Angiocentric glioma (AG) is a supratentorial diffuse low-grade glioma characterized by the MYB::QKI fusion gene, showing angiocentric growth of monomorphous spindle cells with astrocytic and ependymal immunophenotypes. We describe a rare case of MYB::QKI fusion-positive diffuse cerebellar glioma in a 54-year-old male. The patient initially presented with a T2/FLAIR hyperintense lesion in the left cerebellar hemisphere and slowly progressive neurological symptoms. Histopathological evaluation revealed a diffuse glioma characterized by spindle-shaped and small epithelioid cells with perivascular infiltration. Immunohistochemistry showed positivity for glial fibrillary acidic protein and only occasionally positive for Olig2. No dot- or ring-like epithelial membrane antigen immunoreactivity was observed. In this case, the proliferative activity was higher than that in typical AG cases, as manifested by multiple mitoses (four mitoses/slide) and a Ki-67 labeling index of 5%. The tumor cells were negative for IDH1 p.R132H and H3 p.K28M mutation-specific antibodies. Fluorescence in situ hybridization showed a MYB break-apart signal, and reverse transcription-polymerase chain reaction analysis confirmed an in-frame MYB (6q23.3, exon 11, NM_001161659.2)::QKI (6q26, exon 5, NM_006775.3) fusion. IDH1 p.R132, IDH2 p.R172, H3-3A p.K28, H3C2 p.K28, and BRAF p.V600 were all wild type. DNA methylome profiling did not match any of the established methylation classes, including the four subtypes of diffuse glioma, MYB- or MYBL1-altered. Considering the results of DNA methylome profiling, the question remains as to whether this case represents a subset of AG (diffuse glioma, MYB/MYBL1-altered) or a distinct subtype. Although the morphological findings and the presence of fusion indicated that the tumor was a cerebellar AG, the DNA methylome profile did not match that of AG. An accumulation of more cases is needed to determine the precise nature of the tumor, which may lead to an expansion of the tumor concept.
Keywords: MYB; QKI; central nervous system; cerebellum; diffuse glioma.
© 2024 Japanese Society of Neuropathology.