Renal Allograft Biopsy Inflammatory Cell Quantitation Using Image Analysis Algorithms: Correlation with Pathologist Assessment and Rejection Severity
Geoffrey H Smith, Jun Kong, Alton B Farris. Emory University, Atlanta, GA
Background: Pathologists and clinicians often rely on assessment of inflammatory cell infiltrates in renal allograft biopsies when diagnosing rejection and grading the rejection process. Slight histologic variations can make big differences in the subsequent treatment course for patients. However, prior studies have shown limited reproducibility in such evaluations. We tested the utility of immunohistochemistry (IHC) image analysis in assisting with these designations.
Design: Whole slide images were obtained in a cohort of 58 renal biopsies containing allograft rejection, a borderline pattern, polyomavirus nephritis, normal donor tissue, and stable allografts for a variety of stains. CD3 stains were quantitated using a positive nuclear IHC algorithm tuned to detect CD3+ cells (Fig 1). The CD3+ cell density was compared with (a) pathologist assessment of percent inflammatory cell infiltrate on routine slides, (b) diagnosis, and (c) other parameters such as creatinine.
Fig 1. (a) IHC stained CD3+ inflammatory cells in the renal interstitium are brown. (b) Image analysis algorithm detects and quantitates CD3+ cells (red) and CD3- cells (blue).
Results: By linear correlation, the computed CD3+ cell density (# of CD3+ cells/mm2) showed a direct correlation with the pathologist assessment of percent inflammatory infiltrate (R2=0.48, P<0.0001) and with creatinine (R2=0.50, P=0.0022) (Fig 2). Considering cases with acute cellular rejection (ACR), CD3+ cell density increased from borderline (531), to ACR1A (673), to ACR1B (1,336).
Fig 2. (a) CD3+ cell density versus pathologist assessment of percent inflammatory infiltrate (%i). (b) CD3+ cell density versus creatinine.
Conclusions: The cell counting algorithm showed correlations with the pathologist assessment of inflammatory infiltrate as well as creatinine, suggesting its promise in assessing renal allograft biopsies, analogous to flow cytometry on a slide.
Category: Kidney (does not include tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 254, Monday Morning