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Spreading the Word on the ISHLT Working Formulation for Cardiac AMR


Dylan V Miller, MD
ISHLT Pathology Council Chair

Gerald J Berry, MD
Pathology Program Committee Member



Much of the Pathology Council's efforts in recent years have focused on standardizing the diagnostic criteria for antibody-mediated rejection (AMR) in cardiac transplant biopsies. These efforts have been fruitful in terms of finding agreement between pathologists at many centers around the globe as well as coordinating closely with clinical colleagues in revising the Working Formulation for AMR

Still, pathology faces a unique challenge within the ISHLT relative to our colleagues in other specialties. During the "day-to-day" work at our home institutions, reading transplant biopsies occupies only a tiny fraction of our time. Most of us wear many other hats and spend the bulk of our time far removed from transplant pathology on surgical pathology, autopsy, or other pathology services. The Pathology Council members' involvement with the ISHLT stems from our passion for this work and dedication to these patients. Membership and attendance at the annual meeting is a luxury many practicing pathologists who sign out your heart transplant biopsies literally cannot afford. We know this in part because only 47 ISHLT members are pathologists (according to member profile data), while the ISHLT registry data indicate 394 transplant centers worldwide and 241 currently reporting. Just ask yourself, do the pathologists reading my biopsies attend ISHLT? Chances are, the answer will be no. At most centers, transplant biopsies are read by a pathologist who is not a member of ISHLT.

So, the challenge for those of us on the pathology council, besides encouraging recruitment and greater participation from our pathologist colleagues, is ensuring that the "water gets down the furrows in the field" when it comes to the Working Formulation revisions. We realize it is time to stop preaching to the converted and start taking the message abroad.

To that end, we have submitted a new manuscript to the Journal for Heart and Lung Transplantation intended as an exhaustive atlas or monograph type reference to aid pathologists in applying the Working Formulation for Cardiac AMR in biopsy interpretation. It includes numerous illustrations that highlight important histologic and immunopathologic features of AMR from several cases contributed by the authors. Besides further descriptive summaries of criteria for diagnosing AMR, there is also a discussion of controversies and knowledge gaps that deserve further investigation (like what to do with focal C4d staining, how many macrophages is too many, and integrating DSA and clinical signs into the diagnosis of AMR).

Members of the Pathology Council have also collaborated with the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology to help develop an Online Tutorial for grading cellular rejection in cardiac transplant biopsies. An accompanying tutorial for AMR is under development as well and several members of the Pathology Council are participating. These tutorials will be an invaluable resource, not only for pathologists and pathology trainees, but for clinicians, surgeons, nurse coordinators, and anyone else needing an introduction or even "refresher" to the Working Formulation grading scheme for cardiac rejection. The tutorials even include live viewable slides (digital whole slide images) for teaching.

Members of the Pathology Council will also be presenting a CME course at the major annual pathology society meeting (United States and Canadian Academy of Pathology, 2014) next year, focusing on heart and lung transplant biopsy pathology and the revised Working Formulation.

All of these resources will be available to all pathologists regardless of membership in ISHLT. Our ultimate aim is to improve adherence to the revised Working Formulation criteria worldwide, but this is also a public relations campaign of sorts that we hope will encourage greater pathologist participation in ISHLT.

The heart is just the start; efforts are currently underway to better define the diagnostic features of AMR in lung transplant biopsies. As Dr. Gerry Berry states, pulmonary AMR continues to be a vibrant topic of special interest to the Pathology Council. Following up on the success of the pre-meeting in Prague in 2012, a group of thoracic pathologists met in Montreal on Tuesday, April 23, 2013 to further refine diagnostic criteria. A series of cases of AMR were presented and the histopathologic findings and immunophenotypic profiles were each evaluated and discussed to develop diagnostic thresholds for interpretation. Dr. Roden of the Mayo Clinic presented their experience of concurrent IF and IHC staining for C4d on a series of transbronchial biopsy specimens. Further refinement of the morphologic constituents of pulmonary AMR will be the goal of both future meetings and studies.

The coming year in the Pathology Council promises to be exciting and productive as we continue to contribute and refine the histopathologic criteria for grading of rejection in a deliberate and evidence-based manner. We look forward to a vigorous interaction with our clinical colleagues in the Society to meet these goals, and we also hope that our clinical colleagues will help recruit new members to the Pathology Council from Pathology Departments in their medical centers in order to better disseminate and standardize these diagnostic criteria.

Disclosure Statement: The authors have no conflicts of interest to report.




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