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Linda Cendales Composite Tissue Graft Summary Banff 2013 Meeting in Brazil

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Composite tissue graft summary from 12th Banff Conference on Transplant Pathology from the meeting in Comandatuba-Bahia, Brazil on August 23rd, 2013 http://cybernephrology.ualberta.ca/banff/2013

Composite tissue graft summary from 12th Banff Conference on Transplant Pathology from the meeting in Comandatuba-Bahia, Brazil on August 23rd, 2013 http://cybernephrology.ualberta.ca/banff/2013

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  • Today I am going to discuss the role of histopathology in determining the need for therapy in liver transplantation, with an emphasis on concepts used to design current tolerance induction trials.
  • Most difficult ddx can be solved by simply looking at the patient.
  • Photos from patient: redness, dry fingertips & painful wherever it's red Pt#3 – S-08-20886B biopsy – 200X – H&E – Palm -Moderate perivascular dermal inflammation – Grade II – Note: the palm biopsy cannot be evaluated for epidermal involvement due to epidermal sloughing. A more severe degree of rejection could not be evaluated from this specimen Pt#3 – S12-17238B biopsy – 40X – H&E – moderate acute cellular rejection Grade II
  • What is the specificity of isolated dyskeratotic/apoptotic* keratinocytes in: Establishing a histopathologic diagnosis of acute cell-mediated rejection (ACR)? Assigning an appropriate grade of ACR, if Dx is independently established via other criteria? *Terms often loosely applied interchangeably in practice; also, necrotic keratinocytes, cytoid/Civatte/colloid bodies Does location alter the specificity of isolated dyskeratotic/apoptotic cells? Epidermis Follicular epithelium Sweat gland epithelium Basal vs. suprabasal/at all levels Analogous to GVHD? (features to favor…) Follicular/adnexal involvement, basal location Value of a numeric threshold?
  • If the epidermal changes (i.e. spongiosis and/or lymphocyte exocytosis) are only focal, should the biopsy still be called Grade 2 rejection? Should we further expand the criteria for Grade 1 rejection to include focal epidermal changes such as those listed above? Mast cells are thought to play a role in chronic rejection in some solid organ transplants. Has an increase in mast cells been observed in any biopsies from the other groups? What role does C4d staining and/or DIF staining for C4d play in the management of these patients? Should these additional studies routinely be performed?
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    • 1. Composite Tissue Session (Vascularized composite allograft) Banff 2013 Summary Linda Cendales, M.D
    • 2. VCA Banff 2013 Summary • Speakers – Cinthia Drachenberg – Anthony J. Demetris – Christina Kaufman – Norma Uribe • Virtual Case Presentation – Chandra Smart, UCLA – Max Fischer, Johns Hopkins – Emmanuel Morelon, et al, Lyon-Amiens VCA team – Vijay Gorantla, et al. University of Pittsburgh
    • 3. Chronic Rejection in Vascularized Composite Allografts Cinthia Drachenberg, M.D. Professor of Pathology University of Maryland School of Medicine
    • 4. Chronic rejection in CTA • Overview of chronic changes reported in the literature – Pre-clinical and clinical • CTA/VCA share many features with solid organ transplants but have also unique characteristics to be taken in account.
    • 5. Unadkat et al. Vasculopathy at 90 days in rat hind limb model
    • 6. Striking venous inflammation with thickening and occlusion not shown.
    • 7. Synovial biopsy 18 months Sentinel graftl biopsy 36 months Soft tissue biopsy 50 monthsSynovial biopsy 50 months
    • 8. Pathogenesis: of vasculopathy Non-alloimmune factors: trauma. episodic intense or chronic low grade mechanical damage, thermal injury. hyperplasia as well as remodeling . Microsurgery 1996
    • 9. Can we borrow knowledge from other organs? Similarities: •Morphology, distribution, progression, unclear etiology •Variability of course •Potential association with AR Differences: • Venous involvement •C4d distribution? •Role of trauma, need for other surgeries etc.
