skin cancers Flashcards
lifetime risk of nonmelanoma skin cancer?
1 in 5 lifetime risk in US
what is the most common invasive neoplasm in the US?
basal cell carcinoma
what is the frequent mutation in Basal cell carcinoma?
PTCH mutations(30%) in sporadic tumors
what is the function of PTCH
tumor suppressor gene: regulator of basal epidermal cell proliferation
what are five risks for acquiring basal cell CA?
UV exposure, fair complexion, h/o sunburns(especially blistering), family history of BCC and immunosuppression
what is the classic appearance of a basal cell carcinoma?
pearly nodular characteristic, centrally ulcerated, and studded with talengectiasies (dilated BVs)
describe the cells of basal cell carcinoma
basophillic hyperchromatic cells that form nodules, extending from the surface epidermis; cells at the periphery of the aggregations form a palisade
what are tumor nodules set in?
set in a mucnious stroma with retraction from that stroma (clefting, or retraction artifact)
what is the most common subtype of basal cell CA?
nodular
describe the appearance of classic BCC(nodular)
well circumscribed nodule with pearly rolled border and central erosion. note telangiectasias as well
only _____of BCC presents before age 50, and it is rare prior to age 35.
20%
what is Basal cell nevus syndrome aka Gorlin syndrome? what is the mutation in this cancer? at which age do ppl usually present with BCCs?
autosomal domiant and rare. 1 in 56,000 people
characterized by mutation in PTCH1: tumor suppressor gene
BCCs at early age (~23yo)
MSK defects and jaw cysts
increased risk for other neoplasms: medullobastoma, fibrosarcoma
how often does BCC metastasize?
rarely! 0.0028% to 0.55% of cases
what is the most common treatment of BCC?
excision = most common treatment
what are other common treatment of BCC?
electrodessication and currentage
cryosurgery
radiaiton
topical tx for superficial BCC: 5-fu and imiquimod(inhibitor of TLR7 and TLR8 also involved in inhibitng sonic hedgehg pathway)
name one targeted therapy for advanced BCC. what is its MOA?
vismodegib. MOA: small molecle inhibitor. competitive antagonist of SMO.
what is vismodegib approved for?
approved for advanced BCC (metastatic disease, recurrent disease(post surgery) and non-surgical candidates)
how common is squamous cell carcinoma?
second most common skin CA
what are three categories of squamous cell carcinoma?
- minimal atypia = actinic keratosis
- full thickness of epidermal atypia confined above the basement membrane (SCC in situ) (Bowen’s disease, erythroplasia of Queyrat)
- Invasice SCC (well differentiated, moderately differentiated, poorly differentiated)
in actinic keratosis, what is the clue to the superficial nature of the lesions?
lack of inducration
t/f. parakeratosis (keratiznation characterized by retenion of nuclei in the stratum corneum) is a characteristic of actinic keratosis
true
describe squamous cell carcinoma
hyperchromatrophic, pleomorphic nuclei, disorganied growth, mitoses and invasion through basal layer.
cells are pink, keratinizing, like hte stratum spinosum
what is the etiology of SCC
no specific SCC oncogene or tumor suppressor gene has been indentified; increased p53 mutation only
name three risk factors for development of SCC
UV radiation
HPV
immunosuprression (esp with transplant patients)
others: chornic inflammation, certain scars(burns), chemical exposure, especially arsenic, radiaiton exposure, leukoplakia
KNOW: what is the risk of metastasis in cutaneous SCC related to? (4)
tumor size, depth of invasion into dermis, anatomic site, host immune status
size and depth of tumor that are at high risk for metastasis in SCC
larger than 2cm clinically, greater the risk; greater than 4mm in depth or subcutaneous extension
higher risk on lips and ears
what is the overall risk of metastasis of SCC?
<5% (closer to 0.5-1% for actinic induced non-mucosal skin)
in SCC what are some high risk metastasis scenarios?
actinic induced on lip: 2-16%
Marjolin’s ulcers 10-30%
vulvar, perineal, penile HPV-induced 30%
leukoplakia
two common locations of SCC metastasis
lungs and lymph nodes
name 2 subtypes of SCC
keratoacanthoma and marjolin’s ulcer
what is a keratoacanthoma?
which cancer is it related to?
how does it grow?
is it painful?
can it involute?
neoplasm of keratinocytes
related to SCC, possibly a subtype
rapidly grows over 2-6 weeks
painful
may involute spontaneously
what is marjolin’s ulcer?
