Cancer Flashcards
What are the skin cancer progenitors for BCC?
Germinative keratinoctyes (resemble basal layer)
What are the skin progenitors for SCC?
Epidermal keratinocytes (resembles spinous layer)
What are the cancer progenitors for melanoma?
Melanocytes
What are the nonmelanoma skin cancer?
BCC and SCC
What’s the most common invasive neoplasm in the US?
BCC
What mutation is frequently found in sporadic cases of BCC?
PTCH
What’s the significance of the PTCH mutation in BCC?
Tumor suppressor gene: regulator of basal epidermal cell proliferation
What are the risks for BCC?
UV exposure, fair complexion, h/o sunburns (especially blistering), family history of BCC, Immunosuppression
[incidence increased by immunosuppression (10x), but not to same degree as SCC]
What is this?
BCC: nodular type
What’s this?
BCC
What’s this?
BCC: a nodule of basophilic, pleomorphic cells with hyperchromatic nuclei. Note the peripheral palisade of tumor cells and clefting from adjacent stroma
Describe the pathology of BCC
- Basophilic hyperchromatic cells that form nodules, often extending from the surface epidermis
- Cells at the periphery of the aggregations form a palisade
- Tumor nodules are set in a mucinous stroma, with retraction from that stroma (clefting, or ‘retraction artifact’)
Classic BCC (nodular): well circumscribed nodule with pearly rolled border and central erosion. Note telangiectasias as well.
BCC: telangiectasias (superficial dilated vessels) are prominent here
Superficial BCC
Pigmented BCC
Morpheaform BCC
Does BCC often present before age 50?
Nope. Only 20% of BCC presents before age 50 and it is rare prior to age 35.
What’s the genetic mutation that predisposes someone to getting BCC early?
PTCH tumor suppressor gene
What is basal cell nevus syndrome?
Autosomal dominant and rare mutation of PTCH1. Pts get BCCs at early age (~23yo). They also have MSK defects and jaw cysts
If someone has Basal Cell Nevus Syndrome are they at a higher risk of developing other neoplasms?
Yes. Increased risk of other neoplasms like medulloblastoma and fibrosarcoma
Is BCC likely to metastasize?
Nope it’s super rare
What arer the Tx for BCC mets?
Tx= Excision, Electrodessication and curretage, cryosurgery, radiation, and topical treatment for superficial BCC( Imiquimod, 5-flurouraci)
Is there targeted therapy for BCC?
Yep: Vismodegib
How does Vismodegib work?
Small molecule inhibitor: competitive antagonist of SMO
When is Vismodegib approved?
Approved for ‘advanced’ BCC:
Metastatic disease, Recurrent disease (post surgery), and Non-surgical candidates
What is the second most common skin CA?
SCC
What is the progression of SCC?
Actinic keratosis then SCC in situ followed by invasive SCC
What is actiinic keratosis?
Minimal atypia
What is SCC In SItu?
Full thickness epidermal atypia confined above the
basement membrane.
Bowens disease, Erythroplasia of Queyrat
What is the differentiation of invasive SCC?
Can be well, moderately or poorly differentiated.
Actinic Keratosis
Actinic Keratosis
How would one describe Actinic Keratosis?
As thin non ndurated lesions- Lack of induration is clue to superficial nature of lesions
SCC in situ. Note the full thickness of the atypia
SCC, invasive: note the islands of squamous epithelial cells extending into the dermis. Squamous cells make small nodules of keratin, often called keratin pearls.
What genetic mutation has been found in SCC?
No specific SCC oncogene or tumor suppressor gene has been identified. Increased p53 mutations only.
What are the main risks for developing an SCC?
UV, HPV, and immunosuppression
What are some other risk factors for developing SCC?
Chronic inflammation (eg. Osteomyelitis with draining sinustract, some chronic inflammatory dermatoses), Certain scars (eg. burn), Chemical exposure, especially arsenic, Radiation exposure, and Leukoplakia
What are the risks of mets for cutaneous SCC?
The risks are related to size of tumor, depth of invasion into dermis, anatomic site, host immune status. Larger than 2cm clinically=greater the risk; Greater than 4mm in depth (or subcutaneous extension)=greater the risk; and Higher risk on lips and ears
What are the overall chances of a SCC metasasizing?
Less than 5% mets rate. But when they do they go to the lymph nodes and lung
What is the risk of mets in actinic-induced non-mucosal skin?
Closer to 0.5-1%
Is the risk of mets higher or lower in other clinical scenarios than it was in actinic-induced non-mucosal skin?
Higher: Actinic-induced on lip 2-16%, Marjolin’s ulcers 10-30%, Vulvar, perineal, penile HPV,induced 30% Leukoplakia
HPV-associated Periungual SCC
SCC in situ on the lower lip
Other than disgusting, what is this?
