Melanoma: Symptoms, Causes & Treatment

Melanoma is a dangerous skin cancer that originates from melanocytes, the pigment-producing cells responsible for skin color. Although it represents only 5-10% of all skin cancers, it causes the majority of skin cancer deaths worldwide. Melanoma is characterized by its ability to spread rapidly to lymph nodes and distant organs, making early detection critical for successful treatment outcomes.

Global statistics indicate that melanoma affects approximately 300,000 people annually worldwide. In the Middle East and Jordan region, there is a moderate incidence rate significantly affected by ultraviolet radiation exposure and genetic factors. Individuals with fair skin, age 20-40 years, and those with a family history are at highest risk. Early detection using ABCDE criteria (Asymmetry, Border irregularity, Color variation, Diameter, Evolution) can be life-saving, as melanoma in very early stages has a 5-year survival rate exceeding 95%.

Treatment depends on disease stage and extent of spread. Options range from simple surgical excision for very early lesions, to wide surgical removal with lymph node dissection, advanced immunotherapy (such as checkpoint inhibitor blockers), targeted therapy (for specific molecular mutations), and chemotherapy in advanced cases.

Melanoma symptoms vary depending on disease stage and location on the body. In early stages, symptoms may be limited to changes in mole appearance or emergence of an unusual new mole. As the disease progresses, systemic symptoms indicating spread may appear. It is important to monitor any skin changes and seek immediate medical attention upon noticing any of the following warning signs:

• Mole asymmetry: One half of the mole does not match the other half in shape or size.
• Irregular borders: Mole edges are not straight or are wavy or unclear.
• Color variation: Multiple colors present in one mole (light and dark brown, black, red, white, blue).
• Diameter larger than 6mm: Mole is larger than a pencil eraser head.
• Evolution and change: Any change in mole size, shape, color, or elevation within weeks or months.
• Bleeding or oozing: Mole bleeds or oozes fluid without injury.
• Itching or pain: Itching, pain, or tenderness in the mole.
• Surrounding redness: Redness or inflammation around the mole.
• New mole appearing after age 30: Appearance of an unusual new mole after this age requires medical evaluation.
• Lymph node enlargement: In advanced cases, swelling of nearby lymph nodes may be noticed (such as under the arm or groin).
• General symptoms: In cases of distant spread, fatigue, weakness, weight loss, and difficulty breathing may occur.
• Bone pain: In advanced cases that have spread to bones, bone pain may develop.

• Excessive ultraviolet (UV) sun exposure: Cumulative exposure and acute sunburns, especially in childhood and adolescence, significantly increase melanoma risk later in life.
• Tanning bed use: These devices emit artificial UV radiation that increases melanoma risk by approximately 75%.
• Genetic mutations (BRAF, NRAS, KIT): Mutations in specific genes within pigment cells lead to uncontrolled growth; these mutations are present in 40-60% of melanoma cases.
• Family history and genetic predisposition: Individuals with relatives who had melanoma have 8-10 times higher risk than the general population.
• Fair skin and red hair: Individuals with white skin and red or blonde hair have reduced melanin production ability, increasing UV damage exposure.
• Previous skin conditions: Presence of atypical moles (dysplastic nevi) or large numbers of normal moles is associated with higher risk.
• Immunosuppression: Immunocompromised individuals (such as organ transplant recipients) or those with HIV have 100-fold higher risk.
• Personal history of skin cancer: Those previously diagnosed with one type of skin cancer are at increased risk for developing another type.

• Age: Melanoma occurs at all ages but is most common between 20-40 years, with another increase after age 60.
• Male sex: Men are 1.5-2 times more likely to develop melanoma than women.
• Fair skin color: Incidence rate is 20-30 times higher in Caucasians compared to African Americans.
• Number of moles: Having more than 50 moles or atypical moles significantly increases risk.
• Family history of melanoma: Two or more melanoma cases in the family suggests familial melanoma syndrome.
• Immunosuppression: Acquired (HIV, organ transplant) or congenital immunodeficiencies increase risk.
• Occupational chemical exposure: Exposure to substances like arsenic or tar increases risk.
• Xeroderma Pigmentosum syndrome: Rare genetic disorder preventing DNA repair from UV damage.
• Outdoor occupations: Workers exposed to sun for long hours (farmers, construction workers) have higher risk.
• Obesity: Some studies suggest correlation between obesity and increased advanced melanoma risk.

Melanoma diagnosis relies on a combination of careful clinical examination, laboratory tests, and imaging. The physician starts by taking a detailed history of moles and skin changes, then performs comprehensive skin examination using a dermoscope, a device that magnifies skin to detect suspicious characteristics. Any suspicious mole warrants biopsy, the only definitive diagnostic method. After diagnosis confirmation, disease stage and spread potential are determined.

• Clinical Examination and Dermoscopy: Precise visual examination using a specialized magnifying lens to detect suspicious patterns and colors (such as hair-like streaks, radial lines, dots, and streaks).
• Skin Biopsy: Small tissue sample taken under local anesthesia and examined under microscope. This is the gold standard for melanoma diagnosis and subtype determination (Superficial Spreading, Nodular, Lentigo Maligna, Acral Lentiginous).
• Sentinel Lymph Node Biopsy: For melanoma thicker than 1mm, this test determines if cancer has spread to nearby lymph nodes. Radioactive dye is injected near the mole to track the first lymph node cancer cells reach.
• Laboratory Tests: Routine blood tests (complete blood count, liver and kidney function tests) and LDH (Lactate Dehydrogenase) measurement, which may be elevated in advanced melanoma.
• CT Scan: Confirms disease spread to distant organs (lungs, liver, brain, bones), especially in advanced cases.
• MRI (Magnetic Resonance Imaging): Specifically used to check for disease spread to brain and spinal cord.
• PET Scan (Positron Emission Tomography): In advanced cases (stage 3-4), helps detect distant metastases.
• Genetic Mutation Testing: Tumor sample analysis to detect specific mutations (BRAF, NRAS, KIT, c-MET) for prognosis prediction and targeted therapy guidance.

