All About Melanoma
What is a melanocyte?
A melanocyte is a normal cell found in the skin that produces melanin. Melanin is a black or dark brown pigment that is seen in the skin, hair, and parts of the eye. Melanin is transferred from the melanocytes into nearby skin and hair cells. The concentrated areas of color seen on the skin are known as moles or nevi.
What is melanoma?
Melanoma is a type of cancer that forms from melanocytes. Even though melanoma accounts for only about 1% of all skin cancers, it is the most serious form of skin cancer. Other common types of skin cancer include basal cell carcinoma and squamous cell carcinoma.
Melanoma can occur any place that melanocytes reside. The majority of melanocytes reside in the skin; therefore, the majority of melanomas are found on the surface of the skin, which includes nail beds, soles of the feet, and scalp. However, melanoma can also occur in the eye ("uveal melanoma") or on internal mucosal surfaces, which include the mucous membranes lining the sinuses, the anal canal, rectum, and vagina.
The four most common subtypes of melanoma are:
- Superficial spreading melanoma.
- Nodular melanoma.
- Lentigo maligna melanoma.
- Acral lentiginous melanoma.
What causes melanoma and am I at risk?
Each year about 96,480 new cases of melanoma will be diagnosed in the United States. The number of new cases of melanoma has steadily increased for the last 30 years.
The single most important risk factor for melanoma is exposure to ultraviolet radiation from the sun. Other risk factors for cutaneous melanoma include fair skin or complexion, a history of peeling sunburns, prolonged exposure to ultraviolet light (both sun and artificial UV light, such as tanning beds), multiple moles, older age, a personal or family history of non-melanoma skin cancer, and a personal or family history of melanoma. As we age, our years of sun exposure increase, and therefore the risk of melanoma increases.
If you have been diagnosed with melanoma, it is important to share this information with your relatives so that they can undergo appropriate screening. While most melanomas do not arise from moles, certain types of moles, called dysplastic nevi, are associated with an increased risk for melanoma. Dysplastic nevi are moles that are typically large (>5mm in diameter), have uneven pigmentation, and irregular borders. A single dysplastic nevi is associated with a 2-fold increased risk, while 10 or more nevi indicate a 12- fold increased risk of developing melanoma.
People with fair skin and light eyes, or those who have a tendency to freckle or burn easily are all at higher risk. The melanin in dark-skinned individuals has been found to have a natural sun protection factor (SPF) and can filter twice as much ultraviolet light as that of a light-skinned individual. This protection, however, is not complete, and melanoma can develop in dark-skinned people. Melanoma is more commonly found on soles, palms, or nail beds in dark-skinned people.
A history of 3 or more sunburns, particularly blistering sunburns, before age 20, greatly increases risk. A history of severe sunburns in childhood and adolescence may actually double the risk of melanoma in adulthood. For many years, the tanning industry has promoted tanning salons as a safe alternative to natural sun, saying that these devices prevent sunburn; however, artificial UV light has clearly been linked with an increased risk of melanoma and other types of skin cancer. In fact, women under 35 who have ever used a tanning bed are 50% more likely to develop melanoma than women who never used a tanning bed. The bottom line is that tanned skin, whether from a tanning bed or sunlight, is not healthy and actually indicates that the skin has been damaged.
How can I prevent melanoma?
The best way to prevent melanoma is to protect the skin from exposure to ultraviolet light, which includes natural UV light from the sun and artificial UV light from tanning devices.
Some ways to protect your skin from UV light include:
- Do not use tanning salons or expose your self to other artificial sources of UV light.
- Avoid sun exposure between 10am and 4pm.
- Seek the shade when outdoors.
- Wear protective clothing, including long sleeved shirts, pants, a hat, and sunglasses. You may choose to wear clothing that has built in sun protection factor (SPF).
- Use sunscreen with a sun protection factor (SPF) of 15 or greater everyday, even in the winter! Sunscreen use is especially important for children because sunburns during childhood greatly increase the risk of melanoma in adulthood. Consistent use of sunscreen has even shown the ability to reduce further skin damage in people with a history of extensive sun exposure.
