2024 issues

July 2024—Like a long-awaited second act, the FDA’s final rule regulating laboratory-developed tests as medical devices took the stage this spring. As with any FDA performance, this one opened to mixed reviews. The spring curtain-raising followed the earlier proposed rule from last October, which drew some 6,500 responses during the public comment period. If that was an out-of-town tryout, no one quite knew what to expect from the rewrite, or if there would even be one. As it turns out, there were indeed changes, but they didn’t necessarily bring clarity. As Jane Pine Wood, counsel for McDonald Hopkins, puts it, the final rule “certainly raised a whole lot more questions than it answered.” The rule calls for a four-year, five-stage phaseout policy with the FDA enacting greater oversight of in vitro diagnostic products that are offered as LDTs. Stage one, beginning on May 6, 2025, calls for labs to comply with medical device reporting requirements, correction and removal reporting requirements, and quality system requirements regarding complaint files.

July 2024—With the Food and Drug Administration approval in May of two HPV self-collection devices for use in clinic settings, physicians in and out of the laboratory are optimistic the approach can reach underscreened patients, even if FDA approval is only a first step.

July 2024—A Mayo Clinic project is “democratizing artificial intelligence,” its leaders say, by enabling pathologists with varying levels of AI expertise—most of whom had never before participated in an AI project—to create and implement algorithms.

July 2024—Earlier this year the laboratory at King Salman Armed Forces Hospital joined more than 120 other Saudi labs in achieving CAP accreditation. And it did so with a boost from LEAP. The 665-bed hospital needed to adopt standards for nearly all technical specialties and comply with more than 1,000 CAP requirements.

July 2024—In patients with advanced non-small cell lung cancer, a validated PD-L1 immunohistochemistry expression assay should be used, with other targetable genomic biomarker assays where appropriate, for the selection of immune checkpoint inhibitor therapies. And the appropriate validation should be performed on all specimen types and fixatives. Those are two of the six recommendations of the CAP, Association for Molecular Pathology, International Association for the Study of Lung Cancer, Pulmonary Pathology Society, and LUNGevity Foundation, released in April and now in print in their PD-L1 and tumor mutation burden testing guideline for the selection of such therapies.

July 2024—The term value-based care is spoken of often, but what part do laboratories play in it and how can they be paid for it? What is Medicare 2030, and what does it mean for laboratories? How can AI be used to practice the medicine of tomorrow? Myra Wilkerson, MD, in speaking in May at the Pathology Informatics Summit, answered these and other questions. She is chair of the Department of Laboratory Medicine and of the Diagnostic Medicine Institute at Geisinger Health in Danville, Pa. She is a founding member of the Project Santa Fe Foundation, for which she serves on its board and as treasurer. She opened her talk in May about Project Santa Fe’s Clinical Lab 2.0 model—what it looks like now and the work they’re doing. We bring to you here what she shared there.

July 2024—The CAP’s hematopathology online education program, HPATH, is now in its 10th year, with real-world cases for which there’s real-time feedback and hundreds enrolled each year. Interesting cases, ones every hematopathologist should have experience with or be familiar with, are what the expert authors of the cases provide, says Kyle Bradley, MD, chair of the CAP Hematopathology Committee and associate professor of hematopathology at Emory University School of Medicine. Each case includes laboratory data, whole slide images, images of ancillary studies, feedback about the case and test results, and self-assessment questions. “And some of the high quality comes from brevity,” Dr. Bradley says. “We whittle down a lot of information into something very manageable and high yield for busy pathologists.”

July 2024—The University of Maryland Medical Center is one of many sites using low titer O whole blood in trauma cases. As of May, 720 patients at UMMC had received whole blood, and that number of patients treated since the program’s start in 2021 speaks for itself, says Bryon P. Jackson, MD, MHA, Midtown Campus laboratory director and director of blood management and associate director of transfusion medicine services.

July 2024—Instruments, assays, patient flow, and IT were some of what laboratory directors and IVD company representatives spoke of when CAP TODAY publisher Bob McGonnagle convened the group online on May 3. Here’s what they said about what instruments and assays are deployed where and the considerations that come into play in large health systems.

July 2024—Remote sign-out has become a major issue for pathologists, spurred in large part by the COVID-19 pandemic and the CAP’s advocacy efforts that led to our ability to sign out cases from other locations. The Centers for Medicare and Medicaid Services has allowed remote sign-out to continue long after the public health emergency was declared over and is considering making this a permanent rule. I recognize how popular remote sign-out has become and have enjoyed many of its advantages in my own practice. However, I also see a few possible unintended consequences that I think are very important for us to consider before we let things get too far.

July 2024—People with sickle cell disease may undergo treatment with the medication voxelotor, which can increase hemoglobin levels and help reduce hemolysis. A clinician treating a sickle cell disease patient with voxelotor may want to know the whole blood concentration of the drug to better monitor the patient’s treatment response, inform therapy, or confirm the patient is complying with the directions for use of the drug. Voxelotor binds to the alpha subunit of hemoglobin and results in the hemoglobin molecule being more likely to stay in the oxygenated conformation. In vivo concentrations of voxelotor cannot be measured in most clinical settings. However, voxelotor has been found to cause peak splitting in common forms of hemoglobin measurement, such as capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC)—that is, the classic peaks for each hemoglobin species split into a peak that has bound drug and a peak that does not.

