Melanoma: Symptoms, Causes, Treatment & Prevention

What Is Melanoma and Why Is It Dangerous?

Melanoma is a type of skin cancer that develops from melanocytes, the cells that produce melanin (skin pigment). It is the most dangerous form of skin cancer because it can spread (metastasize) to other organs including the lungs, liver, brain, and bones. However, when detected early, melanoma is highly curable with a survival rate exceeding 99%.

Melanoma accounts for only about 1-2% of all skin cancers, but it causes the vast majority of skin cancer deaths. This is because melanoma cells have a greater tendency to spread through the lymphatic system and bloodstream compared to other skin cancers like basal cell carcinoma and squamous cell carcinoma. The good news is that melanoma is one of the most preventable cancers, and when caught early, it is also one of the most curable.

The name "melanoma" comes from the Greek words "melas" (black) and "oma" (tumor), referring to the dark color of most melanomas due to the melanin produced by the cancer cells. However, it's important to know that some melanomas can be pink, red, or even skin-colored (amelanotic melanoma), which can make them more difficult to detect.

Globally, melanoma incidence has been rising steadily for the past several decades. Approximately 325,000 new cases are diagnosed worldwide each year, with the highest rates found in Australia and New Zealand due to high UV exposure and predominantly fair-skinned populations. The increase in melanoma cases is largely attributed to increased recreational sun exposure, tanning bed use, and possibly improved detection methods.

How Does Melanoma Develop?

Melanoma begins in melanocytes, specialized cells located in the basal layer of the epidermis (the outermost layer of skin). Melanocytes produce melanin, the pigment that gives skin its color and provides some protection against UV radiation. When DNA in melanocytes becomes damaged, usually from UV exposure, the cells can begin to grow uncontrollably and form a tumor.

The development of melanoma typically follows a progression. Initially, melanoma cells grow horizontally within the epidermis (radial growth phase). If not detected and treated at this stage, the cancer can progress to a vertical growth phase where cells penetrate deeper into the dermis and potentially gain access to blood vessels and lymphatic channels, enabling spread to distant sites.

Understanding this progression is crucial because it explains why early detection is so important. When melanoma is confined to the epidermis (melanoma in situ), surgical removal is curative in virtually all cases. Once the cancer has grown deeper into the skin, the risk of spread increases significantly with each millimeter of depth.

What Are the Warning Signs and Symptoms of Melanoma?

The most common sign of melanoma is a new mole or an existing mole that changes in size, shape, or color. Use the ABCDE rule to evaluate moles: Asymmetry, Border irregularity, Color variation, Diameter greater than 6mm, and Evolution (any change). A mole that bleeds, itches, or looks different from your other moles ("ugly duckling" sign) should be examined by a doctor.

Recognizing the warning signs of melanoma is the single most important factor in early detection and successful treatment. Melanoma can develop anywhere on the body, but it most commonly appears on sun-exposed areas such as the back, legs, arms, and face. In men, melanoma is most often found on the trunk (especially the back), while in women, it more commonly develops on the legs.

The appearance of melanoma can vary considerably. The majority are pigmented (colored) lesions, ranging from tan to dark brown or black. However, some melanomas lack pigment (amelanotic melanoma) and may appear pink, red, purple, or skin-colored. This variability makes it essential to be familiar with the various warning signs and to examine your skin regularly.

The ABCDE Rule for Melanoma Detection

The ABCDE rule is a widely used guide to help identify suspicious moles that may be melanoma. Each letter represents a characteristic that should prompt medical evaluation:

While the ABCDE rule is an excellent screening tool, it's important to remember that not all melanomas follow these criteria, and some benign moles may have one or more of these features. The "E" for Evolution is often considered the most important criterion because any mole that is changing should be evaluated, even if it doesn't meet the other criteria.

The "Ugly Duckling" Sign

Another helpful method for detecting melanoma is the "ugly duckling" sign. Most of your moles tend to look similar to each other. The ugly duckling is a mole or lesion that looks different from the rest - it stands out as the odd one. This could be a darker mole among lighter ones, a larger mole among smaller ones, or simply one that doesn't fit the pattern of your other moles. Any "ugly duckling" should be examined by a dermatologist.

Additional Warning Signs

Beyond the ABCDE criteria and ugly duckling sign, other symptoms that warrant immediate medical attention include:

• Bleeding: A mole that bleeds spontaneously or with minimal trauma
• Itching: Persistent itching in a mole, especially if new
• Ulceration: A mole that develops an open sore that doesn't heal
• Satellite lesions: Small spots appearing near the main mole
• Inflammation: Redness or swelling extending beyond the mole border
• Textural change: A mole that becomes raised or develops a different texture

What Causes Melanoma?

