Prominent mononuclear cell infiltrate is characteristic of herpes esophagitis

Diagnosis of herpes esophagitis is often difficult since the characteristic nuclear inclusions and/or multinucleate giant cells of herpes virus infection may be absent in endoscopic biopsy specimens. We have noted aggregates of large mononuclear cells with convoluted nuclei adjacent to infected epithelium in the exudates of herpetic esophagitis, and postulate that this is a characteristic inflammatory response to the virus. To test this hypothesis, we reviewed biopsies from 22 cases of ulcerative herpetic esophagitis and from 44 control cases of nonherpetic esophageal ulcers (including nine cases of candidal and five cases of bacterial esophagitis) that contained a quantifiable amount of exudate. The estimated percentage of mononuclear cells present in the specimens was ranked independently by two reviewers using coded photomicrographs of exudate. Wilcoxon's rank sum analysis demonstrated significant correlation between presence of herpes and increased mononuclear cells (P less than .0001). Only one of the 22 herpes cases did not show a prominent mononuclear cell infiltrate. Immunoperoxidase studies performed on Hollande-Bouin's-fixed paraffin-embedded material from 11 herpes cases showed strong staining of the mononuclear cells for KP-1 (CD68), indicating that the majority of these cells are macrophages. These findings suggest strongly that aggregates of macrophages are characteristic of the inflammatory response in ulcerative herpetic esophagitis. The presence of these mononuclear cells in a biopsy specimen that initially does not show herpetic inclusions warrants additional studies to rule out herpes virus infection.