Automated histology—many labs, many tales

October 2007
Feature Story

Karen Lusky

When you've heard one story about a histology lab's experience with automation, you've heard one story. That's because, of course, each lab has its own goals and chooses its own mix of automated solutions to meet them. But most speak of smoother workflow and shorter turnaround and the always tricky question of cost.

Everything was done manually seven years ago in the histology lab at the University of Connecticut Health Center, Farmington, including all of the staining. The laboratory used a 25-year-old tissue processor for overnight processing. Staff labeled the tissue cassettes and slides by hand.

Today, automation reigns at the university-hospital-based lab, which won a state quality improvement award for its automation process in 2003. Automation has boosted production from 9,023 surgical specimens in 2000 to about 13,000 this year with no additional staffing, says histology supervisor Kathy Wiggins, HT (ASCP).

Turnaround times have improved dramatically. "We have been providing answers the same day as surgery for two years," Wiggins says. A small biopsy can be reported in four hours. Pre-automation, the lab reported results for biopsies within 24 hours and within 48 to 72 hours for bigger specimens.

"Everything at the lab is automated with the exception of embedding and cutting, which are difficult to automate," Wiggins says.

With its three Leica Microsystems ASP 300 S conventional automated tissue processors, the lab runs a lot of different programs, including short runs of 1.5 hours for biopsies, rather than include those in overnight processing.

A Leica ST 5020 Multistainer does the H&E staining. An attached transfer station moves racks of slides to the Leica CV5030 glass coverslipper that can coverslip a rack of 30 slides in about two minutes, Wiggins says.

In the past six to nine months, the immunohistochemistry lab improved turnaround times for its immunostains by bringing on a BondMax (Leica Microsystems), which requires less technologist time and does the pretreatment online, Wiggins says.

Melinda Sanders, MD, chair of the pathology department, finds that if she sees an abnormal case in the morning, she can have a panel of IHC markers "ready to go before the end of the day so the case can be complete and signed out." The lab is hoping to use that as a marketing advantage.

The move to complete automation represented a makeover for the lab, allowing it to focus on its specialized muscle, nerve, and kidney biopsy services that require manual processes that cannot be automated, Wiggins says.

Today, labs have the option of using microwave rapid tissue processors or faster automated conventional processors to improve their workflows and turnaround times.

To produce more continuous, smaller batches of tissue cassettes, Nebraska Medical Center is purchasing the Microm STP 420D (Richard Allen Scientific, now part of Thermo Fisher Scientific), a non-microwave rapid processor with two retort chambers that can be operated simultaneously or separately, says David Muirhead, AIMLT, ABMS, MSA, anatomic pathology manager/assistant professor of pathology and microbiology.

The larger chamber has a patented rotational movement. Thus, the lab's staff has nicknamed the processor the "washing machine" because a portal hole makes it possible to view the tissues during processing, Muirhead says. "It can process up to 4-mm thick tissues in two hours and 45 minutes."

Another option for non-microwave rapid tissue processing is Leica's Peloris. "Labs can use the Peloris for conventional overnight processing or it can be an integral part of a Lean laboratory workflow in which smaller, continuous batches are run," says Jim Burris, director of sales for North America-West, Leica Microsystems, Biosystems Division. The Peloris lists for about $131,000.

Using the Peloris, Burris says, a laboratory can run two protocols independently or simultaneously—for example, multiple small batches, a large and small batch, or two large specimen batches for a total capacity of 600 cassettes.

In Florida, Palm Beach Pathology bought a Peloris in the past year, says laboratory manager Judy Collins, CT, HT(ASCP). The lab has found that it processes biopsies in about an hour, and slightly larger specimens in two hours with a maximum of six hours for large, fatty specimens. The tissue goes from there to paraffin.

The Peloris has "evened out" the lab's workflow, Collins says, so the lab produces a continuous cycle of work instead of everything in the morning. As a result, it can handle much more volume without hiring more people. In addition to providing technical and professional pathology services for 42,000 specimens from physician offices and surgical centers, the lab has been able to bring in technical work for 25,000 specimens from hospitals, which it started doing last November, Collins says.

Unlike the Peloris, the Leica ASP 300 S does not allow a lab to process two simultaneous batches of tissue. Wiggins at the University of Connecticut had wanted a Peloris when the lab was in the market for new tissue processors, but the lab's vendor, Leica, didn't own and distribute the Peloris at the time, she says. To "keep our business," Wiggins adds, the rep sold the lab two Leica ASP 300 S processors for less than the price of a Peloris and pointed out that the two Leica ASP 300 S units "gave us two brains and two bodies" compared with the Peloris' one brain and two bodies. (The Leica ASP 300 S lists for $43,450, Burris says.) Each Leica ASP 300 S can process up to 300 cassettes.

