Validation of Whole Slide Imaging for Primary Diagnosis in Surgical Pathology

Abstract

High-resolution scanning technology provides an opportunity for pathologists to make diagnoses directly from whole slide images (WSIs), but few studies have attempted to validate the diagnoses so obtained. To compare WSI versus microscope slide diagnoses of previously interpreted cases after a 1-year delayed re-review ("wash-out") period. An a priori power study estimated that 450 cases might be needed to demonstrate noninferiority, based on a null hypothesis: "The true difference in major discrepancies between WSI and microscope slide review is greater than 4%." Slides of consecutive cases interpreted by 2 pathologists 1 year prior were retrieved from files, and alternate cases were scanned at original magnification of ×20. Each pathologist reviewed his or her cases using either a microscope or imaging application. Independent pathologists identified and classified discrepancies; an independent statistician calculated major and minor discrepancy rates for both WSI and microscope slide review of the previously interpreted cases. The 607 cases reviewed reflected the subspecialty interests of the 2 pathologists. Study limitations include the lack of cytopathology, hematopathology, or lymphoid cases; the case mix was not enriched with difficult cases; and both pathologists had interpreted several hundred WSI cases before the study to minimize the learning curve. The major and minor discrepancy rates for WSI were 1.65% and 2.31%, whereas rates for microscope slide reviews were 0.99% and 4.93%. Based on our assumptions and study design, diagnostic review by WSI was not inferior to microscope slide review (P < .001).