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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TPIS administration at the UPMC.
