PANCREAS SESSION      REPORT2011 BANFF CONFERENCE
GUIDELINES FOR THE DIAGNOSIS OF ANTIBODY MEDIATED           REJECTION IN PANCREAS ALLOGRAFTS –             UPDATED BANFF G...
Co-chairs• Ed Kraus• Brian Nankivell
PROGRAM•   Ugo Boggi•   Christian Margreiter•   Phillip Ruiz•   Erika Rangel•   Dae Un Kim•   John Papadimitriou•   Erika ...
Percutaneous biopsy (graft accessibility)
PROGRAM• Ugo Boggi (Pisa, Italy)• Christian Margreiter• Phillip Ruiz• Erika Rangel• Dae Un Kim
Percutaneous biopsy (graft accessibility)
Percutaneous biopsy (graft accessibility)
PROGRAM• Ugo Boggi (Pisa, Italy)• Christian Margreiter (Innsbruck,  Austria)• Phillip Ruiz• Erika Rangel• Dae Un Kim
PROGRAM• Ugo Boggi (Pisa, Italy)• Christian Margreiter (Innsbruck, Austria)• Phillip Ruiz (Miami, USA)• Erika Rangel• Dae ...
Summary• Cardinal features of T1DR demonstrated in several patients by:    – clinical features (loss of insulin secretion ...
β CELL FAILURE• ACMR and AMR leading to graft fibrosis  with secondary damage to islets• Death of the β cells (preservatio...
Banff Pancreas Allograft Rejection Grading Schema                     - Update 7. ISLET PATHOLOGY -Recurrence of autoimmun...
Islet Amyloid deposition: Type 2 DM related changes
Islet amyloid deposition limits the viability of human islet grafts but notporcine islet grafts K. J. Potter, A. Abedini, ...
PROGRAM• Ugo Boggi (Pisa, Italy)• Christian Margreiter• Phillip Ruiz• Erika Rangel (San Paulo, Brazil)• Dae Un Kim (New Je...
C4d staining in pancreas interacinar              capillariesImmunohistochemical (A) and Immunofluorescence (B) methods.
C4d in Pancreas: IHC vs IF• Both adequate for clinical purposes• IF typically more diffuse and with stronger  staining (10...
PROGRAM (Cont.)• John Papadimitriou (Maryland,  USA)• Erika Bracamonte (Arizona, USA)
Predominance of Histological Features in Stereotypical ACMR and AMR                                               ACMR    ...
Pancreas Allograft Rejection• Acute T-cell mediated rejection• Acute antibody mediated rejection• (Mixed forms)
Acute T-cell mediated rejectionSeptal inflammation  – Veins (venulitis)  – Ducts (ductitis)  – Arteries (intimal arteritis...
Venulitis        Acinitis                   Septal inflammation   Intimal arteritis
Septal area  Islet                          CD3          Septal areaIslet                   CD68
Antibody Mediated Rejection in the           Pancreas
CD68       CD3
Mild acute AMR: The lobular architecture is preserved but thereare interacinar infiltrates predominantly composed ofmacrop...
BANFF GUIDELINES FOR THE DIAGNOSIS OF            ANTIBODY MEDIATED REJECTION  1. Confirmed circulating donor specific anti...
PROGRAM (Cont.)• John Papadimitriou (Maryland, USA)• Erika Bracamonte (Arizona, USA)
Reproducibility Study• Fair to moderate agreement for major  diagnostic categories (k>0.2)    No Rejection orIndeterminate...
Reproducibility Study                           Kappa Agreement    Morphologic Feature              Kappa Agreement• Necro...
Aims for Banff 2013• Evaluation of protocol biopsies• Correlation of rejection related findings in  duodenal cuff and panc...
Aims for Banff 2013 (cont)• Wideworld Survey to evaluate clinical  practices with respect to biopsy  performance and patho...
Pancreas transplant pathology report banff 2011
Pancreas transplant pathology report banff 2011
Pancreas transplant pathology report banff 2011
Pancreas transplant pathology report banff 2011
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Pancreas transplant pathology report banff 2011

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Presentation by Dr. Cinthia Drachenberg summarizing the pancreas sessions from 2011 Eleventh Banff Conference on Allograft Pathology, June -10, 2011 in Paris, France.