July 2024—The 2022 International Society of Urological Pathology consensus conference on urinary bladder cancer working group two was tasked with providing evidence-based proposals on applying grading to noninvasive urothelial carcinoma with mixed grades; invasive urothelial carcinoma, including subtypes and divergent differentiations; and pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has an intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component.

July 2024—Telomeres are repetitive DNA sequences at the end of a chromosome that protect the chromosome from damage. They are maintained in equilibrium, as continual shortening at each round of DNA replication is counterbalanced by the de novo addition of telomere sequence repeats by telomerase. Failure to maintain the length distribution leads to short telomere syndromes that manifest as age-related degenerative diseases, such as pulmonary fibrosis, immunodeficiency, and bone marrow failure. In contrast, long telomeres can predispose people to cancer. Mutations that increase telomerase expression are one of the most common cancer-associated molecular findings.

July 2024—The integration of machine learning models into pathology has revolutionized the field, offering new functionalities and workflows. Numerous machine learning (ML) models are commercially available, and organizations with computational pathology resources can develop their own. These models, whether or not they are imaging based, are intended to enhance clinical practice. However, no formal guidelines pertaining to verifying or validating such systems are available. Therefore, the authors proposed recommendations for evaluating ML systems that are based on evidence and literature that address, among other factors, the scope, strengths, and limitations of the technology.

July 2024 Q. Insulin assays traditionally have been used to work up hypoglycemia, but we are noticing more and more requests for insulin and C-peptide testing. Is there a reason for this shift? Read answer. Q. How should a lot-to-lot formalin comparison be done? Read answer.

July 2024—Earlier this summer, Danbury Hospital completed its first academic year using an integrated pathology informatics curriculum that introduced informatics exercises into seven of the pathology residency program’s 18 rotations. “The goal is for residents to learn informatics alongside the pathology workflows where they can apply it,” says Samuel Barasch, MD, medical director of cytopathology at the Danbury, Conn.-based hospital, part of the Nuvance Health Network.

July 2024—The CAP, Association for Molecular Pathology, and Society for Immunotherapy of Cancer released in June their recommendations for tumor mutational burden assay validation and reporting. The joint publication summarizes the existing knowledge and challenges related to TMB testing. The authors make 13 recommendations related to testing, reporting, and publications on TMB assays.

July 2, 2024—Cepheid has received FDA de novo marketing authorization and CLIA waiver approval for its Xpert HCV, the first point-of-care hepatitis C RNA test.

June 2024—When it comes to detecting cervical precancer (CIN3), p16/Ki-67 dual stain testing cuts down on the number of colposcopies compared with using Pap cytology to triage HPV-positive patients. “Using cytology [for triage], you need to do about 32 colposcopies to identify one cervical precancer [CIN3]. If you were to switch to dual stain, it cuts it in half,” says Thomas Lorey, MD, senior consultant and former director of laboratory services for Kaiser Permanente Northern California, from which much of the data underpinning the guidelines on cervical cancer screening and management have been collected. Dr. Lorey and others are coauthors of new clinical management dual stain test recommendations, released in March by the member organizations of the Enduring Consensus Cervical Cancer Screening and Management Guidelines effort. The new recommendations address only the Roche CINtec Plus Cytology test, which detects both p16 and Ki-67 and was approved by the Food and Drug Administration in 2020.

June 2024—Since ChatGPT sprang on the scene a year and a half ago, debate and concern about the OpenAI chatbot and how closely it can replicate human abilities have been widespread, as have thoughts on how to translate AI-based applications into clinical practice.

June 2024—At-home acute and advanced care testing, ethical quandaries, and the lab’s ecological footprint are three of the topics that ADLM meeting-goers can sign on for next month in Chicago.

June 2024—Meagan Chambers, MD, MS, MSc, feels like she has signed on for a life of being on call for 2 AM autopsies, and she says nothing could please her more. She is a neuropathology fellow at the University of Washington and does many of the rapid autopsies that make possible a range of human research that would otherwise be limited or out of reach.

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—Screening in transgender men with cervices and in transgender women with neovaginas was the focus of a CAP23 session that highlighted screening recommendations and morphologic challenges such as detecting high-grade dysplasia in a background of atrophy (trans men) and dysplasia risks (trans women)—and EHR-related improvements for both.

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.

June 2024—Idiopathic multicentric Castleman disease, which is driven by a cytokine storm with an unknown cause, is a difficult diagnosis and one that’s often delayed, owing to the disease’s rarity and nonspecific symptoms. “Patients often bounce around for months, or even years, to different specialties, based on how they present, before they are diagnosed,” said Jadee Neff, MD, PhD, assistant professor of pathology, Duke University Medical Center, in a CAP TODAY webinar in February made possible by a special educational grant from Recordati Rare Diseases.

June 2024—All of us in the pathology community, no matter how winding our career paths may have been, at some point made the same choice. Of all the medical specialties available to us, we were drawn to become pathologists.

