Randy Jacobs M.D.
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MOLES & MALIGNANT MELANOMA

 

 

Introduction

There has been a sharp increase in awareness of skin cancer in recent years as the result of a worldwide campaign against this disease and reports about the thinning atmospheric ozone layer, which is allowing greater penetration of harmful ultraviolet rays. Skin cancer is the most common cancer. One in three cancers diagnosed in the U.S.A. this year will be a skin cancer. One in six Americans will develop skin cancer in his or her lifetime. In 1991, 600,000 new cases of skin cancer were reported, and an estimated 8,500 deaths occurred from this disease. Melanoma accounted for 6,500 deaths, while non-melanoma skin cancers (basal cell carcinomas and squamous cell carcinomas) accounted for an estimated 2,000 deaths. Malignant melanoma is a skin cancer which occurs mostly in adults, usually on the skin of the head, neck, legs, or back, and rarely in the eye, mouth, vagina, or anus. Malignant melanoma may spread to other areas of the body, primarily the lymph nodes, liver, lungs, and central nervous system. Most melanomas begin in a mole or other pre-existing skin lesion. They are flat or slightly raised and can be black, brown, blue, red, white, or a mixture of all colors. The borders are often irregular and may bleed. Melanoma is caused by uncontrolled growth of cells that give skin its brownish color (melanocytes). When the cells grow down into deep skin layers, they invade blood vessels and lymph vessels and are spread to other body areas. This process represents metastasis.

 

 

Risk of melanoma increases with:

 

- Moles on the skin.

 

- Occupations or activities involving excessive sun exposure, such as farming, construction work, athletics, or sunbathing.

 

- Pregnancy.

 

- Genetic factors. Melanoma is most common in people with light complexions. It is rare in blacks.

 

- Radiation treatment or excessive exposure to ultraviolet light, as with sun lamps or tanning booths.

 

- A family history of melanoma or a family history of dysplastic nevi.

 

Malignant Melanoma: Facts (Are the facts related to a diminishing ozone layer?)

 

-  In 1990 27,600 new cases of melanoma were diagnosed; 14,800 occurred in males, 12,800 in females. An additional 5,000 cases of melanoma in-situ (early, non invasive lesions) were diagnosed.

 

-  Approximately 50% of melanomas occur in individuals younger than 55 years of age and approximately 30% occur in those younger than age 45.

 

-  The number of melanoma cases has nearly doubled in the last decade, whereas the population has increased by only 11%.

 

-  The incidence of malignant melanoma is increasing at a rate faster than that of any other cancer. During the past decade, the annual increase in melanoma was approximately 7% per year.

 

-  In 1935, the lifetime risk of an individual in the United States developing a malignant melanoma was 1:1500. In 1960, the lifetime risk was 1:600; In 1980, the lifetime risk was 1:250; In 1990, the lifetime risk  was 1:105. It now is 1:75.

 

-  For each decade since the 1940's, survival rates have improved by approximately 10%. The 5-year survival rate for malignant melanoma diagnosed between 1979-1984 was 80%. Statistics show that early diagnosis and prompt excision of the lesions leads to cure in virtually all patients.

 

-  Despite the increasing cure rate, the mortality rate is also increasing because the disease incidence is increasing at an even greater rate.

 

-  Ten years ago, Melanoma was the 20th most common cancer in the U.S. Melanoma is now the 8th most common cancer in the U.S.

 

-  A six fold increase in melanoma has occurred in the U.S.A. in the last 50 years.

A. Definition

 

Melanoma is a type of skin cancer involving the pigment producing cells of the skin (called melanocytes, see adjacent diagram) The melanocyte cells are responsible for the color of one's skin, as well as for the darkening of skin seen after sun exposure. Melanocyte number is equal in all races.

