CNS Tumor with BCOR/BCORL1 Fusion: A Rare Tumor Entity - PubMed (original) (raw)

Case Reports

CNS Tumor with BCOR/BCORL1 Fusion: A Rare Tumor Entity

Jerry Lou et al. Int J Mol Sci. 2025.

Abstract

Central nervous system (CNS) tumor with BCL6 corepressor gene BCOR/BCORL1 fusion is an extremely rare tumor entity, with fewer than 40 cases reported. These tumors are distinct from the WHO 2021-defined CNS tumor with BCOR internal tandem duplication. Even rarer are CNS tumors that match to the methylation class of CNS tumors with BCOR/BCORL1 fusion, but lack fusions and instead harbor truncating small nucleotide variants in BCOR. To our knowledge, only two other cases of this scenario have been previously reported. Due to their scarcity and morphological features that mimic oligodendrogliomas and ependymomas, the diagnosis of CNS tumor with BCOR/BCORL1 fusion can be challenging, and misdiagnoses are not uncommon. Histologic findings of Olig2 positivity with focal to absent GFAP warrant further evaluation for this tumor entity. Moreover, no standard of care therapy exists for these tumors, making treatment selection difficult. We present a case of a 37-year-old woman with a midline CNS tumor with BCOR/BCORL1 fusion, harboring a pathogenic BCOR c.626del (p.S209Cfs*7) (Exon 4) variant, who was successfully treated with definitive radiation therapy and adjuvant temozolomide. Notably, EMA showed focal strong dot-like perinuclear immunoreactivity, which has not been previously reported in these tumors. This case adds to the limited but growing body of evidence supporting the use of radiation and temozolomide in treating tumors matching the methylation class of CNS tumors with BCOR/BCORL1 fusion without a detectable fusion.

Keywords: CNS tumor with BCOR internal tandem duplication; CNS tumor with BCOR/BCOR(L1) fusion; PNET; ependymoma; temozolomide.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1

Patient timeline (months).

Figure 2

Initial imaging demonstrating an enhancing (T1 and T1+), diffusion-restricting (DWI and ADC), partially calcified (CT), partially cystic (CT), T2-intermediate (T2), tectal-intraventricular mass causing obstructive hydrocephalus (GRE and FLAIR).

Figure 3

Serial post-contrast imaging demonstrating tumor growth and ventricular shunting (A,B), tumor debulking (C,D), continued tumor growth (E,F), and response to radiation treatment (G,H).

Figure 4

Hematoxylin and eosin staining. (A) Ependymoma-like tumor histomorphology with extensive perivascular pseudorosettes. (B) Elevated mitotic activity with three mitoses (arrows) in 10 high power fields. (C) Focal microcalcifications. (D) Microcysts and myxoid change.

Figure 5

(A) Patchy positive GFAP with a subset of fragments demonstrating more prominent expression in perivascular regions. (B) Strong to moderate OLIG2 immunopositivity in the majority of tumor nuclei. (C) Patchy positive EMA with a strong perinuclear dot-like pattern. (D) High Ki-67 (10–30%).

Figure 6

Methylation-based t-SNE distribution. Reference DNA methylation classes (Bethesda CNS tumor classifier v3.0): CNS_BCOR_FUS: CNS tumor with BCOR/BCORL1 fusion; CNS_BCOR_ITD: CNS tumor with BCOR internal tandem duplication; CNS_PLAG_AMP: CNS embryonal tumor with PLAG-family amplification; EPN_ST_SE: subependymoma and ependymoma, supratentorial; EPN_ST_ZFTA_FUS: supratentorial ependymoma, ZFTA fusion-positive; EPN_SPINE_SE: subependymoma and ependymoma, spinal; and SP_EPN_MYCN_LIKE: spinal ependymoma, MYCN-amplified-like.

Figure 7

Axial and sagittal views of the radiation treatment plan with PTV shown in red, and brainstem shown in blue, with color wash set to 5940 cGy in the top panels, and 5400 cGy in the bottom panels. PTV = planning treatment volume.

References

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CNS Tumor with BCOR/BCORL1 Fusion: A Rare Tumor Entity - PubMed (original) (raw)