Summary

Malignant Melanoma is a proliferation of atypical melanocytes (pigment-producing cells) located in the basal layer of the epidermis. While it accounts for less than 5% of skin cancers, it causes over 75% of skin cancer deaths. The incidence is rising faster than any other solid tumour. Prognosis is directly related to tumour thickness (Breslow thickness) at diagnosis. Early detection is curative; advanced metastatic disease was historically fatal but has been revolutionised by Targeted Therapy (BRAF/MEK inhibitors) and Immunotherapy (Checkpoint inhibitors). It typically presents as a changing pigmented lesion, assessed using the ABCDE criteria and the "Ugly Duckling" sign.

Key Facts

• Most Common Cause: Intermittent, intense UV exposure (Sunburns). "Office worker pattern".
• Key Prognostic Factor: Breslow Thickness (measured in mm from granular layer to deepest invasion).
• Genetics: ~50% harbour BRAF V600E mutation (Targetable).
• Metastasis: Lymphatic (Nodes) and Haematogenous (Lung, Liver, Brain, Bone, Gut - "The tumour that goes to the bowel").
• Subtypes: Superficial Spreading (70%), Nodular (15% - Aggressive), Lentigo Maligna (Elderly/Face), Acral Lentiginous (Darker skin types).

Clinical Pearls

"The Ugly Duckling": Patients often have many moles ("Naevi") that look similar. The melanoma is the one that looks different to the rest. Trust this sign more than ABCDE in patients with many moles.

"Beware the Amelanotic Melanoma": Not all melanomas are black. Nodular melanomas can be pink/red. Any rapidly growing pink nodule that bleeds needs urgent assessment.

"Acral Melanoma Exception": Acral melanoma (soles/palms) is NOT related to UV exposure. It is the most common subtype in Black and Asian populations. Always check the feet!

"Never Shave a Melanoma": A shave biopsy transects the deep margin, making accurate Breslow thickness measurement impossible. This destroys the staging info. Excision Biopsy is the only correct diagnostic procedure.

T-Stage (Breslow Thickness)

• Tis: Melanoma in situ.
• T1: ≤1.0mm.
  • T1a: <0.8mm, no ulceration.
  • T1b: 0.8-1.0mm OR <0.8mm with ulceration.
• T2: 1.01 - 2.0mm.
• T3: 2.01 - 4.0mm.
• T4: >4.0mm.
  • a: No ulceration.
  • b: Ulceration present.

N-Stage and M-Stage

• N: Number of nodes. Micro vs Macro metastasis. Satellite/In-transit mets.
• M: Distant mets. LDH level affects staging (Elevated LDH = worse prognosis).

          SUSPICIOUS PIGMENTED LESION
                      ↓
        DERMOSCOPY + EXCISION BIOPSY (2mm margin)
                      ↓
        HISTOLOGY CONFIRMS MELANOMA
                      ↓
┌───────────────────────────────────────────────┐
│     BRESLOW THICKNESS DETERMINES ACTION       │
└───────────────────────────────────────────────┘
                      │
      ┌───────────────┼───────────────┐
    In Situ         <0.8mm          >0.8mm (or >1.0mmT1b)
      ↓               ↓               ↓
  WLE 0.5cm       WLE 1cm         WLE 1-2cm
  No SLNB         No SLNB         + SENTINEL LYMPH NODE BIOPSY
                                      ↓
                                ┌───────────┐
                                │ SLNB +ve? │
                                └───────────┘
                                 /         \
                               NO          YES (Stage III)
                             (Follow Up)    ↓
                                          ADJUVANT THERAPY
                                          (Immuno/Targeted)
                                          + Surveillance US
                                          (Completion Node Clearance
                                           rarely done now - MSLT-II)

Wide Local Excision (WLE) Margins

• In Situ: 0.5cm - 1cm.
• T1 (<1mm): 1cm.
• T2 (1-2mm): 1cm - 2cm.
• T3/T4 (>2mm): 2cm.

Rationale

The Sentinel Node is the first node that drains the tumour site. If the Sentinel Node is negative, the rest of the basin is negative in >99% of cases.

