August 2024—Digital pathology, FDA oversight of laboratory-developed tests, and the workforce shortage took center stage when CAP TODAY publisher Bob McGonnagle convened a roundtable online to talk about anatomic pathology laboratories. The shortage of pathologists, in particular, “is even greater than one might realize because of generational expectations around work-life balance,” said Andrew Bellizzi, MD, who applauds such balance but notes its significance. Their June 18 conversation follows.
In our roundtable last year we talked about digital pathology as a solution to the shortage of pathologists, subspecialty pathologists, histotechnologists, and cytotechnologists. We have a compelling need for subspecialty pathology and a lot of technology—in instruments, stains, in molecular, and in IT—to deploy in an anatomic pathology service. Andy Bellizzi, is that a fair summary of where we start today?
Andrew Bellizzi, MD, clinical professor, Department of Pathology, University of Iowa Hospitals and Clinics: It is, and I’d like to highlight a new hot-button issue: the FDA asserting regulatory oversight of laboratory-developed tests, which touches all of pathology. I’m a diagnostic immunohistochemist, so I think about regulation of LDTs from my perspective as a local IHC lab director and immediate past chair of the CAP Immunohistochemistry Committee. I run 250 tests in my lab and only one is an FDA-approved assay.
In thinking about these challenges—the increasing complexity in pathology and demands for subspecialization and around implementing digital pathology to, we hope, realize its potential for streamlining workflows—I want to add a lens to view them through, which is an educational one: How do we train pathologists to be successful in the 21st century? We’re still training residents similarly to how I trained 20 years ago. We’re not training them well in digital pathology; there’s not much digital pathology curriculum. The digital pathologists I know are self-taught.
The other threat is the workforce shortage is even greater than one might realize because of generational expectations around work-life balance. I applaud a work-life balance, but through training, we’re raising pathologists who have a 9-to-5 mentality. The loss of repetitions at the microscope as they enter the workforce creates pathologists who are inherently less efficient and less confident than people who entered the workforce a generation ago.
Since you raise the training of pathologists and digital pathology, we must naturally go to our participant from Ohio State, where we have an all-digital shop run by Anil Parwani, who’s been named the chair of pathology there. Zaibo Li, what can you tell us?
Zaibo Li, MD, PhD, MBA, professor of pathology, associate director of digital and computational pathology, Ohio State University Wexner Medical Center: We started our digital pathology implementation in 2017 when the Philips digital system received FDA approval. We purchased a contract with them and began the first digital signing out in 2018, for a prostate biopsy, using digital images. During the first two years only a handful of our 60, 70 anatomical pathologists started to use it. When the pandemic hit, we saw a large rise in pathologists using digital pathology because they didn’t want to touch the glass and wanted to work from home. Now over 80 percent of our pathologists use digital pathology to sign out cases and 40 to 50 percent are fully digital. This applies to surgical pathology, not cytopathology or hematopathology.
Dr. Bellizzi (Iowa): Zaibo is describing the swapping out of glass for digital images. To me, that’s fine. That’s primary diagnosis. But that’s not how we’re going to realize the potential of digital pathology. How do we train our pathology residents not to be end users of digital pathology but to implement systems in the way that Anil Parwani and Zaibo Li have? How do we teach those skills so they can be transmitted to the community?
Rob Monroe, what can you tell us? What are you observing from your perch at Leica Biosystems?
Rob Monroe, MD, PhD, chief medical officer, Leica Biosystems: My observation, based on working with customers at academic centers and reference labs in the U.S., as well as in Europe, including the U.K. and in Scandinavia, is that digital pathology is a skill quickly acquired by pathologists in training or in practice. The pandemic highlighted the ability of pathologists to quickly adapt to using digital images for primary sign-out and for other activities facilitated by digital images, including consultations and case-sharing. We’ve come a long way with implementation as well.
Along with the momentum created by FDA clearances for various scanners, including for Leica Biosystems’ Aperio GT 450 DX scanner in late April, are the advances we are seeing in interoperability. Leica Biosystems’ Aperio GT 450 DX was the first scanner cleared with a DICOM [Digital Imaging and Communications in Medicine] image file format, which allows vendors in the space to develop applications on a standard file format and seamlessly integrate digital pathology images with their software solutions, facilitating advances in digital pathology technology, similar to the role DICOM played in radiology. DICOM clearance is a critical step forward and will help propel adoption of digital pathology.
