Skin Cancer Flashcards
What is a Marjolin ulcer
Malignant transformation of scar with ulcer, mostly scc but can be BCC and Melanoma
What is the metastatic rate of Marjolin ulcer
25-30%
What percent of burn scars undergo malignant transformation
2%
Average time for a malignant degeneration to occur in a Marjolin ulcer
20years
Brigham and Women’s Hospital SCC staging
What is T1?
Zero high risk factors
Brigham and Women’s Hospital SCC staging
What is T2a?
One high risk factor
Brigham and Women’s Hospital SCC staging
What is 2b?
Two-Three High risk factors
Brigham and Women’s Hospital SCC staging
What is T3?
4 or more high risk factors
List the Brigham and Women’s Hospital SCC staging
high risk factors
1 diameter more that 2cm
2 poorly differentiated histology
3 Perineural invasion .1mm or more
4 Tumor invasion beyond the sub Q fat.
AJCC Staging of SCC what is Tx?
Primary SCC not identified
AJCC Staging of SCC what is Tis?
In situ
AJCC Staging of SCC what is T1?
Less than 2 cm in diameter
AJCC Staging of SCC what is T2?
More than 2 cm and less than 4 cm
AJCC Staging of SCC what is T3?
Greater than 4cm or
Deep invasion (beyond subQ fat or more than 6mm)
Perineural invasion of nerve more than .1mm in dia.
AJCC Staging of SCC what is T4?
Invasion of bone
What % of Pagets disease of the nipple will have underlying ductal or invasive breast cancer?
95%
Above 1mm in Breslow thickness what is the surgical margin for a melanoma
2cm
What is the most common form of cell death by radiation.
Mitotic Catastrophe
What is a Marjolin ulcer
aggressive cancer in old burn or poorly healing wound. usually SCC but can be BCC
What margins should be used in an excision of a basal cell carcinoma without frozen sections planned.
4mm
what tumor do you see the eyeliner sign.
SCC in in situ
What is a keratin pearl
a swirl of parakeratosis
naked nuclei are seen in what?
pagetoid spread in SCC
where are there no atypical keratinocytes in the basal layer in an AK
In the follicular epithelium openings. orthokeratosis over the follicular opening.
if you see thick keratin corneal layer with underlying sun damaged skin what do you think of?
AK
what is the stain for DFSP
CD34
What two stains are negative in DFSP
Factor XIIIa …. + in dermatofibroma
Stromelysin 3 ….+ in dermatofibroma
How to excise a DFSP if not mohs?
2cm margin down to fascia.
What is the recurrence rate of DFSP for excision and for Mohs?
excision >20% or more Mohs 1-2%
how many greys of radiation are used for radiation adjunct treatment of DFSP and margins.
50-60 gy and 3 to 5 cm beyond the surgical margin.
what is the best radiologic study for extensive DFSP
MRI with contrast.
What medicine and dosage is used for DFSP
Imatinib Mesylate (Gleevec) 400mg PO bid
What changes are seen in fibrosarcomatous changes in DFSP
Densely packed herring bone pattern.
CD34 may only be weakly +
Less haphazard more worrisome
What causes 90% of DFSPs
Chromasome translocation of a collagen 1 gene and a platelet derived growth factor gene to form an oncogenic fusion gene
What is a DFSP oncogenic fusion gene
t(17:22) q22 q13
what is the 10 year risk transformation for SCC in those that have AKs
17%
What percent of people treated for AK with cryo have complete clearing at 6mo?
<10%
What is tirbanibulin
klisyri inhibits tubulin polymerization and Src kinase signalling used in treatment of AKs
What is the treatment course for tirbanibulin
5 days.
With tirbanibulin what is the peak day of Localized Skin Reactions?
day 8
Name 5 Agents that may help prevent AK & SCC
- Sunscreens
- 5FU bid 30 days
3.Retinol (Vit A) 25,000 IU daily
4 Acitretin 25mg daily - Nicotinamide 500 bid
What % of DFSP metastasis?
5%
What is the most common site of DFSP to metastasize to?
lung
what drug treats DFSP
imatinib
What is the protein made by the oncogenic fusion gene.
COLA1 - PDGFB
What margins should you use with an excision of a bcc (non mohs)?
4mm
What margins should you use for an excision of a high risk SCC. and name 4 high risk features
- > 2cm
- neurotropic
- high risk sites
4 Invasion into fat
6mm
What is the cure rate with curettage alone?
