The only constant in pathology is change. New diseases are discovered; new pathogens emerge; diagnostic criteria, expert opinions, and favorite systems of terminology remain forever in flux. Arcane concepts, techniques, and instruments that were once confined to the research laboratory continually find their way into our daily clinical practice. No sooner have we mastered clusters of differentiation, intracellular signaling cascades, driver mutations, and DNA repair pathways than we must pivot to confront cancer immunotherapy, next-generation sequencing, mass spectrometry in the microbiology laboratory, and torrents upon torrents of terabytes. Far more than other specialists, pathologists also have to stay attuned to the ever-changing methods, ideas, needs, and expectations of our many clinician partners, who turn to us for expert advice and rely on us always to stay abreast of their own diverse fields. Through it all, pathologists learn and adapt. The dynamism of our specialty is key to its mission, its challenges, and its joy.

This Special Section of the Archives celebrates change. Focusing on a handful of subspecialties in one large, university-based pathology department, we invited teams of faculty to highlight some of the major trends that are affecting their own current practices, and how they are adapting their clinical workflows to accommodate. In a profession as fluid as pathology, some waves of change that first come ashore in an academic, quaternary-care health center are destined before long to wash over pathology practices everywhere. So the authors have tried throughout to emphasize trends that already are, or seem likely soon to become, relevant to pathologists in a wide range of practice types and settings. The 10 resulting essays (5 making up Part I that begins after this introduction, and the remainder in Part II that continues in the April issue) provide snapshots of just how deeply various new methodologies and concepts have penetrated each subspecialty, in some cases with transformative effects.

Technology looms large. Not surprisingly, gene-sequencing methods are finding application across the full range of subspecialties represented here, with implications for diagnosis, treatment, and prognostication. For some, this is just the latest in a long string of innovations: In the opening essay of Part I, for example, Fasano and colleagues trace the history of how once-novel serologic assays and mixed-lymphocyte reactions in the histocompatibility laboratory have gradually given way to sequence- and informatics-based approaches to tissue typing, so that “virtual cross-matches” are now a routine first step in bone marrow and solid-organ transplant. Hematopathology is likewise famous as an early adopter of new analytic technologies, and for reinventing its diagnostic schemes accordingly, so it is no surprise to read in the review by S. Li and coauthors that cytogenetic, sequencing, and gene-array methods are now inextricably part of the workup of hematologic disorders, and are yielding revolutionary insights.

But who would have anticipated that neuropathology, too, would now rely so heavily on cytogenetic and mutational information, with genomic data poised to supersede histopathology in the workup, for example, of low-grade gliomas, as reported by Neill et al? Or that next-generation sequencing would be proving useful in the diagnostic evaluation of pancreatic cyst fluid and bile-duct brushings, as Reid et al report? Or that genotyping now offers a more efficient way to identify red cell donors for sickle cell or thalassemic patients who have been highly sensitized by multiple prior transfusions, as Fasano et al describe? For diagnosing salivary tumors, Griffith and colleagues see little impact thus far of gene arrays and targeted therapies, but they find that testing for distinctive chromosomal translocations (using fluorescence in situ hybridization) can be a powerful adjunct to immunostaining, particularly for small biopsy specimens, cytologic cell blocks, or smears. Breast pathology, too, is still dominated by concepts and terminology from traditional histopathology, but X. Li and colleagues (in the essay that opens Part II in this Special Section) make clear that newer genetically based classification schemes are waiting in the wings, jostling for validation, and may soon be ready to move to center stage. In documenting those developments, as well as newly recognized subtypes of renal carcinomas (Ellis et al) or hematologic disorders (S. Li et al) that are defined by pathognomonic mutations or chromosomal anomalies, these essays leave no doubt that new gene-focused technologies are already having a profound, pervasive impact on diagnostic pathology.

It's also hard to overlook the rise of theranostics, in which pathologists apply specific immunostains or genetic tests to interrogate the genomic stability or clonal diversity of an individual cancer or to predict the likelihood that it will respond to targeted therapies. Breast cancer pathology is already far along that road, as X. Li et al indicate, with gene-expression and mutational data now being evaluated for use in conjunction with hormone-receptor status to define new tumor categories and to select optimal treatments. Testing for actionable BRAF mutations is widely accepted as standard of care for melanomas, and tests for the microsatellite instability associated with Lynch syndrome have also recently become routine, particularly for our specialists in gastrointestinal (Xue et al) or gynecologic pathology (Hanley et al). As in the early days of hormone-receptor testing, methods may vary, but there is little question that pathologists today need access to an expanding menu of theranostic assays and must become expert at interpreting them.

