Digital path’s star rises from the mists

Pathologists should embrace digital pathology technologies, Abels says, in part to ensure that algorithm development is not steered by people without a good understanding of pathology. “Without that, I think that digital pathology will start to replace pathologists’ jobs—or at least start bringing harm to patients.”

Digital pathology’s adoption in Europe was faster, she notes, in part because the regulation of IVDs came later. “They’re also allowed to have scanners with other viewers and other displays, which the FDA doesn’t allow in the U.S.”

Fujifilm’s Dr. Lloyd says the United Kingdom, for example, leads the United States in adoption in part “because the government is providing a lot of funding to expedite digital health and make sure that hospitals are starting to implement it to benefit patients.” (In 2020, the U.K. announced an extra £50 million in funding to scale up the work of the existing Digital Pathology and Imaging Artificial Intelligence Centers of Excellence, which were launched in 2018.)

Amid the buzz about digital pathology, some pathologists have reservations.

“Digital pathology can be really useful. It can count numbers of positive cells for biomarkers better than humans and create consistent results,” says Dorothy Wong, MD, chair of pathology at Regional Medical Center of San Jose in California. “But in other areas we have to leave it to the pathologist to diagnose and determine tumor origin. And in being able to see things low power and high power that I don’t think a computer can do, the pathologist is irreplaceable. “

Dr. Wong was briefly contracted to help train computers to arrive at algorithms for reading digital slide images and found it unrewarding and ethically questionable. “I started to feel I was teaching a computer to replace me and to replace all pathologists with the cheapest option available.” At the time, she adds, “There were efforts to find overseas radiologists and other specialists to replace licensed health care professionals in the U.S. And I think there are all sorts of problems with that, including medicolegal liabilities and also taking away that extensive experience, training, and education.”

If a computer is missing something, she asks, “Who’s responsible for that? You’re liable and maybe you haven’t looked at the case as extensively as you would have without it. There’s a disconnect when you become too comfortable with AI. Are you on autopilot then? Are you even a pathologist at all?”

“We should not be supporting the health care system and hospital systems with the cheapest option available,” she insists. “It’s the devaluing of health care as we know it.”

The upfront cost of digital pathology systems is another problem, she says. “Where are people going to get the funding to purchase digital pathology and the software? A lot of hospitals have these archaic LIS systems and digital pathology is likely to be another kind of detached system, which is very cumbersome.” If digital pathology is an add-on service, she argues, insurers and patients are unlikely to want to pay for a redundant process.

Those issues aside, Dr. Wong notes, it is efficient to have digital versions of glass slides for consultations with clinicians or pathologists. Clearly valuable, she says, is “the ability to share images and maybe use digital versions for storage when otherwise we would have just had a bunch of glass slides that could randomly break depending on your storage conditions. So there is a lot of utility to digital pathology; it just has to be under the control of the pathologist.”

New products such as Paige’s Prostate Detect would likely be of interest to many groups, Dr. Wong says. But they probably wouldn’t be able to get such a purchase approved by their hospitals because “there would be a lot of extra costs and there’s no CPT code for them.” A reimbursement solution is necessary, she says, “and there has to be significant oversight when it comes to the diagnostics. At the end of the day, you still want pathologists looking at your material to diagnose your case. I don’t think that’s going to change. People who are trying to go into this space and change health care do not know what they don’t know about pathology.”

In the earliest years of digital pathology, when Dr. Lloyd was involved in projects from 1998 to about 2008 at Moffitt Cancer Center in Tampa, Fla., “Digital pathology was gaining a lot of momentum in research.

I could see some of the first digital pathology tools and technologies beginning to grab hold in a research environment, and I had the opportunity to direct a digital pathology shared-resource facility, and that was phenomenal.”

Motivated to see digital pathology mature into a large-scale clinical tool, soon he had started his first company, bringing together slide-scanning instruments, image management software, and algorithms. That progressed later to his company Inspirata, the digital pathology business that is now part of Fujifilm under Dr. Lloyd’s management.

“We are focusing on enterprise imaging,” Dr. Lloyd says, envisioning a suite of projects to include “everything from gross images in dermatology to endoscopy to intraoperative surgery to radiology and cardiovascular imaging and pathology imaging. That is the kind of scale we are looking at at Fujifilm.”

Radiology was ahead of pathology in going digital, he notes, because PET and CT scans were natively digital, whereas pathology has always started with creating a glass slide and will not be changing the technical component of creating a specimen. “We still make a slide and then we take an image of it. So our value proposition in pathology is very, very different.”

Addressing the fear of replacement some pathologists might have, Dr. Lloyd says: “It’s not the replacement of pathologists that I think any pathologist should be worried about. I am not at all a proponent of ‘Let’s just switch the lights on, now you’re digital—let’s get rid of these microscopes.’ That makes no sense to anyone.”

Rather, alleviating some of the menial tasks and drawing on the promise of artificial intelligence with digital pathology, “we now have a tool that can help physicians do something they couldn’t do themselves.” To Dr. Lloyd, “That’s like the killer application of digital pathology.”

