Melanoma is a growing global concern, with 300,000 new cases diagnosed worldwide in the year of 20201. It is the fifth most common cancer in the United States2 and is the deadliest of all skin cancers. Melanoma is caused by ultraviolet radiation (UV) damage to the DNA of melanocytes. Melanocytes are specialized cells3 that produce melanin, a substance that gives pigment to the skin and hair and protects the skin from UV4. The damaged DNA within melanocytes mutates and leads to unchecked cell division. Melanoma arises as a result of this aberrant cell behavior⁵.

Melanoma is most frequent in white populations, as the enrichment of melanin in darker-skinned individuals lends photoprotection1. People of color, however, have a higher mortality rate due to delays in detection or presentation that lead to diagnosis at later and more aggressive stages of cancer⁶.

The primary sign and symptom of melanoma is a skin lesion. The Skin Cancer Foundation created the ABCDE system to differentiate between a benign skin lesion and a melanoma tumor.

• A stands for asymmetry: if a line is drawn through the middle of the lesion, the two halves do not match.
• B stands for border: the lesion is uneven around the edges instead of round and smooth.
• C stands for color: the tumor has multiple colors instead of the uniform shade of brown found in a benign lesion.
• D stands for diameter: a lesion larger across than ¼ of an inch.
• E stands for evolving: a lesion that changes in size, shape, or color⁶.

Research is ongoing on secondary symptoms in melanoma patients, as most early-stage melanomas are asymptomatic; symptoms are associated with diagnostic and treatment methods. Sentinel lymph node biopsy is a surgical procedure that provides prognostic information for early-stage patients, though many patients who undergo it ultimately do not show evidence of disease in the sentinel node. A side effect of this biopsy is mild lymphedema: localized swelling due to fluid buildup in the lymphatic system. Worsened body image, especially in women, is associated with lymphedema7. Similar symptoms experienced in other cancers are reported in melanoma, including fatigue, sleep disturbances, cognitive problems, depression, and anxiety. Whether these issues stem from the cancer or its treatment remains unclear⁸.

There are four main subtypes of skin melanoma.

• Superficial spreading melanoma is associated with low amounts of sun damage and is typically found on the torso or extremities. It is the most common subtype of skin melanoma; a study of patients diagnosed between 1978 and 2007 found that it comprised about 60% of all cases, and this number has risen to 70% in 20229. SSM presents as an irregularly shaped and variably colored spot. This spot may bleed or show ulceration, which is a breakdown of the epidermis. SSM lesions tend to be thinner, or less penetrative into the skin, than in other subtypes¹⁰.
• Nodular melanoma presents as firm nodes on the skin and represents 20% of skin melanoma cases. This particular subtype requires rapid detection, as it is the subtype with the most aggressive tumors11. Prognosis for nodular melanoma is generally worse than that of SSM, as the lesions are thicker with deeper skin penetrance and ulceration is more common. Metastasis, or the spread of tumors to other sites within the body, is a significant predictor of prognosis; metastatic tumors are more frequent in nodular melanoma⁹.
• Lentigo maligna melanoma appears on chronically sun-exposed areas of the skin. LMM appears as a large patch on the skin with varying shades of tan, brown, or black as well as net-like black pigmentation throughout the patch. LMM tumors are rarely considered high risk in that they do not deeply invade the skin, but they show repeated recurrence despite thorough treatment. LMM represents between 3 and 10% of skin melanoma cases and is most commonly found in the middle-aged and the elderly¹².
• Acral lentiginous melanoma is the rarest of the four subtypes, representing less than 5% of cases. This subtype is the one most frequently found in those of Asian or African descent. Lesions present as pigmented spots on acral skin (e.g. the palms of the hands, the soles of the feet, and the nail beds). Patients, especially the elderly, often have difficulty examining their soles; lesions are also often mistaken for bruises, fungal infections, or hematomas. The resulting delay in diagnosis leads to a worse prognosis¹³.

Melanoma can also be found in other organ systems, including uveal (eye) and mucosal (gastrointestinal, vaginal, and anal) melanomas. These subtypes are rare and therapeutic understanding is ongoing¹⁴.

You and your healthcare provider can use a cardiac risk calculator to assess your risk of developing heart disease. There are many different cardiac risk calculators out there that should give you similar results. However, here are two reputable cardiac risk calculators¹⁶:

• The American College of Cardiology (ACC) Atherosclerotic Cardiovascular Disease (ASCVD) risk calculator – assesses the chance of developing heart disease over the next ten years for people ages 20 to 79.
  • Factors assessed: age, sex, race, blood pressure, cholesterol level, medical history, smoking status, and statin/aspirin therapy.
• Reynolds Risk Score predicts the risk of heart disease over the next ten years in people who do not have diabetes.
  • Factors assessed: age, sex, blood pressure, cholesterol level, family history, and high-sensitivity C-reactive protein (hsCRP) level.

