Patterns of C4d Immunohistochemical Staining in Non-Transplant Myocardial Ischemia: Implications for Interpretation of Post-Transplant Endomyocardial Biopsies
RM Hudacko, S Varghese, BS Fyfe. Robert Wood Johnson Medical School, New Brunswick, NJ
Background: C4d immunohistochemical staining is a marker of recent classical pathway complement activation that is useful for evaluation of antibody-mediated rejection in transplant biopsies. C4d also stains areas of ischemic myocyte necrosis. We describe the pattern and intensity of myocyte, interstitial, and microvascular staining at different stages of ischemic injury/infarction in the non-transplant setting.
Design: Thirty autopsies with ischemic injury were reviewed. Nine acute myocardial infarction, 3 contraction band necrosis, 9 subendocardial ischemic, and 9 chronic ischemic injury cases were stained with polyclonal antibody for C4d.
Results: Acute myocardial infarction cases showed strong staining of necrotic myocytes; larger infarcts showed more intense peripheral versus central staining. Subendocardial ischemic injury stained homogeneously and was easier to quantify versus H&E staining. Necrosis with contraction bands was strongly highlighted in individual myocytes. One case of “contraction band necrosis” noted on H&E was negative and subsequently reclassified as artifactual. Two of 9 cases of scarring/chronic ischemic injury showed rare positive cells. C4d was noted to highlight cardiac amyloid in 4 cases. Microvascular staining was noted in only 2 cases. This staining was faint and not associated with injured areas. Both of these patients were septic; therefore this may be artifactual staining. Autolysis had no effect on staining.
Conclusions: C4d is a useful diagnostic tool to highlight necrotic myocytes, especially in the absence of large areas of obvious necrosis. It is useful for quantitating the degree of subendocardial ischemia, as well as differentiating true from artifactual contraction band injury, and it can be used on autolyzed material. It can be used to outline edges of a large infarct and to define acute extension of an old infarct. Microvascular staining is not seen around areas of infarction. This finding may help in the interpretation of perioperative ischemic injury versus humoral rejection in heart transplants, wherein microvascular staining in post-implantation biopsies should prompt additional clinical investigations to rule out humoral rejection. Finally, C4d highlights amyloid deposition in the myocardium, a finding of interest that should be further investigated.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 4, Monday Morning