Molecular Pathology

June 2024—The Food and Drug Administration’s final rule on laboratory-developed tests was released April 29 and published May 6. Shortly after, Compass Group laboratory leaders met online with CAP TODAY publisher Bob McGonnagle, who asked for their early reactions to what they heard and read. Among the categories for which the FDA has indicated its intent to exercise partial enforcement discretion are LDTs manufactured and performed by a laboratory that is integrated within a health system and that meet an unmet medical need. Here, this month, is the conversation that took place in early May. Next month we will publish our story on the final rule and the views of others. The Compass Group is an organization of not-for-profit IDN system lab leaders who collaborate to identify and share best practices and strategies.

June 2024—In this case report, we aim to elucidate the importance of collaborative molecular and cytogenic testing to offer a diagnosis for complex prenatal situations, such as chimerism, defined by the presence of two genetically distinct cell lines derived from two or more zygotes.

May 2024—Laboratory-developed testing as it relates to next-generation sequencing was up first in the NGS conversation led online by CAP TODAY publisher Bob McGonnagle on March 19. Other topics: in-house NGS testing, artificial intelligence, and bioinformatics. “There’s a reality now where bioinformatics is solid, stable, and reliable,” said José Luis Costa, PhD, of Thermo Fisher Scientific.

April 2024—As the call for fast turnaround of genetic testing results in tumor profiling grows louder, the need for rapid, reliable test methods becomes more pressing. Meanwhile, with new genetic biomarkers emerging at a rapid pace, “everything has tipped the balance toward comprehensive next-generation sequencing analysis,” said Maria E. Arcila, MD.

April 2024—Too few people, too much to do. In that, Duke Health’s molecular diagnostics laboratory is no different from any other laboratory. But competing for staff on the basis of money alone is out. “The reality is that in today’s labor market, any molecular technologist can always find a job that pays more,” says Barbara Anderson, PhD, MB(ASCP)^CM, analytical specialist in Duke’s molecular diagnostics laboratory, Division of Molecular Pathology, Genetics, and Genomics.

April 2024—Primary cutaneous marginal zone lymphoma (PCMZL) is a newly recognized, distinctive subtype of non-Hodgkin’s lymphoma. This low-grade lymphoma predominantly presents as papules or nodules within the skin of middle-aged adults. Formerly grouped under the extranodal marginal zone lymphoma (EMZL) category, the World Health Organization’s fifth edition classification of hematolymphoid tumors now recognizes PCMZL as a distinct entity.

March 2024—From a technologist workforce perspective, clinical genomics laboratories are in trouble. “It’s truly a crisis,” said Marco Leung, PhD, clinical director of the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital in Columbus, Ohio.

March 2024—CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. This month's report comes from Aga Khan University in Karachi, Pakistan. Case. An 87-year-old male with a clinical history of hypertension and sick sinus syndrome presented with a one-month history of fever, generalized weakness, and weight loss. There was no lymphadenopathy or hepatosplenomegaly on physical examination. Bone marrow examination was performed to evaluate for cytopenias.

January 2024—Sometimes even superb ideas can also turn out to be quite, well, bothersome. Zoom meetings. Bridal showers. Bike lanes. Parking apps. QR menu codes. And—if laboratories aren’t careful—the same can be true of pharmacogenomic testing. Just ask Ann Moyer, MD, PhD, associate professor, laboratory medicine and pathology, Mayo Clinic. When it comes to pharmacogenomic testing, laboratory medicine brings significant expertise to the table. But in clinical settings, physicians who prescribe the medications need to be familiar with how to use the test results. They also need to work with the lab to decide which tests, for which genes or gene-drug pairs, will be most helpful for their patients, she says. “Especially if you’re going to start incorporating clinical support alerts into the EHR,” adds Dr. Moyer, who was chair of (until Dec. 31; she is now advisor to) the CAP/ACMG Biochemical and Molecular Genetics Committee. “If the practice doesn’t actually want them, then you’re just going to end up annoying them.”

December 2023—For most, laboratory staffing woes continue, despite some letup post-pandemic. CAP TODAY publisher Bob McGonnagle on Nov. 7 got a sampling of where staffing stands as the year end approaches, in his conversation online with members of the Compass Group, an organization of not-for-profit IDN system lab leaders who collaborate to identify and share best practices and strategies. But first a few words from them about the Food and Drug Administration’s proposed rule on laboratory-developed tests.

CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Washington University School of Medicine in St. Louis. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

November 2023—Few things in the laboratory can do so much at once: boost histotechnologist productivity, safeguard tissue, offer a career path and help retain staff, keep watch on test utilization, and reduce the number of calls to pathologists and turnaround time, all while advocating for the patient.

October 2023—For molecular testing in oncology, the choice is often fast or slow. PCR-based platforms are rapid, and comprehensive genomic profiling by next-generation sequencing is slower, and each has its pros and cons.

