Melanoma is a cancer of the pigment-producing cells-melanocytes-that
occur normally in the skin and eyes and produce the substance that gives
hair, eyes and skin their color. Melanocytes are found in the bottom layer of the epidermis-the outer portion of the skin-about 90 to 100 microns beneath the surface. Depending on the location on the body, there can be anywhere from 6,000 to 8,000 melanocytes per square millimeter.of skin
Melanoma is a malignancy whose progression is analogous to other solid tumors such as colon or breast. In the majority of melanoma cases, researchers think that the melanocytes evolve through a benign tumor stage known as a mole to a disorganized benign tumor called a dysplastic mole. The dysplastic mole can then evolve through several stages of growth to become what is called melanoma in situ, in which the cells are still located in the outermost epidermis and have not broken through the basement membrane that separates epidermis from the dermis. This is one of the most treatable stages of melanoma.
Melanoma begins to become invasive when it enters what is called the radial growth phase - a stage of microinvasion where the tumor is probably still not capable of spreading to a metastatic site, but is just one step away.
When the tumor cells begin to thicken and form a small nodule that invades downward-a process called vertical growth-the risk of spread and recurrence increases substantially.
Contrary to popular belief, melanoma is no more invasive than any other cancer. In fact, the overall cure rate for melanoma is about 83%, which is strikingly higher than the cure rate for other tumors such as lung or colon. That high cure rate is in large part due to the fact that, because melanoma starts on the surface of the skin and is usually pigmented and visible, it can be picked up in its early stages when it is most curable.
But melanoma can be a dangerous malignancy. Except for lung cancer in women, the incidence of melanoma is growing faster than any cancer in the United States, increasing at an alarming rate of 4 to 5 percent per year. It has become one of the more common cancers among young adults aged 20 to 40, accounting for up to one-third of all cancer cases among that age group.
The Melanoma Center at the University of California San Francisco has treated thousands of melanoma patients since its founding 20 years ago. The clinic maintains one of the largest and most extensive databases on melanoma in the country and its staff can analyze data on more than 350 attributes-location of the tumor, thickness, level of invasion, sex of the patient, length of survival, etc.-of each of more than 3,000 melanoma patients.
"Every melanoma patient is different," says Dr. Richard Sagebiel, Director of the Melanoma Center. "You can't treat any one patient like everybody else. Using our database, we have been able to create a prognostic tool that, given certain characteristics, allows us to plan appropriate therapy for an individual melanoma patient.
"On the basis of certain clinical and pathologic features, we can now recognize melanomas that are essentially curable and require very little laboratory work-up and very little therapy-but a lot of reassurance-versus melanomas that are a serious threat to a patient's health."
When Sagebiel and his staff diagnose a melanoma case, they distinguish between high-risk patients and low-risk patients and plan their treatment accordingly. In general, says Sagebiel, the factors they consider are the sex of the patient, the location of the tumor, and the pathology report.
"Women survive melanoma better than men," he says. "Extremity lesions-arms and legs-do better than central body or trunk lesions. The third and most important risk factor is how deep in the skin layers the tumor penetrates. There is more or less a direct line relationship between thickness-the distance from the top of the tumor to the bottom of the tumor, from the surface to the deepest invasion point-and the risk of recurrence."
Once a diagnosis is made, a patient is referred to one of several clinics within the Melanoma Center. One clinic is for high-risk patients who face complex decisions about therapy and follow-up. Patients with a high-risk diagnosis are reviewed by a panel of melanoma experts that includes a surgeon, plastic surgeon, radiation oncologist, medical oncologist, dermatologist, pathologist, and others. That panel makes appropriate treatment decisions for the special problems of the high-risk patient.
Another clinic is for more low-risk patients who have a less complicated therapeutic problem but who need education and reassurance nevertheless.
Every new patient in the Melanoma Center is interviewed by a clinical psychologist who assesses their reaction to the disease and evaluates their ability to cope with the various medical, psychological and psychosocial problems that can accompany a diagnosis of melanoma.
"You have to remember that melanoma affects your everyday life," says Sagebiel. "Your job life, your sex life, your sleeping. It's a tumor that, unfortunately, is not uncommon in the 20 to 40 age group, and it seems to be increasing. So it's affecting a young, generally productive, population-people who are just in the beginning or the prime of their life who are told that they have a potentially fatal disease. Naturally, this comes as a shock. We offer two group therapy sessions and support groups and we're planning an intervention study to evaluate tools such as education, relaxation methods, and visualization."
Surgery is still the primary form of treatment for melanoma, but surgical treatment is now much less drastic than it was a few years ago.
"No matter what stage a melanoma has reached, we know that it's better to cut it out surgically,"says Sagebiel. "But in the last 20 years we have progressed to the point where we know that you don't have to cut enormous amounts. There are no more amputations done, very few grafts, and the excisions have become smaller. The elective removal of normal lymph node groups are probably fewer than they were 20 years ago. This is all based on a recognition of high-risk and low-risk patients."
For some advanced or recurrent cases of melanoma, the Melanoma Center offers several experimental treatment protocols that might not be available elsewhere. These include limb perfusion, in which heated chemotherapy drugs are infused directly into the blood supply of an arm or leg.
In some cases, the body's own immune response is enhanced to destroy melanoma cells. In a new treatment protocol for melanoma, interleukin-2 and lymphokine-activated killer cells-naturally occurring substances found in the body-are used to stimulate the immune system to destroy cancer cells. A new protocol is also being developed that will utilize tumor vaccines where melanoma tissue is used as a tumor antigen to produce tumor antibodies.
"There is still a lot to be learned," says Sagebiel. "Melanoma probably has the same kinds of regulatory systems in terms of oncogene activation and tumor suppressor genes that other tumors such as colon have been shown to have. We also know that, to a certain extent, we can alter the immune response to melanoma, as well as other cancers. That's our hope for the future for all solid tumors - to be able to regulate the growth process in a way that it can be stopped or reversed."