Lung Rejection Study Group

Revision of the 1996 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Lung Rejection

IThe original 1990 working formulation for the classification of pulmonary allograft rejection resulted from an International Society for Heart and Lung Transplantation (ISHLT) workshop to develop a standardized grading system for the pathologic diagnosis of rejection in transplant lung biopsies.1 A core group of pathologists developed a grading scheme for pulmonary allograft rejection that allowed data to be compared between institutions as a result of uniformity of grading. The grading system was intended to be simple, easily taught, and readily reproducible, and was adopted at the majority of institutions performing lung transplantation at the time.

In 1995, an expanded group of international pathologists convened to revise the original 1990 proposal in response to developments in the field and their experience with using the working formulation.2 On this occasion, the lung rejection study group critically assessed the merits of the initial working formulation and improved it on the basis of both published data and practical experience across many centers. The goal was again to maintain a uniform description and grading scheme for lung rejection, to improve communication between clinicians and investigators, to enable comparison of treatment regimes and outcomes between transplant centers, to facilitate multi-center clinical trials, and to promote further studies to determine the clinical significance of the various histologic patterns. The revised classification was based on histologic findings of acute and chronic lung rejection by primarily using transbronchial biopsies for allograft monitoring in both adults and children. It was emphasized that all biopsy data needed to be interpreted in an integrated clinical context to allow optimum patient management and clinical decisions. It was also noted that infection/ rejection often occur together and can be confused histologically and that infection needs to be rigorously excluded for the accurate and reproducible interpretation of pulmonary allograft biopsies.

The 1996 revision was itself widely adopted by the lung transplant community and has served it well for over a decade.3,4 The revised working formulation represented a simplification of the original classification scheme, but it also highlighted some unresolved and complex issues such as the diagnosis and significance of airway inflammation. In 2004, again under the direction of the ISHLT, a multidisciplinary review of the cardiac biopsy grading system was undertaken to address challenges and inconsistencies in its use and also to address recent advances in the knowledge of antibody-mediated rejection. The revised consensus classification was accepted by the board of directors and published in 2005.5 It was clear that the success of the multidisciplinary approach could be usefully adopted for a further revision of the diagnosis of lung rejection to take into account a decade of developments in the clinical, pathologic and immunologic fields. Toward this end, a multi-disciplinary consensus meeting was held at the ISHLT 2006 meeting in Madrid and its conclusions form the basis of this consensus report. The multidisciplinary task forces examined the histopathology of cellular rejection, humoral (antibody-mediated rejection) and clinical issues and future research.

Comments solicited from the ISHLT membership at large and from the transplant pathology community were also taken into account. Compared with the numerous responses from ISHLT members in 2004 regarding the cardiac grading system, only a small number of responses were received concerning lung grading. This was interpreted as most likely reflecting an overall higher level of satisfaction with the existing scheme compared with the 1990 cardiac working formulation. The present study reports on the consensus of revisions to the pathologic classification (Table 1) and is supplemented by the consensus of lung transplant physicians and surgeons focusing on the clinical viewpoint.6

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Last Modified: Thu Oct 11 7:37:00 EDT 2016