Pancreas rejection. Significance of histopathologic findings with implications for classification of rejection.

To determine the significance of various histopathologic features of pancreatic rejection, we reviewed the pathology of 53 biopsies taken to rule out rejection [32 bladder drained, (BD); 18 non-BD]. Twenty-six biopsies from 23 patients with allografts which ultimately failed (FLD) (7 BD, 16 non-BD) were compared with 27 biopsies from 27 patients with allografts which continue to function (FXN) (25 BD, 2 non-BD). The groups are similar in regard to age, sex, and time after transplant to biopsy. The mean follow-up is 13 months for FLD grafts versus 35 months for FXN grafts (p < 0.0001). In BD grafts, decreases in urine amylase usually led to biopsy, while in non-BD grafts, hyperglycemia usually prompted biopsy. More patients with ultimately FLD organs (17 of 26) presented with elevated blood glucose (BG) than patients with FXN grafts (2 of 27) (p < 0.0001). Multiple histologic features were examined related to the acinar tissue, pancreatic ducts, islets, vessels, and nerves. Features which strongly correlated with a negative outcome included moderate to severe inflammation of acinar tissue (p < 0.0001), acinar tissue loss and fibrosis (p < 0.0087) and vascular luminal narrowing due to chronic rejection (p < 0.003). Twenty-one pancreases showed chronic rejection and were treated with OKT3 or anti-lymphocytic globulin (ALG), six of these continue to function 1.6-9 years after biopsy, including two who presented with elevated BG levels. A normal biopsy was found in nine pancreases, all of which continue to function. Vasculitis was only seen in biopsies with moderate to severe inflammation, whereas endothelialitis was also seen in association with mild inflammation, suggesting that vasculitis is a more aggressive lesion. A rejection classification is proposed with endothelialitis partly defining mild rejection and vasculitis defining severe rejection. We conclude that several biopsy features and elevation of BG are strongly correlated with a high probability of failure; however, antirejection therapy is justified because recovery of function occurs in some cases. A normal biopsy obviates the need for therapy and predicts a good outcome, as do mild histological findings of rejection.