You can calculate your cardiac risk using an online risk calculator at any time. All you need is your health history and recent lab results to fill out a brief questionnaire. However, these calculators are only helpful prior to having a heart event. If you have had a stroke, heart attack, or heart failure, you should not use a cardiac risk calculator.

The primary cause of melanoma is UV radiation, either through natural sun exposure or artificial UV lamps and tanning beds. The UV-mediated gene mutations that drive melanoma are usually found in the melanocortin 1 receptor (MC1R) gene¹⁵, which is expressed in melanocytes and is key for producing melanin. Inheritance is a less common cause, with family history present in only 5-10% of cases. Mutations in the genes cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase 4 (CDK4) are most commonly identified in families with hereditary melanoma¹⁶.

Race is the greatest predictor of melanoma. White individuals are the most susceptible, as the low melanin content in fair skin creates a lack of photoprotection against UV. Light eyes, light skin that does not tan, and blond or red hair present the highest risk¹⁷. In the United States, the incidence of melanoma was 24.6 in 100,000 cases for non-Hispanic whites. The second highest incidence was almost six times lesser with American Indian/Alaska Natives at 4.3, then Hispanics at 4.2, Asian/Pacific Islanders at 1.3, and African Americans at 1.018. Further risk factors include:

• Gender: melanoma is more common in men than in women.
• Age: the average age of diagnosis is 65; over two-thirds of diagnoses are in patients between ages 55 and 84².
• Individuals with weakened immune systems, referred to as immunocompromised, are more likely to develop melanoma¹⁹.
• People with an abundance of moles (benign melanocyte growths) are at higher risk².
• Poverty and scarce availability of medical care lead to higher risk, as the prognosis for melanoma worsens the farther it is able to progress⁶.
• Because UV exposure is the primary cause of melanoma, natural sun exposure and use of artificial tanning beds are both significant risks.
• Geography significantly impacts melanoma incidence, as the rate of melanoma within one racial group varies by location. Countries closest to the equator, where sun exposure is strongest, show the highest melanoma mortality rates¹⁸.

To reduce melanoma risk, limit sun exposure during peak hours of sunlight (late morning to mid-afternoon), wear protective clothing like brimmed hats and sunglasses, use sunscreen of at least SPF 15 with frequent reapplication, and avoid tanning salons²⁰.

Melanoma screening is neither practiced nor standardized worldwide. The United States does not generally recommend skin cancer screenings⁵. Europe has carried out the Euromelanoma public campaign for the last two decades, which aims to raise awareness of skin cancer prevention and promote regular screening. Criticism of the campaign points out that the mortality rates of cutaneous melanoma have not changed in the Euromelanoma initiative since 1975, which suggests that primary prevention efforts have been inadequate²¹. A different study of almost 600,000 patients found increased detection of thin melanoma tumors, though overdiagnosis of possibly benign lesions was a concern²².

Most high-risk melanomas can be detected visually by a physician or by patients themselves, as the tumors are usually highly pigmented and irregular in appearance. Patients can self-test at home using the “ugly duckling” rule (meaning a lesion that appears different from other lesions on the body) or with the ABCDE guideline described above.

A clinical melanoma screening comprises of a total body skin examination (TBSE). This examination is performed using the ABCDE guideline, and a patient’s entire body (including the scalp, between fingers and toes, and the genitals) are examined by a physician. Patients are usually asked to wear loose-fitting clothing that can be easily removed and to not wear makeup. In addition to evaluation by eye, a physician may use a dermoscope: a handheld optical device used to inspect skin lesions. Its light source removes obscuring skin surface reflections and its images can be stored with a digitization device⁵.

Some melanomas have a less stark appearance that may be missed in a typical screening. Though a decreased incidence of thicker tumors is associated with TBSE²³, thinner ones require more in-depth detection methods. Several other diagnostic tools are in use for melanoma:

Total body photography (TBP) captures the entire skin surface and allows for long-term monitoring of melanoma progression.

Sequential digital dermoscopic imaging (SDDI) is another method that sequentially captures images from a dermoscope for short or long-term observation, with a focus on lesions that are flat or otherwise lack a typical melanoma appearance.

Other microscopic techniques are currently in development, including apps to take images of skin lesions for sharing with physicians and computer-assisted diagnosis²³.

