Cytomegalovirus and Herpes Simplex Virus Infections

Histopathological Findings

The characteristic histopathological finding of cytomegalovirus (CMV) infection is the presence of intranuclear "owl's eye" inclusion bodies, which are pathognomonic for CMV infection 1, 2, 3
These inclusion bodies consist of large cytomegalic cells with eosinophilic intranuclear inclusions surrounded by a clear halo, creating the characteristic "owl's eye" appearance 1
Immunohistochemistry (IHC) is the gold standard for detecting CMV in tissue, with a specificity of 92-100% and improved sensitivity of 78-93% 1, 3
IHC can detect infected cells that are morphologically normal without classic inclusion bodies, significantly increasing diagnostic sensitivity 3
The characteristic histopathological finding of herpes simplex virus (HSV) infection is the presence of multinucleated giant cells with intranuclear inclusion bodies 4, 5
Biopsies should be taken from both the center/base of ulcers (higher yield for CMV) and the edge (higher yield for HSV) 6

In immunocompromised patients with severe refractory colitis, IHC for CMV should be performed on all biopsies 3
Lymphocytic infiltration is a non-specific finding that can be seen in multiple inflammatory conditions and is not diagnostic of specific viral infection 4, 5
Eosinophilic intranuclear inclusions are a partial description that could apply to both CMV and HSV, but are not sufficiently specific without mentioning distinctive characteristics 1, 2

For suspected viral infection in immunocompromised patients, obtain endoscopic biopsy of affected tissue and request IHC with specific monoclonal antibodies 3
Report the semi-quantitative number of positive cells and affected fragments 3
Correlate with PCR in blood and antigenemia to confirm systemic disease versus colonization 3

Do not confuse viral reactivation (positive PCR) with invasive tissue disease, which requires histopathological confirmation 2
The presence of viremia by PCR or antigenemia can occur without end-organ disease, especially in CMV 2
In neutropenic patients, the typical endoscopic appearance of pseudomembranes in colitis may be absent, requiring a higher index of suspicion 6
Conventional histopathology with H&E may miss infected cells that are only detectable with IHC, especially in CMV 3