EPEN-25. “CONCERNING EPENDYMOMAS, A FURTHER SUBDIVISION IS NEITHER MORPHOLOGICALLY NOR BIOLOGICALLY NECESSARY”: A NARRATIVE REVIEW OF RESEARCH ON EPENDYMOMAS BETWEEN 1865 AND 2024

Abstract

Abstract BACKGROUND The history of research on ependymomas dates back to the nineteenth century. However, ependymomas have received much less attention than other neuro-oncological diseases. This narrative review investigates the history of ependymoma as a distinct tumour entity. METHODS A comprehensive literature search in German, English and French was carried out for publications from 1850 to 2024 in PubMed, the Internet Archive, and the library of Heidelberg University. Additionally, the evolution of the classification of ependymoma throughout the editions of the WHO classification of CNS tumours was analysed. RESULTS The first major systematic description of ependymal tumours was published in 1865 by Rudolf Virchow, who hypothesized that ependymomas originated from chronic irritations to the ependyma. In 1899, perivascular (pseudo-)rosettes were described for the first time. Subsequently, Percival Bailey and Harvey Cushing’s systematic classification efforts laid the groundwork for new advancements. Debates about the classification of ependymomas can already be found in publications by Percival Bailey or Gustave Roussy in 1924, with a major focus on the definition of ependymoblastoma as an independent entity, which was only resolved in 2016 with the introduction of the new diagnosis ETMR. Klaus Joachim Zülch’s important mid-20th-century work highlighted clinical variations within ependymomas but deemed no further stratification necessary. The WHO’s classifications in 1979, 1993, 2000 and 2007 relied on histopathology, with only minor details being adapted over the years. A new era began in 2016 with the recognition of C11orf95-RELA (ZFTA-RELA) as a defining hallmark of supratentorial ependymomas. The latest WHO classification in 2021 adopted a molecular-anatomical approach, incorporating new subgroups and abandoning histomorphological subtypes due to limited prognostic value. Tumor grading became mostly optional. CONCLUSIONS This review summarises the significant evolution in ependymoma research, particularly in the 2010s. Strikingly, many of the questions that Virchow, Bailey or Roussy investigated, remain unanswered in 2024.