Imiquimod for Melanoma in Situ and Lentigo Maligna: A Systematic Review

Melanoma in situ (MIS) and lentigo maligna (LM) present challenges, particularly in anatomically sensitive areas where surgical excision may result in morbidity. Topical imiquimod is increasingly used as a noninvasive alternative for MIS and LM.

To evaluate the efficacy, safety, and optimal treatment protocols of topical imiquimod for MIS and LM.

A review of current literature was conducted using multiple databases. Studies reporting histologically confirmed MIS or LM treated with topical imiquimod were included. Outcomes included histological clearance, recurrence, and adverse events.

Thirteen studies encompassing 129 individual cases were analyzed (2000-2025). Reported histological clearance rates were approximately 84.5% (range, 77%-90%). Treatment duration ranged from 4 to 44 weeks, with most protocols lasting 8 to 16 weeks. Among cases with follow-up data, recurrence rates ranged from 0.5% to 15%. Common adverse effects included erythema and local irritation, and an inflammatory response was strongly associated with treatment success.

Topical imiquimod is a reasonable and efficacious treatment option for MIS and LM, particularly in anatomically challenging locations, and represents a valuable nonsurgical option with an acceptable safety profile; however, heterogeneous protocols, limited long-term follow-up, and small sample sizes limit certainty, and standardized treatment protocols are needed.