Multiple Melanomas in KRT1/KRT10-Nonsyndromic Epidermal Differentiation Disorder-Epidermolytic: A Case Report

KRT1/KRT10-nonsyndromic epidermal differentiation disorder-epidermolytic (KRT1/KRT10-nEDD-epidermolytic), previously known as epidermolytic ichthyosis, is a rare congenital keratinization disorder caused by pathogenic variants in keratin genes. While nonmelanoma skin cancer has been reported in inherited ichthyoses, an association with malignant melanoma remains poorly documented.

We report a 53-year-old man with KRT1-nEDD-epidermolytic who developed multiple malignant melanomas. Since adolescence, the patient had been treated with acitretin and topical keratolytics. His medical history was complicated by systemic lead intoxication, resulting from exposure to lead-containing ointment. The patient had no significant ultraviolet exposure, no clinical signs of chronic sun damage and no personal or familial history of melanoma or nonmelanoma skin cancer. Dermato-oncological follow-up revealed three invasive melanomas, four melanomas in situ, and one lentigo maligna over a 3-year period. Molecular profiling of the melanomas showed heterogeneous mutational patterns involving both high- and low-cumulative sun damage pathways. Extensive germline testing excluded known hereditary melanoma predisposition syndromes.

This is, to our knowledge, the first reported case of multiple malignant melanomas in a patient with KRT1-nEDD-epidermolytic. Chronic skin barrier dysfunction and inflammation associated with KRT1-nEDD-epidermolytic, potentially compounded by long-term cutaneous lead exposure, may contribute to a pro-oncogenic cutaneous environment. However, no causal link has been established, and the co-occurrence may be coincidental. Further studies are warranted to clarify melanoma risk and surveillance strategies in this patient population.