Pathological anatomy is the medical discipline that studies the morphological changes in cells and tissues caused by disease, enabling diagnosis and the identification of molecular targets for targeted therapies. «Like a detective searching for clues, the pathologist examines biological samples for signs of disease, under the microscope or on a computer screen» says Professor Maurilio Ponzoni, Director of the Residency Programme in Pathological Anatomy at Vita-Salute San Raffaele University. We spoke with Ponzoni to map out the profile of the anatomical pathologist and explore the training and research opportunities in this field.
Most cases arriving at the pathology laboratory are biological samples taken from patients awaiting a diagnosis. «It is not simply a matter of establishing whether a disease is present: the pathologist must also determine whether the standard treatment is likely to work for that particular patient, or whether alternative approaches are needed» Ponzoni explains. Important help comes from international disease classifications, such as that of hematological tumors.
The diagnostic process begins with morphological analysis under the microscope. If the picture is clear, the pathologist stops there. If a deeper investigation is required, the next step is immunohistochemistry: a technique that uses antibodies to highlight proteins specifically expressed by a given cell or tissue type. When immunohistochemistry still does not yield a diagnosis, the pathologist turns to molecular investigations targeting mutations associated with specific pathologies, or to the detection of genetic defects using FISH — fluorescent in situ hybridization.
Residents in pathological anatomy are involved in real clinical work from their very first day at UniSR. Under the supervision of experienced pathologists, they sample biological material arriving from operating theatres and outpatient clinics, review cases under the microscope alongside colleagues specialised in specific anatomopathological fields (haematopathology, gastrointestinal pathology, dermatopathology, uropathology, neuropathology, hepatic and pancreatic pathology, and others) and take part in tumour boards. «These are the multidisciplinary groups where oncologists, radiologists, internists, and pathologists discuss the therapeutic management of a patient together» Ponzoni explains, adding: «Here, residents also spend a compulsory period in the molecular pathology laboratory, where they develop expertise in the techniques and the interpretation of the results they produce».
Alongside microscope-based histological work, residents acquire fluency in digital pathology. This technology allows histological specimens to be viewed on a computer screen, at an image quality comparable to — and often exceeding — that of a conventional microscope. The on-screen image is produced by high-definition slide scanning, making it possible to analyse digital images at any time. «Digital pathology allows us to share and discuss cases in real time with colleagues who are physically distant, and to consult images remotely» Ponzoni explains.
The pathology department at San Raffaele Hospital runs what is, in all likelihood, the only large-scale operation in Italy to scan the entirety of its histological slides: «We are talking about roughly half a million slides a year, processed by two scanners running 24 hours a day, seven days a week. Since 2022, more than two million slides have been archived digitally» Ponzoni says.
Complementing digital pathology are the first steps in artificial intelligence applied to diagnostics, a field that will become part of the training curriculum for incoming residents from this academic year. It is worth clarifying that image-analysis algorithms function as a pathology assistant: tools that support the pathologist in diagnosis and therapeutic guidance, not replace them. «The use of artificial intelligence, particularly during residents’ training, will not replace the study of physical slides through direct microscope observation in our unit. The information fed to AI systems presupposes diagnostic experience, which is precisely what allows their conscious and effective use» Ponzoni stresses.
UniSR residents in pathological anatomy are progressively drawn into the school’s research activities, which include independent projects as well as numerous collaborative studies with San Raffaele Hospital laboratories and national and international groups. The department is equipped with technically advanced instrumentation, particularly in the field of spatial biology, including the Akoya system, which allows up to 100 different protein markers to be stained and visualised on a single slide. The technology makes it possible to identify the co-localisation of multiple markers on a single cell, and to see where that cell sits within the tissue context. One of the most significant applications is the study of tumours in relation to the microenvironment that surrounds them.
«A tumour that is morphologically identical can show different molecular alterations or be accompanied by different immune system elements in its microenvironment from one patient to the next. Identifying those mutations or biomarkers is critical for finding new, more precise therapeutic targets. Spatial biology, for instance, can help identify a new specific target for a given tumour type, against which to develop a tailored immunotherapy» Ponzoni explains.
He collaborates, among others, with the laboratories of Professor Chiara Bonini, Professor Matteo Iannacone, Professor Luca Vago, and Dr Marco De Giovanni, across projects in haematology, immunology, and related disciplines.
Residents are actively encouraged to spend part of their training at prestigious international centres, selected on the basis of individual interests and inclinations. Destinations already established include London, New York, Bordeaux, Berlin, and Lyon. «Spending a period abroad, engaging with environments very different from the Italian one, is something we strongly support. It allows residents to consolidate expertise in specific pathologies, observe how other institutions work, build inter-institutional collaborations, and gain experiences that contribute to personal growth, not just professional development».
«Anyone who wants to become a pathologist must have inexhaustible intellectual curiosity and a genuine commitment to continuous learning. In this work, we encounter the most varied and complex cases of disease, which means consulting the scientific literature very frequently. Occasionally, we come across cases that are still poorly described: this is precisely when collaboration becomes essential, not only with other pathologists, but with professionals across medicine, to reach a shared conclusion» Ponzoni says.
Curiosity, scientific rigour, and intellectual humility apply to everyone, residents and senior specialists alike, because the only real gap between a junior doctor and a trained pathologist is experience. «Residents bring different perspectives and can contribute innovative ideas, precisely because they approach the work from a different angle. They must always be listened to. Good ideas do not necessarily depend on age or seniority» Ponzoni says.
At UniSR, residents in pathological anatomy are also engaged as mentors for undergraduate students in the final stages of their degree. This too is a way of building responsibility and preparing them, from the outset, to explain the meaning and method of their work before delegating it.
«The possibilities for studying tissue at multiple levels of depth are now considerable, but technique alone is not enough to make a diagnosis or conduct good research. Our work proceeds through observation, comparison, questioning, hypothesis, and verification, all in pursuit of a single aim» Ponzoni concludes.