What biopsy findings suggest rejection?

Biopsy Findings Suggestive of Transplant Rejection

Biopsy findings that suggest rejection include capillary endothelial changes, macrophages in capillaries, interstitial inflammatory infiltrates, and complement deposition (particularly C4d) in the microvasculature. These histological features are critical for diagnosing both acute and chronic rejection across different types of organ transplants 1.

Key Histological Features of Rejection

Acute Rejection Findings

• Capillary endothelial changes - swelling, vacuolization, and disruption
• Inflammatory cell infiltration:
  • Macrophages in capillaries (required finding)
  • Neutrophils in capillaries (in severe cases)
  • Interstitial lymphocytic infiltrates
• Tissue damage:
  • Interstitial edema/hemorrhage (in severe cases)
  • Tubulitis (in kidney transplants)
  • Myocyte damage (in heart transplants)

Immunopathologic Evidence

• Complement deposition:
  • C4d deposition in capillaries (2-3+ intensity)
  • C3d and/or C1q deposition
• Immunoglobulin deposits:
  • IgG, IgM, and/or IgA deposits (2-3+ by immunofluorescence)
• Cellular markers:
  • CD68+ macrophages in capillaries
  • CD31 or CD34 staining to highlight endothelial damage

Organ-Specific Rejection Findings

Intestinal Transplant Rejection

For intestinal transplants, rejection is the most common cause of graft loss. Multiple biopsies (at least 6) should be performed even from normal-appearing mucosa, as early rejection may not be endoscopically apparent 1. Increased intestinal permeability on nuclear medicine scans also correlates with acute rejection.

Cardiac Transplant Rejection

In heart transplants, the 2013 ISHLT working formulation for pathological diagnosis of antibody-mediated rejection (AMR) includes:

• Histological evidence of acute capillary injury
• Endothelial cell activation
• Macrophage infiltration
• Immunopathologic evidence of antibody-mediated injury 1

Types of Rejection Based on Biopsy Findings

Antibody-Mediated Rejection (AMR)

• Capillary endothelial changes
• Macrophages in capillaries
• C4d deposition in capillaries (2-3+ intensity)
• Serological evidence of anti-HLA or anti-donor antibodies 1

T-Cell Mediated Rejection (TCMR)

• Interstitial infiltration of T-lymphocytes
• Tubulitis in kidney transplants
• Myocyte damage in heart transplants
• Absence of C4d deposition or other AMR features

Chronic Rejection

• Interstitial fibrosis
• Tubular atrophy (in kidney transplants)
• Vascular changes (intimal thickening, fibrosis)
• Transplant vasculopathy (in heart transplants)

Grading Systems

Rejection is typically graded according to standardized systems such as the Banff criteria for kidney transplants or the ISHLT criteria for heart transplants. These systems categorize rejection based on:

• Severity of inflammatory infiltrate (minimal, mild, moderate, severe)
• Extent of tissue damage
• Presence of vascular involvement
• Chronicity of changes

Important Clinical Considerations

1. Differential diagnosis: CMV enteritis can resemble rejection clinically and histologically, requiring experienced pathologist review 1.

2. Sampling adequacy: Multiple biopsies (at least 6) should be obtained even from normal-appearing tissue to avoid sampling error 1.

3. Timing of biopsies: Protocol biopsies performed at regular intervals can detect subclinical rejection before clinical manifestations appear 2, 3.

4. Follow-up biopsies: These are crucial to assess treatment response, as persistent rejection is common even after standard treatment 4.

5. Correlation with antibody testing: Biopsy findings should be correlated with serological evidence of donor-specific antibodies when AMR is suspected 1, 5.

By recognizing these histological patterns, clinicians can diagnose rejection early and initiate appropriate treatment to preserve graft function and improve patient outcomes.