October 2023—Next-generation sequencing of tumor tissue has important implications in solid and hematologic malignancies because it can identify genomic variants that provide diagnostic, prognostic, and predictive information to guide clinical management. Variants identified on tumor sequencing can be classified as somatic (acquired after conception) or inherited through germline.

September 2023—CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Henry Ford Hospital. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

September 2023—What happens when an oncologist cannot confidently determine what type of genetic test to order for their patient? Where can a provider turn if they do not know whether a genetic variant is clinically actionable? As genetic testing becomes a more integral part of personalized medicine and health care in general, there is a growing need to bridge the gap between those skilled in molecular diagnostics and those on the patient-facing side of care. In response to this need, the Center for Integrated Diagnostics (CID), a high-complexity molecular diagnostics laboratory at Massachusetts General Hospital, created its Consultation Service.

August 2023—Analyzing the nasal epigenome can shed light on viral infections, strain differences, and potentially infection severity, and for influenza B in particular the results are striking.

CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Washington University School of Medicine in St. Louis.

July 2023—Bringing new technology into laboratories is important for pathology as a field and for patients—and only getting more difficult. “Each new wave of technology is more complicated than the last,” Jeremy Segal, MD, PhD, said at the USCAP meeting this spring.

July 2023—A germline GATA2 c.121C>G (p.P41A) variant in a patient with an unusual acute promyelocytic leukemia CAP TODAY and the Association for Molecular Pathology have teamed up to bring molecular case reports to CAP TODAY readers. AMP members write the reports using clinical cases from their own practices that show molecular testing’s important role in diagnosis, prognosis, and treatment. The following report comes from Emory University School of Medicine. If you would like to submit a case report, please send an email to the AMP at amp@amp.org. For more information about the AMP and all previously published case reports, visit www.amp.org.

May 2023—Behold the common coin. Note its two sides, its easy flippability. Here is Joseph Pizzolato, MD, with the first coin toss. Given the expanded use of biomarkers with a variety of tumors, and constantly evolving assays, how hard is it for medical oncologists to navigate testing? “It’s not difficult at all now,” says a cheerful Dr. Pizzolato, medical director of the comprehensive therapeutic unit of Sylvester Comprehensive Cancer Center, University of Miami Health System, as well as medical director of the Aventura satellite at Sylvester. With third-party companies integrating test ordering directly into electronic medical records, he adds, “It’s getting even easier to order tests and see the results.” Agreed, says his colleague Rhonda Yantiss, MD, director of surgical pathology, Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine. And therein lies the problem. “It’s kind of a mess,” she says. In practice, precision medicine is becoming both more and less precise.

May 2023—Achieving standardization and setting up processes around the use of next-generation sequencing panels for the care of patients with cancer is a long road requiring a lot of expertise.

May 2023—Bringing next-generation sequencing in-house was at the center of a March 27 roundtable led by CAP TODAY publisher Bob McGonnagle, with costs, reimbursement, equity, and the electronic health record part of the conversation. Jeremy Segal, MD, PhD, of the University of Chicago, explains why the Genomics Organization for Academic Laboratories was formed. “By lowering barriers and encouraging cooperation,” he said, “we’ve seen our labs increase the pace of development and the quality of the assays they’re bringing on.”

April 2023—After years of excitement and scientific breakthroughs, the use of molecular testing to guide cancer therapeutics finally is coming into its own. Unfortunately, it appears to have landed in the wrong place at the right time. That place is a lonely spot, surrounded by gaps in economics and coverage, as well as knowledge, guidelines, ordering patterns, turnaround times, reporting, and the like. So plentiful are the gaps that, put together, they could form a vast, inhospitable space, a veritable Colorado Plateau, with molecular testing as a majestic, enticing but remote rocky pinnacle in the middle. Think Monument Valley. It’s worth the trek. The evidence in support of genomic profiling continues to grow. Simply put, “Patients with the right markers who get the right drugs do better,” says Neal Lindeman, MD, vice chair, laboratory medicine and molecular pathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine/New York Presbyterian Hospital. But as numerous studies are showing, the lag in testing is growing as well.

April 2023—Molecular testing guidelines say that the neoplastic cell content of each specimen should be assessed, but there are no formal recommendations or guidelines on how to do the assessment.

November 2022—Rapid next-generation sequencing in a community hospital setting, performed by histotechnologists and interpreted by anatomic pathologists, is possible and paying off, and it “makes the pathologist a much more meaningful part of the precision oncology team,” says Brandon Sheffield, MD, of the Department of Laboratory Medicine, William Osler Health System, Brampton/Etobicoke, Ontario. “It has changed practice at our hospitals,” he says.

October 2022—As the diagnostic uses for next-generation sequencing have grown, so too has the length of the NGS section of the CAP molecular pathology accreditation program checklist. Now, with the release of the new checklist edition this month, NGS laboratories will find the NGS section in their customized checklists leaner, more relevant, and easier to read.