Classifications and Schemas Arthur H. Cohen, Juan Lechago and Cynthia C. Nast

Over the course of many years, various systems have been suggested to standardize pathology of rejection. Although the initial ones had merit, they did not gain widespread acceptance. In the early 1990s Solez led an effort to develop a schema which would be applicable to multicenter drug trials and also could potentially be used for diagnostic purposes; as the conferences to establish criteria, quantitative methods, etc. were held in Banff, Alberta, Canada, the resulting formulation is known as the Banff Working Schema. Its main emphasis was on acute rejection, although information on chronic rejection and other changes were components. First published in 1993, it initially gained acceptance although it soon became readily evident that certain major deficiencies existed and several subsequent meetings were held to modify the original formulation. Shortly after the original publication, pathologists involved in an NIH funded multicenter study evaluating novel immunosuppression strategies, known as Cooperative Clinical Trials in Transplantation (CCTT), devised a standardized scoring system largely for acute rejection. This proved to be simple to use, highly reproducible with good sensitivity and specificity and to avoid the deficiencies of the early Banff formulation. The latest version of the Banff schema, known as Banff 97, incorporated the major components of CCTT thereby resulting in a more useful classification. The individual features of this schema are too lengthy to report here in detail; the reader is referred to the literature. Banff '97 has been updated to include more precise information, characterization and classification of antibody-mediated rejection; this was done to include C4d-associated acute rejection as a specific category. The Banff schema has two different components: diagnostic criteria and quantitation of the abnormalities. The former were established to provide standardization of morphologic features necessary for the various rejection categories. Although currently reasonably well accepted with the above mentioned major modifications for acute rejection, the category of Borderline changes is still most controversial and perhaps unsettling. Several studies have indicated that biopsies with borderline changes clinically progressed to and/or therapeutically responded as acute rejection in from 30 to 88% of instances. This calls into question the necessity of this category and its criteria for inclusion. The issue of borderline changes and their significance in renal transplant s represent a continuing challenge to the Banff schema . Recent work (Gaber, 2004) indicates and confirms that many biopsies with these features really represent acute rejection; those that did not respond to increased immunosuppression often had additional changes such as chronic rejection. The other aspect of Banff is to provide quantitation of the observed abnormalities. This has two functions: 1) to establish criteria for grading the degree of severity of the diagnostic categories and 2) to provide uniformity of observations, especially for use in multicenter studies. Although some transplant pathologists strictly adhere to the quantitative aspects, many prefer to use their experience and art of pathology to establish both diagnoses and to grade severity. Nevertheless most experience with Banff and emphasis to date has been in the realm of acute rejection. For chronic rejection, while the Banff schema has some merit, the CADI system (chronic allograft damage index) scores certain changes and has been shown to provide some prognostic information. Components scored include interstitial fibrosis, tubular atrophy, glomerular sclerosis, mesangial expansion, glomerular capillary wall double contours and arterial intimal thickening. In general, the sum score of biopsies performed at 2 years correlated reasonably well with function at 6 years and a high score including interstitial lymphocytes at 6 months correlated well with graft loss at 2 to 3 years post transplantation. Liver Similar to experience with kidney transplants, classification schemas for liver transplants have also been developed with, until recently, modest but not widely accepted success. Spurred on by the concept of Banff for kidneys, in the mid-1990s liver transplant physicians met at Banff for their own formulation. Following a series of sessions and modifications, the Banff Schema for Grading Liver Allograft Rejection was created. In contrast to the renal document, the hepatic formulation and diagnostic criteria have gained more widespread acceptance, especially for acute rejection and are widely used for diagnostic and therapeutic purposes. On the other hand, quantitation of the lesions is less commonly used. For pathologies in both kidney and liver transplants, the concept and use of a classification schema such as Banff certainly are very attractive for multicenter studies. Their use as sets of diagnostic criteria is less attractive as the art of pathology may sometimes play as important a role as quantitative criteria and scientific dogma in establishing diagnoses. As with other quantitative and semi-quantitative systems designed to score microscopic pathologic changes, the Banff schema has been shown to be less than reliable. This is largely because of considerable interobserver variability, especially when the systems are considered on an international basis as Banff is meant to be used. Even among experienced renal pathologists, variations may be great especially if criteria for specimen adequacy are misinterpreted. References Banff schema for grading liver allograft rejection: an international consensus document, Hepatology 25:658-663, 1997. Bates WD, Davies DR, Welsh K, Gray DW, Fuggle SV, Morris PJ. An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome. Nephrol Dial Transplant 14:2364-2369, 1999. Colvin RB, Cohen AH, Saiontz C, Bonsib S, Buck M, Burke B, Carter S, Cavallo T, Hass M, Lindblad A, Manivel J, Nast CC, Salomon D, Weaver C, Weiss M. Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation. J Am Soc Nephrol 8:1930-1941, 1997. 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