What are the next steps for enlargement and erythema (redness) in the area where melanoma was treated?

Enlargement and Erythema at Melanoma Treatment Site

Enlargement and erythema at a previously treated melanoma site requires urgent clinical evaluation to distinguish between expected treatment-related inflammation (particularly if imiquimod was used), local recurrence, or infection—with biopsy of any suspicious areas being the definitive next step.

Immediate Assessment Required

The clinical context determines the urgency and approach:

• If the patient received topical imiquimod for melanoma in situ (lentigo maligna type), inflammation with erythema is an expected and even desired response during treatment, typically lasting several months 1
• However, lack of inflammation does not preclude favorable outcomes in the adjuvant setting following surgery, where histologic transection may represent benign changes 1
• If imiquimod was used, several months of induced inflammation may occur, which some patients find less tolerable than surgical excision 1

Critical Differential Diagnosis

Three primary considerations must be evaluated:

1. Local Recurrence (Most Critical)

• Any enlarging lesion at a previous melanoma site warrants immediate biopsy to exclude recurrence 2
• Lentigo maligna on the face has particularly high recurrence risk due to a "field effect" where atypical melanocytes extend laterally beyond clinically detectable margins 2
• After complete excision with adequate margins, local recurrence risk for melanoma in situ should be negligible 2—therefore enlargement suggests either inadequate initial margins or true recurrence

2. Treatment-Related Inflammation

• If imiquimod is being used (5-7 times per week for at least 12 weeks), erythema and inflammation are expected therapeutic responses 1
• Close, ongoing patient follow-up by experienced providers is essential when using nonsurgical interventions to observe for potential local recurrence 1

3. Infection (Particularly in Immunotherapy Patients)

• If the patient is receiving pembrolizumab or other checkpoint inhibitors, infection risk is significantly elevated 3
• Erythema, warmth, purulent drainage, fever, or systemic symptoms mandate immediate evaluation 3
• However, the absence of significant erythema or palpable warmth on exam is reassuring against active infection 3

Recommended Next Steps

The following algorithmic approach should be followed:

1. Obtain detailed treatment history:

   • Was the melanoma treated with surgery alone, imiquimod, radiation therapy, or combination? 1
   • What were the original surgical margins and Breslow thickness? 2, 4
   • Is the patient currently on or recently completed adjuvant immunotherapy? 3, 5

2. Perform focused physical examination:

   • Document exact size, borders, and characteristics of the erythematous area 2
   • Assess for warmth, tenderness, induration, or drainage 3
   • Examine regional lymph nodes 2
   • Take clinical photographs for documentation 2

3. Biopsy any suspicious areas:

   • Excisional biopsy is preferred as a full-thickness skin biopsy including the entire suspicious lesion with 2-5 mm margins and subcutaneous fat 2
   • Shave and punch biopsies are not recommended as they make pathological staging impossible 2
   • For facial lesions, incisional biopsy may be acceptable to establish diagnosis, but should only be performed by specialists within the skin cancer multidisciplinary team 2

4. If imiquimod-related inflammation is confirmed:

   • Continue treatment with close monitoring 1
   • Counsel patient that inflammation may persist for several months 1
   • Ensure follow-up visits are scheduled to detect potential recurrence 1

Common Pitfalls to Avoid

Several critical errors must be prevented:

• Do not assume inflammation is benign without tissue diagnosis—underestimating the extent of lentigo maligna, particularly on the face, can lead to incomplete excision and recurrence 2
• Do not perform incisional biopsies in primary care settings—these should only be done by specialists 2
• Do not delay evaluation in immunotherapy patients—repeated invasive procedures increase infection risk, but diagnostic biopsy when indicated takes precedence 3
• Avoid unnecessary invasive procedures that create portals for bacterial entry in immunotherapy patients, but do not avoid necessary diagnostic procedures 3

Follow-Up Surveillance

Regardless of the cause of enlargement and erythema:

• Patients should be followed annually throughout life to detect potential second melanomas 2
• Self-surveillance should be encouraged with appropriate patient education 2
• Eight percent of melanoma patients develop a secondary melanoma within 2 years of initial diagnosis 1
• Patients with lentigo maligna melanomas have a 35% risk of developing another cutaneous malignancy within 5 years 1

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