Hochner-Ger Anna, Anafi Liat, Veisman Ido, Barshack Iris, Mayer Chen
Institute of Pathology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Virchows Arch. 2025 Sep 11. doi: 10.1007/s00428-025-04226-y.
Cytomegalovirus(CMV) is a major pathogen in immunocompromised individuals, often causing severe gastrointestinal complications. Immunohistochemistry (IHC) is widely used for CMV detection due to its high specificity, but its reliability in cases with sparse CMV-positive cells remains uncertain. This study evaluates the reproducibility of CMV IHC in gastrointestinal biopsies by assessing CMV detection across serial sections. A prospective observational study was conducted at the Pathology Institute of Sheba Medical Center between the years 2023 and 2024. Twenty-five CMV colitis cases diagnosed based on IHC were included and categorized as positive (≥ 2 CMV-positive cells) or equivocal (1 CMV-positive cell). Serial sectioning of the tissue blocks and subsequent CMV IHC staining was performed. Descriptive statistical analysis, including the Friedman test and Wilcoxon signed-rank test, was used to assess variability in CMV detection. CMV-positive cell counts varied significantly across serial sections (p = 0.047, Friedman test). While some cases remained stable, others fluctuated, transitioning from positive to equivocal or negative. Among initially positive cases, 33.3% (7/21) had at least one negative section, and 33.3% (7/21) had at least one equivocal section. Equivocal cases were highly unstable, with all showing at least one negative section and one converting to positive. Pairwise Wilcoxon tests showed no consistent significant differences. CMV IHC exhibits variability in low-positive cases, leading to diagnostic transitions. Serial sectioning enhances confidence but does not fully eliminate variability. A multimodal approach integrating IHC with molecular methods and further standardization of IHC protocols may improve CMV detection accuracy.
巨细胞病毒（CMV）是免疫功能低下个体的主要病原体，常引发严重的胃肠道并发症。免疫组织化学（IHC）因其高特异性而被广泛用于CMV检测，但其在CMV阳性细胞稀少的病例中的可靠性仍不确定。本研究通过评估连续切片中的CMV检测情况，来评估CMV IHC在胃肠道活检中的可重复性。2023年至2024年期间，在舍巴医疗中心病理研究所进行了一项前瞻性观察研究。纳入了25例基于IHC诊断的CMV结肠炎病例，并分为阳性（≥2个CMV阳性细胞）或可疑（1个CMV阳性细胞）。对组织块进行连续切片，随后进行CMV IHC染色。采用包括Friedman检验和Wilcoxon符号秩检验在内的描述性统计分析来评估CMV检测的变异性。连续切片中CMV阳性细胞计数差异显著（Friedman检验，p = 0.047）。虽然有些病例保持稳定，但其他病例则有波动，从阳性转变为可疑或阴性。在最初为阳性的病例中，33.3%（7/21）至少有一个阴性切片，33.3%（7/21）至少有一个可疑切片。可疑病例极不稳定，所有病例都至少有一个阴性切片，且有一例转为阳性。成对Wilcoxon检验未显示出一致的显著差异。CMV IHC在低阳性病例中表现出变异性，导致诊断结果转变。连续切片可增强信心，但不能完全消除变异性。将IHC与分子方法相结合的多模式方法以及进一步规范IHC方案可能会提高CMV检测的准确性。
