Pathology

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.

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.

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.

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.

December 2023—In the 2024 Medicare physician fee schedule final rule, the Centers for Medicare and Medicaid Services reacted favorably to the CAP’s advocacy to mitigate payment decreases to pathologists next year. Overall, payments to pathologists are expected to decrease by an estimated 2.7 percent.

December 2023—Digital pathology and AI—the push, the potential, the changing questions, the reimbursement, and the caution. All that and more came up when CAP TODAY publisher Bob McGonnagle on Oct. 17 led a conversation online with pathologists and industry representatives.

November 2023—It was a mystery, wrapped less in an enigma than a few layers of bafflement, surprise, and mild irritation. Call it the Case of the Split Lung Specimens. The first hint something was amiss came when Alain Borczuk, MD, vice chair of anatomic pathology and co-director of thoracic pathology, Northwell Health, noticed that he and his colleagues were receiving more insufficient bronchoscopy specimens than usual. “When I say ‘increasing’—we don’t get that many bronchoscopies. It’s not like colon polyps,” says Dr. Borczuk, who is also director of oncologic pathology, Northwell Health Cancer Institute. Normally they would get a handful a week, some of them straightforward cancer cases, although these additional cases were tied to noncancerous conditions. And then the plot thickened even further, with missing pieces—literally. Though no guideline clearly states what constitutes an adequate specimen, Dr. Borczuk says, the samples he and his colleagues were seeing fell markedly short.

November 2023—Spatial biology may be an emerging field, but Kenneth Bloom, MD, says he and other pathologists have been doing it “since we got the microscope.” And he argues it’s going to become “the new, most important lens we look through.” The reason is the emergence of new cancer treatments like immunotherapy and, most importantly, antibody drug conjugates like Enhertu, says Dr. Bloom, head of pathology for Nucleai, a company specializing in AI-powered spatial biology.

October 2023—In living up to its promise as a new technology that will revolutionize clinical care through greater ease, speed, and accuracy of diagnosis, digital pathology has been sluggish. While many analysts, starting at least two decades ago, forecasted that digital pathology would elbow aside glass slides for good, that milestone is still far out of reach. As health economist and chief executive officer of the New York City-based digital pathology company Paige, Andy Moye, PhD, puts it bluntly: “In probably 90 to 95 percent of the cases in the U.S., a pathologist still makes the diagnosis of cancer the way they did it back in 1910: by looking at a glass slide under a microscope.” Mark Lloyd, PhD, vice president of pathology for Fujifilm, says he wouldn’t be surprised to hear that perhaps only five percent to 10 percent of hospitals have moved beyond using only glass slides to offer pathologists digital pathology capability. In fact, Dr. Lloyd thinks those percentages are overstated. What is the market share for the clinical use of digital pathology?

August 2023—Seemingly channeling the inspiration of Magritte and his famous pipe, pathologists are painting a new picture of what has long been an everyday object in their own world: HER2. To paraphrase the master: Ceci n’est pas facile. For years, HER2 testing in breast cancer has seemed self-evident, ever since the HER2-targeted therapy trastuzumab and its companion diagnostic arrived on the scene a quarter of a century ago. Pathologists became comfortable using immunohistochemistry to identify 3+ cases and turning to in situ hybridization techniques to sort through less obvious ones. But early last summer, a variant of the drug, trastuzumab-deruxtecan (T-DXd), shook up that routine. When researchers presented results from the Destiny-Breast04 study at the 2022 ASCO annual meeting, showing that T-DXd significantly improves survival in so-called HER2-low metastatic breast cancer, attendees responded with a minutes-long standing ovation. They then returned from the meeting like evangelicals from the revival tent.

August 2023—With patient access to pathology reports now common via online portals, the question some have asked is what can be done to make them easier for patients to understand.  

August 2023—Anatomic pathology laboratories—the pressures, the promise of technology to alleviate them, and the seemingly unprecedented rates of change. CAP TODAY publisher Bob McGonnagle gathered pathologists and company representatives online on June 21 to talk about it all. From pathologist coverage to IT, from tumor boards to questions job candidates in pathology should ask, here’s what they told us.

July 2023—Though it’s been suggested that newer drugs have made cytomegalovirus less relevant in patients with inflammatory bowel disease, CMV remains an important opportunistic infection in patients with IBD. Knowing where to biopsy and how many are needed is one of the histologic challenges, said Joseph Misdraji, MD, associate professor of pathology, Yale School of Medicine, in a CAP22 session.

