Melanoma Arising after Imiquimod Use

Abstract

Imiquimod belongs to the class of 1H-imidazo-[4,5-c]quinolones—drugs originally developed as nucleoside analogues with the aim of finding new potential antiviral agents (Harrison et al., 1988). Indeed, Imiquimod was first released as treatment for genital warts before its actions against skin cancer were studied. Imiquimod is a relatively small sized molecule (Mr = 240.3) and is hydrophobic, allowing it to penetrate the skin epidermal barrier and therefore making it suitable for topical formulations (Gerster et al., 2005). Imiquimod has shown itself effective against skin cancers and precancerous lesions, especially basal cell cancers and actinic keratosis (Salasche et al., 2002, Beutner et al., 1999). There have been reports of Imiquimod being used as topical treatment against cutaneous metastases of melanoma and some authors have reported its use as first-line therapy against melanoma in situ (Smyth et al., 2011, Gagnon, 2011). We report a case of an invasive malignant melanoma arising de novo at the specific site of application of Imiquimod (Aldara cream 5%) for a biopsy-proven superficial BCC. Therefore while Imiquimod has added to our topical armamentarium against skin cancer, care must be exercised in prescribing this treatment and it is especially important to follow up patients regularly.

Rare Cutaneous Side Effects of Imiquimod: A Review on Its Mechanisms, Diagnosis, and Management

“…Hair follicles stay in the telogen phase when their growth cycle is disrupted by some triggers, e.g., drugs, stress, surgery, and chronic inflammation, resulting in diffuse hair loss, which is called telogen effluvium [ 120 – 122 ]. To date, only three cases of hair loss related to the topical application of imiquimod have been reported [ 3 , 122 ].…”

“…In addition to SCC, 5% imiquimod cream has also been used off-label to treat cutaneous metastases of melanoma (MM), and has even been considered the first-line therapy for MM in situ (lentigo maligna) [ 3 , 8 , 142 , 143 ]. However, it should be noted that cases of MM arising following topical imiquimod treatment have also been reported.…”

“…Complete cure of the BCC and a newly emerging pigmented lesion at the application site were observed simultaneously at week 8 after beginning the treatment. The lesion was surgically resected and histologically confirmed to be invasive MM [ 3 ]. Dika et al [ 143 ] reported an 89-year-old woman diagnosed with in-transit melanoma metastases who received a combination of diathermocoagulation ablation and topical imiquimod.…”

“…Recently, there have been increasing reports of the treatment of other diseases benefiting from the off-label application of imiquimod, indicating its important potential in treating skin tumors and infectious diseases [ 6 , 7 ]. Due to its hydrophobicity and molecular size (Mr = 240.3), imiquimod has the property of percutaneous permeation, making it suitable for topical use, which offers patients a noninvasive and nonsurgical treatment modality for skin diseases [ 3 , 8 – 10 ]. Imiquimod is marketed in two concentrations, 5% and 3.75%, with the former being more widely used [ 1 ].…”

Topically Applied Resiquimod versus Imiquimod as a Potential Adjuvant in Melanoma Treatment

“…In addition, IMQ cream can result in side effects (e.g., burning sensation and erosive dermatitis [ 11 , 29 ]), severe enough in some patients to lead to treatment suspension [ 12 ]. There have also been reports of patients developing melanoma after being treated for non-melanoma lesions with topical IMQ cream [ 31 ]. Hence, the use of topical IMQ for melanoma treatment should proceed with caution.…”