Irene Esposito is an academic pathologist and internationally recognized expert in pancreatic and biliary tract pathology. She studied medicine at the University of Pisa, Italy, where she obtained the board certification in pathology. Thereafter, she moved to Germany, holding positions at several leading German institutions, including those in Heidelberg, Munich, and Düsseldorf. She is Director of the Institute of Pathology at Heinrich Heine University and University Hospital of Düsseldorf and currently serves as President-Elect of the European Society of Pathology (ESP).
Here, Esposito joins us to share insights from her well-travelled diagnostic career and discuss the importance of interdisciplinary collaboration in patient care.
What first drew you to pathology?
I often say that I became a pathologist the moment I attended my first pathology course in medical school. Unlike many colleagues, I did not enter medicine with a lifelong ambition to become a physician; in many ways, I chose medicine by chance. But when I discovered pathology, everything clicked.
What drew me in – and continues to inspire me – is the way pathology connects patient care, biology, and scientific discovery. It allows us to observe disease directly at the level of tissues, organs, and cells, providing a unique perspective on how diseases develop and affect the body. That perspective naturally raises important research questions. For me, pathology has always been the bridge between basic science and clinical medicine, linking what we see under the microscope to the care of patients.
How did your experience at Heidelberg University shape your professional “compass” and your expectations of what a modern academic pathology unit should be?
Heidelberg was a defining chapter in my career. At the time, it was already one of Europe’s leading centers for pancreatic surgery, which meant I encountered an exceptional range of pancreatic diseases each week, from common conditions to rare lesions I had never seen before.
Equally important was the opportunity to learn from Günter Klöppel, one of the founders of modern pancreatic pathology. I regularly sent him challenging cases for consultation and learned a great deal from his reports and insights. Those exchanges had a lasting influence on my diagnostic thinking.
Some of these consultations later developed into scientific collaborations. In a few cases, we were able to contribute to the first descriptions of entities that were not yet recognized, including intraductal tubulopapillary neoplasm of the pancreas.
Looking back at your doctoral thesis, what do you think your early work taught you about the interplay between morphology and molecular pathways in pancreatic cancer?
My doctoral thesis focused on p53 and Bcl-2 expression in pancreatic cancer, and it gave me a deep appreciation for immunohistochemistry. Although newer genomic technologies often attract more attention, immunohistochemistry remains a cornerstone of diagnostic pathology. The project taught me the importance of rigor at every stage, from selecting appropriate controls to optimizing staining protocols and accurately interpreting results.
It also introduced me to the concept of tumor heterogeneity. Even then, we observed differences between primary tumors and their corresponding lymph node metastases. Today, technologies such as spatial transcriptomics and advanced sequencing allow us to study these differences in far greater detail, but the underlying biological principle remains unchanged.
Perhaps most importantly, the project showed me that morphology and molecular biology are not competing approaches. Rather, they are complementary tools that help us understand the same disease from different perspectives.
How have your roles in expert committees, pancreas centers, and cancer consortia shaped the way you approach research and complex diagnostic cases?
Interdisciplinary collaboration is one of the most rewarding aspects of academic medicine. Working with surgeons, gastroenterologists, oncologists, radiologists, molecular biologists, and computational scientists continually challenges us to rethink established ideas and consider new perspectives.
Many of my research projects – and some important diagnostic insights – have emerged from conversations outside pathology. These experiences have taught me the value of intellectual humility and reinforced the idea that complex diseases can only be fully understood through collaboration across disciplines.
My colleagues often joke that it can be risky when I return from a conference, because I usually come back with at least ten new project ideas.
Your research has focused on pancreatobiliary tumors and their precursors. What has been the most important change in our understanding of these diseases over the past 10–15 years?
Without question, the most transformative development has been the integration of morphology and molecular biology into disease classification. Early in my career, pancreatic tumors were classified largely by their microscopic appearance. Today, morphology remains essential, but it is complemented by a much deeper understanding of the molecular changes that drive tumor development and progression.
This integrated approach has reshaped how we classify precursor lesions, understand tumor evolution, and stratify patients. It is also a key principle of the recent WHO classifications, to which I have contributed. Perhaps most importantly, these advances are helping us better understand the earliest stages of carcinogenesis, creating new opportunities for earlier diagnosis and prevention. In pancreatic cancer, that may ultimately have the greatest impact on patient outcomes.
How has studying the tumor microenvironment changed your understanding of pancreatic cancer pathology?
The glass slide – whether viewed through a microscope or digitally – has not become less important; it has become more informative. Over the past decade, we have learned that pancreatic cancer is not simply a collection of malignant cells, but a complex ecosystem that includes fibroblasts, immune cells, blood vessels, extracellular matrix, and many other components.
New spatial technologies have revealed how these cell populations interact and evolve during disease progression. What may appear under the microscope as a relatively uniform stromal reaction is, in reality, a highly complex biological environment.
These advances have reinforced the central role of pathology. Pathologists are uniquely positioned to connect molecular findings with tissue architecture, helping to place biological discoveries into their proper morphological context.
What are the strengths and limitations of mouse models when we try to translate findings back to human diagnostic pathology?
Pancreatic cancer is one of the diseases in which genetically engineered mouse models have been especially useful. Their main strength is that they reproduce key features of human pancreatic carcinogenesis and allow us to study disease development in a controlled setting – something that is not possible in patients.
At the same time, every model has limitations. Differences in immune responses, tumor evolution, and tissue biology mean that findings from mouse models cannot always be translated directly to humans. Our recent work comparing mouse and human pancreatic lesions has highlighted important differences in the immune microenvironment, which may affect how therapeutic studies are interpreted.
The goal is not to find a perfect model, but to understand what each model can and cannot tell us, and to interpret the results accordingly.