SCC, invasive
Bowen’s Disease: SCC in situ
Erythroplasia of Queyrat: SCC in situ on the penis
(Because you should always be prepared for a surprise dick pic this week)
Radiation-induced SCC
SCC arising in a plaque of leukoplakia, probably secondary to tobacco use
What is Keratoacanthoma?
Neoplasm of keratinocytes that is related to SCC and possibly a subtype. It rapidly grows over 2-6weeks and is painful
Which neoplasm may involute spontaneously?
Keratoacanthoma
What is an ulcerated invasive SCC arising on a background of chronic inflammation, scarring, radiation, trauma?
Marjolin’s ulcer
SCC Tx?
Depends on degree of progression.
Actinic Keratosis: topical therapy, cryotherapy
SCC in situ: topical therapy, intralesional, excision
Invasive SCC: excision
Who has the highest risk for a melanoma?
Caucasian men >50yo
What’s the most common cancer between 25-29yrs and the second most common cause of cancer between 15-29yrs
Melanoma
Common Acquired Melanocytic Nevus
Common Acquired Melanocytic Nevus (Mole)
Melanoma in situ: a “radial” growth phase
Melanoma invading the dermis: a “vertical” growth phase
What’s the relationship of nevi and melanoma?
Both are comprised by melanocytes
Both can share some mutations (eg BRAF)
High numbers of nevi (esp >50) can increase risk of melanoma
Melanoma can develop from pre-existing nevi:
~20% develop from nevi and ~80% develop de novo
What is the etiology of Melanoma?
It’s “Multifactorial” etiology: including Genetic predisposition (eg. CDNK2, BRAF), Environment (eg. UV), and Underlying immune status
What are the risk factors for melanoma?
Large number of common nevi (>50), giant congenital nevi, atypical nevi, history of blistering sunburns, FH of melanoma, light complexion, tanning bed use, and underlying immune dysfunction
Describe the screening for melanoma
A-Asymmetry
B- Borders: irregular, scalloped
C-Color: mottled, variegated, not uniform
- Diameter: >6mm
E-Elevation “changing mole” “ugly duckling sign”
Melanoma
What is Acral Lentiginous Melanoma?
Defined by anatomic location on palmar, plantar and subungual skin. It’s the most common type of MM in pts with darker skin
Acral Lentiginous Melanoma
Lentigo Maligna: Older patients on sun-exposed skin. In this picture it depicts the slow growing, still in “radial” growth phase (it is still melanoma in situ
Lentigo Maligna Melanoma: a nodule has arisen on the background of a lentigo maligna. This heralds the progression of the in situ lesion to an invasive one
Nodular Melanoma:
Usually on sun exposed skin
“no preceding radial growth”
15% of MM, 2x men > women
Superficial Spreading Melanoma
“Red, white, and blue” sign
Where are melanocytes dervied from?
Neural crest cells
Where can melanomas occur?
Anywhere that neural crest cells migrate. The dermal-epidermal junction is just the most common
How does melanoma metastasize and where does it go?
Via lymph. Most common place it spreads is to more skin.
What is the most common cause of death in melanomas?
CNS involvement
What is the most important prognostic and histiologic factor for melanoma?
Prognostic=Lymph node involvement
Histtiologic=Breslow thickness and ulceration
What is Breslow’s thickness?
Distance of involvement from the stratum granulosum (top) to the deepest tumor cell (bottom)
Tx for melanoma?
Catch it early and cut it out. If metastatic melanoma then IFNa, combination chemotherapy, XRT, vaccine therapy
50% of melanoma’s have what mutation?
BRAF
What is Vemurafenib?
Small molecule inhibitor of BRAF
What is Vemurafenib approved for?
Approved for unresectable or metastatic (stage 4) melanoma. Provides survival benefit (although modest)
What does UVB light do to DNA?
UVB forms dimers between neighboring thymine pairs in DNA. These dimers are usually successfully repaired by endonucleases and other DNA repair enzymes
Relationship between Squamous Cell CA and sunlight?
cumulative lifelong exposure clearly related to development
What is the relationship between BCC and sunlight?
UV important but not clearly related to cumulative doses. Maybe intermittent
What’s the relationship between melanoma and sunlight?
Certainly plays a role, along with genetics, other environmental factors, and immune system
Xeroderma Pigmentosum: go!
- Autosomal Recessive: 1 in 1 million in US
- Defects in genes that function in nucleotide excision repair of thymine dimers
- Lead to increased skin cancers (Squamous Cell CA, Basal Cell CA, Melanoma) by increased sensitivity to ultraviolet light