 

 

B. The Four Forms of Melanoma

 

There are four major forms of melanoma, each is based primarily on the type of growth pattern exhibited by the tumor. The most common type of melanoma is called superficial spreading melanoma, due to its rapid horizontal growth pattern. This kind of melanoma is responsible for approximately 70% of all melanomas seen today. Nodular melanomas, which are responsible for 15% to 30% of all melanomas, grow vertically into the dermis and have a smaller radial component of growth. Nodular melanoma lesions are characterized by a cauliflower like appearance which commonly arises without evidence of a pre-existing lesion. Nodular melanomas are blue to black in color and may lack any pigment at all. These lesions are frequently more aggressive and require immediate treatment. If pigment is absent, the melanoma is called an amelanotic malignant melanoma. Amelanotic malignant melanomas are the most deceptive, as they may closely resemble a variety of benign lesions. Lentigo maligna melanomas make up only 4% to 10 % of melanomas. They tend to be tan colored lesions that have been present for numerous years as an enlarging dark spot on sun exposed skin. Lentigo maligna melanoma begins as a flat, irregularly bordered pigmented lesion called lentigo maligna. Lentigo maligna is an in situ form of melanoma. This pigmented lesion may eventually evolve into malignant melanoma. Because of its relation to malignant melanoma, Dr. Jacobs is very aggressive in his treatment of Lentigo Maligna. The last major type of melanoma is acral lentiginous melanoma. Acral Lentiginous melanomas are responsible for only 2% to 8% of all melanomas, but are the cause of up to 60% of melanomas in dark skinned people. They are flat brown and stain like in nature with irregular borders. They are most commonly found on the palms, soles or nail beds. Melanoma can begin in various ways. depending on the type of melanoma you are dealing with. Superficial spreading melanoma tends to be found most commonly on the legs of females and on the backs of men. This type is generally seen in fifth decade of life. Nodular melanomas are seen more frequently in men and tend to grow fast and have a palpable nodular component early on in the disease. Lentigo melanomas tend to take a long time to grow and are commonly thought to be a freckle prior to diagnosis. They tend to be found on the head and neck of those over 60 years of age. Acral lentiginous melanoma, as mentioned before, are found on the palms, soles and nail beds. This type has both vertical and horizontal growth components, however, may be merely a streak in the nail with irregular tan brown staining of the nail bed. Moles are present in about 1% of babies. Melanomas can often begin in larger congenital nevi. The larger the congenital nevus, the larger the risk of acquiring melanoma. The risk of developing  melanoma in a larger congenital nevus has been reported at 4.6 to 14%, depending on the author. The size is the most important factor. The larger the nevus, the greater the chance. The bottom line with large congenital nevi is that they do have a chance of converting to melanoma. Thus, the benefits may outweigh the risks when considering removal of a large congenital mole. Small ones are less likely to convert. If they appear atypical, these lesions can be removed at any time. It may be wise to wait until a child is able to psychologicall understand the surgery. Ages 9 or 10 are usually appropriate. Dr. Jacobs may or may not suggest removal. If a lesion is obviously atypical, Dr. Jacobs may suggest removal at a younger age. Finally, other less common presentations of melanoma include mucous membrane involvement such as the mouth, vagina, or anus. In addition, certain giant hairy cell nevi or blue nevi can also lead to melanoma. On occasion, melanoma can present in an organ, or metastatically without a demonstrable primary lesion. Lastly, certain families have members with many moles which demonstrate features of the A,B,C,D's (see next page). Some call this condition the dysplastic or atypical nevus syndrome. Family members with this condition are at increased risk for melanoma. If dysplastic nevi do exist in your family, you may want to discuss this with Dr. Jacobs.

 

 

C. What causes it?

Evidence suggests that the most common inducing cause of melanoma is sun exposure. Hereditary forms of melanoma may arise from moles and any suspicious lesions. A dose of sun may be the factor that turns a normal mole into a melanoma. Melanomas arising from congenital moles may undergo malignant transformation after some kind of irritating exposure. Patients with fair complexions, red hair, blue eyes, and those who tend to burn easily in the sun are at a particularly high risk. Other risk factors include those who have received a transplant, or patients with leukemia, lymphoma, or other immunosuppression.

 

D. How does it progress?

 

The expected outcome varies greatly. Early melanomas that have not grown far downward are often curable by surgical removal. Once the tumor has spread to distant organs, the condition may be incurable. Scientific research into causes and treatment, continues, so there is hope for increasingly effective treatment and cure. The progression of the disease depends largely on the type of melanoma you may have. Some types may progress very rapidly, such as the nodular type, where others such as the lentigo maligna type melanomas make take years to progress. Metastatic potential and lethality of the disease depends mostly on the depth of invasion. Metastasis is possible with all types of malignant melanoma tumors. For melanoma, an ounce of prevention is worth a pound of cure. The patient with a history of melanoma should be followed closely for any signs of recurrence. Dr. Jacobs likes to include a total body skin exam at regular intervals throughout the year.

