ISHLT Pathology Council & Pulmonary AMR

12th Banff Conference on Allograft Pathology

Thursday, August 22, 2013

GERRY BERRY

Pulmonary AMR in 2013

• Historical Highlights

• 2012 ISHLT Survey of Pathology Practices

• Recommendations from ISHLT 2012 in Prague

• Future Directions

2012 Survey of Current Practices in Diagnosis and Reporting of Pulmonary AMR

• Survey modeled on successful approach by AECVP for Cardiac AMR *

• Survey consisted of 33 questions created in REDCap and supported by Stanford Center for Clinical Informatics in Stanford SOM

• Survey sent to 38 institutions in North America, Europe and Australia

* Burke M, Andersen C, Ashworth M, et al. J Heart Lung Transplant 2010; 29:S37-38.

Demographics

Experience in Reading Biopsies

Monthly Transbronchial Biopsy Load

Antibodies used in IHC

Conclusions #1

• Group (90%) composed of experienced pathologists (> 5 yrs experience)

• > 80% of groups evaluating > 10 TBBx/mo

• Primary indications for immunostaining are clinical and histopathological findings

• Few centers (25%) perform immunostaining according to protocols

Conclusions #2

Indications of performing Immunostains

• Acute Lung Injury Pattern (66%)

• Neutrophilic Margination (70%)

• Acute Capillaritis (85%)

• Unexplained Graft Dysfunction (2/3)

• High Grade ACR (22%)

J Heart & Lung Transplant 2013; 32:14-21

Histopathologic Indications for Immunopathologic Staining

• Neutrophilic Capillaritis

• Neutrophilic Septal Margination

• High Grade ACR

• Persistent/Recurrent ACR

• Acute Lung Injury Pattern/DAD

• High Grade LB (B2R)

• Persistent low grade LB (Grade B1R)

• Obliterative Bronchiolitis (Grade C1)

• Arteritis in the Absence of Infection or ACR

• Graft Dysfunction without Morphologic Explanation

• Any Histologic Findings in setting of de novo +ve DSA

Interpretative Issues in AMR

• Distribution of C4d Staining:– Multifocal/Diffuse staining >50% of

microvasculature: POSITIVE– Focal or <50% staining: NEGATIVE

– Any C4d staining should be discussed with clinicians as findings might warrant DSA studies and more frequent clinical monitoring

Diagnostic Terminology

• Like ACR, AMR is diagnosis of exclusion

• Requires clinical dysfunction, circulating DSA and C4d immunoreactivity

“No Evidence of AMR”

“Findings Suggestive of AMR”

• Insufficient experience for making recommendations for follow-up intervals

Summary & Future Directions

• Diagnosis of pulmonary AMR requires multidisciplinary approach

• Histopathological findings are nonspecific patterns of injury; patterns should trigger immunostaining

• Qualified terminology should be used with final clinical diagnosis incorporating all modalities

• For centers that do not routinely obtain DSA, studies should be done at or near time of biopsy

• Centers are encouraged to develop protocols that will promote investigations addressing issues of time to onset of AMR, incidence, prevalence, spectrum of temporal, morphological and immunopathological changes, clinical outcomes and risk for chronic allograft dysfunction

• Digital pathology slide technology will be used to promote educational and collaborative efforts

Adriana Zeevi PhD (D) ABHIProfessor of Pathology, Surgery and

ImmunologyUniversity of Pittsburgh Medical Center

Serology of Lung AMR

Summary

Recurrent ACR, refractory to increased immunosuppression is associated with development of de-novo DSA.

The most frequent DSAs in LTx were HLA-DQ specific including Abs towards DQB, DQA and combination of DQB/DQA pairs.

Persistent DQ specific DSAs with C1q reactivity are demonstrated prior to diagnosis of AMR.

Response to AMR treatment is associated with Diminished and/ or Loss of C1q reactive DSAs.

Summary/Conclusions Pre-formed and de-novo DSA are associated

with various forms of antibody injury to allograft Non HLA antibodies need to be evaluated for

the impact on LTX Early detection of DSA post LTx and systematic

monitoring with sensitive solid-phase platforms is recommended

Antibody depletion protocols need to be evaluated: when and how

Anti-human leukocyte antigen antibodies and preemptive antibody-

directed therapy after lung transplantation

Survival wassignificantly worse in recipients who hadpersistent DSA than in those who cleared the DSA.

