Melanocytes, Nevi, and Melanoma Flashcards
Melanocytes
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
What kinds of damage results from UV skin damage?
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
moles
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
dysplastic nevus
multicolored
asymmetric pigment deposition
asymmetric contour-macular and papular
indistinct margins
atypical mole syndrome - (Dysplastic nevus syndrome)
> 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%
familial atypical multiple mole melanoma syndrome (FAMMM)
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
What is the management of the dysplastic nevi patient?
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
What makes up a body mapping studio?
positioning stage
indexed monostand
balanced cross-lighting
high resolution digital camera
body mapping software
What is the procedure of excision of atypical nevi?
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
dermoscopy
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
What are the limitations of dermoscopy?
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
What are some characteristic features of dysplastic nevi?
2 tones in color
asymmetric
What are characteristic findings of melanoma upon dermoscopy?
irregular pigmentation
irregular streaks
blue-whitish veil
atypical pigment network
irregular dots/globules
What is the epidemiology of melanoma?
1 in 58 today
most common cancer in young adults age 20-35
5th most common in males
7th most common in females
What is the prognosis of melanoma?
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
What is the role of CKDN2A in melanoma?
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
What is the role of CKD4 in melanoma?
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
What are some point mutations from environmental damage that can cause melanoma?
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
What is the most important determinant of melanoma prognosis? What are the cutoffs?
melanoma thickness
thicker than 1 mm indicates 68% of 5 year survival
<1 mm indicates a 5 year survival of about 90%
What is the histopathology of melanoma?
low level Brshlow
radial growth phase > vertical grwoth [Phase
lymphatic/vascular invasion - poor prognosis
clarke level provides useful information but less predictive of behavior
What are the prognostic indicators of melanoma from most to least prognostic?
tumor thickness
ulceration
mitotic rate
regression
Clark’s level
What are the melanoma subtypes?
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
How is age prognostic in melanoma?
young > old
How is gender prognostic of melanoma?
female > male
