It was the sort of bad news every patient fears. Merlin Erickson, a 69-year-old retired engineer in Abingdon, Maryland, was told last year that a biopsy of his prostate was positive for cancer. Erickson, worried, began investigating the options: whether to have his prostate removed, or perhaps to have radiation treatment.
But a few days later, the doctor called again. As it turned out, Erickson did not have cancer. The lab had mixed up his biopsy with someone else’s. “Obviously, I felt great for me but sad for that other gentleman,” Erickson said.
The other gentleman was Timothy Karman, 65, a retired teacher in Grandy, North Carolina. At first, of course, he had been told he was cancer-free. The phone rang again a few days later with news of the mix-up and a diagnosis of cancer. Ultimately he had his prostate removed. “I said, ‘Mistakes happen,’” Karman said.
They may be happening more often than doctors realise. There is no comprehensive data on how often pathology labs mix up cancer biopsy samples, but a few preliminary studies suggest that it may happen to thousands of patients each year.
Fortunately, there is now a high-tech solution: a way to fingerprint and track each sample with the donor’s own DNA. But it costs the patient about $300 per sample, and labs have been slow to adopt it, saying that the errors are rare and the test too expensive, and that they have plenty of checks in place already to avoid mix-ups.
Dr John Pfeifer, vice chairman for clinical affairs in the pathology and immunology department at Washington University School of Medicine in St Louis, who has studied the problem, is not quite so sanguine. “All the process improvement in the world does not get rid of human errors,” he said. “Millions get biopsies every year. Is society going to say, ‘Yeah, mistakes happen but we’re not going to look for them?’”
The fingerprinting method, offered by Strand Diagnostics, is simple: A doctor gets a DNA sample by swabbing inside a patient’s mouth. It is sent directly to Strand with a bar code identifying the patient.
That bar code is also used to label the patient’s biopsy. If it shows cancer, the pathologist sends the biopsy cells to Strand. The lab matches the DNA from the swab to that of the biopsy cells.
If these DNA fingerprints did not match, that signalled a lab mix-up. That was how pathologists discovered that samples from Erickson and Karman had been switched.
Despite the best efforts of pathologists to avoid these mix-ups, hints of trouble have been turning up for years. In 2011, researchers conducting a large clinical trial reported that two men who were found to have prostate cancer — and who had their prostates removed — did not to have the disease at all. Instead, their biopsy samples had been mishandled.
The researchers then performed a rigorous DNA analysis of more than 10,000 biopsies taken during the period. Twenty-seven were mislabelled. Among 6,733 blood samples, 31, or 0.05%, had been switched.
The percentage of errors may not be high. But each one may lead a patient down a life-altering path, to a gruelling treatment that was unnecessary, or to the neglect of a cancer that may or may not prove deadly.
Pathologists see lab mix-ups routinely, but often the mistake is obvious — a sample supposed to be from a brain actually is from a lung, for example. “You say, ‘OK, yeah, there’s been a mistake,’” Pfeifer said. “I don’t know many pathologists who haven’t had that occur.”
But what about mix-ups that are not so obvious — two lung tissue samples that are switched, or two breast samples? Pfeifer turned to DNA fingerprinting to determine how often such samples are mixed up at Washington University.
He found a few errors — one man’s lung tissue was cancerous, but DNA analysis showed the lung cells were not his. Another patient had a liver biopsy that showed cancer, but the cells were from somebody else.
To really get an idea of the frequency of these mix-ups nationwide, however, Pfeifer needed a large database. Ted Schenberg, the chief executive at Strand, offered to supply the data: more than 13,000 biopsy results from men evaluated for prostate cancer at a number of laboratories.
Pfeifer documented two types of errors in this large sample: an “absolute switch,” in which one patient’s tissue was mixed up with another’s. And a “partial switch” in which some of one patient’s cells ended up mixed in with cells from someone else.
“Every lab had both of these errors,” Pfeifer said. In general, the rates were low — 0.26% of samples were absolute switches, and 0.6% were partial switches. But the rates were slightly higher among independent labs, including large commercial companies that handle huge numbers of specimens: 0.37% were absolute switches, and 3.14% were contaminated.
DNA fingerprinting
Remedying these infrequent errors is a costly endeavour. Most private insurers are willing to cover the testing; it’s far less expensive than paying for unnecessary treatment, or treatment late in the course of a disease that should have been identified sooner.
Medicare, on the other hand, does not cover DNA fingerprinting of biopsies, and many of the patients receiving cancer biopsies are older. Consumers may request DNA fingerprinting themselves, but there is no guarantee that the pathology lab to which their biopsies are sent will offer the service. The cost of doing DNA fingerprinting, Pfeifer argues “is well within the range of costs we see with other clinical testing.”
While mix-ups do happen, pathologists have put a series of steps in place to try to avoid them, including 26 requirements for labelling containers and identifying patients, and ordering tests, said Dr Raouf Nakhleh, vice chair of the College of American Pathologists’ Council on Scientific Affairs and a professor of pathology at the Mayo Clinic in Jacksonville, Florida.
“We get paid $125 to process a specimen and produce a diagnosis,” he said. He turns to DNA fingerprinting only when he suspects a mix-up — for example, a clinical exam is at odds with a pathology report.
Dr. Sanford Siegel of Chesapeake Urology used to feel the same way. But in 2015, a new patient had a blood test that indicated he might have prostate cancer. He had a biopsy, which confirmed it.
The man had his prostate removed — only to learn he had been the victim of a lab mix-up. His reaction, as Siegel recalled? “I am calling a lawyer.” After that, Chesapeake Urology made the DNA test mandatory.