June 2024—In today’s health care environment, clinical laboratories increasingly must focus on test optimization, or generating quality patient care in a timely manner while controlling costs. A metric that can assist with test optimization is turnaround time (TAT), the reduction of which can lead to earlier diagnosis and treatment. Conducting assays in house is one way to potentially reduce TAT. Laboratories often use test volume and the cost of reagents, equipment, and personnel to determine the benefit of bringing an assay in house. However, it is important not to overlook the impact and costs that extend beyond the laboratory with regard to patient care and potential savings from improved care.

June 2024—Neuroendocrine neoplasms can arise in a variety of anatomic sites, including the gastrointestinal tract, pancreas, and lung. The authors conducted a study in which they examined the diagnostic utility of S100 protein expression by IHC. They reported on the expression of S100 protein in a tissue microarray composed of 919 primary and metastatic neuroendocrine neoplasms from 548 patients. S100 protein is commonly used by laboratories to identify neural and melanocytic neoplasms. It is occasionally used in the workup of neuroendocrine neoplasms when the diagnosis of paraganglioma is being considered.

June 2024—Somatic mutations in SETBP1 occur in a variety of myeloid malignancies, including myelodysplastic/myeloproliferative neoplasms, typically as secondary events during oncogenesis. However, whether SETBP1 alterations can serve as an initiating event for myeloid neoplasia and what other factors may influence the phenotype of SETBP1-mutated myeloid neoplasms remains unclear. To determine if SETBP1 mutations can initiate leukemia in vivo, the authors generated a mouse model expressing mutated SETBP1 in hematopoietic tissue. They reported that SETBP1^G870S-mutated mice developed a chronic myeloid disorder with massive hepatosplenomegaly, myelofibrosis, atypical megakaryocytes, and granulocytic hyperplasia without granulocytic or erythroid dysplasia. SETBP1^G870S precursors showed significant alterations in the transcriptional programs of differentiating hematopoietic cells, promoting granulocytic/monocytic differentiation while suppressing erythroid differentiation.

June 2024 Q. What are the requirements for correcting an automated white blood cell (WBC) count for the presence of megakaryocytes? Is there a formula for correcting it for megakaryocytes, as there is for the presence of nucleated red blood cells (nRBCs)? Read answer. Q. Are there guidelines on how often a patient should be monitored for a blood transfusion reaction? Should reactions be monitored as frequently as vital signs? Read answer.

June 2024—Fairness, like so many principles, is subjective. Yet that is not deterring a growing number of medical informaticists and others interested in health care technology from advocating to incorporate fairness into machine learning algorithms to combat bias.

June 2024—The Food and Drug Administration in May approved the two HPV self-collection approaches from Roche and BD.

May 2024—If anything keeps Arturo Casadevall, MD, PhD, lying awake at night, it’s the frogs. And the bats. Also, the patients (relatively few, at least for now) who are affected by invasive fungal diseases. Dr. Casadevall is a microbiologist and infectious diseases expert in the Johns Hopkins Division of Infectious Diseases, Department of Medicine, and the Bloomberg School of Public Health, where he’s a professor of medicine and chairs the Department of Molecular Microbiology and Immunology. In his waking hours, he looks deeply and broadly at the natural world and how the disturbing growth of fungal infections might impact the medical world. Though the arrows haven’t hit the bull’s-eye, they seem to be flying in that direction, says Dr. Casadevall, who has written widely on this topic, including “Immunity to Invasive Fungal Diseases.” In a recent interview with CAP TODAY, Dr. Casadevall spoke about how he and others in the field are thinking about how medicine might respond to this potential threat.

May 2024—In a time of wellness testing and high rates of levothyroxine prescribing for hypothyroidism, it may also be time to rethink TSH test result interpretation.

May 2024—Many laboratories have brought order to chaos in test ordering by launching initiatives to do so, for cost and staff savings and patient care benefits. TriCore is one—it set its sights on orders for monoclonal gammopathies.

May 2024—What is a lupus anticoagulant (LA)? LA is somewhat of a misnomer. Many patients with this condition do not have systemic lupus erythematosus (SLE) and usually do not bleed. However, the in vitro phenomenon was originally described in patients with SLE, as well as other autoimmune disorders—thus use of the term “lupus,” and this does often lead to prolonged in vitro coagulation testing—thus use of the term “anticoagulant.”

May 2024—The number of “champions” who have joined the CAP’s Future Pathologist Champion program grew from 71 in 2022 to 135 in 2023 and now stands at 222, and the goal is to reach 250 by the end of this year.

Four views of artificial intelligence in pathology and laboratory medicine. That’s what panelists provided for attendees at the 7th Clinical Lab 2.0 workshop in late February in Chicago. The University of Michigan’s Ulysses G. J. Balis, MD, spoke of AI’s use in laboratory operations and diagnostics. Tom Neufelder of Beckman Coulter spotlighted its use in instruments and postanalytically. Gaurav Sharma, MD, of Henry Ford Health is the skeptic, and the University of Pittsburgh’s Michael Becich, MD, PhD, is the rabid enthusiast who is working to unite pathology’s reports and calls himself a data plumber.

