Liver Transplant Pathology: Acute Cellular Rejection

Before we get started, I wanted to give a big shout out to this excellent article in Surgical Pathology Clinics, "Liver Transplant Pathology: Review of Challenging Diagnostic Situations" by Drs. Naini & Lassman. For quick reference purposes during signout, I am summarizing a few of their key points in the next few posts. I STRONGLY suggest you check out the full article for yourself to get the most out of it and to see great histology images of each key finding.

Acute Cellular Rejection (ACR)

Acute Cellular Rejection- Mixed portal inflammation with predominantly lymphocytes. The presence of eosinophils can be a big clue to the diagnosis!

Click on any of the images to examine a virtual slide for Acute Cellular Rejection via pathpresenter.net

Acute cellular rejection (ACR) is the most common type of rejection following liver transplant
Timing: 5-30 days after transplant (most common; can occur within a few days or months after transplant)
Biopsy must contain at least 5 portal tracts to be considered adequate

Key Histology Features

(At least 2 required for diagnosis):

Acute Cellular Rejection- Mixed portal inflammation (Click to open virtual slide in new tab on pathpresenter.net)

1. Mixed portal inflammation

Inflammation can range from mild to severe & involve only a few to all of the portal tracts.
Predominantly lymphocytes- large activated immunoblasts with large nuclei, prominent nucleoli, and abundant basophilic cytoplasm.
Eosinophils = BIG CLUE TO DIAGNOSIS!
Plasma cells, and occasional PMNs seen.
Inflammation is usually confined to the portal tract, but severe/late ACR can cause interface hepatitis (inflammation "spills out" into the surrounding hepatocytes)

2. Bile duct inflammation/damage

Lymphocytic infiltration of BD epithelium
Usually has epithelial cell injury (enlargement of bile duct nuclei with overlapping, pleomorphism, apoptosis, cytoplasmic vacuolization, luminal disruption, and/or loss of nuclear polarity)
Usually there is NOT a significant bile ductular reaction associated with the inflammation/BD damage

3. Endotheliitis of Portal vein (most common) or central vein

MOST SPECIFIC DIAGNOSTIC FEATURE OF ACR! It most commonly involves the portal veins; more severe cases involve the central vein
The example below is from the article in Surgical Pathology Clinics. It demonstrates the prominent subendothelial lymphocytic infiltrate lifting up and disrupting the overlying endothelium from the basement membrane. Notice the swollen, plump endothelial cells