What is Melanoma

Melanoma is a cancer that develops in melanocytes, the pigment cells present in the skin. It can be more serious than the other forms of skin cancer because it may spread to other parts of the body (metastasize) and cause serious illness and death. About 50,000 new cases of melanoma are diagnosed in the United States every year.

Melanoma Skin ImageBecause most melanomas occur on the skin where they can be seen, patients themselves are often the first to detect many melanomas. Early detection and diagnosis are crucial. Caught early, most melanomas can be cured with relatively minor surgery.

Nobody can conclusively diagnose him- or herself. If someone sees a spot that looks as though it is new or changing, he or she should show it to a doctor. When it comes to spots on the skin, it is always better to be safe than sorry.

Everybody gets spots on their skin. The older we are, the more spots of different types we have. Most of these spots are benign. That means they are neither cancerous nor on the way to becoming cancerous.

Moles

The vast majority of moles stay as moles and do not turn into anything else. Most melanomas do not arise in preexisting moles. For that reason, having all of one’s moles removed to “prevent melanoma” does not make sense.

Some people are born with moles. Almost everyone develops them, starting in childhood. On average, people have about 25 moles, though some have fewer and others many more. Moles may be flat or raised, and they may range in color from tan to light brown to black. Moles may lose their color and end up flesh colored. It is unusual to develop new pigmented moles after age 35.

A mole may appear and then get bigger or become raised but still be only a mole. It is normal for many moles to start flat and dark, become raised and dark, and then later lose much of their color. This process takes many years.

Most public-health information about melanoma stresses the so-called ABCDEs:

  • Asymmetry: One half of the mole is different from the other half.
  • Border irregularity: The spot has borders which are not smooth and regular but uneven or notched.
  • Color: The spot has several colors in an irregular pattern or is a very different color than the rest of one’s moles.
  • Diameter: The spot is larger than the size of a pencil eraser (6 mm).
  • Evolving: The mole is changing in size, shape, color, or overall texture. This may also include new bleeding.

These guidelines are somewhat helpful, but the problem is that many normal moles and other benign lesions of the skin are not completely symmetrical in their shape or color. This means that many spots, which seem to have one or more of the ABCDEs, are in fact just ordinary moles and not melanomas. Additionally, some melanomas do not fit this description but may still be spotted by a primary-care physician or dermatologist. Not all melanomas have color or are raised on the skin.

Melanoma may appear to be a thickened area of skin like a scar. These are treated the same way as more typical melanomas but, in the latter case, may be more difficult to determine the exact margins of the tumor.

As a rule, melanoma is not painful unless traumatized. They sometimes itch, but this has no diagnostic or prognostic importance.

The skin changes are rapid or dramatic

When changes such as pain, swelling, or even bleeding come on rapidly, within a day or two, they are likely to be caused by minor trauma, often a kind one doesn’t remember (like scratching the spot while sleeping). If a spot changes rapidly and then goes back to the way it was within a couple of weeks, or falls off altogether, it is not likely to represent anything serious. Nevertheless, this would be a good time to say once again: Nobody can diagnose him- or herself. If one sees a spot that looks as though it is new or changing, show it to a doctor. If one see a spot that doesn’t look like one’s other spots, it should be evaluated.

Individual sunburns do raise one’s risk of melanoma. However, slow daily sun exposure, even without burning, may also substantially raise someone’s risk of skin cancer.

Factors that raise one’s risk for melanoma include the following:

  • Caucasian (white) ancestry
  • Fair skin, light hair, and light-colored eyes
  • A history of intense, intermittent sun exposure, especially in childhood
  • Many (more than 100) moles
  • Large, irregular, or “funny looking” moles
  • Close blood relatives — parents, siblings, and children — with melanoma
  • The presence of close (first-degree) family with melanoma is a high risk factor, although looking at all cases of melanoma, only 10% of cases run in families.

Having a history of other sun-induced skin cancers, such as the much more common basal cell or squamous cell carcinomas, indirectly raises one’s risk of melanoma because they are markers of long-term sun exposure. The basic cell type is different, however, and a basal cell or squamous cell carcinoma cannot “turn into melanoma” or vice versa.

