Lung Rejection Study Group
Revision of the 1996 Working Formulation for the Standardization
of Nomenclature in the Diagnosis of Lung Rejection
Susan Stewart, FRCPath; Michael C. Fishbein, MD; Gregory I. Snell, MD; Gerald J. Berry, MD;
Annette Boehler, MD; Margaret M. Burke, FRCPath; Alan Glanville, MD; F. Kate Gould, FRCPath;
Cynthia Magro, MD; Charles C. Marboe, MD; Keith D. McNeil, FRACP; Elaine F. Reed, PhD;
Nancy L. Reinsmoen, PhD; John P. Scott, MD; Sean M. Studer, MD; Henry D. Tazelaar, MD;
John L. Wallwork, FRCS; Glen Westall, MD; Martin R. Zamora, MD; Adriana Zeevi, PhD; and
Samuel A. Yousem, MD
ABSTRACT
I In 1990, an international grading scheme for the grading of pulmonary allograft rejection was adopted by the
International Society for Heart and Lung Transplantation (ISHLT) and was modified in 1995 by an expanded group of
pathologists. The original and revised classifications have served the lung transplant community well, facilitating
communication between transplant centers with regard to both patient management and research. In 2006, under the
direction of the ISHLT, a multi-disciplinary review of the biopsy grading system was undertaken to update the scheme,
address inconsistencies of use, and consider the current knowledge of antibody-mediated rejection in the lung. This
article summarizes the revised consensus classification of lung allograft rejection. In brief, acute rejection is based on
perivascular and interstitial mononuclear infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3
(moderate) and Grade A4 (severe), as previously. The revised (R) categories of small airways inflammation, lymphocytic
bronchiolitis, are as follows: Grade B0 (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996,
B3 and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis (Grade C), is described as present (C1)
or absent (C0), without reference to presence of inflammatory activity. Chronic vascular rejection is unchanged as
Grade D. Recommendations are made for the evaluation of antibody-mediated rejection, recognizing that this is a
controversial entity in the lung, less well developed and understood than in other solid-organ grafts, and with no
consensus reached on diagnostic features. Differential diagnoses of acute rejection, airway inflammation and chronic
rejection are described and technical considerations revisited. This consensus revision of the working formulation was
approved by the ISHLT board of directors in April 2007. Copyright © 2007
by the International Society for Heart and Lung Transplantation.
The Journal of Heart and Lung Transplantation, December 2007, 1229 - 1242.
From:
From the Papworth Everard Pathology Department, Papworth Hospital,
Cambridge, UK.
Submitted:
Submitted October 29, 2007; revised October 30, 2007; accepted
October 31, 2007.
Copyright:
Copyright © 2007 by the International Society for Heart and Lung
Transplantation. 1053-2498/07/$-see front matter. doi: 10.1016/j.healun.2007.10.017 .
Reprint Requests:
Reprint requests: Susan Stewart, FRCPath, Papworth Everard Pathology
Department, Papworth Hospital, Cambridge CB3 8RE, UK. Telephone:
44-1480-364-304. Fax: 44-1480-364-777. E-mail: susan.stewart@papworth.nhs.uk
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