Ramsey R. Hachem, MD, et al J Heart Lung Transplant 2010;29:973–80

Clinical Overview of Pulmonary AMR

Clinical Overview of Pulmonary AMR

Marie M. Budev DO MPH FCCPMedical Director Lung and Heart Lung

Transplant Program Cleveland ClinicCleveland, OH

Triple Test - Diagnosis of Pulmonary AMR

Triple Test - Diagnosis of Pulmonary AMR

Serologic Evidence

Donor Specific Antibody

+

Graft Dysfunction

Histological Evidence

Histopathology + C4d staining

+

AAMR and SurvivalAAMR and SurvivalAAMR and SurvivalAAMR and Survival

• Survival after Survival after AMR is poor AMR is poor

• Cleared DSA Cleared DSA significantly significantly better survival better survival

Witt CA. In Press : J Heart Lung Transplant. 2013

Clinical Points AAMR StudyClinical Points AAMR StudyClinical Points AAMR StudyClinical Points AAMR Study

• Survival is poor after AAMRSurvival is poor after AAMR• Survival is better if DSA cleared Survival is better if DSA cleared • AAMR may be a reversible cause of AAMR may be a reversible cause of

allograft failure allograft failure • High index of suspicion with protocol for High index of suspicion with protocol for

surveillance in place including HLA testing surveillance in place including HLA testing - C4d still controversial C4d still controversial

• Role of C1q Role of C1q

HLA ANTIBODIES AFTER LUNG HLA ANTIBODIES AFTER LUNG TRANSPLANTATION: EARLY TRANSPLANTATION: EARLY

RESULTS OF THE HALT STUDYRESULTS OF THE HALT STUDY

HLA ANTIBODIES AFTER LUNG HLA ANTIBODIES AFTER LUNG TRANSPLANTATION: EARLY TRANSPLANTATION: EARLY

RESULTS OF THE HALT STUDYRESULTS OF THE HALT STUDY

The HALT InvestigatorsThe HALT Investigators

HALT: Multicenter StudyHALT: Multicenter StudyHALT: Multicenter StudyHALT: Multicenter Study

• Washington UniversityWashington University– R. Hachem, R. Yusen, K. Schechtman, J. Gaut, T. MohanakumarR. Hachem, R. Yusen, K. Schechtman, J. Gaut, T. Mohanakumar

• Cleveland ClinicCleveland Clinic– M. Budev, C. Farver, M. AskarM. Budev, C. Farver, M. Askar

• University of PennsylvaniaUniversity of Pennsylvania– V. Ahya, J. Lee, L. Litzky, M. KamounV. Ahya, J. Lee, L. Litzky, M. Kamoun

• UTHSC San AntonioUTHSC San Antonio– D. Levine, S. Werner-Abboud, M. PollackD. Levine, S. Werner-Abboud, M. Pollack

• Stanford UniversityStanford University– G. Dhillon, D. Weill, G. Berry, D. TyanG. Dhillon, D. Weill, G. Berry, D. Tyan

• University of California San FranciscoUniversity of California San Francisco– L. Leard, J. Golden, K. Jones, L. Baxter-LoweL. Leard, J. Golden, K. Jones, L. Baxter-Lowe

MethodsMethodsMethodsMethods

• Pilot prospective multicenter observational Pilot prospective multicenter observational study study

• Standardize DSA monitoringStandardize DSA monitoring• Determine incidence of DSA development Determine incidence of DSA development

(DSA profiles)(DSA profiles)• Enrollment 12/2011 – 6/2012Enrollment 12/2011 – 6/2012• 4 months follow-up after transplant4 months follow-up after transplant• LABScreen® Single Antigen assayLABScreen® Single Antigen assay

- Days: 10, 30, 60, 90, 120Days: 10, 30, 60, 90, 120- Allograft dysfunctionAllograft dysfunction

Patient flow diagram

Acute cellular rejectionAcute cellular rejectionAcute cellular rejectionAcute cellular rejection

• At least 1 episode of ACR grade ≥ A1At least 1 episode of ACR grade ≥ A1- DSA-: 44/68 (65%)DSA-: 44/68 (65%)- DSA+: 25/36 (69%)DSA+: 25/36 (69%)

• At least 1 episode of ACR grade ≥ A2At least 1 episode of ACR grade ≥ A2- DSA-: 26/68 (38%)DSA-: 26/68 (38%)- DSA+: 16/36 (44%)DSA+: 16/36 (44%)

