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EDITORIAL

Convergence of Digital Pathology and


Artificial Intelligence Tools in Anatomic
Pathology Practice: Current Landscape
and Future Directions
Anil V. Parwani, MD, PhD, MBA*
and Mahul B. Amin, MD†

P athology continues to rapidly evolve as a specialty and solidify its central role in inter-
disciplinary medicine. The past decade has witnessed the impact of molecular pathology
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and precision medicine on our specialty, and this role continues to expand. The convergence of
continued advances in digital pathology, expanded cloud computing capabilities and easier
implementation of Artificial Intelligence (AI) applications to Pathology, allows us to be part of
an exciting digital revolution that will empower our role through Computational Pathology.
The advancement of information technologies during the past 2 decades has facilitated the
development, implementation, and use of novel technologies in the practice of pathology such
as next generation pathology and digital pathology.1 There have been significant technology
gains in pathology imaging (digital pathology) that have led to the adoption of innovative
digital pathology workflows enabling a streamlined digital workflow.2 One such advancement
has been whole slide imaging (WSI), which refers to “scanning” of entire glass slides to produce
a “digitized” version of the glass slide. Although first prototype was built over 20 years ago,3
WSI is now increasingly being used in pathology laboratories as an imaging modality to enable
access to the entire pathology caseload.4–7 In addition, in the last 5 years we have witnessed an
increasing use of machine learning (ML), deep learning (DL) and AI tools in diagnostic
pathology, research, industry, and education applications.8–15
Using digital pathology and AI tools, pathologists can take the driver’s seat in the
patient’s diagnostic journey. They can become the integrator and driver of the information as a
pathologist, instead of watching from the sidelines after looking at the morphology. Patholo-
gists can become the primary provider of the vital information for the care of the patient not
only in cancer but also in other fields such as renal pathology or lung pathology. They can start
to work with other clinical specialties such as radiology, genomics, and oncology and be the
central driving force of the diagnostic space.10
The value of a digital pathology workflow has become ever so relevant in the COVID-19
pandemic period. As laboratories and hospitals around the world continue to navigate the ever-
changing environment of the COVID-19 pandemic, more laboratories and pathologists are
finding themselves amidst situations, which demand providing remote services such as review of
frozen sections, fine needle aspirations, quality assurance (QA), consultations, resident training,
and primary diagnosis. A number of reasons contribute to this such as pathologists who are in
quarantine or are at increased risk due to age or underlying conditions. This has especially
important as pathologists look to additional and novel ways to train residents and fellows
during COVID-19 crisis.16 Furthermore, this approach also remains critical in assuring sub-
specialty input and back up from the right individuals in a practice/department or community
using digital pathology applications.
Even before the pandemic, a small, currently finite, but gradually increasing number of
laboratories around the globe have gone “100%” digital while WSI continues to gain traction
amongst pathologists for diagnostic, educational, and research purposes. With this digital
workflow, the quality of the images produced is of diagnostic quality and with the viewing
software, it is possible to have annotations and clinical metadata presented with the image,

From the *Department of Pathology, The Ohio State University Medical Center, Columbus, OH; and †Department of Pathology and Laboratory
Medicine, University of Tennessee Health Science Center, Memphis, TN.
A.V.P. serves on the advisory board for Contextvision and provides advice on deep learning and artificial intelligence applications in Anatomic
Pathology. M.B.A. serves on the advisory board for Ibex and is a consultant for Advanced Clinical providing consultations for artificial intelligence
applications in Anatomic Pathology for both these organizations.
Reprints: Anil V. Parwani, MD, PhD, MBA, Department of Pathology, The Ohio State University Wexner Medical Center, 410 W.10th AVE,
Columbus, OH 43210 (e-mail: anil.parwani@osumc.edu).
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Editorial Adv Anat Pathol  Volume 27, Number 4, July 2020

