Effectiveness of imiquimod limited to dermal melanoma metastases, with simultaneous resistance of subcutaneous metastasis

Abstract

Successful management of epithelial skin cancers with imiquimod 5% cream (Aldara), an immunomodulatory agent, led to speculation that it may promote an immune response against melanoma. Studies, mostly case reports, have assessed the value of imiquimod as a topical treatment for dermal melanoma metastases that prove difficult to manage surgically. The precise value of imiquimod, however, in treatment of dermal and subcutaneous metastases remains unclear. A case at our institution elucidates histopathologically that subcutaneous metastases may progress despite excellent treatment of superficial dermis in the same location. In preparation for a clinical trial using imiquimod to treat patients with dermal melanoma metastases, we have treated several patients off protocol. We present a case report in which the observed changes are documented photographically and histologically. The patient experienced dramatic improvement in the locally treated dermis with concurrent regional treatment failure in the subcutaneous space. Our experience supports growing evidence that imiquimod for some provides an effective option for dermal disease. The unique histological documentation we provide regarding the differential effectiveness of imiquimod in treating various tissue components may help guide future investigations regarding optimal clinical application of imiquimod therapy for melanoma metastases.

Fig. 1

This figure demonstrates the patient’s scalp melanoma that initially progressed in size between February 2006 (Fig. 1A) and May 2006 (Fig. 1B). During this time, various treatments had been attempted, including high dose interleukin-2, Temozolamide, and a melanoma peptide vaccine trial (UVA MEL-41). With the initiation of Aldara between May 2006 and November 2006, clinical evidence of regression is evident. The regression is evident in that the multipapular melanoma shown in Fig. 1B was replaced by the flatter black discoloration of Fig. 1C. Comparison of Fig. 1C to 1B also shows arrest of radial extension of the dermal disease, which had been rapid prior to May 2006.

Fig. 2

This figure shows an MRI image demonstrating the subcutaneous location of the low T1, bright T2 metastatic melanoma nodule.

Fig. 3

(A) Total magnification (40×, H&E stained) shows a skin biopsy taken prior to beginning Aldara treatment. (B) The atypical melanocytes are readily apparent in nests, (total magnification 200×, H&E stained). (C) (total magnification 20×, H&E stained) shows significant fibrosis and a focus of tumoral melanosis, or residual pigment within macrophages in a treated focus, in the more superficial portion of the treated dermis, consistent with Aldara therapy. (D) (total magnification 100×, H&E stained) shows in higher magnification tumoral melanosis also indicating treatment-associated changes whereas (E) (total magnification 100×, H&E stained) shows dyscohesive melanocytes in the deep subcutis, suggesting persistent subcutaneous tumor.

Fig. 4

Total magnification (20×, H&E stained) reveals a low power (scanning) magnification of metastatic melanoma in the deep subcutis. Note that the metastasis lies deep to the layer of skeletal muscle.