MELANOMA

MAKING THE DIAGNOSIS

Biopsy: The Basis for Diagnosis of Melanoma

Every melanoma diagnosis begins with a thorough examination of the skin growth or pigmented lesion under a bright light. If Board Certified Dermatopathologist, Babar K. Rao, MD, FAAD, sees anything to arouse suspicion, a biopsy will then be performed. This is the most accurate diagnostic test and is almost invariably done.

The goal of a melanoma diagnosis is to totally remove the tumor, although this may not be possible when it is large or located in a hard-to-reach location, such as the nail bed. At the start of the procedure, a local anesthetic is usually administered by a fine needle. Then the tissue is surgically removed with a scalpel. If the lesion is small, Dr. Rap may cut through the full thickness of the skin down to the underlying fat, and take some of the surrounding skin as well; in such cases, the tumor might be removed in its entirety. If the tumor is more extensive, only a small sample of the involved area will be surgically excised. The wound may then be closed by suturing (stitching).

There will often be a scar at the site of the biopsy, but in most cases, this is not cosmetically disfiguring.

Laboratory Studies

The biopsy sample (specimen) is sent to a pathology laboratory where it is prepared and stained for examination under the microscope. The finding as to whether the lesion is benign or malignant is then provided to the physician. If it is malignant, the cancer is classified according to type and thickness. Most melanomas are recognized in this way.

In rare instances, the diagnosis is not clear cut. Certain moles mimic the appearance of melanoma, and certain melanomas mimic the appearance of other cancers or even of benign moles. In such cases, microscopic examination is not conclusive. To establish the diagnosis, a number of highly sophisticated stains have been developed. These stains make use of antibodies, which are formed as an immune response to the antigen or molecule on the surface of the tumor cells. An antibody attaches itself only to one type of antigen. Therefore, a number of different antibodies are tested to see whether reactions to any of the antigens expressed by the tumor cells take place.

An additional approach is to get a second opinion from a pathologist who specializes in melanoma.

The laboratory report provides information to the physician on how far the melanoma has advanced and how serious it is. This knowledge is essential in determining the extent of the treatment that will be undertaken.
 

ABCD's of Melanoma - Four Warning Signs

	ASSYMETRY  A stands for Asymmetry. If you were to draw a line through the middle of the melanoma, the two sides would not match. This is in contrast to a common, benign mole, which is round and symmetrical. Most early melanomas are asymmetrical: Common moles are usually round and symmetrical.
	BORDER B stands for Border. Melanomas are frequently irregular in shape, with scalloped or notched edges.  Common moles have smoother, more even borders. In contrast, a common harmless mole has smooth, even borders.
	COLOR C stands for Color. Melanomas display a variety of shades of brown or black, as well as some unusual shades - mixed red, white, and blue.  Varied shades of brown, tan, or black are often the first sign of melanoma. As melanomas progress, the colors red, white and blue may appear.  In contrast, common moles generally are a rather uniform shade of brown.
	DIAMETER D stands for Diameter. The melanoma is usually larger than 1/4 inch (6 millimeters), the size of a pencil eraser. There are some exceptions, however. Early melanomas tend to grow larger than common moles.
If you detect any of these warning signs, see a physician promptly. AN EARLY WARNING SYSTEM When a melanoma is detected at an early stage and treated, a cure is all but certain. Many, if not most, melanomas can be spotted as soon as they arise - if you know what to look for and check for those signs. How Does a Mole Change? In addition to checking out the ABCDs, you should watch for change. Size The mole suddenly or continuously gets larger. Color A wide variety of colors or color combinations appear. Color might spread from the edge into the surrounding tissue. Elevation A mole that was flat or slightly elevated increases in height rapidly. Surrounding skin The skin around a mole becomes red or develops colored blemishes or swellings. Surface A smooth mole develops scaliness, erosion, oozing. Crusting, ulceration, or bleeding are late signs in the disease. Sensation Itching is the most common early symptom, and there may also be feelings of tenderness or pain. Nonetheless, remember that skin cancers are usually painless. If any of these changes occur, they should be checked by a professional. It is particularly important for you to select a physician who specializes in skin cancer and is trained to recognize a melanoma at its earliest stage.  Make an appointment without delay. Prompt action is your best protection.   Benign   Malignant     Symmetrical       Asymmetrical (the two sides do not match)     Borders are even       Borders are uneven     One shade       Two or more shades     Smaller than 1/4 inch       Larger than 1/4 inch

Dermoscopy Aids in Decision-Making

You may hear about the use of dermoscopy as a diagnostic tool. (Dermoscopy is occasionally referred to by another name, epiluminescence microscopy.) Some physicians are employing this technique before deciding to perform a biopsy. This procedure, which is painless, makes use of a new instrument, the dermoscope. It can provide the physician with more information than is obtained with the naked eye.

Oil is spread on the pigmented lesion and the area around it to make the skin more translucent. One end of the dermoscope is pressed against the skin, and the physician looks at it through a lens with a magnification of 10. Because more light rays penetrate oil-covered skin, certain features of benign or malignant tumors become visible.