The primary cause of melanoma is damage to DNA in melanocytes from ultraviolet (UV) radiation, particularly from sunlight and tanning beds. The risk is especially high for those who have experienced severe sunburns, especially during childhood and adolescence. About 10% of melanomas have a hereditary component involving genetic mutations.

Understanding the causes and risk factors for melanoma is essential for prevention. While anyone can develop melanoma, certain factors significantly increase the risk. The interaction between genetic predisposition and environmental factors, particularly UV exposure, determines an individual's likelihood of developing this cancer.

UV radiation damages DNA in skin cells. While the body has repair mechanisms to fix this damage, repeated or severe damage can overwhelm these systems, leading to mutations that cause cells to grow uncontrollably. The cumulative effect of UV exposure over a lifetime, combined with specific intense exposures (sunburns), creates the conditions for melanoma development.

UV Radiation: The Primary Cause

Ultraviolet radiation from the sun is responsible for the vast majority of melanomas. Both UVA and UVB rays contribute to skin damage and melanoma risk, though UVB is primarily responsible for sunburns. The relationship between UV exposure and melanoma is complex:

Intermittent intense exposure (occasional severe sunburns, typically from recreational sun exposure) is more strongly associated with melanoma than chronic cumulative exposure. This helps explain why melanoma can develop on parts of the body that are not continuously exposed to the sun, and why indoor workers who get occasional intense sun exposure may have higher risk than outdoor workers with chronic exposure.

Childhood sunburns are particularly dangerous. Studies show that severe blistering sunburns during childhood and adolescence dramatically increase melanoma risk later in life, possibly because melanocytes in developing skin are more susceptible to DNA damage or because the damage has more time to accumulate and lead to cancer.

Tanning beds pose significant risk. The World Health Organization classifies UV-emitting tanning devices as Group 1 carcinogens (the highest risk category). Using tanning beds before age 30 increases melanoma risk by 75%. Many countries have banned or restricted tanning bed use for minors due to this substantial risk.

Risk Factors for Melanoma

Several factors increase an individual's risk of developing melanoma:

Genetic Factors

About 10% of melanomas occur in people with a family history of the disease, suggesting a genetic component. Several genes have been identified that increase melanoma susceptibility:

CDKN2A is the most commonly identified high-risk melanoma gene. Mutations in this gene are found in about 40% of families with multiple melanoma cases. People with CDKN2A mutations have approximately a 70% lifetime risk of developing melanoma.

MC1R variants are associated with red hair, fair skin, and freckling. These variants increase melanoma risk even in people with darker skin types, suggesting a direct role in melanoma development beyond just affecting pigmentation and sun sensitivity.

BRAF mutations are found in about 50% of melanomas. While not typically inherited, the presence of BRAF mutations is important for treatment decisions, as targeted therapies are available for BRAF-mutant melanomas.

How Is Melanoma Diagnosed?

Melanoma is diagnosed through a combination of clinical examination, dermoscopy (magnified skin examination), and skin biopsy. If melanoma is confirmed, additional tests including sentinel lymph node biopsy, CT scans, PET scans, or MRI may be performed to determine the stage of the cancer and guide treatment decisions.

The diagnostic process for melanoma typically begins with a thorough skin examination. Dermatologists are trained to recognize suspicious lesions and use specialized tools to evaluate them. If a lesion appears concerning, it will be removed and sent for pathological analysis, which provides the definitive diagnosis.

It's important to understand that a visual examination alone cannot confirm or rule out melanoma with certainty. Many benign conditions can mimic melanoma's appearance, and some melanomas may not have typical features. This is why biopsy and microscopic examination are essential for accurate diagnosis.

Clinical Examination and Dermoscopy

During a skin examination, your doctor will inspect all moles and skin lesions on your body. For suspicious lesions, a dermoscope (a specialized magnifying instrument with polarized light) may be used. Dermoscopy allows visualization of structures beneath the skin surface that are not visible to the naked eye, improving diagnostic accuracy by 10-30% compared to examination with the naked eye alone.

During dermoscopy, the dermatologist looks for specific patterns and structures that help differentiate melanoma from benign lesions. These include irregular pigment networks, atypical vascular patterns, blue-white structures, and other features that have been validated in numerous studies as indicators of melanoma.

Skin Biopsy

If a lesion is suspicious for melanoma, a biopsy is performed. The preferred method is an excisional biopsy, where the entire lesion is removed with a small margin of normal skin. This approach provides the pathologist with the complete lesion to examine and allows for accurate measurement of tumor thickness, which is critical for staging and prognosis.

