Melanocytes, Nevi, and Melanoma

Question 1

Melanocytes

Answer 1

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

Question 2

What kinds of damage results from UV skin damage?

Answer 2

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

Question 3

moles

Answer 3

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

Question 4

dysplastic nevus

Answer 4

multicolored

asymmetric pigment deposition

asymmetric contour-macular and papular

indistinct margins

Question 5

atypical mole syndrome - (Dysplastic nevus syndrome)

Answer 5

> 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%

Question 6

familial atypical multiple mole melanoma syndrome (FAMMM)

Answer 6

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

Question 7

What is the management of the dysplastic nevi patient?

Answer 7

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

Question 8

What makes up a body mapping studio?

Answer 8

positioning stage

indexed monostand

balanced cross-lighting

high resolution digital camera

body mapping software

Question 9

What is the procedure of excision of atypical nevi?

Answer 9

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

Question 10

dermoscopy

Answer 10

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

Question 11

What are the limitations of dermoscopy?

Answer 11

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

Question 12

What are some characteristic features of dysplastic nevi?

Answer 12

2 tones in color

asymmetric

Question 13

What are characteristic findings of melanoma upon dermoscopy?

Answer 13

irregular pigmentation

irregular streaks

blue-whitish veil

atypical pigment network

irregular dots/globules

Question 14

What is the epidemiology of melanoma?

Answer 14

1 in 58 today

most common cancer in young adults age 20-35

5th most common in males

7th most common in females

Question 15

What is the prognosis of melanoma?

Answer 15

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

Question 16

What is the role of CKDN2A in melanoma?

Answer 16

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

Question 17

What is the role of CKD4 in melanoma?

Answer 17

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

Question 18

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

Answer 18

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

Question 19

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

Answer 19

melanoma thickness

thicker than 1 mm indicates 68% of 5 year survival

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

Question 20

What is the histopathology of melanoma?

Answer 20

low level Brshlow

radial growth phase > vertical grwoth [Phase

lymphatic/vascular invasion - poor prognosis

clarke level provides useful information but less predictive of behavior

Question 21

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

Answer 21

tumor thickness

ulceration

mitotic rate

regression

Clark’s level

Question 22

What are the melanoma subtypes?

Answer 22

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

Question 23

How is age prognostic in melanoma?

Answer 23

young > old

Question 24

How is gender prognostic of melanoma?

Answer 24

female > male

Question 25

How is location prognostic for melanoma?

Answer 25

extremity > trunk

Question 26

What is the prognosis of melanoma with and without ulceration?

Answer 26

with ulceration - 66.2% survival in 8 yrs

without ulceratin - 91.6% survival in 8 yrs

Question 27

What are the types of lymph node metastases?

Answer 27

rim met

central met

solid tumor

**solid tumor has the worst prognosis

Question 28

vemurafenib

Answer 28

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

Question 29

high-dose interleukin-2

Answer 29

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

doesn’t have much effect for the rest

Question 30

ipilimumab

Answer 30

anti-CTLA4 antibody

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

risk of colitis induced bleeding and death

Question 31

decarbazine and temozolomide

Answer 31

two older chemotherapy agents used for melanoma

not very effective and very toxic

Question 32

combination therapy for melanoma

Answer 32

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

Question 33

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

Answer 33

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