Update on cardiac transplantation pathology

Context. - The endomyocardial biopsy is the mainstay for monitoring acute allograft rejection in heart transplantation. Objective and accurate assessment of cellular and humoral types of rejection is important to optimize immunosuppressive therapy, avoid therapeutic complications, and improve patient outcome. The grading system for evaluation of heart transplant biopsies published in 1990 was revised in 2004 after more than a decade of implementation. Objective. - In this review, we focus on a practical approach to the evaluation of human heart transplant biopsies as diagnostic surgical pathologic specimens. We discuss the revised International Society of Heart and Lung Transplantation working formulation. Data Sources. - We reviewed pertinent literature, incorporating ideas and vast experience of participants in various work groups that led to the revision of the 1990 grading system. Conclusions. - The grading system for cellular rejection is presented with detailed light microscopic morphology and comparison of the 1990 and 2004 International Society of Heart and Lung Transplantation working formulations. We show how the pathologic recognition of cellular rejection and antibody-mediated rejection has evolved. We emphasize the interpretation of immunostains for complement components C4d and C3d in the diagnosis of antibody-mediated rejection. Evidence of regulation of complement activation in human heart transplant biopsies is presented in this context. We also discuss the pitfalls, caveats, and artifacts in the interpretation of allograft endomyocardial biopsies. Lastly, we discuss the pathology of human cardiac allograft vasculopathy in practical detail.