Address correspondence to : John C. Papadimitriou,M.D.,Ph.D. University of Maryland Hospital Department of Pathology 22 South Greene St. Baltimore, MD 21201 Phone: (410) 328 5560 Fax: (410) 328 5508
In this report we discuss a group of borderline biopsies from patients biopsied for acute allograft dysfunction who received antirejection treatment that appeared to have been beneficial in their clinical course.
In the context of acute allograft dysfunction, if there is a strong clinical suspicion and/or pathologic evidence of acute rejection, treatment with pulse steroids, ATGAM or OKT3 are initiated. Steroids are given initially in cases of mild to moderate rejection. ATGAM or OKT3 are used if no response to steroids is seen within 48-72 hours, or initially for cases of moderate to severe acute rejection. Cases with borderline changes are also treated in that fashion if there is strong clinical suspicion for rejection.
Three hundred fifty one biopsies from 170 renal allografts were graded according to the Banff criteria by two transplant pathologists who were blinded as to the identity and any other clinical information about the patients. Classified following the Banff Working Classification for Rejection, 81 (23%) had "borderline changes", 218 had various degrees of rejection and 52 had no histologic evidence of rejection. The pertinent clinical information including rejection treatments, intercurrent illnesses, and Cr levels were then recorded.
Percentage of biopsy surface (0-100%) with mononuclear infiltrates, degree of eosinophilic infiltrates (0-3+) and degree of polymorphonuclear leukocytes (0-3+) per biopsy were compared in the 81 biopsies with borderline changes vs. 79 biopsies showing clear cut mild rejection according to the Banff scheme. We have previously shown that these three morphological features correlate in various degrees with tubulitis .
Otherwise, most patients with "borderline changes" were treated for acute rejection (61/78,78%). Seventeen patients were not treated because in addition to the borderline changes they had extensive chronic rejection. The mean Cr in patients treated for rejection was 2.3 +/-0.1 mg/dl at baseline, 3.4 +/-0.1 mg/dl at the time of biopsy (p<0.001 vs. baseline), and 2.8 +/-0.2 mg/dl one month after treatment (p<0.01 vs. Cr at biopsy). From the 78 patients treated for rejection a group of 33 was identified in which no other associated pathologic conditions were identified. In this group the mean Cr was 2.0 +- 0.1 at baseline, 3.3 +-0.2 at the time of biopsy (p < 0.001 vs. baseline) and 2.2 +-0.1 one month after treatment (p <0.001 vs. Cr at biopsy).
Follow up biopsies obtained within one month of the initial borderline biopsy in 24 cases showed borderline changes in 21%, mild acute rejection in 33%, and moderate to severe acute rejection in 46%.
Comparison between the histologic features observed in biopsies with borderline changes and mild rejection showed qualitative similarities between these two groups: In both cases many of the lymphocytes showed an "activated" phenotype (cleaved nuclei, prominent nucleoli, etc.), interstitial edema, tubular epithelial reactive changes, and occasionally peritubular capillary dilatation. The quantitative features, however, were significantly different. The mean percentage of biopsy surface covered by inflammatory infiltrates was 19.9% in borderline changes vs. 53.7% in the mild rejection cases (p <.005). The degree of infiltration by eosinophils was 1.7 in the mild rejection biopsies and 1.07 in the borderline cases (p <.005), whereas the degree of neutrophil infiltration was 1.09 and 0.26 respectively (p <.005).
Our results are further indicative of the value of the Banff schema, with the borderline category appearing to be a distinct entity that differs from both the normal condition of non-rejection as well as mild rejection. The interpretation of these findings, however, is heavily dependent on the clinical situation in our cases. In the setting of stable graft function, "borderline" biopsies are viewed with caution and the patients closely followed but not treated for rejection. In the setting of deteriorating graft function, "borderline" is interpreted as a very mild form in the spectrum of acute rejection and treated accordingly.
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Papadimitriou JC, Klassen DK, Hebel JR, Drachenberg CB: Quantitative evaluation of ancillary morphological parameters in the assessment of rejection in renal transplant biopsies. Int J Surg Path 1995;.