Digital pathology: A 1st anniversary report card

Valerie Neff Newitt

April 2018—Nearly one year after the FDA cleared the Philips IntelliSite Pathology Solution for primary diagnosis, Philips is reporting worldwide momentum for the adoption of digital pathology. Last year, it helped two labs in Austria—Pathology Institute in Hall and Pathology Institute at Tirol Kliniken—fully digitize their workflows. In North America, “adoption is accelerating as the U.S. catches up with the rest of the industrialized world in terms of digital pathology,” says Marlon Thompson, PhD, MBA, vice president and general manager for digital pathology solutions, Royal Philips. Worldwide, he says, more than 10 “innovative pathology labs are working 100 percent with digital pathology for their current pathology workload.”

But large-scale adoption in the U.S. may await a few remaining solutions and steps, among them next-generation scanning systems, improved viewing software, solid infrastructure, and an open versus a closed system approach. Full acceptance of the power of artificial intelligence could well be the biggest push of all.

Dr. Thompson calls FDA clearance “a clear differentiator for Philips” and says it has led to movement across all sectors of the U.S. market—clinical institutions, comprehensive cancer centers, academic medical centers, and other laboratory groups. “The customers Philips has engaged fundamentally believe they need our platform because it allows pathologists to feel confident in the primary diagnosis,” Dr. Thompson says.

The downstream economic advantages of digital pathology have not been lost on users, he adds. “Many customers have been able to decipher and appreciate the value proposition of digitization in terms of the efficiency it delivers and translate that to labor savings and ultimately cost savings, which are quite impressive in the U.S. We saw that in the European market where we had early entry into digital pathology. Now the U.S. is experiencing efficiency gains for itself.”

Yet pathology departments appear to be moving slowly and cautiously. Jerome Clavel, general manager of Leica Biosystems Pathology Imaging and a founding member of the Digital Pathology Association, explains why. “While FDA clearance [for primary diagnosis] is going to be necessary, it also is not sufficient for massive adoption.”

Clavel, who offers high praise to Philips for its clearance achievement, says obtaining clinical clearance is one of Leica Biosystems’ top priorities as well. He describes FDA clinical clearance as one of three pillars on which broad adoption of digital pathology will ultimately be seated.

“FDA clearance really is the first leg of the stool. Another leg is next-generation scanning systems, not just fast enough to handle the volume but also simple and easy to use, with minimal human intervention for very easy deployment in the lab,” he says. “The third leg is a leap forward in viewing software. This means we must be able to handle massive amounts of data and render very large images smoothly to enable a seamless workflow.”

“Adoption will be a journey with many stops,” he says, pointing to the uses for digital pathology other than primary diagnosis. “It could be just having quick access to the slides for reference or being able to share with a colleague across the lab or across the world. It’s not all about clinical clearances. There are multiple research and teaching scenarios that do not involve clinical usage, not to mention safe archival and easy retrieval of slides.”

Yukako Yagi, PhD, director of pathology digital imaging for the Warren Alpert Center for Digital and Computational Pathology at Memorial Sloan Kettering Cancer Center, is helping to lead an expanding digital pathology program, one that started with a single whole slide imaging scanner in 2006 and has grown to an installation of 10 WSI scanners. (LIS integration began in 2015.) The systems in use are primarily Leica Aperio AT2s. MSK currently creates about 30,000 digital slides per month—composed of in-house surgical pathology cases, cytology cases, hematopathology cases, consult cases, and frozen sections—selected by pathologists and flagged for digital archive by a sticker attached to the slide. To date, about 500,000 digital slides are available. The goal this year is to create 40,000 digital images per month and start scanning MSK’s glass archives—about 4 million slides. All scanned data are saved at MSK’s data center in New Jersey.

“So far data collected at MSK show improvement in signout time, in having digital images available for review of prior material and consultation, and there is an opportunity to decrease the cost of slide retrieval by a lot,” says Dr. Yagi, a member of the Digital Pathology Association’s board of directors.

Is having an FDA-approved platform essential at this juncture? “Yes and no,” she says. “If we want to use it for primary diagnosis, we will have to have the FDA-approved system. However, to integrate a WSI system with our laboratory information system takes time, effort, and cost to complete, but in our case is very important. We anticipate that the FDA-approved scanner and the ‘best fit’ scanner in our current workflow may not always be the same. Based on our experience at MSK, the best system for us is the one that fits with our workflow and best scans our pathology materials.”

For now, primary diagnosis is not in the digital pathology playbook at MSK, but Dr. Yagi and the MSK team are eager to participate in those discussions, she says, “and ultimately we want to do what’s best for patient safety, safe practices, and optimal patient care.” Today, she and the MSK pathology team, having gained much experience, are focused on building the framework and evaluating and validating new scanners. They’re also developing models for using archived and annotated data for computational pathology; exploring, evaluating, and optimizing new technologies, including 3D imaging; and improving system integration.

J.Mark Tuthill, MD, division head of pathology informatics at Henry Ford Health System in Detroit, agrees that adoption can and should come only after a robust infrastructure is built on which an institution can balance the three-legged stool of digital pathology. And that, he says, takes time.