The features that can be identified with a dermoscope include such structures as a brown "network" resembling a fisherman's net, brown globules, black dots, and color variations.


TREATMENT

What is the prognosis? Anyone who has had a diagnosis of melanoma is worried. That is a natural reaction. Some go so far as to believe that their future is bleak. Fortunately, it is not necessarily true. When it comes to early stage disease, the future could hardly be brighter. Practically every person with a thin, localized melanoma is cured by appropriate surgery.

Therefore, you can see that the sooner the cancer is caught and treated, the better the results. Early detection remains the best weapon in fighting melanoma.

Even for those with more advanced disease, there is good news, as the cure rate keeps rising. The treatments are varied and many; new discoveries are being made to improve the chances of those with the metastatic disease.

The first step in treatment is the removal of the melanoma, and the standard method of doing this is by surgical excision or cutting it out. Surgery has made great advances in the 1990s, and much less tissue is removed than was customary even a few years ago. Patients do just as well after the lesser surgery, which is easier to tolerate and produces a smaller scar.

The surgical excision is also called resection, and the borders of the entire area excised are known as the margins.

Out-Patient/Office Surgery

In most cases, the surgery for thin melanomas can be done in the doctor's office or as an out-patient procedure under local anesthesia. Wound healing takes one to two weeks, and most patients are advised to avoid heavy exercise during this time. Scars are usually small and improve over time.

Discolorations and areas that are depressed or raised following the surgery can be concealed with cosmetics specially designed to provide camouflage. If the melanoma is larger and requires more extensive surgery, a better cosmetic appearance can be obtained with flaps made from skin that is near the tumor, or with grafts of skin taken from another part of the body. For grafting, the skin is removed from areas that are normally or easily covered with clothing.

Setting the Margins

In the new approach to surgery, much less of the normal skin around the tumor is removed and the margins, therefore, are much narrower than they ever were before. Most surgeons today are following the guidelines recommended by the National Institutes of Health (NIH):

When there is an in situ melanoma, the surgeon excises 0.5 centimeter (2.5 cm equals 1 inch) of the normal surrounding skin and in terms of depth, goes down to the layer of fat.

In removing a melanoma, which is 1 mm or less in Breslow thickness, the margins of surrounding skin are extended to 1 cm, and the excision goes through all skin layers and down to the fascia this is the layer of tissue covering the muscles.

For melanomas is 1.1 to 3.99 mm thick a 2 cm margin is recommended, this is classified intermediate.

If there are melanomas 4.0 mm or thicker in Breslow measurement, recommended margins will be 2 to 4 cm.

Today, narrower margins are the "treatment of choice" for all melanomas, regardless of stage.

When you consider that until recently, margins of from 3 to 5 cm were standard, even for comparatively thin tumors, you can see how dramatically surgery has changed for the better.

Lymph Node Involvement

Once the melanoma has progressed beyond stage II, the key question is whether it has spread beyond the original site. If so, it is likeliest to have reached the lymph nodes that are closest to the tumor.

Palpable nodes

To find out whether melanoma cells have escaped the primary tumor, the physician starts by feeling the nearby lymph nodes. If the melanoma is on the arm, the nearest nodes are in the armpit; if on the leg, they are in the groin. For a melanoma on the head, the closest lymph nodes are usually on the neck on the same side. For a tumor on the trunk, the nodes in either the armpit or the groin could be involved.

An enlargement or lump in a lymph node can be recognized by touch, and the word used to describe it is palpable. A lymph node that is palpable is surgically removed in a node biopsy.

This node is sent to the pathology laboratory to be tested for the presence of malignant cells. If any are found, treatments that stimulate the immune system and/or chemotherapy will be recommended.

Non-palpable nodes

Sometimes the lymph nodes are not palpable. When that is the case, one of two approaches will be followed:

"Wait-and-see." Some physicians advise a "wait-and-see" policy. No further surgery is done at this time, but the patient is asked to return at regular intervals for checkups.

Radical dissection. Others believe in removing all the nodes in the region of the tumor on the chance that there are hidden cancer cells. You will hear this procedure described by the technical term of a "radical node dissection."

At the present time both approaches are appropriate. However, there is no definite proof that non-palpable lymph node removal should be performed as a preventive measure. It is a good idea to ask the physician about these options and the reasons why one or the other might be recommended.

Lymphoscintigraphy and the Sentinel Node

A new method, lymphoscintigraphy, has been developed for mapping the lymph system. A small amount of a radioactive substance is injected at the site of the melanoma to trace the flow of lymph fluid draining from it to the nodes. Then, with the help of a scanner, the drainage pattern of the lymph fluid can be determined. Armed with this information, the surgeon can remove only those lymph nodes that receive the fluid preferentially. The procedure is known technically as "lymphoscintigraphy-guided-lymph node dissection."

Another diagnostic technique makes use of a blue dye injected into the skin around the tumor. The dye passes into the lymph fluid, tracing its path. The blue color is picked up first by the node that is closest to the tumor, the sentinel node.