July 2023—Digital pathology, the pathology workforce, and the clinical demand for subspecialty expertise were some of what Compass Group lab leaders took on in their June 6 conversation, with CAP TODAY publisher Bob McGonnagle leading the way.

June 2023—Three initiatives are underway at the American Board of Pathology, one of which its CEO Gary Procop, MD, MS, describes as “a new era of transparency and collaboration.”

June 2023—Although goblet cell adenocarcinoma can label for neuroendocrine markers, it behaves as an adenocarcinoma and is staged as such. And it’s important to distinguish goblet cell adenocarcinoma from tubular neuroendocrine tumor, a rare subtype of neuroendocrine tumor.

May 2023—How to distinguish appendiceal diverticular disease and appendiceal polyps from mucinous neoplasms was just part of a CAP22 course on appendiceal lesions, led by Maryam Pezhouh, MD, MSc, of the University of California, San Diego, and Jacqueline Birkness-Gartman, MD, of Johns Hopkins University School of Medicine.

April 2023—With serous ovarian carcinomas and other gynecologic tumors, it’s molecular testing that increasingly sets the treatment course. “As pathologists, it’s exciting to us,” said Sadia Sayeed, MD, speaking at CAP22. “We’re learning that the immunostains we’re interpreting have greater implications than we ever thought they could.”

April 2023—Another administrative layer and “up in the air” is how lab billing experts describe what the No Surprises Act requires of laboratories and where things stand. When they met online March 3 with CAP TODAY publisher Bob McGonnagle, they talked about this and digital pathology and the problems of no or slow payments. “Compared with five years ago, the number of denials has increased and turnaround time on full payment on a claim has lengthened significantly,” said Tom Scheanwald of APS Medical Billing.

March 2023—With endometrial carcinomas and other gynecologic tumors, molecular testing matters, and not only at the diagnostic stage. “We’re rapidly evolving,” said Leslie M. Randall, MD, MAS, division director of gynecologic oncology, Virginia Commonwealth University Health, speaking at CAP22.

March 2023—Assessing cardiac allograft rejection from endomyocardial biopsy​ and assigning a differential diagnosis to cancers of unknown origin have been shown to get a boost from AI-driven computational pathology models. So too has identifying subregions of high diagnostic value on whole slide images.

February 2023—Like a thriving expat, Deborah Dillon, MD, is comfortable moving within worlds both old and new. Specifically, as a breast and molecular pathologist at Brigham and Women’s Hospital, she appreciates the biomarkers she and her colleagues grew up with, so to speak, as well as those that are part of a more recently arrived-at scenery. Not everyone finds both worlds equally riveting. “A lot of people are much more interested in, and excited by, new markers,” she says. “When I talk to people from pharma, this is what they want to hear about.” So do many pathologists, oncologists, and patients—new markers and new therapies have a way of updating hopes. Dr. Dillon understands the persistent thrill of the new, why people want her to talk the language of PIK3CA, PARP inhibitors, MMR, NTRK fusions, ESR1, and the like. But as an in-demand speaker as well as in a recent interview with CAP TODAY, she also advocates for making the old—the longstanding trinity of ER, PR, and HER2—seem new again.

February 2023—Consensus on the best ways to stem unnecessary laboratory testing, and spare health care systems and patients its negative effects, is still elusive.

February 2023—As this year’s guide to anatomic pathology computer systems was taking shape, CAP TODAY publisher Bob McGonnagle met online with representatives of five companies and with John Sinard, MD, PhD, of Yale University School of Medicine. They talked about the cloud, CPT codes, training of pathology informaticians, and artificial intelligence, for which the time frame in pathology is far longer than it’s been portrayed, in Dr. Sinard’s view. “It will start to impact the careers of some of our trainees, but it’s probably a 10- to 20-year time frame before it plays a major role,” he said. The view of Joe Nollar of Xifin: “Speculation that AI will someday replace pathologists is completely overblown,” though it will help to triage cases and mitigate risk. Their full conversation, which took place Dec. 20, 2022, follows.  

