Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
66 Cards in this Set
- Front
- Back
|
What germline mutation is associated with a high risk for melanoma?
|
CDKN 2A
Cyclin-Dependent Kinase Inhibitor 2A |
|
|
What can impact the penetrance of CDKN2A mutations?
(name 2 phenotypical factors and one gene variant) |
penetrance of CDKN2A mutations increased by
Pigmentation Characteristics Nevus Phenotypes Hair Color Propensity to Suburn Number of Nevi Variants of the Melanocortin-1 Receptor Gene (MC1R) |
|
|
In what manner is germline mutation in CDKN2A transmitted?
|
Autosomal Dominant
|
|
|
Where is the CDKN2A gene located?
|
Chromosome 9;21
|
|
|
Worldwide, what percent of melanoma-prone families carry a germline CDKN2A mutation?
|
About 40%
|
|
|
What is the MC1R gene?
|
MC1R
The Melanocortin-1 receptor gene. |
|
|
What does the MC1R gene do?
|
MC1R
The Melanocortin-1 receptor gene plays a role in the pigmentation process |
|
|
What is the RHC variant of the MC1R gene?
|
MC1R
The Melanocortin-1 receptor gene has a variant called RHC which stands for: Red Hair Color |
|
|
What phenotypic features is the RHC variant of the MC1R gene associated with?
|
red hair
light skin poor tanning ability heavy freckling |
|
|
What two proteins are encoded by the CDKN2A gene?
|
proteins encoded by the CDKN2A gene
p16INK4A p14ARF |
|
|
How prevalent is basal cell carcinoma?
|
Very Prevalent
More than a million per year 3 in 10 Caucasians will develop BCC during their lifetime. |
|
|
What is the prognosis for basal cell carcinoma?
|
Good.
Only 5-10% are difficult to treat. |
|
|
How prevalent is squamous cell carcinoma?
|
Less prevalent than BCC
Only about 250,000 diagnosed per year |
|
|
How many die of basal cell carcinoma and squamous cell carcinoma?
|
Only about 1,000-2,000 per year
|
|
|
Name some non-genetic risk factors for BCC and SCC: (8)
|
UV Exposure
Skin types I - II Male Chemical/ Radiation exposure History of burn or scar HPV infection Immunosuppression Ulcerating Conditions |
|
|
What two genetic conditions are associated with BCC/ SCC?
|
Basal Cell Nevus Syndrome
Xeroderma Pigmentosa |
|
|
How prevalent is melanoma?
|
60,000 diagnosed per year
|
|
|
How many melanoma deaths per year?
|
8,100
|
|
|
Rank the following races in terms of lifetime risk
(black, white, asian) |
White = 2% lifetime risk
Black = 0.089% risk Asian = lowest |
|
|
How is melanoma staged?
|
Standard TNM staging
T= Tumor size N = Node involvement M = metastasis |
|
|
Name two methods for melanoma staging.
|
Breslow depth = based on thickness of the melanoma (most common)
Clark's level = based on the levels of the skin that are involved |
|
|
Give some ideas about 5 year survival based on Breslow depth
< 1 mm 1 - 2 mm 2.1 - 4 mm > 4 mm |
5-year Survival
< 1 mm = 95 - 100% 1 - 2 mm = 80-95% 2.1 - 4 mm = 60 - 75% > 4 mm = 37 - 50% |
|
|
What is Lentigo Maligna Melanoma?
|
A type of melanoma -
The insitu version Can be pre-malignant Often treated with cream Common in sun exposed areas in elderly patients. |
|
|
What is Acral Lentiginous Melanoma?
|
Acral Lentiginous Melanoma
Occurs most commonly in blacks, Asians & Hispanics. Occurs on: hands, feet, subungual areas (under nails) |
|
|
What is Superficial Spreading Melanoma?
|
Superficial Spreading Melanoma is
the most common type in caucasians |
|
|
What is nodular melanoma?
|
nodular melanoma is
The only type associated with a vertical growth phase. Associated with a poor prognosis |
|
|
Name four types of melanoma:
|
Types of Melanoma
Lentigo Maligna (pre-canerous - common in elderly) Acral Lentiginous (Black/ Asian/ Hispanic - on hands/ feet subungual) Superficial Spreding - (caucasians) Nodular (poor prognosis - vertical growth) |
|
|
What Fitzpatrick skin type would you label a person who is very pale, lots of freckles, blue eyes, blond hair?
|
Type I
|
|
|
What Fitzpatrick Skin type would you label someone with black skin?
|
Type VI
|
|
|
What is a melanocytic nevi or a banal nevi?
|
a normal mole
|
|
|
What would you call a dysplastic nevi?
|
a MOLE WITH ABNORMAL FEATURES ON HISTOLOGY
|
|
|
How would you describe a clinically atypical nevi?
|
A nevi that exhibits abnormal phenotypic features:
- > 6mm - irregular border - etc |
|
|
How do you define Atypical Mole Syndrome?
|
having > 50 nevi some of which exhibit abnormal features.
Also called FAMM = Familial Atypical Mole and Melanoma |
|
|
How do you define FAMM
(Familial Atypical Mole and Melanoma) |
having > 50 nevi some of which exhibit abnormal features.