• Indication: Melanoma >0.8mm (T1b) or >1.0mm (T2+).
• Technique (Dual Tracer):
  1. Radioisotope (Technetium): Injected pre-op. Lymphoscintigraphy maps the basin. Intra-op gamma probe finds the "hot" node.
  2. Blue Dye (Patent Blue / Indocyanine Green): Injected intra-op. Visual confirmation of the "blue" node.
• Outcome:
  • Provides powerful prognostic info.
  • Access to Adjuvant Therapy (which requires Stage IIIA+).
  • Therapeutic?: MSLT-I and MSLT-II trials showed SLNB improves disease-free survival but NOT overall survival (melanoma-specific) for the whole cohort. However, it is essential for staging and access to drugs.

Completion Lymphadenectomy (CLND)

• Old Standard: If SLNB positive -> Remove all nodes.
• New Standard (Post-MSLT-II): If SLNB positive -> Ultrasound Surveillance of the basin. CLND is reserved for clinically palpable recurrence. Survival is the same, but morbidity (lymphoedema) is spared.

Historical chemotherapy (Dacarbazine) failure meant metastatic melanoma was a death sentence (survival 6-9 months). Now, 5-year survival is >50%.

1. Immunotherapy (Checkpoint Inhibitors)

• Anti-PD1: Nivolumab, Pembrolizumab. (Releases the "brake" on T-cells).
• Anti-CTLA4: Ipilimumab. (Works in the priming phase).
• Combination: Ipilimumab + Nivolumab ("Ipi-Nivo"). High toxicity (colitis, hepatitis) but highest response rates (~60%).
• Indication: Stage III (Adjuvant) and Stage IV (Metastetic). Works regardless of BRAF status.

2. Targeted Therapy (BRAF/MEK Inhibitors)

• Agents: Dabrafenib + Trametinib.
• Indication: BRAF V600 mutant melanoma ONLY.
• Effect: Rapid tumour shrinkage ("Lazarus effect").
• Problem: Resistance develops after 12-18 months.

Follow-Up Schedule

• Stage I: 3-monthly for 1 year, then annual.
• Stage II/III: 3-monthly for 3 years, then 6-monthly.
• What to look for:
  1. Local Recurrence (Scar).
  2. In-Transit Mets (Lumps between scar and nodes).
  3. Nodal Recurrence.
  4. New Primary Melanoma.

Prognosis (5-Year Survival)

• Stage I (Thin): >98%.
• Stage II (Thick, Node Neg): 80%.
• Stage III (Node Pos): 60% (improving with adjuvant tx).
• Stage IV (Distant): 25-50% (was <10%).

Key Trials

1. MSLT-II (NEJM 2017): Completion lymph node dissection is NOT necessary for positive sentinel nodes. Regular ultrasound is safe.
2. CHECKMATE-238: Nivolumab superior to Ipilimumab for adjuvant therapy.
3. COMBI-AD: Dabrafenib + Trametinib improves survival in adjuvant BRAF+ setting.

What is Melanoma?

Melanoma is the most serious type of skin cancer. It starts in the cells that give skin its colour (melanocytes). It can grow quickly and spread to other parts of the body (lymph nodes, lungs, brain) if not treated early.

What are the warning signs?

Remember ABCDE:

• Asymmetry: The mole looks uneven.
• Border: The edges are jagged or blurry.
• Colour: It has mix of colours (black, brown, pink).
• Diameter: It is larger than a pencil eraser (6mm).
• Evolving: It is changing in size, shape, or itchiness. This is the most important sign.

How is it treated?

• Early: A simple operation to remove the melanoma and a safety margin of skin around it cures most patients.
• Advanced: If it has spread, we use powerful new drugs (immunotherapy) that train your immune system to fight the cancer. These have dramatically improved survival rates.

Can I prevent it?

Yes. Sunburn is the biggest cause.

• Wear SPF 50+.
• Avoid tanning beds completely.
• Wear hats and long sleeves.
• Get regular skin checks if you have many moles.