resulting in a virtual microscope with all the clinical infor- biopsy specimens and grading of cancers (eg, breast or
mation needed to sign-out the case. Many recent studies prostate cancer), diagnoses of gastrointestinal polyps and
have demonstrated the utility of WSI in teaching, QA inflammatory conditions, etc. Potentially, there could be a
assessment, consultation, telepathology, image analysis, and tool that is a “dashboard” for the patient and will highlight
research use.17,18 the prostate or breast cancer on the needle biopsy but also
In terms of technology, WSI captures an entire tissue combine family history, prior pathology results and images
sample on a slide converting into millions of pixels, which as well as biomarker information for the pathologist to
can be shared easily as a digital slide1 or subjected to pat- enable a better, robust and decision-powered diagnosis. This
tern-recognition learning algorithms using specialized digital information fusion is critical to the pathologist and is more
pathology software. The creation of algorithms can be possible and enabled in a digital workflow and is at the core
customized to create “apps” similar to the ones that are now of computational pathology.35
available on smartphones. DL neural networks may be Currently, there are some commercially available DL
trained to not only recognize specific patterns on a whole networks and AI tools for pathologist use. These first gen-
slide image of an hematoxylin and eosin slide but in addition eration tools are promising and more and more pathologists
AI tools may also help in the interpretation of features in the are starting to consider them as part of their diagnostic
tissue that are predictive and/or prognostic.19 workflows. As technology and infrastructure matures, and
Despite much progress in the field of digital pathology, as digital pathology adoption increases, these tools will
adoption in the United States for the last 5 years remained make an even bigger impact on the practice of anatomic
slow and only restricted to few niche applications. Several pathology, as has been the case in radiology.29,36 The suc-
large academic hospitals have started to build digital path- cess of this workflow and adoption of “smart” algorithms
ology programs. Large-scale clinical trials have been will likely also benefit from more powerful computing
conducted and demonstrated the excellent diagnostic resources and annotation of larger image data sets, enabling
concordance between glass and digital slide diagnosis and creating a framework for precision pathology.37–39
rendered.20–23 Digital pathology networks have been created Digital images of glass slides can facilitate acquisition
and “in-sourcing” of pathology consults via digital slides of not only a definitive diagnosis, but also access to other
have started. Image analysis tools are now more commonly pathologists for a second opinion and specialty con-
available and quantitative algorithms may being imple- sultations. Quality QA requirements, especially those for
mented in diagnostic pathology practice.24,25 suspected cancers, can be rapidly executed. Changes in QA
Since 2017, 2 WSI vendors have Food and Drug Admin- and consultation practices can be sufficient to promise div-
istration (FDA) approval in the United States for primary idends for patients in terms of turn-around time, safety, and
diagnosis.26,27 The current relatively slow adoption of digital quality of care. Utilizing AI tools, the QA process of the
pathology workflow before widespread use of AI tools future anatomic pathology laboratory will be more
somewhat parallels what occurred with radiology. In radiol- streamlined and enhanced by algorithms that can provide
ogy, the switch to digital accelerated once workflow algo- “virtual” QA on cases already signed out be pathologists
rithms and computer-aided diagnostic devices became and can be modulated or fine-tuned to focus on problem
available.28 As digital pathology promises to improve pre- areas or “hotspots” in the laboratory such as an error-prone
cision diagnosis and personalized medicine, the incorporation pathology specialty or a new pathologist in the system who
of algorithms in digital pathology could accelerate the adop- has been flagged for a higher diagnostic error rate.31,37,40,41
tion of digital health care in both radiology and anatomic Type B applications of decision support in Anatomic
pathology.29 This greater adoption would allow digital path- Pathology in effect offer a prospective expert grade QA,
ology to realize the benefits for patients and clinicians in terms thereby also allowing the pathologist to focus on charac-
of rapid image sharing, image workflow streamlining, image terizing the pathology catered specifically to management
analysis and building powerful algorithms that can assist in implications.
the all aspects of workflow.30 Applications of AI and ML Operating digital pathology as a clinical service within
techniques tools are the promise of a “true” digital workflow and across working medical centers will require more than
and intelligent systems that will provide the pathologist with imaging scanning systems. To be useful in the clinical
critical decision support and “smart” sign-out systems that are environment, the digital pathology systems must interface
“computer-assisted.” These tools, when fully developed will seamlessly with a range of supportive hospital systems. In
likely to drive the adoption of digital pathology at a more the experience of some early adopters, factors such as the
rapid pace than we seen today do.8,31 stability of the health system’s network, the speed of servers,
As we think about what are the areas in anatomic path- the performance of the pathologist’s workstation and
ology that can benefit from DL and AI tools, we can start monitor, and even the functionality of the image pre-
thinking about categories of “helper” apps for pathologists.32,33 sentation and navigation software proved more important
Using digital images, and broadly speaking, algorithms can be for the pathologists than the performance of the imaging
divided into 2 types. Type A are akin to “workflow devices” systems.42,43 Although hospital systems have not measured
with an objective to improve workflow efficiencies for the all those parameters explicitly, it is clear that such factors,
pathologists. These type of algorithms will aid the pathologist to from scanner to desktop to image integration with the lab-
do “repetitive” tasks such as counting mitosis or counting nuclei oratory Information System and hospital electronic records,
or tumor cells in a microenvironment rapidly. The workflow can have a significant influence on the pathologist’s per-
devices are considered general operating systems, assisting the formance. Quality improvement assessments will investigate
laboratory and/or pathologists in their daily work by processing the performance of hospital informatics systems that inter-
and reviewing patient specimens to make a diagnosis.34 face with the digital pathology network. Network per-
Type B are algorithms that can provide decision sup- formance metrics will be better established to determine the
port and help the pathologists in making better-informed potential impact of system alternatives and recom-
decisions. For example, AI based-recognition of cancer in mendations will be provided to improve performance.41,42,44

