rather than number

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What kinds of damage results from UV skin damage?

A

cyclobutane pyrimdine dimers

6-4 photoproducts

DNA damage occurs immediately upon exposure and cell repair begins

the amount of melanin in the skin plays an important role in UV absorption and photoprotection

genetic - ability to repair damage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

moles

A

everyone gets moles

the can get bigger and darker due to sun burns, pregnancy, and heavy sun exposure

some families make “atypical” or irregula rmoles

benign or healthy

irregular moles - “dysplastic”

melanoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

dysplastic nevus

A

multicolored

asymmetric pigment deposition

asymmetric contour-macular and papular

indistinct margins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

atypical mole syndrome - (Dysplastic nevus syndrome)

A

> 100 melanocytic nevi

1 or more nevi >8 mm in diameter

1 or more dysplastic nevi on exam

10 year risk of developing melanoma of 14%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

familial atypical multiple mole melanoma syndrome (FAMMM)

A

presence of melanoma and dysplastic nevi within families

localization of 2 predominant genes - CDKN2A and CDK4 on chromosome 9p21 in melanoma patients

heterogeneity in Fammm kindreds also showing chromosome 1p36 involved in dysplastic nevi and melanoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the management of the dysplastic nevi patient?

A

close monitoring - full body exams every 6 months

dermoscopy of all atypical appearing nevi

whole body photos

excision of any changing or markedly atypical nevi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What makes up a body mapping studio?

A

positioning stage

indexed monostand

balanced cross-lighting

high resolution digital camera

body mapping software

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the procedure of excision of atypical nevi?

A

excisional speciment preferred over shaved biopsy (due to non-uniformity)

3mm border taken around lesion to fat

if melanoma suspected take 3mm margin around lesion of subq-fascial plane and orient in direction of lymphatic drainage

us suspicious area noted within the lesion, place a suture to makr the area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

dermoscopy

A

powerful tool to aid the diagnosis of benign vs. malignant pigmented skin lesion

hand-held microscope that provides detailed visualization of the structures contained within the epidermis, epidermal-dermal junction, and papillary dermis not visible to the naked eye

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the limitations of dermoscopy?

A

limited to visualizing the pigment patterns or other pigment lesions

non-pigmented lesions such as amelanotic melanomas and basal cell carcinoma are studied by their vascular patterns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some characteristic features of dysplastic nevi?

A

2 tones in color

asymmetric

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are characteristic findings of melanoma upon dermoscopy?

A

irregular pigmentation

irregular streaks

blue-whitish veil

atypical pigment network

irregular dots/globules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the epidemiology of melanoma?

A

1 in 58 today

most common cancer in young adults age 20-35

5th most common in males

7th most common in females

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the prognosis of melanoma?

A

80% of all skin cancer deaths

5% of all skin cancer

mortality of 11% in 2005

85% have localized disease at presentation

30% of melanomas develop within an existing dysplastic nevus

70% of melanomas develop denovo - no precursor lesion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the role of CKDN2A in melanoma?

A

20% with a family history of melanoma have a CDKN2A mutation - results in p16 mutation and causes increased S-phase entry

byproduct of CDKN2A gene binds to the MDM2 protein and accelerates the breakdown of p53 and decreases apoptosis

17
Q

What is the role of CKD4 in melanoma?

A

a protein kinase that regulates cell cycle progression

p16 regulates this activity and the mutation renders the protein kinase resistant to p16

the result is increased s-phase entry

18
Q

What are some point mutations from environmental damage that can cause melanoma?

A

point mutation in Braf gene called V600E

glutamate(E) is substituted for valine at position 600 in the DNA resulting in a BRAF mutation

up-regulates the MAPK pathway and increases cell proliferation

19
Q

What is the most important determinant of melanoma prognosis? What are the cutoffs?

A

melanoma thickness

thicker than 1 mm indicates 68% of 5 year survival

<1 mm indicates a 5 year survival of about 90%

20
Q

What is the histopathology of melanoma?

A

low level Brshlow

radial growth phase > vertical grwoth [Phase

lymphatic/vascular invasion - poor prognosis

clarke level provides useful information but less predictive of behavior

21
Q

What are the prognostic indicators of melanoma from most to least prognostic?

A

tumor thickness

ulceration

mitotic rate

regression

Clark’s level

22
Q

What are the melanoma subtypes?

A

superficial spreading melanoma - most common and associated with intermittant sun exposure

lentigo maligna melanoma - associated with chronically sun exposed skin

acral lentiginous and mucosal lentiginous - not sun related

nodular - vertical growth phase only

23
Q

How is age prognostic in melanoma?

A

young > old

24
Q

How is gender prognostic of melanoma?

A

female > male

25
Q

How is location prognostic for melanoma?

A

extremity > trunk

26
Q

What is the prognosis of melanoma with and without ulceration?

A

with ulceration - 66.2% survival in 8 yrs

without ulceratin - 91.6% survival in 8 yrs

27
Q

What are the types of lymph node metastases?

A

rim met

central met

solid tumor

**solid tumor has the worst prognosis

28
Q

vemurafenib

A

directed at the V600E point mutation in the BRAF gene causing inhibition of the gene

29
Q

high-dose interleukin-2

A

effective in 20% of people - can result in complete remission

doesn’t have much effect for the rest

30
Q

ipilimumab

A

anti-CTLA4 antibody

up-regulation of the immune system by blocking regulatory T cells

risk of colitis induced bleeding and death

31
Q

decarbazine and temozolomide

A

two older chemotherapy agents used for melanoma

not very effective and very toxic

32
Q

combination therapy for melanoma

A

ipilimumab, IL2, IFN-alpha, vemurafenib, biologic agents such as GM-CSF with vaccines to maximize immunostimulatory effect

33
Q

What are some new biologic agents for melanoma treatment, and what do they do?

A

Drabrafenib - Braf V600 mutation positive tumors

Trametinib - Mek inhibition in Braf mutation positive tumors

Imatinib - C-kit mutated tumors

**Drabrafenib and Trametinib shut off squamous cells, so less likely to cause other skin cancers