CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Valerie Neff Newitt
August 2017—The age of FDA-approved whole slide imaging for primary diagnosis has dawned with opportunity for every level of professional who works in the digital pathology environment. It includes not only an expanded professional cachet but also great potential born of collaborative and remote capabilities, and perhaps better patient outcomes as a result.
Yet with this new technological sunrise come “environmental” demands: a requirement for excellence in specimen and slide preparation along with a heightened need for standardization of and adherence to best practices and training to ensure the digital pathology sun never sets. While the kinks are not yet worked out, digital pathology technology is likely to help improve the processes on which it relies.
Ivo Van den Berghe, MD, director of surgical pathology at AZ Sint-Jan Bruges Hospital, Belgium, was an early adopter of the digital pathology platform and says he has “seen firsthand how to achieve maximum benefit.
“I have observed how digital pathology enables the lab to replace the subjective nature of manual slide inspection under the microscope,” he says, “enhancing clinical confidence in my histopathology colleagues and our findings.”
Yet Dr. Van den Berghe and others who spoke to CAP TODAY after the FDA approved Philips’ IntelliSite Pathology Solution for primary diagnosis also recognize the need for labs to sharpen their skills and standardize processes to align with digital pathology. “Certain existing practices do have to change if we are to achieve confidence in the standardization of our results, and setting new parameters for quality control is essential,” he says. A starting point for this, he adds, has to be the quality of H&E-stained slides. “Requiring good quality here is paramount to being confident in the results and making a positive contribution to improving outcomes.”
Eric Glassy, MD, president of the Digital Pathology Association and medical director of Affiliated Pathologists Medical Group in Rancho Dominguez, Calif., sums up an industry dilemma. “One of the big problems is that there is a lack of standardization in histology. The CAP has an excellent book on quality assurance in anatomic pathology by Drs. [Jim] Zhai and [Gene] Siegal, but the focus is not on slide prep and its effect on whole slide scanning. We need to develop best practices for creating an H&E slide. Fixation, embedding, sectioning, reagents, staining, and, finally, coverslipping all need policies and procedures that are tissue-specific and use-specific when a lab adopts whole slide imaging.”
Anil Parwani, MD, PhD, MBA, vice chair of anatomic pathology, director of pathology informatics, and director of digital pathology shared resources at Ohio State University Wexner Medical Center, explains the problem further. “Because histology processing aspects are so variable, an H&E stain differs from one city to another, one facility to another, and even one lab to another within the same facility. If given the exact same tissue, the slides still all look different because of varying concentrations of hematoxylin, varying lots, varying manufacturers, etc. And then there are also differences brought on by pathologists themselves. Some prefer their slides to appear more blue, others prefer them more pink.”
Dr. Van den Berghe believes support from manufacturers like Philips can help solve the problem. “H&E quality can best be achieved with the supply of autostainers which set out the lab’s contractual obligations on quality—removing subjective decisions. This indicates precisely how many H&Es can be safely stained before the color containers must be refreshed. Previously,” he says, “we were able to use the color containers until it was decided that quality had started to decline. For digital pathology, this subjective process should be actively discouraged.”
Why does digital pathology ratchet up the importance of optimal tissue and slide preparation? Once tissue is captured in a digital image, its focus is static. When a slide with air bubbles, folds, or other artifacts is viewed under a light microscope, it is “not necessarily a good thing and yet it may not have a major impact on the assessment of those sections,” says Zoltan G. Laszik, MD, PhD, medical director of renal pathology and director of digital pathology at UCSF Medical Center, San Francisco. (Dr. Laszik was instrumental in designing the 2014 validation study that contributed to FDA approval of the Philips system.)
“But folds and bubbles create uneven thicknesses in a specimen, which can trick a scanner into focusing on the height of the fold, for example, leaving other clusters of cells out of focus,” Dr. Laszik cautions. “What if those clusters of cells contain cancer? Since there can be no refocusing of a digital image, the solution is to have very high-quality sections. That is a requirement of digital pathology.”
For frozen sections, Dr. Laszik says there is one adjustment that must be observed when preparing the slides for digital versus traditional interpretations. “The coverslipping must be changed. The conventional glass coverslipping utilizes a glue that can contaminate and jam the scanner. For that reason, labs using glass coverslipping need to change to plastic to preserve the integrity of the scanner.” It will not change anything in the tissue, Dr. Laszik says. “It will just keep your expensive equipment up and running. And that will keep your administrators happy.”
He calls this solution “absolutely crucial”: “Without it, [scanning frozen sections] would never work well. It is a key step.”
While improvements in slide preparation are important, Dr. Laszik says, they generally do not require significant changes in practice. Rather, they require adherence to what was needed all along: strict quality control. “We must do exactly what we always were supposed to do: create high-quality sections that are placed into the middle of the glass slide, that are not fragmented, that don’t have folds, and that do not have bubbles.”
Dr. Glassy
Dr. Glassy, too, stresses that a poor glass slide equates to a poor digital image. “Departments must develop policies and procedures to properly orient the tissue to the slide that will be scanned. We need to be mindful of embedding—if there are multiple biopsies they are often haphazardly arranged in a block. For digital scanning it is better if they are all lined up,” he advises. And it is important to be sure that tissue is sufficiently trimmed so it does not go to the edge of the slide, “because scanners do not scan to the very edge.”
Thickness of a section makes a difference too, Dr. Glassy says. “Too thin or too thick leads to darker or lighter staining. Uneven sections will result in out-of-focus scans. And while pathologists using conventional microscopes are pretty forgiving in being able to focus through folds and irregularities in the tissue, in digital pathology everything is in a universal focus frame. Issues with poor sections will simply be magnified by digital imaging.”
Digital images are more demanding of high quality, and pathologists and histotechnologists need to be keenly aware of that, Dr. Glassy says. “If you are going to be implementing digital pathology, histotechs must have quality control processes in place so that the final scan is the best it can be.”
Fortunately, it appears that the technology that drives digital pathology may itself play an important role in improving slide and specimen quality. It is a fact that is not lost on Carolyn Compton, MD, PhD, professor of life sciences at Arizona State University, professor of laboratory medicine and pathology at Mayo Clinic College of Medicine, chief medical officer for the National Biomarkers Development Alliance, and chair of the CAP’s Preanalytics for Precision Medicine Project Team.
With a professional interest in ensuring that biomarker specimens are of sufficiently high quality to be reliable, she decries the lack of standardization that has been apparent in the preanalytical phase of specimen preparation and explains the problem as she sees it. “In the practice of pathology we bend over backward to make sure things are done right. We standardize the laboratory environment for tests and seek CLIA and CAP accreditation. We standardize the assays. We test proficiency of those who perform tests, and we do a lot of quality assurance. But we have no enforced standards for the very thing we are testing. For me it is inexplicable.”