Diagnosis is further complicated in people of color, as 60-75% of tumors arise on areas of less pigmented skin such as the palms of the hands or the soles of the feet. This leads to tumors either going unnoticed or being misdiagnosed as dark nail, warts, or fungus. Many people of color also mistakenly believe that they are incapable of getting skin cancer. This, paired with a lack of access to medical resources among racial and ethnic minorities and in second and third world countries, leads to delayed diagnosis in people of color compared to white populations⁶.

A staging model establishes medical criteria to determine disease severity and progression; the higher the stage, the more severe the disease. Stage I and stage II melanoma are considered early in progression and usually have positive outcomes; stage III varies widely in prognosis, and stage IV is very poor. Melanoma staging is defined by the American Joint Committee on Cancer and is evaluated in patients using the TNM system.

T stands for tumor and assesses the primary melanoma tumor.

N stands for node and evaluates the movement, if any, of melanoma from its primary tumor to the lymph nodes.

M stands for metastasis and measures movement, if any, of melanoma to more distant parts of the body¹⁷.

A positron emission tomography (PET) scan has historically been used to detect metastasis in confirmed melanoma patients, as it is particularly sensitive in the liver, lymph nodes, and soft tissues²⁴. Current practice uses an improved version known as 18F-FDG PET that visualizes glucose uptake with a radioactive tracer and can identify tumors based on their increased glucose needs. Patients are requested to hydrate well, eat a high-protein low-carbohydrate diet for 24 hours prior to the scan, and fast for at least six hours before. This reduces sugars as close to baseline as possible and prevents competition in detection between glucose used for digestion and glucose used by the tumor. Patients are further requested not to exercise for 24 hours to reduce uptake of the tracer by skeletal muscles²⁵. After injection of the tracer, patients lie still on a scanning table inside the donut-shaped PET scanner for about 30 to 45 minutes as the table moves through it.

If necessary, the PET scan can be further combined with other scans that provide structural assessment of a tumor’s shape and position. These scans include ultrasounds, contrast-enhanced computed tomography (ce-CT), or magnetic resonance imaging (MRI)²⁶.

A pathology report states your diagnosis and the findings from your biopsy (the removal of a tissue sample for analysis). Pathology reports provide a comprehensive understanding of your condition by which to guide further treatment.

A pathology report includes the following:

• the location on your body of the melanoma lesion or tumor
• a diagnosis of the specific melanoma subtype
• a measurement of the tumor thickness (also called Breslow depth)
• the mitotic rate: the number of actively dividing tumor cells
• the presence or absence of ulceration: the breakdown of the epidermis
• the presence or absence of vascular or lymphatic invasion: whether the tumor cells have entered the blood vessels or lymphatic system
• the presence or absence of neurotropism: tumor cells around or inside the nerves
• the presence or absence of tumor-infiltrating lymphocytes, which measures your immune response to melanoma by counting the amount of lymphocytes in the tumor²⁷.

The majority of melanoma patients have localized tumors and are eligible for surgery to remove them; the 5-year survival rate for localized melanoma is over 95%²⁸. The American Cancer Society refers to the period before surgery as the pre-operative phase, in which patients sign consent forms, receive education about benefits and risks, and undergo testing. These tests may include blood tests, urinalysis to assess kidney function, X-rays and/or EKGs to check the lungs and heart, and other assessments. Patients receiving anesthesia are asked to stop eating and drinking at a certain time before surgery, may have to stop certain medications, and are often sent home with antibacterial soap to wash the intended incision site.

Thinner melanomas are treated with wide excision surgery, in which both the tumor and a margin of healthy skin around it (to minimize chance of recurrence) are cut out and the skin stitched back together. Thicker melanomas may require Mohs surgery, a procedure that takes several hours. The melanoma is removed in thin layers and each layer is checked by microscope for cancer cells; removal is halted only when no further cancer cells are seen. Anesthesia for these procedures may be local to numb a specific area, or general and put the patient to sleep.

Lymph nodes near the tumor site are evaluated for the likelihood of metastasis, either by physical exam or by PET scan, CT scan, or ultrasound. Hardened or enlarged lymph nodes are removed. Lymph nodes that appear normal but that are near the site of a tumor can be evaluated by sentinel lymph node biopsy, which identifies the lymph nodes that melanoma cells are most likely to travel to using a radioactive dye and biopsies them to check for cancer. If melanoma cells are present, the lymph nodes are removed.

