banff vca consensus statemet l cendales sent to kim
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Vascularized Composite AllotransplantationBanff VCA
Linda C. Cendales, M.D.Associate Professor of Surgery
Duke University Medical Center on behalf of
The Banff VCA Working Group
< 250 VCA recipients worldwide
Congratulations to the field of
Vascularized Composite Allotransplantation
for organizing themselves under the Banff Structure
Coming together and agreeing to systematically study VCA pathology is
a significant step
But the hard work starts now
We started talking together in a common language
We can now argue
The Towel of Babel
Painting by Peter Bruegel the Elder, 1583
We cannot have arguments and organize ourselves until we have a
common language.
A common language facilitates disagreement in a good way
A common language allows for collaboration
Diagnosis of Transplant Rejection in the 1980’s
Transplantation 1984 Dec;38(6):709-13.Relationships among the histologic pattern, intensity, and phenotypes of T cells infiltrating renal allografts.Kolbeck PC, Tatum AH, Sanfilippo F.
Histopathology. 1980 Sep;4(5):517-32.The relation of different inflammatory cell types to the various parenchymal components of rejecting kidney allografts.Reitamo S, Konttinen YT, Ranki A, Häyry P.
Common Language
Vascularized Composite Allotransplantation
Before 2007
Nothing
VCA Banff
Now
Keeping this group together under this framework is how this is going to go
forward
We can now answer the questions
Unanswered Questions
Histologic Features of Antibody Mediated Rejection after Face Transplantation
Anil Chandraker MD FASN FAST FRCP
Medical Director of Kidney and Pancreas TransplantationBrigham and Women’s Hospital
Director, Schuster Family Transplantation Research CenterBrigham and Women's Hospital
Associate Professor of Medicine, Harvard Medical School
Pre-Sensitized Recipient of a Full-Face Allotransplant
Acute Cellular Rejection
Complement Deposition (C4d)Pre- cellular rejection Cellular rejection Post-
treatment
Pre-sensitized patient
Not pre-sensitized patient
Graft vasculopathy in the skin in vascularized composite allografts
J. KanitakisDepts. of Dermatology/Pathology Ed. Herriot Hospital, Lyon, France
BANFF‐CST Joint Scientific Meeting
October 8, 2015 Vancouver, British Columbia
Sudden necrotic ulceration
Progression to scaly erythematous maculopapules
SSG
initial aspect
SSGNovember 2014
ID Nov 2014 – 9 years postTx
(face)
CD20
CD4
C4d
Banff grade III
thickening/luminal obstruction of the nutrient SSG artery ≈ graft vasculopathy
SSG ulceration ID Nov 2014 – 9 years postTx - SSG
C4d-
AR rejection on the face (Banff III)Graft vasculopathy of the SSG
Cutaneous Changes among Transplant Patients
Adela Rambi G. Cardones, M.D.Immunodermatology, Chronic GVHD Clinic
Director, Inpatient Consult ServiceAssistant Professor
Duke University Department of Dermatology
Atypical Acute Rejection After Hand Transplantation
Schneeberger S, et al. American Journal of TransplantationVolume 8, Issue 3, pages 688-696, 5 FEB 2008 DOI: 10.1111/j.1600-6143.2007.02105.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2007.02105.x/full#f3
Nails (Distinctive Signs)
Dystrophy, pterygium, longitudinal ridging.
VCA Research Laboratory - Mission
Expanding the Banff VCA Criteria
Gerald Brandacher, MD, FASTAssociate Professor or Surgery
Scientific DirectorReconstructive Transplantation Program
Johns Hopkins University School of MedicineBaltimore, MD, USA
on behalf of the AST VCA Advisory Council Working Group
Question from the AST Working Group
Does biopsy site matter? The skin anatomy and characteristics differ significantly depending where on the hand or face the biopsy is taken. Should this be reflected in the Banff Criteria?
While 4 mm biopsies provide a great deal of information, many centers do not feel a biopsy of this size is practical. Should this criteria be revisited? Additionally would more information be gained from two smaller biopsies, one taken from an area of involvement and one from a “normal” area?
