Melanoma is a form of cancer that begins in melanocytes in the skin (or mucosa). Melanocytes produce the pigment melanin that darkens the skin, hair and eyes when exposed to the sun to protect deeper layers of the skin from sun damage.

Melanoma Cancer Statistics 

Melanoma accounts for approximately 2% of all skin cancers. The American Cancer Society estimates that approximately 73,870 new cases of melanoma will be diagnosed in 2015 and nearly 10,000 deaths. The incidence rate of melanoma is increasing. The lifetime melanoma risk is 1 in 40 Caucasians, 1 in 1,000 blacks and 1 in 200 Hispanics.

What causes Melanoma Cancer? 

Exposure to ultraviolet (UV) light:

Nearly 90% of melanoma can be related to exposure to natural sources of UV light (sunlight) as well as unnatural sources, such as tanning beds.  However, sun exposure/UV light is not the only risk factor, especially for mucosal and uveal melanoma. People with fair skin, blonde or red hair, or blue or green eyes have greater risk of developing melanoma.

Weakened immune system:

People with weakened immune system, such as organ transplant recipients who are on immune suppressive therapy, may have increased risk of melanoma.

Additional risk factors? 

Include having a large number of moles or dysplastic nevi, a family history (one or more first-degree relatives) or personal history of melanoma, as well as some inherited conditions such as xeroderma pigmentosum (XP) with impaired ability to repair UV damage, are at increased risk of developing melanoma.

 

What are early symptoms of Melanoma Cancer? 

Signs of melanoma include change in size, shape or color of an existing mole, or a new spot on the skin (ABCDE rule):

• A - Asymmetry: A mole that has an irregular shape.
• B - Border: Melanoma lesions usually has irregular, blurred, or notched edges.
• C - Color: Uneven distribution of color or more than one color throughout the mole can be a sign of melanoma.
• D - Diameter: Moles larger than 6 mm, the size of a pencil eraser across, although smaller lesions can be melanoma.
• E - Evolution: The dynamic change in size, color and shape is the most important factor.

Other melanoma symptoms may include sores that do not heal, pigment, redness or swelling, itchiness, tenderness or pain, oozing or bleeding from an existing mole.

How does my doctor know I have Melanoma Cancer? 

Early detection is critical as advanced melanoma is very hard to treat. A thorough self-skin examination each month and visiting a dermatologist each year for a professional examination is recommended. It is important to examine all areas, including the toes, nail beds, palms and soles, genitals and even the eyes. If there is any suspicious lesion, a biopsy is the first step to diagnosis. Biopsy is to remove tissue from the skin and examined under a microscope by a specialist. If melanoma is determined in the biopsy and certain high-risk feathers were found, surrounding lymph nodes might be evaluated to determine whether any cells have traveled beyond the initial site. In addition, imaging studies with CT, MRI or PET CT will be utilized to determine whether there are any distant metastases. The extent of lymph node involvement and several other factors will help determine the stage of diagnosis.

What does Classification and Staging of my Lymphoma Cancer mean? 

There are three types of melanoma, cutaneous, mucosal and ocular melanoma. 

Cutaneous melanoma is the most common because most melanocytes are found in the skin, especially in areas exposed to the sun. Cutaneous melanoma can be further divided into superficial spreading, nodular, acral lentiginous and lentigo Maligna melanoma. People who have darker skin have lower risk of developing melanoma in the sun-exposed areas, but have similar risk for the development of melanoma on the palms and soles or under the nail beds.

Mucosal melanoma occurs in the mucous membrane of the body, such as the mouse, throat, sinuses, vagina and anus.

More rarely, melanomas can develop in the eyes, called ocular melanoma, or uveal or choroidal melanoma.

Melanoma that spreads to other parts of the body is called metastatic melanoma. It will usually spread first to the surrounding lymph nodes, and then to other organs such as the liver, lungs, bones or brain.

Recently, certain gene mutations that are found in melanomas help further define melanoma at the molecular level. In cutaneous melanoma, the BRAF mutation is the most common type of genetic mutation (approximately 50% of cases), followed by NRAS mutation (approximately 20% of cases). In mucosal and acral melanoma, the most common mutation is the KIT mutation. Whereas in ocular melanoma, the most common mutations are in the GNAQ and GNA11 genes.

Size or thickness of the melanoma, whether or not it has spread to the lymph nodes or other organs, growth rate, ulceration determines the stage of melanoma.

The American Joint Commission on Cancer has developed the TNM staging system, composed of three key pieces of information:

• Tumor (T) describes features of the tumor, including how deep it grows into the skin (thickness, known as the Breslow measurement), rate of dividing (mitotic rate), and the presence or absence of ulceration.
• Node (N) describes whether or not melanoma has spread to nearby lymph nodes.
• Metastasis (M) describes whether the melanoma has spread to distant organs. The levels of LDH, a substance in the blood, is also a determination factor.

Clinical staging bases on information collected before surgery, including physical exam and imaging results. Pathologic staging combine the clinical information with pathological findings from the surgical or biopsy samples after the procedure, therefore is more accurate.