- You should examine your own skin regularly, approximately once a month. Be aware of the shapes and coloring of any moles you have. Melanoma may develop from an existing mole, causing its appearance to change. Examine your skin routinely in a mirror, including your back, bottom of your feet, nail beds, and scalp. Look for changes in existing moles, or the development of new ones.
Concerning moles are ones that have the "ABCDE" characteristics. You should bring any mole with these features to the attention of your health care provider.
- Asymmetry: Asymmetry refers to the shape of a mole. If an asymmetric mole were divided in half, one side would not look like the other.
- Border irregularity: The border of the mole is the edges of the mole. These should be sharp or well-defined. An irregular border may appear blurry and uneven.
- Color: Most moles have an even color. Moles with multiple colors within them or moles whose color has changed can be a concern, particularly those that become darker.
- Diameter: Most moles are relatively small. Any mole that is larger than the diameter of a pencil eraser (approximately 6 mm in diameter) may be a concern.
- Evolution: Moles don't change very much overtime. A mole that has changed in appearance, color, shape, or elevation over time may be a concern and requires additional evaluation
These rules are not set in stone, which is why you should be aware of your own moles, and report any changes in moles to a provider.
What screening tests are available?
There are not specific guidelines regarding the early detection of melanoma, however, a self skin exam is certainly a way to monitor any changes in your skin that should be reported to a provider. Your healthcare provider should examine your skin during routine physicals, but you should also examine your skin routinely at home. Because you see your skin everyday, you are most likely to notice any changes early on. You should look at every part of your body including your hands, back, soles of your feet and scalp. You can use a mirror to help with this. The prognosis for melanoma is best when lesions are found early, making skin examination very important.
What are the signs of melanoma?
Melanoma often presents as an irregular mole on the surface of the skin, with the "ABCDE" characteristics described above. This can be a preexisting mole that has changed or a newly developed mole. However, many melanomas do not possess these features, so any changes in your skin should be brought to the attention of your health care provider. Additionally, more advanced lesions may have inflammation, oozing, crusting, itching, ulceration or bleeding. Sometimes, specialized photography can be utilized to help monitor a person's skin; these pictures can make it easier for both the patient and the health care provider to detect any changes in moles. This can also cut down on unnecessary biopsies by showing stability of moles over time.
Unfortunately, some patients with melanoma do not present with an abnormal skin lesion and the first signs and symptoms of the disease result from metastatic spread to other organs.
How is melanoma diagnosed?
When melanoma is suspected, a biopsy should be performed. The type of biopsy done will be determined by your provider and depends on where the lesion is and the size of the lesion. Some of the types of biopsies are:
- Shave biopsy: the top layers of the lesion are removed using a blade.
- Punch biopsy: a tool is pressed into the lesion to remove a deep sample of the skin.
- Excisional biopsy: removal of the entire lesion and often a small portion of normal tissue around it.
- Incisional biopsy: removal of part of the lesion.
Melanoma can also arise in the mucosal surfaces, known as mucosal melanoma (i.e. sinuses, gastrointestinal tract, urinary tract and vagina) and in the eye, known as ocular or choroidal melanoma. The type of biopsy done for these types of melanomas will be determined by your provider.
Research is being done into reflectance confocal microscopy, also called an optical biopsy because you can look at the deeper parts of the skin, which prevents the need for cutting the skin. Another is adhesive patch testing. A patch is placed on the lesion and when it is removed it takes off some of the top layers of the skin for testing.
After the initial biopsy is performed, a pathology report is issued by the dermatopathologist. This pathology report further describes numerous aspects of the melanoma, which help determine the overall prognosis, many of which are highly technical and outside the scope of this article. The most important aspects of the pathology report are the depth of the melanoma, whether or not ulceration is present, and the mitotic count in thin melanomas.
The depth of the melanoma is often referred to as the Breslow depth or thickness. It describes the vertical depth of the melanoma in millimeters. Other measurements that may be included on the pathology report are the Clark's level, which describes the layer of skin involved with melanoma, and the diameter of the melanoma; neither of these measurements impact the staging of melanoma. Be careful not to confuse Clark's level with the stage of melanoma.
