Pathologists and clinical laboratory managers will need a strategy for handling incidental findings

When a genetic test for a certain type of cancer provides additional information that could affect the patient’s health, what is the ethical course of action for pathologists and clinical laboratory scientists? Should this information be disclosed to the physician who ordered that cancer test? In turn, should that physician inform his or her patient about these “incidental findings?”

All medical laboratory professionals will soon find themselves regularly dealing with this challenge because of the rapid increase in the number of molecular diagnostic assays and genetic tests that produce large quantities of data about the patient.

Pathologists Will Need Guidelines That Address Incidental Findings

The term to describe this phenomenon is “incidental findings.” In medicine, this is generally acknowledged to describe previously undiagnosed medical or psychiatric conditions that happen to be discovered unintentionally and are unrelated to the current medical or psychiatric condition which is being treated or diagnostic tests being performed.

As the number of incidental findings increases due to greater utilization of molecular diagnostic assays and genetic tests, pathologists and medical laboratory scientists will need to develop guidelines on how to report incidental findings to the referring physician and to the patient. (photo by Genome Research, Ltd.)

The increase in the number of incidental findings creates a new dilemma for pathologists and their physician-clients. What are the ethical, financial, and technological considerations of disclosing—or not disclosing—this information to the patient? The blame rests with the new, cheaper, and more accurate whole-genome and whole-exome technologies that often not only produce an answer to the primary diagnostic question at hand, but can reveal additional genetic data that affects the patient’s health.

This situation now occurs so frequently that medical researchers are conducting studies into incidental findings and publishing their conclusions. One such study about incidental findings was the subject of a recent story reported by Medical Express. “One of the toughest issues facing the rollout of clinical [gene] sequencing is whether there is a responsibility on the part of clinicians and laboratories to seek and return incidental genomic findings,” stated study co-leader, Robert C. Green, M.D., M.P.H., Professor of Neurology, Genetics, and Epidemiology at Boston University Schools of Medicine and Public Health.

Investigators asked 16 medical specialists to independently evaluate 99 commonly ordered genetic conditions and indicate the ones they would recommend reporting to the ordering physician if discovered incidentally through whole exome or whole genome sequencing.

“This is the first study to ask specialists in genetics and laboratory medicine about the conditions they would like to see returned to clinicians who order genome sequencing,” Green declared. “[T]he majority of specialists agreed that many incidental genetic findings should be returned.”

The medical specialists who participated in this research study indicated a high degree of agreement for disclosure to adult patients when the genetic variant was known to be pathogenic, reported Medical Express. These physicians unanimously agreed on the disclosure of 21 conditions to adult patients. Further, 80% of them recommended reporting results for 64 different conditions. This was especially true for conditions with potential for medical intervention, such as cancer predisposition syndromes.

Greater difference of opinion occurred in three instances:

• when the patient was a child;
• when the variant was only “presumed” or “predicted pathogenic”; and,
• in the case of conditions without potential medical intervention (for example, neurodegenerative disorders, such as Alzheimer’s).

A term to describe such medical situations was coined six years ago. A 2006 commentary published in the Journal of the American Medical Association (JAMA ) warned of the potential of the “incidentalome” to undermine the promise of molecular medicine. The authors likened the incidental findings in molecular and genetic testing to the “incidentalomas” often discovered in radiological studies. “If practitioners pursue these unexpected genomic findings without thought, there may be disastrous consequences,” warned the authors of this paper.

Among the concerns they expressed were the possibility that:

• physicians would be overwhelmed by the complexity of pursuing unexpected genomic measurements;
• patients would be subjected to unnecessary follow-up tests; and,
• costs of genomic medicine would increase substantially with little benefit to patients or physicians.

Medical Laboratories Will Need Methods for Handling Incidental Findings

“This study provides us valuable insight,” observed Howard J. Jacob, Ph.D., Director of the Human and Molecular Genetics Center at the Medical College of Wisconsin, and co-leader of the new study. He was quoted in the Medical Express piece. “[T]he next logical step is learning what patients would want to know about their genome.” Co-leader Green added, ”This paper should inform ongoing efforts to seek consensus in this difficult area.”

In a Science article published on the National Institutes of Health website, members of the Working Group on Incidental Findings in Brain Imaging Research suggested that, as future research on the handling of incidental findings evolves, investigators must have protocols and guidelines for grounding their reasoning and choices. Increasingly, the same holds true for clinicians, for clinical laboratory scientists, and pathologists.”

The Science article authors suggested that researchers and physicians should anticipate incidental findings in their protocols and establish a pathway for handling them. Savvy pathologists and clinical laboratory managers will see this as an opportunity to differentiate their laboratories in two important ways: one, by developing guidelines that address how the laboratory staff should handle incidental findings; and, two, by developing strategies for educating clinicians, not only in utilization of molecular and genetic tests, but also in how to handle the associated incidental findings.

—Pamela Scherer McLeod

Related Information:

Exploring Concordance and Discordance for Return of Incidental Findings from Clinical Sequencing

The Incidentalome: A Threat to Genomic Medicine

Incidental Findings in Brain Imaging Research

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