Objective: We aimed to investigate the association between CMV immunohistochemistry positivity and clinical, endoscopic, histologic, and tissue CMV PCR findings in ileocolonoscopic biopsies of inflammatory bowel disease patients, and to assess the diagnostic value of CMV immunohistochemistry as a reflex test during routine histopathologic evaluation.

Material and Methods: We conducted a retrospective analysis of 191 patients (136 ulcerative colitis, 55 Crohn`s disease) between 2018 and 2021. We analyzed clinical data, endoscopic Mayo scores, histologic activity (Simplified Geboes Score), cytopathic changes, CMV immunohistochemistry and tissue CMV PCR results.

Results: CMV immunohistochemistry was positive in 32.4% of cases, significantly associated with ulcerative colitis (p=0.003), symptomatic presentation (p=0.001), extensive colonic involvement (p<0.001), high histologic activity scores (p<0.001), and ulceration (p<0.001). Notably, 74.2% of CMV immunohistochemistry-positive cases had no preliminary clinical suspicion of CMV infection. Viral cytopathic changes were identified in only 30.6% of immunopositive cases on hematoxylin-eosin staining. CMV immunohistochemistry showed a significant correlation with tissue PCR (p<0.001), although some discordant cases occurred. The PCR-positive group had significantly higher immunopositive cell counts compared to the PCR-negative group (p<0.001). The number of biopsy fragments did not affect CMV detection by immunohistochemistry.

Conclusion: While evaluating endoscopic biopsies of patients with inflammatory bowel disease, CMV immunohistochemistry assessment as a reflex test may be considered by the pathologist—even in the absence of identifiable viral cytopathic effects with hematoxylin-eosin— particularly when severe histologic inflammation is present. Although the clinical significance of CMV immunohistochemistry could not be fully determined in this study, this approach may increase the likelihood of detecting CMV infection and, in the appropriate clinical context, could contribute to timely diagnosis and management.