After evaluating the features of the primary melanoma, which are reported on the pathology report, a second surgical procedure, called a wide local excision, is typically performed. At the same time, evaluation of the local lymph nodes, through a sentinel lymph node biopsy may also be performed.
How is melanoma staged?
The staging of a cancer describes how much the cancer has grown and invaded the area, explaining the extent of disease.In order to guide treatment and offer some insight into prognosis, melanoma is staged into four different groups:
- Melanoma in-situ: the melanoma is present only in the epidermis; a Breslow thickness and Clark's level are not determined for this early stage lesion.
- Stage I and II: confined to skin.
- Stage III: spread to local lymph nodes or to the area surrounding the original skin site ("satellite" deposits of melanoma around the original site or "intransit metastases" between the original site and the regional lymph nodes).
- Stage IV: distant metastasis present (most commonly liver, lung, and brain).
Healthcare providers also use the TNM system (also called tumor - node - metastasis system). This system describes the size and locally invasiveness of the tumor (T), which, if any, lymph nodes are involved (N), and if it has spread to other more distant areas of the body (M). This is then interpreted as a stage somewhere from I (one) denoting more limited disease to IV (four) denoting more advanced disease. You may be given a Breslow Depth or Clark Level measurement. These measurements describe the depth of the lesion.
The staging system is very complex, and the entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for a patient's cancer. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed.
How is melanoma treated?
Surgery is the mainstay of curative treatment for melanoma. After melanoma is diagnosed by a biopsy, the next step is to have a "wide local excision.” This surgical procedure removes an area of normal tissue around where the lesion was located. The amount of tissue removed is based on the depth of the melanoma. "Margins" refer to the tissue around a tumor, in this case melanoma. "Negative margins" mean a small amount of normal tissue around the entire tumor was also removed—this ensures the entire melanoma is removed. "Positive margins," on the other hand, indicate that melanoma extends all the way to the edge of the tissue removed, and that it is possible some melanoma may not have been removed. The planned surgical margin depends primarily on the Breslow depth, and generally ranges from 0.5 to 2cm.
Depending on the stage of your melanoma, the depth of the lesion, and your risk of recurrence, it may be suggested that you have a sentinel lymph node biopsy. In a sentinel lymph node biopsy, a blue dye with a radioactive tracer is injected into the site of the original tumor. The dye spreads to the "sentinel node(s)" (the first few nodes to which the cancer would spread). These blue / radioactive lymph nodes are removed, examined under a microscope and tested for cancer. If any of these lymph nodes are positive, the remaining lymph nodes in the region are removed, using a procedure known as a lymph node dissection or lymphadenectomy. If the sentinel nodes do not contain melanoma, a lymph node dissection can be avoided and potential complications eliminated.
A second type of surgery that is more frequently being used is called the MOHS procedure. The MOHS procedure is a surgical procedure in which the melanoma is removed by a surgeon and the margins are checked under a microscope to check for cancerous cells. If there are cancerous cells remaining the surgeon will remove more tissue and visualize it again under a microscope. The surgeon will continue to do this until the margins are clear. This allows for the removal of all cancer cells while sparing normal tissue.
If melanoma returns, surgery can often be used to remove the sites of recurrent disease. Additionally, surgery can be utilized in advanced melanoma to manage symptoms associated with a particular tumor.
Some of the medications used to treat this cancer are considered immunotherapy agents, meaning that they work by stimulating the patient's own immune system, causing it to attack the cancer cells. The medications target specific proteins found on some cancer cells. These include:
As more is learned about the development of melanoma, molecular targets within melanoma cells are being discovered and new therapies are developed to attack these targets. BRAF is a protein kinase that plays a role in regulating the pathways responsible for cell replication and survival. In approximately 50% of melanomas, this protein is altered or mutated. There are therapies that target mutated BRAF and can be utilized in patients with melanoma containing a specific BRAF mutation. These medications only work in melanoma that has a mutated form of BRAF. Testing is performed prior to starting therapy to assure that the therapy is appropriate for the patient. To test for mutated BRAF, a sample of the tumor is sent to a special laboratory that performs the test. BRAF inhibitors that can be used to treat melanoma include vemurafenib, dabrafenib, and encorafenib.