an ulcerated invasive scc arising on a background of chornic inflammation, scarring, radiation, trauma
what does SCC treatment depend on?
degree of progression
what is the tx for actinic keratosis?
topical therapy, cryotherapy
what is the tx for SCC in situ?
topical therapy, intralesional, exicision
how do you treat invasive SCC
exicision
who is at highest risk to get melanoma?
old white men
t/f. most melanomas develop de novo
true (about 20% develop from pigmented lesions)
where do melanomas have to be in order to metastasize?
have to be in the dermis
what are the three types of melanocytic nevi?
junctional, compound, intradermal
do melanomas mature with descent into the dermis (cells get smaller)?
no, melanomas do not mature with descent into the dermis
do nevi have melanocytes above the basal layer?
not usually, melanocytes above the basal layer is more characteristic of melanoma
both nevi and melanoma are comprised of ________
melanocytes
both nevi and melanoma share which mutations?
BRAF
t/f. high numbers of nevi (>50) can incerase risk of melanoma
true (melanocyte burden)
t/f. melanoma can develop from pre-existing nevi
~20% develop from nevi
~80% develop de novo
identify three multifactorial etilogies for melanoma
genetic predisposition (CDNK2, BRAF)
environment (UV)
underlying immune status
what are 9 common melanoma risk factors?
- large number of common nevi (esp >50)
- giant congenital nevi
- atypical nevi
- history of blistering sunburns
- family histor of melanoma
- light complexion, tanning bed use
- underlying immune dysfunction
the ABCDE of melanoma + 2 more signs
A - asymmetry
B- borders: irregular, scallped
C- color: mottled, variegated, not uniform
D- diameter >6mm
E- elevation
changing mole and ugly duckling sign
what are the five subtypes of melanoma?
acral lentigous - arises in palms or soles, often in dark skinned individuals, not related to UV light expsoure
lentigo maligna melanoma -
nodular
superficial spreading
amelononic - non-melanin producing
what are three prognostonic indicators for melanoma
- whether they are in the dermis
- how far they go into the dermis
- wehtehr or not they are ulcerated
describe lentigo maligna
melanoma of older patients on sun-exposed skin
slow growing, still in radial pahse, still melanoma in situ
what defines acral lentiginous melanoma?
defined by anatomic location on plantar, palmar, and subungal skin
most common melanoma in dark-skinned pts.
what heralds the progression of the an situ lesion of lentigo maligna melanoma to an invasive one?
when a nodule arises on the backgroud on lentigo maligna
nodular melanoma. what is the location? do they have preceding preceding radial growth? what is their epidemiology?
usually on sun exposed skin, no preceding radial growth; 15% of MM, 2x men>women
characteristis of a superficial spreading melanoma
wider variation in color, diameter > 6mm, elevated
where are melanocytes derived from?
neural crest cells
melanoma metastasis is often via _____
lymphatics, but not exclusively
what is the #1 organ site for melanoma metastasis?
skin
what is the most common cause of death in melanoma involvement
CNS involvement
KNOW: what is the single most important prognostic factor in melanoma metastasis?
lymph node involvement
KNOW: what is the single most important histological prognostic factor in melanoma?
breslow thickenss and ulceration
what is breslow’s thickness?
distance of involvement from the stratum granulosum (top) to the deepest tumor cell (bottom)
how do you treat melanoma?
catch it early and cut it out!
50% of melanoms harbor which mutaiton
BRAF
MOA for vemurafenib?
small molecule inhibitor of BRAF V600E mutation
what is vemurafenib approved to treat?
unresectalbe or metastastic (stage 4) melanoma
provides survival benefit (although modest)
initial response impressive, but melanoma adpats
new trials focused on combo therapy esp with ipilimumab
what is the MOA for ipilimumab?
blocks CTLA4 –> immune stimulatin
what is role of sunlight in SCC, BCC, and melanoma?
SCC - cumulative lifelong expsoure clearly related to development
BCC - UV important but not clearly related to cumulative doses –> intermittent?
melanoma – certainly plays a role, along with genetics, other environmental facotrs, and immune system
xeroderma pigmentosum: incidence
autosomal recessive: 1 in 1 millin in US
what is the defet in xeroderma pigmentosum
defects in gene that function in nucleotide excision repair of thymine dimers
xeroderma pigmentosum leads to increased risk in skin cancers by which mech?
by increased sensitivity to UV light
Summary: skin cancer is common and incidence is increasing
amenable to prevention and early detection
genetic advances have led to targeted therapies in advanced disease