 

 

 

 

 

 

 

E. How is it diagnosed?

 

Diagnosis is first obtained by a clinical evaluation of the lesion. Suspicious lesions contain at least 2 of the 5 ABCD's of melanoma (see adjacent diagram). The S stands for signs, symptoms, and significant factors (SSS) such as itch, bleeding, enlargement, color change, and a family history of many moles or melanoma. Dr. Jacobs suggests that any lesion with at least 2 of the 5 criteria should be biopsied and sent out for a pathological diagnosis.

 

 

 

F. Ways to treat it.

 

Surgical excision is the most common and longest lasting procedure used to treat melanoma. Surgery, however, is used only on accessible lesions and can be limited by the patient's health and ability to undergo such a procedure. The extent of surgery depends on the depth of invasion. Most authors recommend a wide surgical excision for melanomas. In general, for lesions of the head and neck area, less than 1.0 mm in thickness, a 1 cm margin appears to be adequate. For those of 1-2 mm in thickness, a 2 cm margin. For those more than 2.0 mm in thickness, a 3 cm margin is the maximum used.  If lymph nodes are involved, the surgery may be rather complex and not indicated some cases. In general, an elective lymph node dissection (ELND) will be offered for patients with tumors between 1.5 and 4.0 mm in thickness. Radiation therapy is used primarily as a method of relieving pain from distant metastatic sites. It may be used to control superficial metastasis in the skin or soft tissues, as well. Chemotherapy is used, however, response rates are frequently poor and short lived. Immunotherapy using newer drugs has in some cases been used with limited success, but at this period of time, most immunotherapy is only experimental and not completely effective. Bacillus Calmette-Guerin (BCG) is a non specific immunostimulant which increases the body's own immune reaction to melanoma. BCG may be used in combination with DTIC (Dimethyl triazeno imidazole carboxamide), a chemotherapeutic agent for chemoimmunotherapy. Melanoma tumor vaccines are under investigation, but have not as yet gained FDA approval. Biologic response modifiers such as interleukin 2 and interferon may be used in certain cases, but the side effects are difficult to endure.  Other immunomodulating therapies include monoclonal antibody therapy (injection of antibodies) and adoptive immunotherapy. Adoptive immunotherapeutic methods involve removing, growing, and concentrating the patient's own white blood cells, and reinjecting them. Though immunotherapy is primarily experimental at this time, we expect to have fully functional immunotherapeutic treatment modalities in the next several years. Special case: Pregnancy. Several studies suggest that pregnancy has an adverse effect on melanoma. Dr. Jacobs suggests total skin exams for pregnant patients at risk for melanoma. Melanoma in a pregnant patient should be treated promptly and adequately in a manner that does not compromise the patient's chances for cure.

 

G. What to expect.

 

The prognosis of the disease is dependent upon the location, tumor thickness and type, gender, ulceration, and site of the primary lesion. Those with lymphatic involvement must also consider the number of nodes affected and the possibility of distant metastasis. Lesions which are localized and up to 0.76 - 1.50 mm deep have a 87 - 94% five year survival if treated by surgical excision. It is, therefore, essential that any suspicious lesions be evaluated by Dr. Jacobs as soon as possible. The key to survival is early detection. With melanoma, an ounce of prevention is worth a pound of cure. A stitch in time can save nine. If you have had a melanoma, there is an increased risk of developing a second melanoma. For this reason, most melanoma patients are seen back in Dr. Jacobs' clinic for a total body skin exam at least every three months during the first post operative year, every six months during the second, and every year thereafter.

