Skip to main content
Log in

Microinvasive Melanoma

Cutaneous Pharmacotherapeutic Approaches

  • Review Article
  • Published:
American Journal of Clinical Dermatology Aims and scope Submit manuscript

Abstract

Surgical excision is the treatment of choice for primary melanomas and radiation therapy is the accepted alternative for the subset of lesions not amenable to surgery. With the recent rise in melanoma incidence, especially in the elderly, there are a growing number of cases that are neither amenable to surgery nor radiation therapy. In this article, we review pharmacotherapeutic approaches to microinvasive melanoma (invasive radial growth phase melanoma) that might be considered in such circumstances. There are no approved drugs for the treatment of primary melanoma and randomized controlled trials with 5 or more years of follow-up have not been performed. The limited studies and numerous case series in the literature on pharmacologic treatment of primary melanoma have focused on topical therapies. Accordingly, we provide a review of the potential pharmacotherapeutic agents in the treatment of microinvasive melanoma by extrapolating from the available limited literature on the use of fluorouracil, azelaic acid, retinoic acid derivatives, interferon (IFN)-α, imiquimod, and other agents for melanoma in situ, invasive melanoma, and epidermotropic melanoma metastases. Our review indicates that topical fluorouracil and tretinoin are not effective as single agents. The efficacy of azelaic acid, tazarotene, cidofovir, and intralesional IFN-α, interleukin-2, and IFN-β is undefined. Imiquimod is the most studied and promising agent; however, optimal dosage, therapeutic regimen, and survival rates are unknown. In the face of a growing demand for non-surgical treatments, formal clinical trials are needed to ascertain the role of pharmacotherapeutic agents in the treatment of microinvasive melanoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rigel D. Epidemiology of melanoma. Semin Cutan Med Surg. 2010;29(4):204–9.

    Article  PubMed  CAS  Google Scholar 

  2. Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2011;65(5):1032–47.

    Article  PubMed  Google Scholar 

  3. Elder D. Tumor progression, early diagnosis and prognosis of melanoma. Acta Oncol. 1999;38(5):535–48.

    Article  PubMed  CAS  Google Scholar 

  4. Szymik B, Woosley JT. Further validation of the prognostic model for stage I malignant melanoma based on tumor progression. J Cutan Pathol. 1993;20(1):50–3.

    Article  PubMed  CAS  Google Scholar 

  5. Cook MG, Clarke TJ, Humphreys S, et al. The evaluation of diagnostic and prognostic criteria and the terminology of thin cutaneous malignant melanoma by the CRC Melanoma Pathology Panel. Histopathology. 1996;28(6):497–512.

    Article  PubMed  CAS  Google Scholar 

  6. Guerry D. Lessons from tumor progression: the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent. J Invest Dermatol. 1993;100(3):342S–5S.

    Article  PubMed  Google Scholar 

  7. Tsang RW, Liu FF, Wells W, et al. Lentigo maligna of the head and neck: results of treatment by radiotherapy. Arch Dermatol. 1994;130(8):1008–12.

    Article  PubMed  CAS  Google Scholar 

  8. McKenna J, Florell S, Goldman G, et al. Lentigo maligna/lentigo maligna melanoma: current state of diagnosis and treatment. Dermatol Surg. 2006;32(4):493–504.

    Article  PubMed  CAS  Google Scholar 

  9. Stevenson O, Ahmed I. Lentigo maligna: prognosis and treatment options. Am J Clin Dermatol. 2005;6(3):151–64.

    Article  PubMed  Google Scholar 

  10. Erickson C, Miller S. Treatment options in melanoma in situ: topical and radiation therapy, excision and Mohs surgery. Int J Dermatol. 2010;49(5):482–91.

    Article  PubMed  Google Scholar 

  11. Penneys N. Microinvasive lentigo maligna melanoma. J Am Acad Dermatol. 1987;17(4):675–80.

    Article  PubMed  CAS  Google Scholar 

  12. Agarwal-Antal N, Bowen GM, Gerwels JW. Histologic evaluation of lentigo maligna with permanent sections: implications regarding current guidelines. J Am Acad Dermatol. 2002;47(5):743–8.

    Article  PubMed  Google Scholar 

  13. Somach SC, Taira JW, Pitha JV, et al. Pigmented lesions in actinically damaged skin: histopathologic comparison of biopsy and excisional specimens. Arch Dermatol. 1996;132(11):1297–302.

