Melanoma: Causes, Symptoms and Treatments

Melanoma is one of the most aggressive and deadly types of skin cancer, accounting for 75% of all skin cancer-related deaths despite being less common than basal cell carcinoma or squamous cell carcinoma.

The global incidence of melanoma has been rising, with fair-skinned individuals and those living in high UV exposure areas at greater risk. However, early detection and advancements in treatment have improved survival rates significantly.

This article provides a comprehensive guide to melanoma, covering causes, symptoms, diagnosis, treatment, prognosis, prevention, and the latest research advancements.

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What is Melanoma?

Understanding melanoma is essential before diving into its causes, symptoms, and treatment options.

Definition and Overview

Melanoma is a type of skin cancer originating in melanocytes, the pigment-producing cells in the skin. Unlike basal and squamous cell carcinoma, melanoma is more likely to spread (metastasize) to distant organs if not detected early.

Types of Melanoma

The four major types of cutaneous (skin) melanoma are:

Superficial Spreading Melanoma

The most common type (approximately 70% of melanoma cases); grows horizontally (radially) before spreading deeper.
Common locations: torso, legs, arms

Nodular Melanoma

More aggressive, grows vertically and quickly.
Common locations: Areas with chronic sun exposure (e.g., scalp, chest, back)

Lentigo Maligna Melaoma

Slow-growing, typically evolves from brown to black macule with irregular borders; common in older adults.
Common locations: Chronically sun-damaged skin on the face and neck.

Acral Lentiginous Melaoma

Uncommon; affects palms, soles, and undernails; disproportionately affects individuals with darker skin tones.
Common locations: Hands, feet, nail beds

Early detection and treatment significantly improve prognosis and survival rates.

Global Incidence Rates

The reported incidence varies by region due to differences in UV exposure, genetic susceptibility, and healthcare access. Some populations may have lower documented cases due to differences in screening practices and reporting accuracy. Typically:

Australia and New Zealand have the highest melanoma rates globally due to high UV exposure and fair-skinned populations.
North America and Europe see moderate incidence rates, with increasing cases due to tanning practices.
Asia and Africa have lower reported cases, though acral lentiginous melanoma is more common in darker-skinned individuals.

Causes and Risk Factors

Melanoma is multifactorial, resulting from a combination of genetic, environmental, and lifestyle influences.

Genetic Factors

A family history of melanoma increases risk 2-3 times.
Mutations in genes like CDKN2A and BRAF are associated with an increased risk of melanoma.
Hereditary syndromes like familial atypical multiple mole melanoma (FAMMM) syndrome increase susceptibility.

Environmental Factors

UV radiation (sunlight & tanning beds) damages DNA, leading to cancerous mutations.
Higher risk in sunny climates (Australia, southern U.S., and Mediterranean regions).

Lifestyle Factors

Frequent sunburns in childhood increase melanoma risk later in life.
Occupational exposures (e.g., outdoor jobs) elevate risk.

Rare Causes

Weakened immune system (due to organ transplants, chemotherapy, or autoimmune diseases).
Certain medications, including immunosuppressants, may be associated with an increased susceptibility to melanoma.

Symptoms and Signs

Recognizing the early signs of melanoma is crucial for early detection and better treatment outcomes.

Common Symptoms

Changes in mole size, shape, or color.
New, abnormal skin growths.
Irregular borders, multiple colors, or asymmetry in a mole.

Less common symptoms include moles that itch, bleed, or become tender and sores that do not heal.

How to Perform a Self-Examination

To perform a skin self-examination at home:

Start by standing in a well-lit room with a full-length mirror and a hand-held mirror.
Begin by examining your entire body, including your face, neck, chest, and abdomen. Women should also check under their breasts.
Next, inspect both arms, including your hands, nails, and between your fingers.
Sit down and examine your legs, feet (including soles and between toes), and toenails.
Use a hand-held mirror to check hard-to-see areas such as your back, buttocks, and the back of your neck and scalp.

Look for new, changing, or unusual moles, spots, or lesions using the ABCDE rule - Asymmetry, Border irregularity, Color variation, Diameter over 6mm, and Evolution (Table 1). If you notice any suspicious changes, consult a dermatologist promptly.

Follow the ABCDE rule for detecting suspicious moles

Detecting Suspicious Moles

Diagnosis of Melanoma

Early diagnosis is crucial for the best treatment outcomes.

Early Detection Methods

Early detection of melanoma significantly improves treatment success and survival rates. Regular self-exams can help detect suspicious skin changes, but professional dermatologic evaluation is necessary for an accurate diagnosis.