Equally far-reaching are the effects of new techniques that surgeons, endoscopists, and interventional specialists are using to visualize and sample lesional tissue, particularly from sites that were almost inaccessible in the past. Ellis and colleagues, for example, cite a panoply of technical advances in urologic surgery, including robotic prostatectomy, blue-light cystoscopy for identifying urothelial lesions, needle-core biopsies of kidney masses guided by magnetic resonance imaging (MRI), and a novel positron-emitting tracer for prostatic cancer, each of which poses unique interpretive challenges and opportunities for pathologists. On the one hand, innovative methods such as these have helped uncover entire new constellations of disease processes lurking at those sites; on the other hand, they often confront pathologists with minute snippets of ill-characterized entities and little basis for interpreting them. Those conflicting trends are evident in the articles by Xue et al, on liver and gastrointestinal pathology, and by Reid et al, on the pancreatobiliary tree, which underscore how the pioneering uses of MRI- or ultrasound-guided biopsies and endomicroscopy have increased the need for close coordination between pathologists and endoscopists, while greatly expanding differential diagnoses, particularly for previously uncharacterized intraductal lesions and preinvasive/in situ malignancies. And Hanley and colleagues offer a chilling catalogue of the ways that minimally invasive uterine surgery can artifactually “upstage” tumors of the corpus, such as by mechanically extruding neoplastic cells into the surrounding vasculature. As always, our clinician friends find endlessly inventive ways to keep pathologists on their toes.

The digital revolution in surgical pathology has begun, but not yet in the form that's envisioned. Whole-slide scans are now commonplace and we use them to quantify some tissue biomarkers and occasionally for real-time consultation between hospitals. But long acquisition times, regulatory hurdles, and cumbersome, unfamiliar user interfaces have kept them out of our routine diagnostic workflows so far. As Farris et al describe, such scans show promise for assessing renal and liver fibrosis or hepatic fatty change, as well as for “big data” research aimed at correlating histologic features with radiographic and molecular parameters. For us, and for now, though, their greatest impact has come in storing, retrieving, and sharing histologic images for conferences and teaching.

The traditional skills are still vital, but they need constant updating, too. To that end, Xue and colleagues offer a brief compendium of histomorphologic changes that pathologists may observe in the livers of patients treated with some of the newest targeted anticancer drugs, monoclonal antibodies, or treatments for hepatitis C virus, which are all now in widespread use. S. Li et al remark on the importance of knowing if patients have undergone treatment with monoclonal antibodies, as these may temporarily mask expression of their target antigens on hematopoietic cells or may even select for long-term alterations in the immunophenotype of a malignant clone. Even gross examination nowadays requires staying abreast of changing clinical practice, so that one can recognize, for example, the sequelae of various embolization procedures that may be encountered in liver explants, as Xue et al describe.

The pathologist's work will always be a work in progress. Together with our faculty colleagues in Emory University's Department of Pathology and Laboratory Medicine, we feel honored to have been given the opportunity to contribute these articles. We thank the editors of the Archives for inviting us to compile this Special Section, and to capture these snapshots in time of a department, its doctors, and a discipline that continually strive to advance biomedical science and improve patient care. We hope our perspectives will be of interest to other pathologists.

Tristram G. Parslow, MD, PhD

Tristram G. Parslow, MD, PhD, has been the William Patterson Timmie Professor and chair of Pathology and Laboratory Medicine at Emory University, in Atlanta, Georgia, since 2003. He earned his medical degree and a doctorate in biochemistry through the National Institutes of Health (NIH)–sponsored Medical Scientist Training Program (MSTP) at the University of Iowa, in Iowa City. He then completed a residency in anatomic pathology at the University of California in San Francisco (UCSF) before joining the UCSF faculty in 1985, where he remained for 18 years, eventually rising to become professor and vice chair for research in pathology, director of the Immunology Graduate Program and, for 10 years, director of the UCSF MSTP. Dr Parslow has published extensively on the molecular biology of HIV and influenza viruses, RNA structure, and immunobiology; coedited a leading textbook on medical immunology; serves frequently on NIH grant review panels; and presently collaborates on studies of retroviral pathogenesis and treatment in the macaque model. Dr Parslow is a member of the Executive Advisory Board for the Archives of Pathology & Laboratory Medicine, the editorial boards of 2 other journals, and the Scientific Advisory Committee of the American Foundation for AIDS Research, and he is currently president of the Association of Pathology Chairs.