    Article  PubMed  CAS  Google Scholar 

  14. Toren KL, Parlette EC. Managing melanoma in situ. Semin Cutan Med Surg. 2010;29(4):258–63.

    Article  PubMed  CAS  Google Scholar 

  15. Good LM, Miller MD, High WA. Intralesional agents in the management of cutaneous malignancy: a review. J Am Acad Dermatol. 2011;64(2):413–22.

    Article  PubMed  Google Scholar 

  16. Florin V, Desmedt E, Vercambre-Darras S, et al. Topical treatment of cutaneous metastases of malignant melanoma using combined imiquimod and 5-fluorouracil. Invest New Drugs. 2012;30(4):1641–5.

    Article  PubMed  CAS  Google Scholar 

  17. Litwin MS. Topical chemotherapy of lentigo maligna with 5-fluorouracil. Cancer. 1975;35(3):721–33.

    Article  PubMed  CAS  Google Scholar 

  18. Ryan RF, Krementz ET, Litwin MS. A role for topical 5-fluorouracil therapy in melanoma. J Surg Oncol. 1988;38(4):250–6.

    Article  PubMed  CAS  Google Scholar 

  19. Coleman WP, Davis RS, Reed RJ, et al. Treatment of lentigo maligna and lentigo maligna melanoma. J Dermatol Surg Oncol. 1980;6(6):476–9.

    PubMed  Google Scholar 

  20. Rocamora V. Amelanotic lentigo maligna melanoma: report of a case and review of the literature. Cutis. 1999;64(1):53–6.

    PubMed  CAS  Google Scholar 

  21. Munoz CM, Sanchez JL, Martin-Garcia RF. Successful treatment of persistent melanoma in situ with 5% imiquimod cream. Dermatol Surg. 2004;30(12 Pt 2):1543–5.

    Article  PubMed  Google Scholar 

  22. Breathnach AS. Azelaic acid: potential as a general antitumoural agent. Med Hypotheses. 1999;52(3):221–6.

    Article  PubMed  CAS  Google Scholar 

  23. Yu JS, Kim AK. Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells. J Biomed Sci. 2010;17(Suppl. 1):S45.

    Article  PubMed  CAS  Google Scholar 

  24. Nazzaro-Porro M, Passi S, Zina G, et al. Effect of azelaic acid on human malignant melanoma. Lancet. 1980;1(8178):1109–11.

    Article  PubMed  CAS  Google Scholar 

  25. Leibl H, Stingl G, Pehamberger H, et al. Inhibition of DNA synthesis of melanoma cells by azelaic acid. J Invest Dermatol. 1985;85(5):417–22.

    Article  PubMed  CAS  Google Scholar 

  26. Nazzaro-Porro M, Passi S, Balus L, et al. Effect of dicarboxylic acids on lentigo maligna. J Invest Dermatol. 1979;72(6):296–305.

    Article  PubMed  CAS  Google Scholar 

  27. Rodríguez Prieto MA, Manchado Lopez P, Ruiz Gonzalez I, et al. Treatment of lentigo maligna with azelaic acid. Int J Dermatol. 1993;32(5):363–4.

    Article  PubMed  Google Scholar 

  28. Vereecken P, Heenen M. Recurrent lentigo maligna melanoma: regression associated with local azelaic acid 20%. Int J Clin Pract. 2002;56(1):68–9.

    PubMed  CAS  Google Scholar 

  29. Nazzaro-Porro M, Breathnach AS, Balus L, et al. A case of recurrent (following surgery x2) invasive malignant melanoma with satellitosis (stage IIIA) successfully resolving after azelaic acid treatment administered by several routes. Clin Exp Dermatol. 1996;21(4):321–3.

    Article  PubMed  CAS  Google Scholar 

  30. Nazzaro-Porro M, Passi S, Zina G, et al. Ten years’ experience of treating lentigo maligna with topical azelaic acid. Acta Derm Venereol Suppl (Stockh). 1989;143:49–57.

    CAS  Google Scholar 

  31. Nazzaro-Porro M, Breathnach AS, Zina G. 10 years observations on the effect of azelaic acid on lentigo maligna. J Invest Dermatol. 1986;87(3):438.

