February 23, 2020Isis Ricaño-Ponce, PhD
The microscope has always been a critical instrument for pathologists. Every specimen arriving at the pathology department has to be fixed, sliced into very thin layers, and placed on a glass slide. Indeed, examination of glass slides under the microscope remains the gold standard for primary diagnosis. However, the growing sub-field of digital pathology does not rely on conventional microscopes. Rather, digital pathology makes use of digital technology to speed up and enhance workflows in a pathology lab. Although examination of glass slides under the microscope remains the gold standard for primary diagnosis to this day, digital pathology is making inroads to becoming accepted as equally good or better than regular microscopy for diagnostic purposes in terms of accuracy and efficiency.1
What is digital pathology?
Digital pathology employs whole slide imaging (WSI), in which slides are prepared and stained in the same way as in conventional microscopy, but instead of examining the slide with a microscope, the slide is scanned and visualized on a computer screen. The user can navigate the tissue and annotate any findings using software. The digitization of pathology slides through WSI represents a major step toward quantitative assessment in pathology that avoids human bias and enables the precise and reproducible extraction of data from slides. But digital pathology is more than simply scanning glass slides; it refers to the whole workflow from obtaining the slides to scanning them, managing, storing, and sharing data, and interpreting results.
What are the advantages of digital pathology?
One of the main advantages of digital pathology is that it saves time. Digital pathology reduces the need to manually perform certain tedious everyday processes like sifting through boxes for glass slides, setting up the microscope to match previous settings, and searching for a specific spot on the slide. Automated image analysis is especially efficient compared to manual cell counting; one study found that hand counting of tumor cells took an estimated 100 hours per slide compared to three minutes using automated image analysis.2
Environmental factors can degrade tissue mounted on slides over time. Slides are also prone to breakage, misplacement, or mislabeling, and they take up physical space. Digital slide archives maintain the quality of the slide image over time and provide long-term storage solutions so that only tissue blocks need to be physically stored.
The digitization of histology slides allows them to be accessed anywhere by anyone. Specialists around the world can be sent digital slides in minutes and examine the entire slide instead of relying on the sender to choose a representative section. Access to digitized slides also allows for long-term predictive analysis. The ability to compare the same sample with different dyes or at different time points has the potential to revolutionize disease prognosis.
FDA Approval of Whole Slide Imaging: A Major Step Forward for the Clinical Lab
In 2017, the United States Food and Drug Administration (FDA) approved the first WSI scanner for primary diagnosis in surgical pathology. The scanners are defined as Class III medical devices, and the FDA regulates these instruments to help ensure that images being analyzed for clinical use are safe and effective for their defined purpose.
Before approval was conferred, the whole slide imager was thoroughly validated to show that it produced results comparable to conventional microscopy. Many studies have investigated whether there is a difference in diagnosis when pathologists use conventional microscopy versus WSI. These studies have shown high concordance rates among these two imaging types; however, study participants found that WSI was too slow for routine use when examining slides and that digital images were more difficult to evaluate than were glass slides.
What are the challenges of digital pathology?
Transitioning to a digital pathology system in the clinical lab can be a challenging process in the beginning. Some pathologists are reluctant to make the switch to digital pathology because they feel more confident using light microscopy. Others are resistant to adopting digital pathology due to misinformation about it. For example, although whole slide imaging was initially not as accurate as regular microscopy, studies have shown that it now gives comparable,3 or even superior,1 results, yet some pathologists still believe regular microscopy is more accurate. Fortunately, the teaching of digital pathology in medical school is getting new generations of pathologists familiar with its many advantages.
Digital pathology might still be more time consuming than light microscopy in specific cases. For instance, different magnifications are needed to detect some microorganisms, and changing magnifications might slow down the process. Moreover, digital pathology can produce vast numbers of images that are time-consuming to analyze. To speed up the process, certain algorithms offer steps to follow to screen for abnormalities.4
Digital pathology has shown to be less accurate than regular microscopy in a few circumstances, such as identification and grading of dysplasia, identification of granulocytes, nucleated red blood cells, and amyloid, and locating small diagnostic objects or features such as focal inflammation.5 In these cases, visual inspection of glass slides should be mandatory.
Additionally, it can be difficult to observe features of three-dimensional cell groups and cells across multiple focal planes via digital pathology. Although improvements have been made in stacking multiple images to create 3D structural images, such images become extremely large, requiring better and cheaper storage options.
What can we expect from digital pathology in the near future?
One of the main promises of digital pathology is computer-aided diagnosis. Virtual microscopy generates hundreds of images from the same tissue that can be analyzed simultaneously. With thousands of annotated images from different samples and tissues, computers can be trained to recognize the regular features in a tissue as well as abnormalities. Although computer-aided diagnosis has become a reality, it is not yet commonly use in clinical labs, but its use will only increase in the next few years. Digital pathology is also a step forward for personalized medicine, as it allows the integration of imaging with radiologic, genomics, and proteomics data for better prognosis and predictive outputs.
It is unlikely that digital pathology will completely replace the full diagnostic capabilities of a pathologist in the short term, but this technology is now a useful clinical diagnostic tool that might lead to a change in the role of the pathologist in the clinical lab, speeding up the pathology department.
1. Van Es Simone L. “Digital pathology: semper ad meliora.” Patología. 51.1 (2019): 1-10.
2. Hamilton, Peter W., et al. “Automated tumor analysis for molecular profiling in lung cancer.” Oncotarget 6.29 (2015): 27938.-52.
3. Williams, Bethany J., et al. “A systematic analysis of discordant diagnoses in digital pathology compared with light microscopy.” Archives of Pathology & Laboratory Medicine 141.12 (2017): 1712-1718.
4. Cheng, Chee Leong, et al. “Enabling digital pathology in the diagnostic setting: Navigating through the implementation journey in an academic medical centre.” Journal of Clinical Pathology 69.9 (2016): 784-792.
5. Qi, Xin, et al. “Content-based histopathology image retrieval using CometCloud.” BMC Bioinformatics 15.1 (2014): 287.