Pathophys-Day 2 Skin Cancer Flashcards
BCC, SCC, melanoma arise from which layers?
BCC:germ keratinocytes/basal layer
SCC: epidermal keratinocytes/spiny
Melanoma: melanocytes
PTCH mutations are found in __% of ___ cancers
30% of BCC
What does PTCH do?
Regulate keratinocyte proliferation as a tumor suppressor
Immunosuppressed patients are at greatest risk for which skin cancer
SCC, but also more for BCC
What are some risk factors for BCC?
UV Fair complexion BLISTERING sunburns Family hx Immunosuppression
What are some characteristic features of BCC gross appearance?
Teliangectasia
BCC histo appearance?
Blue nodules in dermis with PALISADES and RETRACTION from stroma which is required for survival (thus low metastasis)
Topical treatment for superficial and nodular?
Not for nodular
5-FU
nodular/’classic’ bcc appearance gross
pearly rolled border
central erosion
telangiectasia
sclerotic/morpheaform bcc appearance gross
crusty, ill-defined
Gorlin syndrome mutation, S/S?
PTCH tumor suppressor AD M/S defects, jaw cysts BCCs in 20's Inc risk of other neoplasms inc medulloblastoma, fibrosarcoma
PTCH signaling overview
PTCH tumor suppressor inhibits SHH from binding to SMO (TKI inhib vesmodegib inhibits SMO)
Does BCC usually metastasize?
Almost never, <1%
Tx for BCC
Excision is first choice
Electrodessication, cryosurgery, radiation…topical for superficial (imiquimod/5FU)
Compare the prognosis for head/neck/cervical vs mucosal/lung SCC
H/N/C less aggressive than mucosal/lung
SCC gross path
Well demarcated and crusty
Contrast SCC mutagenesis to BCC
While BCC often involves an identified gene defect, PTCH, SCC arises from any number of mutants with the ‘2 hit’ hyp.
Classically SCC begins in basal area/lower epi and progress upwards
Compare SCC to SCCis
SCCis is defined as atypical keratinocytes found throughout entire thickness of epidermis
What is the progression of SCC?
Actinic keratosis -> SCCis (i.e. Bowen’s or Erythroplasia of Queyrat - penis) -> SCC
Actinic keratosis micro path
Parakeratosis: nuclei in stratum corneum
Pleomorphic
AK gross path
Thin lesions that lack induration (superficial)
SCC micro path
Pink and keratinizing like stratum spinosum, with islands of squamous cells extending into dermis
keratin pearls
Major risk factors for SCC?
UV, HPV 16, 18 Chronic inflammation Immunosuppression Chronic skin irritation/ulceration Arsenic Radiation
What factors influence SCC metastasis risk?
Size
Depth
Site
Status
**Highest risk sites for metastasis of SCC?
Lips and ears for both mets and local spread
Also vulvar, penile, HPV-induced
What are Marjolin ulcers?
Areas of previously severely/chronic traumatized skin that are at high risk for SCC
Where does SCC met to?
Lymph nodes and lung
SCC gross path
Central ulceration
Rolled borders
Crusty
Describe keratoacanthoma
Neoplasm of keratinocytes Rapid growth over 2-6 weeks Painful Spontaneous involution Well-differentiated
SCC treatment?
AK: topical/cryo
SCCis: topical/intralesion/excision
Invasive: excision
Who is at highest risk for melanoma?
White men over 50
What is the gold standard for melanoma Dx?
biopsy
Who is melanoma on the rise in?
Old men and women with hx of tanning
Contrast SCC and melanoma pathogenesis
Melanoma is not step-wise like SCC; malignant melanocytes from the beginning
Melanoma vs mole?
80% of melanoma de novo not from moles
Where is melanoma in situ?
Just epidermis only
Where is mel in situ common?
face, good for topical
Melanoma must reach the __ to metastasize
dermis
What are the three types of nevi and their characteristics?
Junctional: ?
Compound: dermis+epidermis
Intradermal: nests in bottom?
Describe a common acquired melanocytic nevus
Small, well circumscribed, uniform pigment, symmetrical
Nests in epidermis and dermis
Nev vs melanomas in terms of maturation?
Nevi: melanocytes mature with descent (get smaller); confined to basal layer
Melanoma: melanocytes do not mature with desc
Micro path of melanoma?
Large melanocytes with halo artefacts around; melanocytes will be up above basal layer and look funny/disorganized
Describe radial growth
Growth outward, as opposed to downward which is bad for metastasis
Describe vertical growth
Journey toward metastasis, blue tumor pushes down into dermis
Melanoma riskf actors
Large # moles Giant congenital nevi Blistering sunburns Fam hx Fair skin / tanning bed Immune dysfunction
Melanoma ABCDE
Assymetry Borders: irregular Color: mottled, not uniform Diameter: >6 Elevation
What form of melanoma is commonly found on the hands and feet?
Acral lentiginous
What form of melanoma on face usually?
Lentigo maligna
Nodular mel less or more aggressive?
Aggressive
What is the most common type of malignant melanoma in patients with dark skin?
Acral lentiginous (hands and feet)
Who commonly gets lentigo maligna?
Old people on face with sun exposure
What does it indicate when a nodule arises on top of a lentigo maligna?
metastasis
Nodular melanoma facts
Sun exposed skin
No preceding radial growth
Men > Women
Superficial spreading melanoma gross appearance
Multicolored, partially regressed from immune attack
Red, white, and blue sign?
superficial spreading melanoma
Keratin cysts on the surface of a suspicious dark lesion suggest what?
Not mel
Explain why melanomas can be found outside of the skin
Melanocytes are derived from the neural crest, as are the eyes/retina, inner ear, and medulla
How does melanoma usually spread?
Lymphatics
What is the single most important prognostic factor in Mel met?
lymph node involvement
What is the most important histo prog factor in mel met?
Breslow thickness and ulceration
What is the Breslow thickness for Mel IS?
0
What is Breslow’s thickness?
Distance of involvement from stratum granulosum top to deepest tumor cell
What is the most common single gene mutation in melanoma?
BRAF, 50%
What targeted therapy for melanoma?
Vemurafenib, BRAF inhibitor
Survival benefit is modest
Vemurafenib facts
Metastatic/unresectable mel
Benefit with Ipilimumab combo
50% mel have it, 50% respond
Specific relationships between the cancers and sunlight?
SCC: cumulative clearly
BC: UV imp but maybe not cumulative
Mel: has a role, w other factors
