In Press, 1995, Transplantation Proceedings copyright by Appleton and Lange.

Histologic Grading of Pancreas Acute Allograft Rejection in Percutaneous Needle Biopsies

Cinthia B. Drachenberg, David K. Klassen, Stephen T. Bartlett, Edward W. Hoehn-Saric, Eugene J. Schweitzer, Lynt B. Johnson, Matthew R. Weir and John C. Papadimitriou

University of Maryland School of Medicine, Departments of Pathology, Surgery and Medicine, Baltimore MD 21201

 

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 5508
Key Words: septal inflammation acinar inflammation, ductitis, venulitis, arteritis.

 


 

INTRODUCTION

Allograft rejection is the most important cause of graft loss in pancreas transplants. Current non-invasive methods to detect rejection lack sensitivity and specificity [1] therefore, examination of tissue biopsy is necessary to make this diagnosis with certainty.

With the development of the percutaneous technique [2] 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.

 

MATERIALS AND METHODS

Histologic sections from 94 percutaneous and 6 intraoperative needle pancreas transplant biopsies from 52 bladder-drained allografts were examined. In 92 cases the biopsies were obtained for the evaluation of clinical rejection. Rejection was suspected when there was a decrease in urinary amylase >40% and/or increased serum amylase and lipase (>2 fold) in relationship to the baseline obtained from the mean value in the last 4 weeks. The presence of septal inflammation, acinar inflammation, ductitis, ductal cell atypia, ductal cell necrosis, venulitis, acinar cell vacuolization, acinar cell necrosis, interstitial edema, nerve inflammation, islet inflammation, arteritis, endothelialitis, fibroblastic proliferation and type of inflammatory infiltrates were evaluated.

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:

Grade 0 - Normal: No inflammatory infiltrates present.
Grade I - Borderline: Rare, mononuclear, inactive appearing septal infiltrates.
Grade II - Mild rejection: Mixed septal infiltrates associated with venulitis and/or ductitis and/or focal acinar infiltrates.
Grade III - Moderate rejection: As II but showing multifocal involvement of the acinar parenchyma and often evidence of acinar cell damage or single acinar cell necrosis.
Grade IV - Moderate rejection with vascular changes: As III showing in addition evidence of arterial endothelialitis or arteritis.
Grade V - Severe rejection: Extensive inflammatory infiltrates associated with confluent necrosis of acinar parenchyma. Evidence of vascular rejection depending on sampling.

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).

 

DISCUSSION

A histologic grading of acute pancreas allograft rejection for needle biopsies is proposed. This system has prognostic significant as demonstrated by the correlation between the severity of rejection on biopsy and the ultimate graft loss.

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.

 

REFERENCES

  1. Casanova D, Gruessner R, Brayman K, Jessurun J, Dunn D, Xenos E and Sutherland DER: Retrospective analysis of the role of pancreatic biopsy (open and transcytoscopic technique) in the management of solitary pancreas transplants. Transplant Proc 25(1):1192-1193,1993.

     

  2. Allen RDM, Wilson TG, Grierson JM, Greenberg ML, Earl MJ, Nankivell BJ, Pearl TA and Chapman JR: Percutaneous biopsy of bladder-drained pancreas transplants. Transplantation 51(6), 1213-1216,1991.

     

 


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