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.

May 2024—Classically, immunohistochemical expression of small cell lung cancer (SCLC) is characterized by strong expression of neuroendocrine markers, notably synaptophysin, chromogranin A, insulinoma-associated protein 1 (INSM1), and CD-56. However, up to 20 percent of SCLCs demonstrate low or no expression of neuroendocrine (NE) markers by IHC and are termed “NE-low/negative.”

May 2024—Breast cancer continues to remain a major global health issue and one of the main leading causes of cancer mortality among women worldwide. The majority of breast cancer mortality is attributed to its ability to metastasize. Bone, lung, liver, pleura, and brain are the most common sites of metastatic lesions, often spreading from invasive breast carcinoma of no special type.

May 2024—Fine-needle aspiration has been an important diagnostic tool for the workup of patients with abnormal enlargement of lymph nodes and related organs, including the spleen and thymus.

May 2024—You may have read my column in the March issue about how the CAP is taking care of the next generation of pathologists by helping and engaging our new-in-practice colleagues. If you’re a more seasoned pathologist, you may be wondering: What about me?

May 2024—Massive hemorrhage is a major cause of death in children, and the mortality rate from life-threatening hemorrhage is estimated to be 20 to 51 percent. To counter this high mortality rate, clinicians have sought to standardize massive transfusion protocols and hemostatic resuscitation, ensuring that protocols support balanced blood-based resuscitation or the use of low titer group O whole blood, or both. These protocols may include using the lysine analogue antifibrinolytics tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) in children with life-threatening hemorrhage (LTH). However, use of these antifibrinolytics is much more common in adult trauma patients. Study data suggest that TXA may increase survival outcomes in adults with traumatic injury, postpartum hemorrhage, nontraumatic intracranial hemorrhage, and all-cause bleeding.

May 2024—The Bethesda System for Reporting Thyroid Cytopathology described four subclasses of atypia within the atypia of undetermined significance category: nuclear (AUS-Nuc), architectural (AUS-A), oncocytic (AUS-Onc), and atypia not otherwise specified (AUS-NOS). Accumulating evidence supports the use of a binary AUS subclassification scheme based primarily on the presence of nuclear atypia only. The authors conducted a study to compare the risk stratification of binary versus four-tier AUS subclassification systems among AUS nodules with molecular or histologic follow-up, or both. The study included thyroid aspirates classified as AUS and tested using Afirma (Veracyte Inc.) between June 2013 and July 2021. Histological classification was considered the final outcome for resected nodules.

May 2024—Immunotherapy has revolutionized cancer treatment by recruiting the patient’s immune system to detect and destroy cancer cells. Immunotherapy often involves immune checkpoint blockade (ICB) agents, which target negative regulators of T-cell activation, such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1). Although ICB is used to treat a variety of cancer types, patients’ response to therapy is often unpredictable, and biomarkers such as tumor mutation burden, mismatch repair deficiency, and IHC for PD-L1 have limitations for assessing ICB response. Consequently, there is great interest in discovering additional biomarkers that will improve the ability to predict clinical response to ICB. Recent studies have explored the hypothesis that there may be a correlation between a person’s gut microbiome and therapeutic response.

May 2024 Q. I know that CLIA is changing and more tests/analytes will become CMS regulated, along with other changes. Can you provide some background and an overview of the changes and when they will become effective? Read answer.

May 2024—The FDA has granted marketing authorization, through the de novo pathway, for Prenosis’ Sepsis ImmunoScore artificial intelligence-enabled software as a medical device, or SaMD, for the rapid diagnosis and prediction of sepsis.

May 2024—Risant Health has completed its acquisition of Geisinger as its first health system dedicated to increasing access to value-based care and coverage. Risant says the organizations together will create a new value-based care platform that includes best practices, tools, technology, and services to support community-based health systems.

April 2024—The rise in fungal infections in recent years troubles Sean Zhang, MD, PhD, for reasons near and far. It’s readily apparent in the patient populations at Johns Hopkins Hospital, where he is director of the mycology laboratory. Especially concerning is the increase in Candida auris following the height of the COVID-19 pandemic, both in terms of colonization and infection cases, says Dr. Zhang, who is also associate professor of pathology, Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine. “Since 2022, we suddenly saw an uptick in Candida auris cases across the Johns Hopkins Health System.” But the situation isn’t unique to Johns Hopkins. Pointing to CDC figures, he notes that the tide is rising more broadly as well. The agency reports that in 2020, there were 757 clinical cases and 1,310 screening cases of C. auris in the United States. In 2022, there were 2,377 clinical cases and 5,754 screening cases.

April 2024—With the technology now available, could and should remote diagnostic pathology, or at least a hybrid model, become more the norm in the future? Timothy Craig Allen, MD, JD, and Casey P. Schukow, DO, of Corewell Health in Michigan, in an editorial published recently, say the time for one or the other or both has come.

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—The Food and Drug Administration in February cleared Proscia’s Concentriq AP-Dx digital pathology software for the purpose of primary diagnosis.