    Google Scholar 

  32. Nazzaro-Porro M, Zina G, Breathnach AS, et al. Topical azelaic acid therapy for palpebral lesions of melanoma in situ and for melanoma in situ progressed to invasive melanoma: a report on four cases. G Ital Dermatol Venerol. 1998;133(N. 2):79–85.

    Google Scholar 

  33. Sowden J, Paramsothy Y, Smith AG. Malignant melanoma arising in the scar of lupus vulgaris and response to treatment with topical azelaic acid. Clin Exp Dermatol. 1988;13(5):353–6.

    Article  PubMed  CAS  Google Scholar 

  34. McLean DI, Peter KK. Apparent progression of lentigo maligna to invasive melanoma during treatment with topical azelaic acid. Br J Dermatol. 1986;114(6):685–9.

    Article  PubMed  CAS  Google Scholar 

  35. Ertle TAW, Janner M. Local treatment of lentigo maligna with azelaic acid. Arch Dermatol Res. 1981;271(2):197–203.

    Article  Google Scholar 

  36. Doherty V. Azelaic acid in lentigo maligna. Br J Dermatol. 1987;116(4):605–7.

    Article  Google Scholar 

  37. Nazzaro-Porro M. Azelaic acid. J Am Acad Dermatol. 1987;17(6):1033–41.

    Article  PubMed  CAS  Google Scholar 

  38. Meyskens FL. Modulation of abnormal growth by retinoids: a clinical perspective of the biological phenomenon. Life Sci. 1981;28(21):2323–7.

    Article  PubMed  CAS  Google Scholar 

  39. Orfanos CE. Current use and future potential role of retinoids in dermatology. Drugs. 1997;53(3):358–88.

    Article  PubMed  CAS  Google Scholar 

  40. Levine N, Meyskens FL. Topical vitamin-A-acid therapy for cutaneous metastatic melanoma. Lancet. 1980;2(8188):224–6.

    Article  PubMed  CAS  Google Scholar 

  41. Estler M. Global analysis of gene expression changes during retinoic acid-induced growth arrest and differentiation of melanoma: comparison to differentially expressed genes in melanocytes vs melanoma. BMC Genomics. 2008;9(1):478.

    Article  PubMed  CAS  Google Scholar 

  42. Demary K. Redox control of retinoic acid receptor activity: a novel mechanism for retinoic acid resistance in melanoma cells. Endocrinology. 2001;142(6):2600–5.

    Article  PubMed  CAS  Google Scholar 

  43. Craven NM. Retinoids in the management of non-melanoma skin cancer and melanoma. Cancer Surv. 1996;26:267–88.

    PubMed  CAS  Google Scholar 

  44. Epping MT. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005;122(6):835–47.

    Article  PubMed  CAS  Google Scholar 

  45. Rivers JK, McCarthy WH. No effect of topical tretinoin on lentigo maligna. Arch Dermatol. 1991;127(1):129.

    Article  PubMed  CAS  Google Scholar 

  46. Rivers JK, McArdle CA, Gupta G, et al. Recurrent melanoma after topical tretinoin. Lancet. 1989;2(8676):1393.

    Article  PubMed  CAS  Google Scholar 

  47. Chimenti S, Carrozzo AM, Citarella L, et al. Treatment of lentigo maligna with tazarotene 0.1% gel. J Am Acad Dermatol. 2004;50(1):101–3.

    Article  PubMed  Google Scholar 

  48. Shistik G, Prakash AV, Fenske NA, et al. Treatment of locally metastatic melanoma: a novel approach. J Drugs Dermatol. 2007;6(8):830–2.

    PubMed  Google Scholar 

  49. Cotter MA, McKenna JK, Bowen GM. Treatment of lentigo maligna with imiquimod before staged excision. Dermatol Surg. 2008;34(2):147–51.

    Article  PubMed  CAS  Google Scholar 

  50. Carucci JA, Leffell DJ. Intralesional interferon alfa for treatment of recurrent lentigo maligna of the eyelid in a patient with primary acquired melanosis. Arch Dermatol. 2000;136(11):1415–6.

    Article  PubMed  CAS  Google Scholar 

  51. Cornejo P, Vanaclocha F, Polimon I, et al. Intralesional interferon treatment of lentigo maligna. Arch Dermatol. 2000;136(3):428–30.

    Article  PubMed  CAS  Google Scholar 

  52. Legha SS. Interferons in the treatment of malignant melanoma: a review of recent trials. Cancer. 1986;57(8 Suppl.):1675–7.