Tristram G. Parslow, MD, PhD

Tristram G. Parslow, MD, PhD, has been the William Patterson Timmie Professor and chair of Pathology and Laboratory Medicine at Emory University, in Atlanta, Georgia, since 2003. He earned his medical degree and a doctorate in biochemistry through the National Institutes of Health (NIH)–sponsored Medical Scientist Training Program (MSTP) at the University of Iowa, in Iowa City. He then completed a residency in anatomic pathology at the University of California in San Francisco (UCSF) before joining the UCSF faculty in 1985, where he remained for 18 years, eventually rising to become professor and vice chair for research in pathology, director of the Immunology Graduate Program and, for 10 years, director of the UCSF MSTP. Dr Parslow has published extensively on the molecular biology of HIV and influenza viruses, RNA structure, and immunobiology; coedited a leading textbook on medical immunology; serves frequently on NIH grant review panels; and presently collaborates on studies of retroviral pathogenesis and treatment in the macaque model. Dr Parslow is a member of the Executive Advisory Board for the Archives of Pathology & Laboratory Medicine, the editorial boards of 2 other journals, and the Scientific Advisory Committee of the American Foundation for AIDS Research, and he is currently president of the Association of Pathology Chairs.

N. Volkan Adsay, MD

N. Volkan Adsay, MD, is professor of pathology, vice chair, and director of Anatomic Pathology at Emory University in Atlanta, Georgia. Dr Adsay completed his anatomic pathology and clinical pathology residency at Lenox Hill Hospital followed by a 2-year fellowship in oncologic pathology at the Memorial Sloan Kettering Cancer Center, both in New York City. After 11 years as a faculty member at Wayne State University and Karmanos Cancer Center in Detroit, Michigan, he joined Emory University in 2007. Dr Adsay is internationally recognized in the field of gastrointestinal and pancreatobiliary cancers, having published more than 230 peer-reviewed articles and authored several chapters in the most prestigious textbooks of diagnostic pathology and oncology. He was a member of the Pancreas Review Group of the National Cancer Institute, and a coauthor of multiple chapters in the World Health Organization's “Classification of Tumours” series. Dr Adsay has been instrumental in the pathologic characterization of various tumor types of the pancreas and biliary tract, and was a member of the international group that put forth the definitions and criteria for the early cancerous lesions of these organs and prognostication of tumors of these sites. He serves on the editorial boards of 8 leading journals, including the Archives of Pathology & Laboratory Medicine as a section editor in gastrointestinal pathology, and is currently president of the United States and Canadian Academy of Pathology (USCAP).

N. Volkan Adsay, MD

N. Volkan Adsay, MD, is professor of pathology, vice chair, and director of Anatomic Pathology at Emory University in Atlanta, Georgia. Dr Adsay completed his anatomic pathology and clinical pathology residency at Lenox Hill Hospital followed by a 2-year fellowship in oncologic pathology at the Memorial Sloan Kettering Cancer Center, both in New York City. After 11 years as a faculty member at Wayne State University and Karmanos Cancer Center in Detroit, Michigan, he joined Emory University in 2007. Dr Adsay is internationally recognized in the field of gastrointestinal and pancreatobiliary cancers, having published more than 230 peer-reviewed articles and authored several chapters in the most prestigious textbooks of diagnostic pathology and oncology. He was a member of the Pancreas Review Group of the National Cancer Institute, and a coauthor of multiple chapters in the World Health Organization's “Classification of Tumours” series. Dr Adsay has been instrumental in the pathologic characterization of various tumor types of the pancreas and biliary tract, and was a member of the international group that put forth the definitions and criteria for the early cancerous lesions of these organs and prognostication of tumors of these sites. He serves on the editorial boards of 8 leading journals, including the Archives of Pathology & Laboratory Medicine as a section editor in gastrointestinal pathology, and is currently president of the United States and Canadian Academy of Pathology (USCAP).

