Standardized Cardiac Biopsy Grading

Revised Standardized Cardiac Biopsy Grading System (2004)

go to: Acute Cellular Rejection, Humoral Rejection, Ischemic Injury, Quilty Effect, Miscellaneous, Technical Requirements, Reference

ACUTE CELLULAR REJECTION (go to top)

Grade

Synonym

Equivalent 1990 Grade

Histology

Comment

0 R(evised)
No acute cellular rejection
0
No mononuclear inflammation or myocyte damage

1 R
Mild/low grade acute cellular rejection
1A, 1B, or 2
Perivascular and/or interstitial mononuclear inflammation; may have one focus of associated myocyte damage

2 R
Moderate/intermediate grade acute cellular rejection
3A
Perivascular and/or interstitial mononuclear inflammation;two or more foci of associated myocyte damage; may involve one or more biopsy fragments

3 R
Severe/high grade acute cellular rejection
3B or 4
Diffuse mononuclear and/or mixed inflammation involving multiple biopsy fragments with multiple areas of myocyte damage; may have edema, hemorrhage and/or vasculitis

ACUTE ANTIBODY-MEDIATED (HUMORAL) REJECTION (go to top)

Grade

Synonym

Equivalent 1990 Grade

Histology

Comment

AMR 0
Negative for acute antibody-mediated rejection (AMR) No changes

AMR 1
Positive for acute antibodyAMR OR Histologic features of AMR OR positive immunostain for AMR (i.e., CD68. C4d) Humoral rejection Any combination of: capillary endothelial cell swelling, intracapillary macrophage accumulation, interstitial edema, hemorrhage, intracapillary and/or pericapillary neutrophils, intravascular thrombi, myocyte necrosis These histologic findings and/or onset of hemodynamic compromise suggest follow-up immunostain for complement (C3d, C4d and/or C1q in capillaries) and immunoglobulin on frozen sections,complement (C4d in capillaries) on paraffin section and CD68 stain for macrophages within (CD31, CD34-positive) capillaries

ISCHEMIC INJURY (go to top)

Grade

Synonym

Equivalent 1990 Grade

Histology

Comment

Early ischemic injury
Ischemia within first 6 post transplant weeks Ischemic injury A (up to 3 posttransplant weeks) and some B (late ischemia) Myocyte injury, myocyte vacuolization, fat necrosis, mixed inflammation including neutrophils, mononuclear cells and eosinophils Myocyte injury is usually greater than degree of inflammation, in contrast to acute rejection in which inflammation usually predominates; with neutrophils should also consider possibility of humoral rejection component

Late ischemic injury
Ischemia related to allograft coronary artery disease Ischemic injury B (late ischemia) Secondary myocyte changes such as myocyte vacuolization and microinfarcts Relevant vessels are typically not sampled on endomyocardial biopsy

QUILTY EFFECT (go to top)

Grade

Synonym

Equivalent 1990 grade

Histology

Comment

Quilty effect
Quilty A OR Quilty B Nodular or endocardial mononuclear infiltrate which may or may not extend into underlying myocardium Infiltrating form of Quilty effect must be distinguished from acute rejection. Additional sections, or prominent vascularity, presence of lymphocytes and plasma cells, background fibrosis favor Quilty effect

OTHER (go to top)

Infections
Cytomegalovirus and Toxoplasma may both be associated with lymphocyte predominant inflammation, and must be distinguished from acute cellular rejection

PTLD
Although rare in the cardiac allograft, this requires constant vigilance

TECHNICAL REQUIREMENTS FOR CARDIAC ALLOGRAFT BIOPSY (go to top)

Variable
Minimum number Comment

Number of biopsy samples

3
Samples should not be divided once obtained; an evaluable piece of tissue contains at least 50% myocardium

Number of hematoxylin and eosin slides

3
Additional blank slides may be useful for future studies

Number of levels

3

Number of "routine" special stains

0
Trichrome stain may be helpful in selected cases for evaluation of fibrosis and/or myocyte damage

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. 2005 Nov;24(11):1710-20.