How do you see molecular subtyping being integrated into routine pathology practice in the coming years?
In many tumor types, molecular classification is already part of routine pathology, and pancreatic cancer is moving in the same direction. The emergence of targeted therapies, including KRAS inhibitors, is making molecular profiling increasingly important for treatment decisions.
I expect molecular and morphological findings to become more closely integrated. Rather than choosing between the two, pathologists will combine them to provide a more comprehensive diagnosis. Achieving this will require continued investment in infrastructure, quality assurance, and training, but the direction of travel is clear.
What are the most common diagnostic pitfalls in IgG4-related disease and secondary sclerosing cholangitis?
The most common pitfall is assuming that increased numbers of IgG4-positive plasma cells are sufficient to make the diagnosis. They are not. IgG4-related disease is a clinicopathological diagnosis that requires correlation of histological findings with immunohistochemistry, clinical presentation, and radiological features.
Increased IgG4-positive plasma cells can also be seen in a range of other conditions, including inflammatory reactions associated with malignancy. For that reason, it is important to interpret these findings in the appropriate clinical context. As a general rule, whenever a diagnosis seems straightforward, I become especially cautious.
How have your experiences shaped your views on the future of pathology education?
One of the most rewarding experiences of my career was helping develop an international web-based pathology training program for disease modelling at a time when digital teaching was still relatively new. The project showed me the tremendous potential of digital platforms to make expertise accessible regardless of location, support self-paced learning, and foster international collaboration.
For me, the future is not a choice between digital and traditional education. The greatest opportunities lie in combining the strengths of both. Digital tools can expand access to knowledge and training, but mentorship, collaboration, and personal interaction will remain essential to developing the next generation of pathologists.
With the introduction of AI and digital pathology, where do you see the most realistic short-term gains – and the greatest risks – for patient care?
AI is likely to become one of the most influential technologies in pathology. In the near term, its greatest impact will be in areas such as workflow optimization, quality assurance, image analysis, quantification, and the integration of complex datasets. AI can help pathologists process information more efficiently and identify patterns that may be difficult to detect through visual assessment alone.
The greatest challenge is not the technology itself, but how it is used. AI can create a false sense of certainty, particularly when its decision-making processes are not transparent. It is essential that pathologists continue to apply critical judgment rather than relying blindly on algorithms.
I do not see AI replacing pathologists. Rather, I see pathologists who use AI effectively gaining an advantage. Ultimately, pathology is about understanding disease in its clinical context, and that responsibility will remain with human experts.
As a journal editor and reviewer, how do you see the balance between mechanistic papers and clinically oriented diagnostic studies evolving in pathology?
Pathology occupies a unique position between biology and medicine, and both perspectives are essential. Mechanistic studies help us understand disease processes, while diagnostic and clinical studies determine whether those insights can improve patient care.
There can be a tendency to view one approach as more important than the other, but I disagree. A well-designed diagnostic study that changes clinical practice can be just as impactful as a highly mechanistic investigation. The most valuable research often bridges the two, connecting biological discoveries with clinically relevant questions.
What advice do you give to early-career pathologists trying to build a coherent academic profile in an era of hyper-specialization?
My first piece of advice is simple: follow your curiosity. Academic careers are long, and genuine enthusiasm for a subject is far more sustainable than pursuing a field simply because it is fashionable.
Second, develop expertise in an area that excites you, but remain open to ideas from other disciplines. Many of the most interesting discoveries happen at the intersection of different fields.
Finally, do not focus solely on metrics. Publications, grants, and citations matter, but they should be viewed as outcomes rather than goals. If you consistently ask meaningful questions, work with integrity, and collaborate with good people, success often follows naturally.
Having worked across Europe, what differences in training and healthcare systems have most influenced the role of pathologists in multidisciplinary care?
One of the most fascinating aspects of working across Europe is seeing that there are many successful ways to practice pathology. The key differences are often cultural rather than technical. Some systems emphasize individual autonomy, while others place greater value on consensus-building and multidisciplinary collaboration. Both approaches have their strengths.
What has impressed me most in Germany is the strong integration of pathology into clinical decision-making. Pathologists are not simply diagnostic service providers; they are active members of multidisciplinary teams and important contributors to translational research. I believe this close partnership between pathology and the clinical disciplines is one of the greatest strengths of modern academic medicine.
What are your key priorities as President-Elect of the ESP?
In line with the mission of the ESP, one of my priorities is to expand educational, training, and research opportunities across Europe, particularly for early-career pathologists. Talent is widely distributed, but opportunities are not always equally accessible, and professional societies can help bridge that gap.
I also want to strengthen the visibility of pathology as a central medical discipline. Pathologists play a key role in precision medicine, cancer prevention, biomarker development, and translational research, yet our contributions are not always fully recognized outside the field.
Finally, I would like the society to continue embracing innovation while remaining grounded in the core principles of pathology. Technologies such as artificial intelligence, digital pathology, molecular diagnostics, and spatial biology are transforming our profession, but they should complement – not replace – the diagnostic expertise, critical thinking, and scientific curiosity that define it.
Looking ahead, what question in pancreatobiliary pathology excites you most, and what would you like your team in Düsseldorf to be known for in ten years?
The question that fascinates me most is how pancreatic cancer begins. Despite decades of research, we still do not fully understand the earliest stages of pancreatic carcinogenesis. Which precursor lesions are truly important? Why do some progress while others remain indolent? And can we identify high-risk patients early enough to intervene before invasive cancer develops?
I believe advances in morphology, spatial technologies, molecular pathology, and artificial intelligence will help answer many of these questions. Ten years from now, I would like our team in Düsseldorf to be known for advancing the early detection, understanding, and prevention of pancreatic cancer.
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