Skin Cancer (Fisher) Flashcards
What mutation is frequently found in sporatic BCC tumors?
PTCH
tumor suppressor gene which regulated basal epidermal cell prolif
BCC risk factors:
UV exposure Fair complexion H/o sunburns (especially blistering) Family history of BCC Immunosuppression
Characteristic histology of BCC
- peripheral palisade
- clefting from adjacent mucinous stroma
- Basophilic hyperchromatic cells
- nodules, often extending from surface epidermis
Characteristic gross appearance of BCC
rolled pearly edges
telangiectasias
central erosion
BCC subtypes
– Nodular – Superficial – Pigmented – Morpheaform (sclerotic) – Micronodular – Cystic – Infiltrative
Disorder which includes:
Mutation of PTCH1 and BCCs at early age (~23yo)
musculoskeletal defects and jaw cysts
increased risk of other neoplasms
Basal Cell Nevus Syndrome
Gorlin Syndrome
BCC treatment:
Treatment – Excision – Electrodessication and curretage – Cryosurgery – Radiation – Topical treatment for superficial BCC
Do BCC commonly metastasize?
no–exceedingly rare
Targeted therapy for advanced BCC:
What does “advanced” include?
Vismodegib
Metastatic disease, Recurrent disease (post surgery), Non-surgical candidates
A 2-hit hypothesis explains what type of abnormality?
squamous cell dysplasia
2nd most common skin cancer
Sq cell
How does SCC progress?
- Minimal atypia (actinic keratosis)
- Full thickness epidermal atypia, above BM (SCC in situ)
- Invasive (SCC)**
**ranges from well to poorly differentiated
What is actinic keratoses?
Thin non- indurated lesions
no induration = clue to superficial nature of lesions
SCC histology:
- Hyperchromatic pleomorphic nuclei
- disorganized growth with mitoses
- invasion through the basal layer.
- keratin pearls
3 biggest risk factors for SCC development?
UV
HPV
Immunosuppression
Risk of metastasis of SCC related to:
- size of tumor (>2 worse)
- depth of invasion into dermis (>4mm worse)
- anatomic site (lips/ears worse)
- host immune status
Vulvar, perineal and penile HPV-induced SCC have a (higher/lower) rate of metastasis than the overall rate.
higher–30% compared to like…1%
Other “types” of SCC (2)
- Keratoacanthoma
- Marjolin’s Ulcer
(likely entirely inconsequential)
What is Keratoacanthoma?
Painful neoplasm of keratinocytes
Grows rapidly over 2-6 weeks
What is Marjolin’s Ulcer?
ulcerated invasive SCC arising on a background of chronic inflammation, scarring, radiation, trauma
How do you treat Actinic Keratosis?
cryotherapy
topical therapy
SCC treatment generally depends on…
degree of progression
How do you treat SCC in situ?
topical therapy
intralesional
excision
How do you treat invasive SCC?
excision
Who is at the highest risk for melanoma?
white men > 50
Melanoma is the most common type of cancer in what population?
25-29yo
Melanoma is the 2nd most common type of cancer in what population?
15-29yo
Horrible fact: 1 American dies every hour from melanoma.
Let’s go cherry bomb some tanning beds. And, if we’re already at it, let’s eliminate a few taco bell’s.
Nevi histology?
- Small
- Symmetric
- Well-circumscribed
- Organized/discrete, uniform size/shape
- Melanocytes ‘mature’ with descent into dermis
- No melanocytes above the basal layer
Melanoma histology?
- Large
- Asymmetric
- Poorly circumscribed
- Nests are confluent, irregular spacing and sizes/shapes
- Melanocytes do not ‘mature’ with descent
- Melanocytes located above the basal layer
Melanoma in situ has a ____ growth phase.
Invading melanoma has a _____ growth phase.
radial
vertical
Both nevi and melanoma are/can…
- comprised by melanocytes
- share some mutations (eg BRAF)
~20% of melanoma develop from
pre-existing nevi
High numbers of nevi (esp >50) can increase…
risk of melanoma
Etiology of melanoma (general)
– Genetic predisposition (eg. CDNK2, BRAF)
– Environment (eg. UV)
– Underlying immune status
Melanoma risk factors:
- Large number of common nevi (esp. >50)
- Giant Congenital Nevi
- Atypical Nevi
- History of blistering sunburns
- Family History of Melanoma
- Light complexion, tanning bed use
- Underlying immune dysfunction
Melanoma screening alphabet
- A Asymmetry
- B Borders: irregular, scalloped
- C Color: mottled, variegated, not uniform
- D Diameter: >6mm
- E Elevation
- “changing mole”
- “ugly duckling sign”
5 melanoma subtypes
- Acral lentiginous
- Lentigo Maligna Melanoma
- Nodular
- Superficial spreading
- Amelonotic
What subtype of melanoma is defined by anatomic location on palmar, plantar and subungual skin?
Acral lentiginous
What subtype of melanoma is frequently in older patients on sun-exposed skin?
Lentigo Maligna Melanoma
What subtype of melanoma has a red, white and blue sign?
superficial spreading melanoma
What subtype of melanoma is the most common type in pts with darker skin?
Acral lentiginous
What type of melanoma appears on sun exposed skin, but has no preceding radial growth?
nodular melanoma
What subtype of melanoma has preceding radial growth?
Lentigo Maligna Melanoma
What subtype of melanoma has a lot of color variation, asymmetrical/irregular borders and it large and elevated?
superficial spreading melanoma
Melanocytes are _______ derived cells
neural crest
In addition to skin, melanoma can be found:
inner ear
iris
vulva
Melanoma metastasis mostly occurs via
lymphatics
1 organ site for melanoma metastasis
skin
Most common cause of death in melanoma
CNS involvement
Single most important prognostic factor for melanoma:
Lymph node involvment
Most important histological prognostic factors for melanoma:
reslow thickness and ulceration
“Breslow’s thickness” is defined as distance of melanoma involvement from the _______ (top) to the deepest tumor cell (bottom)
stratum granulosum
Melanoma Treatment:
Catch it early and cut it out
50% of melanomas harbor ____ mutations
BRAF
Small molecule inhibitor of BRAF
Vemurafenib
Approved for unresectable or metastatic (stage 4) melanoma
Vemurafenib
New treatment for unresectable or metastatic (stage 4) melanoma involves:
Why?
combination therapy, especially with ipilimumab
Initial response to Vemurafenib very impressive but melanoma adapts
Forms dimers between neighboring thymine pairs in DNA
UVB
What type of cancer?
Sunlight certainly plays a role, along with genetics, other environmental factors, and immune system
melanoma
What type of cancer?
Cumulative lifelong UV exposure clearly related to development
Squamous Cell CA
What type of cancer?
UV important but not clearly related to cumulative doses.
Basal Cell CA
Xeroderma Pigmentosum is caused by:
Defects in genes that function in nucleotide excision repair of thymine dimers
