Standardized Cardiac Biopsy Grading
Heart Transplantation

2005 Cardiac Biopsy Grading of Cellular Rejection with 2013 Update for Antibody Mediated Rejection

go to 1990 Heart Grading System

Acute Cellular Rejection
Histopathological Findings
No rejection See example- Grade 0R
Focal OR diffuse interstitial AND/OR perivascular inflammation WITH up to one focus of myocyte damage

Incorporates old grades 1A, 1B and 2 into a single category. (See examples- 1A, 1B, 2).

Inflammation usually mononuclear with some eosinophils. Neutrophils not present except in severe forms, plasma cells not typically present.

Myocyte damage may be manifest by clearing of cytoplasm and nucleus with nuclear enlargement, sometimes nucleolar prominence; also by irregular scalloped borders with associated inflammation

Two or more foci of inflammation WITH associated myocyte damage (i.e., more than one focus of myocyte damage). Equivalent to old grade 3A (See example- 3A)
Diffuse inflammation WITH multiple foci of myocyte damage WITH OR WITHOUT any combination of: edema, hemorrhage, vasculitis. Incorporates old grade 3B and 4 into a single category (See example).
Acute Antibody-Mediated Rejection (AMR)
pAMR 0
Negative for pathologic AMR: No histologic or immunopathologic features of AMR  

pAMR 1 (H+)

Histopathologic AMR alone: Histologic features of AMR present AND negative immunopathologic findings

Histologic features include intravascular activated mononuclear cells, including macrophage accumulation in capillaries and venules, and/or endothelial cells with enlarged nuclei and expanded cytoplasmic projections that appear to narrow or occlude lumens.

Severe AMR (see below) can contain hemorrhage, interstitial edema, myocyte necrosis, capillary fragmentation, mixed inflammation including neutrophils, and endothelial pyknosis or karyorrhexis.

Intact myocardium should be assessed, avoiding areas of ischemic injury, prior biopsy sites, Quilty lesions and fibrous scars.


pAMR 1 (I+)
Imunopathologic AMR alone: Immunopathologic features of AMR present AND negative histologic findings

Paraffin C4d and CD68 or frozen section C4d, C3d, HLA-DR recommended as primary panels.

C4d interpretation: <10% capillary uptake: Negative; 10-50% uptake: focal; >50%: diffuse. Interpreted as positive if >50% uptake regardless of intensity (intensity 0= no stain; 1=faint stain, 2=strong stain) Assessment limited to capillaries. Ignore any staining of venules, arteries, arterioles, capillaries in Quilty lesions, vessels in scars, subendocardial connective tissue and necrotic myocytes.

CD68 interpretation: interpretation based on intravascular macrophages, which have chain-like, linear or beading stainingn profiles in capillaries and small venules, in contrast to interstitial macrophages. <10%: negative; 10-50% focal; >50% diffuse. Interpreted as positive if 10% or more.

Positive C4d or CD68 alone is considered sufficient to establish immunopathologic features of AMR.



pAMR 2 Pathologic AMR: Both histologic and immunopathologic features of AMR present

See descriptions of pAMR (H+) and pAMR (I+) above.



pAMR 3
Pathologic AMR: Immunopathologic features of AMR present AND negative histologic findings

See descriptions of pAMR (H+) and pAMR (I+) above.



Other (Non-Rejection) Biopsy Findings
Early ischemia

Myocyte injury or necrosis (contraction band necrosis, coagulative necrosis) often with myocyte vacuolization, fat necrosis. Myocyte injury disproportionately high for small amount of inflammation, or no inflammation in early stages.

Related to perioperative ischemic injury, seen up to 6 weeks posttransplant.

Over time, inflammation develops, contains neutrophils in addition to other cells.

Acute rejection usually has more inflammation relative to myocyte injury; neutrophils uncommon in acute rejection unless severe. However, neutrophils may also occur in antibody mediated rejection.

Trichrome or C4d stains may be helpful in detecting myocyte damage in some cases.

See example: Ischemia

Late ischemia
Histologic features of ischemia similar to above Related to graft coronary artery disease.
Quilty effect
Mononuclear cell infiltrate restricted to endocardium OR with infiltration into underlying myocardium.

Incorporates older terminology encompassing both infiltrating (Type A) and non-infiltrating (Type B) Quilty lesions.

Tangential section may obscure relationship between infiltrating portion and endocardial portion. Additional sections may be helpful.

Presence of B cells, plasma cells, background fibrosis and prominent vascularity favor Quilty effect over acute rejection.

Examine especially for CMV, toxoplasma Both infections may have lymphocyte-predominant inflammation that may mimic acute rejection.
Lymphoproliferative disorder
Uncommon in heart, findings similar to spectrum seen elsewhere. See example: Lymphoproliferative disorder
  • For evaluation need minimum of 3 samples, each at least 50% myocardium, and excluding prior biopsy site, scar, adipose tissue, blood clot. At least 3 levels H&E stained for microscopy.
Reference Stewart S et al. Revision of the 1990 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Heart Rejection J Heart Lung Transplant 24:1710-20, 2005.

Last Modified: Sat Jun 13 2020, 10:28 PM EST


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