Dr. David Leffell, Prevention and Early Detection of
Melanoma
August 30, 2009
Welcome to Yale Cancer Center Answers with Drs. Ed Chu and Francine Foss, I am Bruce Barber. Dr. Chu is Deputy Director and Chief of Medical Oncology at Yale Cancer Center and he is an internationally recognized expert on colorectal cancer. Dr. Foss is a Professor of Medical Oncology and Dermatology and she is an expert in the treatment of lymphomas. If you would like to join the conversation, you can contact the doctors directly. The address is canceranswers@yale.edu and the phone number is 1888-234-4YCC. This evening Ed and Francine welcome Dr. David Leffell. Dr. Leffell is the Deputy Dean for Clinical Affairs at Yale School of Medicine, the David Paige Smith Professor of Dermatologic Surgery, and author of the book "Total Skin."
Chu
David, in past shows, we have discussed the two most common types
of skin cancers, namely basal cell and squamous cell cancer, but
this evening we are going to focus our discussion on the third type
of skin cancer called melanoma. Perhaps we could start off by
defining what is melanoma?
Leffell
Melanoma is a cancer of the pigment cells of the skin. Basal
cell cancer and squamous cell cancer arise in the epidermis, or the
top layer of the skin. Melanoma, however, arises from the
bottom of cells of the top layer of the skin, the epidermis, and
these are pigment cells that are designed to respond to ultraviolet
radiation from the sun, and when they respond to the sun, they lead
to the tanning reaction.
Foss
David, how common is melanoma?
Leffell
Melanoma is quite common and unfortunately its incidence appears
to be increasing. I think that there will be about 70,000 new
cases diagnosed this year and approximately 8000 people will die
from melanoma.
Foss
Is the increased incidence of melanoma related at all to the
changes in the ozone layer, and to what degree does global warming
and all the other things happening in the environment influence the
incidence of melanoma?
Leffell
It's not really clear. It's important to note that not all
melanomas are due to ultraviolet radiation from the sun. It's
a difficult thing to figure out, but it's estimated that only about
60% of melanomas are in someway related to sun exposure.
Melanoma can definitely occur where the sun doesn't shine and we
will talk a little later about the proper steps with respect to
full body skin examination to diagnose melanoma at its earliest
treatable stage. We think that lifestyle, probably more than
changes in the ozone, have a greater impact on those melanomas that
are in someway related to ultraviolet radiation, not just from the
sun, but from these tanning parlors as well.
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Chu
Is there any age in which you tend to see a higher incidence of
melanoma, and also, is there any particular predilection, males
versus females etc.?
Leffell
That's a great question because recently there was a report that
demonstrated that the incidence of melanoma in young women in their
20s and 30s was increasing and at a greater incidence rate then for
individuals, males and females, in other age groups.
Typically, melanoma is more common in men over 50 and its
increasing incidence in younger women is concerning.
Chu
Is the increasing incidence in younger women perhaps due to the
fact that a lot of these individuals are going to tanning salons
and trying to have that 'wonderful tan'?
Leffell
We don't really know, but it's certainly a possibility. Back
in the early 90s, the incidence for younger women had leveled off
and then it started taking off again and it is difficult to
necessarily take a behavior or social behavior pattern and try to
link it definitively to a change in the incidence of any particular
cancer, especially when we are dealing with a relatively short
period. But the reality is that we know that ultraviolet
radiation causes mutations in the skin, we know that it plays an
important role in causing basal cell cancer and squamous cell
cancer that I mentioned at the outset, and we know that it does
play a role in certain melanomas.
Foss
David, could you talk a little bit about potential genetic
connections with melanoma, does it run in families for
instance?
Leffell
There are forms of melanoma that are familial and there are genes
that are associated with it, but in the scheme of things, they
actually represent the minority of cases. So, individuals
that have a family history of melanoma are at increased risk for
developing the disease and need to be monitored especially
closely. There have also been studies recently that have
looked at the gene that controls for red hair and light
pigmentation, and a variety of complex interpretations suggest that
that gene may result in biological events that increase the risk of
developing melanoma. We have always known that red hair and
blonde hair are independent risk factors for developing skin cancer
and now there seems to perhaps be a genetic link.
Chu
What about say darker colored skin, like African Americans or
Hispanics, is that the same level of risk or perhaps because of
their darker skin color, there is a reduced risk for developing
melanoma?