On the other hand, although he is principal investigator on three grants involving AI work, he is concerned that AI is overhyped in the media, particularly as it reports on ChatGPT. “I don’t want to dampen anyone’s enthusiasm about the potential for AI. But I would caution them that this might not be the reason to buy digital pathology today, unless you have a use case where you and your organization have validated an AI technology that you really believe in.”

Pathology is very much a blackbox to people, says Paige’s Dr. Andy Moye.

“What gets the press are multi-cancer early detection breakthroughs or liquid biopsies to attack cancer and screen for it, or a new drug that came out.”

“But at the end of the day, we believe this field is sort of the last frontier in digitization,” he says. “Medical records have gone digital, radiology has gone digital, cardiologists are going digital. So this whole space will also move to digital, and the tools that are available, like AI, will help pathologists to do their jobs.”

Dr. Moye distinguishes between digital pathology, AI, and computational pathology. “Digital pathology is the use of a scanner to take a glass slide and make it a digital image,” he says. “‘Computational’ means using computation to provide an answer about what’s on the screen, what’s on the tissue,” and AI provides tools that can provide further answers. “We use machine learning or artificial intelligence techniques to build algorithms that enable that and give the information to the doctor. AI is a tool to be used—just as you would interrogate the antibodies with a chemical using immunohistochemistry.” Through training and data sets—Paige has robust data sets, he says, with partner Memorial Sloan Kettering—“we create an algorithm that with very high sensitivity and specificity provides an answer about what’s on that tissue.”

With AI, he says, that answer can be not only “There’s cancer” but also “That’s at least grade seven.”

“You can also find patterns in tissue that pathologists were never trained to see, meaning the machine can pick up patterns showing the patient has a genomic mutation or microsatellite instability.” Paige has an algorithm that’s trained on mRNA expression to predict whether a patient has HER2 expression, he notes.

Reimbursement can be a formidable obstacle but also a powerful ally, Dr. Moye says, citing radiology as an example. In the 1990s, radiology was still analog. Then disincentives were imposed.

“Basically, Medicare said, ‘If you continue to bill analog, we’re going to deduct 20 percent of your reimbursement.’” That drove most of radiology to digital, he says, adding that studies show it takes two or three years to recoup the cost of converting to digital diagnosis. “Almost always, there is a positive net present value to going digital, but you have to have the capital to invest in it.”

The CPT category III codes for digital pathology are being reported now by laboratories that use digital pathology for primary diagnosis. “Ultimately CMS will ask how many people are using this code, and hopefully they’ll assign a reimbursable number to them.”

Two factors may shift the tide in digital’s favor, Dr. Moye says. One is that pathologists are coming out of medical school where most classes are taught using digital pathology. Second, since there is a shortage of pathologists now, pathologists who are willing to work only remotely are not likely to be overlooked for the open jobs.

“I think that’s going to be the biggest driver over the next year or two. The hospitals and health care systems are going to have no pathologists,” and possibly little recourse except to rely on telemedicine.

The fear of being replaced by digital pathology is off base, Dr. Moye says. “When radiology went digital, there was this same fear, but in fact the number of consults exploded and the number of radiologists exploded. The number of radiologists has tripled. The reason is that the digital environment, the digital ecosystem, has made that number giant. So now images move everywhere.” His view is that digital pathology might be healthy for the profession.

“AI does a few things for us. First the simple detection of cancer, what type of cancer it is. Whether you’re looking at lobular or ductal, it provides information about the mitotic count, it counts them up quickly and easily. It saves a lot of time.” With other algorithms, “we provide the AI that does very typical quantitative analysis for HER2 that most pathologists have to report on. Then we provide an algorithm called HER2Complete and it helps pathologists with the HER2-low dilemma.”

“We’re a full workflow solution for pathologists and labs that extends to research and pharmaceuticals and life sciences, but clinical care is the core of our business.”

The U.K.’s National Health Service is sponsoring a two-year prospective study by Paige, slated for completion in 2024. “What we expect to come out of that study is the cost-effectiveness of using AI tools like Prostate Detect on the health system,” he says. “That usually helps to dictate whether a health system or a payer is going to pay for it. We’re excited about the results of that. We think using something like Prostate Detect will save the payer money in the long term because you’re not missing cancers, you’re catching them earlier, and you’re getting the right results.”

Dr. Moye has two messages for pathologists, health care executives, and laboratories.

“One, AI is not coming. It’s here. I’ve had conversations with pathologists and lab directors who say, ‘Wow, that’s going to be really cool in a few years.’ I’m like, ‘Guys, this is FDA approved right now. And we’ve treated 7,500 patients who have been impacted by our AI this year.’”

“Second, AI is just a tool. It’s just like IHC and PCR and special stains and anything else in a laboratorian’s toolbox. It’s a tool to enable pathologists to do their jobs in a way that they probably couldn’t before and that provides more information and better care. It’s not taking anyone’s job.”

Anne Paxton is a writer and attorney in Seattle.