Saturday, February 10, 2007

Transplant Pathology

I had another biopsy last weekend. It's become a familiar routine of 6 AM departures, four hours bedrest, and waiting for a phone call in the evening with results. The details vary by organ, by institution, and by patient, but biopsies are a part of life for almost everyone involved in transplantation.

Biopsy samples, of course, go to pathology, and the development of transplant pathology is one of the more interesting spinoffs in the history of transplants and of pathology. Rejection was identified in early laboratory research in transplantation, and characterizing rejection pathologically led to several important insights into transplantation. In this way, pathology played a role similar to pharmacology, as the identification and development of immunosuppressant drugs helped show exactly what was needed for transplantation to be a success. However, from the pathology standpoint, transplantation isn't a "natural" condition like cancer--it has similarities to autoimmunity, but pathologists had to identify and diagnose rejection and other problems with transplanted organs only after surgeons and other clinicians began transplanting organs. Even if the role of pathologists wasn't thought of initially, they willingly came along for the ride, and certainly got to work in developing the field.

Transplant pathology is fairly standardized, and much of this standardization started from the Banff conferences. These began as meetings to reach a consensus on what characterized kidney transplant rejection, later weaving in the NIH-CCTT (Cooperative Clinical Trials in Transplantation) guidelines, and expanding to describe rejection of the pancreas and liver. The ISHLT (International Society of Heart and Lung Transplantation) took a similar lead in characterizing heart and lung transplant rejection. Having these standards is invaluable for the transplant world to communicate clearly about rejection (diagnosing and treating it) when many individuals may focus more on an organ or organ system rather than transplantation itself. Many of these standards, and all sorts of other information, can be found at the TPIS (Transplant Pathology Internet Services) site.

It hasn't stopped there, though. One purpose of making the early systems was to have a standard way to describe rejection for clinical studies, but thanks to these clinical studies, serious acute rejection and graft loss aren't nearly as common as it once was. So pathologists have worked on developing new ways of characterizing rejection and organ function to serve as "surrogate endpoints" to identify more subtle issues in transplant function. These have successively incorporated the latest techniques in biology, such as cytokine profiles, DNA microarrays, and genomics and proteomics. They have also helped describe problems such as acute humoral rejection (by C4d staining) and infections (such as BK virus) that wouldn't be nearly as well-understood without pathology input.

My biopsy turned out fine--recovered quickly, got the results, no huge surprises, a few changes in treatment, but still some unanswered questions. For now, transplant pathology can recede in my mind, but I'm sure the field will continue to develop and will be there the next time I need them.

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