Leffell
There is probably a reduced risk for developing the most common
types of melanoma, which
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are superficial spreading melanoma and nodular melanoma, but
people with darker skin actually can be afflicted by a different
type of melanoma and its a mouthful so I will try to get it out
correctly, acral lentiginous melanoma, or ALM, and this is a form
of melanoma that develops on hands and feet and in the nails, and
can be especially concerning.
Foss
There have been conflicting reports in the medical literature and
in the press about exposure to sunlight and balancing the risk of
melanoma with the need for vitamin D, can you give us a little bit
of guidance about how much sun exposure is enough sun exposure?
Leffell
Sure, the amount of sun exposure that results in production of
vitamin D in the skin, and that's really what you are referring to
it, and it turns out that ultraviolet light will convert
cholesterol molecules in your skin to forms of pre-vitamin D, and
vitamin D actually is not a vitamin as we understand it, its more
correctly a hormone and it is an important hormone, and ultraviolet
radiation in our environment can be used to stimulate normal
vitamin D production in the skin with as little as 15 minutes twice
a week of exposure, say at lunch time when the sun is high.
The real question is, and there has been a lot in the media about
this, whether one has to go out of their way to get extra sun
exposure to get vitamin D. One of the issues that is driving this
is the recognition now that vitamin D plays a role in certain
cancers, perhaps in other diseases, such as diseases of
aging, and there is a legitimate question about what normal vitamin
D levels should be. The general feeling though is that the
risk of developing melanoma and other skin cancers probably far
outweighs the risk of not developing enough what we call endogenous
vitamin D, because it is so easily provided with vitamin
supplementation.
Foss
So, you are generally recommending the use of sunscreens for
everybody.
Leffell
The use of sunscreen with a sun protection factor of 30 and
ultraviolet A blocking is recommended for everyone, especially
those who are at risk for developing skin cancer.
Chu
All of us have these moles on various parts of our skin. When
does one need to begin to worry that this mole might in fact be a
melanoma?
Leffell
You are right, the average adult has about forty moles, and moles
are a normal part of the skin and they represent benign,
noncancerous collections of pigment cells. There is an entity
that is referred to as an atypical mole. These are moles that
have, if you will, gone sour and they can be related to the
development of melanoma. In some cases they can be a red flag
and they tell you to get in to see the doctor, while that
particular growth may not be a melanoma, it certainly gets your
attention and the attention of your physician. The
question
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about how often to be examined really relates to the risk
factors. Standard recommendations
are that after the age of 50 you should have an annual full
body skin examination, but certainly if you have a family history
of melanoma, if you have any of the independent risk factors such
as light hair or red hair that I mentioned before, blue, gray, or
green eyes, a single blistering sunburn in childhood, that is
before the age of 18, all of these are factors that put you at
increased risk for melanoma, and you should have a complete skin
examination as soon as you are aware of the fact that you fall into
those risks groups.
Foss
I would like to get back to something you mentioned earlier, which
is the incidence of melanoma in non-sun exposed areas; how frequent
is this? I am sure this is certainly something that people miss
because often times we only focus on our arms and our legs.
Can you tell us a little bit about that and what we can do to
screen for that?
Leffell
That's an extremely important question because while we talk about
the sun and protection against ultraviolet radiation, which is
extremely important, somehow in that message another important
point does get lost, and that is that not all melanomas occur on
sun exposed areas. It's essential that you have a full body
skin examination by someone who is trained in doing skin exams and
that they look through the scalp all the way to the bottoms of the
feet, and that includes looking between the toes. Many other
dermatologist and I have diagnosed melanomas between the toes,
certainly in the scalp, and it can be a challenge for individuals
with full heads of hair, something I can't really sympathize with,
but you have to very carefully go through the scalp with a comb or
blow dryer on low and really make sure that you have examined every
inch of the scalp. The genital area is important to examine
as well. We have certainly seen melanomas in that location
and I think that its very common for patients to come in and we
say, okay, you are here for your full body skin exam, we will give
you a gown, please change into it. They will say, "No, no,
no, just look at my face, I am sure I don't have anything else."
Then we ask the patient whether they are familiar with what they
have on their back and very quickly they recognize the importance
of having a full body skin exam, but you know, your question is
important for another reason in that there is a sense that the
majority of melanomas are actually first identified by the patient
or by the spouse or partner. I can't tell you the number of
times that a melanoma patient is sitting in front of me, usually a
male with their girlfriend or wife sitting in the corner shaking
her fingers saying, I told him to come in six months ago or
whatever. In general, the doctor will do a full skin exam as
much for educating you about what to look for as to find worrisome
lesions. Worrisome lesions don't develop on a schedule and
patients have a sixth sense of when
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something is not right. They may not know the biological explanation for what they see, but they to say, "Doctor, I just do not like it." And if the patient says that, it gets biopsied even if I think that it looks normal.