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Pancreas transplant pathology report banff 2011

  1. 1. PANCREAS SESSION REPORT2011 BANFF CONFERENCE
  2. 2. GUIDELINES FOR THE DIAGNOSIS OF ANTIBODY MEDIATED REJECTION IN PANCREAS ALLOGRAFTS – UPDATED BANFF GRADING SCHEMACinthia B. Drachenberg, Jose R. Torrealba, Brian J. Nankivell, Erika B. Rangel,Ingeborg M.Bajema, Dae Un Kim, Lois Arend, Erica R. Bracamonte, JonathanS.Bromberg, Jan A.Bruijn, Diego Cantarovich, Jeremy R.Chapman, Alton B.Farris, Lillian Gaber,Julio C. Goldberg, Abdolreza Haririan, Eva Honsová,Samy S. Iskandar, David K. Klassen, Edward Kraus, Fritz Lower, Jon Odorico, Jean L. Olson, Anuja Mittalhenkle, Raghava Munivenkatappa, Steven Paraskevas, John C. Papadimitriou, Parmjeet Randhawa, Finn P. Reinholt, Karine Renaudin, P.Revelo, Phillip Ruiz, Milagros D. Samaniego, Ron Shapiro, Robert J. Stratta, David E.R. Sutherland, Megan L.Troxell, Luděk Voska, Surya V. Seshan,Lorraine C. Racusen and Stephen T. Bartlett Am J Transplant In Press
  3. 3. Co-chairs• Ed Kraus• Brian Nankivell
  4. 4. PROGRAM• Ugo Boggi• Christian Margreiter• Phillip Ruiz• Erika Rangel• Dae Un Kim• John Papadimitriou• Erika Bracamonte
  5. 5. Percutaneous biopsy (graft accessibility)
  6. 6. PROGRAM• Ugo Boggi (Pisa, Italy)• Christian Margreiter• Phillip Ruiz• Erika Rangel• Dae Un Kim
  7. 7. Percutaneous biopsy (graft accessibility)
  8. 8. Percutaneous biopsy (graft accessibility)
  9. 9. PROGRAM• Ugo Boggi (Pisa, Italy)• Christian Margreiter (Innsbruck, Austria)• Phillip Ruiz• Erika Rangel• Dae Un Kim
  10. 10. PROGRAM• Ugo Boggi (Pisa, Italy)• Christian Margreiter (Innsbruck, Austria)• Phillip Ruiz (Miami, USA)• Erika Rangel• Dae Un Kim
  11. 11. Summary• Cardinal features of T1DR demonstrated in several patients by: – clinical features (loss of insulin secretion and diabetes symptoms in the presence of normal pancreas transplant exocrine function) – biochemical autoantibody assays – pancreas transplant biopsy (isletitis) – autoreactive T cells, possibly representing memory responses• T1DR observed in ~5% of SPK recipients, despite immunosuppression• Its frequency is not dissimilar from that of chronic rejection.• T1DR may occur even after several years of secretory function• The immunosuppression used does not restore self-tolerance
  12. 12. β CELL FAILURE• ACMR and AMR leading to graft fibrosis with secondary damage to islets• Death of the β cells (preservation of the exocrine pancreatic component)
  13. 13. Banff Pancreas Allograft Rejection Grading Schema - Update 7. ISLET PATHOLOGY -Recurrence of autoimmune DM (insulitis and/or selective ß cell loss) - Islet amyloid (amylin) deposition
  14. 14. Islet Amyloid deposition: Type 2 DM related changes
  15. 15. Islet amyloid deposition limits the viability of human islet grafts but notporcine islet grafts K. J. Potter, A. Abedini, P. Marek, A. M. et alProc Natl Acad Sci U S A. 2010 March 2; 107(9): 4305–4310
  16. 16. PROGRAM• Ugo Boggi (Pisa, Italy)• Christian Margreiter• Phillip Ruiz• Erika Rangel (San Paulo, Brazil)• Dae Un Kim (New Jersey, USA)
  17. 17. C4d staining in pancreas interacinar capillariesImmunohistochemical (A) and Immunofluorescence (B) methods.