“Our adoption is still very nascent,” Dr. Tuthill says. “We have had a couple of systems running for two years that we use for a variety of ad hoc processes, particularly tumor boards and clinical and resident conferences. It is a major improvement in what we’ve been able to do in those areas. We find we need to move ancillary studies—immunostains, trichrome stains, iron stains, etc.—and get more bang for our buck moving digital images for those types of assets and workflow than we would for diagnostic tissues.”

For primary diagnosis, uptake is slow. “One of the key problems is that there is only one system that is FDA approved out of the box for primary diagnosis,” Dr. Tuthill says. “Even with that system approval, anyone who wants to adopt it and use it would have to go through local validation, do comparative and consensus work to make sure that use of the system in its environment is appropriate.” While other system components that were not approved as part of the Philips system clearance can be pressed into service if a laboratory undertakes a laboratory-developed solution, “it requires a lot of work and validation time.” For now Henry Ford pathologists are using digital pathology for the clinical conferences, education, and distribution of ancillary study slides—“things that don’t require the FDA’s diagnostic approval,” he says. Their plan is to use it for secondary diagnosis and ancillary studies. “Then the next phase, down the road a bit, will be to see how we can use it for primary diagnosis.”

In the meantime, Henry Ford is taking steps to ready its infrastructure. “Even with an approved system, if you have not integrated it into your daily workflow in a way that allows you to push materials through the systems very rapidly, you will not reap the high-throughput, high-volume, high-efficiency benefits of the technology,” Dr. Tuthill says.

The Henry Ford team has interfaced its digital systems with the laboratory information system so that barcodes that are read on the whole slide imager tell the system who the patient is, what tissue is being scanned, and what the stains on that tissue are so the system has awareness of the context of the material.

“Regardless of how high the quality of the digital picture is, it is moot if you have the wrong patient,” Dr. Tuthill notes. “Instead of being deeply involved in validation of a closed-box system for primary diagnosis, we first have to set our systems up for success so that we always have the right patient.” High-fidelity barcodes drive the digital pathology workflow. “We are not manually typing in names and medical record numbers. In fact, labeling fidelity has been moved all the way out to the order with an electronic orders interface to the EMR system.”

The importance of this preparation is something often overlooked when digital solutions are set up, he says. “There is already a lot of focus on the imaging quality. But we’ve tried to move the bar by integrating these systems into the workflow of an LIS and, if possible, the patient identification processes. Most of the digital pathology solutions that have been deployed up to now have not been interfaced.”

It is not hard to achieve the necessary interfaces, Dr. Tuthill says. “We were the pioneers and got vendors aboard. So the next people who come along will have a much easier time of it. They just have to plan interface into projects and ask vendors, ‘Will your system be able to read the barcodes that our LIS generates? Will it be able to interface with our LIS?’ Vendors now are paying attention to these next-level requirements. They know that our success is their success and that we all need to do this right.”

Slow adoption doesn’t surprise Michael Montalto, PhD, president of the Digital Pathology Association and executive director and head of translational pathology and biomarker technologies at Bristol-Myers Squibb. “FDA approval for primary diagnosis is not enough to create rapid adoption of the technology. What would be enough? That is the million-dollar question,” he says, “but we probably don’t need to overthink that. In any technology, it becomes a simple cost-value equation—whether or not something costs too much for the value it provides, period.” His sense is that the digital pathology technology is expensive in the current health care climate of restricted dollars. “And the benefit may simply not outweigh the cost, not only measured in dollars but also infrastructure and time to implement.”
Dr. Montalto believes enormous value eventually will be seen in the artificial intelligence that can be attached to digital imaging and that its worth might be most evident and enticing not to pathologists but to oncologists. “The face value of AI to pathologists would be either a more rapid diagnosis because a computer is helping with or actually doing the diagnosis, or a decrease in labor and the cost associated with a diagnosis,” Dr. Montalto says. “Workflow efficiencies and faster diagnoses—who is going to pay for just that? Is that enough?”

In his view, no. “I believe the digital pathology community is selling to the wrong constituency. It will be the oncologists in the future who will be interested in a technology like this, and will ask their pathologists to use it.”

With more and more work in immuno-oncology, a space in which Dr. Montalto works, oncologists are being bombarded with data that demonstrate the power of the immune system against certain cancers. “Oncologists will be increasingly interested in having a pathology report that provides quantitative information that can be delivered through digital pathology.”

“They appreciate that recognizing the immune phenotype in the context of a tumor and a tumor’s microenvironment is valuable to them,” he says. “Knowing how many T cells are in a tumor versus how many are not matters to them, and determining if these specific cells will respond to a particular treatment is invaluable. A computer can deliver that information much better than a human. Humans can’t repeatedly identify types and amounts of immune cells in a tumor. But a computer can do that really well.”

Dr. Tuthill agrees that image analysis will be “a huge driver.”

“In the space of 10 years,” he says, “digital pathology will be the primary way we interact with tissue-based images because of all the things we can do with a computer that we cannot do with a microscope, like cell counting, morphometrics, finding similar cases through a database image search, superimposing slides, and doing analytic measurements that we cannot do on a microscope. We will move from subjectivity to objectivity. But right now pathologists using microscopes are just starting to get the hint.”

Dr. Montalto thinks a thrust toward adoption also will occur “when we think about value in medicine being driven by treatment outcomes.