April 2024—In billing for pathology and laboratory services, the hurdles are only getting higher. Narrow networks, prior authorizations, claims denials. Payers “have deeper pockets and figure they can outlast us,” said Joe Saad, MD, chair of the CAP Council on Government and Professional Affairs, in a Feb. 14 roundtable led online by CAP TODAY publisher Bob McGonnagle. He and others talked about AI, digital pathology codes and molecular Z-Codes, biomarker testing, and unity within the laboratory community.

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.

CAP Publications released this month its newest book, Quality Management in Clinical Laboratories: Optimizing Patient Care Through Continuous Quality Improvement. It is a second edition; the first was published in 2005. Twenty-one contributors cover everything from laboratory staff and informatics to all phases of testing and the laboratory quality management plan.

April 2024—When Tip O’Neill, former speaker of the U.S. House of Representatives, said many years ago that all politics is local, he was talking about how elections, legislation, and all of politics affect people where they live. I believe the concept applies just as much to pathology advocacy. When it comes to the issues we care about for our profession and for our patients, our efforts in advocacy, lobbying, educating, and persuading all need to happen at the local level just as much as at the national level.

April 2024—Neonatal anemia is a common comorbidity of premature infants and may result from certain obstetric conditions or diseases, or, in the case of iatrogenic anemia, from multiple phlebotomies in the first days of life. Once infants enter the neonatal intensive care unit (NICU), they undergo a series of laboratory tests at baseline and then as needed for treatment or monitoring. These tests commonly include blood cultures, CBCs, coagulation profiles, metabolic screens, blood gases, blood glucose, and chemistry profiles. Phlebotomy-associated blood loss is more clinically relevant in lower birth-weight neonates since they have lower total circulating blood volumes. When blood is drawn from an indwelling umbilical catheter, even more blood is removed due to the need to flush residual intravenous fluid from the line.

April 2024—Fumarate hydratase-deficient renal cell carcinoma is a rare and distinct subtype of renal cancer caused by FH gene mutations. FH negativity and s-2-succinocysteine (2SC) positivity on IHC can be used to screen for FH-deficient renal cell carcinoma (RCC), but their sensitivity and specificity are imperfect. The expression of AKR1B10, an aldo-keto reductase that catalyzes cofactor-dependent oxidation-reduction reactions, in RCC is unclear. The authors compared AKR1B10, 2SC, and FH as diagnostic biomarkers for FH-deficient RCC. They included genetically confirmed FH-deficient RCCs (n=58), genetically confirmed TFE3 translocation RCCs (TFE3-tRCC; n=83), clear cell RCCs (n=188), chromophobe RCCs (n=128), and papillary RCCs (pRCC; n=97).

April 2024—Personalized medicine is revolutionizing cancer therapy, with targeted treatments customized to a person’s cancer-specific mutational profile leading to substantially improved health outcomes. Personalized medicine can also be applied to cancer prevention for high-risk groups based on genetic predisposition or lifestyle factors. However, there is a significant gap in cancer research resulting from a lack of equitable representation of racial and ethnic groups in cancer databases. Most research data are derived from white patients in the United States and Europe, creating racial disparities in understanding cancer development and therapies. The underrepresentation of patients of African, Asian, and Native American descent in observational, translational, and clinical cancer studies is particularly notable.

April 2024—Transitioning to digital pathology can seem complex and costly. And for some, but not all, laboratories, cost in particular can be a barrier to adoption. So how do you determine which camp your lab falls into? You calculate, according to Orly Ardon, PhD, director of digital pathology operations at Memorial Sloan Kettering Cancer Center.

April 2024 Q. Ordering clinicians are requesting that our laboratory flag abnormally high absolute neutrophil counts (ANC) on peritoneal fluids. We cannot find sources for reference ranges, but there is literature that states that a polymorphonuclear cell count greater than 250/μL is a reliable discriminatory test for bacterial peritonitis. We would like to use this as our reference and flag results with an ANC greater than 250 cells/μL as abnormally high. Is this acceptable? Read answer. Q. How do you code fallopian tubes submitted for sterilization with a finding of a paratubal cyst? Read answer.

April 2024—The article “Test adds twists to lung disease diagnosis” (November 2023, page 1) virtually ignores the major problem of clinicians in the hospital thinking that it is perfectly okay to take specimens from patients in the hospital and send them directly to whatever laboratory they choose without input from the hospital’s laboratory administration or medical director. The laboratory medical director is legally responsible for approving the menu of laboratory tests to be performed in-house and all of the reference laboratories to be used.

April 2024—Member organizations of the Enduring Consensus Cervical Cancer Screening and Management Guidelines effort released in March their recommendations for the use of p16/Ki-67 dual stain for managing individuals who test positive for HPV.

