Low-grade neuroepithelial tumor with FGFR1::TACC1 fusion: a clinicopathologic analysis of seven cases.

PURPOSE: To characterize the clinicopathologic, radiologic, immunophenotypic, and molecular features of low-grade neuroepithelial tumor harboring FGFR1::TACC1 fusion.

METHODS

Seven cases with confirmed FGFR1::TACC1 fusion were retrospectively analyzed. Clinical information, histopathological features, immunohistochemical profiles, next-generation sequencing (NGS) results and DNA methylation–based clustering analyses were reviewed.

RESULTS

All patients were male, with a median age of 14 years. Tumors were predominantly located in the cerebellum. Magnetic resonance imaging revealed mainly cystic–solid lesions with hypointensity on T1-weighted imaging and relatively well-defined margins on FLAIR sequences. Histologically, all tumors exhibited oligodendroglia-like cells with round nuclei and perinuclear halos, accompanied by neurofibrillary islands and edematous stroma. Branching capillaries (6/7), calcifications (4/7), and Rosenthal fibers (3/7) were variably observed. One case demonstrated morphologic and immunophenotypic features overlapping with extraventricular neurocytoma. Immunohistochemistry demonstrated GFAP and Olig2 expression in all cases; Syn positivity was identified in four cases and focal NeuN positivity in two cases. Focal CD34 expression was found in one. The Ki-67 was below 5% in all tumors. NGS confirmed FGFR1::TACC1 fusion in every case. DNA methylation profiling assigned tumors to multiple reference classes, including low-grade glioma (LGG), dysembryoplastic neuroepithelial tumor (DNT), pilocytic astrocytoma, posterior fossa (PA PF) and anaplastic pilocytic astrocytoma (ANA PA). No significant chromosomal arm-level copy number alterations were detected. All patients underwent gross resection, with one receiving adjuvant radiotherapy. No tumor recurrence was observed during follow-up (36–60 months).

CONCLUSION

Low-grade neuroepithelial tumors with FGFR1::TACC1 fusion represent a heterogeneous entity where a single recurrent gene fusion may be associated with diverse histomorphologic features and variable DNA methylation profiles.