PATH-30. BCR-ABL1 Fusion Glioma: Two Exceptionally Rare Cases with Distinct Histopathological Features

OBJECTIVE Molecular diagnostics have become essential in the evaluation of brain tumors. However, the pathogenesis of gliomas remains incompletely understood. Here, we present two rare cases of IDH-wildtype gliomas harboring the BCR-ABL1 fusion gene—also known as the Philadelphia chromosome—typically associated with hematologic malignancies and rarely reported in brain tumors. Case 1: A 63-year-old man presented with recent-onset dysphasia and abnormal behavior. MRI revealed a 6.6 cm heterogeneously enhancing mass in the left temporal lobe. Gross total resection was performed. Histologically, the tumor exhibited high cellularity, marked nuclear atypia, brisk mitotic activity, microvascular proliferation, and necrosis—consistent with glioblastoma, IDH-wildtype, WHO grade 4. Despite treatment with Avastin and Irinotecan-based chemo-radiotherapy, the patient died 11 months post-diagnosis. Case 2: A 58-year-old man presented with syncope and language disturbances. MRI revealed a 5 cm T2 hyperintense, non-enhancing lesion in the left anterior temporal lobe and insula. Surgical resection was performed. Histology showed mild cellularity and nuclear atypia without mitoses, necrosis, or microvascular proliferation—were consistent with the previous classification of diffuse astrocytoma, WHO grade II. The patient remains recurrence-free 38 months post-surgery. Both tumors were strongly positive for GFAP, confirming glial differentiation. There were no clinical or radiologic signs of hematologic disease. Next-generation sequencing (NGS) revealed BCR-ABL1 fusion in both tumors, confirmed by fluorescence in situ hybridization (FISH) analysis. Interestingly, in case 1, amplification of chromosome 22q, where the BCR gene is located, was also observed. CONCLUSION BCR-ABL1 fusion is an exceptional finding in gliomas. Despite sharing this genetic alteration, the two cases demonstrated distinct histological features and clinical outcomes. Although Imatinib was not administered, its potential efficacy in BCR-ABL1-positive gliomas warrants further clinical investigation.