Melanoma is one of the most dangerous forms of skin cancer. There are approximately 75,000 new cases of melanoma diagnosed and 9,000 melanoma related deaths in the United States each year.
Melanoma may appear on normal skin or could start as a mole that changes in appearance. Melanomas that start on the skin are called cutaneous melanomas. Less commonly, melanoma can originate in other locations such as the eyes (ocular or uveal melanoma) or lining surfaces such as the sinuses or vaginal tract (mucosal melanoma). Over 90 percent of melanomas are caused by mutations in DNA of skin cells called melanocytes, which produce the pigment melanin.
There are various types and stages, and symptoms of cutaneous melanoma.
Types of Melanoma
Specific types of cutaneous melanomas include the following:
- Superficial spreading melanoma: makes up approximately 70 percent of cases. It can grow on the surface of the skin (radial phase) for several years before growing downward (vertical phase). Common locations include the back, and in women, on the legs.
- Nodular melanoma: makes up approximately 10-15 percent of melanomas and lack a radial growth phase, but grow downward vertically, appearing flat and can grow over a broad area as a radial growth phase over many years. It tends to develop in the elderly with an average age of 69 years. It often develops on the head, neck, and back of the hands.
Stages of Melanoma
At the time of your diagnosis, your physician will stage your melanoma based one the following criteria:
- Melanoma in situ: Has not invaded the lower layers of skin
- Stage I: Detected at the primary site (starting spot on the skin) only, and based on the Breslow thickness is a thin melanoma invading the skin less than one mm
- Stage II: Detected at the primary site (starting spot on the skin) only, and based on the Breslow thickness is a deep melanoma invading the skin more than four mm, or a thin melanoma with cells that have divided, or if the primary site has ulcerated
- Stage III: Spread to the draining lymph nodes or along the lymph channels on the way to the lymph nodes (in-transit metastases)
- Stage IV: Spread distantly in the body either by the blood or the lymph system
A skin lesion may be melanoma if it exhibits certain telltale characteristics, including:
- Uneven shape
- Ragged edges
- Uneven coloration
- Changes in size
- Changes in texture
Causes and Risk Factors
Risks for developing cutaneous melanoma include:
- Personal history of melanoma
- Family history of melanoma
- Multiple atypical moles or dysplastic nevi
- Fair skin
- Sun exposure
- Certain inherited mutations in the DNA in a very small subset of melanomas
Screening and Diagnosis
With the incidence of melanoma increasing, it is of the utmost importance that you are proactive in getting screened diagnosed for any skin abnormalities. While the median age of diagnosis is 59 years, whatever age you are, you can develop melanoma.
Treatments for Melanoma
Treatments for melanoma may incorporate both surgical procedures such as wide excision, sentinel lymph node biopsy, and completion lymph node dissection, and medications such as chemotherapies and immune therapies for stage II, III, and IV melanomas.
The preferred treatment starts with excision, in which the surgeon numbs the skin, then cuts out the skin cancer and a section of surrounding skin that looks normal. Most excisions are performed in a physician’s office. Specimens of the tumor are sent to a dermatopathologist for analysis.
In addition to surgery to treat melanomas, we offer immunotherapy, radiation therapy, and systemic chemotherapy therapy. Immunology uses the patient’s own immune system to fight the cancer. The patient applies a cream (its generic name is Imiquimod) to the skin as directed. Radiation therapy works by gradually destroying the cancer cells through repeated exposure to radiation. A patient may receive 15 to 30 treatments. Systemic chemotherapy goes throughout the body to cancer that spreads beyond the skin to kill the cancer cells. This medicine, containing a mix of chemicals, can be swallowed, taken by injection, or intravenously infused. As the medicine travels through the body, it kills the cancer cells. Because it also destroys some normal cells, a patient can experience side effects, such as vomiting and hair loss. When the chemotherapy stops, the side effects usually do.
Surgical Procedures to Treat Melanoma
- Wide Excision: A surgical procedure to remove the cancerous tissue plus a margin of healthy skin surrounding it, which may require skin grafting. The size of the wide excision depends on the depth of invasion seen on the initial narrow biopsy.
- Sentinel Lymph Node Biopsy (SLNB): A surgical procedure to determine if the initial lymph nodes draining from the primary melanoma have cancer cells within them. This procedure helps with staging and is of prognostic value. It is often performed along with the wide excision. The decision to perform this procedure is determined on a case-by-case basis.
- Completion Lymph Node Dissection: A surgical procedure to consider if the sentinel lymph node is involved.
Medications to Treat Melanoma
To Treat Deep Stage II and Stage III Melanoma
- High Dose Interferon Alpha-2b: This is administered intravenously five days a week for four weeks and then as an injection into subcutaneous tissue three times a week for 11 months.
- Pegylated Interferon: These are weekly injections for five years. Approved only for stage III melanomas, interferon alpha was studied in several large studies and more consistently delays the time to relapse by approximately one year.
To Treat Stage IV Melanoma
- Dacarbazine (DTIC): A chemotherapy administered by vein often once every three weeks. It acts by modifying and damaging the DNA. The response rate to treatment with DTIC is under 20 percent. There is no proven overall survival benefit to this treatment.
- High Dose Interleukin-2 (HD-IL2): An immune treatment that activates T-cells to help the immune system fight the melanoma. Patients are admitted to the hospital for this treatment. Side effects can be significant and need intensive monitoring. The response rate is 16 percent, but approximately five percent of patients develop complete durable responses.
- Ipilimumab (Yervoy): An antibody that binds to a protein called CTLA-4, which is present on certain types of immune cells. This treatment is administered by vein once every three weeks for four treatments. It works by letting your immune system attack the melanoma. This treatment has the potential to create very durable responses, and treatment has overall survival benefits.
To understand how this treatment works, consider what happens to your immune system when you develop an infection. Your immune system is activated to fight the infection. Once the infection is treated, the immune system then starts to shut itself off. In order to do this, a type of immune cell called the suppressor T-cell, which suppresses the immune system, starts to express on its surface CTLA-4, which then binds to proteins such as B7 found on other immune cells to suppress their activity. Ipilimumab binds to CTLA-4 and prevents CTLA-4 from doing its job as it can no longer bind effectively to other proteins such as B7. As such, the immune system is not suppressed and remains active.
- Vemurafenib (Zelboraf): A targeted therapy administered orally two times a day every day. It blocks a protein called BRAF, which is mutated and activated in approximately 50 percent of melanomas. BRAF is part of a signaling pathway called the Mitogen Activated Protein Kinase (MAPK) pathway. When the MAPK pathway is activated, cells are better able to divide and stay alive. In melanoma, over 90 percent of activating mutations in BRAF occur at portion 600 of the protein, and the most common mutation is called a V600E BRAF mutation. Such mutations are seen in the majority of melanomas that arise on skin surfaces that are only intermittently exposed to the sun (such as the chest and back) but still can be detected with lower incidence in melanomas arising on chronic sun-exposed skin (head and neck), mucosal surfaces, and the palms, soles, and finger nails.
The response rate to treatment with vemurafenib in patients whose melanoma expresses a V600E BRAF mutation is approximately 50 percent, and a significant overall survival benefit is seen with this treatment. These benefits are not seen in melanomas lacking mutations in BRAF.