Current Problems in Establishing Quantitative Histopathologic Criteria for the Diagnosis of Lymphocytic Myocarditis by Endomyocardial Biopsy

Both the clinical and the biopsy diagnoses of myocarditis are prone to false-positive and false-negative interpretations. False-positive clinical diagnoses probably most commonly result from a failure to recognize other disorders, such as cardiomyopathy and myocardial infarction, that may mimic myocarditis. False-negative clinical diagnoses may occur in patients with myocarditis in whom the signs and symptoms are atypical, absent, or misinterpreted. The two most common errors made by pathologists that produce false-positive tissue diagnoses appear to be a failure to recognize the number of lymphocytes that occupy the normal myocardial interstitium and a misinterpretation of noninflammatory interstitial cells as lymphocytes. Sampling error may be the most usual cause of false-negative tissue diagnoses. Since myocarditis is characterized by leukocytic and reparative responses, the most important features to evaluate in endomyocardial biopsy tissues are the type, distribution, and extent of the inflammatory infiltrate and the presence and extent of interstitial and endocardial fibrosis. Although no single histopathologic criterion is both sensitive and specific for myocarditis, it appears that quantitative evidence of an interstitial leukocytic infiltrate is currently the best available hallmark for myocarditis in biopsy specimens. It is suggested that a mean lymphocyte count greater than 5.0/high-power (X 400) microscopic field be considered indicative of lymphocytic myocarditis and that a mean count less than this be interpreted as myocarditis only if discrete clusters of lymphocytes are identified, since differentiation of low-grade diffuse infiltrates from expected normal lymphocytic populations is problematic at levels less than 5.0.