Histopathologic Comparison Among Drug Eruptions Induced by Enfortumab Vedotin, Brentuximab Vedotin, and Taxanes

Microtubule-stabilizing agents (enfortumab vedotin and brentuximab vedotin) and microtubule-disrupting agents (docetaxel and paclitaxel) are used as anticancer agents but can also induce drug eruptions. Recently, mitotic arrest figures have been reported in various non-neoplastic cells as the histopathologic side effect of these drug eruptions. Therefore, we performed a comparative analysis of drug eruptions associated with these microtubule-targeting agents. Enfortumab vedotin-, brentuximab vedotin-, docetaxel-, and paclitaxel-associated drug eruptions were retrieved from 4 hospitals in 5, 5, 5, and 7 patients, respectively. Ring mitotic and other mitotic arrest figures were observed in the epidermis in all types of drug eruption but were most frequently (100%) observed in enfortumab vedotin-induced eruptions. Such a finding was also occasionally observed in the sweat ductoglandular units but not in the follicular epithelium. Keratinocyte multinucleation and apoptotic keratinocytes distributed predominantly in the upper part of the epidermis were also observed in these eruptions, particularly in enfortumab vedotin-induced eruptions (4/5, 80%). In conclusion, drug eruptions associated with microtubule-targeting agents, particularly enfortumab vedotin, can often exhibit mitotic arrest figures, keratinocyte multinucleation, and apoptotic keratinocytes predominantly observed in the upper part of the epidermis. These characteristic histopathologic features can be the diagnostic clues of drug eruptions induced by microtubule-targeting agents.