Vitiligo-Like Primary Cutaneous Melanoma One of the Winning Presentations Given by Dermatology Residents at the Cosmetic Surgery Forum in December 2013
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RESIDENT REPORTS Vitiligo-like Primary Cutaneous Melanoma One of the winning presentations given by dermatology residents at the Cosmetic Surgery Forum in December 2013. BY HADAS SKUPSKY, MD, JENNIFER K. CHEN, MD, AND KENNETH G. LINDEN, MD melanotic melanomas comprise two percent of all melanomas. The clinical presentation is varied and may include erythematous patches, papules, or plaques.1,2 Depigmented macules and patches Ahave been described in association with both primary and metastatic melanomas. This phenomenon often represents regression of a melanoma or a side effect of melanoma- targeted immunochemotherapy. In addition, vitiligo may present at sites remotely from a melanoma.3-5 However, primary melanoma presenting as a vitiligo-like patch with- out histopathologic evidence of regression is an exceedingly rare phenomenon. To our knowledge, there is only a single Figure 1 Figure 2 report of two cases of vitiligo-like primary melanoma in situ in the literature to date.6 We herein report a case of invasive inferior shoulder with no subcutaneous nodules. She had no lentigo maligna melanoma presenting as a vitiliginous patch cervical, axillary, or supraclavicular lymphadenopathy. Biopsy of and review the possible immunopathogenesis of this lesion. the erythematous macule at the center of the patch revealed a proliferation of typical melanocytes, solitary and in irregular CASE REPORT nests, throughout the lower aspect of the epidermis and focal A 70-year-old female presented with a five-year history of an dermal invasion consistent with a lentigo maligna melanoma asymptomatic hypopigmented patch on her left upper arm. 0.2mm in depth. Biopsy of the superior aspect revealed lentigo Although the patch had initially grown slowly, the patient had maligna melanoma in situ (Figure 3). Immunohistochemistry noticed more rapid growth over the several months prior to studies including pan-Keratin, Melan-A, and S-100 confirmed presentation. She reported that the lesion had initially been the melanocytic nature of the lesion (Figure 4). Further biopsies biopsied by an outside dermatologist and found to be benign. at the lateral, medial, and inferior margins of the white patch A review of records from her previous dermatologist revealed also revealed lentigo maligna melanoma in situ. Neither dermal only a history of a basal cell carcinoma at that location. Past fibroplasia nor evidence of regression was found in multiple medical history was significant for a history of superficial spread- sections. A wide local excision of the lesion with 1cm margins ing melanoma on the right posterior inferior shoulder, 1mm in confirmed the lesion as a lentigo maligna melanoma with no depth with negative sentinel lymph node biopsy, for which she evidence of regression. had undergone wide local excision five years previously. On physical exam, she was noted to have a 6.5x4.8cm DISCUSSION hypopigmented patch with a central erythematous macule The relationship between melanoma and skin depigmen- that the patient reported to be secondary to her previous biop- tation is a fascinating and still controversial topic. Although sy (Figure 1, 2). The patient denied previous pigmented lesion the association of melanoma and vitiligo has been reported or nevus in the area. There was no evidence of vitiligo elsewhere widely, the usual clinical scenarios are those of a patient on skin exam. She had a well-healed scar on the right posterior with melanoma developing vitiligo at distant sites, as halo MAY 2014 PRACTICAL DERMATOLOGY 55 RESIDENT REPORTS suppression of tumoral antigen presentation may Figure 3 Figure 4 underlie the unique presentation of vitiligo-like mela- noma. CONCLUSION We present this rare case to underscore that mela- noma may be considered a great mimicker, both clini- cally and histopathologically. Amelanotic melanoma can present as a depigmented, hypopigmented, or phenomena around preexisting nevi, or areas of depigmen- erythematous lesion with or without scale and/or tation within the primary melanoma lesion.3-9 Patients with apparent lichenification of skin. It may evoke a long list of simi- melanoma may also develop vitiligo while on treatment for lar-looking and completely unrelated cutaneous inflammatory melanoma with immunochemotherapeutic agents such as or neoplastic lesions.1,2 It behooves the clinician to be aware of interleukin-2 or interferon alfa.7,10-12 this unique presentation and retain a high index of suspicion When depigmentation occurs within a primary melanoma fort the diagnosis of amelanotic melanoma. n lesion, regression is recognized histopathologically by the presence of a lymphocytic infiltrate, frequent expansion Hadas Skupsky, MD is a third-year dermatology resident of the papillary dermis, ‘wiry’ fibrosis and disappearance at the University of California, Irvine. Dr. Skupsky is pursuing of neoplastic melanocytes. Old regression is characterized a career as an academic dermatopathologist, and