    Article  PubMed  CAS  Google Scholar 

  53. Legha SS. The role of interferon alfa in the treatment of metastatic melanoma. Semin Oncol. 1997;24(1 Suppl. 4):S24–31.

    PubMed  CAS  Google Scholar 

  54. Turner ML, Moshell AN, Corbett DW, et al. Clearing of melanoma in situ with intralesional interferon alfa in a patient with xeroderma pigmentosum. Arch Dermatol. 1994;130(12):1491–4.

    Article  PubMed  CAS  Google Scholar 

  55. Ikić D, Spaventi S, Padovan I, et al. Local interferon therapy for melanoma patients. Int J Dermatol. 1995;34(12):872–4.

    Article  PubMed  Google Scholar 

  56. Ikić D. Application of human leucocyte interferon in patients with urinary bladder papillomatosis, breast cancer, and melanoma. Lancet. 1981;1(8228):1022–4.

    PubMed  Google Scholar 

  57. von Moos R, Schnaffer R, Cathomas R. Intratumoral therapy with interferon-alpha in a locoregional advanced malignant blue nevus: a brief communication. J Immunother. 2010;33(1):92–5.

    Article  CAS  Google Scholar 

  58. von Wussow P. Intralesional interferon-alpha therapy in advanced malignant melanoma. Cancer. 1988;61(6):1071–4.

    Article  Google Scholar 

  59. Kirkwood JM. Role of interferons in the therapy of melanoma. J Invest Dermatol. 1990;95(6 Suppl.):180S–4S.

    Article  PubMed  CAS  Google Scholar 

  60. Micali G, Lacarrubba F, Dinotta F, et al. Treating skin cancer with topical cream. Expert Opin Pharmacother. 2010;11(9):1515–27.

    Article  PubMed  CAS  Google Scholar 

  61. Woodmansee C. The role of topical immune response modifiers in skin cancer. Drugs. 2006;66(13):1657–64.

    Article  PubMed  CAS  Google Scholar 

  62. Steinmann A, Funk JO, Schuler G, et al. Topical imiquimod treatment of a cutaneous melanoma metastasis. J Am Acad Dermatol. 2000;43(3):555–6.

    PubMed  CAS  Google Scholar 

  63. Ahmed I, Berth-Jones J. Imiquimod: a novel treatment for lentigo maligna. Br J Dermatol. 2000;143(4):843–5.

    Article  PubMed  CAS  Google Scholar 

  64. Rajpar SF, Marsden JR. Imiquimod in the treatment of lentigo maligna. Br J Dermatol. 2006;155(4):653–6.

    Article  PubMed  CAS  Google Scholar 

  65. Ormond P. Treatment of lentigo maligna with imiquimod. Br J Dermatol. 2002;147:57.

    Article  Google Scholar 

  66. Borucki U, Metze D. Topical treatment of lentigo maligna melanoma with imiquimod 5% cream. Dermatology. 2003;207(3):326–8.

    Article  PubMed  CAS  Google Scholar 

  67. Chapman MS, Spencer SK, Brennick JB. Histologic resolution of melanoma in situ (lentigo maligna) with 5% imiquimod cream. Arch Dermatol. 2003;139(7):943–4.

    Article  PubMed  Google Scholar 

  68. Epstein E. Extensive lentigo maligna clearing with topical imiquimod. Arch Dermatol. 2003;139(7):944–5.

    Article  PubMed  Google Scholar 

  69. Fisher GH, Lang PG. Treatment of melanoma in situ on sun-damaged skin with topical 5% imiquimod cream complicated by the development of invasive disease. Arch Dermatol. 2003;139(7):945–7.

    Article  PubMed  Google Scholar 

  70. Naylor MF, Crowson N, Kuwahara R, et al. Treatment of lentigo maligna with topical imiquimod. Br J Dermatol. 2003;149(Suppl. 66):66–70.

    Article  PubMed  CAS  Google Scholar 

  71. Curiel-Lewandrowski C, Williams CM, Swindells KJ, et al. Use of in vivo confocal microscopy in malignant melanoma: an aid in diagnosis and assessment of surgical and nonsurgical therapeutic approaches. Arch Dermatol. 2004;140(9):1127–32.

