Tissue samples from patients can contaminate each other on their way to the histology laboratory, reports a single-hospital study that experts say reveals longstanding issues in pathology processing.

Experiments implicated the practice of packing cassettes of tissue samples on racks in a shared formalin bath for transport. The agitation of fluid sloshing back and forth between and through the cassettes presumably dislodges small fragments of tissue that get trapped in other samples, even when protective packaging is used, report the authors, who are pathologists at University of Chicago Medical Center.

"The common approach of submitting and transporting tissue in wet media poses a significant risk of contamination that is casually accepted by most practices," lead author Timothy Carll, MD, told Medscape Medical News. "And as we showed, even using occlusive packaging material within the cassettes themselves does not guarantee the avoidance of contamination."

He concludes by calling for change: "There is a need for practical techniques and technological innovations to reduce this risk."

The study was published this month in the American Journal of Clinical Pathology.

The study originated soon after a hospital construction project separated the grossing room from the histology lab, locating them at opposite ends of the medical campus.

As a temporary solution, the lab chose the hospital's pneumatic tube system to transport dissected tissue to minimize staff traveling between the two locations.

A mysterious source of increased contamination began plaguing the pathology department. Extraneous pieces of tissue from other patient specimens were finding their way into pathologists' slides at an alarmingly high rate. Fortunately, no patients were affected, because the pathologists were able to identify and report these contaminants immediately.

To track down what had gone awry, the investigators designed an experiment to determine if the tube system was the contamination culprit. After ruling out other processing steps as sites of contamination, de-identified specimens known to be common contaminants were subjected to the routine conditions of fixation in formalin, pneumatic tube agitation, and processing.

Steps were taken to minimize contamination throughout the process, including processing specimens at two different benches and placing tissue in protective packaging, including mesh tissue bags, lens paper, and sponges. As a control, some of the tissue was not placed in protective packaging. The specimens were transported to histology as usual via the pneumatic tube system. After processing occurred, samples of formalin were collected from the formalin storage bins, transport containers, and processor waste containers, then spun in a centrifuge for cytologic preparation.

The pathologists found 14.9% of the experimental tissue samples were contaminated by tissue carryover, including those in protective packaging. Cytologic preparations showed viable tumor cells in both formalin storage containers and processor waste fluid, implicating more than just the tube system.

The pathology lab has seen a decrease in contamination since the study, and now sends cassettes removed from liquid, but still wet, via courier to histology.

The authors write that it's not just lab workers using pneumatic tube systems who should be concerned. Agitation of cassettes in liquid of any kind presents a risk. Another form of agitation includes cassette transportation by courier, used by many labs. The study also mentions that contamination could be a concern within tissue processors.

"It seems likely that as long as cassettes are processed adjacent to one another on racks with no filters intervening between them, contamination in the processor retort cannot be ruled out," Carll said.

The study rekindled examination of a century-old dilemma, according to Richard Zarbo, DMD, MD, chairman of the pathology and laboratory medicine department at Henry Ford Health, Detroit, Michigan, who wrote an accompanying editorial.

Zarbo has been on a crusade to reduce contamination ever since a 1994 study, where he and colleague Gordon Gephardt, MD, documented contaminants in 2.9% of 57,083 slides from 275 laboratories. On retrospective review, they reported, 12.7% of the tissue contaminants were found to be neoplastic, and 0.4% were deemed to pose a severe threat to patient care.

Zarbo implicates antiquated slide preparation processes as the main culprit. Slides for microscopic examination in pathology have been prepared the same way for over a century.

Dissected tissue samples are initially placed in hollow, plastic cases with slits called cassettes. Cassettes soak in a formalin bath for several hours, then are loaded into a machine called a processor, which automatically dehydrates the tissue by progressive immersion in alcohols and solvents in order to infiltrate it with paraffin wax in a final step. The paraffin-infiltrated tissue is then embedded in additional paraffin for sectioning into ultra-thin slices which are mounted onto a slide.

The danger of picking up contamination is present at every step of this process — during initial dissection and subsequent fixation, processing, embedding, and sectioning.

To eliminate contaminants, radical change needs to happen, Zarbo writes in his editorial. "Radical means doing things differently, not putting band-aids on the existing separate modes of work," he told Medscape Medical News.

Current processes need serious revision, he contends. "The new process should become seamless, as automated as possible, and with built-in quality control checks," he said. "This will require innovation of technology to continue to provide a substrate for tissue-based pathologic interpretation. This will also require definition of a standardized human interaction with that technology to minimize human error in the new process."

After a patient safety event in his department, for example, Zarbo purchased 1000 reusable forceps for single use with each cassette during embedding. The forceps are decontaminated at night.

Zarbo advises clinicians to "trust but verify" pathology findings. The contaminant numbers may be small overall, but for the individual patient just one such misdiagnosis because of a contaminant is too many.

He continued: "So, for the submitting surgeon or proceduralist, if you receive a pathologic diagnosis that just doesn't make sense, question why. Ask for the case to be re-reviewed for that possibility.

"If you are a pathologist, think twice before making a great diagnosis on the evidence of a minute tissue fragment that doesn't add up in the context of the rest of the tissue or the clinical history. Solve your suspicion by molecular profiling, and if your lab can't perform that test, send it out to one that can microdissect and confirm identity.

"And if you are a patient questioning your surprise diagnosis that doesn't make sense, Zarbo emphasized, "don't be fearful to reach out to your doctor and have the diagnostic material re-reviewed for assurance that your biopsy diagnosis is not due to a misleading contaminant. Everyone involved will thank you." 

Am J Clin Pathol. Published in the July 2022 issue. Abstract, Editorial

Alyse Gray is a pathologist's assistant who also despises slide contamination.

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Cite this: How Can Pathology Labs Better Protect Patient Safety? - Medscape - Jul 29, 2022.

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