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Default Expert Answers About Melanoma - 09-22-2010, 03:17 AM

September 20, 2010, 11:56 am Expert Answers About Melanoma

By THE NEW YORK TIMES Monica Almeida/The New York Times Thomas McLaughlin, a melanoma patient, was recently featured in Amy Harmon’s article “New Drugs Stir Debate on Rules of Clinical Trials,” about the ethical dilemmas of new drug testing.
This week, Dr. David E. Fisher of Harvard Medical School joined the Consults blog to answer readers’ questions about melanoma. Here, Dr. Fisher addresses readers concerns about aging skin and the risk of melanoma, recurrences of the deadly skin cancer and melanoma that has spread to the nasal cavity.
Aging Skin vs. Melanoma
Please differentiate between changes on fair skin due to aging that can be expected and are likely harmless and changes on fair skin that should be seen by a dermatologist because they are likely harmful.
KW, West Virginia
Dr. Fisher responds:
Skin changes due to aging are significantly accelerated by ultraviolet radiation. UV radiation causes formation of the most common types of skin cancer, most commonly basal cell carcinoma, squamous cell carcinoma and melanoma.
While the precise mechanism through which UV radiation stimulates melanoma formation is still incompletely understood, the link between UV exposure and melanoma formation seems a virtual certainty. UV also stimulates nonmalignant changes in the skin, such as tanning, burning and inflammation, and wrinkle formation. All of these, including tanning, appear to be the result of UV’s damaging effects on the cells and vital molecules, including DNA and proteins, within skin.
While tanning, inflammation and wrinkles are usually relatively harmless, they typically signify UV damage, which could indicate a risk of cancer formation. That being said, fortunately the vast majority of skin lesions — either pigmented or unpigmented — are not cancerous and are benign and harmless. The ability to distinguish harmless growths from cancerous and harmful ones requires medical evaluation, and optimally involves repeated skin check-ups yearly, or more often, as recommended by your physician. Unfortunately, due to subtle features of these lesions, it is not possible to provide simple rules that permit self-diagnosis with accuracy.
Recurrences of Melanoma
Dear Dr. Fisher,
I have had two melanomas, both 0,5 Gleason scale and both detected very early. After the biopsy, in both cases I had surgery to extract flesh in 0,5 extra centimeters around the tumor. Further biopsy has indicated that the margins were free on any malignant cell. My doctors here say I am cured on the two cases. My question is what are the chances of a recurrence? I am the first in my family to have had this health problem. Is there any link with exposure to the sun? What precautions should I take besides checking every three months with my dermatologist? Thank you very much for responding.
Luiz, Rio de Janeiro
Dr. Fisher responds:
Dear Luiz,
The risk of developing a melanoma is increased after the prior diagnosis of melanoma. While we cannot give a precise risk figure for you, it is important that you continue to be followed closely by your dermatologist, because the early detection and removal of melanomas will provide the best chance of cure. Currently about six of seven melanomas are detected at a stage early enough that surgical removal with clear margins around the tumor can be curative (in some cases with additional treatment).
While we cannot be absolutely certain that your melanomas were caused by sunlight, it is likely that there was such a link. This is particularly true if you have no family history of melanoma. In addition to close follow-up with your dermatologist, you should also practice safe sun exposure habits. This includes avoiding the brightest sun for extended periods of the day, wearing protective clothing (including broad-rimmed hats that cover your ears), and liberal and repeated use of sunblocks that protect against both UVA and UVB.
Melanoma in the Nasal Cavity
My brother (45) has mucosal melanoma. He had it in his nasal cavity three years ago and it was removed. Eighteen month ago it had spread to his lungs and was also removed. We have just found that it has come back in both of his lungs, and from what I understand, it is inoperable. (I try not to ask too many medical questions, I just try to be a supportive brother and use our conversations as more of a pleasant distraction.) He too is hoping to get on a clinical trial. A few questions:
  • What would be the reasons that they would not try to remove these?
  • What side effects, and how toxic are these drugs?
I’m sure this is the million dollar question of your field but, is there any rhyme or reason to this form of cancer occurring (i.e., environmental, gender, previous medical conditions…?) Thank you.
Derek, Hartsdale, N.Y.
Dr. Fisher responds:
Dear Derek,
Mucosal surfaces are the linings of cavities that are exposed to the external environment or internal organs, such as the lining inside the mouth, nose, sinuses, throat, airway passages and intestinal and reproductive organ systems. Perhaps because these surfaces are contiguous with our skin, they contain small numbers of melanocytes, or pigment cells, and on very rare occasions those cells can become malignant, giving rise to melanoma of the mucosal variant.
Unfortunately these melanomas tend to be diagnosed at a more advanced stage than cutaneous melanomas, because they arise in less visible locations and are therefore less likely to be observed until they produce symptoms. These melanomas are unlikely to be caused by UV radiation, based on epidemiologic data — probably because mucosal surfaces are not exposed to the sun. We do not know the cause of these cancers.
When these melanomas have spread to distant locations, as in your brother’s case, it presents a particularly difficult challenge because each melanoma lesion is thought to exhibit its own significant risk of spreading further to other locations in the body. There are certain circumstances in which isolated metastases of melanoma that have spread to other locations are removed surgically, and it is important that an experienced physician review the specific situation to determine if it is feasible. But unfortunately, in most cases the likelihood of benefit is extremely small, whereas the likelihood of significant debility from surgery may be certain.
However, one important breakthrough has occurred recently for the field of mucosal melanoma. Dr. Boris Bastian, currently at Memorial Sloan-Kettering Cancer Center in New York City, discovered several years ago that a fraction of these tumors contain mutations in a gene called c-Kit. The importance of this discovery is that several drugs exist that are capable of blocking c-Kit; their mechanism is related to the manner in which the drug PLX4032 blocks the B-RAF gene mutation in more common forms of melanomas (see Amy Harmon’s earlier story on melanoma, “A Roller Coaster Chase for a Cure.”)
Preliminary clinical data, mostly still unpublished, are suggesting that patients whose melanoma contains mutations in c-Kit might benefit from such c-Kit targeted drugs, though the precise nature and degree of benefit is not yet certain. Therefore, these patients should be evaluated for c-Kit mutations in their tumors. The c-Kit targeted drugs, like B-RAF targeted drugs, represent a new era in cancer therapy. These drugs do have significant side effects, but they are different from many of the traditional chemotherapy side effects. Such drugs are usually administered in the setting of clinical trials that provide close follow-up.
Check back later in the week for additional responses from Dr. Fisher. And for more information, see The Times Health Guide: Melanoma.
Melanoma patient
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