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Updates from the Pathology Council, with a Focus on AMR

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Brandon Larson, MD, PhD
University of Arizona Medical Center
Tucson, AZ, USA

As in recent years, AMR, both cardiac and pulmonary, has remained a strong focus of our efforts in the Pathology Council over the course of 2014. We expect that AMR will likely remain an important focus in the coming year as we seek to better understand this phenomenon and refine our diagnostic criteria for such.

Tutorial for Pathologists on Cardiac AMR

Most pathologists working in transplant centers who evaluate endomyocardial biopsies for rejection do so as a very small component of their broader clinical duties. In addition, most of these pathologists lack subspecialty training in cardiovascular or transplant pathology, and unfortunately, many of them are not members of ISHLT. One of our ongoing challenges in transplant pathology remains dissemination of knowledge about the practical application of rejection criteria to practicing pathologists on the "front lines."

In 2012, members of the Pathology Council, in partnership with the Society for Cardiovascular Pathology and Association for European Cardiovascular Pathology, began to address this challenge by developing an online tutorial on acute cellular rejection for pathologists (http://scvp.net/acr/index.html). This tutorial has been well received, and has been translated into multiple other languages, including Spanish, Italian, Japanese, Russian, and French.

To expand upon these educational efforts, this year the Pathology Council, also in partnership with the SCVP and AECVP, has developed a similar, companion tutorial on cardiac AMR (http://scvp.net/amr/index.html). This tutorial is nearly complete in its English form, and recently "went live." The tutorial includes an appropriately detailed, yet succinct and practically oriented overview of endomyocardial biopsy evaluation for AMR, including a discussion of specific grading criteria, along with a lavishly illustrated guide to usage of immunohistochemistry and immunofluorescence for this purpose. This tutorial also includes considerations specific to the pediatric population and a valuable discussion on artifacts and potential mimics of cardiac AMR (also well illustrated). A quiz component of this tutorial remains under construction and will be available in the near future. We expect that this tutorial on cardiac AMR will be similarly well received and will represent a valuable resource to pathologists around the world who are asked to evaluate these specimens, particularly to those who may not be members of ISHLT or who do not routinely encounter these specimens. We welcome feedback and suggestions for improvement from anyone who uses this tutorial.

Progress in Pulmonary AMR

Members of the Pathology Council actively participated in the Consensus Meeting on Pulmonary AMR that was held during the 34th Annual Meeting and Scientific Sessions held in San Diego, California in April 2014. The published literature, diagnostic practices, and areas for future investigation were discussed. The recommendations of the 2012 Pathology Council review were reaffirmed with a proposal to further evaluate the utility of C4d staining in the diagnosis of pulmonary AMR.

The experience of most members of the Council is the infrequent demonstration of C4d staining of interstitial capillaries in the setting of circulating de novo DSA and clinical evidence of graft dysfunction. Technical, interpretative, and mechanistic considerations were discussed with a goal to investigate possible explanations for the insensitivity of the marker.

To address these technical and interpretative issues, unstained slides from cases showing strong C4d staining will be circulated to multiple transplant pathologists at multiple institutions, for individual center staining and evaluation. Additional cases will be collected and digitalized for review and grading by pathologists, with the intended goal to present the findings at the 35th Annual Meeting and Scientific Sessions in Nice, France.

2015 Annual Meeting & Scientific Sessions in Nice, France

Please join us for the following pathology-oriented sessions in Nice next spring:

  • Antibodies in Lung Transplant: Mayhem, Mediators, Mechanisms, and Management, where our rapidly evolving understanding of pulmonary AMR, its diagnosis, and its treatment will be reviewed and discussed.

  • When Worlds Collide: Heart and Kidney, where the role of venous congestion in heart failure and the cardiorenal syndrome will be discussed.

  • B-Cells in Transplantation 2015, where our current understanding of the role of B-cells in humoral rejection will be reviewed and therapeutic implications discussed.

  • Chronic Lung Disease Associated Pulmonary Hypertension: Mechanism, Pathology, and Clinical Impact, where the pathology of pulmonary vascular disease in the setting of pulmonary fibrosis will be reviewed, along with a discussion on the somewhat controversial treatment approaches for this condition.

  • Clinically Relevant Thoracic Transplant Pathology: A Primer for Clinicians, Nurses, Pharmacists, and Other Members of the Transplant Team, where our pathologists will present a broad yet practical overview of cardiac and pulmonary transplant pathology for their non-pathologist colleagues, including discussions on acute cellular rejection, antibody-mediated rejection, and chronic allograft vasculopathy in each of these organs.

For more details about these and other exciting symposia, please visit the 2015 Preliminary Program at http://www.ishlt.org/meetings/annualMeeting.asp.

See you all in Nice! ■

Disclosure Statement: The author has no conflicts of interest to discolse

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