March 2024—Like identifying the shift in battle that leads to victory, or the battle that wins the war—let alone declaring a war’s ultimate victor—it’s hard to gauge the whens, ifs, and hows that mark progress in medicine. For those who are deeply rooted in bringing advances to testing in urothelial cancers, current research is flourishing and flummoxing. In early and late stage, both for bladder and upper tract disease, recently approved therapies are leading to better outcomes for patients. More immunotherapies and antibody-drug conjugates are on their way, and with them come new options for testing. But as with any cancer, researchers follow numerous promising paths, knowing that some will dead-end and others will succeed primarily (albeit usefully) in raising more questions. Nevertheless, they continue to rally the work forward, with multiple breaches, and Agincourt, ever in sight. For experts such as David McConkey, PhD, progress will best be measured by how regularly precision makes its way into the clinical setting.

March 2024—Pathology trainees and training programs vary, as do first jobs, but the first year in pathology practice is generally said to be a tough one, largely because of the transition to fully independent case sign-out.

March 2024—For patients with type 2 diabetes, the cardiac biomarkers are a better predictor of early-stage heart failure than conventional risk prediction scores. “We need to use biomarkers,” says Petr Jarolim, MD, PhD.

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—Anatomic and clinical pathology reporting—what’s working, what’s missing. Three pathologists (all board certified in informatics) and representatives of three information system companies met online Dec. 19 with CAP TODAY publisher Bob McGonnagle to talk about reporting needs and what’s optimal. The first half of their discussion was published in the February issue, with CAP TODAY’s guide to anatomic pathology computer systems. The second half begins here.

March 2024—For urine toxicology screening, immunoassays are automated and rapid but have variable sensitivity and specificity and results are considered presumptive. Mass spectrometry, used for confirmation, has superior sensitivity and specificity but is labor-intensive and slow and requires significant expertise.

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.

March 2024—Reflex criteria, middleware, bladder cancer screening, point of care, controls, and collections came up in CAP TODAY’s Jan. 16 roundtable on urinalysis. Six people weighed in, with CAP TODAY publisher Bob McGonnagle leading. Their take on where things stand and where they can be better follows. CAP TODAY’s guide to urinalysis instrumentation begins here. Tim Skelton, in last year’s ...

March 2024—During the 12 years I spent as director of a pathology residency program, one thing I worried about was how to better prepare our residents for their first roles as attending pathologists or laboratory directors. For many pathologists, the transition from always having someone looking over their shoulder to being on their own is very challenging.

March 2024—Despite research into colorectal cancer screening and clinical experience, screening uptake remains low. Colorectal cancer (CRC) screening involves noninvasive tests, such as a fecal immunochemical test (FIT) and stool-based DNA tests, as well as invasive tests, such as colonoscopy. The latter has the best performance characteristics for early cancer and adenoma detection. The average adherence to CRC screening is 60.6 percent for U.S. patients aged 50 to 75 years, which is well below the 80 percent goal for adherence set by the National Colorectal Cancer Roundtable and American Cancer Society. Offering stool-based tests to patients who refuse colonoscopy results in only a modest increase in adherence, to 67 percent.

March 2024—Lung transplantation is the definitive therapy for end-stage pulmonary sarcoidosis. While several case reports have described recurrent sarcoidosis in allografts, the incidence and clinicopathologic characteristics remain unclear. The authors conducted a study in which they characterized the clinical and histopathologic features of recurrent sarcoidosis diagnosed in post-transplant lung surveillance transbronchial biopsies (TBBx). They identified 35 patients who underwent lung transplant for pulmonary sarcoidosis during the study period. Eighteen (51 percent) of the patients experienced recurrent sarcoidosis post-transplant—seven females and 11 males (mean age at recurrence, 51.6 years).

March 2024—Human epidermal growth factor receptor 2 is a critical biomarker in breast cancer, gastrointestinal malignancies, and other cancers. HER2 protein expression can be evaluated using IHC, and the DNA copy number of its encoding gene, ERBB2, can be evaluated using FISH. In most clinical settings, IHC evaluation is categorized as positive (3+), equivocal (2+), or negative (0 to 1+), with equivocal cases being reflexed to FISH. Patients with HER2-positive tumors, defined as either 3+ or 2+/FISH positive, have been eligible to receive HER2-targeted therapy for many years. More recently, the FDA approved the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) to treat patients with HER2-low breast cancer, defined as tumors with IHC 1+ or 2+/FISH negative. This promising treatment has allowed many more patients to receive molecular-targeted therapy.

March 2024 Q. Is it a requirement that routine bacteriology cultures (for example, urine, sputum) be plated in a biological safety cabinet in your typical hospital biosafety level 2 laboratory? Is it safe to read these cultures on an open bench? Read answer. Q. What source should a laboratory use for reference intervals for analytes? Read answer.

March 2024—While Dr. Seuss’ assertion that “the more that you read, the more things you will know” is generally accurate, it doesn’t address the fact that how information is presented affects comprehension, a truism that is not lost on Edward Klatt, MD, who knows whereof he speaks when it comes to sharing information on patient portals.

March 2024—The Food and Drug Administration approved in December the AvertD test, which assesses whether an individual may have an elevated risk of developing opioid use disorder. Its intended use is to inform the decision-making of patients and physicians about the use of oral opioids for acute pain relief.

