Astrocytoma and oligodendroglioma are histologically and genetically well-defined entities. The majority of astrocytomas harbor concurrent TP53 and ATRX mutations while most oligodendrogliomas carry the 1p/19q co-deletion. Both entities share high frequencies of IDH mutations. In contrast, oligoastrocytomas (OA) appear less clearly defined and, therefore, there is an ongoing debate whether these tumors indeed constitute an entity or whether they represent a mixed bag containing both, astrocytomas and oligodendrogliomas. We investigated 43 OA diagnosed in different institutions employing histology, immunohistochemistry and in-situ hybridization addressing the molecular genetic markers IDH1R132H, TP53, ATRX and 1p/19q loss. In all but one OA the combination of nuclear p53 accumulation and ATRX loss was mutually exclusive with 1p/19q co-deletion. In 31/43 OA only alterations typical for oligodendroglioma were observed while in 11/43 OA only indicators typical for astrocytomas were detected. A single case exhibited both, nuclear expression of p53, ATRX loss, IDH1 mutation and 1p/19q loss. However, this was the only patient undergoing radiotherapy prior to surgery, possibly resulting in acquisition of this uncommon combination. In fact, evaluation of the initial lesion demonstrated retained ATRX expression and no p53 upregulation. In OA with oligodendroglioma typical alterations, the portions corresponding to astrocytic part were determined as reactive (harbouring none of the alterations), while in OA with astrocytoma typical alterations the portions corresponding to oligodendroglial differentiation were neoplastic (harbouring identical alterations as the histologically astrocytic part). These data provide strong evidence against the existence of an independent OA entity. (under revision for Acta Neuopathologica)
approximately 15 months following standard of care therapy.However, 10 % survival at 5 years was observed in a randomized phase III study.At GBM recurrence, the addition of bevacizumab (BEV), a humanized monoclonal antibody against circulating vascular endothelial growth factor (VEGF), resulted in a 3-4 month prolongation of progression-free survival (PFS) without improving overall survival (OS).A 45-year-old female who underwent surgery for left fronto-temporal WHO grade II astrocytoma associated with epilepsy in 2005, 125I seed implantation at disease progression in 2009 and seed explantation 9 months later, was diagnosed with MGMT methylated GBM on the occasion of partial tumor resection in 2010 followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) chemotherapy, which was stopped after 4 months due to resection of a left temporal tumor cyst and recurrent cyst within 1 month.TMZ treatment causing prolonged thrombocytopenia was discontinued after 1 additional cycle.Immediately after this cycle, the patient experienced left median cerebral artery stroke resulting in right hemianopia, Broca's aphasia and severe hemiparesis of the right side.Three months later, BEV 10 mg/kg i.v.q14d was initiated, shortly interrupted for abdominal herniotomy in 2012, and continued for 3 years.Since 2014, concurrent low molecular weight heparin was given because of right lower limb deep venous thrombosis suspicion.Whereas GBM progression had not been detected for 2 years during anti-VEGF therapy, methionine PET MRI 6 months after BEV discontinuation revealed left temporal tumor recurrence.Rechallenge with BEV was initiated and the patient remained in stable clinical and radiographical condition for 10 months until now.This case highlights the utility of sequential BEV treatment in a patient being at high risk to develop chemotherapy-induced myelotoxicity.Long-term survival (> 3 years after diagnosis) in GBM has been attributed to patient-derived rather than tumor-derived factors.To our knowledge, this is the first description of effective long-term monotherapy with BEV for GBM and ongoing therapeutic response to single-agent BEV rechallenge in a patient with recurrent secondary GBM.
