Malignant Melanoma Arising in the Setting of Epidermolysis Bullosa Simplex: An Important Distinction From Epidermolysis Bullosa Nevus

IMPORTANCE Patients with epidermolysis bullosa (EB) do not carry a significantly increased risk of melanoma but are prone to developing large, markedly atypical melanocytic nevi (EB nevi), which may mimic melanoma clinically and histologically. Many authors now favor a conservative approach in managing atypical pigmented lesions in patients with EB. OBSERVATIONS We present the case of a 30-year-old woman with severe EB simplex who sought care for a large red and black ulcerated plaque. The clinical differential diagnosis included EB nevus and melanoma. An incisional punch biopsy specimen revealed an atypical melanocytic proliferation with focal florid pagetoid spread and involving elongated rete ridges, consistent with invasive acral lentiginous melanoma. The subsequent amputation was confirmatory. Micrometastasis was detected in 1 of 5 sentinel lymph nodes. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first reported case of melanoma arising in EB simplex–affected skin. It highlights the difficulty in differentiating melanoma from an EB nevus. Despite the increasing awareness of EB nevi, a high index of suspicion for melanoma should be maintained, and early biopsy is recommended when evaluating large pigmented lesions in patients with EB.