Also called Atypical nevi syndrome |
|
|
True or false:
Freckles are melanocytes? |
False
Freckles are just melanin protein, they are not a type of cell. |
|
|
True or False:
Freckles can turn into cancer |
False
|
|
|
True or False:
Moles can turn into cancer |
True
|
|
|
What kind of radiation activates melanocytes to increase melanin production causing freckles to become darker and more numerous?
|
UV-B
|
|
|
What are the ABCD & E of Clinically Atypical Nevi?
|
Asymmetry
Border = uneven edges Color = two or more shades Diameter = > 6 mm Evolving Moles |
|
|
What is meant by be aware of evolving moles?
|
moles that appear where none have been before
dissappear change in size, shape or color become symptomatic (itch, bleed, tender) |
|
|
Which ultraviolet light penetrates deeper into the skin?
|
UVA
(the one responsible for cancer/ not the UVB responsible for burn) |
|
|
Which ultraviolet light is more associated with burning?
|
UVB
|
|
|
True or False:
UV intensity is associated with how long it will take you to burn? |
True
|
|
|
True or False:
Sunburn increases risk for melanoma? |
Maybe, maybe not.
It may not be the act of burning that causes the risk of melanoma, but the burn is an indicator that someone has had sun exposure and they have a prone phenotype. |
|
|
True or False:
A person with a high density of freckles has an increased risk (RR = 2.1) for melanoma because some of the freckles are likely to become cancerous? |
False.
They have a higer relative risk because of their skin type. |
|
|
Name one risk factor for melanoma that is higher than having a history of blistering sunburn (RR 2.0)
(there are 4 listed in the lecture) |
Having 5 atypical nevi (RR = 10.5)
Previous Melanoma (RR - 8.6) 100 or more nevi (RR = 6.9) Red Hair (RR = 3.6) |
|
|
How much UVA radiation is delivered in a tanning bed?
|
5 - 15 x the amount delivered by the mid-day sun on a Mediterranean beach
|
|
|
What is considered first-line sun protection vs. second-line?
|
First Line:
-protective clothing/ hats/ glasses -avoid sun during peak hours Second Line: -sunscreen |
|
|
What level of SPF is needed?
|
SPF 30 - going much over doesn't give much better results
|
|
|
True or False:
SPF 30 offers more protection from overall UV exposure than SPF 2 |
False:
SPF protects against burn, not overall UV exposure |
|
|
In Sunscreen what is the difference between a chemical block vs. a physical block?
|
Chemical blocks replicate the same chemical reaction in the melanin that converts UV exposure to heat.
Zinc and Titanium are physical blocks |
|
|
How often should you reapply sunscreen?
|
Every 30 min if in water or sweating
Otherwise every 2 hours |
|
|
How is it possible that using sunscreen could increase the risk of cancer?
|
-Sunscreens prevent burning and allow individuals to stay in the sun longer, increasing UVA exposure.
-Strong correlation between sunscreen use and melanoma prone phenotype |
|
|
True or False:
Strong scientific data indicates that sunscreens prevent the major type of skin cancer. |
False - the evidence is limited
|
|
|
If a family carries a CDKN2A/p16 mutation (melanoma).
The family members who test negative will have what kind of risk for melanoma? |
Slightly higher than average risk because of shared modifying genes.
|
|
|
How do you manage someone with CDKN2A /p16 mutation regarding melanoma risk?
|
-Clinical exam every 6-12 months - begin age 10
-baseline photography -monthly self exam -minimize sun exposure -prevent sunburns remove susqicious nevi |
|
|
How do you manage someone with CDKN2A /p16 mutation regarding pancreatic cancer risk?
|
CDKN2A/p16 Mgt for Pancreas:
Pancreatic ca screening begins 50 yo or 10 yrs prior *annual immaging (avoid CT d/t radiation - use MRCP or Endoscopic US) *Annual Serum CA 19-9 Consider new onset diabetes an alarm. Quit smoking |
|
|
Controversies around testing for CDKN2A/p16 (melanoma/ pancreas)
|
-not good screenings
-variable penetrance estimates |
|
|
What factors increase the likelihood of detecting the CDKN2A/p16 gene?
|
factors that increase the likelihood of detecting the CDKN2A/p16 gene:
increased # family members with melanoma Multiple primary melanomas Presence of pancreatic cancer |
|
|
What factors don't predict as strongly (even though it seems like they should) that you will find a CDKN2A/p16 mutation?
|
Not strong predictors of CDKN2A/p16
-isolated early onset melanoma -isolated pancreatic cancers -multiple atypical nevi |
|
|
How does the rules of 3 work in deciding to test for CDKN2A/ p16?
|
CDKN2A/ p16 testing Candidates Include
* 3 melanomas in a family (any degree of relation) 12-41% * 3 melanomas in an individual 5-23% * 3 cancer events in a family (combination melanoma/ pancreatic) 68% |
|
|
CDKN2A/ p16
What happens to the "rule of threes" if you live in a low melanoma incidence area/ or if you have a dark complexion family? |
CDKN2A/ p16
You change it to a "rule of two's" |
|
|
What gene mutation is associated with the Basal Cell Nevus Syndrome?
|
Basal Cell Nevus Syndrome
PTCH gene |
|
|
Basal Cell Nevus Syndrome -PTCH gene
What kind of inheritance? |
Basal Cell Nevus Syndrome -PTCH gene
Autosomal Dominante 20-30% de novo |
|
|
Basal Cell Nevus Syndrome -PTCH gene
What are the major Criteria? |
Basal Cell Nevus Syndrome -PTCH gene
Basal Cell Cancers Palmar Pits Jaw Cysts (90%) Calcification of Falx |
|
|
Basal Cell Nevus Syndrome -PTCH gene
Clinical Management? |
Basal Cell Nevus Syndrome -PTCH gene - Clinical Managment
Skin exam every 3-4 months Systemic treatment with retinoids Jaw x-ray every 12-18 months beginning at age 8 Surgical treatment of ovarian fibromas Cardiac fibromas monitored by pediatric cardiologist |
