A Randomized Study Comparing Digital Imaging to Traditional Glass Slide Microscopy for Breast Biopsy and Cancer Diagnosis

Abstract

Background:Digital whole slide imaging may be useful for obtaining second opinions and is used in many countries. However, the U.S. Food and Drug Administration requires verification studies.Methods:Pathologists were randomized to interpret one of four sets of breast biopsy cases during two phases, separated by ≥9 months, using glass slides or digital format (sixty cases per set, one slide per case, n = 240 cases). Accuracy was assessed by comparing interpretations to a consensus reference standard. Intraobserver reproducibility was assessed by comparing the agreement of interpretations on the same cases between two phases. Estimated probabilities of confirmation by a reference panel (i.e., predictive values) were obtained by incorporating data on the population prevalence of diagnoses.Results:Sixty-five percent of responding pathologists were eligible, and 252 consented to randomization; 208 completed Phase I (115 glass, 93 digital); and 172 completed Phase II (86 glass, 86 digital). Accuracy was slightly higher using glass compared to digital format and varied by category: invasive carcinoma, 96% versus 93% (P = 0.04); ductal carcinoma in situ (DCIS), 84% versus 79% (P < 0.01); atypia, 48% versus 43% (P = 0.08); and benign without atypia, 87% versus 82% (P < 0.01). There was a small decrease in intraobserver agreement when the format changed compared to when glass slides were used in both phases (P = 0.08). Predictive values for confirmation by a reference panel using glass versus digital were: invasive carcinoma, 98% and 97% (not significant [NS]); DCIS, 70% and 57% (P = 0.007); atypia, 38% and 28% (P = 0.002); and benign without atypia, 97% and 96% (NS).Conclusions:In this large randomized study, digital format interpretations were similar to glass slide interpretations of benign and invasive cancer cases. However, cases in the middle of the spectrum, where more inherent variability exists, may be more problematic in digital format. Future studies evaluating the effect these findings exert on clinical practice and patient outcomes are required.

Accuracy is in the eyes of the pathologist: The visual interpretive process and diagnostic accuracy with digital whole slide images

“…It is worth noting that variation in the number of ROIs across cases was not correlated with reference case difficulty. Furthermore, expert interpretations of these 24 cases were highly concordant (21/24 cases) between the digital and glass versions (for a more in depth examination of this issue, see 36 ).…”

Diagnostic Reproducibility: What Happens When the Same Pathologist Interprets the Same Breast Biopsy Specimen at Two Points in Time?

“…Our previous studies found that accuracy was slightly higher when pathologists used glass slides, as the current study did, compared to digital whole slide imaging (WSI), an emerging technology for pathology interpretation. 18,23 Although currently understudied, intra-observer variability also has the potential to be greater using WSI.…”

A validation study of whole slide imaging for primary diagnosis of lymphoma

“…Whole slide imaging (WSI), also known as virtual microscopy, is the transformation of glass slides of the tissue section to digital images by WSI scanners which are run with computer workstations and specific software . WSI has various pragmatic uses such as diagnosis, education, research, and telepathology consultation .…”

“…Another dynamic use of WSI results in promotion of the workflow by avoiding the extra‐work of slide allocation . The swift increase of improvements in this field and their various advantages may lead to a change from light microscopy to digital pathology for routine pathological diagnosis . At present there are many WSI scanners, related workstations and specific software available that are capable of performing good quality digitalization …”