Utilizing Whole Slide Images for Pathology Peer Review and Working Groups

Abstract

This article describes the results of comparisons of digitally scanned whole slide images (WSIs) and glass microscope slides for diagnosis of tissues under peer review by the National Toxicology Program. Findings in this article were developed as a result of the data collected from 6 pathology working groups (PWGs), 1 pathology peer review, and survey comments from over 25 participating pathologists. For each PWG, 6-14 pathologists examined 10-143 tissues per study from 6-and 9-month perinatal studies and 2-year carcinogenicity studies. Overall it was found that evaluation of WSIs is generally equivalent to using glass slides. Concordance of PWG consensus diagnoses based upon review of WSIs versus glass slides ranged from 74% to 100% (median 86%). The intra-and interobserver diagnostic variation did not appear to influence the conclusions of any study. Based upon user opinions collected from surveys, WSIs may be less optimal than glass slides for evaluation of subtle lesions, large complex lesions, small lesions in a large section of tissue, and foci of altered hepatocytes. These results indicate that, although there may be some limitations, the use of WSIs can effectively accomplish the objectives of a conventional glass slide review and definitely serves as a useful adjunct to the conduct of PWGs.

Digital Whole Slide Imaging Compared With Light Microscopy for Primary Diagnosis in Surgical Pathology

“…Methods and technologies to convert glass slides into digital whole slide images (WSI) that can be viewed on digital monitors over a similar range of magnifications have been tested for utility in a variety of applications. [2][3][4][5] Previous studies have compared pathologists' use of WSI with microscopy for primary diagnosis in surgical pathology. [6][7][8][9][10] Some studies tested a relatively small number of cases, others have had relatively short ''washout'' times between interpretations, some have been limited to a specific tissue type/organ, and only a few have compared diagnoses of each modality with a reference diagnosis.…”

Toxicologic Pathology Forum*: Opinion on Considerations for the Use of Whole Slide Images in GLP Pathology Peer Review

“…For WSI to be more widely accepted in the regulatory space, it may require a reevaluation of WSI versus glass slides using optimal image viewing hardware and software. Many of the issues encountered by Malarkey et al (2015) related to the time taken for images to render (static and when scrolled). With the use of high refresh rate monitors, adequate graphics cards, and images stored on local caches, seamless rendering of images is now possible (personal observation).…”

“…Due to the large file sizes of WSI, there are also logistical implications for securely handling the large volume of data that would result. There is also a level of concern among some pathologists that WSI may be less optimal than glass slides for the evaluation of subtle lesions as outlined by Malarkey et al (2015). The acceptance of WSI for use in GLP peer review should be the logical first step toward the potential adoption of WSI in the routine evaluation of pathology from regulatory toxicology studies.…”

“…This article was focused on the technical aspects relating to the validation of a digital pathology system in the nonclinical environment rather than its context of use. While Malarkey et al (2015) undertook a comparison of the use of WSI versus glass slides for reviewing histopathology findings in rodent studies run at the U.S. National Toxicology Program, their paper concentrated on the level of “diagnostic agreement” between the two approaches and did not provide details concerning any validation of the methodology employed (slide scanner, viewing software, etc.). The current article aims to provide an overview of the main considerations for the use of WSI for GLP pathology peer review based on AstraZeneca’s extensive use of WSI for pathology peer review of non-GLP studies run at Charles River Laboratories facilities and discussions with individuals experienced in quality assurance and GLP compliance.…”

The Application, Challenges, and Advancement Toward Regulatory Acceptance of Digital Toxicologic Pathology: Results of the 7th ESTP International Expert Workshop (September 20-21, 2019)

“…Proof of noninferiority is currently conceived as an empirical assessment based on a specific configuration of hardware and software. Since few examples of this type of qualification have been published, it is advisable to consult current recommendations 5,6 before undertaking the qualification to ensure that the test adequately establishes the sensitivity and specificity of the comparison.…”