Chu
David, there is a thing called the ABCs or I guess, ABCDs of
worrisome lesions, can you take us through that.
Leffell
The A stands for asymmetry. If you imagine the lesion that you are
looking at and fold it over in half, if the two halves don't match,
then it's asymmetric. B is for border. If there is an
irregular, notched, or scallop border, that's a problem. If
there is abnormality in color, for example if you see red, black,
brown and white, or any combination of those that's an indication
that the body's immune system may be having it out with the
melanoma cells and the redness is actually a sign of inflammation.
Sometimes the white is a sign that the battle is over and the body
has successfully destroyed those abnormal cells, but in other areas
of the lesion it's clear that the melanoma is still there.
Diameter is the other factor and we talk about any lesion that is
greater than a pencil eraser, or 7 millimeters, but you know all of
these guidelines came up many years ago and they are generally very
gross. One of the most important criteria that I alluded to
before, is whether the patient is concerned about the lesion, to me
that says a lot.
Foss
We have to take a break right now. I would like to talk a
little bit more about the biopsy and the procedure for treating
patients with melanoma when we come back.
Foss
Welcome back to Yale Cancer Center Answers. This is Dr.
Francine Foss and I am joined by my co-host Dr. Ed Chu and Dr.
David Leffell, the David Paige Smith Professor of Dermatologic
Surgery at Yale School of Medicine. We are today talking
about early stage
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melanoma. So David, could we open this section by having you describe to us how the diagnosis of melanoma is made?
Leffell
The diagnosis of melanoma is made by a skin biopsy. First,
as we talked about in the first segment, the patient or the doctor
is concerned about a lesion and the only way to know what that
lesion or growth is, is to take a sample of it and study it under
the microscope, and this is a very straight forward office
procedure. First, the area is numbed with local anesthesia,
lidocaine, similar to what the dentist might use, and then the
specimen of skin is removed. If it is very tiny, the whole
growth may be removed by what is called a saucerization biopsy, or
if it's larger then can easily be removed in its entirety, one
might take a sample of the melanoma itself. This biopsy is
very important for a few reasons. First, it tells you whether
or not we are dealing with a melanoma as opposed to a benign growth
or just an atypical or abnormal mole. Secondly, it gives you
information about various aspects of the melanoma under the
microscope, perhaps the most important of which is how thick the
melanoma is. This is important because the thickness of the
melanoma is the single most important factor that determines the
prognosis. In other words, how well you are going to do. The
melanoma diagnosis that we have been talking about today is
extremely important because the vast majority of melanomas are
diagnosed at the earliest highly treatable stage, probably more
than 90%, and when we hear about melanoma and the seriousness of
the condition, it really relates to those cases that are more
advanced that may have been thicker at the time of diagnosis.
But melanoma that's up to 1 mm in thickness at the time of
diagnosis is easily treated simply by going back and having an
office based surgical procedure that removes the melanoma and a
margin of tissue around it.
Chu
Who would be the person to do this biopsy? Would it be a general
dermatologist or would it be someone like yourself who specializes
in dermatologic surgical procedures?
Leffell
Skin biopsies, including skin biopsies for melanoma, are routinely
done by dermatologists, by plastic surgeons, and certainly by
general surgeons, anyone who is trained in the proper techniques
and is comfortable in terms of making the clinical diagnosis, so
they know what kind of biopsy to do and should be very comfortable
performing a melanoma biopsy. The question after that is,
once you have the diagnosis the type of referral you should have
for proper management of the melanoma.
Foss
Can you tell us a little bit about what you do with a patient who
has a very early stage melanoma, and in contrast, what you would do
with the patient who has one of the deeper, more advanced
melanomas.
