Cutaneous pathology following etoposide therapy

Etoposide (VP-16) is a semisynthetic podophyllotoxin derivative that is active against a number of solid and hematologic malignancies. Previously reported cutaneous complications include Stevens-Johnson syndrome and radiation recall. We report 4 cases of cutaneous eruptions with distinctive histopathologic changes following etoposide therapy. Diffuse erythematous macules and papules developed 5-9 days after initiation of etoposide therapy and resolved spontaneously within 3 weeks. Histologic examination revealed epidermal maturation disturbances with scattered markedly enlarged individual keratinocytes. These cells had pale cytoplasms and fragmented, haphazardly dispersed nuclear chromatin in a starburst pattern ("starburst cells"). Many keratinocytes showed notable nuclear enlargement with multiple prominent nucleoli. In addition, numerous dyskeratotic cells and basilar mitotic figures in metaphase were present. Some of these changes have been described in condylomata acuminata treated with topical applications of podophyllin, a compound structurally related to etoposide. Starburst cells have not been reported in cutaneous eruptions produced by other chemotherapeutic agents. These cells may represent abnormal mitotic arrest secondary to podophyllin and its related compounds.