Malignant Melanoma

Malignant melanoma is an aggressive malignant tumor arising from melanocytes, the pigment-producing cells of the skin. It is characterized by a high potential for local invasion and early metastasis compared with other skin cancers. Early diagnosis and complete surgical excision provide the best chance of cure, while advanced disease may require systemic therapy and palliative treatment.

The most important clinical indicator is a change in a pre-existing nevus (mole), including changes in size, color, surface characteristics, or symptoms such as itching and ulceration.

Epidemiology

Malignant melanoma is less common than non-melanoma skin cancers but accounts for a significant proportion of skin cancer-related deaths because of its metastatic potential. The incidence varies according to geographic location, ultraviolet radiation exposure, and genetic susceptibility.

Risk factors

Risk factors for malignant melanoma include:

• Excessive ultraviolet radiation exposure.

• History of previous melanoma.

• Multiple or atypical nevi.

• Changes occurring in pre-existing nevi.

• Light-colored skin.

• Family history of melanoma.

• Immunosuppression.

• Previous severe sunburns.

Pathophysiology

Malignant melanoma develops from malignant transformation of melanocytes. Genetic mutations and environmental factors, particularly ultraviolet radiation exposure, contribute to uncontrolled melanocyte proliferation.

The tumor may initially remain localized within the skin but can progressively invade deeper layers and spread through lymphatic and hematogenous routes to distant organs, including:

• Lymph nodes.

• Lungs.

• Liver.

• Brain.

• Bone.

Tumor depth is a major determinant of prognosis.

Clinical presentation

Malignant melanoma commonly presents as a changing pigmented skin lesion. It may arise from a pre-existing nevus or appear as a new lesion on normal skin.

Suspicious lesions require prompt evaluation and biopsy because early treatment improves outcomes.

Symptoms

Symptoms include:

• Itching of a pre-existing nevus.

• Change in color of a mole.

• Increase in size of a mole.

• Development of satellite lesions.

• Elevation of the surface of a lesion.

• Ulceration.

• Oozing or bleeding from the lesion.

• Pain or discomfort in advanced lesions.

• Symptoms related to metastatic disease.

Clinical signs

Clinical features suggestive of malignant melanoma include:

• Asymmetrical pigmented lesion.

• Irregular borders.

• Uneven pigmentation.

• Recent enlargement of a nevus.

• Elevated lesion surface.

• Ulcerated lesion.

• Oozing or bleeding lesion.

• Satellite lesions around the primary tumor.

• Regional lymphadenopathy.

• Signs of metastatic disease in advanced stages.

Differential diagnosis

Conditions that may mimic malignant melanoma include:

• Benign melanocytic nevus.

• Dysplastic nevus.

• Seborrheic keratosis.

• Pigmented basal cell carcinoma.

• Pigmented squamous cell carcinoma.

• Dermatofibroma.

• Hemangioma.

• Kaposi sarcoma.

• Post-inflammatory hyperpigmentation.

Diagnostic criteria

Malignant melanoma should be suspected in patients with:

• A pre-existing nevus that has recently changed.

• New symptoms such as itching, ulceration, or oozing from a mole.

• Increase in lesion size.

• Change in lesion color.

• Development of satellite lesions.

• Raised or irregular surface of a pigmented lesion.

Definitive diagnosis requires histopathological examination of the suspicious lesion.

Investigations

Histopathological investigation

• Excisional biopsy of the suspicious lesion for histopathology.

Imaging investigations

Imaging is performed for staging and evaluation of metastatic disease:

• Chest X-ray (CXR).

• Ultrasound or computed tomography (CT) scan of the abdomen and pelvis.

• Positron emission tomography-computed tomography (PET/CT).

Diagnostic staging

Staging is based on tumor characteristics and depth of invasion.

Clark classification

Assesses the anatomical level of skin invasion.

Breslow classification

Measures tumor thickness and closely correlates with prognosis.

Tumor thickness is an important predictor of:

• Risk of metastasis.

• Survival outcomes.

• Treatment planning.

Management

Management depends on:

• Tumor thickness.

• Disease stage.

• Presence of metastasis.

• Resectability.

• Patient factors.

Surgery is the primary treatment for localized disease.

Non-pharmacological treatment

Surgical treatment

Wide local excision

The primary treatment is:

• Wide local excision of the melanoma with appropriate margins.

Skin grafting may be required following excision of large lesions.

Amputation

Amputation may occasionally be performed for:

• Advanced disease.

• Affected limbs where preservation is not practical or useful.

Radiotherapy

Radiotherapy is mainly used for palliation.

Indications

• Inoperable lesions.

• Positive or very close excision margins.

• Palliative treatment for metastatic symptoms.

Palliative radiotherapy doses

For inoperable lesions:

• 30 Gy in 6 fractions over 1 week.

For other palliative indications:

• 30 Gy in 10 fractions.

OR

• 20 Gy in 5 fractions.

Indications include:

• Brain metastases.

• Fungating tumors.

• Profuse bleeding.

• Bone pain.

Pharmacological treatment

Systemic chemotherapy may be used for advanced or metastatic disease.

Regimen 1

Cisplatin

• 20 mg/m² intravenously over 30 minutes daily on Days 1–4.

AND

Vinblastine

• 1.6 mg/m² intravenously as a bolus daily on Days 1–5.

AND

Dacarbazine

• 800 mg/m² intravenously over 30 minutes on Day 1.

Repeat every 21 days for 6 cycles.

Regimen 2

Dacarbazine

• 250 mg/m² intravenously over 30 minutes on Days 1–5.

Repeat every 21 days for 4 cycles.

Regimen 3

Temozolomide

• 200 mg/m² orally on Days 1–5.

Repeat every 28 days.

Management according to disease stage

Localized melanoma

• Wide local excision.

• Skin grafting where required.

• Histological assessment of tumor characteristics.

Advanced limb disease

• Wide local excision where possible.

• Amputation may be considered for non-functional advanced disease.

Metastatic melanoma

• Systemic chemotherapy.

• Palliative radiotherapy for symptomatic metastatic lesions.

• Supportive care.

Referral

All patients with suspected or confirmed malignant melanoma should be referred to a specialized oncology center for:

• Histological confirmation.

• Staging.

• Definitive treatment planning.

• Long-term follow-up.

Urgent referral is required for:

• Rapidly changing pigmented lesions.

• Ulcerated or bleeding lesions.

• Evidence of lymph node involvement.

• Suspected metastatic disease.

Complications

• Local recurrence.

• Regional lymph node metastasis.

• Distant metastasis.

• Brain metastases.

• Bone metastases.

• Pain.

• Bleeding from ulcerated lesions.

• Functional impairment.

• Death.

Prognosis

Prognosis depends mainly on:

• Tumor thickness (Breslow depth).

• Presence of ulceration.

• Disease stage.

• Lymph node involvement.

• Presence of distant metastases.

Early-stage melanoma treated with complete surgical excision has a good prognosis. Advanced metastatic melanoma has a poorer prognosis due to widespread disease.

Prevention

Prevention and early detection include:

• Regular self-examination of the skin.

• Screening of high-risk individuals.

• Prompt evaluation of changing nevi.

• Early treatment of suspicious skin lesions.

• Avoidance of excessive ultraviolet radiation exposure.

• Use of protective clothing and sun protection measures.

Follow-up

Patients require regular follow-up after treatment to detect:

• Local recurrence.

• New primary melanoma.

• Regional lymph node involvement.

• Distant metastasis.

Follow-up should include:

• Clinical skin examination.

• Assessment of lymph node regions.

• Imaging when clinically indicated.