Reimbursement is an issue for labs looking into implementing digital pathology. It’s capital intensive. It requires change management and new workflows throughout the lab, not just for pathologists but also for the entire histopathology and operations staff. Figuring out how we as vendors can streamline the implementation of new workflows and enable efficiencies to offset the costs of the technology is key to the success and continued adoption of digital pathology. We have seen successful adoption in the U.K., Sweden, and a number of academic medical centers in the U.S. But we need to make it easier for the types of practices and labs that don’t have the same infrastructure as universities, academic centers, and large reference labs.
Valerie Cortright, what do you see as the supervisor of histology at Vermont? Is digital pathology an important part of your planning?
Valerie Cortright, BA, HTL (ASCP)CM, QIHC, supervisor, histology, Department of Pathology and Laboratory Medicine, University of Vermont Medical Center: Yes, it’s at the forefront of our planning currently. We are in the middle of a request for proposal for software and scanners. The cost justification for it has been challenging, but we’re finally in a space where we have a lot of motivated people to bring it onboard.
The shortage is an issue here, especially among pathologists. We’ve been lucky with histology. We train histotechnologists on the job and it’s been successful. We are also subspecialized, which has its own challenges with recruiting pathologists. We’re a network hospital, so we have smaller hospitals that are not subspecialized and we do a lot of consulting and sharing of cases, moving work back and forth based on technical and professional staffing issues.
Dan Albertson, give us your thoughts about the state of anatomic pathology labs at the University of Utah and ARUP Laboratories in terms of the LDT ruling, the pathologist shortage, and digital pathology.
Dan Albertson, MD, professor and chief, Division of Anatomic Pathology and Molecular Oncology, University of Utah and Huntsman Cancer Hospital, and president, University of Utah business unit, ARUP Laboratories: We’re unique because for most of the surgical pathologists, upward of 80 percent of our work is within the hospital system itself, so in some ways the LDT rule is not a huge problem for us locally. But when we get into the reference work and providing stain and return or additional testing, in particular solid tumor FISH, it has become challenging. We’re fortunate because we’ve done a lot of work for clients out of New York State, and we have a long history of working with New York State’s Clinical Laboratory Evaluation Program.
Regarding the pathologist shortage, we have an advantage because we have a lot of good folks who come up through residency and fellowship. Many have ties to Utah or a strong desire to remain in the Intermountain West. One of the biggest challenges for us—for junior pathologists and especially for operations and technical staff—is the increase in cost of living.
We’re hoping as we grow as an institution across the valley we can find workflows that make us a flexible workforce and take advantage of digital pathology for the purpose of remote sign-out and frozen sections. That degree of flexibility helps us manage our space constraints on central campus.
Kathy Bowden, are these themes familiar to you? Is this the daily consumption of concepts and problems you hear at Agilent as you seek solutions for and bring solutions to laboratories and pathologists?
Kathy Bowden, Americas marketing program manager, pathology solutions, Agilent Technologies: Absolutely. Cost is currently a major factor when it comes to digital; it is being looked at and will continue to be looked at. More and more testing is coming down the pike, multiplexing, et cetera, and having the ability to scan these modalities of testing and to centralize the testing is important. We hear about workflows every day—the need to make it easier for staff so it’s easier for pathologists too.
Smaller hospitals are struggling with how they will be able to afford digital pathology. We feel there should be opportunity to go with different vendors and for vendors to work together easily and bring in different testing modalities to further drive efficiencies and lower cost.
Last year we talked about a perfect storm for anatomic pathology. We have a lot of technology and sophisticated IT that needs to be deployed and a shortage of labor across the board. Promise Okeke at NovoPath, you have to pull it all together, don’t you? Tell us what you’re seeing, what your top-of-mind concerns are, and what our readers should know about what they’re facing and what you’re offering.
Promise Okeke, MBA, CEO, NovoPath: Many of our laboratories are pushing toward being more digital, expanding their test menu, and bringing tests in-house. The new LDT regulation and the reporting that needs to be done is another challenge. We are thinking about how we can empower labs to unify those things.
There’s a need for interoperability with digital. It’s one thing to have a digital viewer, the scanner, everything working functionally, but the data repository, the data management solution is through the LIS. The data needs to be able to go in and out to viewers but also back into the data repository. We’ve been trying to make it easier for other vendors to integrate with us by leveraging some of the newer technologies that facilitate better interoperability.