Types of Melanoma

The main types of melanoma are as follows:

Superficial spreading melanoma: This type accounts for about 70% of all cases of melanoma. The most common locations are the legs of women and the backs of men, and they occur most commonly between the ages of 30-50. (Note: Melanomas can occur in other locations and at other ages, as well.) These melanomas are flat or barely raised and have a variety of colors. Such melanomas evolve over one to 5 years and can be readily caught at an early stage if they are detected and removed. An “in situ” melanoma (malignant melanoma in situ) refers to a very thin superficial spreading melanoma that does not extend beyond the junction of the dermis and epidermis, the normal location for melanocytes.

Melanoma Skin ImageNodular melanoma: About 20% of melanomas begin as deeper, blue-black to purplish lumps. They may evolve faster and may also be more likely to spread. Untreated superficial spreading melanomas may become nodular and invasive.

Lentigo maligna: Unlike other forms of melanoma, lentigo maligna tends to occur on places like the face, which are exposed to the sun constantly rather than intermittently. Lentigo maligna looks like a large, irregularly shaped or colored freckle and develops slowly. It may take many years to evolve into a more dangerous melanoma or may never become a more invasive form. Because of the unpredictability of future behavior, removal is recommended.

There are also other rarer forms of melanoma that may occur, for example, under the nails (subungual), on the palms and soles (acral lentiginous), uveal or choroidal (ocular), oral or vulvar mucosa, or sometimes even inside the body.

How is melanoma diagnosed?

Most doctors diagnose melanoma by examining the spot causing concern and doing a biopsy. A skin biopsy refers to removing all or part of the skin spot under local anesthesia and sending the specimen to a pathologist for analysis.

The biopsy report may show any of the following:

A totally benign condition requiring no further treatment, such as a regular mole

An atypical mole which, depending on the judgment of the doctor and the pathologist, may need a conservative removal (taking off a little bit of normal skin all around just to make sure that the spot is completely out).

A thin melanoma requiring surgery

A thicker melanoma requires more extensive surgery or extra tests in which the lymph nodes are examined. Removing lymph nodes causes physical problems even when there is no tumor present and, for that reason, is not recommended for thinner melanomas.

Some doctors are skilled in a clinical technique called epiluminescence microscopy (also called dermatoscopy or dermoscopy). They may use a variety of instruments to evaluate the pigment and blood vessel pattern of a mole without having to remove it. Sometimes the findings support the diagnosis of possible melanoma, and at other times, the findings are reassuring that the spot is nothing to worry about. The gold standard for a conclusive diagnosis, however, remains a skin biopsy.

What is the treatment for melanoma

In general, melanoma is treated by surgery alone. Doctors have learned that surgery does not need to be as extensive as was thought years ago. When treating many early melanomas, for instance, surgeons only remove 1 centimeter (less than ½ inch) of the normal tissue around the melanoma. Deeper and more advanced cancers may need more extensive surgery.

Depending on various considerations (tumor thickness, body location, age, etc.), the removal of nearby lymph nodes may be recommended. For advanced disease, such as when the melanoma has spread to other parts of the body, treatments like immunotherapy or chemotherapy are sometimes recommended. Many of these treatments are still experimental and, for that reason, their use may be limited to patients willing to participate in a research study.

The most useful criterion for determining prognosis is tumor thickness. Tumor thickness is measured in fractions of millimeters and is called the Breslow’s depth. A related prognostic measure is the Clark’s level, which describes how many skin layers the melanoma penetrates. The lower the Clark’s level and the smaller the Breslow’s depth, the better the prognosis. Any spread to lymph nodes or other body locations dramatically worsens the prognosis.

Thin melanomas, those measuring less than 1 millimeter, have excellent cure rates. The thicker the melanoma, the less optimistic the prognosis. Early diagnosis and treatment are essential.

To help prevent melanoma?

Reducing sun exposure: Avoidance of sun exposure is the best means of helping to prevent melanoma, followed by wearing hats and tightly woven clothing, and then followed by broad-spectrum waterproof sunscreens applied liberally and often. The consensus among dermatologists is that sunscreens are at least partially helpful and are certainly preferable to unprotected sun exposure. (Despite sensational articles in the popular press, there is no credible evidence that sunscreens can cause melanoma. Data to indicate increased melanoma risk did not take into consideration that the sunscreens used by the subjects [at least as well as they could remember after decades] were far inferior to current products, which usually have much higher ultraviolet B SPF protection as well as ultraviolet A protection.)

Melanoma Skin ImageEarly detection: Get one’s skin checked at least once. Then, if it is recommended, have one’s skin checked on a regular basis. The American Academy of Dermatology sponsors free skin cancer screening clinics every May all over the country. Special “Pigmented Lesion Clinics” have also been established in many medical centers to permit close clinical and photographic follow-up of patients at high risk.