96%
list 3 cancers you can ed&c
bcc, scc in situ, well diff scc <1cm
List two criteria for not doing an ed&c
hair follicle involvement and involvement of the deep dermis.
which field TX for AKs has the best non recurrence rate at 5 years.
5FU
what is the mnemonic for the Brigham & Women’s Hospital staging system?
3 D’s and large caliber perineural
what are the four risk factors in Brigham & Women’s Hospital staging system for mets or death ?
Diameter >2cm
Deep penetration fat
Differentiation poor
Perineural involvement >.1mm
What are the four stages of Brigham & Women’s Hospital staging system?
T1 0 risk factors
T2a 1 risk factor
T2b 2-3 risk factors
T3 4 risk factors or bone involvement
What are the four stages of the AJCC staging..
T1 <2cm and no other risk factors
T2 2-3.9 cm and no other risk factors
T3 - one of the following risk factors
*4cm diameter
*invasion >6mm or beyond fat
*perineural >.1mm or subdermal nerve involve
*minor bone erosion
T4- deep bone or base of skullWhat is a risk factor in Brigham & women’s staging that is not listed as a risk factor in AJCC?
Poor differentiation.
Is the NCCN (National Comprehensive Cancer Network) a staging system.
No. It is treatment recommendations only.
Does NCCN high risk predict recurrence or death?
No
With Brigham & Women’s Hospital staging system what is the risk for recurrence mets or death in T2a SCC tumors Mohs vs excision.
Mohs 3.5 %
Non Mohs 10%
With Brigham & Women’s Hospital staging system what is the risk for recurrence mets or death in T2b-T3 with Mohs vs excision.
15 to 22%
What % of T2b cases that had sentinal node bx were positive.
30%
What % of nodal SCC mets are found in first 2 years?
80%
What studies should be done with patients high risk for mets (T2b-T3)
serial CTs or ultrasound.
What study is done if major nerve involvement with SCC
MRI
If a person has CLL with lymph node involvement what study can separate SCC nodes from CLL nodes?
PET scan
What was the first systemic treatment for approved for treatment of SCC.
Cemiplimab
what is the response rate to Cemiplimab
50%
If you do get response what % is durable over 1 year?
80%
Pembrolizumab is what?
anti -PD1 therapy like Cemiplimab 2nd to be released
What is the death rate of organ transplant patients with Anti-PD1 Treatments
50%
What other diseases will flare with Anti-PD1 tx
autoimmune
People who get more than 10 dermal invasive SCCs have either transplants or what.
CLL
What is the normal presentation of a merkel cell carcinoma
rapidly growing violaceous nodule 2-3 mo duration on sun exposed skin/
What is the aeiou mnemonic for merkel cell (MCC)
Asymptomatic Expanding rapidly Immune depressed Older than 50 UV damaged skin
Which has a higher rate of metastasis Merkel Cell or Melanoma
Merkel Cell
Approximately what % have regional or distant mets in Merkel cell carcinoma MCC at time of presentation.
nodes 25%
distant mets 10%
Total 35%
What cell line is a merkel cell carcinoma considered.
neuroendocrine
What stain is used for Merkel Cell Carcinoma (MCC)?
CK20
what is the staining pattern of CK20 in MCC (merkel cell)
paranuclear dot like pattern
What is merkel cell carcinoma hard to tell apart from on H& E
metastatic small cell carcinoma (presumably from the lung)
what stain is positive in small cell lung cancer and negative in Merkel cell
TTF-1 (thyroid transcription Factor 1)
what are the two causes of Merkel cell carcinoma
- merkel cell polyomavirus mutated
2. DNA mutations from UV
In those with polyomavirus and merkel cell what can you follow lab wise.
oncoprotein antibody levels. high at diagnosis may rise again with recurrence.
Will there be a oncoprotein antibody titer in merkel cell carcinoma without viral infection.
no
What are the surgical margins with merkel cell carcinoma (MCC)
1-2 cm or Mohs
In MCC (merkel cell carcinoma) how should nodes be evaluated?
If no clinically apparent nodes then a sentinel node bx should be done. If palpable nodes then a needle bx is done.
Which is better Cytotoxic Tx or Checkpoint immuno TX for Merkel cell carcinoma?
Cytotoxic therapies are only palliative. Check point immuno TX have longer durability.