The biopsy is performed under local anesthesia, and the wound is typically closed with sutures. The sample is sent to a pathology laboratory where it is examined under a microscope by a pathologist, often one specializing in skin pathology (dermatopathologist). The pathology report will include:

• Breslow thickness: The depth of the tumor in millimeters, the most important prognostic factor
• Ulceration status: Whether the surface of the melanoma has broken down
• Mitotic rate: How rapidly the cancer cells are dividing
• Margins: Whether cancer cells extend to the edges of the removed tissue
• Lymphovascular invasion: Whether cancer cells are present in blood or lymph vessels

Staging and Further Testing

If melanoma is confirmed, additional tests may be needed to determine whether the cancer has spread. This process is called staging and is crucial for treatment planning. The main staging tests include:

Sentinel lymph node biopsy (SLNB): This procedure identifies and removes the first lymph node(s) to which cancer cells would likely spread from the primary tumor. If the sentinel node is negative (no cancer cells), it's unlikely that the cancer has spread to other lymph nodes. SLNB is typically recommended for melanomas thicker than 0.8mm or those with ulceration.

Imaging studies: For patients with higher-risk melanomas or symptoms suggesting spread, imaging tests may be performed:

• CT (computed tomography) scan: Provides detailed images of internal organs
• PET (positron emission tomography) scan: Detects metabolically active cancer cells throughout the body
• MRI (magnetic resonance imaging): Particularly useful for evaluating possible brain metastases
• Ultrasound: May be used to evaluate lymph nodes

What Are the Stages of Melanoma?

Melanoma is staged from 0 to IV based on tumor thickness, ulceration, lymph node involvement, and distant spread. Stage 0 (in situ) is confined to the epidermis with near 100% cure rate. Stage I-II involves the skin only, Stage III involves lymph nodes, and Stage IV indicates spread to distant organs. Earlier stages have significantly better prognosis.

Staging is a crucial part of melanoma diagnosis and treatment planning. The stage describes how far the cancer has progressed and helps determine the most appropriate treatment approach. Melanoma staging uses the TNM system (Tumor, Nodes, Metastasis) developed by the American Joint Committee on Cancer (AJCC).

Understanding your melanoma stage helps you and your medical team make informed decisions about treatment and provides information about prognosis. It's important to note that survival statistics are based on large populations and may not accurately predict an individual's outcome, as many factors influence prognosis.

*Note: Stage IV survival rates have improved significantly with modern immunotherapy and targeted therapy. Recent data show that some patients with advanced melanoma achieve long-term remission with these treatments.

How Is Melanoma Treated?

Melanoma treatment depends on the stage. Early-stage melanoma is treated with surgical excision with appropriate margins. For more advanced disease, treatment may include immunotherapy (checkpoint inhibitors), targeted therapy (BRAF/MEK inhibitors), radiation therapy, or chemotherapy. Modern immunotherapy has dramatically improved outcomes for advanced melanoma.

The treatment of melanoma has been revolutionized over the past decade, particularly for advanced disease. While surgery remains the cornerstone of treatment for early-stage melanoma, the development of immunotherapy and targeted therapy has transformed outcomes for patients with metastatic disease. Treatment decisions are based on the stage of the cancer, molecular characteristics of the tumor, and individual patient factors.

A multidisciplinary team typically manages melanoma treatment, including dermatologists, surgical oncologists, medical oncologists, radiation oncologists, and pathologists. This collaborative approach ensures that patients receive comprehensive, coordinated care.

Surgery

Surgery is the primary treatment for melanoma that has not spread beyond the skin and nearby lymph nodes. The type and extent of surgery depend on the characteristics of the tumor:

Wide local excision: After the initial biopsy confirms melanoma, a second surgery is performed to remove additional tissue around the biopsy site. The margin (amount of normal skin removed) depends on the tumor thickness:

• Melanoma in situ: 0.5-1cm margin
• Melanoma up to 2mm thick: 1-2cm margin
• Melanoma greater than 2mm thick: 2cm margin

Lymph node surgery: If the sentinel lymph node biopsy is positive, or if there are clinically obvious lymph node metastases, complete lymph node dissection may be recommended. This involves removing all lymph nodes in the affected region (neck, armpit, or groin). However, for patients with only microscopic disease in the sentinel node, surveillance with regular ultrasound is now considered an acceptable alternative to immediate complete dissection.

