Melanoma in skin affected with keratoderma palmoplantaris hereditaria (Mal de Meleda): Treatment with excision and grafting

To the Editor: Palmoplantar keratodermas are a heterogeneous group of disorders (inherited or acquired) that are characterized by a thickening of the skin of the palms and the soles. In most cases, the abnormal skin involves only the palms and soles (non-transgradient), but sometimes it extends to the dorsal surface of the hands and feet (transgradient); in some cases, the abnormal skin involves also the distal part of the limbs (progrediens) and other sites.1 Mal de Meleda is an autosomal recessive disease with an estimated prevalence of 1 case per 100,000 population. This dermatosis was described by the Italian Luca Stulli in 1826 on the Dalmatian island of Meleda (now Mljet). Mal de Meleda is characterized by the presence of diffuse, thick keratoderma with a prominent erythematous border; lesions spread onto the dorsal surfaces of the hands and feet (transgredient) and can be associated with the presence of well circumscribed, psoriasis-like plaques on the knees and the elbows, perioral erythema, brachydactyly, and nail abnormalities.1 Molecular studies have demonstrated mutations in the ARS-B gene, encoding for secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1). Proteins of the SLURP family have been implicated in transmembrane signal transduction, cell activation, and cell adhesion.2 Only a single case of malignant melanoma arising in the hyperkeratotic lesions of Mal de Meleda has been described in the literature.3 We present a patient with malignant melanoma arising in an area of keratoderma resulting from Mal de Meleda with maintenance of the skin autograft that had been performed to repair the affected area. In 2003, a 64-year-old white man with a previous diagnosis of Mal del Meleda was referred to us because of the development of a large mass in an area involved with keratoderma on the dorsal surface of his left hand (Fig 1, A). A histologic examination showed the presence of a malignant melanoma with vertical growth, ulceration, an elevated mitotic index (7X10 HPF), and a Breslow thickness of 5.70 mm; hyperkeratosis, probably reflecting the underlying keratoderma, was also observed (Fig 2). Complete removal of the lesion, including 2 cm of normal-appearing skin, was performed. Sentinel node staging was negative. A full thickness skin autograft from the right inguinal region was used to repair the affected area. After 4 years of follow-up, the patient is in good health and the skin graft is not affected by Mal de Meleda (Fig 1, B). To our knowledge, this case provides the first evidence of the maintenance of a skin graft in a cutaneous area affected by Mal de Meleda. The preservation of the skin graft in the involved area unequivocally demonstrates that the genetic alteration is confined only to lesional skin. Our case was also interesting because it was characterized by the rapid development of a malignant melanoma with a striking Breslow thickness. It is plausible that the skin immune system impairment in the involved area determined by the genetic alteration might have initiated and sustained this neoplastic event. In this regard, it has been shown that SLURP-1 is expressed in immune cells and is involved in the regulation of immune function by regulating lymphocyte activity via nicotinic acetylcholine receptor–mediated pathways.