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Enhancing the Value of Histopathological Assessment of Allograft Biopsy Monitoring

Wood-Trageser, Michelle A. PhD1; Lesniak, Andrew J.1; Demetris, Anthony J. MD1

doi: 10.1097/TP.0000000000002656

Traditional histopathological allograft biopsy evaluation provides, within hours, diagnoses, prognostic information, and mechanistic insights into disease processes. However, proponents of an array of alternative monitoring platforms, broadly classified as “invasive” or “noninvasive” depending on whether allograft tissue is needed, question the value proposition of tissue histopathology. The authors explore the pros and cons of current analytical methods relative to the value of traditional and illustrate advancements of next-generation histopathological evaluation of tissue biopsies. We describe the continuing value of traditional histopathological tissue assessment and “next-generation pathology (NGP),” broadly defined as staining/labeling techniques coupled with digital imaging and automated image analysis. Noninvasive imaging and fluid (blood and urine) analyses promote low-risk, global organ assessment, and “molecular” data output, respectively; invasive alternatives promote objective, “mechanistic” insights by creating gene lists with variably increased/decreased expression compared with steady state/baseline. Proponents of alternative approaches contrast their preferred methods with traditional histopathology and: (1) fail to cite the main value of traditional and NGP—retention of spatial and inferred temporal context available for innumerable objective analyses and (2) belie an unfamiliarity with the impact of advances in imaging and software-guided analytics on emerging histopathology practices. Illustrative NGP examples demonstrate the value of multidimensional data that preserve tissue-based spatial and temporal contexts. We outline a path forward for clinical NGP implementation where “software-assisted sign-out” will enable pathologists to conduct objective analyses that can be incorporated into their final reports and improve patient care.

1 Division of Transplant Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Received 31 August 2018. Revision received 4 January 2019.

Accepted 27 January 2019.

The authors declare no conflicts of interest.

This work was supported by Immune Tolerance Network (grant 1UM1AI109565), Clinical Trials in Organ Transplantation in Children (grants 1U01AI104336 and 4U01AI104347), National Institutes of Health/National Institute of Allergy and Infectious Diseases (grants 1U19AI131453, 4U01AI104347, and U01AI100807), National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (grant 1R01DK114180), TransMedics, UPMC Enterprises, and the Enduring Hearts Foundation.

M.A.W.T., A.J.L., and A.J.D. contributed to writing of the manuscript, supplement, and production of figures.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Correspondence: Anthony J. Demetris, MD, Division of Transplant Pathology, Department of Pathology, University of Pittsburgh School of Medicine, E741 UPMC Montefiore, 200 Lothrop St, Pittsburgh, PA 15213, USA. (

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