    Article  PubMed  Google Scholar 

  72. Powell AM, Russell-Jones R, Barlow RJ. Topical imiquimod immunotherapy in the management of lentigo maligna. Clin Exp Dermatol. 2004;29(1):15–21.

    Article  PubMed  CAS  Google Scholar 

  73. Powell A-M. Amelanotic lentigo maligna managed with topical imiquimod as immunotherapy. J Am Acad Dermatol. 2004;50(5):792–6.

    Article  PubMed  Google Scholar 

  74. Kupfer-Bessaguet I, Guillet G, Misery L, et al. Topical imiquimod treatment of lentigo maligna: clinical and histologic evaluation. J Am Acad Dermatol. 2004;51(4):635–9.

    Article  PubMed  CAS  Google Scholar 

  75. Fleming CJ, Bryden AM, Evans A, et al. A pilot study of treatment of lentigo maligna with 5% imiquimod cream. Br J Dermatol. 2004;151(2):485–8.

    Article  PubMed  CAS  Google Scholar 

  76. Michalopoulos P. Characterization of the cellular infiltrate during successful topical treatment of lentigo maligna with imiquimod. Br J Dermatol. 2004;151(4):903–6.

    Article  PubMed  CAS  Google Scholar 

  77. Kamin A, Eigentler TK, Radny P, et al. Imiquimod in the treatment of extensive recurrent lentigo maligna. J Am Acad Dermatol. 2005;52(2 Suppl. 1):51–2.

    Article  PubMed  Google Scholar 

  78. Wolf IH, Cerroni L, Kodama K, et al. Treatment of lentigo maligna (melanoma in situ) with the immune response modifier imiquimod. Arch Dermatol. 2005;141(4):510–4.

    Article  PubMed  CAS  Google Scholar 

  79. Noel B, Kunzle N. Image in clinical medicine: lentigo maligna. N Engl J Med. 2005;353(20):2176.

    Article  PubMed  CAS  Google Scholar 

  80. Ray CM, Kluk M, Grin CM, et al. Successful treatment of malignant melanoma in situ with topical 5% imiquimod cream. Int J Dermatol. 2005;44(5):428–34.

    Article  PubMed  Google Scholar 

  81. Micantonio T. Usefulness of dermoscopy to monitor clinical efficacy of imiquimod treatment for lentigo maligna. Arch Dermatol. 2006;142(4):530–1.

    PubMed  Google Scholar 

  82. Hopson B, Richey D, Sajben FP. Treatment of lentigo maligna with imiquimod 5% cream. J Drugs Dermatol. 2007;6(10):1037–40.

    PubMed  Google Scholar 

  83. van Meurs T, van Doorn R, Kirtschig G. Recurrence of lentigo maligna after initial complete response to treatment with 5% imiquimod cream. Dermatol Surg. 2007;33(5):623–7.

    Article  PubMed  CAS  Google Scholar 

  84. Spenny ML, Walford J, Werchniak AE, et al. Lentigo maligna (melanoma in situ) treated with imiquimod cream 5%: 12 case reports. Cutis. 2007;79(2):149–52.

    PubMed  Google Scholar 

  85. Murchison AP, Washington CV, Soloman AR, et al. Ocular effects of imiquimod with treatment of eyelid melanoma in situ. Dermatol Surg. 2007;33(9):1136–8.

    Article  PubMed  CAS  Google Scholar 

  86. du Plessis PJ. Lentigo maligna successfully treated with imiquimod. S Afr J Surg. 2007;45(2):72.

    PubMed  Google Scholar 

  87. Micali G, Lacarrubba F, Nardone B, et al. Videodermatoscopy of lentigo maligna treated with imiquimod. J Drugs Dermatol. 2008;7(11):1077–80.

    PubMed  Google Scholar 

  88. Craythorne EE, Lawrence CM. Observational study of topical imiquimod immunotherapy in the treatment of difficult lentigo maligna. Clin Med Oncol. 2008;2:551–4.

    PubMed  CAS  Google Scholar 

  89. Mahoney MH, Joseph MG, Temple C. Topical imiquimod therapy for lentigo maligna. Ann Plast Surg. 2008;61(4):419–24.

    Article  PubMed  CAS  Google Scholar 

  90. de Troya-Martín M. Lentigo maligna managed with topical imiquimod and dermoscopy: report of two cases. Dermatol Surg. 2008;34(11):1561–6.

