Topical Imiquimod for Melanoma In Situ? A Word of Caveat

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The authors read with interest the article “Long-Term Outcomes of Melanoma In Situ Treated With Topical 5% Imiquimod Cream: A Retrospective Review.”1 Park and colleagues report 12 patients with MIS having been treated with topical imiquimod. During a follow-up of 5.5 years, only 2 relapses occurred: one was treated with punch biopsy excision and the other patient developed an invasive melanoma (1.6 mm) with fatal outcome. The authors conclude that imiquimod represents an option, if surgical interventions are not possible.
The authors share their view and also appreciate and use imiquimod for MIS at regions problematic for radical excision. Recently, we treated a patient whose course indicated the limitations of this therapy.
An 81-year-old male patient presented with histologically verified MIS on the left side of the nose in August 2015 (Figure 1A). The lesion was rather broad, not well circumscribed, and close to the nostril. The patient declined wide excision, thus 5% imiquimod was applied twice daily over 16 weeks. The inflammatory response resulted in clinical remission (Figure 1B). A biopsy to confirm clearance was denied by the patient.
In September 2016, a new small pigmented lesion developed. Again, the patient refused a biopsy and insisted on the reintroduction of imiquimod, which caused clinical remission after 6 weeks.
In February 2017, a nonpigmented nodule appeared in the area of the previously pigmented lesion (Figure 1C). Histopathology revealed a nodular invasive melanoma (1.4 mm). Radical excision with removal of the ala of the nose and cervical sentinel node biopsy (result: no metastasis) were performed. The patient was included in the authors' melanoma follow-up program.
As a topical immunomodulator, imiquimod has turned out to be effective for not only viral warts but also superficial neoplastic processes such as superficial nonmelanoma skin cancers (NMSCs).2,3 Field cancerization is a typical feature of this entity, and topical therapy is most suitable. Hence, imiquimod filled this therapeutic gap except for its limited efficacy in nodular lesions, constituting a contraindication.
Melanoma in situ responds quite well to imiquimod.4,5 Currently, the use of imiquimod in this indication represents an off-label use with all limitations and risks, but the authors are convinced that imiquimod will be more frequently used in the future. However, one has to be aware that melanoma is a much more aggressive disorder than NMSC. Therapeutic failure of imiquimod in the latter usually results “only” in a delay of the surgical procedure without prognostic impairment. The consequences in melanoma are more severe because early metastasis might occur. Although the patient responded initially well to imiquimod, the final outcome was unfavorable. This could have been avoided by subsequent biopsies, which the patient repeatedly declined.
The authors share the view of Park and colleagues and consider imiquimod valuable in MIS. Nevertheless, the authors think that the surgical excision should still be the primary therapy. If not possible, imiquimod may be an alternative. However, the authors emphasize that subsequent biopsies to prove remission and careful follow-up are warranted. If the patient is not compliant in this regard, topical imiquimod should be better avoided.

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