January 2023—Laura Esserman, MD, MBA, can still recall her Eureka moment. She had just seen a talk on residual cancer burden by pathologist W. Fraser Symmans, MB.ChB, a pioneer in the field. “When I saw Fraser present this,” says Dr. Esserman, director, University of California San Francisco Breast Care Center, “I knew immediately that MRI would work and that residual cancer burden would complement it. MRI was basically a snapshot of RCB over time. I realized that we had to institute RCB—we had to standardize our approach.” Until then, she and her colleagues across the I-SPY trial sites relied on individual pathologist assessment for each case. The pathologic complete response rate, or pCR, hovered at about 34 percent. That insight was soon followed by another. Intrigued by what she heard, Dr. Esserman and her pathologist colleagues from all the I-SPY sites traveled to MD Anderson, where Dr. Symmans helped develop the residual cancer burden system, for training.

Nearly 800 registrants were at the Digital Pathology Association’s Pathology Visions meeting this fall, and 54 companies exhibited. “There was a great vibe at the meeting. People were mingling, collaborative. Digital pathology is picking up,” says DPA president Esther Abels. Her term as president will end this month and Liron Pantanowitz, MD, PhD, MHA, of the University of Michigan, will step in as president on Jan. 1.

December 2022—In September, when CAP TODAY publisher Bob McGonnagle met with pathologists and representatives of companies to talk about laboratory information systems (“Lab information systems—where the needs are greatest,” https://bit.ly/LIS_112022), they talked also about artificial intelligence—innovations, clinical impact, how much interest there is. That part of their conversation follows.

November 2022—Burnout among Canadian pathologists is prevalent, pain related for some, and workload driven for many. “There needs to be more of us,” says Julia Keith, MD, associate professor in the Department of Laboratory Medicine and Pathobiology at the University of Toronto.

October 2022—HER2-low breast cancers are now of greater clinical interest, given Enhertu’s recent approval for use in treating such cancers. How to achieve accurate and reproducible results in scoring HER2-low tumors was at the center of a CAP TODAY webinar on new perspectives on the full spectrum of HER2 expression in breast cancer.

September 2022—It may not be the oldest story in the world, but in clinical laboratories it’s an oft-told tale: Tumor meets biomarker; drug meets companion diagnostic; both meet FDA approval; clinicians meet with patients offering new hope—and those in the lab are left trying to figure out how to make it all work. That story is playing out again in the realm of measuring tumor mutational burden. In mid-2020 the FDA approved pembrolizumab as a new treatment option in adult and pediatric patients with TMB-high (≥10 mutations/megabase) solid tumors, as determined by the FDA-approved FoundationOne CDx assay. “That doesn’t sound too controversial, right?” says Alain Borczuk, MD, vice chair of anatomic pathology and director of oncologic pathology, Northwell Health Cancer Institute. “It’s not the only way in, but it’s one of the ways in. If you’re arguing for your patient that this is the biomarker that makes them eligible for the drug, then the next questions will be, What was the number? And what was the test?” And it’s off to the races.

September 2022—Beginning next year, two additional predictive marker tests will require enrollment in proficiency testing (PT), but for any predictive marker using immunohistochemistry or in situ hybridization, only laboratories that perform both staining and interpretation must participate in CAP-accepted PT.

August 2022—In cases of borderline melanocytic neoplasms, which have overlapping histopathologic features of benign and melanocytic lesions, additional immunohistochemical studies sometimes help to differentiate the two. But a subset of lesions will show overlapping features.

August 2022—The atypia in Epstein-Barr virus-positive mucocutaneous ulcers can mimic diffuse large B-cell lymphoma or classical Hodgkin lymphoma, a diagnostic pitfall that can result in overtreatment. And esophageal ulcers in immunocompromised patients should trigger cytomegalovirus immunohistochemistry in addition to GMS and herpes simplex virus-1 and -2 stains.

August 2022—HER2 is a known oncogenic driver and emerging biomarker in non-small cell lung cancer, and while the therapeutic implication is not yet fully known in NSCLC, “we need to pay attention to it,” said Fred R. Hirsch, MD, PhD, executive director of the Mount Sinai Center for Thoracic Oncology and associate director, Tisch Cancer Institute, in a CAP TODAY webinar sponsored by Daiichi-Sankyo and AstraZeneca.

July 2022—Gut pathogens, their histologic features, and a GI pathology and microbiology team approach to diagnosis were the focus of a CAP21 session, “What’s Bugging the Gut?” Maryam Zenali, MD, Alina Iuga, MD, and Christina Wojewoda, MD, presented a series of cases and highlighted the features, the differential diagnoses, and the integrated workups. Three of their cases follow here, with others to be reported in an upcoming issue.