New technology is transforming digital pathology and has the potential to enhance cancer diagnostics in several ways. These include improving the integration of data, consultation among experts, and quantitative and qualitative image analysis.
Whole slide imaging (WSI) uses computerized technology to scan and convert entire pathology glass slides into digital images at high resolution, which are then made available to pathologists. One of the most important aspects of digitization of slides is the ability to perform image analysis and computer-aided diagnostic tools on WSI. For instance, it automates everything from high-fidelity/high-throughput slide scanning to specialized pathology software for managing digitized histology slides to integrated data feeds from clinical systems around the world.
Integration
Digital pathology enables a pathologist to convert manual/analog information into digital information by integration with the laboratory information system (LIS) and by providing key data that enhances the cancer diagnosis into one unified space. Some refer to this integrated environment as a digital cockpit or pathologist cockpit.
What is the intersection between some of the traditional molecular techniques, such as FISH and karyotyping, and digital pathology? All of these techniques are image-based and can be incorporated more easily into a digital workflow. They also make it easier to share images and quantitate signals more accurately, overall improving cancer diagnostics.
Consultation
As cancer treatments become more specialized, more careful review of the slides and more molecular testing are required, in turn requiring pathologists to integrate more information from multiple sources as well as consult experts. Often, a pathologist has a very basic knowledge of molecular testing. Pathologists are increasingly turning to subspecialists now to ensure the diagnosis is correct. Sharing digital images rapidly has the power to enable these activities, which depend on rapid consultations and integration of key information to treat the cancer patient.
During the past five years, there have been significant improvements in the quality of cancer diagnosis due to ease of consultation and peer review of cases, as well as more widespread use of digital images in training and quality assurance activities by pathology labs, ASCP, and CAP. More international sites are now sending consults to U.S.-based hospitals. For example, institutions such as the Cleveland Clinic and the University of Pittsburgh Medical Center (UPMC) are now utilizing WSI to help pathologists serve patients in China.1
UPMC has recently reported on a three-year experience in international telepathology consultation.2 A total of 1,561 cases were submitted for telepathology consultation, including 144 cases in 2012, 614 cases in 2013, and 803 in 2014. Digital consults to experts led to an overall improvement in accuracy of cancer diagnostics. Data showed that from a total of 855 cases (54.7 percent) where a primary diagnosis or impression was provided by the referring local hospitals in China, the final diagnoses rendered by UPMC pathologists were identical in 25.6 percent of cases and significantly modified (treatment plan altered) in 50.8 percent of cases. In other words, more than 50 percent of the patients got the correct diagnosis due to the use of digital pathology consults. This does not include the indirect benefits gained by providing teaching and training to the Chinese pathologists by review of their most challenging cases.
Quantitative/qualitative data
When a patient is treated with a drug, digitized slides can easily compare today’s diagnosis with yesterday’s, with better access to previous images. As cancer diagnostics becomes more personalized, and we see an increase in companion diagnostics, the data driven from those tests is very objective. But, with digital pathology, we can quantify those slides and better interpret and respond to the data. It’s no longer “Is it cancer?” but “How much cancer is there?” “How big is the cancer?” “How deep is it?” “What is the stage and the grade?” With digital pathology, we have tools now that can share images and provide that information.
Immunohistochemistry (IHC) remains a routine test in the laboratory. However, up to 15 percent to 20 percent of the IHC results may be unreliable due to variability in staining as well as other limitations, including errors in interpretation. The availability of quantitative image analysis biomarker algorithms for cancers, such as breast (ki67, ER, or, HER2-neu), lung, etc., have the potential to improve the reliability and accuracy of grading and quantitating the signals. New markers, such as immune check point inhibitors like PDL1, can also be quantified using digital pathology-enabled algorithms. A number of commercial vendors have created software packages which can be implemented and validated for a specific immunostain such as ER, PR, etc. Overall, quantitative image analysis of pathology slides is becoming an important component of the diagnostic workflow, and laboratories are now starting to implement these for improvement of patient care in their daily practice.
Digital pathology equips the pathologist with qualitative tools to better stage and grade cancer, such as accurate tumor volume and the depth of the tumor’s invasion. It also provides tools to help pathological diagnosis, such as finding micomets in lymph nodes, counting mitosis, etc. There are now algorithms available that enable assessment of tumor behavior and risk of progression by looking at features such as nuclear size, color of cytoplasm, texture, or stromatolites changes to answer a prognosis-related question which then impacts therapeutic decisions.
By improving integration of data, consultation among experts, and quantitative and qualitative image analysis and data integration, digital pathology can enrich cancer diagnostics. But how much will the benefits of digital pathology cost a patient? Currently, if a pathologist uses images and image analysis tools, there is a separate billing code, 88361, for that. Other than that, there is no separate charge for using digital images for diagnostic purposes. If a case is sent for consultation, the charge is no different than glass slide consultation. Overall, the value that digital pathology brings is to provide important, cost-effective enhancements that will advance the future of cancer diagnosis and treatment.
REFERENCES
- Kaplan, K, Cleveland Clinic Laboratories announce two international digital pathology consultation services, Digital Pathology Blog, Jan. 19, 2015. http://tissuepathology.com/2015/01/19/cleveland-clinic-laboratories-announce-two-international-digital-pathology-consultation-services/#axzz4ULYGHfOP.
- Zhao, C, Parwani, A, et al, International telepathology consultation: Three years of experience between the University of Pittsburgh Medical Center and KingMed Diagnostics in China, Journal of Pathology Informatics, 2015;6:63. http://www.jpathinformatics.org/article.asp?issn=2153- 3539;year=2015;volume=6;issue=1;spage=63;epage=63
Anil V. Parwani, MD, PhD, MBA, FASCP, is a Professor of Pathology and Biomedical Informatics at The Ohio State University Wexner Medical Center, where he also serves as the Vice Chair of Anatomic Pathology as well as Director of Pathology Informatics and Digital Pathology Shared Resources. He also serves on the USCAP Education Committee and on the board of the Digital Pathology Association.