There appears to be distinct differences between infiltrates and histology of skin from hand vs. face transplants. Should these differences be reflected in the histological grade of rejection?
Question from the AST Working Group
Specific criteria to be reconsidereda.Is the PAS stain still relevant and routinely performed?b.CD163 may be a preferable marker to CD68 for macrophages.c.What is the rationale to include both CD19 and CD20?d.Why is CMV proposed as a recommended immunohistological stain (would be unusual in the differential of rejection).e.Inclusion of additional immunohistochemistry markers e.g. FoxP3.
Question from the AST Working Group
Many centers continue to report histological grades of 0-I, I-II and II-III from review of VCA skin biopsies. As it is still unclear what histology that is less severe than a grade I means, should we expand the criteria?
Is the granularity of the current criteria sufficient?
Discussion
• Unanswered questions collected over the years by the Banff VCA group
• Reviewed results of Banff VCA survey• Reviewed Proposal for collection data
form• Reviewed AST VCA advisory council
questions• VCA Working Group Workshop, May 21,
2016, Durham, NC
• Challenges grading Banff VCA 0-I-II• Specificity of isolated dyskeratotic/apoptotic
keratinocytes • Does location alter the specificity of isolated
dyskeratotic/apoptotic cells?– Epidermis– Follicular epithelium– Sweat gland epithelium– Basal vs. suprabasal/at all levels
• Analogy to GVHD • Value of a numeric threshold• Role of mast cells in chronic immune injury• Role of C4d staining and/or DIF staining for C4d in the
management of rejection
Banff VCA – Unanswered Questions
Banff VCA – Unanswered Questions
• Significance of focal epidermal changes (i.e. spongiosis and/or lymphocyte exocytosis) in Banff VCA grades
• Study of effector functions of antibody and its manifestations in tissues (acute and chronic)
• Detection of antibody functions – Biopsy: histology, genomics– Blood: serological, cellular
• Chronic changes• Relationship of graft function and rejection
– Acute and Chronic
Banff VCA – Unanswered Questions
•Interpretation of long-term changes and related biomarkers•Differential diagnosis of inflammation vs. rejection•Scope of Disease - Antibody Mediated Rejection•Significance of myointimal proliferation•Vasculopathy, role of antibody
Banff VCA Survey
We translated these results into a one-page form to standardize
the collection of data
Banff VCA Resource
Human and Animal Histology/Immunohistochemistry Core
• VCA clinical samples (>2000)– Tissue samples: muscle, skin, tendon, nerve, artery, vein
• Histopathology Core• Digital Library
– Digital slide scanning – Aperio AT [400 slide scan capability]
• Dedicated Lab Space• Histology Staff
Digital Library
AST VCA advisory council questions
• Many centers continue to report histological grades of 0-I, I-II and II-III from review of VCA skin biopsies. As it is still unclear what histology that is less severe than a grade I means, should we expand the criteria?
• New information is accumulating regarding the importance of loss of capillaries and importance of evaluating small vessel vasculopathy. Should a grading scale for early signs of “chronic” rejection be proposed?
• There appears to be distinct differences between infiltrates and histology of skin from hand vs. face transplants. Should these differences be reflected in the histological grade of rejection?
• While 4 mm biopsies provide a great deal of information, many centers do not feel a biopsy of this size is practical. Should this criteria be revisited? Additionally would more information be gained from two smaller biopsies, one taken from an area of involvement and one from a “normal” area?
• While the current criteria do note that the level of involvement in the graft should be reported, this is not reflected in the histological score. Practically, this histologic score is used interchangeable as “Grade of Rejection”. Should the working group propose an actual “Grade of Rejection” vs. “grade of histology” that would reflect clinical parameters such as a. level of involvement, b. Edema, c. Induration
• Does biopsy site matter? The skin anatomy and characteristics differ significantly depending where on the hand or face the biopsy is taken. Should this be reflected in the Banff Criteria?
AST VCA advisory council questions
Workshop on VCA Pathology
May 21, 2016 Durham, NC
Thank you
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