Agreement in Histological Assessment of Mitotic Activity Between Microscopy and Digital Whole Slide Images Informs Conversion for Clinical Diagnosis

Bih-Rong Wei PhD; Charles H. Halsey DVM, PhD; Shelley B. Hoover BS; Munish Puri PhD; Howard H. Yang PhD; Brandon D. Gallas PhD; Maxwell P. Lee PhD; Weijie Chen PhD; Amy C. Durham MS, VMD; Jennifer E. Dwyer MS; Melissa D. Sánchez VMD, PhD; Ryan P. Traslavina DVM; Chad Frank MS, DVM; Charles Bradley VMD; Lawrence D. McGill DVM, PhD; D. Glen Esplin DVM, PhD; Paula A. Schaffer DVM, MS; Sarah D. Cramer DVM, PhD; L. Tiffany Lyle DVM, PhD; Jessica Beck DVM; Elizabeth Buza DVM; Qi Gong MS; Stephen M. Hewitt MD, PhD; R. Mark Simpson DVM, PhD

doi:10.1177/2374289519859841

Academic Pathology (Jul 2019)

Agreement in Histological Assessment of Mitotic Activity Between Microscopy and Digital Whole Slide Images Informs Conversion for Clinical Diagnosis

Bih-Rong Wei PhD,
Charles H. Halsey DVM, PhD,
Shelley B. Hoover BS,
Munish Puri PhD,
Howard H. Yang PhD,
Brandon D. Gallas PhD,
Maxwell P. Lee PhD,
Weijie Chen PhD,
Amy C. Durham MS, VMD,
Jennifer E. Dwyer MS,
Melissa D. Sánchez VMD, PhD,
Ryan P. Traslavina DVM,
Chad Frank MS, DVM,
Charles Bradley VMD,
Lawrence D. McGill DVM, PhD,
D. Glen Esplin DVM, PhD,
Paula A. Schaffer DVM, MS,
Sarah D. Cramer DVM, PhD,
L. Tiffany Lyle DVM, PhD,
Jessica Beck DVM,
Elizabeth Buza DVM,
Qi Gong MS,
Stephen M. Hewitt MD, PhD,
R. Mark Simpson DVM, PhD

Affiliations

Bih-Rong Wei PhD: Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA
Charles H. Halsey DVM, PhD: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Shelley B. Hoover BS: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Munish Puri PhD: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Howard H. Yang PhD: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Brandon D. Gallas PhD: Division of Imaging, Diagnostics, and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA
Maxwell P. Lee PhD: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Weijie Chen PhD: Division of Imaging, Diagnostics, and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA
Amy C. Durham MS, VMD: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA
Jennifer E. Dwyer MS: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Melissa D. Sánchez VMD, PhD: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA
Ryan P. Traslavina DVM: Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Chad Frank MS, DVM: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA
Charles Bradley VMD: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA
Lawrence D. McGill DVM, PhD: Animal Reference Pathology, Salt Lake City, UT, USA
D. Glen Esplin DVM, PhD: Animal Reference Pathology, Salt Lake City, UT, USA
Paula A. Schaffer DVM, MS: Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA
Sarah D. Cramer DVM, PhD: Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
L. Tiffany Lyle DVM, PhD: Women’s Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Jessica Beck DVM: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Elizabeth Buza DVM: Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA
Qi Gong MS: Division of Imaging, Diagnostics, and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, USA
Stephen M. Hewitt MD, PhD: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
R. Mark Simpson DVM, PhD: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

DOI: https://doi.org/10.1177/2374289519859841
Journal volume & issue: Vol. 6

Abstract

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Validating digital pathology as substitute for conventional microscopy in diagnosis remains a priority to assure effectiveness. Intermodality concordance studies typically focus on achieving the same diagnosis by digital display of whole slide images and conventional microscopy. Assessment of discrete histological features in whole slide images, such as mitotic figures, has not been thoroughly evaluated in diagnostic practice. To further gauge the interchangeability of conventional microscopy with digital display for primary diagnosis, 12 pathologists examined 113 canine naturally occurring mucosal melanomas exhibiting a wide range of mitotic activity. Design reflected diverse diagnostic settings and investigated independent location, interpretation, and enumeration of mitotic figures. Intermodality agreement was assessed employing conventional microscopy (CM40×), and whole slide image specimens scanned at 20× (WSI20×) and at 40× (WSI40×) objective magnifications. An aggregate 1647 mitotic figure count observations were available from conventional microscopy and whole slide images for comparison. The intraobserver concordance rate of paired observations was 0.785 to 0.801; interobserver rate was 0.784 to 0.794. Correlation coefficients between the 2 digital modes, and as compared to conventional microscopy, were similar and suggest noninferiority among modalities, including whole slide image acquired at lower 20× resolution. As mitotic figure counts serve for prognostic grading of several tumor types, including melanoma, 6 of 8 pathologists retrospectively predicted survival prognosis using whole slide images, compared to 9 of 10 by conventional microscopy, a first evaluation of whole slide image for mitotic figure prognostic grading. This study demonstrated agreement of replicate reads obtained across conventional microscopy and whole slide images. Hence, quantifying mitotic figures served as surrogate histological feature with which to further credential the interchangeability of whole slide images for primary diagnosis.

Published in Academic Pathology

ISSN: 2374-2895 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Pathology
Website: https://www.sciencedirect.com/journal/academic-pathology

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