what cell type are melanocytes derived from?
neural crest cells
where can melanoma and nevi occur?
anywhere neural crest cells migrate
where is the most common site for melanoma formation histologically?
What are the 5 general criteria for a gross diagnosis of melanoma?
A - asymmetry B - irregular borders C - color variation D - large diameter E - evolving/ elevated
what is the most important factor contributing to melanoma prognosis
ulceration and depth of dermal involvement
what do nevi and melanoma have in common?
both comprised of melanocytes, both can share mutations such as BRAF
in general, are nevi pre-melanomas? what percentage of melanomas are derived from nevi?
no only 20% of melanoma develop from nevi
how are nevi related to risk of melanoma
an increased number of nevi (more than 50) increase risk of melanoma
what are the 3 types of acquired melanocytic nevi?
junctional, compound, intradermal
What is this? and define
junctional nevus - nests of melanocytes are present within epidermis only
what is this? and define
compound nevus - nests of melanocytes are present within epidermis and dermis
what is this? and define
Intradermal nevus - nest of mealnocytes within dermis only
what is the classic definition of nevus?
any congenital lesion of the skin - a birthmark
2-3 mm in diameter, deeply pigmented and macular, arising at the dermal-epidermal junction above the BM - what type of nevus?
3-4 mm, slightly raised, moderately pigmented, melanocytes found both intradermally and dermally - what type of nevus
large and dome shaped lesion, cells exclusively in the dermis - what type of nevus
define halo nevi. what pt population is it more common in?
common acquired nevus with a surrounding zone of depigmentation common in 1st 3 decades of life, equal in males and females, more common in patients w/ vitiligo, familial tendency
what is the etiology of halo nevi
highlights the relationship between melanocytic neoplasia and host immunity - body recognizes somewhere there is melanoma, starts attacking all nevi everywhere - causes clearing
how do you classify congenital nevi?
according to size (small less than 1.5 cm, medium 1.5-20 cm, large more than 20 cm)
congenital nevi classified according to size - how do you apply this classification to children
the number cutoffs are for adults; must adjust these numbers for neonate (know this)
describe the clinical features of a congenital nevus
pigmentation varying from brown to black, grossly irregular surface, and hypertrichosis (hair is a key finding)
for congenital nevi, what is the rule of 5s? ($$)
5 cm or greater, in the first 5 years of life, 5% risk of melanoma - 5 cm - this is considered large for neonate (hence the adjustment of number cutoffs)
for atypical "dysplastic" nevi, do most pts carry an increased risk of melanoma? are dysplastic nevi precursors to melanoma?
in what case do atypical dysplastic nevi carry an increased risk of melanoma? ($$)
familial history of melanoma + great numbers of atypical nevi
what is the general clinical appearance of atypical nevi?
irregular borders, variegated pigment, and asymmetry - they break the ABCDE rules, and thus get biopsied b/c they resemble melanoma - but are not
epidemiology, who is at highest risk for melanoma
Caucasian me older than 50
how do melanocytes normally mature? how is this different in melanoma
normally - melanocytes decrease in size as they dive deeper into dermis
melanoma - do not decrease in size - thus do not mature
where do melanocytes normally reside? where would growth be abnromal?
melanocytes normally live in the basal layer - growth above the basal layer is abnormal
what is melanoma in situ? what growth phase is it in?
unorganized melanocytes, increased in number and located above the basal layer - "radial" growth phase
when is a melanoma capable of metastasis? how is this relevant for detection and treatment $$
until melanoma is located within the dermis, it cannot metastasize - find and treat early, imperative
what is the growth phase called when a melanoma is capable of metastasis? what routes do melanoma metastasize by?
vertical growth phase mets via lymphatics (mainly)
melanoma is multifactorial etiology - what 3 factors
genetic predisposition (BRAF) environment - UV underlying immune status
what are the risk factors for melanoma?
large number of common nevi (esp more than 50)
Giant congenital Nevi
Atypical nevi, mostly if multiple and familial
History of blistering sunburns
FH of Melanoma
Light Complexion, tanning bed use
Underlying immune dysfunction
ABCDE - what number is cutoff for diameter (D)
what is the ugly duckling sign in screening for melanoma
one lesion that stand out from all the others
define acral lentiginous melanoma; who is it more common in?
melanoma on palms and soles - palmar, plantar, and subungual (under the nails) skin more common in ppl of color
define Lentigo Maligna Melanoma; who is it more common in
melanoma arising on the sun exposed areas of the face in older patients
what type of melanoma is a Lentigo Maligna variant? what does this mean for prognosis
melanoma in situ slow growing, still in "radial" growth phase - does not have capacity to mets - not yet
what clinical finding heralds the progression of the in situ lesion of Lentigo Maligna to an invasive one?
the formation of a nodule arising in the background of a lentigo maligna - it has progressed to the dermis - vertical growth - evident by the lifting up of the skin
define nodular melanoma; discuss the characteristic progression and what growth phase it is in
a black nodule arising on sun exposed skin "no preceding radial growth" - the lesion is already in the vertical growth phase (already in the dermis) at the time of presentation - has capcity to mets
what pt population is nodular melanoma is more common in?
2x more in men
what is a superficial spreading melanoma variant? what growth phase?
largely in radial growth phase - not nodular - but can have a nodular component can have a central nodular part, but towards the edges may only be in radial growth phase
describe the clinical appearance of superficial spreading melanoma; what is the characteristic sign?
asymmetrical, irregular borders, wide variation in color, diameter more than 6 mm, elevated "red white and blue sign"
How do melanoma usually metastasize? $$
lymphatics, but not exclusively (can do blood)
what is the number one organ site for melanoma mets? $$
what is the most common cause of death in melanoma? what organ involvement?
What is the single most important prognostic factor in melanoma? $$
lymph node involvement
what are the two most important histological prognostic factors for melanoma?
Breslow thickness and ulceration
define Breslow's thickness
distance of involvement from the stratum granulsoum (top) to the deepest tumor cell (bottom) you are measuring the depth of invasion, starting in granulosum
what are some potential tx modalities for metastatic melanoma
IFNa, combination CTX, XRT, vaccine therapy
what small molecule drug targets BRAF? what BRAF mutation in particular?
Vemurafenib targets V600E pt melanoma must harbor an activating mutation in BRAF V600E to approve treatment
melanoma in situ
melanoma in iris
recall: melanocytes derived from neural crest cells, so melanomas can arise anywhere neural crest cells migrate