Melanoma

Overview

Melanoma is the most dangerous form of skin cancer, developing in the melanocytes—cells that produce melanin, the pigment that gives skin its color. While melanoma accounts for only about 1% of skin cancers, it causes the vast majority of skin cancer deaths. This aggressive cancer has the ability to spread rapidly to other organs if not detected and treated early, making awareness and early detection crucial for survival.

The incidence of melanoma has been rising steadily over the past few decades, with approximately 100,000 new cases diagnosed annually in the United States alone. However, when detected early, melanoma is highly treatable, with a 5-year survival rate of 99% for localized disease. This dramatic difference in outcomes between early and late-stage disease underscores the critical importance of regular skin examinations and prompt medical attention for suspicious lesions.

Melanoma can develop anywhere on the body, including areas not typically exposed to sun, such as the soles of feet, palms, nail beds, and even internal organs. While it most commonly appears as a new spot on the skin or a change in an existing mole, melanoma's presentation can vary significantly. Understanding risk factors, recognizing warning signs, and adopting preventive measures are essential components of reducing melanoma's impact on public health.

Symptoms

Melanoma symptoms primarily involve changes in the skin's appearance. Early detection through recognition of these changes dramatically improves treatment outcomes and survival rates.

Primary Skin Manifestations

The ABCDE Warning Signs

• Asymmetry: One half of the mole doesn't match the other half
• Border: Edges are irregular, ragged, notched, or blurred
• Color: Color is not uniform; may include shades of brown, black, pink, red, white, or blue
• Diameter: Larger than 6mm (about the size of a pencil eraser), though melanomas can be smaller
• Evolving: The mole is changing in size, shape, color, or symptoms

Additional Warning Signs

• A sore that doesn't heal
• Spread of pigment from the border into surrounding skin
• Redness or swelling beyond the border
• Change in sensation: itchiness, tenderness, or pain
• Change in surface: bleeding, oozing, or crusting
• Itchy eyelid or other unusual itching
• Irregular appearing scalp lesions

Advanced Stage Symptoms

• Swollen lymph nodes - May indicate spread to lymphatic system
• Skin swelling around the primary site
• Hard lumps under the skin
• Unexplained weight loss
• Fatigue
• Headaches (if spread to brain)
• Cough or breathing difficulties (if spread to lungs)

Locations of Concern

• Men: Most common on trunk (chest and back)
• Women: Most common on legs
• Hidden areas: Between toes, on palms/soles, under nails, in mouth, genital area
• Scalp: Often hidden by hair, requiring careful examination

Causes

Melanoma develops when melanocytes undergo malignant transformation due to DNA damage. This process involves multiple factors that lead to uncontrolled cell growth and the potential for metastasis.

Primary Cause: UV Radiation

The leading cause of melanoma is exposure to ultraviolet (UV) radiation, which damages DNA in skin cells:

• UVB rays: Cause direct DNA damage and sunburns
• UVA rays: Penetrate deeper, causing indirect DNA damage through oxidative stress
• Artificial sources: Tanning beds increase risk by 75% with first use before age 35
• Intermittent intense exposure: Blistering sunburns, especially in childhood
• Cumulative exposure: Long-term sun exposure over years

Genetic and Molecular Factors

• BRAF mutations: Found in about 50% of melanomas
• NRAS mutations: Present in 15-20% of cases
• NF1 mutations: Associated with certain melanoma subtypes
• CDKN2A mutations: Hereditary melanoma syndrome
• MC1R variations: Red hair gene associated with increased risk

Contributing Factors

• Immune suppression: Organ transplant recipients, HIV/AIDS patients
• Chemical exposure: Certain pesticides and industrial chemicals
• Previous melanoma: 5-10% chance of developing second melanoma
• Xeroderma pigmentosum: Rare genetic condition with defective DNA repair
• Large congenital nevi: Giant moles present at birth

Risk Factors

Understanding risk factors helps identify individuals who need closer monitoring and more aggressive prevention strategies.

Major Risk Factors

• Fair skin: Less melanin provides less UV protection
• History of sunburns: One or more severe, blistering sunburns
• Excessive UV exposure: From sun or tanning beds
• Many moles: 50+ ordinary moles or several atypical moles
• Family history: 10% of melanomas occur in families with history
• Personal history: Previous melanoma or other skin cancers
• Weakened immune system: From disease or medications

Demographic Factors

• Age: Average age at diagnosis is 65, but common in young adults
• Gender: Higher rates in men, but more common in young women
• Race: 20x more common in whites than African Americans
• Geographic location: Higher rates in sunny climates and high altitudes

Physical Characteristics

• Blue or green eyes
• Blonde or red hair
• Freckling tendency
• Inability to tan
• Dysplastic nevus syndrome

Genetic Risk Factors

• CDKN2A mutations: 40% lifetime risk
• CDK4 mutations: Rare but high risk
• BAP1 mutations: Associated with uveal melanoma
• MITF mutations: Melanoma and renal cell carcinoma syndrome

Diagnosis

Early and accurate diagnosis of melanoma is crucial for successful treatment. The diagnostic process involves clinical examination, dermoscopy, biopsy, and staging procedures.