Alyssa M. Krasinskas, MD

Alyssa M. Krasinskas, MD, is an eminent gastrointestinal (GI) pathologist who serves as a professor and director of the GI Pathology Clinical Service at Emory University in Atlanta, Georgia, as well as director of Surgical Pathology at Emory University Hospital. After earning her MD from the University of Rochester School of Medicine in Rochester, New York, Dr Krasinskas completed a residency in anatomic and clinical pathology at the University of Pennsylvania (UPenn) in Philadelphia, during which she performed 3 years of laboratory research in transplantation immunology. She then completed a clinical fellowship in surgical and GI pathology at UPenn before joining the faculty of the University of Pittsburgh/UPMC in Pennsylvania in 2002. While at UPMC, she was director of both the highly regarded GI Pathology Service and GI Pathology Fellowship Program, was a member of the Surgical Pathology Committee of the College of American Pathologists, won acclaim for her frequent GI “short courses” at USCAP, and served as national president of the Rodger C. Haggitt GI Pathology Society. She moved to her current position at Emory in 2013. Dr Krasinskas currently serves on the Education Committee of the USCAP, on the editorial boards of leading pathology journals, including the Archives of Pathology & Laboratory Medicine as a section editor in Residents Affairs, and as vice president of the newly formed international Pancreatobiliary Pathology Society.

Alyssa M. Krasinskas, MD

Alyssa M. Krasinskas, MD, is an eminent gastrointestinal (GI) pathologist who serves as a professor and director of the GI Pathology Clinical Service at Emory University in Atlanta, Georgia, as well as director of Surgical Pathology at Emory University Hospital. After earning her MD from the University of Rochester School of Medicine in Rochester, New York, Dr Krasinskas completed a residency in anatomic and clinical pathology at the University of Pennsylvania (UPenn) in Philadelphia, during which she performed 3 years of laboratory research in transplantation immunology. She then completed a clinical fellowship in surgical and GI pathology at UPenn before joining the faculty of the University of Pittsburgh/UPMC in Pennsylvania in 2002. While at UPMC, she was director of both the highly regarded GI Pathology Service and GI Pathology Fellowship Program, was a member of the Surgical Pathology Committee of the College of American Pathologists, won acclaim for her frequent GI “short courses” at USCAP, and served as national president of the Rodger C. Haggitt GI Pathology Society. She moved to her current position at Emory in 2013. Dr Krasinskas currently serves on the Education Committee of the USCAP, on the editorial boards of leading pathology journals, including the Archives of Pathology & Laboratory Medicine as a section editor in Residents Affairs, and as vice president of the newly formed international Pancreatobiliary Pathology Society.

John D. Roback, MD, PhD

John D. Roback, MD, PhD, is professor, vice chair, and director of the Division of Laboratory Medicine at Emory University in Atlanta, Georgia. He is a specialist in transfusion medicine and has served since 2009 as director of Emory's highly regarded Center for Transfusion and Cellular Therapies. Dr Roback joined the Emory faculty in 1999 after completing his 2 doctorates at the University of Chicago in Illinois, an anatomic pathology residency at Albert Einstein College of Medicine in New York City, and clinical pathology training followed by a transfusion medicine fellowship at Emory. His research interests extend broadly over the fundamental and translational aspects of blood-cell and transfusion biology, and are reflected in his current leadership of NIH-sponsored program project and training grants, and by the 2 start-up companies he has cofounded, all in the field of transfusion medicine. His national leadership roles have included chairing the Clinical Transfusion Medicine Committee of the AABB, serving as a trustee of the National Blood Foundation and on several advisory panels to the National Institutes of Health and Centers for Disease Control and Prevention, and serving as lead editor for 2 recent editions of the authoritative “AABB Technical Manual,” which is regarded as the premier reference in the blood-banking field.

John D. Roback, MD, PhD

John D. Roback, MD, PhD, is professor, vice chair, and director of the Division of Laboratory Medicine at Emory University in Atlanta, Georgia. He is a specialist in transfusion medicine and has served since 2009 as director of Emory's highly regarded Center for Transfusion and Cellular Therapies. Dr Roback joined the Emory faculty in 1999 after completing his 2 doctorates at the University of Chicago in Illinois, an anatomic pathology residency at Albert Einstein College of Medicine in New York City, and clinical pathology training followed by a transfusion medicine fellowship at Emory. His research interests extend broadly over the fundamental and translational aspects of blood-cell and transfusion biology, and are reflected in his current leadership of NIH-sponsored program project and training grants, and by the 2 start-up companies he has cofounded, all in the field of transfusion medicine. His national leadership roles have included chairing the Clinical Transfusion Medicine Committee of the AABB, serving as a trustee of the National Blood Foundation and on several advisory panels to the National Institutes of Health and Centers for Disease Control and Prevention, and serving as lead editor for 2 recent editions of the authoritative “AABB Technical Manual,” which is regarded as the premier reference in the blood-banking field.

The authors thank Corey Anderson, MA, for assistance in preparation of this Special Section, and Donna Martin for the photos accompanying this article.

Author notes

The authors have no relevant financial interest in the products or companies described in this article.