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Published on: July 9, 2014
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Beyond the first cut: evaluating CMV IHC reliability in serial gastrointestinal biopsy sections
Anna Hochner-Ger1, Liat Anafi1, Ido Veisman2,3
1Institute of Pathology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Virchows Archiv : an International Journal of Pathology
|September 11, 2025
Summary
Cytomegalovirus (CMV) immunohistochemistry (IHC) shows variability in detecting sparse infections in gastrointestinal biopsies. Serial sectioning improves confidence but highlights the need for multimodal diagnostic approaches for accurate CMV detection.
Area of Science:
- Gastroenterology
- Infectious Diseases
- Pathology
Background:
- Cytomegalovirus (CMV) is a significant opportunistic pathogen, particularly in immunocompromised individuals, frequently leading to severe gastrointestinal pathology.
- Immunohistochemistry (IHC) is a standard diagnostic tool for CMV detection in gastrointestinal biopsies, valued for its specificity.
- The reliability of CMV IHC in cases with a low burden of CMV-positive cells remains a concern, potentially impacting diagnostic accuracy.
Purpose of the Study:
- To evaluate the reproducibility of CMV immunohistochemistry (IHC) in gastrointestinal biopsies.
- To assess the impact of serial sectioning on CMV detection variability in cases with sparse viral presence.
- To determine the diagnostic stability of CMV IHC results across multiple tissue sections.
Main Methods:
- A prospective observational study involving 25 cases of CMV colitis diagnosed via IHC.
- Tissue blocks were subjected to serial sectioning, followed by CMV IHC staining.
- Statistical analysis, including Friedman and Wilcoxon signed-rank tests, was employed to assess variability in CMV detection across serial sections.
Main Results:
- CMV-positive cell counts demonstrated significant variation across serial sections (p=0.047).
- A notable proportion of initially positive cases showed fluctuations to equivocal or negative results in different sections (33.3% negative, 33.3% equivocal).
- Equivocal cases exhibited high instability, with all showing negative sections and one converting to positive.
Conclusions:
- CMV IHC demonstrates inherent variability, especially in cases with low viral loads, potentially leading to diagnostic shifts.
- While serial sectioning enhances diagnostic confidence, it does not entirely resolve the observed variability.
- A multimodal diagnostic strategy, combining IHC with molecular methods and protocol standardization, is recommended for improved CMV detection accuracy.