• Stage 0 melanoma means the cancer cells are confined to the top layer of the skin (epidermis).
• Stage I melanoma means the cancer cells have grown beyond epidermis, but have not spread to the lymph nodes or other parts of the body.
  • Stage IA: The cancer is less than 1 mm deep, does not appear ulcerated, nor dividing rapidly.
  • Stage IB: The cancer is either less than 1 mm deep but is ulcerated or dividing more rapidly, OR the cancer is between 1-2 mm deep without any sign of ulceration.
• Stage II melanoma means the cancer cells have grown deeper into the skin, or have more high-risk features, but have not spread to the lymph nodes or other parts of the body.
  • Stage IIA: The cancer cells have grown 1-2 mm deep into the skin, and the tumor appears ulcerated, OR the cancer is 2-4 mm deep but is not ulcerated.
  • Stage IIB: The cancer is 2-4 mm thick with ulceration, OR thicker than 4 mm but not ulcerated.
  • Stage IIC: The cancer is more than 4 mm thick, and it is ulcerated.
• Stage III melanoma means the melanoma cancer cells have spread to nearby lymph nodes, but not to distant organs.
• Stage IV melanoma means the cancer cells have spread beyond the skin and regional lymph nodes to distant organs such as the liver, lungs or brain, or distant lymph nodes and areas of the skin.

What are treatments for Melanoma Cancer? 

Surgery: For early stage of melanoma that has not spread to distant sites yet, a wide local excision to completely remove the cancer with a wide margin is usually performed.  In highly selected metastatic setting, complete resection of disseminated disease might improve the survival time of the patient. Whether a patient is a candidate for surgery or not depends on factors such as the type, size, location, grade and stage of the tumor, as well as general health factors such as age, physical fitness and other coexisting medical conditions the patient may have. Sometimes surgery can be done to relieve the discomfort that a patient might have.

Lymphatic mapping and sentinel lymph node biopsy: if the melanoma is equal to or more than 0.75 mm in thickness, or has high risk features (ulceration, high growth rate, or evidence of invasion into the lymphatic or vascular system), then the surgeon will inject a traceable dye into the tumor to determine which lymph node it drains to, and evaluate this lymph node for any evidence of tumor cells. If tumor cells are found in this lymph node, more extensive resection of the surrounding lymph nodes will be performed.

Radiation therapy: Radiation therapy is to use X-rays or radioactive substances to destroy cancer cells. It may be used alone or in combination with other treatments. It can be used before another treatment to reduce the size of a tumor (for example to make surgery feasible) or after another treatment to kill any remaining cancer cells.
Sometimes radiation therapy can be used to relieve the discomfort that a patient might have.

Chemotherapy: Cytotoxic chemotherapy is to use drugs designed to slow or stop the growth of rapidly dividing cancer cells in the body. Melanoma does not respond well to chemotherapy. Only up to one in five patients would respond to chemotherapy but no improved survival.

Immunotherapy: Melanoma is one of the few tumors types that can be eliminated by a strong immune system. Immunotherapy works by stimulating the patient’s own immune system to attack cancer cells. This can be accomplished by either helping the immune system to recognize the tumor, or by taking away the inhibitory signals that prevent the immune system from attacking the tumor. In the past several years, significant advances has been made and several classes of immunotherapy drugs were approved to treat advanced melanoma, including checkpoint inhibitors (inhibit brakes of the immune system) such as ipilimumab (anti-CTLA4), pembrolizumab and nivolumab (anti-PD1), and talimogene laherparepvec (T-VEC, a genetically engineered herpes simplex virus that can specifically kill the tumor cells and activate the immune system). Sustained control of the tumor growth and prolonged patient survival has been observed with these immunotherapy agents. Many other drugs that modulate the immune system are in clinical testing (clinical trials) to treat melanoma and other types of cancer. One common side effect of immunotherapy is autoimmunity against the patient’s normal organs, such as the thyroid, pituitary glands, skin, guts, lungs, etc., therefore, close monitoring of the patients while on treatment is very important.

Targeted therapy: Genetic mutations are common in melanoma. Some of these gene mutations are key contributors to make a melanoma cell cancerous, and we have drugs that can target these mutations. For example, for patients whose tumor has BRAF gene mutation (approximately 50% of cutaneous melanoma), BRAF inhibitors vemurafenib and dabrafenib can block the growth and spread of cancer by preventing cancer cells from dividing or destroying them directly. Majority of patients with BRAF mutation positive melanoma would benefit from this treatment; however, the cancer can become resistant to this therapy quickly. In addition, patients receiving BRAF inhibitor treatment can develop another form of skin cancer called cutaneous squamous cell carcinoma. Fortunately his type of skin cancer rarely spreads to other parts of the body and can be treated with surgical resection. Combining BRAF inhibitors with another targeted therapy call MEK inhibitors (trametinib or cobimetinib) can help eliminate this side effect of cutaneous squamous cell carcinoma, and further control the tumor growth and spread.

The optimal treatment of melanoma in each individual patient depends on many factors including the cancer stage, the subtype of cancer, BRAF mutation status, the location of cancer, patient’s age, patient’s general health status, and patient’s preferences. Surgery and radiation therapy are types of local treatment because the goal of these therapies (in stage 0-III) is to remove the tumor and prevent the tumor from recurring. Systemic treatment such as immunotherapy, targeted therapy and rarely chemotherapy, are medicine that goes throughout the body to try to kill any cancer cells that have spread from the original site. For patients whose cancer has not spread to distant sites but do have high risk factors for cancer recurrence, such as positive lymph nodes or surgical margins, or deep tumors, adjuvant treatment can help eliminate the residual tumor cells after surgery is completed. The FDA approved drugs that can be used in this situation for melanoma are interferon and ipilimumab (anti-CTLA4).