Vitiligo Associated with Melanoma in a Malagasy Woman

Malignant melanoma is the first fatal skin cancer. Vitiligo is a leukoderma or a multifactorial depigmentation acquired but especially of autoimmune origin. We report the first Malagasy case affected by both melanoma and Vitiligo. The appearance of Vitiligo during a melanoma could testify to an immunological response against melanocytes. Despite the association of melanoma and Vitiligo, the prognosis of melanoma is still fatal.


Introduction
Malignant melanoma is the most aggressive malignant tumor of skin cancer. Vitiligo is a multifactorial acquired leukoderma. e association of a malignant melanoma with various clinical forms of skin depigmentation is known in particular the association with a Vitiligo [1]. We report the first Malagasy case of melanoma associated with and Vitiligo.

Case Presentation
A 44-year-old woman, farmer, presented asymptomatic skin depigmentations associated with a non-painful right inguinal swelling evolving for 6 months. Two years ago, she had an excision of a tumor lesion pigmented in the pressure zone of right heel, but no histology screen was performed. e pigmented lesion of the heel recurred one year later, motivating a second surgical resection of which histology analysis shown specific signs of lentiginous melanoma, Breslow >4 mm, Clark IV, with ulceration and positive margin. She had no family history of melanoma or Vitiligo. Physical examination show that the patient was in good general condition. She had multiple achromic patches varying in size from a few millimeters to 20 cm in diameter, in the face (Figure 1), chest, arms, thighs, right inguinal swelling, and backs of the feet. She had also a hard right inguinal lymphadenopathy 15 cm in diameter adhering to the deep plane ( Figure 2). On the right heel, she had a pigmented ulcero-crusty lesion of 4 cm in diameter ( Figure 3). e rest of the physical examination was normal. e extension assessment found liver metastases and necrotic lymphadenopathy on the right iliac chain. en, a diagnosis of acral lentiginous melanoma, Stage IV according to American Joint Committee on Cancer 2009 (AJCC) associated with recent generalized Vitiligo was made. She received palliative treatment. Unfortunately she died 2 months later.

Discussion
In Madagascar skin cancers account for 9% of cancers and melanomas account for 23% of malignant skin tumors [2]. Vitiligo is an acquired leukoderma due to destruction or loss of melanocytes. It is probably a multifactorial disease: genetic and environmental factors as well as autoimmune and auto-inflammatory mechanisms have been advanced [3][4][5]. Various pathogenetic mechanisms have been suggested, most evidence supports an autoimmune basis for the Vitiligo. Different genome-wide association studies of generalized Vitiligo have been reported, identifying a total of 17 confirmed generalized Vitiligo susceptibility loci. Almost all of these genes encode immunoregulatory proteins. In melanocytes HLA-A * 02:01 presents the major Vitiligo autoimmune antigen, TYR (encoding tyrosinase), which in turn, activates and recruits anti-melanocytes auto-reactive cytotoxic T lymphocytes to the skin within the target and destroy melanocytes. Moreover, the biological interaction between these generalized Vitiligo susceptibility genes, HLA-A and TYR, points to show inverse relationship between susceptibility to generalized Vitiligo versus malignant melanoma, suggesting that generalized Vitiligo may result, in part, from dysregulation of normal processes of immune surveillance against melanoma. Unfortunately, we could not do genetic study for our patient to confirm this hypothesis [6,7].
Vitiligo-like lesions may appear during primary or metastatic melanoma [8]. It affects 3% to 6% of melanoma cases. Leukoderma can precede, from a few months to several years, the appearance of melanoma [1,9]. Or it can appear on primary or metastatic melanoma spontaneously or during melanoma treatment. e development of Vitiligo during melanoma maybe the result of an immunological response against melanocytes. Humoral and cellular immunity is involved [9]. In particular, the antityrosinase antibodies and the CD8 + oligoclonal in vitro T lymphocytes were involved in the destruction of normal melanocytes during the immune response to melanoma antigens [10,11]. During immunotherapy by pembrolizumab in patients with metastatic melanoma, the appearance of Vitiligo demonstrates a good therapeutic response [12]. In common Vitiligo, there is a greater history of autoimmune disease and family history of Vitiligo compared to patients with Vitiligo-like lesions during melanoma. Achromic lesions can localize around cutaneous and distant metastases. ey are o en generalized bilateral, symmetrical and without Koebner phenomenon in case of Vitiligo associated with melanoma [10,13]. For our patient she had a generalized Vitiligo with achromic lesion next to lymph node metastasis. Although the presence of Vitiligo indicates a strong immune response against melanoma, our patient died quickly. In Madagascar the management of melanoma especially in the metastatic stage is disappointing. e treatment is expensive, we do not have molecular biology yet. Immunotherapy and targeted therapy are not yet available. Table 1 shows some cases of Vitiligo associated with melanoma reported in the literature.

Conclusion
Our patient's case illustrates an occurrence of concomitant Vitiligo and melanoma, presumably the first reported case in Madagascar. Although the melanoma-Vitiligo association is an indication of an immunological response against normal melanocytes and melanoma antigens, the prognosis of melanoma is still fatal. In Madagascar the treatment of melanoma is difficult especially in case of metastatic forms. More attention should be given to the examination of melanocyte lesions in adult patients in order to detect melanoma at the onset stage. Malignant melanoma can be overlooked by patients, as in the case of our patient who was concerned about the presence of cosmetic disfiguring achromic lesions.

Conflicts of Interest
All authors declare that there is no have no conflict of interests regarding the publication of this paper.