Intracranial Mesenchymal Tumor with FET-CREB Gene Fusion: A Case Report of Late Recurrence.

Intracranial mesenchymal tumors with FET‑CREB fusion represent a rare tumor entity newly defined in the 5th edition of the WHO classification of central nervous system tumors. Due to overlapping morphological features, these neoplasms were previously diagnosed under different names, including intracranial angiomatoid fibrous histiocytoma and intracranial myxoid mesenchymal tumor. Clinically, they need to be differentiated from meningioma, high‑grade glioma, solitary fibrous tumor, and other intracranial neoplasms. Most supratentorial lesions achieve good outcomes after gross total resection, and tumor recurrence is considered uncommon. We present a 58‑year‑old female patient who experienced local tumor recurrence 27 months after complete resection of a primary supratentorial cystic mass located in the right temporoparieto‑occipital region. The primary lesion was predominantly cystic with minimal solid components. Microscopically, oval and spindle‑shaped tumor cells infiltrated the cystic wall without obvious brain parenchymal invasion, accompanied by linear hemosiderin deposition. Immunohistochemically, tumor cells were diffusely positive for vimentin, MUC4, CD99, synaptophysin, EMA, and ALK (D5F3). Focal positivity was observed for CD68 and broad‑spectrum cytokeratin. All other markers including SMA, MyoD1, HMB45, myogenin, TFE3, MelanA, SOX10, SSTR2, PR, GFAP, and Oligo2 were negative. INI1 expression was intact in all tumor nuclei. The Ki‑67 proliferation index increased from 5%-10% in the primary lesion to 10%-15% in the recurrent specimen. Both primary and recurrent tumors harbored identical EWSR1::ATF1 fusion confirmed by next‑generation sequencing and FISH analysis. The patient received no adjuvant therapy after the first operation, and delayed recurrence was detected during routine MRI follow‑up. A combination of radiological findings, histopathology, immunohistochemistry, and molecular testing is essential for accurate diagnosis of this rare tumor. This case describes late tumor recurrence in an adult patient with typical low‑risk features, including supratentorial location and complete surgical resection. Our findings expand the clinical and pathological spectrum of EWSR1::ATF1‑fused intracranial mesenchymal tumors. Long‑term imaging surveillance is necessary even for patients with favorable clinical factors. Standardized follow‑up protocols and optimal adjuvant treatment strategies remain undefined and require further validation in larger cohorts.