    Article  PubMed  CAS  Google Scholar 

  91. Buettiker UV, Yawalkar NY, Braathen LR, et al. Imiquimod treatment of lentigo maligna: an open-label study of 34 primary lesions in 32 patients. Arch Dermatol. 2008;144(7):943–5.

    Article  PubMed  Google Scholar 

  92. Ramsdell AM, Zeitouni N. Long-term follow-up of a hemifacial lentigo maligna treated using 5% imiquimod. Dermatol Surg. 2009;35(2):287–90.

    Article  PubMed  CAS  Google Scholar 

  93. Junkins-Hopkins J. Imiquimod use in the treatment of lentigo maligna. J Am Acad Dermatol. 2009;61(5):865–7.

    Article  PubMed  Google Scholar 

  94. Missall TA. The use of imiquimod to minimize the surgical defect when excising invasive malignant melanoma surrounded by extensive melanoma in situ, lentiginous type. Dermatol Surg. 2009;35(5):868–74.

    Article  PubMed  CAS  Google Scholar 

  95. Powell AM, Robson AM, Russell-Jones R, et al. Imiquimod and lentigo maligna: a search for prognostic features in a clinicopathological study with long-term follow-up. Br J Dermatol. 2009;160(5):994–8.

    Article  PubMed  CAS  Google Scholar 

  96. Woodmansee CS, McCall MW. Recurrence of lentigo maligna and development of invasive melanoma after treatment of lentigo maligna with imiquimod. Dermatol Surg. 2009;35(8):1286.

    Article  PubMed  CAS  Google Scholar 

  97. Van Meurs T, Van Doorn R, Kirtschig G. Treatment of lentigo maligna with imiquimod cream: a long-term follow-up study of 10 patients. Dermatol Surg. 2010;36(6):853–8.

    Article  PubMed  CAS  Google Scholar 

  98. Demirci H. Topical imiquimod for periocular lentigo maligna. Ophthalmology. 2010;117(12):2424–9.

    Article  PubMed  Google Scholar 

  99. Martires KJ. Failed treatment of amelanotic lentigo maligna with imiquimod followed by pigment production. Arch Dermatol. 2010;146(9):1047–8.

    Article  PubMed  Google Scholar 

  100. Missall TA, Hurley MY, Fosko SW. Lentiginous melanoma in situ treatment with topical imiquimod: need for individualized regimens. Arch Dermatol. 2010;146(11):1309–10.

    Article  PubMed  CAS  Google Scholar 

  101. Nadiminti H. Use of reflectance confocal microscopy to monitor response of lentigo maligna to nonsurgical treatment. Dermatol Surg. 2010;36(2):177–84.

    Article  PubMed  CAS  Google Scholar 

  102. Costa MC, Abraham LS, Barcaui C. Lentigo maligna treated with topical imiquimod: dermatoscopy usefulness in clinical monitoring. An Bras Dermatol. 2011;86(4):792–4.

    Article  PubMed  Google Scholar 

  103. Lapresta A, García-Almagro D, Sejas AG. Amelanotic lentigo maligna managed with topical imiquimod. J Dermatol. 2012;39(5):503–5.

    Article  PubMed  CAS  Google Scholar 

  104. O’Neill J. Periocular lentigo maligna treated with imiquimod. J Dermatol Treat. 2011;22(2):109–12.

    Article  CAS  Google Scholar 

  105. Zattra E. Achromic superficial spreading melanoma accidentally treated with imiquimod. Acta Derm Venereol. 2012;92(1):107–8.

    Article  PubMed  CAS  Google Scholar 

  106. Ly L, Kelly JW, O’Keefe R, et al. Efficacy of imiquimod cream, 5%, for lentigo maligna after complete excision: a study of 43 patients. Arch Dermatol. 2011;147(10):1191–5.

    Article  PubMed  CAS  Google Scholar 

  107. Bong AB, Bonnekoh B, Franke I, et al. Imiquimod, a topical immune response modifier, in the treatment of cutaneous metastases of malignant melanoma. Dermatology. 2002;205(2):135–8.

    Article  PubMed  CAS  Google Scholar 

  108. Ugurel S. Topical imiquimod eradicates skin metastases of malignant melanoma but fails to prevent rapid lymphogenous metastatic spread. Br J Dermatol. 2002;147(3):621–4.