February 2024—From her vantage at the University of Texas MD Anderson Cancer Center, Donna Hansel, MD, PhD, has a clear view of cancer’s latest frontiers. Progress and breakthroughs are the norm. But even she sounds impressed when she surveys the changes in her specialty, urothelial cancer. “We are now thinking what we never before thought was possible: We are thinking about cures and lifelong remission from disease,” says Dr. Hansel, division head and professor of pathology and laboratory medicine. It’s been a long time coming, says Dr. Hansel, who is also the Dr. Eva Lotzova and Peter Lotz memorial research chair. The disease historically has been caught in a sort of prepositional triangle—underfunded, overlooked, and underdiagnosed—with serious consequences. For years, she says, “We thought bladder cancer had only one treatment”—BCG, or Bacillus Calmette-Guérin, therapy. Because the field lacked a large volume of research to propel better diagnostics and treatments, “people died of this disease because it progressed.”

February 2024—Artificial intelligence is sizzling, so much so that New Yorker magazine, evoking the dazzling and the potentially devouring nature of AI technology, tagged 2023 as “The Year A.I. Ate the Internet.”

February 2024—When multimodality testing reveals discordant biomarker results, which method is correct? Annette S. Kim, MD, PhD, and JinJuan Yao, MD, PhD, in a CAP23 session last fall used their cases to share strategies for resolving discrepancies—or, in some cases, what look like discrepancies.

February 2024—Artificial intelligence and Medicare Advantage contracts were at the center of the Jan. 2 Compass Group virtual roundtable led by CAP TODAY publisher Bob McGonnagle. “If you want to get into the AI world, there are many lanes you can swim in,” said Michael Feldman, MD, PhD, of Indiana University School of Medicine.

February 2024—Ethiopia’s health care system is at a crossroads as it grapples with the dual burden of infectious diseases and a surge in noncommunicable ailments.

February 2024—Efficiency can be hard to measure. But Kenneth Batts, MD, of Hospital Pathology Associates in Minneapolis, which contracts with Allina Health to provide anatomic pathology coverage, is sure that a pathology aide program the group started long ago makes its pathologists far more efficient.

February 2024—Xylazine prevalence, lab-developed testing, and new technology are converging at Yale New Haven Health in a way that gives rise to questions, worry, and new hope for faster drug testing.

February 2024—Anatomic and clinical pathology reporting—what’s working, what’s missing. Three pathologists (all board certified in informatics) and representatives of three information system companies met online Dec. 19 with CAP TODAY publisher Bob McGonnagle to talk about reporting needs, the changes, what’s optimal. The first half of their discussion begins here; the second half will be published in the March issue.

February 2024—Even before the pandemic, burnout had become a major issue in medicine. Today, the effects of too much stress, staff shortages, and increasing demands have become so widespread in health care that they cannot and should not be ignored.  

February 2024—Patients receiving a pathology report may have many outstanding questions that can cause anxiety and confusion. The 21st Century Cures Act has increased patients’ access to pathology reports via delivery to patient portals. However, reports sent without further explanation can exacerbate the anxiety and confusion. Many health care institutions are creating new communication methods to help patients interpret these reports and develop a better understanding of their health status. One such approach is the pathology explanation clinic (PEC), which is an interactive visit between patients and pathologists to discuss the pathology report and review the patient’s slides.

February 2024—The gold standard for prostate cancer diagnosis is the pathological examination of prostate biopsy tissue by light microscopy. The application of artificial intelligence (AI) to digitized whole slide images (WSIs) can aid pathologists in cancer diagnosis, but robust, diverse evidence in a simulated clinical setting is lacking. The authors conducted a study to compare the diagnostic accuracy of pathologists who read WSIs of prostatic biopsy specimens with and without AI assistance. Eighteen pathologists, two of whom were genitourinary subspecialists, evaluated 610 prostate needle core biopsy WSIs prepared at 218 institutions, with the option for deferral. Two evaluations were performed sequentially for each WSI: the first without assistance and the second, conducted immediately thereafter, aided by Paige Prostate (Paige, New York City).

February 2024—Precision cancer medicine relies heavily on understanding the genomic landscape of tumors. Prior comparisons between African and European ancestry, though based on limited data, have indicated distinct differences in the landscape of cancer driver alterations between these populations. Whether these discrepancies are mediated by genetic variants or environmental influences is still unclear. Accurately characterizing ancestry-associated genomic alterations is essential to not only improving genomic diagnostic testing but also to developing targeted therapies, biomarkers, and personalized cancer care for diverse populations. The authors conducted a study that leveraged two large genomic cohorts to investigate the relationship between genomic alterations and African ancestry in six common cancers: prostate, pancreas, ovary, nonsmall cell lung cancer (NSCLC), colorectal, and breast.

Feburary 2024 Q. In a case of suspected drug-related death, how specific can an autopsy be in identifying the drug(s) that might have caused the person’s death and the amount of drugs present? For example, can a toxicology report say a person’s death was caused by a fake oxycodone pill containing fentanyl? Read answer. Q. A nephrology patient who has been treated with vitamin D₂ for several years contacted our laboratory to find out why their 25-hydroxyvitamin D level of 60 ng/mL is now considered elevated when before it was within the normal range. How can we explain this? Read answer.