Sonora Quest Laboratories/Laboratory Sciences of Arizona in Tempe, which handles 125,000 specimens a year, is using Sakura Finetek's rapid microwave tissue processor, the Tissue-Tek Xpress, in its Lean and Six Sigma laboratory. Turnaround time is down, thanks to work process changes and the Xpress, from six days to two, and the lab is now aiming to reduce it further, says William DeSalvo, BS, HTL (ASCP), system production manager in histology.

The lab had in 2005 "pretty well pushed the envelope" with conventional processing times when it bought two Xpresses to replace 12 conventional processors (Tissue-Tek VIP 5), DeSalvo says. The conventional processors had a three-hour to 3.5-hour processing cycle, followed by a 45-minute cleaning cycle. "So it was four to five hours before we could reload a processor."

Using the Xpress, the laboratory can load specimens every 20 minutes, producing a continuous workflow. "You can load 36 specimens [on the Xpress] using the magazine, which is what we use, or 40 with the basket."

The standard processing time using the Xpress is two hours, 20 minutes for processing up to 4-mm specimens, he adds. "If you use the biopsy run, it's one hour and seven minutes, but you must dissect tissues to 2 mm or less thickness."

Sakura will roll out this month a second generation of its continuous rapid tissue processors geared toward the smaller-volume histology lab, says Gilles Lefebvre, vice president of sales, marketing, and customer relations. "We have perfected the technology where you can now run larger tissues...," he says. The new equipment will sell for about $120,000, compared with $200,000 for the Xpress, he says.

For labs interested in automating the embedding step, Sakura is the only game in town. The company is set to deliver the first of about 12 of its Tissue-Tek AutoTec machines in the next couple of months, including some in Europe, Lefebvre says. "The core of the technology" for the AutoTec is a sectionable cassette made out of a special resin that Sakura calls Paraform, he says.

Using the Sakura autoembedder, the pathologist or pathologist assistant doing grossing orients the tissue into the AutoTec Paraform cassettes. The cassettes then go to the Sakura Xpress for tissue processing. When the processing is completed, the cassettes go onto the embedding equipment. The next stop is microtomy. Paraform "has the same cutting characteristics as paraffin, so the microtome blade is not damaged," Lefebvre says.

Some labs have expressed concerns that the tissue could move in the cassette. But Lefebvre says the cassette is designed to immobilize the tissue between the lid and the bottom without damaging the tissue. So the only time the tissue could move is if the lab uses a standard cassette for a small biopsy. If that happened, the technologist could melt the block to recover the tissue and re-embed it using the correct cassette, Lefebvre adds.

Sakura has introduced a cassette for biopsies that is compatible with the AutoTec. "The paraffin button size is 13 ¥ 13 mm, so you can place up to 12 sections on a slide," he says.

Sonora Quest, which is a Sakura demo lab, is passing on the automatic embedder for now. DeSalvo says that's because about 70 percent or more of the lab's tissues "are small skin shave biopsies and we are not convinced that Sakura has the right orientation cassettes for us."

"Once Sakura resolves that issue, we are very interested [in the AutoTec] because it's the next step in the automation process," DeSalvo says. It would be able to do the work of three FTEs.

Options for automated H&E staining and coverslipping abound. Capabilities and costs vary.

Ventana Medical Systems' Symphony, the only discrete system that integrates staining and coverslipping, is the newest option, albeit, labs say, an expensive one.

Unlike so-called dip-and-dunk stainers, the H&E stainer drops fresh reagent on each slide, ensuring each stain is as pristine as the last. Users have to buy the prepackaged H&E reagent packs from Ventana.

"The Symphony is designed like the old Xerox machines where you can make the stain darker or lighter," says Stephen Hagan, vice president of marketing. "But you don't have to handle reagents to do that." Of Symphony's higher costs, Hagan says those who believe they aren't justified haven't "taken into full consideration the inefficiencies inherent in the dip-and-dunk H&E method and risk management associated with cross-contamination."

Palm Beach Pathology wanted the Symphony for consistency in H&E staining, Collins says. "The problem with our H&E stainer is that you have to pour the solution from jars into the equipment and change the solution at appropriate intervals. If we get busy and forget to change it at the right moment, we don't get good results." But the Symphony would have added more than $200,000 a year in costs, and the lab couldn't afford it, Collins says.

