Standardized Cardiac Biopsy Grading
Heart Transplantation

2004 Revision of Standardized Cardiac Biopsy Grading

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)
No histologic or immunopathologic features of AMR  
Histologic features of AMR AND positive immunostain for AMR

Histologic features can include capillary endothelial swelling, denudation, intravascular macrophage accumulation, intravascular thrombi, interstitial edema, hemorrhage, myocyte necrosis without cellular infiltration.

Immunostains include paraffin demonstration of diffuse capillary C4d and intracapillary CD68 positive macrophages, or frozen section immunofluorescence showing capillary immunoglobulin (IgG, IgM, and/or IgA) and complement (C3d, C4d and/or C1q) deposition

NOTE: It was decided at Banff 2009 meeting to recommend screening ALL allograft heart biopsies for C4d.

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 stain 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: Mon Aug 24 8:00:00 EDT 2009


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