摘要： 研究背景 菊形团形成型胶质神经元肿瘤（RGNT）为低级别混合性神经元-胶质肿瘤，好发于小脑、第四脑室顶或颅后窝，故也称为第四脑室菊形团形成型胶质神经元肿瘤，以病灶中含神经细胞性“菊形团”和（或）围血管假“菊形团”结构，以及毛细胞型星形细胞瘤成分为特点。目前文献共报道约50 例，主要发生于第四脑室及其邻近区域，仅少数发生于第四脑室外，本文报告1 例临床罕见的发生于脑实质内的RGNT 病例，根据组织学检测方法分析其诊断要点，以期提高临床对该肿瘤的鉴别诊断能力。方法与结果 女性患者，12 岁。因反复肢体抽搐2 年伴轻微间歇性头痛1 周入院。MRI显示左侧额叶占位性病变，未累及脑室和硬脑膜，T₁WI 低信号、T₂WI 呈不均匀高信号，增强后病灶呈不均匀强化。术中可见病灶位于脑实质内伴囊性变，无包膜，与周围组织分界清楚，手术全切除。肿瘤细胞形成小Homer-Wright 样“菊形团”和围血管假“菊形团”结构，并可见典型的毛细胞型星形细胞瘤区域；形成“菊形团”结构的肿瘤细胞突触素和少突胶质细胞转录因子2 表达阳性，胶质纤维酸性蛋白表达阴性。结论 相对于经典部位，脑实质内RGNT 更为罕见，术前难以明确诊断。鉴于发病部位罕见、组织学构象复杂且缺乏特征性影像学表现，临床应提高对脑实质内RGNT 的鉴别诊断能力，并注意与其他具有相似组织学构象的中枢神经系统肿瘤相鉴别。

关键词: 脑肿瘤, 神经胶质, 神经元, 免疫组织化学, 病理学

Abstract: Background  Rosette-forming glioneuronal tumor (RGNT) is a rare and novel brain tumor. It affects mainly young adults and arises in the midline, primarily involving the cerebellum, and the walls or floor of the fourth ventricle. The tumor is composed of distinctive histological components, uniform neurocytes forming rosettes and (or) perivascular pseudorosettes, as well as astrocytic component resembling pilocytic astrocytoma. To our best knowledge, no more than 50 cases of RGNT have been described in the literatures to date and found commonly in association with the ventricular system. Only a few cases have been known to occur at sites outside of its usual location. Herein, we present a rare case of RGNT of brain parenchyma. Due to its rarity and non-specific appearance in radiological examination, it is a diagnostic challenge for radiologists and histopathologists to differentiate RGNT in unusual sites from other intracranial lesions because of its similarities in radiological and histological findings. The aim of this study is to summarize the clinicopathological features of RGNT and discuss the differential diagnosis of histologically similar tumors in brain.  Methods  The clinical manifestation of a patient with RGNT occurring in left frontal lobe was presented retrospectively. Resected mass was routinely paraffin-embedded and stained with Hematoxylin and Eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including glial fibrillary acidic protein (GFAP), S-100 protein (S-100), cytokeratin (CK), neuronal nuclear antigen (NeuN), synaptophysin (Syn), neuron-specific enolase (NSE), chromogranin A (CgA), oligodendrocytes transcription factor-2 (Olig-2), epithelial membrane antigen (EMA) and Ki-67 (MIB-1).  Results  A 12-year-old girl presented with 2-year history of twitches and mild headache. MRI revealed a solid well-circumscribed lesion in left frontal lobe with mild heterogeneous enhancement. The lesion was observed to locate in brain parenchyma and there was no evidence of tumor infiltrating in ventricular system. Craniotomy was performed and the tumor was removed totally. Histological examination revealed that the tumor was distinctive in its juxtaposition of patterned neurocytic and pilocytic astroglial components. The neurocytic component showed the tumor cells had small, uniform round nuclei with scant cytoplasm and formed narrow perivascular pseudorosettes or Homer-Wright-like rosettes arrays of neurocytic nuclei around delicate eosinophilic neuropil cores. The glial component tended to exhibit pilocytic astrocytoma-like morphology with long, hair-like processes and Rosenthal fibers. Immunohistochemical staining showed that the tumor cells in glial component were diffusely positive for GFAP and S-100, but negative for NeuN, Syn and NSE. However, perivascular pseudorosettes or Homer-Wright-like rosettes were positive for Syn and Olig-2, and negative for GFAP. Ki-67 index was low and less than 1%. Based on clinical presentation and histological findings, a final histological diagnosis of RGNT in brain parenchyma, WHO grade Ⅰ, was made according to the criteria of WHO classification. The patient has not received chemotherapy and attended follow-up for 12 months, without any neurological deficit or signs of recurrence.  Conclusions  RGNT is a rare tumor and classified as mixed neuronal-glial tumor. RGNT probably derives from a common progenitor cell originated from subependymal plate or brain parenchyma, able to differentiate toward both glial and neuronal phenotype. RGNT in brain parenchyma is also observed to have the similar biological behaviors and histopathological characteristics with its intra-ventricular counterpart. With similarities in histological findings, it may be difficult to differentiate RGNT from extraventricular neurocytoma, dysembry oplastic neuroepithelial tumor (DNT), and ependymoma with neuronal differentiation or neuropil-like islands. The presence of distinct low-grade glial component in the tumor and appropriate immunohistochemical profile are necessary for correct diagnosis.

Key words: Brain neoplasms, Neuroglia, Neurons, Immunohistochemistry, Pathology