Self-Exams: Individuals should check their skin monthly, looking for new or changing moles using the ABCDE rule (Asymmetry, Border irregularity, Color variation, Diameter >6mm, and Evolving appearance).
Dermatology Visits: People at higher risk (family history, fair skin, history of sunburns, or many moles) should have a yearly full-body skin exam by a dermatologist (a doctor specializing in diagnosis and treatment of conditions of the skin, hair, and nails).
Dermatoscopy (Epiluminescence Microscopy): A non-invasive imaging tool that magnifies skin lesions to assess suspicious moles more closely, helping dermatologists decide if a biopsy is needed.

Advanced Diagnostic Procedures

If a suspicious lesion is identified, a biopsy should be performed to determine whether it is melanoma. Biopsy methods include:

Excisional Biopsy

The entire mole and a small margin of normal skin are removed for lab testing.
Preferred for most suspicious moles.

Incisional Biopsy

A portion of the lesion is removed for analysis.
Used if the lesion is too large for full removal.

Punch Biopsy

A circular tool removes a small, deep sample.
Used when deeper tissue examination is required.

Shave Biopsy

The top layers of the skin are removed.
Shave biopsy is generally not preferred for suspected melanoma but may be considered in select cases.

Imaging Tests for Advanced Melanoma

If melanoma is suspected to have spread beyond the skin, imaging tests may be ordered:

CT Scans & MRI: Useful in melanoma assessment to detect metastases, evaluate tumor depth, and assess the involvement of lymph nodes or internal organs, aiding in staging and treatment planning.
PET Scan: Assess metabolically active cancer cells, allowing for the identification of distant metastases and assessment of disease progression.

Staging Melanoma

After diagnosis, melanoma is staged using the TNM (Tumor, Nodes, Metastasis) staging system to guide treatment decisions (Table 2). Treatment strategies vary based on the severity and spread of the disease.

Melanoma Staging

Differential Diagnosis

The differential diagnosis for melanoma includes skin lesions that may appear similar. For example:

Atypical fibroxanthoma
Pigmented basal cell carcinoma
Blue nevus
Epithelioid tumor
Halo nevus

A definitive melanoma diagnosis requires histopathological evaluation by a qualified pathologist.

Treatment Options

Melanoma treatment depends on stage, location, patient health, and genetic factors. Earlier-stage melanomas are often curable with surgery, while advanced cases may require systemic therapies like immunotherapy or targeted therapy.

Conventional Treatments

Surgical Removal (Excision or Mohs Surgery)

Stage 0 to II melanoma is treated with wide excision, where the tumor and a margin of surrounding healthy tissue are removed.
Mohs micrographic surgery is used for certain melanomas on the face or sensitive areas, allowing layer-by-layer removal while preserving healthy tissue.
Lymph Node Dissection: If melanoma has spread to regional lymph nodes, surgical removal may be needed.

Radiation Therapy

Used after surgery for high-risk cases to eliminate residual cancer cells.
Also used palliatively for metastatic melanoma that has spread to the brain, bones, or other organs.

Chemotherapy

Previously a main treatment for advanced melanoma, chemotherapy is now used less frequently due to the success of immunotherapy and targeted therapies.

Advanced Treatments

Recent breakthroughs in melanoma treatment have led to more effective therapies with improved survival rates.

Immunotherapy (Checkpoint Inhibitors)

Boosts the immune system’s ability to attack melanoma cells.
Common drugs:
- Pembrolizumab (Keytruda), Nivolumab (Opdivo): PD-1 inhibitors that block immune suppression.
- Ipilimumab (Yervoy): A CTLA-4 inhibitor that enhances T-cell activation.

Targeted Therapy

For patients with BRAF mutations (50% of melanomas):
- BRAF inhibitors: Vemurafenib, Dabrafenib.
- MEK inhibitors: Trametinib, Cobimetinib.
These drugs shrink tumors and slow the progression of advanced melanoma.

Combination Therapy

Using immunotherapy and targeted therapy together has shown promising results in improving survival.

Treatment Based on Stage

Effective treatment improves survival rates, but prognosis depends on factors such as tumor thickness and metastasis.

Prognosis and Survival Rates

Factors Affecting Prognosis

Several factors influence melanoma prognosis:

Tumor Thickness: Thicker tumors have a higher chance of spreading and a worse prognosis.
Ulceration: If the tumor breaks through the skin, the prognosis worsens.
Lymph Node Involvement: The more lymph nodes affected, the lower the survival rate.
Distant Metastasis: Stage IV melanoma has the lowest survival rate, especially if it spreads to the brain or liver.

