Melanoma

Symptoms, Doctors, Treatments, Advances & More

Melanoma is the most serious type of skin cancer and develops in cells (melanocytes) that make the pigment (melanin) for skin color.  Melanoma is characterized by an irregularly-shaped skin growth that can be a variety of colors, such as white, pink, red, brown, black, or blue, can develop from an existing mole that becomes cancerous, or can appear as a separate skin growth.  There are three subtypes of melanoma: 1) acral lentiginous melanoma, 2) juvenile melanoma, and 3) malignant lentigo melanoma. While melanoma more frequently appears on skin (cutaneous melanoma) that is occasionally exposed to the sun, this cancer can also appear in other areas of the body that have little or no exposure to the sun (acral lentiginious melanoma), such as the scalp, palms, genitals, toes, and soles of the feet (hidden melanoma). More rarely, melanoma can also form in the eyes (ocular melanoma) or inside the nose or throat. While melanoma can appear at any age, it occurs more frequently in older people between the ages of 50 and 70 (malignant lentigo melanoma); however, the rates of melanoma have been increasing over the last thirty years, as well as appearing more frequently in young adults. Juvenile melanoma can be either a cancerous or non-cancerous form of melanoma and usually occurs before puberty. Melanoma tumors are more commonly found on the back in men and on the legs in women. While melanoma more commonly affects the outer layer of skin (epidermis), as the cancer grows, involving more layers of skin, it can also spread to other parts of the body (metastasize). Melanoma is classified by the following stages: Stage 0 (Melanoma in situ) – In this stage of melanoma, abnormal cells that produce melanin (melanocytes) are present in the outer layer of the skin (epidermis) and may become cancerous and spread (metastasize). Stage I (IA & IB) – In this stage of melanoma, the tumor is no larger than 1 millimeter thick, with or without a break in the skin (IA), or the tumor is more than 1, but not more than 2, millimeters thick, without a break in the skin (IB). Stage II (IIA, IIB, & IIC) – In this stage of melanoma, the tumor is no larger than 1, but not more than 2, millimeters thick, with a break in the skin, or the tumor is more than 2, but not more than 4, millimeters thick, without a break in the skin (IIA), or the tumor is more than 2, but not more than 4, millimeters thick, without a break in the skin (IIB), or the tumor is more than 4 millimeters thick, with a break in the skin (IIC). Stage III (IIIA, IIIB, IIIC, & IIID) - In this stage of melanoma, the tumor is not larger than 1 millimeter thick, with a break in the skin, or not larger than 2 millimeters, without a break in the skin, and the cancer has spread to multiple lymph nodes, or it is unknown where the primary cancer began, or the cancer is found in 1 lymph node, and there is tumor spread (metastases) on or under the skin, or the tumor is no larger than 1 millimeter thick, with a break in the skin, or not larger than 2 millimeters thick, without a break in the skin, and one of the following has also been found: 1) the cancer has spread to 1-to-3 lymph nodes, or there are microscopic tumors or tumor spread (metastasis) on or under the skin, or the tumor is larger than 1, but not more than 2, millimeters thick, with a break in the skin, or larger than 2, but not more than 4, millimeters thick, without a break in the skin. Stage IV – In this stage melanoma, the cancer has spread (metastasized) to other parts of the body, such as distant lymph nodes, soft tissue, muscle, the brain, spinal cord, lung, liver, gastrointestinal tract, and bone, and the cancer may have spread far from the primary tumor.

There are several alternative names for melanoma, including acral lentiginous melanoma, cutaneous melanoma, hidden melanoma, juvenile melanoma, malignant lentigo melanoma, melanoblastoma, melanocarcinoma, melanotic carcinoma, melanoscirrhus, melanoepithelioma, melanosarcoma, nevus pigmentosa, and ocular melanoma.

While the exact cause of melanoma is unknown, researchers believe this cancer may have a genetic component as the gene CDK4 has been associated with an increased risk of developing melanoma. In individuals with a genetic predisposition for melanoma, the risk of transmitting the disorder to their children is 50%. In addition to a genetic predisposition, the environmental factor of excessive sun exposure, especially before puberty, as well as living in equatorial or tropical climates or high altitudes, increases the risk of developing melanoma. Additional risk factors for developing melanoma include being of European descent, Caucasian, having blue or green eyes and fair skin, red or blonde hair, or skin that freckles and burns easily, having several blistering sunburns as a child or teenager, or being an individual who does not tan or barely tans. Individuals with more than 25 moles or atypical moles, or who have genetic skin disorders, such as xeroderma pigmentosum, or who have a family history of melanoma, and individuals with a weakened immune system also have an increased risk of developing melanoma. Additional environmental factors that increase the risk of developing melanoma include the use of artificial sunlight (UV radiation; tanning lamps and beds), exposure to radiation, solvents, vinyl chloride, and PCBs.

