LGG-17. EPIGENETICALLY DEFINED ANGIOCENTRIC GLIOMAS MAY LACK ANGIOCENTRIC GROWTH AND INSTEAD SHOW A VARIETY OF GROWTH PATTERNS

Abstract

Abstract Angiocentric glioma mainly occurs in children and young adults. It is associated with a good prognosis (CNS WHO grade 1). Molecularly, most angiocentric gliomas have a MYB-QKI fusion. Histologically, angiocentric gliomas were initially defined by an angiocentric growth of the tumor cells. However, we noticed that epigenetically defined angiocentric gliomas often get different diagnoses based on their histology as they may lack this angiocentric growth pattern. We collected 48 epigenetically defined angiocentric gliomas from 46 patients with sufficient tissue for histological and molecular analyses (DNA methylation analyses; RNA sequencing of a subset; 37 supratentorial and 11 infratentorial cases). The classification was done using unsupervised hierarchical cluster analyses from DNA methylation data and the brain tumor classifiers v11b4 and v12.5 (www.molecularneuropathology.org). Angiocentric gliomas were epigenetically distinct from the diffuse astrocytomas, MYB- or MYBL1-altered. A MYB-QKI fusion was detected in 69% (n = 18/26) of angiocentric gliomas, confirming the diagnosis. Other fusions detected were fusions of MYB with intergenic sites, mainly close to QKI (19%; n = 5/26), and MYBL1-QKI (8%; n = 2/26). We then did a histological workup of these cases. Only 75% showed the typical angiocentric growth pattern that often was not very pronounced. Many angiocentric gliomas displayed an unspecific growth while others resembled pilocytic astrocytoma or ependymoma. Hence, about 59% of angiocentric gliomas were initially misdiagnosed without molecular analyses (supratentorial 50%, infratentorial 100%). We obtained similar results expanding the cohort with further epigenetically defined angiocentric gliomas for which no tissue for a histological re-evaluation was available (total 68 cases; 50 supratentorial, 12 infratentorial; 65 patients). In this expanded cohort, 54% of cases were initially misdiagnosed (45% of supratentorial and 100% of infratentorial cases). In summary, we show that angiocentric glioma often does not show the typical angiocentric growth pattern. Thus, molecular analyses are needed for a reliable diagnosis.