Abstract

ZIP6 is a zinc transporter protein with elevated expression in several types of cancer cells. Antibodies against ZIP6, conjugate to microtubule disrupting agents, are an investigational therapy for metastatic breast cancer, lung cancer, gastric adenocarcinoma, melanoma and head and neck squamous cell carcinoma. Reported adverse events associated include nausea, fatigue, alopecia, peripheral neuropathy, anemia and neutropenia;however, cutaneous adverse events and histopathologic findings associated have not been previously reported. Herein, we describe a case of a patient with angiosarcoma of the breast who developed a diffuse erythematous eruption with intertriginous accentuation three days following infusion with a ZIP6 inhibitor. Two skin biopsies showed similar histopathologic findings. In the epidermis, necrotic keratinocytes were present at variable levels, including within the follicular epithelium. There was marked epidermal dysmaturation with numerous mitoses present at all epidermal levels. In the superficial dermis, there was a mild perivascular lymphocytic infiltrate, extravasated erythrocytes and focal vascular ectasias. Eccrine glands were uninvolved, and there was no eccrine squamous syringometaplasia or eccrine gland necrosis. Overall, the findings of interface dermatitis with marked epidermal dysmaturation, taken together with clinical history, were those of toxic erythema of chemotherapy (TEC). TEC can present with a spectrum of clinical and histopathologic findings, with interface vacuolar dermatitis and keratinocyte dysmaturation most commonly described on microscopy. A long list of chemotherapy agents have been associated with TEC, most cases being reported with anthracyclines. Antibody conjugated microtubule disrupting agents are becoming more common in clinical practice, and there is limited information about associated cutaneous histopathologic findings. With this report, we hope to aid in the early recognition of potentially serious cutaneous reactions that may occur with ZIP6 inhibitor administration.

Financial Disclosure: No current or relevant financial relationships exist.