• CARS: sum of all A scoresCARS: sum of all A scores- DSA-: mean = 1.5 ± 1.5, median = 1.0DSA-: mean = 1.5 ± 1.5, median = 1.0- DSA+: mean = 1.7 ± 1.6, median = 1.5DSA+: mean = 1.7 ± 1.6, median = 1.5

P = 0.63

P = 0.54

P = 0.70

Antibody-mediated rejectionAntibody-mediated rejectionAntibody-mediated rejectionAntibody-mediated rejection

• 4 cases of AMR (adjudicated)4 cases of AMR (adjudicated)• Occurred on POD 22, 46, 75, and 92Occurred on POD 22, 46, 75, and 92• Clinical allograft dysfunctionClinical allograft dysfunction• DSA to class I & II (n = 4)DSA to class I & II (n = 4)

– Pre-tx DSA (n = 1): higher MFI and new DSAPre-tx DSA (n = 1): higher MFI and new DSA– De novoDe novo DSA (n = 3) DSA (n = 3)

• Alveolar septal neutrophilia (n = 2), no biopsy (n = Alveolar septal neutrophilia (n = 2), no biopsy (n = 2)2)– C4d & C3d negative (n = 2)C4d & C3d negative (n = 2)

• Clinical response to IVIG, high-dose steroidsClinical response to IVIG, high-dose steroids

ConclusionsConclusionsConclusionsConclusions

• DSA is common early after transplantationDSA is common early after transplantation• DSA to HLA class II more commonDSA to HLA class II more common• HALT follow-up too short to examine HALT follow-up too short to examine

impact on clinical outcomesimpact on clinical outcomes• Some patients did clear DSA during Some patients did clear DSA during

follow-upfollow-up• Long-term follow-up is necessary & Long-term follow-up is necessary &

planned with HALT II Trial planned with HALT II Trial

Banff Study of Banff Study of Pathologic Changes Pathologic Changes

in Lung Allograft in Lung Allograft Biopsies with Donor Biopsies with Donor Specific AntibodiesSpecific Antibodies

Comandatuba, BrazilComandatuba, Brazil

August 2013August 2013

Banff 2011Banff 2011Paris, FranceParis, France

Lung Group DiscussionLung Group DiscussionData for pathology of lung Data for pathology of lung AMR was limited/lackingAMR was limited/lackingThe data on C4d was The data on C4d was inconsistent, probably inconsistent, probably unreliableunreliableAMR in lung allograft was AMR in lung allograft was not a pathologic diagnosis not a pathologic diagnosis at that timeat that timeLarge study needed to Large study needed to gather pathologic data on gather pathologic data on lung transplant biopsieslung transplant biopsies

Should be multi-institutionalShould be multi-institutionalResults to be presented at Results to be presented at Banff 2013 in BrazilBanff 2013 in Brazil

Mengel M, et al. Banff 2011 Meeting report: new concepts in antibody-mediated rejection. Am J Transplant. 2012 Mar;12(3):563-70.

Banff StudyBanff Study• Team Leaders: Carol Farver, W. Dean WallaceTeam Leaders: Carol Farver, W. Dean Wallace• Lung transplant transbronchial biopsies were Lung transplant transbronchial biopsies were

compiled from UCLA and Cleveland Clinic compiled from UCLA and Cleveland Clinic • 253 lung transplant biopsies (62 biopsies have C4d 253 lung transplant biopsies (62 biopsies have C4d

stains)stains)– Mean age: 55.8, Range: 18-74Mean age: 55.8, Range: 18-74

– Gender: 111 females (43.9%), 142 males (56.1%)Gender: 111 females (43.9%), 142 males (56.1%)

• Inclusion criteria:Inclusion criteria:– All biopsies have full serologic antibody studies performed All biopsies have full serologic antibody studies performed

within (within (++) 30 days of biopsy) 30 days of biopsy• 98 de novo DSAs (38.7%) 98 de novo DSAs (38.7%) • 46 non-DSAs (18.2%)46 non-DSAs (18.2%)• 109 never antibodies (43.1%)109 never antibodies (43.1%)

– Full clinical/infectious disease work up dataFull clinical/infectious disease work up data– At least 1 year old at beginning of studyAt least 1 year old at beginning of study

PathologistsPathologists• Biopsies are scanned for whole slide image Biopsies are scanned for whole slide image

analysis for ease of sharinganalysis for ease of sharing• Eleven pathologists participated in blinded studyEleven pathologists participated in blinded study