Name two treatments for Merkel Cell Carcinoma
Avelumab 2017
Pembrolizumab 2018
Show the staging AJCC of merkel cell carcinoma
Stage 0 In situ primary (? WTF)
Stage 1 < 2cm no nodes
Stage 2a >2cm no nodes
Stage 2b tumor invades muscle bone no nodes
Stage 3a node + no primary or + sentinel node
Stage 3b nodes involved
Stage 4 distant disease
What is the latency for exposure of ionizing radiation and development of BCC
20 years
what type of drugs have a lower risk for BCC in the immunosuppressed.
mTOR inhibitors
What are increased risk of BCC Melanoma and SCC with HIV infection
2.1 none reported 2.6
Which in order of risk are the skin cancer types with immunosuppression.
BCC about 6-16 Melanoma 1.4 8 SCC 20-250
What type of transplant immunosuppression does not increase risk of skin cancer as much as other types.
hematopoetic transplants
what does the hedgehog signaling pathway do?
regulates cell differentiation, proliferation and tissue polarity
hydrochlorothiazide increases incidence of BCC and SCC by how much?
BCC two fold SCC four fold
show the hedgehog signaling pathway
- Extracellular signaling molecules (Shh sonic hedgehog protein)
- attach to trans membrane receptors (PTCH 1 & 2)
- PTCH suppresses signal transducer SMO (smoothened) in cell membrane.
- SMO activates transcription factor Gli1, 2, 3)
- if SuFu does not hibit then Gli enters nucleus
what chromosome is sonic hedgehog gene located?
chromosome 7
How does cancer come from the hedgehog signaling pathway.
Too much activation of the pathway.
In BCC what is the mutation that causes >50% of the bcc
TP53 mutation p53 in UV damaged cells stops replication and induces apoptosis
Beside inactivation of PTCH 1 what are two other mutations that can cause GLI to enter the nucleus to cause BCC?
activation of SMO or inactivation of SUFU
What is the staging system for BCC
There is no staging system for BCC
What is the risk for mets in BCC
.0028%
In the sonic hedgehog pathway activating or inactivating of each of these cause BCC which is it for each one PTCH1, Smoothened, SUFU, GiL
inactivating PTCH1
activating Smoothened (SMO)
inactivating SUFU
activating GIL
Does UV light from gel nail manicures increase risk for Nail SCC.
No
Name an immunosuppressive drug used in organ transplants and Crohn’s disease that increases SCC risk by %56
Azathioprine
What is the primary cause of BCC?
Intermittent intense UVB & sunburns at any age.
What is the primary cause of SCC and AKs?
cumulative UV exposure & childhood sunburns
How much do tanning beds increase risk of SCC
2.5 x
How much do tanning beds increase risk of BCC
1.5
PUVA therapy is assoc with increased risk of SCC in what fashion.
dose related increase risk.
What is the increase risk from narrow band uvb 311-312nm
none
wavelengths below this number in phototherapy increase your risks for burning and cancer
300nm
With ionizing radiation what is increase of risk of BCC and SCC in 20 years based on in proportion to dosage?
3x the risk
What two co-carcinogens increase risk for SCC
HPV and UV
What percent of transplant patients have HPV in their SCC
90%
What is the increased risk for SCC and BCC in transplant patients?
SCC 40-250x
BCC 5-10 x
What are the HPV types associated with SCC in transplant patients
1,2,5,6,11,16,18
what vaccination if injected into a SCC might clear it?
HPV
Name five classes of the immunosuppressive drugs that might increase risk for SCC
- Biologics
- steroids
- Nibs (Braf inhibitors)
- Calcineurin inhibitors (cyclosporin, tacrolimus, pimecrolimus
- Mycophenolate Motetil Cellcept
What gene is most commonly mutated in SCC?
P53 the tumor suppressor gene
What % of BCCs have a mutated P53 gene
about 50%
What is the most frequently altered gene in all human cancers.
P53 mutated in over 50% of all human cancers
What are the three ways that p53 gene stops tumorigenesis.
- Stops cell growth arrest by stimulating p21 which produces Cdk and stops mitosis in S phase.
- Causes Apoptosis by stimulating BAX
- Increases thrombospondin which decreases angiogenesis.
what is P63
a gene similar to P53 and found in many skin cancers.
In order what are the three most common mutations in BCC
PTCH
P53 (most common in SCC)
SMO
what do you call a gene that has the potential to turn into an oncogene?
Proto-oncogenes
HHV-8 is found in what percent of Kaposi’s sarcoma patients?
Almost all.
