Mostyka M, Shia J, Neumann WL, et al. - The clinicopathologic characteristics of varicella zoster virus (VZV)-related gastrointestinal injury were described in this study. Six patients with VZV infection were identified that had involvement of the upper gastrointestinal tract, affecting the esophagus (n = 3), stomach (n = 2), or both (n = 1). All participants were immunocompromised and had hematologic malignancies (n = 5) or a heart transplant (n = 1). Three participants who had hematologic malignancies received stem cell transplants. When compared with 14 herpes simplex virus (HSV)-related esophagitis controls, hemorrhagic ulcers with nodularity or erythema were caused by VZV relative to round, shallow ulcers on a background of nearly normal mucosa seen in HSV. Fibrin-rich, pauci-inflammatory exudates were noted in VZV-related ulcers vs the macrophage-rich exudates of HSV. All levels of the squamous epithelium showed the cytopathic changes of VZV, particularly in a peripapillary distribution. HSV inclusions, in contrast, were observed in the superficial layers and detached keratinocytes. On the contrary to HSV, VZV involved the stomach, giving rise to hemorrhage accompanied by striking apoptosis in the deep glands. Per these findings, VZV generates distinctive patterns of gastrointestinal injury that aid in its diagnosis. As gastrointestinal VZV infection heralds potentially life-threatening disseminated disease, making its recognition important.