– Carol Farver, Cleveland ClinicCarol Farver, Cleveland Clinic– W. Dean Wallace, UCLAW. Dean Wallace, UCLA– Claus B. Andersen, Rigshospitalet, CopenhagenClaus B. Andersen, Rigshospitalet, Copenhagen– Valeria Arrossi, Cleveland ClinicValeria Arrossi, Cleveland Clinic– Roberto Barrios, The Methodist Hospital, HoustonRoberto Barrios, The Methodist Hospital, Houston– Gerry Berry, StanfordGerry Berry, Stanford– Matthew DeNicola, UCLAMatthew DeNicola, UCLA– Desley Neil, Queen Elizabeth Hospital, Birmingham, UKDesley Neil, Queen Elizabeth Hospital, Birmingham, UK– Elizabeth Pavlisko, Duke UniversityElizabeth Pavlisko, Duke University– Myriam Remmelink, Brussels, BelgiumMyriam Remmelink, Brussels, Belgium– Birgit Weynand, Brussels, BelgiumBirgit Weynand, Brussels, Belgium

Histologic VariablesHistologic Variables

• Biopsy AdequacyBiopsy Adequacy• Acute Cellular RejectionAcute Cellular Rejection• Airway InflammationAirway Inflammation• Obliterative BronchiolitisObliterative Bronchiolitis• Acute Lung InjuryAcute Lung Injury• EndotheliitisEndotheliitis• Alveolar HemosiderosisAlveolar Hemosiderosis• Capillary InflammationCapillary Inflammation• Suspicion for Aspiration?Suspicion for Aspiration?• Other Infection?Other Infection?• C4d depositionC4d deposition

Primary questions to be Primary questions to be asked…asked…

• Is there correlation with capillary inflammation Is there correlation with capillary inflammation and/or acute lung injury and DSAs?and/or acute lung injury and DSAs?

• What is significance of C4d deposition?What is significance of C4d deposition?Secondary questions…Secondary questions…• Does ACR correlate with DSAs?Does ACR correlate with DSAs?• Is there correlation between endothelialitis Is there correlation between endothelialitis

and DSAs?and DSAs?• Percent of biopsies suboptimal or inadequatePercent of biopsies suboptimal or inadequate• Percent of biopsies without airwaysPercent of biopsies without airways• What is inter-observer reliability for various What is inter-observer reliability for various

histologic categorieshistologic categories

Limitations of StudyLimitations of Study

• Whole slide imaging not as good as Whole slide imaging not as good as glass slides for capillary analysisglass slides for capillary analysis

• Only 1 level examinedOnly 1 level examined• Restriction of choices by dropdown Restriction of choices by dropdown

menumenu• Variability in interpretation of ALI and Variability in interpretation of ALI and

capillary inflammation (do we need capillary inflammation (do we need better definitions?)better definitions?)

• C4d performed at one institution onlyC4d performed at one institution only• Have not included antibody titer levelsHave not included antibody titer levels

Acute Cellular RejectionAcute Cellular Rejection

Frequency for pooled Frequency for pooled datadata

Comparisons between D, A , Comparisons between D, A , and N and N

Average ACR Score 0.336 0.365 0.304

Acute Lung InjuryAcute Lung Injury

• Regarded as a spectrum from reactive Regarded as a spectrum from reactive pneumocytes with interstitial/alveolar pneumocytes with interstitial/alveolar edema (above baseline) to diffuse alveolar edema (above baseline) to diffuse alveolar damage (DAD). damage (DAD).

• Any degree of ALI less than DAD was Any degree of ALI less than DAD was categorized as “ALI”. categorized as “ALI”.

• Hyaline membranes indicated DADHyaline membranes indicated DAD• If acute inflammation consistent with acute If acute inflammation consistent with acute

pneumonia, “Acute pneumonia, favor pneumonia, “Acute pneumonia, favor infection”infection”

DSA

Frequency of ALIFrequency of ALI

Comparison Data

Average ALI Score 0.187 0.322 0.128

EndothelialitisEndothelialitis

EndothelialitisEndothelialitis

Capillary InflammationCapillary Inflammation• Capillary inflammation determined by degree Capillary inflammation determined by degree

of neutrophils in alveolar capillaries.  of neutrophils in alveolar capillaries.  • Does not include areas with hemorrhage or Does not include areas with hemorrhage or

crush artifact.  crush artifact.  • Best area with preserved lung architecture.  Best area with preserved lung architecture. 

