AB036. The contribution of H.K. Müller-Hermelink to the understanding of human thymic pathology

Background: The human thymus plays a pivotal role in the development/function of immune system and its epithelial compartment is affected by rare tumors, the thymic epithelial tumors (TETs). Our purpose here is to report on the enormous contribution of the late Prof. H.K. Müller-Hermelink in defining TET’s diagnostic criteria based on the concepts of “cortical” and “medullary” differentiation in thymoma since his first studies in Kiel and then in Würzburg, where he was Chair of the Pathology Institute.

Methods: During his time in Kiel (till 1985), Prof. Müller-Hermelink investigated the normal human thymus during fetal and postnatal development by light/electron microscopy and, later, by immunohistochemistry. At the Würzburg Pathology Department [1985–2009], TETs were extensively characterized and the Institute became the major reference center for TET diagnosis in Germany. Moreover, in Würzburg Prof. Müller-Hermelink established the ‘thymus working group’, initially working with Thomas Kirchner and, later on, with Alex Marx and Philipp Ströbel in order to push thymic research. Marx A’s group originally focused on thymoma-associated myasthenia gravis (MG) using tissue/cell-based ex vivo-techniques, and also provided the landmark paper on chromosomal gains/losses in thymomas and thymic carcinomas in 2000. A database including detailed demographical, surgical, immunological and oncological aspects was established by P. Ströbel.

Results: Remarkably, Prof. Müller-Hermelink’s original proposal of a “corticomedullary” differentiation in TET, only based on morphological and clinicopathological data, formed the basis for a new thymoma classification that has become known as the “histogenetic” classification. Despite considerable debate among pathologists in the beginning, this classification formed the basis of TET “1999 WHO classification”, which has gained almost world-wide consensus and, with minor updates, has been maintained in Prof. Müller-Hermelink’s spirit in the subsequent editions of the World Health Organization (WHO) classification (2004-2015-2021). For the last 25 years, myriads of scientific investigations all over the globe, addressing thymoma-related morphological, molecular, immunological and treatment-related (still burning) issues, have been based on this classification.

Conclusions: In summary, Prof. HK Müller-Hermelink’s outstanding scientific and educational achievements have had an enormous, lasting impact on the understanding of the normal and diseased thymus, with obvious prospects for the future of the field.

Keywords: Thymoma; carcinoma; classification; pathology; genetics