  18. 18. C4d in Pancreas: IHC vs IF• Both adequate for clinical purposes• IF typically more diffuse and with stronger staining (10-50%)• Focal C4d often correlate with DSA. Threshold for positivity ≥5%.• The results of this analysis will be prepared for publication under the leadership of Surya Seshan
  19. 19. PROGRAM (Cont.)• John Papadimitriou (Maryland, USA)• Erika Bracamonte (Arizona, USA)
  20. 20. Predominance of Histological Features in Stereotypical ACMR and AMR ACMR AMRSeptal infiltrates +++ - to +Eosinophils + to +++ - to +Neutrophils - to ++ +/- to +++T- Lymphocytes ++ to +++ +/- to +Macrophages ++ ++++Venulitis ++ -Ductitis ++ -Acinar cell injury +/- to ++ +++Acinar inflammation - to +++ + to +++Acinitis (mononuclear infiltrates within the + to +++ - to +/-basement membrane of individual acini)Interacinar Capillaritis - to +/- + to +++Intimal arteritis + +Necrotizing vasculitis / thrombosis - to + +++Confluent hemorrhagic necrosis - to ++ - to ++++Active transplant arteriopathy + +
  21. 21. Pancreas Allograft Rejection• Acute T-cell mediated rejection• Acute antibody mediated rejection• (Mixed forms)
  22. 22. Acute T-cell mediated rejectionSeptal inflammation – Veins (venulitis) – Ducts (ductitis) – Arteries (intimal arteritis, transmural arteritis)Acinar inflammation – Acinitis – Acinar cell damage
  23. 23. Venulitis Acinitis Septal inflammation Intimal arteritis
  24. 24. Septal area Islet CD3 Septal areaIslet CD68
  25. 25. Antibody Mediated Rejection in the Pancreas
  26. 26. CD68 CD3
  27. 27. Mild acute AMR: The lobular architecture is preserved but thereare interacinar infiltrates predominantly composed ofmacrophages (CD68 stain on the right).
  28. 28. BANFF GUIDELINES FOR THE DIAGNOSIS OF ANTIBODY MEDIATED REJECTION 1. Confirmed circulating donor specific antibody (DSA) 2. Morphological evidence of tissue injury 3. C4d positivity in interacinar capillaries- Acute AMR (all 3 diagnostic components present).- Suspicious of acute AMR (2 diagnostic components present).- Not sufficient for diagnosis of AMR (1 diagnostic component present). Heightened clinical vigilance recommended.
  29. 29. PROGRAM (Cont.)• John Papadimitriou (Maryland, USA)• Erika Bracamonte (Arizona, USA)
  30. 30. Reproducibility Study• Fair to moderate agreement for major diagnostic categories (k>0.2) No Rejection orIndeterminate vs. Acute k = 0.55 Cellular RejectionGrade of Acute Cellular k = 0.32 Rejection Chronic Active Cellular k = 0.31 Rejection Antibody Mediated k = 0.41 Rejection
  31. 31. Reproducibility Study Kappa Agreement Morphologic Feature Kappa Agreement• Necrotizing arteritis 0.65• Active septal inflammation 0.61• Acinar inflammation 0.42• Perineural inflammation 0.40• Intimal arteritis 0.35• Venulitis 0.32• Acinar cell injury 0.30• Chronic allograft arteriopathy 0.29• Ductitis 0.27• Capillaritis 0.17
  32. 32. Aims for Banff 2013• Evaluation of protocol biopsies• Correlation of rejection related findings in duodenal cuff and pancreas parenchyma• Detailed evaluation of the incidence and characteristics of recurrent Type I and II DM• Development of an official Banff lesion scoring system in combination with the preparation of a didactic training set in preparation for further reproducibility studies. (MI lesions, special stains)
  33. 33. Aims for Banff 2013 (cont)• Wideworld Survey to evaluate clinical practices with respect to biopsy performance and pathological practices – C4d staining – Protocol biopsies – Characterization of chronic active AMR

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