    Article  PubMed  CAS  Google Scholar 

  109. Wolf IH, Smolle J, Binder B, et al. Topical imiquimod in the treatment of metastatic melanoma to skin. Arch Dermatol. 2003;139(3):273–6.

    Article  PubMed  Google Scholar 

  110. Vereecken P, Mathieu A, Laporte M, et al. Management of cutaneous locoregional recurrences of melanoma: a new therapeutic perspective with imiquimod. Dermatology. 2003;206(3):279–80.

    Article  PubMed  Google Scholar 

  111. Hesling C, D’Incan M, Mansard S, et al. In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases. Br J Dermatol. 2004;150(4):761–7.

    Article  PubMed  CAS  Google Scholar 

  112. Zeitouni NC, Dawson K, Cheney RT. Treatment of cutaneous metastatic melanoma with imiquimod 5% cream and the pulsed-dye laser. Br J Dermatol. 2005;152(2):376–7.

    Article  PubMed  CAS  Google Scholar 

  113. Heber G, Helbig D, Pönitzsch I, et al. Complete remission of cutaneous and subcutaneous melanoma metastases of the scalp with imiquimod therapy. J Dtsch Dermatol Ges. 2009;7(6):534–6.

    PubMed  Google Scholar 

  114. Kowalzick L. Progress of multiple cutaneous and subcutaneous melanoma metastases of the face during imiquimod treatment. J Dtsch Dermatol Ges. 2009;7(6):538–40.

    PubMed  Google Scholar 

  115. Turza K, Dengel LT, Harris RC, et al. Effectiveness of imiquimod limited to dermal melanoma metastases, with simultaneous resistance of subcutaneous metastasis. J Cutan Pathol. 2010;37(1):94.

    Article  PubMed  Google Scholar 

  116. Miller AK, Dusing R, Meggison A, et al. Regression of internal melanoma metastases following application of topical imiquimod to overlying skin. J Drugs Dermatol. 2011;10(3):302–5.

    PubMed  Google Scholar 

  117. Tiodorovic-Zivkovic D, Argenziano G, Catricalà C, et al. Adjuvant treatment with topical 5% imiquimod cream for resected stage IIIb melanoma. Eur J Dermatol. 2011;21(3):410–1.

    PubMed  Google Scholar 

  118. Santos-Juanes J, Esteve A, Mas-Vidal A, et al. Acute renal failure caused by imiquimod 5% cream in a renal transplant patient: review of the literature on side effects of imiquimod. Dermatology. 2011;222(2):109–12.

    Article  PubMed  CAS  Google Scholar 

  119. Truchetet F. D.N.C.B. for malignant melanoma: significance in the treatment strategy. Anticancer Res. 1989;9(6):1531–6.

    PubMed  CAS  Google Scholar 

  120. von Nida J. Successful treatment of in-transit melanoma metastases using topical 2-4 dinitrochlorobenzene. Aust J Dermatol. 2003;44(4):277–80.

    Article  Google Scholar 

  121. Illig L. Epifocal dinitrochlorobenzene therapy in malignant melanoma (experience during the last eight years). Anticancer Res. 1984;4(4–5):293–8.

    PubMed  CAS  Google Scholar 

  122. Damian DL, Shannon KF, Saw RP, et al. Topical diphencyprone immunotherapy for cutaneous metastatic melanoma. Australas J Dermatol. 2009;50(4):266–71.

    Article  PubMed  Google Scholar 

  123. Damian DL. Treatment of extensive cutaneous metastatic melanoma with topical diphencyprone. J Am Acad Dermatol. 2007;56(5):869–71.

    Article  PubMed  Google Scholar 

  124. Damian DL. Dramatic regression of cutaneous, nodal, and visceral melanoma metastases. J Am Acad Dermatol. 2011;65(3):665–6.

    Article  PubMed  Google Scholar 

  125. Martiniuk F, Damian DL, Thompson JF, et al. TH17 is involved in the remarkable regression of metastatic malignant melanoma to topical diphencyprone. J Drugs Dermatol. 2010;9(11):1368–72.