 

 

 

 

 

H. Sentinal Lymph Node Dissection (SLND)

 

When clinically undetectable cancer cells from a primary melanoma have spread (metastasized) to the regional lymph nodes, these microscopic cells are most likely to be found in the sentinel node, the first node in the lymphatic drainage channel closest to the site of the primary tumor. This node can be located (mapped) by injecting a vital blue dye intradermally around the primary tumor, or around the biopsy site if the primary was previously removed. The dye is taken up by the surrounding lymphatics and drains into the regional lymph node basin, accumulating in the first node. A small incision is made over the basin, where this now blue-tinted sentinel node can be visually detected. It is removed and examined by a pathologist, and if no melanoma cells are found, surgery is terminated and all other nodes can be spared (unlike ELND, which always entails radical removal of all nodes). If cancerous cells are found in the sentinel node, surgery continues to remove the rest of the nodes.

 

Dr. Morton of UCLA, in his original 1992 study found that the sentinel node could be identified 80 percent of the time and accurately reflected the presence or absence of disease in 95 percent of patients evaluated. Many physicians soon embraced this selective surgical technique in lieu of ELND, hoping to avoid the high cost, disfigurement, and potential complications of unnecessary extensive surgery. All that remained was for other research to confirm Morton's findings.

 

SLND has rapidly made its way into clinical practice, due to its cost-saving, morbidity-sparing possibilities. It has been spurred further by FDA approval of interferon alfa-2b therapy for melanoma patients who are at high risk of recurrence after tumor surgery. Many surgeons are using SLND to search for regional microscopic metastases to determine whether patients should receive interferon treatment.

 

I. INTERFERON

 

Interferons are natural substances produced by the normal cells of most body tissues in response to viral infections and disease. Manufactured forms of interferons have been shown to help the body's immune system fight disease more effectively. There are three general types of interferons that are used to treat human diseases, interferon alfa, interferon beta, and interferon gamma. To date only interferon alfa has been found to be useful in treating cancer.

 

The immune system enables the body to distinguish cells that are native to the body from those cells and sub-cellular organisims that are foreign. These foreign invaders include viruses, bacteria, and other disease-causing organisms. The body recognizes foreign, diseased, or cancerous cells by special marker substances known as antigens on their surfaces. These markers allow your body's immune system to distinguish abnormal or foreign cells from healthy cells in the tissues of your body. When this occurs, the immune response sends an array of immune cells to contain and destroy or wall off the foreign or cancerous invading cells.

 

Cells of the body's immune system that have been stimulated or recognized antigens against which they are targeted will begin to produce interferons and other natural immune signalling substances. These substances not only combat foreign invaders, which may cause infection, they can also prevent the growth and spread of other diseased cells, including cancer.

 

One type of interferon, interferon alfa-2b, has been shown in two randomized prospective trials to prolong disease-free and overall survival in patients with high-risk melanoma. These results led to the U.S. Food and Drug Administration approval of interferon alfa-2b as adjuvant therapy for melanoma in 1996. In other studies, high dose interferon produced promising results in terms of delaying relapse in stage II patients, while little if any benefit was seen in high-risk patients.

 

Clinical trials are currently underway to further evaluate whether the highly significant benefit of high-dose interferon given for a full year can be duplicated with the treatment given for only one month, or a new form of long-acting less toxic (PEG) interferon given weekly for many years. Other promising approaches may include melanoma vaccines or combinations of interferon with other forms of immunotherapy, such as interleukin-2.

 

Interferon Administration

Interferon therapy cannot be administered orally because strong acids and enzymes in our digestive systems would destroy it. Therefore, interferon must be delivered directly into the blood stream or into tissue. In the first phase of interferon therapy, called the induction phase, interferon is administered to the patient intravenously. This may be done in a hospital or in an office setting. The induction phase generally involves five days of interferon therapy per week for a four-week period. Each subcutaneous injection should take about twenty to thirty minutes.

 

The second phase of interferon therapy, called the subcutaneous injection maintenance phase, begins in the fifth week and involves three injections per week. This routine continues for the remainder of the year. During this phase many patients and their loved ones learn to administer the injections of interferon themselves.

 

Interferon Side Effects

As with any treatment, the side effects of interferon therapy depend on the prescribed dose. In addition, all people differ in their individual responses to therapy. Thus, some patients will have many side effects, while others may have none at all. Often, patients experience the most side effects during the first few weeks of therapy. After this period, many patients find that their side effects diminish greatly. Many patients tolerate low dose therapy very well, while high-dose interferon therapy tends to produce more severe and consistent side effects.

