Malignant melanoma

Disease Description (Causes and Symptoms)

• Definition: A malignant cutaneous neoplasm arising from melanin-producing cells (melanocytes), which can occur not only in the skin but also in the eye (uvea), mucous membranes (oral cavity, nasal cavity, esophagus, anus, etc.), and nails (nail unit).
• Causes·pathophysiology:
  • Although the exact mechanism of development is unknown, it is associated with genetic factors, ultraviolet exposure (particularly important in groups with fair skin, fine body hair, and a family history), skin type, and pre-existing nevi (moles).
  • In Asia, cases arising in acral areas less associated with ultraviolet exposure (the soles of the feet and nails) are relatively common (acral lentiginous type).
  • Pathologically, abnormal proliferation of melanocytes → invasion into the dermis → possible lymphatic and hematogenous metastasis. Tumor thickness (Breslow depth), ulceration, and dedifferentiation (high mitotic rate) affect prognosis.
• Main symptoms (features requiring attention — "ABCDE"):
  • A(Asymmetry): Asymmetry
  • B(Border): Irregular borders
  • C(Color): Uneven coloration (a mixture of black, brown, red, white, blue, etc.)
  • D(Diameter): Often 6 mm or larger, but can be smaller
  • E(Evolving): Changes in size, color, or shape; bleeding, ulceration, itching, or pain
• Pattern of occurrence: Approximately 2/3 develop newly on normal skin, while 1/3 develop through transformation of a pre-existing mole.

Treatment Methods

• Summary of standard treatment according to staging and lesion characteristics after diagnosis:
  1. Biopsy and pathology (excisional biopsy recommended): For suspicious lesions, a full-thickness excisional biopsy should be performed when possible, including measurement of depth (Breslow depth). Partial biopsy may be performed for large lesions.
  2. Surgery: Wide local excision of the primary lesion (the excision margin is determined according to Breslow depth)
     • Melanoma in situ (MIS): Usually 0.5–1 cm
     • Breslow ≤1.0 mm: 1 cm
     • 1.01–2.0 mm: 1–2 cm

     • 2.0 mm: 2 cm

  3. Lymph node evaluation
     • Sentinel lymph node biopsy (SLNB): Generally considered when Breslow ≥0.8–1.0 mm, or even when <1 mm if high-risk features such as ulceration or a high mitotic rate are present.
     • If SLNB is positive, complete lymph node dissection (selective under current guidelines; individualized because a clear survival benefit has not been established compared with observation in studies such as MSLT-II).
  4. Adjuvant treatment
     • Immune checkpoint inhibitors (anti-PD-1 agents): nivolumab, pembrolizumab — standard use for resectable lesions with a high risk of recurrence (e.g., stage III/IV).
     • Targeted therapy: In cases positive for a BRAF V600 mutation, combination adjuvant and systemic therapy with a BRAF inhibitor (e.g., dabrafenib) + a MEK inhibitor (e.g., trametinib) may be used.
     • Interferon and other previous therapies have been used in some settings, but immunotherapy and targeted therapy are currently prioritized as standard adjuvant treatments.
  5. Treatment of metastatic (unresectable) and advanced disease
     • Anti-PD-1 monotherapy or combination anti-CTLA-4 + anti-PD-1 therapy (e.g., ipilimumab + nivolumab) — selected according to the patient's condition and adverse-effect profile.
     • BRAF/MEK inhibitor combination therapy when BRAF-positive.
     • Radiation therapy: Used for local symptom relief in brain or bone metastases or as adjuvant treatment after surgery.
• Imaging for diagnosis and assessment of metastasis: CT, PET-CT, MRI (particularly of the brain), etc., may be used when necessary.
• Lifestyle management and precautions:
  • Regular self-examination of the skin and follow-up skin examinations by a specialist.
  • Wound care after surgery and lymphedema prevention education when lymph node dissection is performed.
  • During treatment with immune checkpoint inhibitors or targeted therapy, monitoring for drug-specific adverse effects (immune-related adverse events, fever, skin toxicity, etc.) is necessary.

Checklist Before an Outpatient Visit (Including Example Questions)

• Items and records to prepare:
  • Photos of the lesion (if possible, showing changes over time), and when changes began and how they have changed (size, color, bleeding, itching, etc.)
  • Whether any pre-existing moles (nevi) are present and whether they have changed
  • History of previous skin cancer diagnosis, family history (particularly melanoma), and previous severe sunburns (including during childhood)
  • List of currently used medications (including immunosuppressants) and allergy history
  • Underlying conditions (autoimmune diseases, infectious diseases, etc.) and overall physical condition
  • Previous tests (skin biopsy results, imaging, pathology reports, etc.)
• Things to do before the outpatient visit:
  • Take full-body photos and close-up photos of the lesion, if possible
  • Record recent symptoms (pain, bleeding, discharge, rapid growth)
• Example questions (phrased for asking the doctor)
  • "Does this lesion appear to require a biopsy? Does it need to be excised immediately?"
  • "Is this a situation in which SLNB (sentinel lymph node biopsy) is needed?"
  • "Are BRAF mutation testing or additional genetic tests needed?"

Examples of General Questions to Ask the Doctor

• Regarding diagnosis
  • "What does the current biopsy result mean? What is the stage?"
  • "Are any additional imaging or pathology tests needed?"
• Regarding treatment
  • "What will the extent of surgery and the expected excision margin be?"
  • "Is SLNB needed, and if so, what is the next treatment plan based on the results?"
  • "Is adjuvant immunotherapy or targeted therapy recommended, and what are the criteria for choosing it?"
• Regarding prognosis and follow-up
  • "What is the risk of recurrence after treatment, and how often should I have regular checkups?"
  • "What should I be careful about in daily life (sun protection, frequency of skin examinations, etc.)?"
• Regarding medications and adverse effects
  • "What are the main adverse effects of immunotherapy or targeted therapy, and how should they be managed?"

Examples of Disease-Specific Questions

• When the suspicious lesion is on the sole, nail, or mucous membrane:
  • "How likely is it that this lesion is acral lentiginous melanoma (sole/nail type), and does the diagnostic or treatment approach differ?"
• When changes are observed in a pre-existing mole (nevus):
  • "A mole that was already there has changed. Does it need to be widely excised immediately, or should a partial biopsy be performed first?"
• Regarding adjuvant treatment by stage (after excision):
  • "If SLNB is positive after excision, do I need to undergo complete lymph node dissection immediately, or can it be replaced with observation and imaging?"