The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.
BACKGROUND
In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.


METHODS
We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI.


RESULTS
The number of glomeruli annotated was consistently higher than those reported (p<0.001); this difference was proportional to the number of glomeruli. In contrast, percent globally sclerotic were similar when calculated on total glomeruli, but greater in FSGS when calculated on average number of glomeruli (p<0.01). The difference in percent globally sclerotic between annotated and those recorded in pathology reports was significant when global sclerosis is greater than 40%.


CONCLUSIONS
Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli.
Department of Pathology, Children's National Medical Center, Washington, DC, United States of America.|National Institute of Digestive Diseases and Kidney, National Institutes of Health, Bethesda, MD, United States of America.
Avi Z
AZ
Rosenberg
Department of Pathology, University of Pennsylvania, Philadelphia, PA, United States of America.
Matthew
M
Palmer
Department of Pathology, University of Miami, Miami, FL, United States of America.
Lino
L
Merlino
Department of Pediatrics, Division of Pediatric Nephrology, University of Michigan, Ann Arbor, MI, United States of America.
Jonathan P
JP
Troost
Department of Pathology, University of North Carolina, Chapel Hill, NC, United States of America.
Adil
A
Gasim
Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD, United States of America.
Serena
S
Bagnasco
Department of Pathology, Toronto General Hospital, Toronto, Ontario, Canada.
Carmen
C
Avila-Casado
Department of Medicine, Section of Nephrology, Hypertension and Kidney Transplantation Temple University, Philadelphia, PA, United States of America.
Duncan
D
Johnstone
Department of Pathology, University of Michigan, Ann Arbor, MI, United States of America.
Jeffrey B
JB
Hodgin
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America.
Catherine
C
Conway
Biostatistics Department, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America.
Brenda W
BW
Gillespie
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.
Cynthia C
CC
Nast
Department of Pathology, University of Miami, Miami, FL, United States of America.
Laura
L
Barisoni
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States of America.
Stephen M
SM
Hewitt
D001706:Biopsy; D005922:Glomerulonephritis, IGA / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D015433:Glomerulonephritis, Membranous / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D005923:Glomerulosclerosis, Focal Segmental / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007678:Kidney Glomerulus / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D008853:Microscopy / Q000379:methods; D009404:Nephrotic Syndrome / Q000000981:diagnostic imaging* / Q000473:pathology / Q000601:surgery; D012815:Signal Processing, Computer-Assisted