Immunohistochemistry Improves the Detection of Adenovirus, but Not Cytomegalovirus, in Gastrointestinal Biopsies from Hematopoietic Stem Cell Transplant Recipients
Sophie R Weidner, Jose Jessurun, Rhonda K Yantiss, Nicole C Panarelli. Weill Cornell Medical College, New York, NY
Background: Gastrointestinal (GI) infections by cytomegalovirus (CMV) and adenovirus (ADV) may complicate hematopoietic stem cell transplantation (HSCT). Histologic evaluation is commonly used to detect these infections and to differentiate them from other complications such as graft versus host disease and drug toxicities. Although these viruses produce recognizable cytopathic changes, they may be subtle, and thus, viral immunohistochemistry (IHC) may aid in their identification. The aim of this study is to evaluate whether routine IHC is necessary to detect these viral infections.
Design: Hematoxylin and eosin (H&E) stained sections were prepared from 105 GI biopsy cases from 77 HSCT recipients and reviewed by 3 pathologists. Biopsies were classified as showing 1) no evidence of, 2) cellular changes suspicious for, or 3) cytopathic changes diagnostic of CMV and/or ADV infection. Cases were evaluated for other features suggestive of infection: apoptosis, ulcers and crypt injury (cryptitis, abscesses, loss, degeneration and remodeling). CMV and ADV IHC stains were performed on all cases and the results compared to interpretations of H&E stained sections.
Results: The study group contained 77 adult HSCT patients (mean age: 54 years) with GI symptoms. Samples were obtained from the upper GI tract (n=51), lower GI tract (n=23), or both (n=31), (mean: 5 biopsies/case). One reviewer classified 10 and 13 cases as suspicious for or diagnostic of CMV and ADV infection, respectively, compared to 6 and 10 for the second and 2 and 1 for the third reviewers. Two CMV and 2 ADV positive cases were detected by IHC. The 2 cases that were positive for CMV were recognized in H&E sections by all reviewers. By contrast, all reviewers identified only 1 of the 2 ADV positive cases and missed the second one, the latter of which contained rare viral inclusions in only 1 of 6 biopsies on retrospective review of the H&E stained slides. All 4 positive cases showed only minimal or focal inflammatory changes.
Conclusions: CMV infection may be reliably identified on H&E stained section of GI biopsies from HSCT recipients and, thus, confirmatory IHC should be reserved for select cases. However, routine IHC stains for ADV are necessary since cytopathic changes may be difficult to discern and easily missed on H&E stained sections. Since both viruses may elicit only minimal inflammatory/degenerative changes, the absence of these features does not exclude an infection.
Tuesday, March 5, 2013 8:45 AM
Proffered Papers: Section D, Tuesday Morning