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The aim of the present study was to clarify relationship between macroscopic and microscopic features of herpes simplex esophagitis (HSE), and localization of herpes simplex virus type 1 (HSV-1)-infected cells in esophageal lesions from autopsy cases of histopathologically proven HSE. The study comprised morphological, immunohistochemical, cultural and electron microscopic investigations for 24 HSE patients collected from 1307 serial autopsy cases in the past 10 years. Macroscopic characteristics of HSE were divided into three types. Types I and II showed small punched-out lesions with and without raised margins, respectively. Type III revealed that multiple ulcers became confluent like a map. Microscopic findings showed that the HSV infection process seemed to begin in squamous epithelium and to induce vertical cellular change into the intact epithelial layer. Intranuclear inclusion bodies were observed at the centers of lesions, and ballooning changes of squamous cells at the margins. Both localization of HSV-1-infected cells and presence of HSV-1 in the esophageal lesions were confirmed with immunohistochemical staining, viral culture and electron microscopy. The present results suggest that the macroscopic and microscopic postmortem features of HSE may provide useful information for clinical diagnosis of HSE. [ABSTRACT FROM AUTHOR]