{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T09:29:21Z","timestamp":1786786161879,"version":"build-2736575974"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004375","name":"Tel Aviv University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004375","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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 (\u2265\u20092 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 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.047, 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.\n                  <\/jats:p>","DOI":"10.1007\/s00428-025-04226-y","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T21:39:36Z","timestamp":1757626776000},"page":"369-374","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the first cut: evaluating CMV IHC reliability in serial gastrointestinal biopsy sections"],"prefix":"10.1007","volume":"489","author":[{"given":"Anna","family":"Hochner-Ger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liat","family":"Anafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido","family":"Veisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Barshack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-6338","authenticated-orcid":false,"given":"Chen","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"4226_CR1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.4174\/astr.2023.104.2.119","volume":"104","author":"S Kim","year":"2023","unstructured":"Kim S, Yoon KW, Gil E et al (2023) Emergency gastrointestinal tract operation associated with cytomegalovirus infection. Ann Surg Treat Res 104:119\u2013125","journal-title":"Ann Surg Treat Res"},{"key":"4226_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/v16030452","volume":"16","author":"PJ Yeh","year":"2024","unstructured":"Yeh PJ, Wu RC, Tsou YK et al (2024) Comparative analysis of cytomegalovirus gastrointestinal disease in immunocompetent and immunocompromised patients. Viruses 16:452","journal-title":"Viruses"},{"key":"4226_CR3","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1097\/PAS.0b013e31827fcc33","volume":"37","author":"AM Mills","year":"2013","unstructured":"Mills AM, Guo FP, Copland AP et al (2013) A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue. Am J Surg Pathol 37:995\u20131000","journal-title":"Am J Surg Pathol"},{"key":"4226_CR4","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/s00428-015-1741-8","volume":"466","author":"N Zidar","year":"2015","unstructured":"Zidar N, Ferkolj I, Tepe\u0161 K et al (2015) Diagnosing cytomegalovirus in patients with inflammatory bowel disease\u2014by immunohistochemistry or polymerase chain reaction. Virchows Arch 466:533\u2013539","journal-title":"Virchows Arch"},{"key":"4226_CR5","doi-asserted-by":"publisher","first-page":"985","DOI":"10.5858\/arpa.2018-0235-OA","volume":"143","author":"M Ambelil","year":"2019","unstructured":"Ambelil M, Saulino DM, Ertan A et al (2019) The significance of so-called equivocal immunohistochemical staining for cytomegalovirus in colorectal biopsies. Arch Pathol Lab Med 143:985\u2013989","journal-title":"Arch Pathol Lab Med"},{"key":"4226_CR6","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1097\/PAS.0000000000002071","volume":"47","author":"Y Ono","year":"2023","unstructured":"Ono Y, Gonzalez RS (2023) Apoptosis, crypt dropout, and equivocal immunohistochemical staining may indicate cytomegalovirus infection in inflammatory bowel disease patients. Am J Surg Pathol 47:933\u2013941","journal-title":"Am J Surg Pathol"},{"key":"4226_CR7","doi-asserted-by":"publisher","first-page":"360","DOI":"10.5858\/arpa.2020-0425-OA","volume":"146","author":"G Goyal","year":"2022","unstructured":"Goyal G, Zinger T, Warfield D et al (2022) The trends of immunohistochemistry for tissue-invasive cytomegalovirus in gastrointestinal mucosal biopsies. Arch Pathol Lab Med 146:360\u2013365","journal-title":"Arch Pathol Lab Med"},{"issue":"6","key":"4226_CR8","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.14309\/ajg.0000000000003463","volume":"120","author":"DT Rubin","year":"2025","unstructured":"Rubin DT, Ananthakrishnan AN, Siegel CA et al (2025) ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol 120(6):1187\u20131224","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"4226_CR9","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1093\/ecco-jcc\/jjab052","volume":"15","author":"T Kucharzik","year":"2021","unstructured":"Kucharzik T, Wilkens L, Maconi G et al (2021) ECCO guidelines on opportunistic infections in IBD. J Crohns Colitis 15(6):879\u2013913","journal-title":"J Crohns Colitis"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-025-04226-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-025-04226-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-025-04226-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T09:25:09Z","timestamp":1786785909000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-025-04226-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":9,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["4226"],"URL":"https:\/\/doi.org\/10.1007\/s00428-025-04226-y","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"assertion":[{"value":"15 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was conducted using archived, anonymized biopsy material collected during routine diagnostic procedures. As such, institutional review board approval and informed patient consent were not required under local regulations for non-interventional retrospective analysis.","order":1,"name":"Ethics","label":"Ethics approval statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No previously published material was reproduced in this manuscript.","order":2,"name":"Ethics","label":"Permission to reproduce material from other sources","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}