Address correspondence to : Cinthia B. Drachenberg, M.D. University of Maryland Hospital Department of Pathology 22 South Greene St. Baltimore, MD 21201 Phone: (410) 328 5560 Fax: (410) 328 5508Key Words: septal inflammation acinar inflammation, ductitis, venulitis, arteritis.
With the development of the percutaneous technique  the availability of material for histologic examination has greatly increased.
Based on the examination of multiple histologic parameters and correlation with the ultimate graft survival rate, we attempted to develop a grading system that is relatively simple, reproducible and has prognostic significance.
The biopsies were considered adequate if 2-3 m2 or more of pancreatic parenchyma surface was present per section. Biopsies with changes consistent with chronic rejection were excluded from the study.
The biopsies were obtained with an 18 gauge automated biopsy needle. The success rate for the percutaneous biopsy procedure was 88.6%. Complications were present in 2 cases.
The biopsies were classified in 6 grades based on the histologic parameters
described above, by two pathologists blinded as to the clinical status of the
patients. The grading system is as follows:
Histologic features observed inconsistently and not essential for the grading of rejection were: Ductal epithelial atypia and necrosis, interstitial edema, nerve inflammation, islet inflammation, acinar cell vacuolization and presence of plasma cells.
Eosinophils were seen in 60 of the 73 biopsies showing rejection and neutrophils were seen in cases of rejection with acinar cell damage and necrosis in the form of microabscesses.
High degree of intraobserver agreement (92% and 90%) was observed when the slides were reviewed for a second time. Interobserver agreement was seen in 95% of the biopsies, with all the discrepancies being between grades II and III.
The patients were followed-up for a mean of 17.5 months ±1.65 months and the highest degree of histologic rejection on each patient was correlated with the ultimate graft loss (chi square). Graft loss was defined as the inability to maintain adequate glucose homeostasis.
Eight patients with normal or borderline biopsies (Grades 0 and I) continued to have functional grafts (0% loss). One graft loss (8.3%) was seen out of 12 patients with biopsies showing mild rejection (Grade II). In patients with biopsies showing moderate rejection (Grade III), graft loss was seen in 13 out of 18 patients (27.7%). In patients with moderate rejection with vascular changes, graft loss was seen in 4 out of 8 cases (50%). All grafts corresponding to biopsies showing severe rejection ultimately failed (100%). The increasing proportion of graft loss correlating with the severity of histologic rejection was statistically significant (p< 0.003).
In the lower grades in this system (I and II), sampling may represent a problem due to the fact that the histologic findings described are essentially focal.
The significance of the borderline category (Grade I) is not clearly defined at the present time. The presence of sparse septal infiltrates may be non-specific (seen in 2 grafts with normal function) or represent very early or resolving acute rejection. In the present study 12 out of 13 episodes of probable rejection with biopsies showing borderline features (Grade I) were treated. In 7 cases the abnormal laboratory values returned to baseline, and in 3 cases a subsequent biopsy showed clear cut rejection.
The patients with biopsies showing mild rejection (Grade II) were all treated for rejection and 22 out of the 31 responded clinically. In six cases a subsequent biopsy showed a higher degree of rejection.
In addition to the presence or absence of acute rejection, the presence of increased dense septal fibrosis with acinar loss and transplant arteriopathy, both consistent with chronic rejection, should be stated in the pathology report.
This study indicates that percutaneous needle biopsy of the pancreas provides adequate material for the diagnosis of rejection with a small risk of complications.