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Adv Anat Pathol  Volume 27, Number 4, July 2020 Editorial

Digital pathology is bridging the gap of time and dis- pathology. The important aspect of this is that images are of
tance by delivering care at the point of need in a clinically diagnostic quality and provide an accurate representation of
time-sensitive manner, regardless of location. Real time and the scanned glass slide. Several studies have shown that
delayed case reviews can easily be conducted through the when those conditions are met, there is little to no difference
use of digital imaging, allowing pathologists in remote areas between a diagnoses rendered via image versus a slide and
to work with colleagues more immediately to obtain information management is an important benefit of creating
potentially medically significant and even lifesaving con- a digital workflow for enabling the pathologist an access to
sultations, second opinions, diagnostic collaborations, and the relevant patient information in a SMART cockpit.51–53
subspecialty reviews.45 The latter has now been apparent in By providing rapid access to this information, time is saved
laboratories where during COVID-19 pandemic, patholo- and quality of the information is enabled.50 Once this
gists have been successful in maintaining social distancing information and images are managed in the SMART
which achieving excellent patient care using remote sign- cockpit, the second important aspect of the value pyramid
outs and reviews with residents and fellows.46 can become available which is the ability of “image
Another advantage of adopting WSI is that smaller sharing.”
practices will benefit from the ability to organize virtual The image sharing enabled by digital pathology
practices by integrating their smaller clinic operations into workflow can be for access to experts for consultation,
virtual hospitals. An example of this to create virtual frozen showing cases to a colleague for clinical and treatment
section services that provide coverage to multiple sites by decisions or for QA or for “work-load balancing.”53,54 As
few pathologists in difficult and challenging areas such as these applications of image sharing are rapidly used, the
neuropathology or lung pathology.45,47 Efficiencies realized value of digital pathology workflow will make an enormous
by implementing digital solutions will increase utilization of impact on the care of the cancer patient. These benefits are
available pathology resources at a time of diminishing not nearly as powerful as the third and yet not fully devel-
pathologist availability. Improved resource utilization will oped and exploited value of digital pathology, which is the
maximize productivity, expand access to care, reduce out- field of image analysis and computer-aided diagnosis.
sourcing costs, and offer pathologists the ability to retain a Advances in the area of image analysis will provide the
high level of technical proficiency through interpretation of pathologists with powerful tools or “helper” applications to
a variety of medical images not available in their day-to-day enable the pathologist to do manual and labor-intensive
practice. Furthermore, digital pathology systems will pro- tasks more automated including detecting “rare events”
vide support to community practices with ready access to such as finding tumor metastasis within a lymph node or
expert pathologists and pathology subspecialists. A subset of accurately quantitating the volume of tumor in specimen.9
these consults, in the future, may be triaged by intelligent Today’s information-based world is changing anatomic
digital pathology systems.48 pathology practice. Pathologists are increasingly turning a
A routine “analog” pathology workflow generally digital workflow with some systems, which have integrated
involves the procurement, processing and interpretation of digital slides into electronic medical records.41 These sys-
glass slides locally within each hospital. In some instances, tems now allow pathologists to log into the electronic
specific cases are sent from the general/community pathol- medical record and with an integrated view of the pathology
ogist) to a subspecialist/academic pathologist for an over- and the patient journey, are able to provide the best diag-
read consult. This can also be implemented in niche areas nosis for their patients. Morphology-based assessment of
such as cytopathology or dermatopathology. Nonetheless, slides is not enough.55 Patient management teams are
the general pathologist serves as the “gate keeper” at com- demanding more information and even patients are
munity hospitals, making the initial diagnosis and then demanding more accuracy. Implementing a digital workflow
determining which cases, if any, are referred to a sub- allows pathologists to take better control of the daily work
specialist. A WSI scanner may be considered as a micro- and the “technology environment” and give the best possi-
scope that is under full robotic control, attached to highly ble diagnosis, or “outsource” it to the plethora of multiple
specialized cameras containing high-performance photo entities that can “complete” the diagnosis by adding the
sensors and serves to produce diagnostic quality images. molecular data, immune-oncology markers56 and mutation
Once the slides are digitized and converted to millions of panels that will drive the care of the patient towards “pre-
pixels, we now have massive pixel pipelines, which allow cise” medicine.10,57
pathologists to remotely view the images and share them. In Today, there are multihospital practices or commercial
addition, these pixels can now be interrogated to look for labs which have taken big steps forward by implementing
distinct features or image “signatures” using image analysis, digital pathology workflows for both general and subspeci-
DL and AI tools.49 For example, an expert urological alty sign-out.18,54,58 With the advent of supercomputing and
pathologist on a busy consult day may be able to have a the rise of cloud technology, it is easy to rapidly share
“digital” assistant or “fellow” who can rapidly scan digital images across the globe. A challenging pathology slide from
slides and prepare the “sign-out” process for the day, ena- a community hospital from rural regions can be transformed
bling the expert pathologist to rapidly turn around the digitally to connect to the experts with the ones who need
consults. This is a win-win situation for patients, health care help with the diagnosis in minutes.59 Today, digital path-
systems and the pathologist. Studies have demonstrated that ology slides once digitized have information and integrated
there is a value proposition for institutes who have imple- data that makes the review process more efficient and
mented digital pathology in the workflow in terms of effi- streamlined than ever before. These technologies continue to
ciencies gained and reduced errors with improved quality of transform the practice of pathology. With integrated AI
care.50 tools, the combination of digital pathology and connectivity
Today, with all the innovations in computing and to patient electronic medical records, pathologists are poised
infrastructure, it is technically feasible to use WSI for rou- to utilize all the powerful tools that will enable them to be
tine pathologic diagnosis for general and subspecialty on par with other medical professionals who heavily

