What Happens to Atypical Nevi Treated With 5% Imiquimod Cream?
What Happens to Atypical Nevi Treated With 5% Imiquimod Cream?
Somani N, Martinka M, Crawford RI, Dutz JP, Rivers JK
Dermatol Surg. 2007;33:S76-S80
In this small but informative study, Somani and colleagues asked the question "What happens to atypical nevi treated with 5% imiquimod cream?" This question is important because the topical immune response modifier has been advocated as an off-label treatment for dysplastic and even malignant melanocytic proliferative lesions. Furthermore, because imiquimod is frequently applied to photodamaged skin as a treatment for actinic keratoses, atypical nevi are likely inadvertently exposed to topical imiquimod with some frequency.
To assess the effect topical imiquimod has on atypical nevi, Somani and colleagues enrolled 3 patients with clinically atypical nevi. These patients applied 5% imiquimod cream 5 nights per week for 12 weeks to the selected nevi, which were all judged clinically to be "mildly to moderately atypical." Patients with a personal or family history of melanoma were excluded from the study. Two-millimeter punch biopsies were taken to assess baseline lesion histology. Following 12 weeks of imiquimod treatment, the nevi were completely excised for histologic evaluation, including immunohistochemical staining for CD4+ and CD8+ cells and MxA (myxovirus resistance 1: a surrogate marker for interferon type I expression).
None of the nevi cleared following 12 weeks of aggressive (5 nights per week) imiquimod therapy. All 3 patients showed highly variable local tissue responses to imiquimod (mild to moderate inflammation, significant inflammation, and minimal inflammation). The nevus that became minimally inflamed showed less histologic dysplasia than the nevi that developed a brisk inflammatory response. The inflamed nevi showed immunophenotypic features similar to those seen in halo nevi, including increased lymphocytic infiltration (both CD4+ and CD8+) and increased MxA staining.
Although this study is too small to yield general conclusions, some interesting results are evident: (1) atypical nevi may respond to imiquimod cream more or less briskly depending on their level of underlying cellular dysplasia. Such differences may reflect underlying cellular differences between mildly, moderately, and severely dysplastic nevi. (2) Topical imiquimod does not appear to clear atypical nevi, even when applied aggressively. (3) Imiquimod-treated atypical nevi may easily be misinterpreted histologically as severely dysplastic or malignant melanocytic proliferations. Therefore, nevi sampled from skin undergoing topical imiquimod therapy should be identified as such.
In sum, although some advocate using imiquimod as an off-label treatment for lentigo maligna and melanoma in situ, this therapeutic approach should be limited to situations in which surgical treatment is not a feasible option. Clearly, imiquimod should not be viewed as an appropriate treatment for atypical nevi. Nevi that become inflamed in the context of topical imiquimod therapy may be more likely to have underlying dysplastic features.
Abstract
Somani N, Martinka M, Crawford RI, Dutz JP, Rivers JK
Dermatol Surg. 2007;33:S76-S80
In this small but informative study, Somani and colleagues asked the question "What happens to atypical nevi treated with 5% imiquimod cream?" This question is important because the topical immune response modifier has been advocated as an off-label treatment for dysplastic and even malignant melanocytic proliferative lesions. Furthermore, because imiquimod is frequently applied to photodamaged skin as a treatment for actinic keratoses, atypical nevi are likely inadvertently exposed to topical imiquimod with some frequency.
To assess the effect topical imiquimod has on atypical nevi, Somani and colleagues enrolled 3 patients with clinically atypical nevi. These patients applied 5% imiquimod cream 5 nights per week for 12 weeks to the selected nevi, which were all judged clinically to be "mildly to moderately atypical." Patients with a personal or family history of melanoma were excluded from the study. Two-millimeter punch biopsies were taken to assess baseline lesion histology. Following 12 weeks of imiquimod treatment, the nevi were completely excised for histologic evaluation, including immunohistochemical staining for CD4+ and CD8+ cells and MxA (myxovirus resistance 1: a surrogate marker for interferon type I expression).
None of the nevi cleared following 12 weeks of aggressive (5 nights per week) imiquimod therapy. All 3 patients showed highly variable local tissue responses to imiquimod (mild to moderate inflammation, significant inflammation, and minimal inflammation). The nevus that became minimally inflamed showed less histologic dysplasia than the nevi that developed a brisk inflammatory response. The inflamed nevi showed immunophenotypic features similar to those seen in halo nevi, including increased lymphocytic infiltration (both CD4+ and CD8+) and increased MxA staining.
Although this study is too small to yield general conclusions, some interesting results are evident: (1) atypical nevi may respond to imiquimod cream more or less briskly depending on their level of underlying cellular dysplasia. Such differences may reflect underlying cellular differences between mildly, moderately, and severely dysplastic nevi. (2) Topical imiquimod does not appear to clear atypical nevi, even when applied aggressively. (3) Imiquimod-treated atypical nevi may easily be misinterpreted histologically as severely dysplastic or malignant melanocytic proliferations. Therefore, nevi sampled from skin undergoing topical imiquimod therapy should be identified as such.
In sum, although some advocate using imiquimod as an off-label treatment for lentigo maligna and melanoma in situ, this therapeutic approach should be limited to situations in which surgical treatment is not a feasible option. Clearly, imiquimod should not be viewed as an appropriate treatment for atypical nevi. Nevi that become inflamed in the context of topical imiquimod therapy may be more likely to have underlying dysplastic features.
Abstract