Robert Babkowski, MD, chief of pathology at Stamford (Conn.) Hospital, agrees that the costs with Symphony are higher. But for his lab, the instrument has proved to be an "enormous productivity improvement tool." And the slides, he says, are "absolutely beautiful."

Using the Symphony has allowed the histotechs to focus more on producing slides, special stains, IHC, and CISH than on "the mundane work of H&E staining and coverslipping," Dr. Babkowski says. And that has increased the lab's revenue, offsetting the costs of the Symphony.

"In our lab, the same three histotechs are able to do twice the number of immunostains and special stains with much increased surgical specimen and outreach volume and faster turnaround time," Dr. Babkowski says.

Alegent Health in Omaha is going to do a study soon on how Symphony fits into its Lean process, and to see if the lab can maintain its current throughput using the instrument, says Janice Mahoney, HT(ASCP), histology-cytology coordinator. "Given the stellar quality of the stain," Mahoney suspects "that the instrument may also reduce the need for second opinions or showing the case around the department."

Alverno Clinical Laboratories, Hammond, Ind., looked at Symphony but couldn't justify the cost at this time, says Thomas Roberts, MD, medical director. "Maybe we don't have high-definition eyes," Dr. Roberts says, but "we could not see a meaningful difference. Others claim that for certain specimens, particularly prostate biopsies, the high-definition H&E stain from the Symphony is superior, and I don't doubt that is true for them."

Kaiser Foundation Health Plan Northwest uses the Sakura Tissue-Tek Prisma for H&E staining, and at CAP TODAY press time had just completed a cost analysis of the H&E staining, says Robert Milewski, histopathology technical specialist. The analysis showed the lab is paying "approximately less than 12 cents a slide if we do it the most efficient way, which is to completely load three baskets," Milewski says. "We do that about 80 percent of the time." Thus, 80 percent of the slides cost under 12 cents; the rest are under 20 cents, he says.

For immunohistochemistry staining, the lab at Touro Infirmary, a community-based hospital in New Orleans, likes the Nemesis 7200 (Biocare Medical).

Jane Goodman, HT (QIHC), Touro's lead histology technologist, finds the Nemesis software allows for "good record keeping, storing all of the quality control on the machine. And it allows you to change the instructions for one run—for example, changing the staining time for one case." Then it automatically reverts to the routine settings, acting as a safety feature, she says. The Nemesis is an open system, adds Goodman, who likes "using lots of products."

The Nemesis, which can also do immunofluorescence applications, can be programmed for double and triple immunostains. It can stain a maximum of 72 slides with 84 reagents or 84 slides with 40 reagents, depending on rack configuration, says Fatima Natar, BS, HT (ASCP), QIHC, senior technical applications specialist for Biocare Medical. The user can program up to 50 different steps per slide. With Nemesis the user can generate a two-dimensional bar-coded slide and reagent labels. The system scans the slides and ensures that all reagents have been loaded and that sufficient volumes are present to complete programmed slides. If not, then the system will not start, Natar says.

The software solutions that accompany automation are becoming increasingly smart. Nebraska Medical Center recently purchased the Dako Link solution, a computerized system that can connect all of a lab's Dako immunostainers and autostainers to function as one, Muirhead says.

Using the Link system, says Ferran Prat, Dako VP of sales for North America, "one personal computer can be used to control up to three instruments and perform laboratory administrative tasks simultaneously, allowing for a more effective way of managing daily workload." And each patient specimen is assigned a true positive ID that is maintained throughout the entire laboratory process. "The system verifies the specimen true positive ID at every stage, virtually eliminating errors that are associated with redundant data entry," Prat says.

As Muirhead explains it, the Dako Link system allows the pathologists at Nebraska Medical Center to place their requests for immunostains in the Cerner Co-Path pathology information system. The requests cross to the local area network and populate the worklist in the pending file in the Dako Link system. The system then prints labels for the slides, which have the requested antibody written on them, such as a CD4 antibody, and a bar code that the IHC instrument, Autostainer Link, reads to know which reagents to put on the slides.

The Link system allows pathologists to use the software to see where the sections are and the estimated time to completion. The software can also detect errors, such as a missing or wrong antibody on the instrument or missing slides, Muirhead explains.

For now, the lab will link only the Dako immunostainers. But it plans to eventually interface the Dako Artisan, which does special stains, and the ACIS III image analysis system. Soon, Muirhead says, the lab hopes to expand the Link system to "add specimen tracking from the operating room to the pathologist's microscope."

Automated computer solutions in histology are virtually eliminating patient misidentification errors and specimen mixups.