– 0=normal, generally few or no neutrophils.  0=normal, generally few or no neutrophils.  – 1=more than normal but no back-to-back (touching) 1=more than normal but no back-to-back (touching)

neutrophils neutrophils – 2=more than baseline AND back-to-back neutrophils2=more than baseline AND back-to-back neutrophils– 3=frank capillaritis with karyorrhectic debris and 3=frank capillaritis with karyorrhectic debris and

hemorrhagehemorrhage

Normal alveolar Normal alveolar capillariescapillaries

Above baseline and 2 or Above baseline and 2 or more neutrophils back-to-more neutrophils back-to-

backback

Capillary InflammationCapillary Inflammation

DSA

DSA

DSA

DSA

Non-DSA

DSA vs NegativeDSA vs Negative

Comparisons between D, A Comparisons between D, A and N and N

Average CI Score 0.264 0.362 0.224

Capillary inflammation vs Capillary inflammation vs ALIALI

C4d DepositionC4d Deposition

• C4d measured as:C4d measured as:– NegativeNegative– Positive, <50%Positive, <50%– Positive, >50%Positive, >50%– Not performedNot performed

• Measured in alveolar capillaries onlyMeasured in alveolar capillaries only• 62 biopsies had C4d stains62 biopsies had C4d stains• Full data from Cleveland Clinic 177 Full data from Cleveland Clinic 177

cases with C4dcases with C4d

DSA

C4d is correlated with ALI with DAD, increasing ACR and Capillary Inflammation but not ALI alone.

Cleveland Clinic DataCleveland Clinic Data

Inter-Observer Variability Inter-Observer Variability

Where were we in 2011?Where were we in 2011?

Putative Stages of Humoral Putative Stages of Humoral Response to an Organ Graft – Response to an Organ Graft – 2003 NIH recommendations2003 NIH recommendations

I: Latent humoral responseI: Latent humoral responseCirculating antibody alone (without biopsy findings Circulating antibody alone (without biopsy findings or graft dysfunction)or graft dysfunction)

II: Silent humoral reactionII: Silent humoral reaction (accommodation vs pre- (accommodation vs pre-rejection state)rejection state)Circulating antibody, (without Circulating antibody, (without histologic changes or graft dysfunction)histologic changes or graft dysfunction)

III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejectionCirculating antibody, tissue Circulating antibody, tissue pathology (without graft dysfunction)pathology (without graft dysfunction)

IV: Humoral rejectionIV: Humoral rejectionCirculating antibody, tissue Circulating antibody, tissue pathology, graft dysfunctionpathology, graft dysfunction

Takemoto SK, et al. National conference to assess antibody-mediated rejection in solid organ transplantation. Am J Transplant 2004;4:1033–41.

C4d C4d depositiondeposition

C4d C4d deposition,deposition,

C4d C4d deposition,deposition,

Putative Stages of Humoral Putative Stages of Humoral Response to an Organ Graft – Response to an Organ Graft – 2003 NIH recommendations2003 NIH recommendations

I: Latent humoral response/Silent humoral I: Latent humoral response/Silent humoral reactionreaction Circulating antibody alone (without biopsy Circulating antibody alone (without biopsy findings or graft dysfunction)findings or graft dysfunction)

III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejectionCirculating antibody, (without Circulating antibody, (without graft dysfunction)graft dysfunction)

IV: Humoral rejectionIV: Humoral rejectionCirculating antibody, graft Circulating antibody, graft dysfunctiondysfunction

tissue pathologytissue pathology

tissue pathology,tissue pathology,

I: Latent humoral response/Silent humoral I: Latent humoral response/Silent humoral reaction/Sub-clinical humoral rejectionreaction/Sub-clinical humoral rejectionCirculating antibody alone (without biopsy Circulating antibody alone (without biopsy findings or graft dysfunction)findings or graft dysfunction)

II: Humoral rejectionII: Humoral rejectionCirculating antibody, graft dysfunctionCirculating antibody, graft dysfunction

Where are we in 2013?Where are we in 2013?