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Leffell
As I mentioned, the most important factor is the depth of the
lesion. There are other factors
as well that help you determine whether it is a high-risk lesion
or a low-risk lesion. If it's a very low-risk lesion,
that includes an assessment of where on the body the growth is
occurring and simple removal with 1 cm margins, for example, a
third of an inch or more, is sufficient to result in the maximal
cure rate. However, increasingly when we were dealing with
higher risk lesions, even within the category less than a
millimeter, we may consider doing a sentinel lymph node biopsy, and
that's a procedure where one identifies what lymph nodes that
particular area drains to, and in a operating room the sentinel
lymph node, or the gatekeeper lymph node, is sampled to determine
whether melanoma has spread there or not. When you do that
procedure and you find that that lymph node is negative for cancer,
that provides great prognostic information, it doesn't necessarily
have an impact on how well the patient is going to do, but it
certainly helps guide an assessment of what other therapies might
have to be provided. With more advanced melanomas, the
sentinel lymph node biopsy becomes almost routine, and with
extremely advanced melanomas, in other words in melanomas where it
has already spread to the lymph nodes, there is obviously no need
to do a sentinel lymph node biopsy, and these are complex
issues. There is a huge amount of data emerging about the
value of the sentinel lymph node biopsy and Yale Cancer Center
surgeons Dr. Stephan Ariyan and Dr. Deepak Narayan are very skilled
in performing this procedure and managing the surgical aspects of
advanced melanoma.
Chu
David, if the sentinel lymph node biopsy comes out negative, does
that mean then that there is no risk for the melanoma having spread
to the regional lymph nodes?
Leffell
No, it doesn't, and there are large population studies that are
looking at the significance of a negative sentinel lymph
node. There is even a procedure where, unsatisfied with
looking at the cells under the microscope, we actually look at
fragments of the DNA to see if we can find fragments of DNA of the
melanoma. It is an evolving area and I think one of the
reasons it's so important for research to go in this area is
because as we mentioned at the outset, melanoma affects a lot of
young people and we don't really know where this trend is going to
go, and importantly, if it is diagnosed early, it is virtually
curable. So the opportunity to do self skin exams, full body skin
exams, and to be appropriately suspicious of lesions that you
develop can be life saving.
Foss
David, is there anything easy like a simple blood test or a
molecular test that can be done on the blood that would help us to
know which melanoma patients have distant disease? Has that been
developed yet?
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Leffell
That has not been developed and is certainly not in general
use.
Foss
That gets me to my next point, which is that Yale Cancer Center
actually has received a skin SPORE from the NCI, the National
Cancer Institute, and is doing a lot of research related to skin
diseases. Can you tell us a little bit about what they are doing
with respect to melanoma?
Leffell
That's right, the SPORE covers a study on basal cell cancer in
young people that I am directly involved with, but in the area of
melanoma, there is a variety of efforts looking at tumor markers
and means of identifying antigens or other proteins in the blood
that will help not only identify whether melanoma is present
systemically in the system, but also provide an opportunity for
tracking progress.
Chu
For the patients with early stage melanoma, and as you say, the
vast majority really are potentially curable once the skin lesion
has been removed, is there any other treatment that needs to be
done once that melanoma lesion has been removed by the surgeon?
Leffell
Generally no, for early-stage melanoma. There are cases
where you are at the interface between low risk and medium risk and
there are questions about the use of interferon, but even the use
of interferon itself has really not held out consistently in the
literature, and it highlights the point that treatment of early
melanoma is relatively easy and the only limitation to treating
early melanoma is making the diagnosis.
Foss
How often do patients who have already had a melanoma develop a
recurrence or a different melanoma?
Leffell
The chance of developing a second primary melanoma, in other
words, another melanoma different than the one that was originally
diagnosed, is probably about 6%. Therefore, it's very important for
those patients to be monitored. The risk of developing a
recurrent melanoma, in other words the chances of the melanoma that
was treated coming back, really varies with the type of melanoma
and how it was treated.
Chu
How frequently should these individuals be followed up by their
dermatologist to make sure that there is no recurrence of the
melanoma?
Leffell
A person that has a single melanoma identified should be followed,
and the protocols vary but are routine in the Cutaneous Oncology
Unit at Yale, that a person should be followed every four months
for the first year, and then you can go back to twice a year after
that. But as Francine implied before, these patients are at
increased risk for developing second
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melanomas so careful monitoring of them is extremely important,
and some of these patients
have lesions that look very innocuous and then turn out to be
melanoma. You really have to get to know your patient's skin
just as the patient needs to get to know his or her own skin.
Foss
Is there any role for CAT scans or PET scanning as you follow
these patients who have already had a melanoma?
Leffell
Not for early stage melanoma.
Chu
What are your general recommendations for sun exposure and the use
of sunscreen once the melanoma has been removed?
