Transcript BANFF SCHEMA FOR GRADING PANCREAS ALLOGRAFT REJECTION

BANFF SCHEMA FOR GRADING
PANCREAS ALLOGRAFT
REJECTION
2007-2009
Meeting Summary
• Pancreas Tx are only performed in selected
centers and pancreas biopsies are few in
comparison to those of other organs.
– Progress has been slow
– Immunosuppression has improved
– Indications have been re- and re-evaluated
– Ongoing need for beta cell replacement
– Overall the number of whole pancreas tx has
stabilized
• New pancreas transplant programs continue to be
established (explosive growth in some regions)
Banff 2007
• Pre-meeting discussions were concluded in
the formal and “working lunch” sessions.
• Consensus agreement
– Definitions of the histological lesions
– “cell mediated” grading schema
– General histopathology guidelines including
adequacy, recommendations for reporting, etc
• Completion of consensus manuscript through group
e-mail discussions.
Banff 2009
Pancreas Session
Session Chairs:
Edward Kraus
Brian Nankivell
Additional working breakfast the following morning
Banff 2009 Pancreas Session
1. Gene expression based categorization of pancreas
transplant biopsies
Fu Luan
- First attempt to correlate histological rejection
with gene expression by using techniques and
gene selection that has been used in the kidney
- Demonstrated differential expression of a variety
of genes that correlated with histological rejection
grades and graft outcome.
Banff 2009 Pancreas Session
AMR in pancreas allografts
3.Ingeborg Bajema
4.Jose Torrealba
5.Erika Bevilaqua Rangel
Banff 2009 Pancreas Session
AMR in pancreas allografts
Ingeborg Bajema: Retrospective experience on C4d
IHC. A combination of DSA+ and C4d+ correlate
with worse graft outcome.
Jose Torrealba: Summarized their large experience
with AMR in pancreas tx /SPK. Pattern of C4d
staining.
Erika Bevilaqua Rangel: AMR in a cohort of patients
transplanted in San Paulo (Brazil). Largest
experience with IF C4d. DSA available on few pts.
Banff 2009 Pancreas Session
6. Lois Arend: Controversial lesions in pancreas biopsy
grading.
Drug toxicity, acinar inflammation.
Discussed experience with AMR cases and confirmed
findings in previous presentations.
Proposal for Diagnosis of Acute
Antibody Mediated Rejection
• Consensus discussion
– Importance of defining AMR in the pancreas.
– Recommendation to evaluate C4d staining in all
biopsies
– Both IHC and IF work well: comparison between
methods to be performed in the future.
– Interacinar staining pattern strongly correlates
with AMR (in contrast to other staining patterns).
Proposal for Diagnosis of Acute
Antibody Mediated Rejection
– Focal staining for C4d appears to be important:
Agreement to recommend guidelines for reporting
C4d as in the kidney schema.
2007 Proposed Banff Schema
2009 Proposal for Diagnosis of
Acute Antibody Mediated
Rejection
Remove requirement for “graft dysfunction”
for the pathology diagnosis of acute AMR.
Working Proposal for diagnosis of
AMR
Acute antibody mediated rejection
1.C4d+
2.Morphologic evidence of chronic tissue injury
(margination of inflammatory cells in
interacinar capillaries (capillaritis), acinar cell
damage, arteritis, etc).
3.DSA/HLA confirmatory testing
Two of 3 criteria necessary for diagnosis
Rule out AMR
- C4d+ with no tissue injury
?Recommendation to do CD68 stain pending
further discussions
• Chronic Active antibody mediated rejection
category remains. Final wording will be
discussed.
Acute
AMR
C4d+
2. Erica Bracamonte
Preliminary results: Reproducibility of Banff schema
for grading of acute pancreas rejection.
Reproducibility Study Materials
• 12 Digital whole slides (Aperio system)
• Only one case had C4d stain.
Participants
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Lois Arend
Ingeborg Bajema
Jan Bruijn
Helen Cathro
Billie Fyfe-Kirschner
Lillian Gaber
Julio Goldberg
Danielle Hollanda
Ramesh Nair
Jean Olson
John Papadimitriou
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Lorraine Racusen
Karine Renaudin-Autain
Finn P Reinholt
Monica Patricia Revelo
Phillip Ruiz
Edward B Stelow
Jose Torrealba
Megan Troxell
Matthew Turner
Ludek Voska
Matthew Yeh
Participants
• 22, from 19 institutions
• Level of experience (self reported)
– Novice: <2 yrs experience (n=5)
– Competent: 2-5 yrs experience (n=12)
– Expert: >5 yrs experience (n=4)
Preliminary Results
Reproducibility study (E.Bracamonte)
• Data still being collected
• Rejection vs no rejection Kappa score 0.55
Further studies of Banff Schema
Reproducibility (E.Bracamonte)
First Phase: Better Define Morphologic
Features
• Recognition of histological features should be
tested.
• Wording in schema should be simplified.
Lesions grouped in categories for easier
understanding.
Specific plan:
• Images for each of the morphologic features
to be posted at the University of Pittsburg
website.
• The selection of images will be done by
“consensus” agreement with the goal of
making more uniform the diagnostic
interpretation of the cases.
• The images and web site will be also used for
discussion of Banff scoring categories similar
to kidney .
• The material will be used for “training” of
interested pathologists and clinicians
(overlapping with the current didactic plan of
the ASTS).
Second Phase – Retest Scoring of Cases
• By consensus , another set of test cases
should be passed around for restudy after the
addition discussion of the morphologic
features.
• All cases will include a C4d Stain and more
cases of humoral rejection will be included.
• The biopsy worksheet will be revised and
simplified (? online responses)
• “Gold standard” diagnoses to be defined.
Probably by using a small panel of two or
three pathologists who come to a consensus.
• All agreement statistics will be re-run based
on the second set of testing, and compared to
the prior set already performed.
Main goal of the study
• Assess reproducibility of the schema.
• Ultimately, improve the Banff schema by
decreasing complexity and increasing
applicability for the average practicing
pathologist.
• Many thanks to the Banff Conference
Organizing committee that provided excellent
support for the Pancreas sessions.