Takeuchi Hiroaki, Kubota Toshihiko, Kitai Ryuhei, Matsuda Ken, Hashimoto Norichika, Sato Kazufumi
Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui, 910-1193, Japan.
J Neurooncol. 2009 Jan;91(1):33-8. doi: 10.1007/s11060-008-9690-6. Epub 2008 Sep 10.
Malignant glioneuronal tumors (MGNT) are suggested to be a new entity of glioma defined morphologically as any malignant glioma showing immunohistoichemical evidence of neuronal differentiation. We encountered seven cases of MGNT with oligodendroglioma-like component and investigated alternations of chromosome 1p and 19q in these tumors. Seven patients ranged from 33 to 62 years of age, four females and three males. Immunohistochemical study of these tumors was performed using neuronal markers (synaptophysin, neurofilament, beta-tubulin, chromogranin A and NeuN), astrocytic marker (GFAP) and Ki-67. We undertook a molecular cytogenetic study of tumor specimens obtained from seven patients using fluorescence in situ hybridization (FISH) with DNA probes mapping to chromosome 1p36, 1q25, 19p13 and 19q13. Histologically, these tumors resembled anaplastic oligodendroglioma. Immunohistochemically, tumor cells were immunoreactive for synaptophysin (7/7), neurofilament (6/7), beta-tubulin (5/7), chromogranin A (4/7), NeuN (2/7) and GFAP (7/7). The Ki-67 labeling index ranged from 4.5% to 20.7%. FISH analysis demonstrated either 1p or 19q deletion in all seven cases (100%) and both 1p and 19q deletions in five cases (71%). The 1p deletion was detected in six of seven cases (86%) and 19q deletion was also detected in six (86%). 1p and 19q deletions were present in MGNT, especially those with oligodendroglial components. We suggest that the oligodendroglial-like feature was associated with not only 1p or 19q loss but also differentiation along neuronal cell lines as a factor of favorable prognosis in glial tumors. It is inappropriate to make a diagnosis of oligodendroglioma based only on morphological resemblance to oligodendroglia.
恶性神经胶质神经元肿瘤(MGNT)被认为是胶质瘤的一种新类型,在形态学上定义为任何显示神经元分化免疫组化证据的恶性胶质瘤。我们遇到了7例伴有少突胶质细胞瘤样成分的MGNT,并对这些肿瘤中1号染色体短臂(1p)和19号染色体长臂(19q)的改变进行了研究。7例患者年龄在33岁至62岁之间,4例女性,3例男性。使用神经元标志物(突触素、神经丝、β-微管蛋白、嗜铬粒蛋白A和神经元核抗原)、星形细胞标志物(胶质纤维酸性蛋白,GFAP)和Ki-67对这些肿瘤进行了免疫组化研究。我们使用与定位于1号染色体短臂36区(1p36)、1号染色体长臂25区(1q25)、19号染色体短臂13区(19p13)和19号染色体长臂13区(19q13)的DNA探针进行荧光原位杂交(FISH),对7例患者的肿瘤标本进行了分子细胞遗传学研究。组织学上,这些肿瘤类似于间变性少突胶质细胞瘤。免疫组化方面,肿瘤细胞对突触素呈免疫反应阳性(7/7)、神经丝(6/7)、β-微管蛋白(5/7)、嗜铬粒蛋白A(4/7)、神经元核抗原(2/7)和GFAP(7/7)。Ki-67标记指数范围为4.5%至20.7%。FISH分析显示所有7例(100%)均存在1p或19q缺失,5例(71%)同时存在1p和19q缺失。7例中有6例(86%)检测到1p缺失,6例(86%)也检测到19q缺失。MGNT中存在1p和19q缺失,尤其是那些具有少突胶质细胞成分的肿瘤。我们认为少突胶质细胞瘤样特征不仅与1p或19q缺失有关,还与沿神经元细胞系的分化有关,这是胶质肿瘤预后良好的一个因素。仅基于与少突胶质细胞的形态相似性做出少突胶质细胞瘤的诊断是不合适的。