Biopsy Limitations And Tissue Artifacts

Myocarditis is often a focal process, and sampling error remains a major consideration in the clinical management of patients. From the cardiac transplant literature, statistical analysis has shown an expected false-negative rate of 5% with 3 pieces and 2% with 4 pieces obtained by a 9F bioptome.13 The reported false-negative rate in myocarditis is higher than in acute cardiac rejection. A Mayo Clinic study of endomyocardial samples obtained post mortem from hearts of patients who died of myocarditis reported a false-negative rate of 37% for the right ventricle.14 Rather than negating the role of the endomyocardial biopsy for the diagnosis of clinically suspected myocarditis, as has been proposed by some investigators,15-17 we think it remains the standard for this purpose. Recognition of the diminished sensitivity of the biopsy, careful patient selection, adequate biopsy sampling, and liberal use of leveled sections improve the diagnostic yield. For these reasons, a minimum of 4 to 5 pieces is recommended to minimize sampling error. Samples obtained by smaller bioptomes may require at least 5 or 6 pieces.

Various artifacts occur in endomyocardial biopsy specimens, which may mimic pathologic processes, and the surgical pathologist must be aware of these patterns. These have been reviewed in detail18 and only selected topics are reviewed here. The most common biopsy artifact is the presence of contraction bands within myocytes. They are identical to the bands observed in acute ischemic necrosis and catecholamine (pressor) effect. These changes are induced by the biopsy procedure and can be diminished by using fixatives at room temperature. In ischemic injury, the nuclei of surrounding myocytes are usually pyknotic, whereas in artifactually induced contraction bands, the nuclei appear normal.

Another frequent artifact is intussusception or telescoping of small arteries that mimics luminal occlusion by thrombus. Connective tissue stains such as Masson trichrome or elastic van Gieson highlight the internal elastic membranes of both vessel segments. Intramyocardial accumulations of mature adipose tissue can simulate epicardial tissue, especially if associated with vessels of relatively large caliber. Both can be found in the right ventricular apical region, and adipose tissue is found not uncommonly in women and elderly patients. This should not be confused with arrhythmogenic right ventricular dysplasia or ventricular perforation; the latter is identified by the presence of mesothelial cells.

Accumulations of fresh platelet, fibrin-rich thrombus may be identified along the endocardial surface of biopsy fragments. These form by repeated placement of the biop-tome along the endocardium and do not indicate chronic mural thrombi. Crush artifactual distortion of cellular components can be mistaken for inflammatory cell infiltrates. This can be reduced by gently extracting the specimen from the bioptome with a needle. Finally, artifactual widening of the interstitium may be caused by tissue procurement and processing and does not imply interstitial edema. We require the presence of interstitial, eosinophilic proteinaceous material as a minimum criterion for edema.

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