What are the diagnostic and treatment approaches for a patient suspected of having melanoma?

Melanoma: Diagnostic and Treatment Approach

Diagnosis

For any suspicious pigmented lesion, perform a full-thickness excisional biopsy with 2-5 mm margins extending into subcutaneous fat—this is the only acceptable diagnostic approach for suspected melanoma. 1, 2

Clinical Recognition

• Use the ABCDE criteria to identify suspicious lesions: Asymmetry, Border irregularity, Color heterogeneity, Diameter >6 mm (though 38% of melanomas are ≤6 mm), and Evolution over time 1, 3
• Apply the "ugly duckling" concept—melanomas often don't fit the patient's overall nevus pattern and stand out from other lesions 3
• Evolution (changes in size, color, or elevation) is the most critical criterion, particularly for rapidly growing nodular or amelanotic melanomas that may lack other ABCDE features 3
• Dermoscopy by an experienced examiner improves diagnostic accuracy beyond clinical examination alone 1, 4

Physical Examination Requirements

• Perform complete skin examination including full body surface inspection, regional lymph node palpation, abdominal examination, and documentation of lesion characteristics 2
• Examine for tumor satellites, in-transit metastases, and signs of regional or systemic spread 1

Biopsy Technique

• Full-thickness excisional biopsy is mandatory—includes deep reticular dermis and subcutaneous fat to allow accurate Breslow thickness measurement 1, 2, 5
• Use 2-5 mm clinical margin of normal skin laterally 2, 4
• Avoid incisional or superficial shave biopsies as they may miss depth and lead to inaccurate staging 5

Pathology Report Requirements

The histology report must include 1, 2:

• Breslow thickness in millimeters (most critical prognostic factor)
• Clark level of invasion (I-V)
• Presence and extent of ulceration
• Presence and extent of regression
• Surgical margin clearance status
• Histological type and variants

Staging Investigations

Low-Risk Disease (Stage I, II, IIIA)

• No routine imaging is recommended for pT1a melanomas or stage I-IIIA disease—false-positive rates are high and true-positive pickup rates are low 1

High-Risk Disease (Stage IIIB, IIIC, IV)

• Perform CT imaging of chest/abdomen/pelvis prior to surgery for stage IIIB or IIIC disease 1
• Measure lactate dehydrogenase for stage IV disease 1
• Screen tumor tissue for BRAF-V600 mutation in all metastatic melanoma patients to guide systemic therapy 1

Surgical Treatment

Wide Local Excision Margins

Surgical margins are determined by Breslow thickness 1:

Breslow Thickness	Lateral Excision Margin
In situ	0.5 cm
<1 mm	1 cm
1.01-2 mm	1-2 cm
2.1-4 mm	2-3 cm
>4 mm	3 cm

• Margins extend to muscle fascia 1
• Modifications may be needed for functional preservation on fingers, toes, or ears 1

Sentinel Lymph Node Biopsy

• Perform sentinel lymph node biopsy for melanomas >1 mm Breslow thickness and/or ulceration for accurate staging 1
• Consider for pT1b melanomas >0.75 mm 1
• Provides prognostic information but has not demonstrated overall survival benefit 1
• Should only be performed by skilled teams in experienced centers 1
• If sentinel node is positive, sample clinically suspicious nodes with fine needle aspiration cytology before formal block dissection 1

Systemic Therapy for Metastatic Disease (Stage IV)

First-line treatment options include anti-PD1 antibodies (nivolumab, pembrolizumab), ipilimumab (anti-CTLA4), or BRAF/MEK inhibitor combinations for BRAF-mutant melanoma. 1, 6

• Anti-PD1 antibodies are appropriate for all patients with metastatic melanoma 1
• BRAF/MEK inhibitor combinations are reserved for patients with confirmed BRAF-V600 mutations 1
• If approved immunotherapies or targeted agents are unavailable, dacarbazine or temozolomide may be used with modest palliative activity 1
• Consider surgical resection or stereotactic radiation for oligometastatic disease (skin, brain, gut) in fit patients 1

Adjuvant Therapy

• Evaluate all resected stage III melanoma patients for adjuvant interferon therapy 1
• Patients with microscopic nodal involvement and/or ulcerated primaries are most likely to benefit 1
• Encourage participation in clinical trials for stage IIIB and higher 1

Follow-Up Schedule

Follow-up intensity is stratified by stage 1:

Stage	Follow-Up Schedule
In situ	No follow-up required
IA	2-4 visits over 12 months, then discharge
IB-IIIA	Every 3 months for 3 years, then every 6 months to 5 years
IIIB, IIIC, resected IV	Every 3 months for 3 years, every 6 months to 5 years, then annually to 10 years
Unresectable IV	According to clinical need

High-Risk Patient Management

Urgent Referral Criteria

• Refer all melanoma-suspicious lesions urgently to a dermatologist or surgeon with pigmented lesion expertise within 2 weeks 2
• All patients with metastatic melanoma, multiple primary melanomas, children <19 years with melanoma, or uncertain malignant potential require Specialist Skin Cancer Multidisciplinary Team management 1

Surveillance for High-Risk Individuals

• Educate patients with atypical mole phenotype, prior melanoma, or organ transplant recipients on self-examination 1, 2
• Patients with giant congenital pigmented nevi require long-term follow-up due to increased melanoma risk 1, 2
• Refer families with ≥3 melanoma cases to clinical genetics; consider referral for 2 cases if one had multiple primaries 1, 2
• Prophylactic excision of small congenital nevi is not recommended 1

Patient Education

• Instruct all melanoma patients on lifelong avoidance of sunburns and extended unprotected UV exposure (solar or artificial) 1
• Teach monthly self-examination of skin and peripheral lymph nodes 1, 2

Critical Pitfalls to Avoid

• Do not perform superficial shave biopsies—they prevent accurate Breslow depth measurement 2, 5
• Do not rely solely on diameter >6 mm criterion—many melanomas are smaller 1, 3
• Do not dismiss symmetric, dome-shaped nodules—nodular melanomas often lack classic ABCDE features 3
• Maintain low threshold for biopsy in high-risk populations (prior skin cancer, immunosuppression, genetic syndromes) 2
• Do not perform routine imaging for early-stage disease—high false-positive rates lead to unnecessary interventions 1