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2007 Banff Schema for Grading of Acute Pancreas Allograft Rejection

Acute Cell-Mediated Rejection(return to top)

No inflammation OR inactive septal mononuclear inflammation not involving veins, arteries, ducts, or acini 1. Fibrous tissue limited to septa in appropriate amounts; no injury or atrophy of acinar regions
Indeterminate for Acute Rejection
"Active" septal inflammation without other criteria for rejection (see below)

1. Any venulitis or ductitis qualifies for at least mild acute rejection (or more depending on other features)

2. Active inflammation refers to blastic lymphoctyes with variable numbers of eosinophils

Grade I (Mild acute cell-mediated rejection)

"Active" septal inflammation with involvement of septal veins (venulitis) and/or ducts (ductitis)

AND/OR focal (1-2 foci/lobule) acinar "active" inflammation with minimal/no acinar cell injury

1. Any venulitis or ductitis is sufficient for diagnosis; nerve branches usually involved but rarely sampled; focal acinar "active" inflammation alone also adequate for diagnosis
Grade II (Moderate acute cell-mediated rejection)

Minimal intimal arteritis

AND/OR multiple (3 or more foci/lobule) foci of acinar "active" inflammation with single cell injury/dropout

1. Minimal intimal arteritis refers to occasional subendothelial lymphocytes without obvious endothelial swelling/activation or injury

Grade III (Severe acute cell-mediated rejection) Widespread acinar inflammation with confluent areas of acinar cell injury/necrosis

AND/OR moderate to severe intimal arteritis

AND/OR necrotizing arteritis

1. Any of these three findings is sufficient for the diagnosis

2. Acinar inflammation may contain variable lymphocytes, eosinophils, and neutrophils as well as edema and/or hemorrhage

3. Moderate/severe intimal arteritis consists of more frequent subendothelial lymphocytes with evidence of intimal injury, such as cell swelling, fibrin leakage, etc.

4. Necrotizing arteritis may also occur in antibody-mediated rejection and C4d stain should be performed.

Chronic Active Cell-Mediated Rejection (return to top)

Chronic active cell-mediated rejection Arterial luminal narrowing due to intimal proliferation of fibroblasts, myofibroblasts, smooth muscle cells, with admixed T lymphocytes and macrophages ("active" transplant arteriopathy)

1. May represent transition between intimal arteritis and chronic transplant arteriopathy related to suboptimal immunosuppression

2. Rarely seen in needle biopsies, more often seen in allograft resection related to chronic rejection

Antibody-Mediated Rejection (return to top)

Hyperacute antibody-mediated rejection Widespread deposition of immunoglobulin (usu. IgG) and complement (e.g., C4d) with resultant arteritis and venous thrombosis, hemorrhagic necrosis and allograft failure usually within 1 hour after revascularization

1. In all cases, diagnosis is dependent upon demonstration of a) graft dysfunction, b) capillary complement deposition (i.e., C4d positivity), AND c) donor specific antibodies in serum.

2. If C4d and only 1 of the other 2 features is found, then the diagnosis"suspicious for" antibody-mediated rejection is more appropriate

3. In cases in which vascular thrombosis is the predominant finding, the differential diagnosis lies between antibody-mediated rejection and "technical failure".

Accelerated antibody-mediated rejection Similar to hyperacute, but changes evolve over hours to days after revascularization.
Acute antibody-mediated rejection Allograft dysfunction in first posttransplant weeks; histology varies from normal to margination of neutrophils and mononuclear cells to thrombosis and necrosis;

Chronic Active Antibody-Mediated Rejection (return to top)

Chronic active antibody-mediated rejection Features of chronic rejection/graft sclerosis together with C4d positivity in capillaries

1. May also have vascular fibrinoid necrosis/thrombosis indicating ongoing antibody-mediated rejection

2. C4d positivity, graft dysfunction, and donor-specific antibodies are all required for a diagnosis as in other forms of antibody-mediated rejection

Chronic Rejection (Graft Sclerosis) (return to top)

Chronic allograft rejection Stage I (mild graft sclerosis) Fibrous septa expanded but comprise less than 30% of biopsy surface area. Acinar lobules have irregular contours due to erosion  
Chronic allograft rejection Stage II (moderate graft sclerosis) Fibrous septa expanded to 30-60% of biopsy surface area. Most lobules have irregular contours and central areas are affected, with fibrous strands extending between lobules  
Chronic allograft rejection Stage III (severe graft sclerosis) Fibrous septa comprise over 60% of biopsy surface area with only a few areas of residual acini and/or islets  
Reference: Drachenberg CB et al. Banff schema for grading pancreas allograft rejection: Working proposal by a multi-disciplinary international consensus panel. Am J Transplant 8:1-13, 2008.
Last Modified: Thu Jun 18 10:14:08 EDT 2009