 

The main side effects of interferon therapy are fatigue and flu-like symptoms. Flu-like symptoms include fever, chills, headache, and general body aches. Another common symptom is loss of appetite. Diminished appetite can sometimes be attributed to feelings of nausea or the development of a metallic taste in the mouth. Less common side effects include mild hair thinning, dry itchy skin, palpitations, and lightheadedness. If side effects are severe, you should inform your doctor about and ask about all possible solutions.

Some laboratory tests may become abnormal with high-dose interferon including blood counts (5%), liver enzymes (14%) and kidney and thyroid function (> 10%). These side effects are generally reversible when therapy is stopped. If the symptoms or signs are significantly abnormal, the treatment may be interrupted for a time, and then resumed at a lower dose. Throughout the course of the therapy, treatment may be stopped and restarted at different dosages as needed.

 

J. Scar Abrasion and Cosmetic Appearance

After skin cancer surgery, Dr. Jacobs may use a small sanding device to "sand down" the scar, or may perform some other procedure to improve the site. Again, this type of work is exceedingly uncommon, and most patients do very well with just a simple surgical removal. Finally, with all surgical therapies rendered, there is always a small chance of incomplete removal or recurrence. Dr. Jacobs handles each case individually, based on the patient's tumor, the location, the size, the patient's wishes, and overall health. Please understand that skin cancer therapy is often more than on step. The patient may need one or more sessions in order to remove the cancer. Also, the patient may need additional cosmetic work to restore the appearance of the site. Time and patience is needed to achieve the desired result. For example, if an eyebrow or nose is stretched after surgery, a second procedure may be needed to restore the appearance. If a scar is large, a second procedure may be needed to improve its appearance. This all takes time and waiting as the human body takes time to decrease swelling, stretch, and heal after surgery.

 

K. Preventative Measures

 

Early Detection and Diagnosis

 

It is important to detect melanoma as early as possible. A self-examination of the skin is also important to detect new growths or other changes. If you notice any changing, new, or odd-looking mole or skin change, contact Dr. Jacobs promptly. He will take a medical history and give you a physical examination.

 

Importance of early detection of melanoma

 

*Survival rates of patients with thin primary melanomas are much higher than those for patients with thick primary melanoma

*The probability of 10-year survival for patients with melanomas less than 1 mm is about 95%

*The probability of 10-year survival for patients with melanomas greater than 4 mm is less than 50%

*Recent improvements in survival rates can be attributed to earlier detection

— Greater than 80% of patients diagnosed in the 1990s are anticipated to survive long-term

 

If Dr. Jacobs thinks the mole or skin change looks suspicious, a procedure known as a biopsy should be performed. To perform a biopsy, Dr. Jacobs will inject a local anesthetic under the skin to numb the area. The entire mole, or a piece of the mole, will be removed and examined in a laboratory to determine if it is cancerous. In general, superficial shave biopsies (slicing through the outer layers of the mole) are not recommended if melanoma is suspected because the sample obtained may not take the complete melanoma, and accurate measurement of the entire thickness of a melanoma is then not possible. However, a deep shave biopsy is adequate. Therefore, Dr. Jacobs may offer you a deep shave biopsy, a punch biopsy, or an excisional biopsy each of which can go down deep enough to attain an adequate diagnosis. Protect yourself from excessive sun exposure. Wear broad-brimmed hats and protective clothing. Use maximum protection UVA & UVB sun block preparations on exposed skin. Examine your skin, including soles of the feet, regularly for changes in pigmented areas. Ask a family member to examine your back. See Dr. Jacobs about any other skin areas (especially brown or black) that become multicolored, develop irregular edges or surfaces, bleeds, or changes in any way. Use the space on the back of this page to write down any findings from your own self exam. Please notify Dr. Jacobs if there are any positive findings.

 

L. Photos

 

As a picture is worth a thousand words, here are photos to help you understand melanoma:

 

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Ken Alpern, M.D. Charity Morris, PAC Eleni Litras,
PAC

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Hello, and welcome to our dermatology office. My name is Randy Jacobs, MD, FAAD. Some people are blessed with the most beautiful skin, and it’s all natural. Others have to work at it. Healthy skin is lovely to behold, comfortable to live in, and a pleasure to touch.
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