Initial Evaluation

• Visual examination: Full-body skin check by dermatologist
• Dermoscopy: Magnified examination of suspicious lesions
• Digital monitoring: Photography for tracking changes over time
• Medical history: Risk factors, family history, sun exposure

Biopsy Types

• Excisional biopsy: Preferred method - removes entire lesion with narrow margin
• Incisional biopsy: Removes portion of large lesions
• Punch biopsy: Cylindrical sample for smaller lesions
• Shave biopsy: Generally avoided due to inadequate depth assessment

Pathology Assessment

Microscopic examination determines:

• Breslow thickness: Depth of invasion (most important prognostic factor)
• Clark level: Anatomic depth of invasion
• Ulceration: Presence indicates worse prognosis
• Mitotic rate: Number of dividing cells
• Margins: Whether cancer cells extend to edge of specimen
• Regression: Evidence of immune response

Staging Procedures

Stage 0-II (Early Stage)

• Physical examination
• Sentinel lymph node biopsy for tumors >1mm or with high-risk features
• No routine imaging needed

Stage III-IV (Advanced Stage)

• CT scan of chest, abdomen, and pelvis
• PET/CT scan for comprehensive staging
• Brain MRI
• LDH blood test
• Molecular testing for targeted therapy options

TNM Staging System

• T (Tumor): Size and characteristics of primary tumor
• N (Nodes): Spread to nearby lymph nodes
• M (Metastasis): Spread to distant organs

Treatment Options

Melanoma treatment depends on stage, location, patient health, and molecular characteristics. Recent advances in immunotherapy and targeted therapy have dramatically improved outcomes for advanced disease.

Surgical Treatment

Primary Tumor Excision

• Wide local excision: Removes tumor with safety margin
• Margins based on thickness:
  • In situ: 0.5-1 cm margin
  • <1 mm: 1 cm margin
  • 1-2 mm: 1-2 cm margin
  • >2 mm: 2 cm margin
• Mohs surgery: For facial melanomas where tissue preservation is critical

Lymph Node Management

• Sentinel lymph node biopsy: Identifies first draining node
• Completion lymph node dissection: If sentinel node positive
• Therapeutic lymph node dissection: For clinically evident disease

Systemic Therapy

Immunotherapy

• Checkpoint inhibitors:
  • Pembrolizumab (Keytruda)
  • Nivolumab (Opdivo)
  • Ipilimumab (Yervoy)
  • Combination nivolumab + ipilimumab
• Interleukin-2: High-dose for select patients
• Oncolytic virus therapy: Talimogene laherparepvec (T-VEC)

Targeted Therapy

• BRAF inhibitors: Vemurafenib, dabrafenib, encorafenib
• MEK inhibitors: Trametinib, cobimetinib, binimetinib
• Combination BRAF/MEK: Improved outcomes over monotherapy
• KIT inhibitors: For specific mutations

Radiation Therapy

• Adjuvant radiation after lymph node dissection
• Palliative radiation for brain metastases
• Stereotactic radiosurgery for limited brain lesions
• Radiation for symptomatic bone metastases

Treatment by Stage

• Stage 0: Wide excision only
• Stage I-II: Wide excision ± sentinel node biopsy
• Stage III: Surgery + adjuvant immunotherapy or targeted therapy
• Stage IV: Systemic therapy, consider surgery for limited disease

Prevention

Most melanomas are preventable through sun protection and early detection strategies. A comprehensive approach combining primary prevention and screening can significantly reduce melanoma incidence and mortality.

Sun Protection Strategies

• Sunscreen use:
  • Broad-spectrum SPF 30 or higher
  • Apply 30 minutes before exposure
  • Reapply every 2 hours and after swimming
  • Use 1 ounce (shot glass) for full body
• Protective clothing:
  • Wide-brimmed hats
  • UV-protective clothing
  • Sunglasses with UV protection
• Behavioral measures:
  • Seek shade during peak hours (10 AM - 4 PM)
  • Avoid tanning beds completely
  • Be extra cautious near water, snow, and sand

Early Detection

• Self-examination: Monthly full-body skin checks
• Partner checks: For hard-to-see areas
• Professional screening: Annual dermatologist visits for high-risk individuals
• Photography: Document moles for comparison
• Dermoscopy apps: Aid in monitoring but don't replace professional evaluation

High-Risk Prevention

• More frequent dermatology visits (every 3-6 months)
• Total body photography
• Consider genetic counseling and testing
• Extra vigilance with sun protection
• Education of family members

Vitamin D Considerations

• Sun protection doesn't eliminate vitamin D production
• Consider supplementation if deficient
• Dietary sources: fatty fish, fortified foods
• Brief incidental sun exposure usually sufficient

When to See a Doctor

Early detection of melanoma dramatically improves outcomes. Know when to seek professional evaluation for skin changes.

Immediate Evaluation Needed

• Any new pigmented lesion after age 30
• Changes in existing moles (ABCDE criteria)
• Lesions that bleed, itch, or don't heal
• Rapidly growing skin lesions
• Multiple new moles appearing quickly
• Dark streaks under nails

Regular Screening Recommended

• High risk: Every 3-6 months
• Moderate risk: Every 6-12 months
• Average risk: Annual skin exam
• History of melanoma: Per oncologist/dermatologist guidance

Warning Signs Requiring Urgent Care

• Swollen lymph nodes near a suspicious lesion
• Multiple new lesions appearing simultaneously
• Symptoms suggesting metastasis (headaches, cough, bone pain)
• Any concerning changes in previously biopsied sites

Related Conditions

Several conditions are associated with or may be confused with melanoma:

Other Related Conditions

• Actinic Keratosis - Precancerous lesions
• Merkel Cell Carcinoma - Rare aggressive skin cancer
• Lentigo Maligna - Melanoma in situ subtype
• Blue Nevus - Benign but can be confused with melanoma
• Spitz Nevus - Benign tumor in children

Frequently Asked Questions

References

1. American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024.
2. Swetter SM, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019;80(1):208-250.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Melanoma. Version 2.2024.
4. Gershenwald JE, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-492.
5. Long GV, et al. Cutaneous melanoma. Lancet. 2023;402(10400):485-502.