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Pathomorphology is the study of morphological changes in tissues and organs that occur in the course of a disease. Pathomorphological examination is used in the treatment of neoplastic diseases, which is nowadays more and more personalized. Often it depends, among others on the type and subtype of the cancer. To assess them, tests performed by a pathologist are necessary. We talk to prof. dr hab. n. med. Monika Prochorec Sobieszek, Head of the Department of Pathology and Laboratory Diagnostics at the Oncology Center - Institute in Warsaw.

Pathomorphologyis the study of morphological changes in tissues and organs resulting from disease.Pathomorphological examinationis used in the treatment of neoplastic diseases, which is nowadays more and more personalized. It often depends on the type and subtype of the tumor as well as on the presence of receptors, antigens and mutations in the tumor cells. if you have lung cancer. To evaluate them, tests performed bypathomorphologistare necessary. We talk to prof. dr hab. n. med. Monika Prochorec Sobieszek, Head of the Department of Pathology and Laboratory Diagnostics at the Oncology Center - Institute in Warsaw.

  • Professor, what does a pathologist do?

Pathomorphology is one of the fields of medicine that deals with cancer diagnostics. The most important part of our work is examining the tissue material taken from the patient, examining it under a microscope, determining the type of tumor and assessing the presence of receptors and antigens on the surface of the cell, which we determine with the immunohistochemical method, i.e. by staining them with appropriate reagents (monoclonal antibodies).

  • Why is it important to know the type of cancer and if there are any receptors on the cell?

The treatment of the patient depends on it. There are two main types of cancer in lung cancer - small cell and non-small cell, towhich includes adenocarcinoma and squamous cell carcinoma, each treated differently. Additionally, lung cancer cells may have EGFR gene mutation, ALK gene rearrangement and show different expression of PD1, PD-L1 antigens. The presence of certain mutations and rearrangements is a predictor of what kind of treatment we should apply.

  • Can the examination also determine whether it is a primary tumor or a metastasis?

Yes, we can tell, although sometimes it's not easy. There are some nuances in the structure and size of neoplastic cells and, for example, lung adenocarcinoma can look very much like intestinal adenocarcinoma or stomach cancer. Then we have to mark the next markers to assess where this cell comes from. In such cases, information from the attending physician is very important as to whether the patient has had any cancer before. This definitely makes it easier for us to recognize.

  • What is the effect of the determination of receptors and antigens that the Professor mentioned on the treatment of the patient?

We do this in order to establish the diagnosis as quickly and as accurately as possible and so that the oncologist who conducts the patient can start appropriate treatment. At the moment, in lung cancer, in addition to chemotherapy, molecularly targeted drugs and immunotherapy can be used, but to turn them on, you need to know if the cell has receptors that the drug will act on and the degree of expression.

  • Why is this degree of expression important?

Unfortunately, most of the drugs I mentioned are not reimbursed in Poland yet, but patients can receive them in clinical trials. However, the qualification for such a test depends on many factors, one of which is the expression of specific receptors or antigens (e.g. PD-1, PD-L1). Patient with the expression of 8% will qualify for the study, where the threshold is 5 percent, but already for the study, where 25 percent is required. expressions will not qualify.

  • How does the pathologist assess the degree of expression?

We evaluate it by examining the preparation under a microscope, so you can say "by eye". So everything depends on the experience of the pathologist and his management of such cases.

  • Your work is extremely important and responsible, the patient's life depends on this assessment …

Therefore, in cases where we have any doubts, we consult the preparation with a second pathologist to compare the results. In some cancers there are methods that help us count what interests us. This is the case, for example, in cancerbreast when we define the expression of progesterone receptors, estrogen and HER2 protein. In lung cancer, the PD-L1 antigen is present not only on neoplastic cells, but also on inflammatory cells, and only a skilled human eye is able to distinguish them. But a lot also depends on what material we have to evaluate, i.e. who, how and from which place of the tumor will take it.

  • What are the differences then?

Tumors in lung cancer are heterogeneous, which means that their structure is extremely diverse. It may happen that the section taken from one place will differ from the section taken 2 mm next to it. In one place, expression can be very strong and the patient will qualify for therapy, and in another, completely different, which is not sufficient for qualification. If we have a lot of material from which we can prepare preparations for evaluation, that's good, because then we look at various fragments of the tumor. It happens, however, that the specimens are not collected during the operation, but during the fine-needle biopsy, and then we have very little material, which makes my task even more difficult.

  • Wouldn't it be easier if you viewed such clippings not under a microscope, but on your computer, as digital images?

Digital pathology is a relatively new method that has not been as widely adopted as digital imaging in radiology. It has its advantages - the microscopic image can be viewed in various directions and magnification, and if necessary, quickly sent via a computer network to a pathomorphologist in another center for consultation. This is important, especially in those places where pathologists are absent or absent. However, making such digital photos from microscopic slides made of the collected material takes time, and besides, such photos are quite large, which makes them difficult to store, archive and transfer. One photo takes up as much space as a 2.5 hour HD movie. So you would need appropriate servers, a computer network, appropriate software and screens with appropriate resolution, i.e. a very expensive infrastructure.

  • And wouldn't some computer program or robot be helpful in assessing the preparation under the microscope, without the need to take digital photos of it?

Such attempts have been made in the evaluation of gynecological cytology. There, perhaps, it would be possible to replace humans with a robot, because the criteria are repeatable and the computer program is able to make an assessment. Of course, in cases where there is something suspicious, the human ultimately has to view and evaluate the sample. When it comes to lung cancer, there are a lot of atypical variables,which the machine cannot learn. Sometimes non-cancerous cells, such as macrophages and inflammatory cells, react to reagents and stains. Man knows how to catch them and knows that he has to ignore them, and the machine is not able to do it flawlessly. Besides, such a test must be signed by the person who takes responsibility for it.

  • You mentioned the professor that there are no pathologists. How many of them are there in Poland and is that enough?

At the moment, there are approx. 450 professionally active pathologists in Poland. Theoretically, such a specialist should be in every hospital. There are about 700 state hospitals. It should be remembered that one, several or even a dozen or so pathologists do not work in academic centers. Therefore, it happens that samples of the collected material are sent to another city for testing, and this is associated with time. Then the diagnosis and treatment of the patient are delayed, which is very unfavorable.

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