There are two medications available that target cells with c-KIT changes. These melanomas are commonly found on the palms of the hands, soles of the feet, under the nails, inside the mouth, mucosal areas, or in areas that get chronic sun exposure. Imatinib and nilotinib are used to treat these melanomas.
There are a number of targeted therapies currently being studied in clinical trials for the treatment of various mutations. Some of these other mutations are NRAS and GNAQ.
Another type of targeted therapy that is used to treat melanoma is called oncolytic virus therapy. Talimogene laherparepvec is a medication that works as a virus therapy used to infect and break down cancer cells. The medication is directly injected into the cancerous lesion or lymph node.
Chemotherapy is the use of medications that travel to all tissues throughout the body to kill any cancerous cells. These therapies have an effect on melanoma that can be seen on imaging studies, as well as melanoma cells that cannot be seen. Chemotherapy agents commonly used in melanoma treatment include: dacarbazine, carboplatin, temozolomide, and paclitaxel.
Isolated Limb Perfusion/Infusion
Another option for patients with multiple melanoma tumors confined to one limb is isolated limb perfusion (ILP) or isolated limb infusion (ILI). These procedures involve temporarily interrupting circulation to the affected limb and administering high doses of chemotherapy (such as melphalan) to the limb, along with heat. These procedures must be performed under anesthesia in the operating room. They are associated with local side effects, but have limited toxicity to the rest of the body. This is usually reserved for melanoma that is isolated to a single limb and is not amenable to surgical resection. Response rates ILP/ILI are variable. Some studies have shown a benefit to overall survival in those patients who respond completely (no residual disease) to ILP.
Radiation therapy uses high energy x-rays to kill cancer cells and is a localized treatment, meaning it only affects the tissues directly treated with radiation. Radiation is not routinely used to treat all cases of melanoma. It can be used in some cases where there is a high likelihood of recurrence or metastasis to the brain or other solid organs.
Stereotactic radiosurgery (SRS, Gammaknife, Cyberknife) is a highly precise form of radiation therapy that is used to treat metastases. Stereotactic radiotherapy delivers radiation from many different angles to focus the radiation at one small point, like a magnifying glass. It is generally given in 1-5 treatments, unlike traditional radiation, which is given daily, over a period of weeks.
Clinical trials play a pivotal role in the treatment of melanoma. There are many new therapies being evaluated in clinical trials for use in various stages of melanoma. Clinical trials provide patients access to these new and exciting therapies. In addition to testing new treatment options for patients, clinical trials also can provide access to the use of new combinations of existing therapies, not previously used together. Current clinical trials may include: the identification of new targets for melanoma treatment, targeted therapies that work on newly discovered targets in melanoma, vaccines (which can be made from the patient's own tumor cells or parts of melanoma cells), new combinations of chemotherapy and immunotherapy, and new surgical techniques.
New medications and techniques are continually being tested to find more effective therapies for this disease. It is crucial that patients with a diagnosis of stage III or IV melanoma be treated by a melanoma specialist who is well-versed in current treatments, available clinical trials, and works with an interdisciplinary team (radiation, surgery, supportive care services) to manage patients with all available treatments. Patients with Stage IV disease will require regular clinical, laboratory and imaging evaluations to monitor their disease and response to treatment.
You can learn more about ongoing clinical trials and find those that may be right for you using the OncoLink Clinical Trials Matching Service.
Follow-up Care and Survivorship
After a diagnosis of melanoma, patients remain at risk for the development of a new melanoma or non-melanoma skin cancer and for a recurrence of the previously diagnosed melanoma. Having one melanoma in a patient's lifetime places him/her at higher risk for developing a second melanoma and follow up with a dermatologist is a mainstay of on-going treatment, with a complete skin exam at least once a year. All patients require ongoing follow up with their dermatologist and depending on the stage of the original melanoma, may require ongoing monitoring by their surgeons and medical oncologists.
