Visual Assessment of 2-Dimensional Levels Within 3-Dimensional Pathology Data Sets of Prostate Needle Biopsies Reveals Substantial Spatial Heterogeneity

Can Koyuncu; Andrew Janowczyk; Xavier Farre; Tilak Pathak; Tuomas Mirtti; Pedro L Fernandez; Laura Pons; Nicholas P Reder; Robert Serafin; Sarah S L Chow; Vidya S Viswanathan; Adam K Glaser; Lawrence D True; Jonathan T C Liu; Anant Madabhushi

doi:10.1016/j.labinv.2023.100265

Visual Assessment of 2-Dimensional Levels Within 3-Dimensional Pathology Data Sets of Prostate Needle Biopsies Reveals Substantial Spatial Heterogeneity

Lab Invest. 2023 Dec;103(12):100265. doi: 10.1016/j.labinv.2023.100265. Epub 2023 Oct 18.

Authors

Affiliations

¹ Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia.
² Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia; Department of Oncology, Division of Precision Oncology, University Hospital of Geneva, Geneva, Switzerland; Department of Clinical Pathology, Division of Clinical Pathology, University Hospital of Geneva, Geneva, Switzerland.
³ Public Health Agency of Catalonia, Lleida, Catalonia, Spain.
⁴ Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia; Department of Pathology, University of Helsinki and Helsinki University, Hospital, Helsinki, Finland; Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN-Digital Precision Cancer Medicine Flagship, Helsinki, Finland.
⁵ Department of Pathology, Hospital Germans Trias i Pujol, IGTP, Universidad Autonoma de Barcelona, Barcelona, Spain.
⁶ Department of Pathology, Hospital Germans Trias i Pujol, IGTP, Barcelona, Spain.
⁷ Department of Mechanical Engineering, University of Washington, Seattle, Washington; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, Washington.
⁸ Department of Mechanical Engineering, University of Washington, Seattle, Washington.
⁹ Department of Laboratory Medicine & Pathology, University of Washington, Seattle, Washington; Department of Urology, University of Washington, Seattle, Washington.
¹⁰ Department of Mechanical Engineering, University of Washington, Seattle, Washington; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, Washington; Department of Bioengineering, University of Washington, Seattle, Washington.
¹¹ Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, Georgia; Atlanta VA Medical Center, Atlanta, Georgia. Electronic address: anantm@emory.edu.

Abstract

Prostate cancer prognostication largely relies on visual assessment of a few thinly sectioned biopsy specimens under a microscope to assign a Gleason grade group (GG). Unfortunately, the assigned GG is not always associated with a patient's outcome in part because of the limited sampling of spatially heterogeneous tumors achieved by 2-dimensional histopathology. In this study, open-top light-sheet microscopy was used to obtain 3-dimensional pathology data sets that were assessed by 4 human readers. Intrabiopsy variability was assessed by asking readers to perform Gleason grading of 5 different levels per biopsy for a total of 20 core needle biopsies (ie, 100 total images). Intrabiopsy variability (Cohen κ) was calculated as the worst pairwise agreement in GG between individual levels within each biopsy and found to be 0.34, 0.34, 0.38, and 0.43 for the 4 pathologists. These preliminary results reveal that even within a 1-mm-diameter needle core, GG based on 2-dimensional images can vary dramatically depending on the location within a biopsy being analyzed. We believe that morphologic assessment of whole biopsies in 3 dimension has the potential to enable more reliable and consistent tumor grading.

Keywords: 3D pathology; Gleason grading; Gleason grading variability; intrabiopsy variability; prostate cancer.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Biopsy
Biopsy, Large-Core Needle
Humans
Male
Neoplasm Grading
Prostate* / pathology
Prostatic Neoplasms* / pathology

Abstract

Publication types

MeSH terms

Grants and funding