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Editorial Adv Anat Pathol  Volume 27, Number 4, July 2020

leverage technology in their medical practices such as radi- applications for pathologist that will be more powerful;
ologists and cardiologists. This will pave the way to provide integrating these into scanner/LIS workflow cockpits will be
meaningful, accurate, and more structured information in essential for practice transformation and adoption.
pathology reports to move precision medicine forward.60,61 As we navigate the COVID-19 pandemic, there is
Today as there is a gradual increase in the number of sense of a new and renewed energy to influence patient
departments and laboratories that are taking steps to con- outcomes by all disciplines within medicine. There is
verting to a digital workflow and starting to use them for increase in adoption and a “trust” that digital pathology
primary diagnosis, there is an increase in adoption and systems are clinical-grade and produce diagnostic quality
greater awareness of digital pathology. The latter has been images. There is a newfound excitement about these next-
accelerated by the notion that digital pathology workflow is generation tools such as AI and DL. These technologies
a prerequisite for using smart AI algorithms. Digital path- are no longer either a hype or a myth; they are here to stay
ology is beyond the curiosity and bells and whistles phase and empower. It is our opportunity to harness their infinite
and is now becoming a more critical strategy in developing potential to empower our discipline. It was a big idea at its
pathology services such that more institutes and laboratories inception, but many small and big insights by creative
are buying WSI systems. The price of converting an hema- vendors, researchers, ML experts and pathologists working
toxylin and eosin slide to digital is getting lower in part due together have enabled the availability of these tools to the
to lowering image storage costs. The information techno- pathology community. This novel, integrated, workflow
logy infrastructure that is needed to sustain a digital path- will be the new norm for the future of pathology diagnostic
ology program is steadily growing more affordable. Some of pathway. It is already, partially there, and in some
the adoption challenges are starting to become easier to laboratories today is now part of the diagnostic workflow
resolve. More vendors are building better and more process, with demonstrable impact on transforming
affordable scanners of all shapes and sizes, and more ven- patient care.
dors are starting to build value-based applications sur- Our goal for this special issue of Advances in Ana-
rounding digital pathology—some for consultation and tomical Pathology is to bring together a series of key and
others for image analysis.62,63 Pathology images are now timely reviews from experts in the field. We dedicate this
becoming incorporated into imaging standards such as special issue on digital pathology and AI to the pioneers and
DICOM (Digital Imaging and Communications in Medi- next generation of pathologists and AI scientists who will
cine) and efforts have been underway to create enhanced continue to be innovators, inventors so that we as a specialty
connectivity between systems.64 are better prepared to accelerate the practice of anatomic
Much of the progress in pathology including digital pathology beyond the glass slide.
pathology, image analysis, DL, next generation sequencing
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Adv Anat Pathol  Volume 27, Number 4, July 2020 Editorial

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