Philipp Ströbel1, Jin Ye Yeo2
1Institute of Pathology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany; 2MED Editorial Office, AME Publishing Company
Correspondence to: Jin Ye Yeo. MED Editorial Office, AME Publishing Company. Email: med@amegroups.com
Expert introduction
Dr. Philipp Ströbel (Figure 1) is the director of the Institute of Pathology at the University Medical Center Göttingen in Germany and Co-Chair of the Comprehensive Cancer Center in Göttingen. He is currently also president of the German Division of the International Academy of Pathology (IAP) (2023-2025). Dr. Ströbel is an international reference pathologist for mediastinal tumors and his research and diagnostic expertise are particularly focused on oncology, with special attention to rare tumors such as sarcomas, thymic tumors, lymphomas, and leukemias.
He has co-authored numerous chapters of 2004, 2015, and 2021 editions of the World Health Organization (WHO) Classification of Tumors Volume on “Pathology and Genetics of Tumors of the Lung, Pleura, Thymus, and Heart” and is a co-author of > 70 scientific publications related to mediastinal pathology. During the first years of his career, his main research topic was paraneoplastic myasthenia gravis. His recent research mainly focused on preclinical and translational oncology in thymomas and thymic carcinomas to explore new therapeutic opportunities and avenues for these tumors.
Figure 1 Dr. Philipp Ströbel
Interview
MED: What inspired you to focus your research on rare tumors such as sarcomas and thymic tumors?
Dr. Ströbel: I was initially fascinated by the morphological diversity and complexity of these rare tumors. In the case of thymomas, there was also the association with paraneoplastic autoimmunity, which challenged me intellectually because of the immunological issues involved (for which a pathologist is ill-prepared). During my training and specialization, my diagnostic and scientific interests focused on hematological diseases, sarcomas, germ cell tumors, and neuroendocrine neoplasms. At some point I realized that all of these diseases can occur in the mediastinum. I think the wide range of possible differential diagnoses is one of the reasons why many pathologists feel uncomfortable with mediastinal biopsies. I became convinced that it is important to give patients with rare tumors the best possible care and that I can also contribute to this with my work as a pathologist, even though I do not normally have direct contact with patients.
MED: How have you seen the field of thymic tumors evolve over the years?
Dr. Ströbel: The field is still small and we continue to struggle with a lack of attention from the scientific community and the pharmaceutical industry. It is difficult to get young doctors and scientists interested in these rare tumors. Nevertheless, much has been achieved in recent years. One of the most important achievements has been the creation of the International Thymic Malignancy Interest Group (ITMIG), which was initiated by a patient and her husband. This global network brought together experts from a wide range of disciplines for the first time. The international acceptance of the WHO classification, to which the ITMIG contributed, has helped to improve the comparability of study results from different continents. Another stroke of good fortune for thymoma research was the Cancer Atlas (TCGA) study, which did not produce any directly therapeutically useful results, but generated a valuable treasure trove of data from which scientists around the world are now benefiting. I believe that new capabilities in artificial intelligence (AI)-based data analysis can help to better understand the biology of these tumors and develop new therapeutic approaches.
MED: Can you discuss some of the latest advancements in molecular pathology that your lab has contributed to, particularly in the context of thymic tumors and lymphomas?
Dr. Ströbel: My group was deeply involved in the TCGA study that established the molecular basis for the classification of thymic tumors. We also carried out the first comprehensive molecular characterization of thymic neuroendocrine tumors (TNETs), providing an experimentally validated basis for their classification. We were able to show that TNETs are very similar to neuroendocrine tumors in other organs, such as the gastrointestinal tract. For the first time, we were able to define a new subcategory in the thymus, which we named NET G3, in analogy to similar tumors in the gastrointestinal tract. Similar tumors have also been described in the lung. These findings have therapeutic relevance and I expect that they will be included in the next edition of the WHO classification.
Another focus of my group is preclinical and translational research. We are constantly trying to find new therapeutic approaches for patients with advanced thymoma and thymic carcinoma. This work has focused on overcoming chemoresistance and gaining a better understanding of the mechanisms of action of tyrosine kinase inhibitors such as sunitinib.
Another important topic has been and continues to be the study of apoptosis resistance. I believe that this mechanism plays an important role in thymoma and thymic carcinoma and hopefully can be addressed therapeutically in the future.
MED: How do you see the role of molecular diagnostics in the future of personalized medicine, especially concerning rare and complex tumors?
Dr. Ströbel: In my opinion, the importance of molecular diagnostics cannot be emphasized enough. Molecular markers have helped us pathologists enormously in recent years to better differentiate between existing entities and to define new entities. You can compare working with and without molecular methods to a building that is half obscured by fog on one day and is only vaguely recognizable, whereas on a sunny day it is clear and can be seen in all its details. Precise diagnostics are always a prerequisite for the development of new personalized therapeutic approaches. By molecular diagnostics, we currently generally mean next generation sequencing (NGS) methods, which primarily detect mutations and other structural changes in DNA, but only map part of the relevant molecular changes in a cell. The results of such analyses in thymomas and neuroendocrine tumors were not particularly successful because hardly any recurrent mutations were found. However, other methods such as epigenetic analyses or proteomics are already being used and will change our understanding in the foreseeable future.
MED: What are the most significant challenges and difficulties associated with rare or thymic tumors, and how do you overcome them?
Dr. Ströbel: It is difficult to interest a broader public in rare tumors, by which I mean health policy, health insurers, third-party funders, and also high-impact scientific journals. I have already talked above about the problem of getting young scientists interested in the topic. Imagine awarding a doctoral thesis to a young scientist who sometimes has to wait weeks or months for a new thymoma to arrive from which he or she is to isolate living cells. It takes a very long time to build up tissue and databases that adequately map the entire complexity of these tumors. Another major problem with rare tumors: even at large centers (including comprehensive cancer centers) there is not always sufficient expertise in all disciplines relevant to diagnosis and treatment. It is rare for thoracic surgeons, oncologists, radiotherapists and pathologists at one single institution to be equally interested in a disease such as thymoma. The solutions are obvious: it is a matter of building national and international networks that create public awareness, cooperate with each other and address the most important scientific and clinical problems step by step in the most coordinated and strategic way possible. The ITMIG network or comparable organisations such as the RYTHMIC network in France are good examples of this.
MED: What has been the most rewarding aspect of your career so far?
Dr. Ströbel: It is now relatively common for treating doctors, relatives or the patients themselves to call me, even though as a pathologist I am not directly involved in any treatment context. These are often desperate people who have already been through a long odyssey because nobody knows anything about their illness. I then try to help them by offering a second opinion, providing relevant literature or referring them to competent clinical contacts. Of course, there are also cases with an unfavourable prognosis in which not much can be done with the current state of knowledge, but this motivates me enormously to continue researching in this direction.
MED: How has your experience been as an Editorial Board Member of MED?
Dr. Ströbel: I am very grateful that there is a specialist journal that deals exclusively with mediastinal diseases and thus offers the small international community an excellent joint platform. The work is excellently supported by the superb dedicated editorial team.