What is the mechanism of action of HHV-8 in Kaposi’s sarcoma.
Reactivation of a virus rather than primary infection.
Of the 4 clinical variants of Kaposi’s how many are associated with HHV-8
all four
What are Bcl-2 and Bcl-xL proteins
promote cell survival and inhibit pro-apoptotic proteins.
What are BAD, BAX, BID, and BAK proteins
proteins that promote apoptosis
what percent of porokeratosis develops SCC
10%
What is the one porokeratosis that does not develop SCC
punctate porokeratosis on palms and soles around adolescence.
What is the cause of DSAP
Autosomal dominant disorder with a mevalonate mutation.
What is the hyperkeratotic layer of porokeratosis called?
cornoid lamella
In which merkel cell carcinomas should sentinel node biopsies be done?
all
Risk of progression of ak to scc is what?
.1 to1%
NCCN guidelines recommend a sentinel node bx in all patients with merkel cell carcinoma because clinically negative node patients have what percent of nodal involvement on sentinel node biopsy?
25-35%
In Merkel cell carcinoma what percent eventually get’s node mets and what percent gets distant mets.
50% and 35%
What are the three types of verrucous carcinoma
Giant condyloma of Buchske-Lownstein
Oral florid papillomatosis
Epithelioma cuniculatum (on bottom of foot assoc with wart)
How likely is verrucous carcinoma likely to metastasize?
rarely. It is considered a well differentiated variant of SCC. Can penetrate deep.
Is UV exposure implicated in verrucous carcinoma?
Yes
Although excision and Mohs is considered the best treatment for verrucous carcinoma what treatment should be avoided.
Radiation. May induce anaplastic changes, risk is likely low.
HPV vaccination may be preventative for verrucous carcinoma because of its association with what viruses.
6 & 11 low risk
16 & 18 high risk
For merkel cell carcinoma if you have a positive sentinel node biopsy what are the next steps.
- PET CT scan
- referral for adjuvant therapy clinical trial
- if above not available radiation or node dissection or both
which of the following cancers have been associated with arising out of Hailey Hailey disease , SCC BCC Melanoma
all
With SCC and regional node involvement what is the NCCN guideline for derm f/u
2-3 months for one year
2-4 for year two
4-6 for years three - five
6-12 afterward
What is the polyomavirus associated with merkel cell carcinoma?
MCPyV
what percent of the population has been exposed to the polyomavirus MCPyV
60 to 80%
What happens if you are seronegative for MCPyV with merkel cell carcinoma at baseline?
you are at high risk for recurrance.
What two antibodies for MCPyV are important in Merkel cell carcinoma?
Major capsid antibody (VP1) found in general population oncoprotein antibody (T1) found in merkel cell cases
Which of the two MCPyV antibodies are found in the general population and low baseline with merkel cell carcinoma diagnosis portends more metastatic disease.
Major capsid antibody
Which of the two MCPyV antibodies can you track to follow for recurrance.
oncoprotein antibody. (not useful in people that are seronegative at baseline)
What is the most important feature in differentiating Atypical Fibroxanthoma from pleomorphic dermal sarcoma
depth of invasion. They look the same histologically.
What is the highest risk factor for death from SCC at time of treatment.
Tumor diameter. tumors over 2cm have a 20 risk of death for tumors under 2 cm.
Risk for death with perineural involvement that is clinical is what. And risk for death from PNI on histology only is what?
30% and 13%
Being able to determine perineural involvement on biopsies require a depth of how much?
3-4 mm
Is a sentinel node biopsy done before or after the malignancy is resected?
before the tumor is removed
What drug has been shown to reduce skin cancers by 63 % in patients with xeroderma pigmentosa
Isotretinoin
What type of leukemia has an increased risk for nonmelanoma skin cancer.
CLL
Is arsenic exposure a risk factor for BCC
Yes, chronic arsenic exposure is a risk factor.
what type of solid organ transplant has the least risk for development of SCC
Liver
Which has higher SCC assoc. Liver Kidney transplants or Lung Heart transplants
Heart and Lung transplants have the most risk for SCC
what is the increased risk of scc in organ transplant patients.
6-100 fold
Mucinous carcinoma can be primary or metastasize from cancers of what organs?
breast, GI, Lung, ovary, prostate
Why is mohs the treatment of choice for Mucinous carcinoma?
poor response to radiation and chemo. Recurrence rate of 13% with Mohs over double that with excision.
