Gliomatosis cerebri: molecular pathology and clinical course

Abstract

Gliomatosis cerebri is a rare, diffusely growing neuroepithelial tumor characterized by extensive brain infiltration involving more than two cerebral lobes. Among 13 patients with gliomatosis cerebri (median age, 46 years), biopsies showed features of diffuse astrocytoma (n = 4), oligoastrocytoma (n = 1), anaplastic astrocytoma (n = 5), anaplastic oligoastrocytoma (n = 1), or glioblastoma (n = 2). Molecular genetic investigation showed TP53 mutations in three of seven tumors and both PTEN mutation and epidermal growth factor receptor overexpression in one tumor. Amplification of CDK4 or MDM2 or homozygous deletion of CDKN2A was not detected. Three of 10 patients receiving radiotherapy showed a partial response (one patient) or had stable disease (two patients) lasting for more than 1 year. Four of six patients treated with procarbazine, carmustine, vincristine chemotherapy demonstrated partial remission (one patient), minor response (two patients), or stable disease (one patient). Median survival time from diagnosis was 14 months (range, 4-91+ months). Infratentorial involvement was associated with shorter survival. We conclude that (1) the molecular genetic alterations in gliomatosis cerebri resemble those in diffuse astrocytomas; (2) the prognosis of gliomatosis cerebri is variable but for at least 50% of patients as poor as for glioblastoma; and (3) some patients respond to radiotherapy and/or procarbazine, carmustine, vincristine chemotherapy.