For patients in advanced stages of melanoma, surgery may not be viable depending on the location and severity of metastatic tumors. Though radiation therapy (use of high-powered energy beams to kill cancer cells) and chemotherapy are still used, combined checkpoint antibody therapy is the current standard of care. Combined refers to the use of two drugs: ipilimumab and nivolumab. These drugs target proteins that prevent the immune system from attacking cancer, which allows more efficient treatment. Other therapies, such as those centered on BRAF and MEK inhibition, shut down cell pathways whose constant signaling aids melanoma progression; this allows long-term disease control²⁹.

Bruising, swelling, and bleeding can all occur immediately after surgery, though a doctor should be consulted if bruises do not heal within several weeks and bleeding does not stop within a few days. A treatment team will prescribe painkillers, follow up about wound care to prevent infection, and make specific post-surgery recommendations if necessary (such as eating a particular diet or not lifting heavy objects). Areas numbed with local anesthesia may remain numb for several hours, and patients should call their doctor if the numbness persists.

Scarring is common in melanoma tumor removal surgery. The MD Anderson Cancer Center cites a 3-month period for scars to stabilize and soften in appearance; scars complete formation by a year post-treatment. High-quality moisturizer is recommended to keep skin hydrated, and sunscreen prevents scars from darkening or becoming hyper-pigmented. Massaging the scar tissue maintains flexibility and promotes collagen remodeling to aid the healing process.

Avoidance of excessive sunlight remains important for patients post-treatment. Cancer Research UK suggests wearing close-weave cotton clothing, long sleeves and pants, sunglasses, and wide-brimmed hats that protect the face and neck. Sunscreen of at least SPF 50 is recommended. If possible, foods such as eggs, red meat, cereals, and oily fishes (mackerel, sardines, and salmon) should be incorporated into the diet for adequate Vitamin D.

There is no universal standard for the structure and frequency of post-treatment care, but stage I and IIa melanoma patients are generally recommended to receive examinations every 3-12 months for the first 5 years followed by annual checkups. Stage IIb to IV patients are recommended for follow-up every 3-6 months for 2 years, then every 3-12 months for 3 years after that, then annually. Surveillance monitors relapse, as 8% of melanoma patients develop a secondary melanoma within two years of their initial diagnosis and have an increased risk for other skin tumors³⁰. Low-intensity surveillance consists of visual skin examinations, while high-intensity includes regular lab screening and imaging³¹.

Psychosocial issues are common after surviving any type of cancer, and melanoma is no different. These issues, as defined by the American Cancer Society, may include:

• trouble coping with one’s cancer experience
• changed feelings about one’s body and sexuality
• feeling isolated from family and friends
• work and financial concerns
• issues opening up about feelings
• fear of cancer recurrence
• fear of death

There is little research on the effect of melanoma on sexuality and intimacy for patients, but scarring after melanoma skin excision and the size of the excision itself are strongly associated with negative body image, especially in women and in younger patients. Health providers setting realistic expectations ahead of time of how the scar will appear helps to mitigate decreases in confidence and body image after surgery. Patients should keep in mind that scars often look worse when healing than in their final appearance.

Social support is crucial in minimizing the impact of melanoma on daily life and bolsters efforts to cope with the diagnosis. The American Cancer Society recommends both support groups and one-on-one counseling in addition to support from family and friends. Speaking to others who have also battled cancer in a support group can help patients feel more understood and less alone. A trained professional in one-on-one counseling can narrow down which experiences throughout diagnosis and treatment have been the most detrimental. Developing coping mechanisms with a professional to better weather life changes, handle symptoms, and navigate family issues is highly beneficial.

There is likewise little research on the impact that melanoma has on caregivers, but it is known that social training and support for caregivers helps to mitigate the stress of managing symptoms and of providing emotional support⁷.

Myth: Skin cancer isn’t dangerous.
Fact: Though skin cancers can be readily treatable and have high survival rates, melanoma is the deadliest kind and has a very poor prognosis at later stages.

Myth: People of color cannot get skin cancer.
Fact: People of color can get skin cancer. This belief contributes to delayed diagnoses of melanoma, which then leads to a poor prognosis once the disease is eventually discovered.

Myth: Tanning beds are safer than the sun.
Fact: Tanning bed radiation is considered a carcinogen by the International Agency for Research on Cancer, as there are generally higher levels of UV exposure in one sitting than that from the sun.

Myth: Going out without sunscreen is necessary for Vitamin D.
Fact: Eating foods high in Vitamin D or taking Vitamin D supplements are safer ways to maintain healthy levels than direct sun exposure.

Myth: You don’t need sunscreen when it’s cloudy.
Fact: The sun’s UV rays can penetrate through clouds and reach your skin even without direct sunlight.