Leffell
Patients need to be very vigilant about sun protection even if
their melanoma developed in a non-sun exposed area, because that
suggests to me that from a genetic point of view their body has a
capability of making a melanoma. And maybe for the non-sun exposed
melanoma that they had, the stimulus was not the sun, but the sun
could equally act as a stimulus, a second hit almost, for someone
who is predisposed. Sun protection programs include using a
sunscreen with a sun protection factor of 30 with ultraviolet A
block, because remember SPF just refers to ultraviolet B block,
they should wear a brimmed hat, and everyone thinks that a baseball
cap does the trick, but I cant tell you the number of melanomas
that I have seen on the tips of the ears, so you need to wear a
brimmed hat and avoid the sun, and this makes me sounds like a
killjoy, but during the peak hours between 10am and 4pm when the
sun is strongest. If you find a way to have your leisure activity
outdoors before 10 o'clock and after 4, you will probably have an
easier time getting a tee time, the marina wouldn't be as busy, and
the tennis court wouldn't as busy and you will be protecting your
skin.
Foss
My 12-year-old tries to tell me that on cloudy days he doesn't
need to wear his sunscreen, can you clarify for our listeners
whether or not you need sunscreen on a cloudy day?
Leffell
I am pleased to tell you on public radio that you are right and he
is wrong. The ultraviolet radiation does penetrate haze and
clouds and people get sunburns, they could be out at baseball
practice, it is a hazy day, and they think they don't need
sunscreen and they come in to see me Monday morning with a full
blown pink sun-burned face.
Chu
Obviously the recommendation to avoid sun exposure is particularly
relevant now that we are in the summer months presently.
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Foss
There is one other question I wanted to ask earlier, and that is
the issue of the non-pigmented melanoma. I know that it is
relatively rare, but can you just tell us how often it occurs?
Leffell
Everything we have talked about from the outset, when I talked
about the melanocyte, the pigment producing cell, and when it goes
abnormal it becomes a cancer and the cancer is known as
melanoma. All of that really relates to irregularly pigmented
or dark growths, which I think many people can have in their minds
eye. One of the most worrisome things for dermatologists,
especially dermatologists that have been in practice for a long
time, is something called amelanotic melanoma. Amelanotic melanoma
is a melanoma without pigment, and if you think about it and if you
look at your arm or the back of your hand or your leg, I think you
will all see that you may have flesh colored growths that are not
concerning and you have no way to really consider that there is
something to worry about. I am not suggesting that you should
start worrying about them, but amelanotic melanomas are lesions
that dermatologists can often be suspicious of and the patient
too. The patient, as I mentioned a couple of times, might
come in and say that they don't like the appearance of it. In
a red-haired, very-fair skin individual it may be reddish in
appearance, it may be a little dome shaped papule, but it can have
other appearances as well and I think it highlights the need for
very careful examination by a dermatologist.
Chu
David, there is also this entity called ocular melanoma, is there
any relationship between the development of ocular melanoma and sun
exposure?
Leffell
Ocular melanoma is a type of malignancy that develops on the
retina, and the relationship between that and ultraviolet radiation
I don't believe is as strong as the relationship between
ultraviolet radiation and cutaneous melanoma. It's a good
point that you make and when people have their routine eye exam,
they need to make sure that they are getting a comprehensive eye
exam because that's the only way it can be diagnosed.
Chu
Is there any research ongoing to try to identify agents that might
be able to help prevent the recurrence of melanoma, or is the key
to try to minimize or avoid sun exposure?
Leffell
I think the one area that we didn't really have much time to talk
about, but that is quite special with respect to melanoma, is its
relationship with the immune system. For a variety of
reasons, melanoma cells are either exquisitely sensitive to aspects
of the immune system, or very clever in evading it, and it's that
unique interface with the immune system that has raised the
possibility on an ongoing basis of developing a melanoma
vaccine. A year doesn't go by that you do not hear about a
new melanoma vaccine. The fact that every year you hear
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about a new melanoma vaccine tells you how challenging it is to
develop a means to harness the bodies own immune system to fight
melanoma, but we will get there.
Chu
Great. David, thank you so much for being with us on the show
this evening and we look forward to having you come back and talk
about the different types of skin cancer.
Leffell
Thank you for having me.
Chu
You have been listening to Yale Cancer Center Answers and we would
like to thank our special guest Dr. David Leffell for another
terrific program. Please join us again next Sunday
evening. Until then, I am Ed Chu from Yale Cancer Center
wishing you a safe and healthy week.
If you have questions or would like to share your comments, go to yalecancercenter.org where you can also subscribe to our podcast and find written transcripts of past programs. I am Bruce Barber and you are listening to the WNPR Health Forum from Connecticut Public Radio.