The Significance of So-Called Equivocal Immunohistochemical Staining for Cytomegalovirus in Colorectal Biopsies

Abstract

Context.— Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV. Objectives.— To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies. Design.— Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history. Results.— Fifty-two cases (24% of all tested, 63% of positive cases) showed equivocal staining for CMV, and of these, 41 had follow-up information. Polymerase chain reaction for CMV was performed largely on blood samples and was not found to be sensitive for the detections of CMV proctocolitis. Of 25 patients who received antiviral treatment, 21 (84%) had complete resolution of symptoms, compared with 8 of 16 (50%) who did not receive antivirals (P = .02). There was no statistically significant difference in response to antiviral drugs in patients with equivocal and unequivocal CMV staining (P = .17). Conclusions.— Equivocal CMV staining likely represents true CMV proctocolitis. Prospective studies are needed to confirm these findings.

Immunohistochemistry and special stains in gastrointestinal pathology practice

“…CMV IHC aids in identifying the virus-infected cells in cases with a high index of suspicion. 38 It is of greatest utility when the inclusions are equivocal and other entities enter the differential, chiefly inflammation/regeneration-associated nucleolar prominence, and a positive result in this case will always highlight more infected cells than appreciable on H&E. On the other hand, indiscriminate application of CMV IHC will detect latently infected cells, which may lead to an erroneous assignment of aetiology. 39 Lastly, pigment-laden macrophages may simulate CMV-infected cells on IHC, due to their size and haemosiderin content.…”

The Trends of Immunohistochemistry for Tissue-Invasive Cytomegalovirus in Gastrointestinal Mucosal Biopsies

“…Notably, cases with single cell positive staining in biopsies from the GI tract have been described as rare, isolated, or occasionally positive in several recent studies, and the significance of rare CMV-positive cells for clinical management is in dispute. [20][21][22] In our institute, the observed case with more than 1 epithelial or stromal cell (including 1 cell) showing strong unclear staining was reported as positive for CMV. The absolute number of CMV-positive cells was generally not stated in the pathology report, except when only a single cell stained positively, in which case a description such as ''single cell positive'' or ''a rare positive cell'' was usually included.…”

“…Similar findings were also reported in a recent study on CMV in colorectal biopsies. 20 There are several limitations in this study. This was a retrospective study conducted in 1 tertiary center.…”

Involvement of HHV-4 (Epstein–Barr Virus) and HHV-5 (Cytomegalovirus) in Inflammatory Bowel Disease and Colorectal Cancer: A Meta-Analysis

“…Still, the detection of HHV-4 in tissues is tricky and requires ISH approaches that are not routinely performed [ 78 ]. Similarly, the detection of HHV-5 has not been standardized [ 80 ], increasing the discrepancies in the viral prevalence between the studies. This might explain why Herpesviruses are still not consistently observed in gastric or colorectal tissues, and/or in different frequencies or quality.…”