Giordana M T, Ghimenti C, Leonardo E, Balteri I, Iudicello M, Duò D
Department of Neuroscience, University of Turin, Turin, Italy.
J Neurooncol. 2004 Feb;66(3):265-71. doi: 10.1023/b:neon.0000014519.61604.da.
Extracranial spread of neuroectodermal tumors is an unusual event, most frequently expected from glioblastomas and medulloblastomas. Single cases of metastatic oligodendrogliomas have been described, but no genetic data are reported. Oligodendrogliomas are characterized by distinct genetic alterations, i.e. loss of heterozygosity (LOH) of 1p and 19q; therefore, molecular genetic analysis of metastatic cases is of considerable interest. It may be instrumental in defining the distant tumor as metastatic oligodendroglioma and give clues to the genetic events associated with the highly malignant transformation. We present the case of a patient with multiple bone metastases from a cerebral oligodendroglioma. Oligodendroglioma grade II was the diagnosis both at original and second operation, performed 7 and 1 years before the extracranial dissemination. The extraneural spread presented before the local intracranial recurrence. The patient received procarbazine, lomustine, vincristine chemotherapy and radiotherapy after the second surgery. The computed tomography-guided biopsy of the bone lesions revealed tumor cells positive for GFAP, S-100 and Leu-7 and negative for cytokeratin, LCA and EMA. The genetic analysis of DNA from the original tumor, the bone metastasis and the autoptic brain tumor showed LOH of 1p; heterozygous deletion of CDKN2A/p 16 was detected as additional alteration in the metastasis and in the intracranial tumor at autopsy. TP53, MDM2 and CDKN2A/p14ARF genes were unchanged. Repeated brain surgery and extended survival may have acted as promoter of extraneural dissemination. Loss of CDKN2A most probably played an important role in the malignant progression: its involvement in metastatic potential remains to be clarified. Our data confirm that malignant transformation of oliogodendrogliomas may be undetected by histology and underscore the importance of genetic analysis. Coincidentally with intensive anticancer therapy, chemotherapy included, employed in patients with oligodendroglioma and the ensuing long survival, the frequency of metastatic oliogodendrogliomas may increase.
神经外胚层肿瘤的颅外扩散是一种不常见的情况，最常见于胶质母细胞瘤和髓母细胞瘤。已有转移性少突胶质细胞瘤的个别病例报道，但未报告基因数据。少突胶质细胞瘤具有独特的基因改变，即1p和19q的杂合性缺失（LOH）；因此，对转移性病例进行分子遗传学分析具有重要意义。这可能有助于将远处肿瘤定义为转移性少突胶质细胞瘤，并为与高度恶性转化相关的基因事件提供线索。我们报告一例患有脑少突胶质细胞瘤多发骨转移的患者。原发手术和第二次手术时均诊断为二级少突胶质细胞瘤，两次手术分别在颅外播散前7年和1年进行。神经外扩散发生在局部颅内复发之前。患者在第二次手术后接受了丙卡巴肼、洛莫司汀、长春新碱化疗和放疗。计算机断层扫描引导下的骨病变活检显示肿瘤细胞GFAP、S-100和Leu-7阳性，细胞角蛋白、LCA和EMA阴性。对原发肿瘤、骨转移灶和尸检脑肿瘤的DNA进行基因分析，显示1p存在LOH；在转移灶和尸检时的颅内肿瘤中检测到CDKN2A/p16杂合性缺失作为额外改变。TP53、MDM2和CDKN2A/p14ARF基因未改变。重复的脑部手术和延长的生存期可能是神经外播散的促进因素。CDKN2A的缺失很可能在恶性进展中起重要作用：其在转移潜能中的作用仍有待阐明。我们的数据证实少突胶质细胞瘤的恶性转化可能无法通过组织学检测到，并强调了基因分析的重要性。巧合的是，随着少突胶质细胞瘤患者采用包括化疗在内的强化抗癌治疗以及随之而来的长期生存，转移性少突胶质细胞瘤的发生率可能会增加。