Screening of high-risk individuals: Anyone at high risk, such as anyone with a close relative who has melanoma, should be screened by a doctor for melanoma.

New research highlights how vital it is to treat melanoma in an age-appropriate manner, suggesting anti-oxidants may be a more effective treatment for older patients.

Cancer risk increases with one’s age as accumulated damage to our cells and chronic inflammation occur over time. Now, an international team of scientists led by The Wistar Institute have shown that aged tumor cells in melanoma behave differently than younger tumor cells, according to study results published in the journal Nature.

Changes in the microenvironment make these older tumor cells more metastatic and more resistant to treatment with targeted therapies. In light of these findings, the scientists demonstrated how antioxidants could serve as a better treatment strategy for older patients with melanoma.

“It’s fascinating to see that the microenvironment can have such a profound effect on both metastasis, and response to a therapy that is specifically targeted to a mutation in a gene. This tells us that no tumor is an island, and even therapies targeted against these driver mutations are affected by the way the tumor cell communicates with its microenvironment,” said lead author Ashani Weeraratna, Ph.D., associate professor in the Tumor Microenvironment and Metastasis Program at Wistar.

Melanoma is the deadliest form of skin cancer, and patients with advanced cases of the disease only have a 20 percent chance of surviving five years after their diagnosis. Multiple targeted therapies for melanoma have been approved in the last few years, but patients who receive these drugs eventually relapse and become resistant to these treatment options.

While multiple factors may contribute the age-related increases in cancer, for the first time, the Weeraratna Lab has pinpointed age-related changes that occur in the microenvironment of tumor cells. Cells found in the skin called dermal fibroblasts help the skin recovery from injuries, and can contribute to the growth and invasion of melanoma cells. The researchers used dermal fibroblasts from healthy donors 25-35 years of age or from donors 55-65 years of age to understand what factors contribute to the difference in melanoma progression in aging cell populations.

Weeraratna and colleagues determined that a secreted factor sFRP2 was present in aging cells. SFRP2 regulates another protein called β-catenin that normally blocks the invasion of melanoma cells. In addition, b-catenin loss has been shown to promote oxidative stress in some cell types. The researchers showed that in an aged microenvironment, there are fewer scavengers of free oxygen to more activity of reactive oxygen species (ROS). At the same time, the age-induced loss of beta-catenin renders melanoma cells less capable of dealing with ROS, resulting in a genetically unstable tumor.

Melanoma Skin ImageTreatment resistance experienced by older melanoma patients was found with increased activity of ROS and decreased levels of β-catenin all contribute to increased resistance to treatment with drugs that inhibit a gene, BRAF, mutated in approximately half of all cases of melanoma. Wistar scientists also showed how antioxidants might be a more effective strategy for treating older melanoma patients. An antioxidant called N-acetylcysteine (NAC) killed melanoma cells in aged dermal fibroblasts.

“Our findings highlight how vital it is to treat that melanoma in an age-appropriate manner,” said Amanpreet Kaur, a graduate student in the Weeraratna lab and first author of the study. “With other studies confirming the effectiveness of anti-oxidants in treating BRAF-mutated cancers, we have more evidence of how an older population may benefit from new therapeutic strategies.”

Skin self-exam

The best time to do a skin self-exam is after a shower or bath. You should check your skin in a well-lighted room using a full-length mirror and a hand-held mirror. It’s best to begin by learning where your birthmarks, moles, and blemishes are and what they usually look and feel like.

Check yourself from head to toe. Don’t forget to check all areas of the skin, including the back, the scalp, between the buttocks, and the genital area.

Look at your face, neck, ears, and scalp. You may want to use a comb or a blow dryer to move your hair so that you can see better. You also may want to have a relative or friend check through your hair because this is difficult to do yourself. 2. Look at the front and back of your body in the mirror, then raise your arms and look at your left and right sides. 3. Bend your elbows and look carefully at your fingernails, palms, forearms (including the undersides), and upper arms. 4. Examine the back, front, and sides of your legs. Also look between your buttocks and around your genital area. 5. Sit and closely examine your feet, including the toenails, the soles, and the spaces between the toes.

By checking your skin regularly, you will become familiar with what is normal for you. It may be helpful to record the dates of your skin exams and to write notes about the way your skin looks. If you find anything unusual, see your doctor right away.

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