For example, before the University of Connecticut Health Center histology laboratory started using the Leica IPC cassette labeler, it was averaging about three mislabeled blocks a day, which staff caught, says pathologist assistant Tim Greenwood. The cassette labeler has not only eliminated the errors but also freed staff from having to stop slide production in the morning to fix them, he adds.

DermPath Diagnostics/AmeriPath of Pittsburgh has adopted the Shandon CheckMate system (Thermo Fisher) to prevent patient misidentification errors. Wayne Holland, HT (ASCP), the histology lab manager there, has found that such errors tend to occur when specimens "move from one process to another"—for example, from the specimen container to the cassettes or from the cassette block to the slide.

Using the CheckMate system, the lab staff matches the bar-coded specimen container to the 2-D bar code placed on the tissue cassettes during accessioning. The lab uses a software program to print the bar-coded labels for the specimen container.

"The slides are bar-coded with corresponding information that the lab wants to put on them in addition to the patient name and other unique identifiers, including processing instructions" and more, Holland says.

When the histologist does microtomy, he or she also scans the 2-D bar code on the cassette and each pre-bar-coded slide to ensure a match, he says. "If there is a mismatch, the computer system produces a warning sound that can be individualized by the user." The computer screen also has a color-coded system to let the user know if there's a match or mismatch, Holland says.

Automation has helped histology labs do much more work with the same number of histotechnologists and lab assistants. Yet in some labs, the faster pace has shifted a bottleneck downstream to the pathologist reading slides.

As Sonora Quest's DeSalvo puts it: "We have changed courier routes, processing, and transcription, but our pathologists still work traditional hours." And that's led to a "very emotional discussion at this company" as it seeks to further reduce its turnaround time from two days.

In Alverno's "extremely competitive market" in Indiana, Dr. Roberts says, "we have practices that have a second shift of pathologists work from 1 PM to 9 PM to sign out specimens taken in the morning that same afternoon. These anatomic practices and their labs use same-day turnaround as a selling point to differentiate themselves from others. It's like the 15-minute oil change being viewed as a more customer-friendly service than using the dealer."

But some pathologists, Dr. Roberts among them, question the goal of ever faster turnaround times in some cases.

"Equating being quick with being good is a seriously flawed premise in the minds of many pathologists," he says.

Pathologist Dominick DiMaio, MD, of Nebraska Medical Center, observes that a lot of the demand for faster TAT comes from the outpatient side even though physicians aren't going to see the patient after a biopsy for a week. "And to produce a 24-hour turnaround time drives up costs."

Dr. DiMaio sees a benefit in an inpatient setting of providing a cancer diagnosis more quickly because some clinicians want to begin treating a high-grade lymphoma, for example, in the hospital. "But for breast and colon carcinomas, as examples, the person can be discharged and see the oncologist on an outpatient basis in most cases."

Automation that produces continuous flow will expedite turnaround times when digitizing slides routinely becomes the next step in automation, in the view of Kenneth Bloom, MD, chief medical officer and medical director of Clarient Inc., Aliso Viejo, Calif.

"The wave of the future will be imaging pathology slides so that pathologists can consult with pathologists in other parts of the world," he says. "For example, large consultative networks may have U.S.-certified pathologists in London or Australia who can review slides at 8 AM there when it's evening or nighttime here. A continuous flow will ensure those cases are reported in a timely fashion."

The times may be changing automationwise in other ways for histology labs.

Though "histology has always been the orphan department in the lab," Sakura's Lefebvre says, many are realizing there is profit in anatomic pathology, especially with the more specialized staining, such as IHC. So "instead of companies selling $50,000 equipment for histology labs, we are now reaching the $200,000 level per transaction," he says. This "wind change in histology," as he puts it, has caught the attention of companies like Roche Diagnostics, which has a bid to acquire Ventana, and Danaher, which recently acquired Leica Microsystems and Vision BioSystems.

And as companies "with large-scale automation in clinical chemistry and hematology enter the market and start introducing equipment, anatomic pathology labs will find that things change even more rapidly than they have seen in the past," Lefebvre predicts. "We think what will happen in automation in histology is similar to what happened in chemistry and hematology": Labs get the new equipment every three to four years.

If that's the case, some of the best advice for histology labs navigating the brave new world of automation might include the ageless caveat emptor.

After all, says Alverno's Dr. Roberts, no one pays you extra for having the most big-ticket automation. So "choose wisely," he advises, based on validation in your setting that the equipment's greater productivity or personnel savings justifies the purchase.