Immunotherapy

Immunotherapy has transformed the treatment of advanced melanoma and is now also used in earlier stages to reduce the risk of recurrence. These drugs work by helping the immune system recognize and destroy cancer cells:

Checkpoint inhibitors are the most commonly used immunotherapy drugs for melanoma. They block proteins that prevent immune cells from attacking cancer cells. The main checkpoint inhibitors used in melanoma include:

• Pembrolizumab (Keytruda) and Nivolumab (Opdivo): Block PD-1, a protein on T cells that acts as an "off switch"
• Ipilimumab (Yervoy): Blocks CTLA-4, another immune checkpoint protein
• Combination therapy: Nivolumab plus ipilimumab can be more effective than either drug alone, though with more side effects

These treatments can produce durable responses lasting years in many patients. Some patients with advanced melanoma have achieved complete remission that persists for more than a decade. However, immunotherapy can cause immune-related side effects affecting various organs, requiring careful monitoring.

Targeted Therapy

About 50% of melanomas have mutations in the BRAF gene. For these tumors, targeted therapy using BRAF inhibitors and MEK inhibitors can be highly effective:

BRAF inhibitors (dabrafenib, vemurafenib, encorafenib) block the abnormal BRAF protein. MEK inhibitors (trametinib, cobimetinib, binimetinib) block another protein in the same signaling pathway. These drugs are typically used in combination, which improves effectiveness and reduces resistance.

Targeted therapy often produces rapid responses, making it particularly useful when quick tumor shrinkage is needed. However, resistance typically develops over time, which is why immunotherapy is often preferred for first-line treatment when both options are available.

Radiation Therapy

While melanoma is traditionally considered less responsive to radiation than some other cancers, radiation therapy plays an important role in certain situations:

• After lymph node surgery to reduce the risk of recurrence
• To treat brain metastases (stereotactic radiosurgery can be highly effective)
• For palliation of symptoms from metastases
• When surgery is not possible due to location or patient factors

Chemotherapy

Chemotherapy is now less commonly used for melanoma since immunotherapy and targeted therapy have proven more effective. However, it may still be considered when other treatments have failed or are not suitable. Dacarbazine (DTIC) was historically the most commonly used chemotherapy agent for melanoma.

How Can You Prevent Melanoma?

The most important melanoma prevention strategy is protecting yourself from UV radiation. This includes avoiding excessive sun exposure (especially between 10 AM and 4 PM), using broad-spectrum SPF 30+ sunscreen, wearing protective clothing and hats, seeking shade, and never using tanning beds. Regular skin self-examinations and professional skin checks are also essential for early detection.

Prevention is crucial because melanoma is largely a preventable cancer. While you cannot change genetic factors like skin type or family history, you can significantly reduce your risk through sun-safe behaviors. Additionally, regular skin surveillance enables early detection of any melanomas that do develop, dramatically improving outcomes.

Sun Protection Guidelines

Protecting your skin from UV radiation is the most effective way to prevent melanoma. The following guidelines can significantly reduce your risk:

Limit sun exposure during peak hours: UV radiation is strongest between 10 AM and 4 PM. During these hours, seek shade whenever possible. A useful rule is the "shadow test" - if your shadow is shorter than you are, UV radiation is intense, and you should take extra precautions.

Use sunscreen correctly: Apply a broad-spectrum (UVA and UVB protection) sunscreen with SPF 30 or higher to all exposed skin. Apply generously (most people use too little) about 15-30 minutes before sun exposure. Reapply every 2 hours, and more frequently if swimming or sweating. Remember that no sunscreen blocks 100% of UV rays, so sunscreen should be combined with other protective measures.

Wear protective clothing: Tightly woven fabrics in dark colors provide better protection than thin, light-colored fabrics. Consider clothing specifically designed for sun protection (rated with UPF - Ultraviolet Protection Factor). Wear a wide-brimmed hat (at least 3 inches) to protect your face, ears, and neck. Wear sunglasses that block UV rays to protect your eyes and the delicate skin around them.

Avoid tanning beds completely: There is no safe way to tan using UV radiation. The myth of a "base tan" providing protection is false - any tan indicates skin damage. The World Health Organization recommends avoiding tanning beds entirely, especially before age 30.

Protect children: Childhood sun exposure and sunburns are particularly important risk factors for melanoma. Children under 6 months should be kept out of direct sunlight entirely. Older children should wear protective clothing and sunscreen. Establishing sun-safe habits early creates lifelong patterns that reduce melanoma risk.