    • 10. Histopathological Observations in CTA with Clinical Correlation A.J. Demetris Thomas Starzl Transplant Institute Dept. of Pathology Division of Transplantation University of Pittsburgh Medical Center Pittsburgh, PA
    • 11. Cell-mediated Injury Cornell et al Annu. Rev. Pathol. Mech. Dis. 2008. 3:189–220
    • 12. Antibody Mediated Injury PMN anti-HLA Abanti-HLA Ab Fc ReceptorFc Receptor Mediated BindingMediated Binding C’ ActivationC’ Activation Donor HLADonor HLA MACMAC Platelet microthrombiPlatelet microthrombi EndotheliumEndothelium ADCCADCC CDCCDC C4dC4d C4a +C4bC4a +C4b C4C4 C1C1 Courtesy of Peter Nickerson
    • 13. Differential diagnosis in skin allograft biopsies, other than acute cellular rejection • Graft localized – Trauma – Insect bites – Infections – Allergic or irritant contact dermatitis – Posttransplant lymphoproliferative disorder (PTLD)/lymphoma • Systemic – Drug reactions/toxicity – Eosinophilic dermatitis – Graft vs. host disease • Other Cendales LC, Kanitakis J, Schneeberger S, Burns C, Ruiz P, Landin L, Remmelink M, Hewitt CW, Landgren T, Lyons B, Drachenberg CB, Solez K, Kirk AD, Kleiner DE, Racusen L. The Banff 2007 working classification of skin- containing composite tissue allograft pathology. Am J Transplant. 2008 Jul;8(7):1396-400.
    • 14. Conclusions • CTA allografts are grossly visible allowing for closer and perhaps novel methods of monitoring • Unexpected development of obliterative arteriopathy is not uncommon in all solid organ allografts and arterial wall thickness monitoring is helpful • Early experience suggests that chronic CTA rejection will be more similar than different from solid organ allografts • Novel immunosuppressive and treatment strategies are needed.
    • 15. Case Presentation
    • 16. Graft Appearance, Clinical Course, Skin Biopsy Histology and Outcomes: Five Cases in Hand Transplant Recipients THE LOUISVILLE VCA PROGRAMTHE LOUISVILLE VCA PROGRAM CL Kaufman, MR Marvin, R Ouseph, R Zaring, Y Manon-Matos, B Blair, JE Kutz
    • 17. Case Description Overall Grade Actual Treatment Hindsight View 1 Patient with extensive rejection not equally reflected in biopsies – Grade 0 and Grade II ? Significant based on clinical symptoms Solumedrol IV and steroid taper Chronic rejection of skin? 2 Skin histology at year 6 does not seem to reflect chronic rejection Grade I-II possible complications from chronic superficial venous thrombus Year 6 Solumedrol IV and pred taper Venous obstruction? 3 This patient routinely has Grade I infiltrates, showed a Grade 3 biopsy in the absence of clinical symptoms Grade 3, no symptoms, Grade 0 in local area subsequently No additional treatment So far, fine. 4 Banff grade 2 in year 11 and year 12 skin biopsy Year 11 –grade II Year 12 –grade I-II No additional treatment Allograft seems fine Pt does have DSA (C1q-) Summary of cases
    • 18. Bilateral forearm transplantation (México) Dr. Armando Gamboa Hernández Dr. Martín Iglesias (corresponding author) Dra. Patricia Butrón Gandarillas Dra. Josefina Alberú Gómez Dr. Mario Vilatoba Dr. Luis Eduardo Morales Dra. Norma Bobadilla
    • 19. Banff VCA Group Case Discussion August 22, 2013 Max K. Fischer, MD, MPH Assistant Professor Division of Dermatopathology Johns Hopkins University
    • 20. 12th Banff Conference on Allograft Pathology: Diagnostic challenges in diagnosing rejection in vascularized composite allografts Chandra Smart, MD Scott Binder, MD UCLA Department of Pathology and Laboratory Medicine Section of Dermatopathology August 22, 2013
    • 21. Pathological aspects suggestive of skin chronic rejection in a face transplant recipient after reduction of immunosuppression Banff-VCA conference 2013 Emmanuel Morelon, Sylvie Testelin, Palmina Petruzzo, Lionel Badet, Bernard Devauchelle, Jean Kanitakis On behalf of the Lyon-Amiens VCA team
    • 22. Composite Tissue Session (Vascularized composite allografts) Discussion No changes to the Classification System at this time