Recent StudiesRecent Studies• Yousem and Zeevi Yousem and Zeevi (Am J Surg Pathol (Am J Surg Pathol

2012;36:987–992).2012;36:987–992).– Found 23 pts with HLA Abs and lung dysfunctionFound 23 pts with HLA Abs and lung dysfunction– 17 had concurrent high grade ACR17 had concurrent high grade ACR– 18% had capillaritis18% had capillaritis– C4d seen in 76% (vs 24% of controls)C4d seen in 76% (vs 24% of controls)

• DeNicola, Weigt, Wallace et al. DeNicola, Weigt, Wallace et al. (J Heart (J Heart Lung Transplant 2013;32:326-332).Lung Transplant 2013;32:326-332).– 41 pts, 16 with anti-HLA abs41 pts, 16 with anti-HLA abs– Capillary neutrophilic inflammation and DAD were Capillary neutrophilic inflammation and DAD were

tested as histologic markers for AMRtested as histologic markers for AMR

ISHLT and BanffISHLT and Banff

• G Berry, et al. Pathology of G Berry, et al. Pathology of pulmonary antibody-mediated pulmonary antibody-mediated rejection: 2012 update from the rejection: 2012 update from the Pathology Council of the ISHLT. Pathology Council of the ISHLT. JHLT 2013; 32: 14-12. JHLT 2013; 32: 14-12.

• Banff StudyBanff Study

Putative Stages of Humoral Putative Stages of Humoral Response to an Organ Graft – Response to an Organ Graft – 2003 NIH recommendations2003 NIH recommendations

I: Latent humoral responseI: Latent humoral responseCirculating antibody alone (without biopsy findings Circulating antibody alone (without biopsy findings or graft dysfunction)or graft dysfunction)

II: Silent humoral reactionII: Silent humoral reaction (accommodation vs pre- (accommodation vs pre-rejection state)rejection state)Circulating antibody, (without Circulating antibody, (without histologic changes or graft dysfunction)histologic changes or graft dysfunction)

III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejectionCirculating antibody, tissue Circulating antibody, tissue pathology (without graft dysfunction)pathology (without graft dysfunction)

IV: Humoral rejectionIV: Humoral rejectionCirculating antibody, tissue Circulating antibody, tissue pathology, graft dysfunctionpathology, graft dysfunction

Takemoto SK, et al. National conference to assess antibody-mediated rejection in solid organ transplantation. Am J Transplant 2004;4:1033–41.

C4d C4d depositiondeposition

C4d C4d deposition,deposition,

C4d C4d deposition,deposition,

Putative Stages of Humoral Putative Stages of Humoral Response to an Organ Graft – Response to an Organ Graft – 2003 NIH recommendations2003 NIH recommendations

I: Latent humoral response/Silent humoral I: Latent humoral response/Silent humoral reactionreaction Circulating antibody alone (without biopsy Circulating antibody alone (without biopsy findings or graft dysfunction)findings or graft dysfunction)

III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejectionCirculating antibody, (without Circulating antibody, (without graft dysfunction)graft dysfunction)

IV: Humoral rejectionIV: Humoral rejectionCirculating antibody, graft Circulating antibody, graft dysfunctiondysfunction

tissue pathologytissue pathology

tissue pathology,tissue pathology,

Is it that simple?Is it that simple?

• NoNo• The histologic differences are The histologic differences are

significant but are neither sensitive significant but are neither sensitive nor specific for the presence of DSA. nor specific for the presence of DSA.

• Who would care if they were?Who would care if they were?• The question is: The question is:

– Are the findings sensitive or specific Are the findings sensitive or specific for graft deterioration in the setting for graft deterioration in the setting of DSA????of DSA????

InvestigatorsInvestigators

• PathologistsPathologists– Carol FarverCarol Farver– W. Dean WallaceW. Dean Wallace– Claus B. AndersenClaus B. Andersen– Valeria ArrossiValeria Arrossi– Roberto BarriosRoberto Barrios– Gerry BerryGerry Berry– Matthew DeNicolaMatthew DeNicola– Desley NeilDesley Neil– Elizabeth PavliskoElizabeth Pavlisko– Myriam RemmelinkMyriam Remmelink– Birgit WeynandBirgit Weynand

• UCLAUCLA– Sam WeigtSam Weigt– Ning LiNing Li– Elaine ReedElaine Reed– Jennifer ZhangJennifer Zhang

• Cleveland Clinic Cleveland Clinic – Marie BudevMarie Budev– Medhat AskarMedhat Askar– Rene SlawRene Slaw– Sol Cristomo Sol Cristomo