Molecular genetic study of a metastatic oligodendroglioma

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/p16 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.