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C4d staining is a valuable marker in identifying chronic GVHD in colonic biopsies following BMT

Bone Marrow Transplantation volume 42, pages 209–211 (2008)Cite this article

All three cases had some features in common. First, all three patients had a medical history of biopsy-proven GVHD of the skin. Second, all three patients had gastrointestinal symptoms, and the GVHD occurred at least 4 months following BMT. Except for the second case with occasional apoptotic cells in the colonic epithelium, the first and the third cases did not demonstrate definite features of intraepithelial apoptosis. No necrosis, thrombi or microorganisms were seen in any of the colonic biopsies. All three colonic biopsies showed distortion of glands, edema, vascular dilatation in the lamina propria, and slightly increased intraepithelial lymphocytes. All of these features were consistent with chronic GVHD,4 which is different from acute GVHD of the colon, since acute GVHD is characterized by prominent intraepithelial apoptosis or more severe features ranging from crypt abscesses to epithelial denudation.5 Third, C4d staining was strongly and diffusely present in dilated capillaries of colonic biopsies. In the first case, the C4d staining was also seen pre-mortem in the gastric biopsy and post-mortem in multiple internal organs such as heart, stomach and liver. None of the control colon cases (normal morphologic colon (n=3), acute colitis (n=4) or pseudomembranous colitis (n=3)) stained positively for C4d. Control cardiac, liver and gastric specimens were also negative for C4d staining. Fourth, the three patients all died shortly after colonic GVHD developed (2 weeks–2 months). The autopsy of the first patient revealed a systemic GVHD, including severe cardiac GVHD. The second patient died of recurrent large-cell lymphoma that involved her lungs and brain. Two months after initial colonic biopsies, the third patient developed a severe form of pseudo-membranous colitis and eventually died of multiple organ failure. Fifth, we believe that positive C4d staining in the colonic biopsies of these cases could provide decisive evidence assisting the final diagnosis of chronic GVHD, as described in the figure.

Because of the novelty of the findings that antibody-mediated rejection concurred with chronic GVHD, no serum test for donor-specific antibody was obtained from any of the three deceased patients. In conclusion, our data suggest that C4d staining is a valuable marker for assisting diagnosis of chronic GVHD in patients with BMT.

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Authors and Affiliations

  1. Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI, USA

    P L Zhang

  2. Division of Laboratory Medicine, Geisinger Medical Center, Danville, PA, USA

    M L Wilkerson

  3. Weis Center for Research, Geisinger Medical Center, Danville, PA, USA

    C M Schworer

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  1. P L Zhang
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  2. M L Wilkerson
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  3. C M Schworer
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Correspondence to P L Zhang.

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Zhang, P., Wilkerson, M. & Schworer, C. C4d staining is a valuable marker in identifying chronic GVHD in colonic biopsies following BMT. Bone Marrow Transplant 42, 209–211 (2008). https://doi.org/10.1038/bmt.2008.132

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