Once a specific area of lymph drainage has been pinpointed by either method, that node or nodes can be removed surgically and tested in the pathology laboratory. If no cancer cells are found, no further surgery is performed. If there are cancer cells in the sentinel node, the additional nodes will be removed. This procedure is still undergoing clinical trials, and is not a standard part of practice. You may, therefore, wish to discuss it with your physician.

Local vs. Distant Spread

In Stage IV, there may be distant metastases, rather than either the local spread to the lymph nodes or in-transit metastases. As you will recall, in-transit metastases were described in Chapter Three as a sub-group in Stage III. In this form of the disease, the tumor involves skin or subcutaneous tissue more than 2 cm from the primary tumor, but not beyond the regional lymph nodes.

Once the disease has advanced to Stage IV, melanoma cells have traveled through the body via the bloodstream, going far from the original (primary) tumor site They could have reached distant lymph nodes or invaded the internal organs.

When distant metastases are suspected, the physician may call for imaging of the chest, head, abdomen, and pelvis with a CT (computed tomography) scan. In this technique, x-rays of the body are taken from many different angles, and are then recorded by means of computer technology. MRIs (magnetic resonance imaging) and nuclear (radioactive) scans are also sometimes used.

Additional (Adjuvant) Treatment

For patients with Stages III and IV disease, surgery may be followed with additional or adjuvant therapy. The patient can ask the physician to explain the possibilities and grounds for selection of one adjuvant over the other.

Chemotherapy

Several drugs that act on cancer cells are being used in the treatment of melanoma, either one at a time or in combinations. They may also be accompanied by drugs that act on the immune system. Dacarbazine (DTIC) is the most frequently employed anticancer drug. A combination of DTIC and carmustine(BCNU), cisplatin, and tamoxifen is coming into more widespread use. Other agents you may be hearing about include: vindesine, vincristine, vinblastine, and bleomycin. There is not yet documented evidence of total efficacy.

Immunotherapy

A number of newly-developed treatments are now being tested with some success, and this is one of the most exciting and changing fields in medicine.

Some advances are being made in treatments designed to help the body's own immune system help itself. Among the immunotherapies, experimental melanoma vaccines are receiving a lot of attention now, and several different ones are being utilized for patients with disease in Stages III and IV. Unlike the influenza vaccine given when you are well to prevent disease, these are given to people who already have the disease to prevent it from getting worse, and to promote longterm survival.

Another type of immunotherapy (also described as biologic therapy) makes use of chemicals that occur naturally in the body. The one you are most likely to hear about for Stage III patients is interferon-alpha. High-dosage interferon alfa-2b ("Intron A") is the only systemic drug to improve five-year survival of Stage III patients that has been approved by the Food and Drug Administration (FDA).

Tumor-necrosis factor is another of these naturally-occurring substances. Both of these - especially interferon-alpha - are produced by white cells (lymphocytes) after contact with viruses or tumor cells, and have been shown to kill some tumors, including melanomas. They also have "anti-angiogenic" properties that prevent the formation of new blood vessels that would otherwise supply and nourish the tumor.

An experimental treatment tried when the melanoma is on an arm or leg consists of adding chemotherapy, interferon-alpha, and tumor-necrosis factor in very high dosages to the blood flowing through that limb. Additional forms of experimental immunotherapy for Stage IV patients include systemic use of lymphokines, which are also chemicals normally produced in small quantities in the body, or in lymphocytes specially stimulated to kill malignant cells, including melanoma.

The best known of these therapies utilizes the lymphokine interleukin-2, with or without tumor-infiltrating lymphocytes which attack the melanoma. The interleukin-2 stimulates the lymphocytes of the immune system in general. The FDA has approved the use of a high-dose IL-2-only regimen ("Proleukin") for treatment of patients with metastatic (Stage IV) melanoma.

Therapy frequently makes newspaper headlines, as it is being tested on a wide range of illnesses. Therefore, you will find the following explanation helpful. However, keep in mind that this form of treatment is in the very earliest stages of research, and is not widely available. Its effectiveness is yet to be proven.

One form of gene therapy is based on creating alterations in the melanoma cells themselves. The cells are removed from the patient, grown outside the body, and treated so as to increase in number. Then genetic material is introduced that changes the melanoma cells by stimulating the growth of two types of white blood cells, granulocytes and macrophages. These have the effect of making the melanomas more readily recognizable to the immune system. The more recognizable melanoma cells are returned to the patient's body in an effort to stimulate the immune system to kill the metastatic disease.

Possibilities

Many patients, especially those with advanced disease, are participating in clinical trials in order to get new treatments while they are still experimental and not generally available.

As you can see, more treatment possibilities exist than ever before, giving new hope to people with melanoma.

If you have any questions about Babar K. Rao, MD, FAAD, or any questions about our dermatology or dermatopathology (skin cancer) procedures please feel free to contact Board Certified Dermatologist, Board Certified Dermatopathologist, Babar K. Rao, MD, FAAD at his Manhattan, New York, Newbrunswick, New Jersey, or Fresno, California offices.