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Epithelial to Mesenchymal Transition in Endomyocardial Biopsies from Orthotopic Heart Transplant Recipients

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Introduction Heart transplant patients are at high risk of organ rejection and require close monitoring with frequent endomyocardial biopsies (EMB), especially during their first post-transplant year. We encountered a hypercellular,… Click to show full abstract

Introduction Heart transplant patients are at high risk of organ rejection and require close monitoring with frequent endomyocardial biopsies (EMB), especially during their first post-transplant year. We encountered a hypercellular, atypical endocardial lesion composed of enlarged, pleomorphic cells in a 54-year-old male heart transplant recipient 7.5 months post-transplantation. Our initial impression was post-transplant lymphoproliferative disorder or malignancy. We later identified two additional cases with similar histopathologic findings and hypothesized that these were actually reactive changes or so called epithelial-mesenchymal transition (EMT). EMTs have not been previously reported in EMB from heart transplant recipients and we identified 3 cases in less than a one year time period. Methods For these 3 cases, we further evaluated their clinical history and analyzed the EMB with additional immunostains (CD3, CD68, CD20, PAX-5, Kappa, Lambda, WT1, CK AE1/3, CD34, adenovirus, and EBV) to determine the etiology of the lesions. Right heart EMB are conducted at our institution weekly for the first 8 weeks and then every 3 months thereafter. Results All 3 patients had undergone orthotopic heart transplant replacement 2-7 months prior to having the EMB in which the lesions were observed and received similar induction and immune suppression regimens (MMF and tacrolimus). The IHC stains showed that the atypical-appearing cells were forming a new layer on the endocardial surface and were transitioning from epithelial-like (AE1/3+) to mesenchymal-like (CD34+), and were thus undergoing EMT. Underlying this reactive process was mixed inflammation including macrophages and scattered aggregates of CD3+ T cells; there was no evidence of a lymphoproliferative disorder and EBV was negative. All 3 patients had similar EM findings. Their subsequent biopsies showed similar lesions, although slightly less cellular, with increased fibrosis. Graft function remained normal in all patients. Conclusion The presence of atypical appearing cells on EMB can raise suspicion for rejection or post-transplant lymphoproliferative disorder; however, this appears to often be a reparative process, namely EMT. Similar to reports in kidney transplant patients on tacrolimus, EMT does not seem to play a role in the development of allograft rejection. Due to our small sample size, further investigation is needed.

Keywords: mesenchymal transition; endomyocardial biopsies; heart; transplant; heart transplant; epithelial mesenchymal

Journal Title: Journal of Cardiac Failure
Year Published: 2018

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