Composite Tissue Session(Vascularized composite allograft)

Banff 2013 Summary

Linda Cendales, M.D

VCA Banff 2013Summary

• 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

Chronic Rejection in Vascularized

Composite Allografts

Cinthia Drachenberg, M.D.Professor of Pathology

University of Maryland School of Medicine

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.

Unadkat et al. Vasculopathy at 90 days in rat hind limb model

Striking venous inflammation with thickening and occlusion not shown.

Synovial biopsy 18 months Sentinel graftl biopsy 36 months

Soft tissue biopsy 50 months Synovial biopsy 50 months

Pathogenesis: of vasculopathyNon-alloimmune factors: trauma. episodic intense or chronic low grade mechanical damage, thermal injury.

hyperplasia as well as remodeling .

Microsurgery 1996

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.

Histopathological Observations in CTA with Clinical Correlation

A.J. DemetrisThomas Starzl Transplant Institute

Dept. of PathologyDivision of Transplantation

University of Pittsburgh Medical CenterPittsburgh, PA

Cell-mediated InjuryCornell et al Annu. Rev. Pathol. Mech. Dis. 2008. 3:189–220

Antibody Mediated Injury

PMN

anti-HLA Abanti-HLA Ab

Fc ReceptorFc ReceptorMediated BindingMediated Binding

C’ ActivationC’ Activation

Donor HLADonor HLA MACMACPlatelet microthrombiPlatelet microthrombi

EndotheliumEndotheliumADCCADCC

CDCCDC

C4dC4d

C4a +C4bC4a +C4b

C4C4C1C1

Courtesy of Peter Nickerson

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

• OtherCendales 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.

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.

Case Presentation

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

Case Description Overall Grade ActualTreatment

HindsightView

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 IIYear 12 –grade I-II

No additional treatment

Allograft seems finePt does have DSA (C1q-)

Summary of cases

Bilateral forearm transplantation (México)

Dr. Armando Gamboa HernándezDr. Martín Iglesias (corresponding author)Dra. Patricia Butrón GandarillasDra. Josefina Alberú GómezDr. Mario VilatobaDr. Luis Eduardo MoralesDra. Norma Bobadilla

Banff VCA GroupCase Discussion

August 22, 2013

Banff VCA GroupCase Discussion

August 22, 2013

Max K. Fischer, MD, MPHAssistant Professor

Division of DermatopathologyJohns Hopkins University

12th Banff Conference on Allograft Pathology:

Diagnostic challenges in diagnosing rejection in vascularized composite

allografts

Chandra Smart, MDScott Binder, MD

UCLA Department of Pathology and Laboratory Medicine

Section of DermatopathologyAugust 22, 2013

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

Composite Tissue Session(Vascularized composite allografts)

Discussion

No changes to the Classification System at this time