For most patients diagnosed with stage I and II melanoma, follow up will consist of clinical full body skin examinations with a dermatologist every 6-12 months for 5 years and then annually. Routine blood and radiology tests are not recommended for stages I-II, but should be performed to investigate any concerning symptoms.
For patients with Stage III-IV melanoma, a clinical full body skin examination should be performed every 3-6 months for 2 years, every 3-12 months for 3 years and then annually. In addition to examination of the skin, the lymph nodes should also be examined. Radiology testing may be done to routinely monitor for recurrence or if you have any new symptoms of recurrence. This testing may include ultrasound, CT scans, or MRI.
In addition to clinical total body skin exams, all patients should perform self skin examinations about once a month, checking for any new or changing skin lesions, looking for the ABCDEs of melanoma risk, and looking for any new lumps or bumps in the area of the prior melanoma. Individuals diagnosed with a melanoma should practice safe sun habits to minimize their risk for developing a second melanoma or non-melanoma skin cancer.
Melanoma survivors should report any of the following to your healthcare providers:
- Changes in existing moles.
- New moles.
- Changes in the scar from the previous surgery, including any changes in color, nodularity (lumps), or swelling around the site.
- Swelling in the limb where the original melanoma was.
- Yellowing of the skin or eyes.
- New or worsening shortness of breath or cough.
- Neurologic symptoms including headache, vision changes, nausea.
- Unexplained weight loss.
Fear of recurrence, financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by melanoma survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.
Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.
This article is meant to give you a better understanding of melanoma. Use this knowledge when meeting with your healthcare providers, making treatment decisions, and continuing your search for information.
Resources for more information:
Skin Cancer Foundation
Strive to education the public and medical professionals about the dangers of skin cancer, prevention methods and sun protection. Provides information on skin cancer and treatment.
Melanoma Research Foundation
Committed to the support of medical research in finding effective treatments, the MRF also educates patients about the prevention, diagnosis and treatment of melanoma. Provides a web based support community as well.
Melanoma International Foundation
Help patients and caregivers understand pathology reports, prognosis, and therapy options, including clinical trials, as well as where to get the best possible care.
National Institute of Health Medline Plus
The United States medical research agency. Provides information on treatment and research. Includes Spanish language resources as well. http://www.nlm.nih.gov/medlineplus/melanoma.html
Appendix: Complete Melanoma Cancer Staging
American Joint Committee on Cancer
Primary Tumor (T)
Primary tumor cannot be assessed
No evidence of primary tumor
Melanoma in situ
Melanaomas 1.0 mm or less in thickness
Melanomas 1.01 – 2.0 mm
Melanomas 2.01 – 4.0 mm
Melanomas more than 4.0 mm
less than or equal to 1.0
a: less than 0.8 and without ulceration
b: less than 0.8 with ulceration or 0.8-1.0 with or without ulceration
1.00 – 2.0
a: w/o ulceration
b: with ulceration
2.00 - 4
a: w/o ulceration
b: with ulceration
Greater than 4
a: w/o ulceration
b: with ulceration
Regional Lymph Nodes (N)
Patients in whom the regional lymph nodes cannot be assessed
No regional metastases detected
Regional metastases based upon the number of metastatic nodes and presence or absence of intralymphatic metastases
Number of metastatic nodes
a. One clinically occult
b. One clinically detected
c. No regional lymph node disease
a. Two or three clinically occult
b. Two or three, at least one of which was clinically detected
c. One clinically occult or clinically detected
4 or more metastatic nodes, or matted nodes, or in transit met(s)/satellite(s) with metastatic nodes
a. Four or more clinically occult
b. Four or more, at least one of which was clinically detected, or presence of any number of matted nodes.
c. Two or more clinically detected and/pr presence of any number of matted nodes.
Distant Metastasis (M)
No detectable evidence of distant metastases
Metastases to skin, subcutaneous, or distant lymph nodes
Metastases to lung
Metastases to all other visceral sites or distant metastases to any site combined with an elevated serum LDH
Distant metastasis to CNS with or without M1a, M1b, or M1c sites of disease
Any T, Tis
Greater than or equal to N1
T1a/b, T2a/b, T3a
Any T, Tis
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