Kaposi sarcoma: What to do with a negative human herpesvirus 8 immunohistochemical stain?

Kaposi sarcoma (KS) is an intermediate vascular sarcoma that can cause significant morbidity and mortality in patients if left untreated. It is associated with human herpesvirus 8 (HHV-8) infection. Definitive diagnosis is supported by classic histopathology including slit-like vascular spaces, spindle cells, lymphocyte infiltration, and extravasated red blood cells on H&E stain and positive immunohistochemical (IHC) staining for HHV-8. We present a challenge we encountered in detecting HHV-8 by IHC in a mucosal lesion demonstrating classic histopathology for KS.