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

Abstract

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.

Mitotic Figures—Normal, Atypical, and Imposters: A Guide to Identification

“…Most studies comparing LM and WSI obtained MC using 400Â magnification images (image resolution: 0.25 mm/pixel). 3,13,32,64 For MCs obtained from canine melanomas, WSI at 400Â or 200Â magnification had similar inter-and intraobserver concordance with one another and with LM. 64 Based on published information as well as personal experiences among the authors, diagnostic evaluation and MC can be readily performed with WSI.…”

“…There is generally good agreement between WSI and light microscopy (LM) with regard to cytologic and histologic diagnosis and MC in animal and human tumors. 2,3,13,16,18,29,32,48,53,64 A better correlation was observed in cases with higher MCs as compared to those with lower MCs. 3 Some studies reported a trend toward underestimating the MC with WSI as compared to LM and attributed this to difficulty of identifying MF via WSI.…”

“…Although multiple focal planes ( z axis) can be captured to simulate fine focusing, and high scanning magnification is technically possible, the scan time and storage space required is impractical in the current typical diagnostic setting. 3,11,13,14,54,61,64…”

Ureteral location is associated with survival outcomes in upper tract urothelial carcinoma: A population‐based analysis

“…Notably, a central pathologist revision of cases was not available, so the accuracy of histological diagnosis could be biased. 27 Also, SEER classified UTUC with grading from I to IV, whereas the most recent WHO classification and current guidelines classify low-grade and high-grade tumors. 28 Another limitation is the absence of information regarding further treatment.…”

“…Indeed, the presence of preoperative hydronephrosis 21 or inflammation, 22 the impact of preoperative and postoperative ureteroscopy, 23,24 and tumor architecture 25,26 are all factors that could be associated with prognosis, but we were not able to account for them. Notably, a central pathologist revision of cases was not available, so the accuracy of histological diagnosis could be biased 27 . Also, SEER classified UTUC with grading from I to IV, whereas the most recent WHO classification and current guidelines classify low‐grade and high‐grade tumors 28 .…”