I am a surgical pathologist and Head of the Department of Histopathology and Autopsy at the Institute of Medical Genetics and Pathology at University Hospital Basel, Switzerland. Currently, I am chairing the European Bone Marrow Working Group. I am a joined expert in the field of pathology for the Swiss Accreditation Authority.
A long-standing research topic of my group has been the deciphering of the clonal relationship and evolution of recurrent lymphomas. Recurrences of lymphoid neoplasms, even after long-lasting clinical remission, were previously regarded as direct outgrowths of the primary tumor. We hypothesized that clonally unrelated (true "de novo") cases of "recurrent" lymphoma occur more frequently than generally assumed. We showed that a proportion of recurrent classical Hodgkin's lymphomas are unrelated and therefore do not represent true "relapses" of the original malignant clone, which may be important as it raises the question of current aggressive clinical therapies in such cases. Along this, we developed a novel cell enrichment technique for robust genetic analysis of Reed-Sternberg cells. We then extended the hypothesis to diffuse large B-cell lymphomas (DLBCL). Here, too, we were able to show that clonally unrelated recurrences occur. We identified two distinct patterns of genetic evolution in clonally related relapses (early divergent/branching evolution versus late divergent/linear progression). As part of this project, a Next Generation Sequencing (NGS) panel for lymphoma was developed in our laboratory, which, after validation and accreditation, was the first laboratory in Europe to introduce it into clinical routine (https://www.unibas.ch/en/Research/Uni-Nova/Uni-Nova-128/Uni-Nova-128-New-treatmentconcepts-for-recurrent-lymphoma.html).
The above NGS panel was expanded and applied to extranodal and marginal zone lymphomas (MZL). In the study of nodal MZL, we identified for the first time recurrent and diagnostically useful and therapeutically relevant BRAF mutations. In MZL of the ocular adnexal structures, we showed that TNFAIP3 mutations are highly specific and discovered that lymphoid proliferations at that site harboring mutations of genes encoding NF-κB components and/or mutations of acetyltransferase genes represent lymphomas. We were he first to decipher the point mutation landscape of pulmonary MZL, finding a higher frequency of cases without point mutations but with chromosomal translocations and showing that DLBCL and MZL of the lungs are unrelated. Supported by cutting-edge methods, we were recently able to characterize primary DLBCL of bone providing molecular evidence that they are a specific entity.
The COVID-19 pandemic has dominated the period 2020-2022, causing more than 8 million confirmed and 30 million suspected deaths. Although the origin of the virus, its cellular entry mechanisms and epidemiology have been rapidly elucidated, in situ observations of the viral interactions with human organs and tissues have long been lacking. By the end of April 2020, when 150,000 patients had already died, no autopsy series had been described in the literature. In the absence of reliable data on SARS-CoV-2 infectivity in deceased individuals, various authorities advised against performing autopsies and so scientific activities to elucidate the underlying mechanisms of COVID-19 came to a standstill. Clinical and scientific activities of my research group made it possible to conduct the first systematic autopsy study on COVID-19 deceased. The collected material enabled uncovering characteristic vascular features in lethal COVID-19, namely severe endothelial damage, widespread thrombosis, microangiopathy and intussusceptive angiogenesis, leading to the conclusion that COVID-19 is an angiocentric clinical syndrome. The tissue-based research of my group further provided multiple insights into the immunopathology of COVID-19 with possible explanations regarding long-COVID. Finally, we succeeded in demonstrating that changes in the cell fitness marker hFwe-Lose can predict the outcome of COVID-19. The application of my research group was granted by the Botnar Research Centre for Child Health with around CHF 1.3 million until 2023. In an interdisciplinary approach with researchers from pathology, immunology, imaging, internal medicine, intensive care medicine and neurology, we generated knowledge about the pathogenesis of COVID-19 and freely-accessible published our results (https://pubmed.ncbi.nlm.nih.gov/?term=tzankov+a+COVID-19&show_snippets=off&sort=date&size=100).