February 2024—The key to using ChatGPT and other large language models effectively in pathology is understanding not only what they are designed to do but, just as importantly, what they are not designed to do, says Eric Glassy, MD, medical director at Affiliated Pathologists Medical Group, Rancho Dominguez, Calif., and past chair of the CAP Information Technology Leadership Committee.

February 2024—Members of the CAP Machine Learning Working Group, Informatics Committee, Digital and Computational Pathology Committee, and Council on Informatics and Pathology Innovation have proposed 15 recommendations for evaluating the performance of machine learning-based clinical decision support systems in pathology.

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.”

January 2024—Thrombophilia testing has been shown to be performed far more often than indicated in thromboembolic events, at significant cost to the patient and hospital.

January 2024—The Food and Drug Administration’s proposed rule on laboratory-developed tests would phase out its existing enforcement discretion approach for oversight of LDTs. Instead, the FDA would classify in vitro diagnostics offered as LDTs as class I, II, or III medical devices depending on their risk to patients.

January 2024—Much has been said and written about scoring HER2-low breast cancer, and it has its difficulties. But there are steps and tools to support scoring, and Savitri Krishnamurthy, MD, last fall shined a light on them and several HER2-low breast cancer-related studies.

January 2024—Seven recommendations for the use of cardiac troponin measurement at the point of care were published last year and reported in a session at the Association for Diagnostics and Laboratory Medicine annual meeting, shortly after the recommendations appeared in print.

January 2024—Thoracic SMARCA4-deficient undifferentiated tumor (TSDUT), formerly known as SMARCA4-deficient thoracic sarcoma and SMARCA4-deficient thoracic sarcomatoid tumor, is a relatively newly defined entity with a distinct clinical history, morphology, immunohistochemical profile, molecular findings, and clinical behavior.

January 2024—The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a widely endorsed and globally adapted standardized reporting system of thyroid fine-needle aspiration specimens.

January 2024—Urinary cytology is widely used to screen for high-grade urothelial carcinoma (HGUC) and to monitor for recurrence. Several reporting systems have been proposed over the past few decades, but The Paris System (TPS) for Reporting Urinary Cytology is the most widely applied worldwide.

January 2024—Viscoelastic assays and other coagulation tests were front and center when CAP TODAY publisher Bob McGonnagle on Nov. 20 convened seven people in an online roundtable. Oksana Volod, MD, and Eric Salazar, MD, PhD, and five company representatives weighed in on, among other things, appropriate test use, automation, and laboratory-developed tests. What they said begins here.

January 2024—I was planning to write about a much more pleasant topic this month, but instead I’ll use this column to address something that’s gnawing at all of us now: the prospect of FDA regulation of laboratory-developed tests.

January 2024—People respond differently to SARS-CoV-2 infection, with some having a very severe clinical course and sequelae while others recover quickly. Several research studies have used laboratory data to identify patient populations most at risk for severe outcome from COVID-19. However, many of these studies were conducted in China and did not represent the demographics of the U.S. population. Among the drawbacks of these studies were that most analyzed variance between two patient groups, yet statistical differences don’t always correlate with clinically useful predictions. Furthermore, these studies used data from throughout patients’ disease course, and clinicians would like to identify patients at risk during their initial interaction.

January 2024—Diffuse parenchymal lung disease is a well-recognized complication of systemic connective tissue disease but rarely arises in patients with psoriasis or psoriatic arthritis, which are poorly understood. Therefore, the authors conducted a study to characterize diffuse parenchymal lung disease (DPLD) associated with psoriasis or psoriatic arthritis, with or without prior immunomodulation. Their pathology consultation files were searched for patients having psoriasis or psoriatic arthritis and DPLD. After excluding cases with active infection or smoking-related DPLD only, 44 patients (22 of whom were women; median age, 60 years; range, 23–81 years) were enrolled in the study. Clinical history and pathology slides were reviewed.

January 2024—DDX41 is involved in multiple cellular processes, including RNA metabolism and splicing. Inherited variants have been linked to an increased risk of the blood neoplasms myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

January 2024 Q. Can a person who has a bachelor of science degree in health care administration sign off on competency assessments? Read answer. Q. Our laboratory uses a total protein assay from Beckman Coulter that has an analytical measurement range of 3–12 g/dL for serum determinations. The assay sensitivity states 1 g/dL of total protein. Can we loop sensitivity into our AMR and make our reporting range 1–12 g/dL? Will this make our assay a laboratory-developed test? Quite often our clinicians need assays reported to 1 g/dL, since they need to calculate the ratio of total protein serum to body fluid as per Light’s criteria. If we report to 1 g/dL, we have to loop sensitivity into our AMR. Read answer.

January 2024—When the medical microbiology laboratory at Yale-New Haven Hospital makes operational changes, it uses data analytics to monitor their impact. Yet the process of implementing laboratory analytics can be challenging.

January 2024—The Association for Molecular Pathology on Dec. 14 published a joint report on what to consider for a slice testing strategy for diagnostics, including gene selection, analytic performance, coverage, quality, and interpretation. Slice testing is the practice of bioinformatically selecting a subset of genes from exome or genome sequencing assays.