Revised Standardized Cardiac Biopsy Grading System (2004) go to: Acute Cellular Rejection, Humoral Rejection, Ischemic Injury, Quilty Effect, Miscellaneous, Technical Requirements, Reference
ACUTE CELLULAR REJECTION (go to top)
Grade	Synonym	Equivalent 1990 Grade	Histology	Comment
0 R(evised)	No acute cellular rejection	0	No mononuclear inflammation or myocyte damage
1 R	Mild/low grade acute cellular rejection	1A, 1B, or 2	Perivascular and/or interstitial mononuclear inflammation; may have one focus of associated myocyte damage
2 R	Moderate/intermediate grade acute cellular rejection	3A	Perivascular and/or interstitial mononuclear inflammation;two or more foci of associated myocyte damage; may involve one or more biopsy fragments
3 R	Severe/high grade acute cellular rejection	3B or 4	Diffuse mononuclear and/or mixed inflammation involving multiple biopsy fragments with multiple areas of myocyte damage; may have edema, hemorrhage and/or vasculitis
ACUTE ANTIBODY-MEDIATED (HUMORAL) REJECTION (go to top)
Grade	Synonym	Equivalent 1990 Grade	Histology	Comment
AMR 0	Negative for acute antibody-mediated rejection (AMR)		No changes
AMR 1	Positive for acute antibodyAMR OR Histologic features of AMR OR positive immunostain for AMR (i.e., CD68. C4d)	Humoral rejection	Any combination of: capillary endothelial cell swelling, intracapillary macrophage accumulation, interstitial edema, hemorrhage, intracapillary and/or pericapillary neutrophils, intravascular thrombi, myocyte necrosis	These histologic findings and/or onset of hemodynamic compromise suggest follow-up immunostain for complement (C3d, C4d and/or C1q in capillaries) and immunoglobulin on frozen sections,complement (C4d in capillaries) on paraffin section and CD68 stain for macrophages within (CD31, CD34-positive) capillaries
ISCHEMIC INJURY (go to top)
Grade	Synonym	Equivalent 1990 Grade	Histology	Comment
Early ischemic injury	Ischemia within first 6 post transplant weeks	Ischemic injury A (up to 3 posttransplant weeks) and some B (late ischemia)	Myocyte injury, myocyte vacuolization, fat necrosis, mixed inflammation including neutrophils, mononuclear cells and eosinophils	Myocyte injury is usually greater than degree of inflammation, in contrast to acute rejection in which inflammation usually predominates; with neutrophils should also consider possibility of humoral rejection component
Late ischemic injury	Ischemia related to allograft coronary artery disease	Ischemic injury B (late ischemia)	Secondary myocyte changes such as myocyte vacuolization and microinfarcts	Relevant vessels are typically not sampled on endomyocardial biopsy
QUILTY EFFECT (go to top)
Grade	Synonym	Equivalent 1990 grade	Histology	Comment
Quilty effect		Quilty A OR Quilty B	Nodular or endocardial mononuclear infiltrate which may or may not extend into underlying myocardium	Infiltrating form of Quilty effect must be distinguished from acute rejection. Additional sections, or prominent vascularity, presence of lymphocytes and plasma cells, background fibrosis favor Quilty effect
OTHER (go to top)
Infections				Cytomegalovirus and Toxoplasma may both be associated with lymphocyte predominant inflammation, and must be distinguished from acute cellular rejection
PTLD				Although rare in the cardiac allograft, this requires constant vigilance
TECHNICAL REQUIREMENTS FOR CARDIAC ALLOGRAFT BIOPSY (go to top)
Variable	Minimum number	Comment
Number of biopsy samples	3	Samples should not be divided once obtained; an evaluable piece of tissue contains at least 50% myocardium
Number of hematoxylin and eosin slides	3	Additional blank slides may be useful for future studies
Number of levels	3
Number of "routine" special stains	0	Trichrome stain may be helpful in selected cases for evaluation of fibrosis and/or myocyte damage
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. 2005 Nov;24(11):1710-20.

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Last updated: Tuesday, 21-Feb-2006 17:14:08 EST