Am J Transplant. 2020 May;20(5):1341-1350. doi: 10.1111/ajt.15752. Epub 2020 Jan 23.
Katelynn Madill-Thomsen 1 , Agnieszka Perkowska-Ptasińska 2 , Georg A Böhmig 3 , Farsad Eskandary 3 , Gunilla Einecke 4 , Gaurav Gupta 5 , Philip F Halloran 1 6 , MMDx-Kidney Study Group
1 Department of Medicine, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada.
4 Department of Nephrology, Medizinische Hochschule Hannover, Hannover, Germany.
5 Division of Nephrology, Virginia Commonwealth University, Richmond, Virginia.
6 Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada.
Discrepancy analysis comparing two diagnostic platforms offers potential insights into both without assuming either is always correct. Having optimized the Molecular Microscope Diagnostic System (MMDx) in renal transplant biopsies, we studied discrepancies within MMDx (reports and sign-out comments) and between MMDx and histology. Interpathologist discrepancies have been documented previously and were not assessed. Discrepancy cases were classified as "clear" (eg, antibody-mediated rejection [ABMR] vs T cell-mediated rejection [TCMR]), "boundary" (eg, ABMR vs possible ABMR), or "mixed" (eg, Mixed vs ABMR). MMDx report scores showed 99% correlations; sign-out interpretations showed 7% variation between observers, all located around boundaries. Histology disagreed with MMDx in 37% of biopsies, including 315 clear discrepancies, all with implications for therapy. Discrepancies were distributed widely in all histology diagnoses but increased in some scenarios; for example, histology TCMR contained 14% MMDx ABMR and 20% MMDx no rejection. MMDx usually gave unambiguous diagnoses in cases with ambiguous histology, for example, borderline and transplant glomerulopathy. Histology lesions or features associated with more frequent discrepancies (eg, tubulitis, arteritis, and polyomavirus nephropathy) were not associated with increased MMDx uncertainty, indicating that MMDx can clarify biopsies with histologic ambiguity. The patterns of histology-MMDx discrepancies highlight specific histology diagnoses in which MMDx assessment should be considered for guiding therapy.
Keywords: basic (laboratory) research/science; biopsy; kidney transplantation/nephrology; microarray/gene array; molecular biology; rejection.