Is primary mucinous carcinoma a low or high grade malignancy?
Low grade with low rate of mets but high recurrence rate.
although mucinous carcinoma can be found in multiple locations which are the most common?
eyelid #1 scalp Neck axillae trunk
Diets low in what have been shown to reduce AK risk
Fat
what are the subclinical spread numbers at 1cm 3cm and 5 cm for DFSP
1cm 75%
3cm 15%
5cm 5%
What is the cure rate for DFSP with Mohs
98%
Where are the most common areas for finding basosquamous cell carcinoma.
perinasal, periocular, preauricular skin
What sites are most common for microcystic adnexal carcinoma.
cutaneous upper and lower lips
What is the earliest sign of Gorlin’s syndrome
Odontogenic keratocysts
what is the followup for merkel cell carcinoma with skin check and lymph node exam
3-6 months for 3 years
6-12 forever
In immunocompromised pts do they get more or less superficial BCC compared to normal pts.
more
Who has higher recurrence rates for treated BCCs immunocompromised or normal patients.
rate of recurrence is the same for BCC, but SCC is worse for immunocompromised.
Who gets more non head and neck BCCs immunocompromised or normal patients.
immunocompromised
Who gets BCCs at a younger age immunocompromised or immunocompetent.
immunocompromised
what is the number one skin cancer in the US and how many are diagnosed each year?
BCC 2million
what is your lifetime risk of getting a BCC
20%
how many cases of SCC are diagnosed in US a year
about 1 million
How many cases of melanoma are diagnosed in the US each year
80K+
What locations are KAs less likely to regress
mucosal and periungual (those arising in non-hairbearing areas.
in the asian/hispanic population what #1 feature of a pigmented basal would be expected to show more subclinical extension.
Ulceration
In the asian/hispanic population with a pigmented basal cell what features increase risk for subclinical extension and more layers.
Ulceration #1
under age 50
Location on nose
Size over 1 cm (unlike caucasion size over 2cm)
In a asian/hispanic population one sign of a BCC that makes it more likely to be cleared in one stage.
pigmentation
After the risk factor of size over 2cm for risk of disease specific death what is the second highest risk factor in SCC.
Depth
as compared to non clinical perineural involvement..
acantholytic SCCs are not associated with what lesion that other SCCs are commonly associated with?
AKs
what is the most common skin cancer in african americans and what is the most common location
SCC lower extremities (associated with chronic inflammation and scarring)
What is considered the UV signature mutation
a Cytosine to Thymine mutation at a dipyrimidine site
found in the PCTH gene in basal cell, the p53 gene in SCC and the CDKN2A gene in melanoma
what is opposite with gay men and women when it comes to skin cancer.
gay men use tanning beds more than non-gay men and have a higher incidence of skin cancer.
Gay women have less tanning bed use that Hetrosexual women and have fewer skin cancers.
Malignant peripheral nerve sheath tumor (a sarcoma) which can occur with neurofibromatosis type1 has what gene mutation
p53
What type of gene is p53
tumor suppressor gene - mutated by UV at the C to T transitions on the dipyrimidine sites
What is the risk for a Marjolin ulcer to metastasize?
30%
The leg is the most common site for a marjolin ulcer, but what location on the leg is the most common site.
Plantar surface of the foot.
in merkel cell carcinoma which patients have a better survival. Those with a known primary or those with an unknown primary.
unknown primary
what % of melanoma in situ is found to have invasive melanoma on excision
4-6%
of the three types of congenital nevi small <1.5cm medium <20 cm or large have a risk for melanoma compared to the general population.
Large only with a 6% risk
When is the risk for melanoma the highest in a giant congenital nevus
The first ten years.
although the overall incidence of melanoma is increasing what two age groups is it decreasing in.
adolescents (10-19) Young adults (20=29)
Blueberry muffin syndrome is associated with what disease and what mutation that is shared by melanoma.
Langerhans cell histiocytosis (caused by cells from bone marrow)
BRAF V 600E +
what viruses are associated with organ transplant SCC 80% of the time.
HPV 5 & 8 Same as Epidermodysplasia Verruciformis
When if you see halo nevi would give the better prognosis for what factor in a melanoma.
Early new melanoma lesions.
when doing mohs on a toe vs amputation which has lower recurrence rates.
They both have the same recurrence rates.
why is the bar lower for taking another layer with a low grade melanoma on acral skin.
There are fewer melanocytes on acral skin so it is easier to miss subtle positive margins.
