Melanoma

Melanoma

• Definition and Incidence
  • Melanoma originates in the melanocytes, which produce the pigment melanin.
  • Although it accounts for a smaller percentage of skin cancer cases compared to basal cell and squamous cell carcinomas, it causes the majority of skin cancer–related deaths.
• Risk Factors
  • Ultraviolet (UV) Radiation: Excessive sun exposure (especially blistering sunburns in childhood), use of tanning beds.
  • Fair Skin and Light Hair/Eyes: Less melanin protection.
  • Family History: Certain inherited genetic mutations (CDKN2A, CDK4) or familial atypical multiple mole melanoma (FAMMM) syndrome.
  • Multiple or Atypical Moles: Dysplastic nevi, large congenital moles.
  • Immunosuppression: Weakened immune systems (e.g., transplant recipients) are at higher risk.
• Common Sites
  • Men: Often on the trunk (back, chest).
  • Women: Often on the legs.
  • Can appear in non–sun-exposed areas too, such as the palms, soles, and under the nails (acral lentiginous melanoma).
• Signs and Symptoms
  • Melanoma can appear as a new mole or change in an existing mole.
  • The ABCDE rule helps identify suspicious lesions:
    • A: Asymmetry
    • B: Border irregularity
    • C: Color variegation
    • D: Diameter >6 mm
    • E: Evolving or changing over time

Disease Progression

• Local Growth
  • Early melanoma typically remains within the epidermis (in situ) or dermis.
  • The depth of invasion (measured as Breslow thickness) is the most important prognostic indicator.
• Lymphatic Spread
  • Melanoma cells can spread to nearby lymph nodes—an important consideration in staging and prognosis.
• Distant Metastases
  • Common metastatic sites include lungs, liver, brain, and bones.
  • Once melanoma has spread beyond local lymph nodes, it is more challenging to treat.

Screening*

• Self-Examination
  • Monthly skin self-checks using the ABCDE guideline.
  • Note any new or changing moles, sores that won’t heal, or other suspicious lesions.
• Clinical Skin Exams
  • A dermatologist or qualified healthcare provider may perform a full-body skin exam in patients with high risk.
  • Frequency depends on personal or family history, number of moles, and prior history of skin cancers.
• Imaging or Dermoscopy
  • Dermoscopy (a specialized magnifying device) improves the accuracy of clinical diagnoses.
  • Photography / Mole Mapping: Can help track changes over time, especially in individuals with many moles or dysplastic nevi.
• No Universal Screening Guidelines
  • General population screening is not universally recommended; however, vigilance and early detection are key to improving outcomes.

Treatment Approaches

Treatment depends on the stage of melanoma, determined by the thickness of the lesion (Breslow depth), ulceration, involvement of lymph nodes, and any distant spread.

• Surgery
  • Wide Local Excision: For early-stage melanoma, removing the lesion with an appropriate margin of normal tissue.
  • Sentinel Lymph Node Biopsy (SLNB): Performed if the Breslow depth or other features suggest higher risk of nodal spread.
  • Complete Lymph Node Dissection: Historically performed if the sentinel node was positive, though current practice often favors close observation and adjuvant therapy over full dissection.
• Adjuvant Therapy
  • After surgery, immunotherapy or targeted therapy may be recommended in certain high-risk or stage III patients to reduce recurrence.
• Advanced/Metastatic Melanoma
  • Immunotherapy:
    • Checkpoint Inhibitors (e.g., nivolumab, pembrolizumab targeting PD-1; ipilimumab targeting CTLA-4).
    • These agents can significantly prolong survival in metastatic or high-risk melanoma.
  • Targeted Therapy:
    • BRAF Inhibitors (e.g., vemurafenib, dabrafenib) for melanomas with a BRAF V600 mutation.
    • MEK Inhibitors (e.g., trametinib, cobimetinib) often combined with BRAF inhibitors.
    • These combinations can shrink tumors and delay progression in mutated melanoma.
  • Combination Therapies:
    • Checkpoint inhibitors and targeted therapies used in combination or sequence, depending on mutation status and overall patient condition.
• Radiation Therapy
  • May be used for local control, particularly in metastatic sites (e.g., brain metastases).
  • Stereotactic radiosurgery (SRS) for limited brain mets.
• Palliative Care
  • Symptom management (pain control, managing side effects) and preserving quality of life in advanced disease.

 

Summary

Melanoma is a potentially serious form of skin cancer that can spread rapidly if not detected early. Surgical removal of thin, localized melanomas offers an excellent chance of cure. Sentinel lymph node biopsy helps in staging and deciding on additional treatments. The advent of immunotherapies (checkpoint inhibitors) and targeted therapies (BRAF/MEK inhibitors) has greatly improved outcomes for advanced or metastatic melanoma, transforming a once-frequently fatal disease into one that can often be controlled long-term or even achieve remission. Early detection through self-examination and timely clinical evaluation remains critical for optimal survival.

 

* Please note that screening programs may vary among different countries.