Enfortumab vedotin-induced cutaneous eruption: Ring mitotic figures as a distinctive histopathologic feature

Abstract

Enfortumab vedotin (EV), a nectin-4-binding agent that affects microtubules, has become standard therapy for advanced urothelial carcinoma. The agent, now given in combination with pembrolizumab, frequently induces cutaneous reactions. Here, we report a severe EV-induced cutaneous eruption. A 58-year-old woman with metastatic urothelial carcinoma developed a rash after receiving simultaneous first doses of EV and pembrolizumab. The eruption began on the flank and spread to involve her trunk and extremities with prominent involvement of folds, including the axillae and medial thighs. Skin biopsy revealed extensive vacuolar alteration of the basal epidermis and numerous epidermal keratinocytic mitotic figures, often suprabasilar, including ring and “starburst” forms. The findings supported a diagnosis of EV-induced eruption. With EV cessation and systemic corticosteroids, the rash resolved over a few weeks. Pembrolizumab was restarted as monotherapy, and the patient's cancer showed a significant radiographic treatment response at 3 months. An emerging literature of small series and case reports, largely from oncologic literature, presents the histopathology of EV-induced cutaneous eruption as a vacuolar interface dermatitis with the inconsistently reported feature of arrested mitotic figures. This case study demonstrates distinctive clinical and histopathologic features of EV-induced eruption, which may inform dermatologic and oncologic management.