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.

Gliomatosis cerebri: no evidence for a separate brain tumor entity

“…The highly variable course of disease, with median survival of about 30 months after diagnosis and broad variation from a few months to >40 months [7,8,21], also challenges the view that GC comprises a distinct glioma entity. Moreover, molecular studies on GC have reported genetic alterations that are also common in diffuse and anaplastic astrocytic gliomas or glioblastomas, such as isocitrate dehydrogenese 1 (IDH1) mutation, tumor protein 53 (TP53) mutation and epidermal growth factor receptor (EGFR) amplification [4,5,7,9,11,13,14,18,21]. No GC-specific genetic alteration or molecular signature has been reported to date.…”

EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma

“…3 Extent of resection is a prognostic factor in these tumors, too. 7,15 Although RT (54)(55)(56)(57)(58)(59)(60) Gy, 1.8-2 Gy-fractions) has been considered standard of care for anaplastic oligodendroglial tumors, their chemosensitivity to nitrosoureas and TMZ has long been recognized, and ongoing controversies do not focus on whether to give RT or alkylating chemotherapy at all, but rather when and in what sequence. Long-term results of the two early large independent randomized clinical trials -EORTC 26951 and Radiation Therapy Oncology Group (RTOG) 9402 -that explored the value of PCV polychemotherapy, either prior to or immediately after RT, indicate that the inclusion of chemotherapy in the first-line treatment confers a survival advantage which becomes evident only after follow-up of more than six years and only in the subgroup of patients with 1p/19q-co-deleted tumours.…”

“…55,56 The NOA-05 trial explored the efficacy of primary PC chemotherapy, omitting vincristine because of poor blood brain barrier penetration, and observed treatment failure at 8 months in less than half of the patients, and a median overall survival of 30 months. 54 …”

Gliomatosis of the spinal cord in a cat: a case report

“…Peretti-Viton et al (2002) characterised gliomatosis in humans as a heterogeneous glial proliferation with various degrees of anaplasia. Prognosis of gliomatosis is variable but for at least 50% of patients it is as poor as for glioblastoma (Herrlinger et al 2002). The poor outcome for these patients and low survival rates was also mentioned by Bruna and Velasco (2010).…”