As labs face other mounting challenges such as increased labor costs, security of patient data, need to leverage data analytics, and expanded test menus, we have partnered with our labs to build out point solutions for these challenges. We see ourselves as the technology partners for our customers in the mission to provide quality patient care.
Valerie Cortright, there’s almost no choice but to look for solutions in all kinds of technologies, made available by a Leica or an Agilent or that come through sophisticated LISs. You serve many hospitals—does the administration at the University of Vermont understand the scale of the challenge you face and of what they’ll need to provide for you to optimally solve their problem?
Valerie Cortright (UVM): I like to think so. We have great senior leadership for the laboratory and pathology and they are great advocates for us. They’re doing all the right things at a higher level to make sure we get what we need.
We have the same issues with space as others do. We’re looking out three, four years from now and saying we’re going to need to move some people offsite, and if we bring digital on, what else can we do to create more flexible workflows and opportunities for staff so we can attract the best staff and best pathologists.
Dr. Li, is Ohio State an attractive place to practice pathology in the eyes of young pathologists, given your technological leadership?
Dr. Li (Ohio State): Yes. Before the digital era, we had a difficult time recruiting faculty, even residents and fellows. Recently we’ve seen a smooth process to get faculty onboard when they come and see our platform and practice. Many faculty and residents are enjoying this technology. They can preview slides at home after work; they don’t have to stay late. They can preview slides at the same time with the attending. Everyone can look at slides when they have time.
I’ve observed how individualistic pathologists tend to be about their workflow. We all know the pathologist who wants to be there as soon as the slides come out of the processor and read out cases by 7 AM. Others don’t like to get to the slides until late afternoon, when things quiet down. Rob Monroe, can this standardization of workflow be a challenge when you have different personalities?
Dr. Monroe (Leica Biosystems): Absolutely. Because digitization adds additional steps and time before images are available for review, schedules and workflows may need to be adjusted to meet pathologists’ preferences. But the new workflows bring in benefits that outweigh the potential challenges of adjusting schedules to build in time for digitizing. For example, labs can implement AI tools for QC to assess the quality and consistency of stains, including H&E and IHC, in order to standardize the appearance of various stains across the different sites of a practice or hospital system. QC tools for stains are becoming increasingly important as we think about additional AI applications that are coming into play to help pathologists with a variety of diagnostic tasks such as mitosis counting, IHC scoring, and tumor detection. For these applications to work optimally and avoid mistakes, the stains need to be consistent and of high quality.
Overall, the workflow efficiencies and AI applications that digitization enables have the potential to help tremendously with some of the issues raised in this discussion, such as pathologist shortages and the need to create more flexible opportunities to attract new physicians and laboratorians to the field.
I want to make sure we properly emphasize the importance of special stains. Under the guise of the FDA, there’s a gatekeeper function we have with these special stains, not to mention the molecular aspects. Kathy Bowden, how is this playing out in your mind and what is the LDT anxiety level of customers?
Kathy Bowden (Agilent): The LDT anxiety is high. There’s a lot of pages to the LDT ruling, and until we get the information in a human-speak form rather than a legal form, it’s a little hard for people to understand and grasp how they’re going to handle it, work with it, and deal with the future of testing. We need webinars and other education on this to get pathologists and laboratory managers onboard so they know what they’re looking at. People who work with New York State have been doing this for a long time. But if you’re in a smaller area and don’t know how this was done, it’s a big fear. As a company, we can’t give guidance. We can tell them where to go for guidance.
Rob Monroe, if a customer is trying to deal with a lab-developed test, you as a company cannot promote that test; it’s illegal. It’s important for customers to understand what a company like Leica or Agilent can and can’t do legally, correct?
Dr. Monroe (Leica Biosystems): Yes—our place is to provide instruments and reagents. If we’ve obtained regulatory clearance of certain products from the FDA, such as the Aperio GT 450 DX digital pathology scanner, then we can provide customers with training and education around the product’s intended use. Without FDA clearance or approval, we’re not allowed to promote or speak to the use of an instrument or reagent for a specific indication or to suggest how a lab might use that instrument or reagent to develop an LDT.
Dr. Bellizzi, it seems the initial 500 pages were not terribly clear when it came to immunohistochemistry. Do you agree?
