by Christos Evangelou, MSc, PhD – Medical Writer and Editor

In a recent multicenter study, researchers at the University of California Davis demonstrated that pathologists can make accurate diagnoses using digital slides viewed either locally or remotely, matching the reliability of traditional microscope-based methods. This large-scale study validates the Aperio GT 450 DX system for both local and remote digital pathology diagnosis and could improve access to expert diagnostic services.

“This study and the study data for FDA approval submission are the first to validate remote viewing for primary pathology diagnosis,”

explained Alexander D. Borowsky, Professor of Pathology and Laboratory Medicine at the University of California Davis School of Medicine and the study’s lead author.

“The research represents a crucial step forward as healthcare systems increasingly adopt digital pathology solutions.”

The report was published in Archives of Pathology & Laboratory Medicine.

Study Rationale

The adoption of digital pathology has accelerated since the COVID-19 pandemic, with the US Food and Drug Administration (FDA) granting regulatory exceptions in March 2020 to allow remote viewing of digital slides. Although several digital pathology systems have received FDA clearance, questions remain about the reliability of remote diagnosis using digital slides compared to traditional microscopy.

Led by Dr. Borowsky, the research team sought to evaluate whether diagnoses made using the Aperio GT 450 DX system, both locally and remotely, were comparable to those made using conventional light microscopy. This question has become increasingly important as healthcare systems look to implement more flexible and efficient diagnostic workflows and address geographic disparities in access to pathology expertise.

Study Design

The researchers conducted a large-scale, multicenter study involving three clinical sites: Intermountain Healthcare in Salt Lake City, University of California Davis in Sacramento, and TriCore Reference Laboratories in Albuquerque. The study included 1,152 cases spanning 20 different organ types.

“The study design included intentional overrepresentation of difficult cases, or cases that fall in the middle of a continuous spectrum of morphologic changes,” Dr. Borowsky noted. “For example, biopsies of the bladder included equal numbers of inflammatory, dysplasia, carcinoma in situ, and invasive carcinoma. Distinguishing dysplasia from carcinoma in situ is particularly nuanced and prone to subjective reader training and preference bias.”

Ten reading pathologists across the three sites reviewed digital slides either locally (connected directly to the image server) or remotely (via internet connection). Each pathologist’s diagnosis was evaluated by a separate team of three adjudication pathologists who compared the results to the original reference diagnosis. The study design incorporated several features to ensure reliability, including random assignment of cases for local or remote viewing, a washout period of more than three years from previous exposure to the cases, multiple organ types, and quality checks at multiple stages of the scanning process.

Diagnostic Accuracy

The study demonstrated that diagnoses made using digital pathology were statistically noninferior to those made using traditional microscopy. The difference in major discrepancy rates between digital and microscope-based diagnosis was 2.40% (95% confidence interval [CI], 1.40%–3.39%), which was within the predefined acceptance criterion of 4% or less. Notably, the digital pathology system performed slightly better in remote viewing than in local viewing, with major discrepancy rates of 5.51% (95% CI, 4.40%–6.88%) and 6.13% (95% CI, 4.99%–7.51%), respectively.

Bladder tissue proved to be the most challenging across both modalities, with discrepancy rates of 14.79% for digital pathology and 12.87% for traditional microscopy. However, digital pathology showed particular strength in several tissue types, including brain, liver, bladder, gynecologic, gastroesophageal, and stomach cases, sometimes outperforming traditional microscopy.

According to Dr. Borowsky, the validation of the Aperio GT 450 DX system for remote digital pathology has significant implications for clinical practice, particularly in addressing workforce shortages and improving access to specialized expertise.

“With a significant national shortage of qualified pathologists in the US and the world, digital pathology promises to enable improved pathology diagnostic efficiency and quality,” Dr. Borowsky said. “Rather than trying to staff every site with qualified pathologists and pathologists with special expertise in specific disease categories, the digital assignment of cases to remote pathologists with the appropriate expertise enables high quality, allows pathologists to practice within their areas of expertise, and facilitates rapid consultative review of difficult cases.”

Diagnostic Efficiency

The system showed a relatively low rescanning rate of 3.1%. Network latency for remote viewing averaged between 23.1 and 35.9 milliseconds across sites, enabling smooth operation of the system. The median time required to review cases was similar for local (3 minutes 11 seconds) and remote (3 minutes 19 seconds) viewing, suggesting that remote diagnosis does not compromise efficiency.

“With the addition of computer-aided tools superimposed on the digital images, pathologists can spend more time assessing all of the data available to provide an accurate diagnosis,” Dr. Borowsky noted. “They can also spend less time doing more time-consuming and arduous activities, which are better achieved with computer image analysis and supervised by the pathologist, such as counting mitotic figures.”

Dr. Borowsky emphasized that the learning curve for digital pathology is an important consideration:

“Most pathologists today, including those who participated in this study, were trained using manual slide review/reading of glass slides at an upright light microscope. Although they adapted to WSI digital reads viewed on the computer monitor very well, I anticipate that this will only improve over time as pathologists become more familiar and experienced with the WSI digital reads.”

Looking Ahead

Dr. Borowsky pointed out that regulatory hurdles still exist:

“Although this study documents the non-inferiority of remote WSI reading for primary diagnosis, and although this was approved by the FDA, regulatory guidelines still do not permit WSI reading except in CLIA-regulated and approved buildings. Apparently, a broom closet in a CLIA-certified building is okay, but a well-appointed office space at home or in another building that is not CLIA-certified is not permitted.”

The digital workflow allows pathologists to access computer image analysis tools and reporting tools that promise increased efficiency with increased quality. As Dr. Borowsky concluded, the potential of digital pathology systems will likely continue to grow as pathologists become more experienced with digital tools and regulatory frameworks evolve to accommodate remote diagnosis.

The study received financial support from Leica Biosystems Imaging, Inc.

References

1. Borowsky AD, Miller DV, Bauer TW, et al. A Multicenter Study to Evaluate Diagnostic Accuracy by Pathologists Using the Aperio GT 450 DX in Local and Remote Viewing Stations. Arch Pathol Lab Med. Published online February 13, 2025. doi:10.5858/arpa.2024-0204-OA