Background. Tissue samples for the diagnosis of pancreatic allograft r
ejection are now obtained routinely through the application of the per
cutaneous needle biopsy technique. The availability of biopsy material
(89% adequate for diagnosis in our setting) presents a challenge for
pathologists who are asked to provide a fast and accurate diagnosis of
rejection and its severity, while at the same time being able to diff
erentiate rejection from other causes of graft dysfunction. Methods. T
o differentiate rejection from other pathologic processes, 26 histolog
ic features were assessed in 92 biopsies performed for confirmation of
clinical diagnosis of rejection and the results were compared with 31
protocol biopsies, 12 allograft pancreatectomies with non-rejection p
athology, and 30 native pancreas resections with various disease proce
sses. Results. Based on these comparisons, a constellation of findings
relating to the vascular, septal, and acinar inflammation was identif
ied for the diagnosis of rejection. Application of these features led
us to revise our scheme for grading rejection (ranging from O-normal t
o V-severe rejection) to include the categories of ''inflammation of u
ndetermined significance'' and ''minimal rejection.'' The scheme was u
sed by five pathologist to grade 20 biopsies independently of any clin
ical data and the interobserver level of agreement was highly signific
ant (kappa=0.83, P<0.0001). This grading scheme was applied blindly to
all (183) biopsies from 77 patients with 6-52 months of follow-up. Th
e correlation of the highest degree of rejection on each patient and u
ltimate graft loss (0% for grades 0-I, 11.5% for grade II, 17.3% for g
rade III, 37.5% for grade IV, and 100% for grade V) was highly statist
ically significant (P<0.002). The fraction of grafts lost due to pure
immunologic causes increased proportionally to the grade of rejection
(0, 50, 66, and 100% for grades II, III, IV, and V, respectively). Con
clusions. This study provides strong support for the proposed pancreas
rejection grading scheme and confirms its potential for practical use
.