Dr. Bellizzi (Iowa): The CAP has had a clear framework to describe the validation of laboratory-developed tests, including a publication from the CAP Pathology and Laboratory Quality Center for Evidence-based Guidelines. The initial guideline [“Principles of Analytic Validation of Immunohistochemical Assays”] was published in 2014 and then translated into a number of requirements in the CAP anatomic pathology and all common checklists. The guideline was updated in 2024 [doi.org/10.5858/arpa.2023-0483-CP]; I’m the senior author. We have a lot of expertise and oversight infrastructure in the form of guidelines and checklists.
There seems to be a fundamental misunderstanding by the FDA or industry around what a laboratory-developed test is and what an FDA-approved assay is. I spend a lot of time validating, revalidating, and re-revalidating immunohistochemical assays. In the last year I had to revalidate 40 tests offered by Agilent because the format of the primary antibody changed from concentrate to ready to use. These are all marketed as IVD, so that sounds like an FDA-approved assay. But what’s marketed as an IVD is the primary antibody, which is only one component of the assay. So every one of these IVDs, even though it seems like it’s an FDA-approved assay, is only one component of a laboratory-developed test that I have to assemble because the vendor only makes recommendations for platform, incubation duration, and retrieval.
The last optimization and validation we did was to revalidate beta hCG. The vendor’s website says IVD. The format changed to ready to use. We still had to optimize and validate every one of these ready-to-use antibodies. We validated it at a dilution of one to two, because at the neat dilution, the ready-to-use dilution, the test failed the validation. We validated with low pH retrieval. The vendor recommended high pH retrieval, and at high pH retrieval, the test failed the validation. From the immunohistochemist’s perspective, something marketed as an IVD means it’s marketed as an IVD, but a lot of work goes on behind the scenes to build a test.
FDA regulation of LDTs is a big deal. Unless you’re performing the test from a kit exactly according to the manufacturer’s instructions, everything else is an LDT. The only true FDA-approved assays are the pharmDxs and CDxs, and there’s about a half dozen.
Promise Okeke, does the LDT decision create a potential for the FDA to look more closely at IT systems that serve clinical departments and regulations? The FDA ground blood bank software to a halt long ago when it decided to regulate that software. Is there a threat to other applications that you’ve been hearing or thinking about?
Promise Okeke (NovoPath): When the ruling came out, we had our lawyers look through it and make sure we were exempt from the regulation as an IT provider, and we are. But this is still a fluid process with new findings emerging. Could the FDA impose more stringent regulations on IT software providers in 10 years? It’s possible, but that will stifle innovation, and I don’t see why the solutions we provide alter the diagnosis a patient receives.
At NovoPath, we ensure we follow policy and software standards. We are ISO certified and HIPAA, GDPR, and SOC 2 compliant. We have invested heavily in our compliance readiness and maintained a high burden of proof for the safety of our customers. We’ll continue to accelerate our investment in this area to ensure their needs are well served.
Dr. Albertson, are labs budgeting more and more for cybersecurity, in addition to all the other expenses?
Dr. Albertson (ARUP): Yes. If you look at what it costs for people to do the work, we’ve probably seen a year-over-year one percent increase just in the labor costs associated with IT. That doesn’t include all the software. The old software model was you purchase it and you use it. Now you have ongoing contracts where you are locked into paying annual fees associated with using that software, and those fees are increasing.
This gets back to the point that people have inferred, which is that regulatory compliance, IT support, and software and hardware costs to run a lab are all increasing, and we have not seen reimbursements increase, nor do I expect them to. One of the biggest challenges for pathologists, physician leaders, as well as operational leaders is how to distribute the funds to keep your lab going and in compliance. I hope the consolidation of labs does not continue to accelerate at the same pace it has in the past 10 years, because I worry about the quality of health care we can provide if we don’t have laboratory professionals in most institutions across the United States.
Valerie Cortright, you’ve seen many problems come and go and be solved. What are your thoughts as we sum up the future for histotechnologists, cytotechnologists, pathologists, and AP labs?
Valerie Cortright (UVM): We’re a resilient group. Pathology is special because everybody is passionate about the work, and we will figure it out. Whatever the challenges are, we’ve proven in the past to be able to figure them out. It takes coming together, as we’re doing now, getting all the subject matter experts in a room and saying, How are we going to work through this? It’s all for patient care.