    PubMed  Google Scholar 

  126. Redondo P. Cidofovir inhibits growth of B16 melanoma cells in vivo. Br J Dermatol. 2000;143(4):741–8.

    Article  PubMed  CAS  Google Scholar 

  127. Calista D. Treatment of lentigo maligna with topical 1% cidofovir. Br J Dermatol. 2007;157(2):421–3.

    Article  PubMed  CAS  Google Scholar 

  128. Calista D. Regression of a cutaneous melanoma metastasis after intralesional cidofovir. Melanoma Res. 2003;13(2):205–6.

    Article  PubMed  Google Scholar 

  129. Kubo H. Interferon-beta therapy for malignant melanoma: the dose is crucial for inhibition of proliferation and induction of apoptosis of melanoma cells. Arch Dermatol Res. 2008;300(6):297–301.

    Article  PubMed  CAS  Google Scholar 

  130. Fujimura T. Perilesional treatment of metastatic melanoma with interferon-beta. Clin Exp Dermatol. 2009;34(7):793–9.

    Article  PubMed  CAS  Google Scholar 

  131. Ulmer A, Metzger S, Fierlbeck G. Successful palliation of stenosing anorectal melanoma by intratumoral injections with natural interferon-beta. Melanoma Res. 2002;12(4):395–8.

    Article  PubMed  CAS  Google Scholar 

  132. Rapprich H, Hagedorn M. Intralesional therapy of metastatic spreading melanoma with beta-interferon. J Dtsch Dermatol Ges. 2006;4(9):743–6.

    Article  PubMed  Google Scholar 

  133. Gutwald JG, Groth W, Mahrle G. Peritumoral injections of interleukin 2 induce tumour regression in metastatic malignant melanoma. Br J Dermatol. 1994;130(4):541–2.

    Article  PubMed  CAS  Google Scholar 

  134. Radny P, Caroli UM, Bauer J, et al. Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases. Br J Cancer. 2003;89(9):1620–6.

    Article  PubMed  CAS  Google Scholar 

  135. Weide B. High response rate after intratumoral treatment with interleukin-2: results from a phase 2 study in 51 patients with metastasized melanoma. BMC Cancer. 2010;116(17):4139–46.

    CAS  Google Scholar 

  136. Green DS, Bodman-Smith MD, Dalgleish AG, et al. Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma. Br J Dermatol. 2007;156(2):337–45.

    Article  PubMed  CAS  Google Scholar 

  137. Garcia MS. Complete regression of subcutaneous and cutaneous metastatic melanoma with high-dose intralesional interleukin 2 in combination with topical imiquimod and retinoid cream. Melanoma Res. 2011;21(3):235–43.

    Article  PubMed  CAS  Google Scholar 

  138. Cohen MH. Intralesional treatment of recurrent metastatic cutaneous malignant melanoma: a randomized prospective study of intralesional Bacillus Calmette-Guerin versus intralesional dinitrochlorobenzene. Cancer. 1978;41(6):2456–63.

    Article  PubMed  CAS  Google Scholar 

  139. Si Z. Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF. Melanoma Res. 1996;6(3):247–55.

    Article  PubMed  CAS  Google Scholar 

  140. Schallreuter KU. Local treatment of cutaneous and subcutaneous metastatic malignant melanoma with fotemustine. Cancer Chemother Pharmacol. 1991;29(2):167–71.

    Article  PubMed  CAS  Google Scholar 

  141. Oratz R. Intratumoral cisplatin/adrenaline injectable gel for the treatment of patients with cutaneous and soft tissue metastases of malignant melanoma. Melanoma Res. 2003;13(1):59–66.

    Article  PubMed  CAS  Google Scholar 

  142. Thompson JF, Hersey P, Wachter E. Chemoablation of metastatic melanoma using intralesional rose bengal. Melanoma Res. 2008;18(6):405–11.

    Article  PubMed  Google Scholar 

  143. Testori A. Local and intralesional therapy of in-transit melanoma metastases. J Surg Oncol. 2011;104(4):391–6.

    Article  PubMed  Google Scholar 

  144. Triozzi PL, Tuthill RJ, Borden E. Re-inventing intratumoral immunotherapy for melanoma. Immunotherapy. 2011;3(5):653–71.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

No funding was received to prepare this article. The authors have no conflicts of interest that are directly relevant to the contents of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elizabeth A. Quigley.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Quigley, E.A., Halpern, A.C. Microinvasive Melanoma. Am J Clin Dermatol 14, 125–137 (2013). https://doi.org/10.1007/s40257-013-0012-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40257-013-0012-1

Keywords

Navigation