Medications

• Checkpoint Inhibitors: Such as Pembrolizumab, Nivolumab, and Ipilimumab, which release immune brakes allowing immune system to attack cancer cells. Used for advanced and metastatic melanoma. Response rates 40-60% with potential immune-related side effects.
• Targeted Therapy: Such as Vemurafenib and Dabrafenib (BRAF inhibitors) and Trametinib (MEK inhibitor), for patients with BRAF mutations. Provide rapid response but resistance may develop after 6-12 months. Response rates 50-70%.
• Chemotherapy: Such as Dacarbazine and Temozolomide, used in very advanced cases where other options have failed. Lower response rates (10-20%) with significant side effects.
• Adjuvant Therapy: After surgical excision in melanoma thicker than 1mm, checkpoint inhibitor (such as Pembrolizumab) or targeted therapy may be given to reduce recurrence risk.

Procedures and Surgery

• Wide Surgical Excision: Removal of the mole with safety margins of surrounding healthy skin. Excision depth depends on tumor thickness (5mm to 2cm). This is primary treatment for all primary melanomas.
• Lymph Node Dissection: Removal of nearby lymph node group if biopsy shows cancer spread. Arm or leg swelling may occur after surgery.
• Laser Therapy: Using laser beam to remove suspicious skin lesions, used for very small or atypical surface lesions.
• Cryotherapy: Using liquid nitrogen to freeze the skin lesion, used for small superficial lesions.
• Electrocautery: Burning the lesion using electrical current, for superficial lesions.
• Radiation Therapy: May be used after surgery to reduce recurrence risk in high-risk cases, or to treat distant metastases (especially brain).

Lifestyle Changes and Support

• Sun Protection: Use sunscreen SPF 30 or higher daily, wear protective clothing (hats, sunglasses, long-sleeved shirts), avoid sun exposure between 10am-4pm when rays are strongest.
• Regular Self-Examination: Full body examination monthly using mirrors to notice any new or suspicious mole changes, especially in hard-to-reach areas.
• Regular Medical Follow-up: Regular dermatologist visits (every 3-6 months) especially in first years after diagnosis to detect any early recurrence.
• Psychological and Social Support: Counseling and patient support groups may help cope with diagnosis and treatment psychological effects.
• Dietary Modification: Healthy diet rich in antioxidants (fruits and vegetables) may support immune function.
• Avoid Smoking and Alcohol: Smoking and alcohol weaken immunity and increase complications.

• Regional Lymph Node Metastasis: Cancer spread to nearby lymph nodes, making cancer more aggressive and reducing survival rate. May require lymph node dissection and additional treatment.
• Distant Metastasis: Cancer spread to distant organs such as lungs, liver, brain, and bones. Represents advanced disease stage requiring systemic treatment (chemotherapy or immunotherapy). 5-year survival rate drops to approximately 10-15%.
• Surgical Site Bleeding or Infection: After surgical excision, bleeding or infection may occur at wound site, requiring immediate treatment.
• Lymphedema: Fluid accumulation and chronic swelling in arm or leg after lymph node dissection. May be permanent requiring lifelong management.
• Immune-Related Adverse Events: Checkpoint inhibitors may cause skin, bowel, lung, thyroid inflammation and even kidney failure in severe cases.
• Psychological and Social Effects: Depression, anxiety, sleep disorders, and negative impact on social and professional life are very common after cancer diagnosis.
• Local Recurrence: Cancer return at original excision site, especially if adequate safety margins were not taken during excision.
• Secondary Skin Cancers: Melanoma patients have higher risk (10-20%) of developing another skin cancer in the future.

• Avoid Direct Sun Exposure: Stay in shade during peak hours (10am-4pm), especially in Jordan where sun is very intense. Wear wide-brimmed hat and sunglasses providing 100% UV protection.
• Use Sunscreen Daily: Use sunscreen with SPF 30 or higher, reapply every 2 hours or after swimming. Use adequate amount (1 teaspoon for face).
• Wear Protective Clothing: Choose tightly-woven clothes providing UV protection (such as UPF swimwear), wear long-sleeved shirts and long pants when spending extended time outdoors.
• Avoid Tanning Beds: Do not use artificial tanning beds, as studies prove they increase melanoma risk by 75%.
• Regular Dermatology Screening: People with risk factors (fair skin, family history, many moles) should be examined at least annually by a specialist.
• Monthly Self-Examination: Learn ABCDE criteria and examine your body monthly; ask partner or family member to check your back and scalp.
• Protect Children: Sun protection in childhood and adolescence is critical, as sunburns in these stages significantly increase later risk. Use child-safe sunscreen (without PABA or oxybenzone).
• Avoid Smoking: Smoking weakens immune system and increases cancer-related complications.
• Maintain Healthy Weight: Obesity may correlate with increased advanced melanoma risk and poor outcomes.
• Strengthen Immunity: Get adequate sleep, exercise regularly, eat balanced diet rich in antioxidants and vitamins to help immune system fight cancer.