Abstract
Herpes simplex virus (HSV) infections are among the most common sexually transmitted infections in humans. However, atypical presentations may occur in immunocompromised patients such as nodules, condylomatous masses, or hypertrophic lesions. Even further, HSV pseudotumors with negative histologic staining have been incompletely discussed in previous literature. We present a 51-year-old patient with a history of well-controlled HIV-1, who presented with a rectal mass, originally concerning for underlying bacterial infection or malignancy. Despite negative HSV immunohistochemical staining on biopsy, the mass improved with empiric intravenous acyclovir therapy, ultimately suggestive of a rectal HSV pseudotumor.