Feldmann João Felipe Lima, Feldmann João Henrique Lima, Canedo Felipe Sales, Restini Felipe Cicci Farinha, Mattedi Romulo Loss, de Lima Luiz Guilherme Cernaglia A, Feher Olavo
Clinical Oncology Department, Hospital Sírio-Libanês, São Paulo, SP, Brazil.
Radiotherapy Department, McGill University Health Center, Montreal, QC, Canada.
Front Oncol. 2025 Jun 12;15:1604479. doi: 10.3389/fonc.2025.1604479. eCollection 2025.
Neuroepithelial tumors (NEpT) harboring fusions remain an enigma. Initially described in sarcomas, these tumors display remarkable histomorphological diversity and unpredictable clinical behavior based on histologic or molecular features, with no established management protocols. To date, this subgroup of neoplasms has not been acknowledged as a entity by the WHO classification system, and it is currently designated as 'NEC'/'NOS'. This retrospective case series describes two young adults (32-35 years old) without cancer predisposition or risk factors, diagnosed with -fused NEpT. Case 1, a female with seizures, presented a heterogeneous left parietal lobe lesion (4.0 × 3.2 × 3.6 cm), classified as high-grade NEpT with promoter methylation, a calibrated score of 0.95 (≥ 0.9), and a co-occurring somatic mutation. Case 2, a male with chronic headaches and mild right-sided paresthesia, had a left frontotemporal lesion (3.0 × 2.8 × 3.4 cm), initially diagnosed as an extraventricular neurocytoma but later reclassified as a NEpT with low-to-intermediate grade features, without MGMT methylation, and a calibrated score of 0.92. Case 1 received upfront resection, followed by Stupp protocol chemoradiation and temozolomide maintenance, resulting in 14 months of progression-free survival (PFS). Case 2 underwent subtotal resection and adjuvant radiotherapy after an 8-month recurrence, achieving 11 months of PFS to date. Both patients are asymptomatic, off corticosteroids, with the latest imaging revealing no disease progression. Our cases emphasize that -fused NEpT displays a unique signature (ventricular localization, glioneuronal differentiation, and a distinct methylation cluster), supporting their inclusion in the WHO classification. Moreover, we present the first documented somatic co-mutation involving . At present, despite the theoretical risk of temozolomide resistance due to overexpression, our results suggest that conventional glioma therapies remain the preferred approach.
携带融合基因的神经上皮肿瘤（NEpT）仍是一个谜。这些肿瘤最初在肉瘤中被描述，基于组织学或分子特征，它们表现出显著的组织形态学多样性和不可预测的临床行为，且没有既定的管理方案。迄今为止，这一肿瘤亚组尚未被世界卫生组织（WHO）分类系统确认为一个独立实体，目前被指定为“未另行规定的肿瘤（NEC）”/“未特指的肿瘤（NOS）”。本回顾性病例系列描述了两名无癌症易感性或危险因素的年轻成年人（32 - 35岁），他们被诊断为携带融合基因的NEpT。病例1是一名有癫痫发作的女性，其左顶叶有一个异质性病变（4.0×3.2×3.6厘米），被分类为高级别NEpT，伴有启动子甲基化，校准评分0.95（≥0.9），且同时存在体细胞突变。病例2是一名有慢性头痛和轻度右侧感觉异常的男性，有一个左额颞叶病变（3.0×2.8×3.4厘米），最初被诊断为脑室外神经细胞瘤，但后来重新分类为具有低至中级特征的NEpT，无MGMT甲基化，校准评分为0.92。病例1接受了 upfront 切除术，随后进行了Stupp方案放化疗和替莫唑胺维持治疗，实现了14个月的无进展生存期（PFS）。病例2在复发8个月后接受了次全切除和辅助放疗，迄今为止实现了11个月的PFS。两名患者均无症状，停用了皮质类固醇，最新影像学检查显示无疾病进展。我们的病例强调，携带融合基因的NEpT表现出独特的特征（脑室定位、神经胶质神经元分化和独特甲基化簇），支持将它们纳入WHO分类。此外，我们首次记录了涉及的体细胞共突变。目前，尽管由于过表达存在替莫唑胺耐药的理论风险，但我们的结果表明，传统的胶质瘤治疗方法仍然是首选方法。