While early melanoma may not produce any symptoms, it may appear later as lesions on the face, arms, palms, fingernail beds, back, legs, or soles of feet that will not heal or occur as an existing mole that changes in size or color or has irregular edges or borders, is more than one color, is larger than ¼ inch, grows in size or changes shape, is asymmetrical, itches, oozes, bleeds, or is ulcerated, or as new moles appearing near existing moles.

Treatments for melanoma depend on the type and stage of the cancer; however, standard treatments for melanoma include surgery, chemotherapy, radiation therapy, immunotherapy, and targeted therapy. Surgery – Surgery is the primary treatment for melanoma and is focused on removing all of the tumor. A very small melanoma may be removed entirely by biopsy. If a wide area must be removed, then a skin graft may be necessary. In addition, the adjacent lymph nodes may be biopsied or removed (lymphadenectomy). If the melanoma has spread (metastasized) to other areas of the body, such as the brain, lung, or gastrointestinal tract, further surgery may be necessary.  Chemotherapy – Chemotherapy drugs kill cancer cells and can be used alone or in combination with other treatments and can be administered orally (pill), intravenously (IV), or directly into the area affected by melanoma. Chemotherapeutic agents used for melanoma include the drug, dacarbazine, which has been effective for temporary remission in some patients, and other high-dose alkylating chemotherapy drugs, such as carmustine, cisplatin, and cyclophosamide, which may be effective for malignant melanoma. Radiation therapy – Radiation therapy uses high-energy X-rays, protons, or other types of radiation to stop cancer cells from growing or to kill them. Radiation treatment for melanoma is usually administered by external radiation therapy that directs the radiation at the cancer either to kill the cancer cells or to help relieve symptoms. Immunotherapy (Biotherapy or biologics) – Immunotherapy helps the patient’s immune system to kill melanoma cells and includes immune checkpoint inhibitor therapy to help the body’s T cells kill the cancer cells in advanced or unresectable melanoma. There are two types of immune checkpoint inhibitor therapies used for melanoma: 1) the CTLA-4 inhibitor, ipilimumab; and 2)  the PD-1 inhibitors, pembrolizumab and nivolumab. Targeted therapy – Targeted therapy uses drugs to kill melanoma cells in advanced or unresectable melanoma and include signal transduction inhibitor therapy, such as the BRAF inhibitors, dabrafenib, encorafenib, and vermurafenib, and the MEK inhibitors, such as bininmetinib, cobimetinib, and trametinib. Combination therapy of BRAF and MEK inhibitors may also be used, such as dabrafenib plus trametinib, enorafenib plus binimetinib, and vemurafenib plus cobimetinib. An additional targeted therapy for melanoma is oncolytic virus therapy, such as talimogene laherparpvec, which is injected directly into the melanoma to stop cancer growth by using the immune system to kill it. A newer therapy that has been approved for metastatic melanoma is the drug aldesleukin (Proleukin), while the drug Intron-A (alpha interferon) has been approved for malignant melanoma that has also been treated with surgery.

There are several online, local, national, and international support groups for melanoma, including the following: The American Melanoma Foundation - https://melanomafoundation.org/ CancerCare - https://www.cancercare.org/support_groups/132-melanoma_patient_support_group Impact Melanoma - https://impactmelanoma.org/get-support-just-diagnosed/support-groups/

If you notice any unusual skin changes or note any lesion that becomes itchy, burns, softens or hardens, forms a scab, bleeds, or becomes reddened, changes color, size, or shape, make an appointment with your doctor as soon as possible.

Possible complications of melanoma include a recurrence of the cancer after it has been treated, the cancer may spread (metastasize) to other areas of the body, such as the brain, lung, or liver, scarring, swelling of the lymph nodes of the arms or legs (lymphoedema), pain, depression, and anxiety. Cancer treatment-related complications may also occur, for which treatment is an essential part of cancer care.

If you notice any unusual skin changes or note any lesion that becomes itchy, burns, softens or hardens, forms a scab, bleeds, or becomes reddened, changes color, size, or shape, make an appointment with your doctor as soon as possible.

It is possible to decrease the risk of developing melanoma by avoiding damaging the skin with sun or UV light exposure by avoiding outdoor and indoor tanning and protecting from the sun when outdoors by wearing a wide-brimmed hat, sunglasses, and protective clothing, staying in the shade, especially during mid-day, and using broad-spectrum sunscreen with SPF 15 or above. In addition, individuals previously diagnosed with melanoma have an increased risk (9 times the normal population) of melanoma recurrence, and therefore must have frequent follow-up visits to their doctor to continue surveillance for recurrence of the disease.