Prevention and Risk Reduction

Adopting protective measures can significantly lower the risk of developing melanoma.

Sun Protection Strategies

Protecting your skin from harmful UV radiation is one of the most effective ways to reduce melanoma risk. Here are some tips:

Use Broad-Spectrum Sunscreen

The FDA recommends using a broad-spectrum sunscreen with SPF 30 or higher to reduce UV exposure risk.
Reapply every two hours and immediately after swimming or sweating.
Choose broad-spectrum formulas that protect against UVA and UVB rays.

Wear Protective Clothing and Accessories

Wide-brimmed hats, long sleeves, and sunglasses reduce UV exposure.
Ultraviolet Protection Factor (UPF-rated) clothing provides additional protection.

Avoid Tanning Beds and Excessive Sun Exposure

Tanning beds emit concentrated UV radiation, increasing melanoma risk. The WHO and FDA classify tanning beds as carcinogenic, with evidence linking them to an increased risk of melanoma.
Limit direct sun exposure between 10 AM and 4 PM, when UV rays are strongest.

Monitor UV Index and Seek Shade

Use weather apps to check the daily UV index.
When UV levels are high, stay in shaded areas and avoid prolonged sun exposure.

Lifestyle Changes for Melanoma Prevention

A healthy lifestyle may lower the risk of developing melanoma. Examples include:

Antioxidant-Rich Diet: Foods rich in antioxidants (berries, leafy greens, nuts) may help protect skin cells from UV damage. Omega-3 fatty acids from fish may have anti-inflammatory effects that benefit skin health.
Avoid Smoking and Limit Alcohol
Maintain a Healthy Immune System: Immunosuppression (due to organ transplants, autoimmune diseases, or chronic illnesses) may increase melanoma risk. Staying physically active and managing stress can support immune function.

Regular Screenings and Dermatological Exams

Routine skin checks are essential in catching melanoma early, when treatment is most effective.

Who Should Get Screened?

Individuals with a family history of melanoma.
People with fair skin, freckles, or numerous moles.
Those with a history of severe sunburns or tanning bed use.

Professional Skin Exams

Annual dermatologist visits are recommended for high-risk individuals.
Total-body photography helps track mole changes over time.

Melanoma Research and Future Directions

Medical advancements have transformed melanoma from a high-mortality cancer to one with increasingly better survival rates. Research is focused on enhancing early detection, developing novel treatments, and improving patient outcomes.

Latest Research Findings

Artificial intelligence (AI) tools are being developed to detect melanoma more accurately in early stages using imaging technology.
Gene Editing & CRISPR-Based Treatments: Scientists are exploring gene therapy to correct genetic mutations responsible for melanoma.

New Developments in Immunotherapy

Dual checkpoint inhibitors (combining PD-1 and CTLA-4 blockers) are being studied to enhance immune response further.
T-cell therapy (adoptive cell transfer) is being investigated to improve treatment for advanced melanoma.

Targeted Therapy Advances

Next-generation BRAF inhibitors aim to prolong treatment response and reduce drug resistance.
Combination therapies using targeted drugs and immunotherapy are showing higher survival rates.

Living with Melanoma

Melanoma treatments can cause short-term and long-term side effects. For example:

Surgery may result in scarring and pain. Scar creams and pain relief medications may help.
Immunotherapy may cause fatigue, skin rash, and inflammation. Hydration, rest, and managing autoimmunity may provide relief.
Radiation may cause skin irritation and fatigue. Moisturizers and gentle exercises (yoga, walking, swimming) may help manage treatment-related fatigue.

Support Systems and Resources

Emotional and Mental Health Support

A melanoma diagnosis can be overwhelming, leading to anxiety or depression.
Therapy, mindfulness techniques, and patient support groups can help individuals cope.

Support Groups & Online Communities

The Skin Cancer Foundation provides education and patient advocacy.
Melanoma Research Alliance offers access to clinical trials and new treatments.

Financial and Practical Assistance

Nonprofits like the American Cancer Society provide grants and financial aid for treatment costs.
Transportation services are available for patients who need assistance getting to medical appointments.

After completing treatment, melanoma survivors should follow their healthcare provider’s recommendations for surveillance and follow-up visits.

Understanding melanoma is essential for recognizing risk factors and seeking timely medical care. This article provides general information and should not replace professional medical evaluation or treatment.