Revision of the 1990 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Heart Rejection

Myocardial biopsy showing acute cellular rejection with an inflammatory infiltrate composed of mainly lymphocytes in a perivascular distribution and not extending into interstitium or damaging myocytes. Hematoxylin and Eosin. (H&E)

Myocyte damage characterized by encroachment of mononuclear cells at the perimeter of myocytes resulting in irregular, scalloped borders and distorting the cellular architecture. Several myocytes are surrounded by infiltrating cells. (H&E).

Grade 0 R: Normal endomyocardial biopsy showing no evidence of cellular infiltration. (H&E).

Grade 1 R: Low power view of endomyocardial biopsy showing three focal, perivascular infiltrates without myocyte damage. Previously Grade 1A (H&E).

Grade 1 R: Higher power view of focal, perivascular mononuclear cell infiltrate without myocyte encroachment or damage. Previously Grade 1A. (H&E).

Grade 1 R: Both perivascular and interstitial infiltrates are present but without definite evidence of myocyte damage. Previously Grade 1A (H&E).

Grade 1 R: Diffuse mononuclear cell infiltrate with an interstitial pattern of lymphocytes between and around myocytes without associated myocyte damage. Previously Grade 1B. (H&E).

Grade 1 R: High power view of a mononuclear infiltrate extending from a perivascular position into adjacent myocardium with damage to myocytes and distortion of architecture. This is a single focus in the biopsy series and therefore is included in the revised mild grade of acute rejection, previously described as Grade 2. (H&E).

Grade 2 R: Low power view showing three foci of damaging mononuclear cell infiltrate with normal myocardium intervening. Prevously Grade 3A. (H&E).

Grade 2 R: Higher power view of one focus of figure 9 damaging infiltrate with myocyte damage and architectural distortion (a “space occupying lesion”). (H&E).

Grade 3 R: Diffuse damaging infiltrates with encroachment of myocytes and disruption of normal architecture. This contrasts with the non-damaging infiltrates of figure 7. Prevously Grade 3B. (H&E).

Grade 3 R: Severe acute rejection with widespread myocyte damage and some necrosis. The diffuse infiltrate includes polymorphs as well as lymphocytes, macrophages and plasma cells. Previously Grade 4. (H&E).

Peritransplant injury showing a focus of ischemic injury with myocytolysis and vacuolization. Note the relative lack of infiltrating inflammatory cells compared with acute cellular rejection. Macrophages are present. (H&E).

Low power view of non-encroaching endocardial infiltrate or Quilty lesion with normal underlying myocardium. (H&E).

Higher power view of another area of the same biopsy as figure 14, showing some superficial encroachment of the endocardial lesion into underlying myocardium. Note the prominent vascularity of this endocardial infiltrate which can be a very useful feature for distinguishing tangentially cut infiltrates from foci of acute cellular rejection. (H&E).

A deeper section of the biopsy in figure 15 showing much greater encroachment into myocardium and less vascularity. (H&E).

Endomyocardial biopsy showing a small endocardial infiltrate and focus of deeper intramyocardial cellular infiltration which raises the possibility of acute cellular rejection until deeper sections are examined. (H&E).

Deeper section of figure 17 clearly shows extension of the surface endocardial infiltrate into myocardium confirming the correct diagnosis of Quilty lesion rather than acute cellular rejection. (H&E).

Antibody mediated rejection (AMR 1). Low power view of endomyocardial biopsy with scattered cellular infiltrates and intervening normal tissue. (H&E).

AMR 1. Higher power view shows that the cellular infiltrates are within vessels and include polymorphs. Endothelial cell swelling is present. The increased cellularity seen at low power is due to the presence of these intravascular cells and not perivascular inflammation. Compare with . (H&E).

AMR 1. High power view confirms the intravascular location of the cells which have the appearance of macrophages and illustrates the endothelial cell swelling. (H&E).

AMR 1. Immunofluorescence positivity for IgG clearly shown in and around capillaries.

AMR 1. Immunofluorescence positivity for C4d in capillaries with characteristic “doughnut” appearance.

AMR 1. Immunoperoxidase staining is strongly positive for CD68, confirming the intravascular cells to be macrophages.

AMR 1. Immunoperoxidase staining is strongly positive for C4d in capillaries allowing a diagnosis of AMR to be made in the appropriate context. (see text).