Skin Self-Examination

Regular skin self-examinations help you detect melanoma early when it is most treatable. Examine your entire body once a month, using mirrors to check hard-to-see areas, or ask a partner to help. Be systematic and thorough, checking:

• Face, ears, and scalp (use a comb or hair dryer to expose scalp)
• Front and back of your body, including arms and underarms
• Both sides of your arms, including palms and between fingers
• Backs of your legs, including soles of feet and between toes
• Genital area and buttocks

Take photos of your moles to help track changes over time. Note any new moles or changes to existing ones. Remember the ABCDE criteria and ugly duckling sign. If you notice anything concerning, see a dermatologist promptly.

Professional Skin Examinations

Annual full-body skin examinations by a dermatologist are recommended for people at increased risk of melanoma, including those with:

• Personal or family history of melanoma
• Many moles (more than 50) or atypical moles
• Fair skin that burns easily
• History of severe sunburns
• History of tanning bed use
• Weakened immune system

Even if you don't have these risk factors, having a baseline skin examination by a dermatologist can be valuable for comparison in future examinations.

How Does Melanoma Affect Daily Life?

Most people treated for early-stage melanoma can return to normal activities after surgical treatment with few lasting effects. However, long-term follow-up is essential as there is an ongoing risk of recurrence or new melanomas. Psychological support may be needed to cope with the diagnosis and concerns about recurrence. Sun protection becomes a lifelong priority.

The impact of melanoma on daily life varies greatly depending on the stage at diagnosis and the treatments received. For many patients with early-stage melanoma, treatment involves a relatively minor surgical procedure, and they can return to normal activities within a few weeks. For those with more advanced disease requiring immunotherapy or other systemic treatments, the impact can be more significant.

After Treatment

After completing melanoma treatment, patients enter a period of surveillance. The intensity and duration of follow-up depend on the stage of the original melanoma and individual risk factors. Follow-up typically includes:

Regular clinical examinations: Your doctor will examine your skin and lymph nodes at regular intervals. For higher-risk melanomas, this may be every 3-6 months initially, decreasing over time if there is no recurrence.

Imaging studies: For patients with higher-stage melanomas, periodic imaging (CT, PET, or MRI scans) may be recommended to detect any recurrence or new metastases early.

Self-examination: You should continue monthly skin self-examinations indefinitely, as people who have had melanoma have an increased risk of developing additional melanomas.

Risk of New Melanoma

People who have had melanoma have approximately a 9-fold increased risk of developing another melanoma compared to the general population. This is why ongoing surveillance and sun protection are so important. The second melanoma can develop anywhere on the body, not necessarily near the site of the first one.

Psychological Support

A melanoma diagnosis can cause significant emotional distress, even for early-stage disease with an excellent prognosis. Common concerns include anxiety about recurrence, changes in body image (particularly with visible scars), and general cancer-related worry. These feelings are normal, and support is available:

• Cancer support groups, either in-person or online
• Individual counseling or therapy
• Patient advocacy organizations
• Social workers at your cancer treatment center

Can Melanoma Occur During Pregnancy?

Pregnancy does not increase the risk of developing melanoma, and melanoma in pregnant women is treated similarly to non-pregnant patients, with some modifications to protect the fetus. Hormonal changes during pregnancy can cause normal moles to change, but any concerning changes should still be evaluated. Surgery can be performed safely during pregnancy, and many other treatments can be adapted.

While melanoma during pregnancy is uncommon, it is the most common cancer to be diagnosed during pregnancy. This is partly because melanoma affects people of reproductive age. The management of melanoma in pregnant women requires balancing effective cancer treatment with fetal safety.

Normal Skin Changes During Pregnancy

Pregnancy causes various skin changes due to hormonal fluctuations. These include darkening of the nipples, a dark line from the navel downward (linea nigra), and darkening of existing moles. These changes are typically benign and often resolve after pregnancy. However, any mole that is growing rapidly, changing significantly, or has concerning features should be evaluated by a dermatologist, as pregnancy does not protect against melanoma.

Treatment During Pregnancy

If melanoma is diagnosed during pregnancy, treatment can usually proceed, though with some modifications:

• Surgery: Surgical excision can be performed safely during pregnancy with local anesthesia or, if needed, general anesthesia
• Sentinel lymph node biopsy: This can be performed using techniques that minimize radiation exposure to the fetus
• Imaging: Ultrasound is preferred when imaging is needed. If CT or PET scans are necessary, they can be performed with shielding to protect the fetus
• Systemic therapy: Chemotherapy can be given after the first trimester if needed. Immunotherapy and targeted therapy during pregnancy are less well-studied, and decisions are made individually

Melanoma does not spread to the fetus except in extremely rare cases, and pregnancy does not appear to worsen melanoma prognosis. Treatment decisions should be made jointly by the oncology team and obstetric care providers, considering both maternal and fetal well-being.