Background: Lentigo maligna (LM) is a melanoma in situ on sun-damaged skin, with a strong predilection to the head and neck area of the elderly. Many therapeutic modalities have been proposed in the treatment of this pathology, including surgery, cryotherapy, radiotherapy and topical imiquimod. Up to date surgical excision remains the treatment of choice with the lowest recurrence rate. Recently, a new topical treatment with ingenol mebutate has been described to be efficacious and well tolerated in the treatment of melanoma in situ. Objective: We sought to demonstrate that ingenol mebutate might be an efficacious and well-tolerated treatment in a patient suffering from LM on an aesthetically challenging location. Methods: Case report. Results: After therapeutic failure with imiquimod 5% cream, a new topical treatment with ingenol mebutate gel 0.015% once daily on 3 consecutive days was initiated. Despite visible inflammation, no macroscopic lesion clearance was observed. While the first follow-up using reflectance confocal microscopy (RCM) performed at 6 weeks after the completion of the therapy showed no signs of LM, the second follow-up examination at 12 weeks using RCM and biopsy confirmed recurrence of the lesion. Conclusion: Ingenol mebutate cannot be considered a standard treatment modality for all types of LM. Further studies are needed to evaluate the prerequisites that can ensure therapeutic success.

1.
Ciocan D, Barbe C, Aubin F, Granel-Brocard F, Lipsker D, Velten M, Dalac S, Truchetet F, Michel C, Mitschler A, Arnoult G, Buemi A, Dalle S, Bernard P, Woronoff AS, Grange F: Distinctive features of melanoma and its management in elderly patients: a population-based study in France. JAMA Dermatol 2013;149:1150-1157.
2.
Tannous ZS, Lerner LH, Duncan LM, Mihm MC Jr, Flotte TJ: Progression to invasive melanoma from malignant melanoma in situ, lentigo maligna type. Hum Pathol 2000;31:705-708.
3.
Erickson C, Miller SJ: Treatment options in melanoma in situ: topical and radiation therapy, excision and Mohs surgery. Int J Dermatol 2010;49:482-491.
4.
Higgins HW 2nd, Lee KC, Galan A, Leffell DJ: Melanoma in situ: part II. Histopathology, treatment, and clinical management. J Am Acad Dermatol 2015;73:193-203; quiz 203-204.
5.
Mansuy M, Nikkels-Tassoudji N, Arrese JE, Rorive A, Nikkels AF: Recurrent in situ melanoma successfully treated with ingenol mebutate. Dermatol Ther (Heidelb) 2014;4:131-135.
6.
Ramsay JR, Suhrbier A, Aylward JH, Ogbourne S, Cozzi SJ, Poulsen MG, Baumann KC, Welburn P, Redlich GL, Parsons PG: The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers. Br J Dermatol 2011;164:633-636.
7.
Lebwohl M, Shumack S, Stein Gold L, Melgaard A, Larsson T, Tyring SK: Long-term follow-up study of ingenol mebutate gel for the treatment of actinic keratoses. JAMA Dermatol 2013;149:666-670.
8.
Keating GM: Ingenol mebutate gel 0.015% and 0.05%: in actinic keratosis. Drugs 2012;72:2397-2405.
9.
Ottawa (ON): Canadian Agency for Drugs and Technologies in Health: Ingenol Mebutate (Picato): Topical Treatment of Non-Hyperkeratotic, Non-Hypertrophic Actinic Keratosis in Adults. CADTH Common Drug Reviews, 2014.
10.
Anderson L, Schmieder GJ, Werschler WP, Tschen EH, Ling MR, Stough DB, Katsamas J: Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad Dermatol 2009;60:934-943.
11.
Braun SA, Homey B, Gerber PA: [Successful treatment of Bowen disease with ingenol mebutate]. Hautarzt 2014;65:848-850.
12.
Cantisani C, Paolino G, Cantoresi F, Faina V, Richetta AG, Calvieri S: Superficial basal cell carcinoma successfully treated with ingenol mebutate gel 0.05%. Dermatol Ther 2014;27:352-354.
13.
Javed S, Tyring SK: Treatment of molluscum contagiosum with ingenol mebutate. J Am Acad Dermatol 2014;70:e105.
14.
Ogbourne SM, Suhrbier A, Jones B, Cozzi SJ, Boyle GM, Morris M, McAlpine D, Johns J, Scott TM, Sutherland KP, Gardner JM, Le TT, Lenarczyk A, Aylward JH, Parsons PG: Antitumor activity of 3-ingenyl angelate: plasma membrane and mitochondrial disruption and necrotic cell death. Cancer Res 2004;64:2833-2839.
15.
Ersvaer E, Kittang AO, Hampson P, Sand K, Gjertsen BT, Lord JM, Bruserud O: The protein kinase C agonist PEP005 (ingenol 3-angelate) in the treatment of human cancer: a balance between efficacy and toxicity. Toxins (Basel) 2010;2:174-194.
16.
Gillespie SK, Zhang XD, Hersey P: Ingenol 3-angelate induces dual modes of cell death and differentially regulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in melanoma cells. Mol Cancer Ther 2004;3:1651-1658.
17.
Cozzi SJ, Parsons PG, Ogbourne SM, Pedley J, Boyle GM: Induction of senescence in diterpene ester-treated melanoma cells via protein kinase C-dependent hyperactivation of the mitogen-activated protein kinase pathway. Cancer Res 2006;66:10083-10091.
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