will be a by the presence of vascular fibrous tissue with without fellow at the Ackerman Academy of Dermatopathology, New melanophages and a variable lymphocytic infiltrate.13 Our York in 2015. case is a unique presentation of vitiligo-like lentigo maligna Jennifer K. Chen, MD, and Kenneth G. Linden, melanoma without histopathologic evidence of regression. MD are with the Department of Dermatology, To our knowledge, as indicated above, a single report of University of California, Irvine. two primary vitiligo-like melanoma in situ cases exists in the 1. Rahbari H, Nabai H, Mehregan AH, Mehregan DA, Mehregan DR, Lipinski J. Amelanotic literature to date, and we present the first case of invasive lentigo maligna melanoma: a diagnostic conundrum-- presentation of four new cases. Cancer. vitiligo-like primary melanoma.6 1996;77(10):2052-7. Epub 1996/05/15. 2. Kaufmann R, Nikelski K, Weber L, Sterry W. Amelanotic lentigo maligna melanoma. Journal of the American Academy The association between melanoma and hypomelanosis of Dermatology. 1995;32(2 Pt 2):339-42. Epub 1995/02/01. is thought to be the consequence of the immune-mediated 3. Arpaia N, Cassano N, Vena GA. Regressing cutaneous malignant melanoma and vitiligo-like depigmentation. Interna- tional journal of dermatology. 2006;45(8):952-6. Epub 2006/08/17. response against antigens shared by normal melanocytes 4. Gul U, Kilic A, Tulunay O, Kaygusuz G. Vitiligo associated with malignant melanoma and lupus erythematosus. The and melanoma cells. It has been demonstrated that mela- Journal of dermatology. 2007;34(2):142-5. Epub 2007/01/24. 5. Schallreuter KU, Levenig C, Berger J. Vitiligo and cutaneous melanoma. A case study. Dermatologica. 1991;183(4):239-45. noma and vitiligo are associated with humoral responses to 6. Lugo-Somolinos A, et al. Vitiligo-like primary melanoma. The American Journal of dermatopathology. 2008;30(5):451-4. similar antigens.14 In melanoma-associated vitiligo, specific 7. Harris J, Bines S, Das Gupta T. Therapy of disseminated malignant melanoma with recombinant alpha 2b-interferon and piroxicam: clinical results with a report of an unusual response-associated feature (vitiligo) and unusual toxicity (diffuse CD8+ lymphocytes directed against melanocytic antigens pulmonary interstitial fibrosis). Medical and pediatric oncology. 1994;22(2):103-6. Epub 1994/01/01. have been recognized, and immunization to melanoma cells 8. Koh HK, Sober AJ, Nakagawa H, Albert DM, Mihm MC, Fitzpatrick TB. Malignant melanoma and vitiligo-like leukoderma: 3,15,16 an electron microscopic study. Journal of the American Academy of Dermatology. 1983;9(5):696-708. Epub 1983/11/01. can cause vitiligo in animal models. 9. Lerner AB, Kirkwood JM. Vitiligo and melanoma: can genetically abnormal melanocytes result in both vitiligo and In melanoma, vitiligo is generally considered a positive melanoma within a single family? Journal of the American Academy of Dermatology. 1984;11(4 Pt 1):696-701. 10. Sacchi S, Kantarjian H, O’Brien S, Cohen PR, Pierce S, Talpaz M. Immune-mediated and unusual complications during prognostic factor indicating effective immunity to melanocyt- interferon alfa therapy in chronic myelogenous leukemia. Journal of clinical oncology : official journal of the American ic cells.17 Cases have been reported, however, in which depig- Society of Clinical Oncology. 1995;13(9):2401-7. Epub 1995/09/01. 11. Le Gal FA, Paul C, Chemaly P, Dubertret L. More on cutaneous reactions to recombinant cytokine therapy. Journal of the mentation of skin and hair was not accompanied by effective American Academy of Dermatology. 1996;35(4):650-1. Epub 1996/10/01. tumor shrinkage.15 Melanoma cells can escape the immune 12. Gogas H, Ioannovich J, Dafni U, Stavropoulou-Giokas C, Frangia K, Tsoutsos D, et al. Prognostic significance of autoim- munity during treatment of melanoma with interferon. The New England journal of medicine. 2006;354(7):709-18. response in such cases by downmodulating MHC class I cell 13. Blessing K, McLaren KM. Histological regression in primary cutaneous melanoma: recognition, prevalence and surface expression or by reducing processing and presentation significance. Histopathology. 1992;20(4):315-22. Epub 1992/04/01. 14. Cui J, Bystryn JC. Melanoma and vitiligo are associated with antibody responses to similar antigens on pigment cells. of target antigens, leaving tumor cells invisible to tumor-infil- Archives of dermatology. 1995;131(3):314-8. Epub 1995/03/01. trating lymphocytes. The downmodulation of melanosomal 15. Yee C, Thompson JA, Roche P, Byrd DR, Lee PP, Piepkorn M, et al. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of t cell-mediated vitiligo. The Journal of experimental medicine. antigens may be mediated by interferon gamma, a cytokine 2000;192(11):1637-44. Epub 2000/12/06. shown to suppress the expression of MART-1, TRP-1 and 16. Le Gal FA, Avril MF, Bosq J, Lefebvre P, Deschemin JC, Andrieu M, et al. Direct evidence to support the role of antigen- 18 specific CD8(+) T cells in melanoma-associated vitiligo. The Journal of investigative dermatology. 2001;117(6):1464-70. gp100 by M14 melanoma cells in vitro.