Myocarditis associated with doxorubicin cardiotoxicity

In contrast to previous reports, the authors were impressed by the frequency of myocarditis in the endomyocardial biopsy specimens of patients treated with anthracyclines. To examine this, they reviewed the histologic and electron microscopic results and immunoperoxidase stains of myocardial biopsy specimens from 11 patients with doxorubicin cardiotoxicity grades 1.0-3.0. Immunoperoxidase stains for lymphocytes, macrophages, and endothelial cells and induced expression of Class II antigen were performed using the avidin-biotin complex procedure. A full panel of monoclonal antibodies was employed on fresh-frozen tissue; a smaller panel was used with formaldehyde-fixed paraffin-embedded material. Four of the 11 endomyocardial biopsy specimens showed myocarditis, and 2 showed borderline myocarditis by the Dallas criteria. The infiltrating lymphocytes were generally characterized as T lymphocytes and were associated with induced Class II antigen expression by arterial endothelial cells. In addition, foci of replacement fibrosis, suggesting a chronic process, were identified. Although this association does not prove a causal relationship, these results suggest that myocarditis can be a component of doxorubicin-induced myocardial injury.