Makindo Medical Notes

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If you find a lesion suspicious for melanoma, always check local lymph nodes, examine the liver, and refer to a specialist.

About

• Malignant melanoma is the most lethal type of skin cancer, responsible for approximately 1,500 deaths annually in the UK.
• Early diagnosis is crucial, as early-stage melanoma has a 95% cure rate, but this rate drops significantly with delayed presentation.
• The incidence of melanoma is increasing, and half of melanomas arise in normal skin rather than preexisting moles.

Aetiology

• Melanoma originates from melanocytes and is the most deadly skin neoplasm, capable of spreading rapidly to lymph nodes and distant organs.
• While many melanomas develop from existing moles, others arise in previously normal skin, highlighting the importance of monitoring all skin changes.
• Melanocytes in various locations (skin, eyes, ears, gastrointestinal tract, leptomeninges, and mucous membranes) can also develop melanoma.

Risk Factors

• Family history of melanoma
• Fair skin, freckles, and a tendency for sunburn
• Excessive sun exposure, especially with early severe sunburn
• Having over 50 moles or a diagnosis of dysplastic nevus syndrome
• Atypical or congenital moles
• Older age
• Xeroderma pigmentosum (a rare genetic disorder increasing UV sensitivity)

Clinical Presentation

• Suspicious skin lesions, which can be flat, nodular, or pigmented. Use the ABCDE rule for self-examination:

ABCDE Rule for Self-Examination

• Asymmetry: One half of the mole does not match the other.
• Border irregularity: Edges may be ragged or blurred.
• Colour variation: Varies with shades of brown, black, pink, blue, or red.
• Diameter: Greater than 6 mm.
• Elevation or changes in size, shape, or bleeding.

Breslow’s Depth and Prognosis

• Breslow’s Depth: Measured from the epidermal granular layer to the deepest point of tumor invasion.
• Prognosis depends on Breslow’s depth:
  • < 0.5 mm: 100% 5-year survival
  • 0.6-1.0 mm: 98% 5-year survival
  • 1.1-1.5 mm: 90% 5-year survival
  • 1.6-2.0 mm: 80% 5-year survival
  • 2.1-3.0 mm: 60% 5-year survival
  • > 3.0 mm: 50% 5-year survival

Additional Poor Prognostic Indicators

• Ulcerative lesions
• Increased mitotic rate
• Lesions on the trunk
• Male gender

Melanoma Subtypes

• Superficial spreading melanoma: 70% of cases
• Nodular melanoma: 15%, often arising de novo
• Lentigo maligna melanoma: 10%, typically in elderly patients
• Acral lentiginous melanoma: 5%, common on palms and soles

Investigations

• Wide local excision and biopsy for Breslow depth measurement
• Staging workup if Breslow depth > 1 mm
• Tests for metastatic spread:
  • LFTs (liver involvement)
  • Biopsy of enlarged lymph nodes
  • Lymphoscintigraphy for sentinel node identification
  • LDH, CT, MRI, ultrasound, chest X-ray

Staging of Melanoma

• Based on tumor thickness (Breslow depth), ulceration, and mitotic rate:
  • Stage I: Tumor confined to epidermis (in situ), non-invasive.
  • Stage II: Breslow depth of 1-4 mm, with or without ulceration.
  • Stage III: Metastasis to nearby lymph nodes, skin, or underlying tissue (in-transit or satellite metastases).
  • Stage IV: Distant metastasis to organs (lung, liver, brain, bone) or distant lymph nodes.

Management

• Wide Local Excision: Surgical removal with clear margins based on Breslow depth.
• Sentinel Lymph Node Biopsy: Recommended for tumors >1 mm thickness or if lymphadenopathy is present, to assess metastatic spread.
• Metastatic Melanoma:
  • Interferon alpha-2B for 1 year (high cost and side effects)
  • Chemotherapy: Dacarbazine (DTIC) and combinations (limited efficacy)
  • Immunotherapy and targeted treatments (described below)

New Immune-Modulating Therapies

• Ipilimumab: Recommended for advanced melanoma; administered as an infusion every three weeks (four doses).
• Nivolumab: Intravenous treatment every two weeks; used alone or with ipilimumab for advanced cases.
• Pembrolizumab: Infused every three weeks for advanced melanoma; common side effects include diarrhoea, rash, and fatigue.
• Talimogene Laherparepvec: Injected directly into tumors; often used if other immunotherapies are unsuitable.

Targeted Treatments for Genetic Mutations

• Approximately 40-50% of melanomas have BRAF V600 mutations:
  • Vemurafenib: Targets BRAF V600 mutations; commonly used with cobimetinib.
  • Dabrafenib: Another BRAF inhibitor, often combined with trametinib.
  • Trametinib: Blocks abnormal BRAF protein; used alone or with dabrafenib.

Radiotherapy and Chemotherapy

• Radiotherapy: May be used after lymph node removal or to relieve symptoms of advanced melanoma. Treatment frequency varies, often daily over several weeks with weekends off.
• Chemotherapy: Rarely used for melanoma, as newer targeted and immune therapies have shown greater efficacy.

Melanoma Vaccines

• Research is ongoing to develop vaccines for melanoma, aimed at treating advanced cases or preventing recurrence in high-risk patients. Currently available only in clinical trials.

Conclusion

• Early detection and wide excision are critical in managing melanoma due to its high metastatic potential.
• Advanced melanoma treatment is evolving with new immune-modulating and targeted therapies, though prevention and early intervention remain paramount for better prognosis.