Analysis of a synchronous gliosarcoma and meningioma with long survival: A case report and review of the literature
A previously healthy 51-year-old woman, with no family history of cancer, was admitted in another institution in October 2003 with a history of dysarthria and left hemibody paresthesias followed by generalized tonic-clonic seizure. On physical examination the patient was full awake with mild dysarthria and a grade 4 left hemiparesis with brachiofacial predominance. She had no signs of intracranial hypertension. The Karnofsky performance status (KPS) was 70. A computed tomography (CT) scan was performed showing a right frontal cortico-subcortical hypodense area resembling a secondary lesion in nature. Primary neoplasm investigation was negative and the patient was referred to our institution (Hospital S. João, Porto; Portugal). A magnetic resonance imaging (MRI) was done and revealed a right frontal parasagittal and well-demarcated hyperintense lesion with homogeneous contrast-enhancement and a second lesion in the posterior right frontal lobe with poorly demarcated borders and heterogeneous contrast-enhancement. The patient underwent a right frontal craniotomy with gross total removal of the two lesions in December 2003. There was no complication and the patient was discharged with a grade 4 hemiparesis and a complete recovery of the dysarthria. The KPS at discharge was 80. The pathological examination revealed two distinct lesions being the anterior a meningioma and the posterior a gliosarcoma []. The patient received postoperative radiotherapy with a total dose of 60 Gy given in 30 fractions with margin of 1 cm in the area of the gliosarcoma. The patient remained asymptomatic until September 2005 when she developed dysarthria and worsening of the hemiparesis. The MRI showed a regrowth of the initial gliosarcoma and the patient was re-operated with macroscopically complete removal of the recurrent gliosarcoma []. The patient recovered again from the neurological deficits and started temozolomide treatment with 150 mg/m2 followed by 200 mg/m2. In November 2005, the patient showed progressive neurological deterioration with headaches, disorientation episodes, and paresis worsening with left arm plegia. The MRI showed an early new regrowth with no indication for surgical removal and the patient underwent palliation with dexamethasone. In June 2006 a new MRI showed a growth of the right frontal lesion with involvement of the basal ganglia and corpus callosum, crossing the midline and development of hydrocephalus. The patient died in October 2006 after a progressive neurological deterioration. The overall survival was 36 months. No postmortem examination was performed.\nHistological examination of the initial anterior lobular frontal and posterior lobular frontal lesions revealed two clear distinct tumors: A meningioma (M) depicting positivity for epithelial membrane antigen (EMA) staining and a gliosarcoma (GS) exhibiting typical features of intermingled GFAP and reticuline neoplastic regions. The analysis of recurrent lesion showed the presence of a gliosarcoma (GS-R) with a more prominent glial component.\nIn order, to determine the presence of mutations in the TP53 (exons 5-8) and BRAF (exon 11 and 15) genes, DNA was isolated from the formalin-fixed and paraffin-embedded tissues of all three lesions. The screening of mutations was carried out by polymerase chain reaction (PCR)-single-strand conformational polymorphism (PCR-SSCP), followed by direct DNA sequencing, as previously described.[] None of lesions showed TP53 or BRAF mutations [].\nWe further investigated for the presence of MGMT protein expression by immunohistochemistry, using the mouse anti-MGMT monoclonal antibody (dilution 1:400; clone MT3.1, Chemicon International) and correlated with MGMT gene promoter hypermethylation, assessed by methylation-specific PCR (MSP) as previously described.[] As illustrated in , MGMT methylation was found in both primary and recurrent gliosarcoma. The meningioma lesion was negative for MGMT methylation [ and ]. In concordance with methylation status, MGMT expression was only present in the meningioma and absent in both primary and recurrent gliosarcoma [ and ]. Next, we analyzed the presence of EGFR alterations at both gene and protein levels by CISH (EGFR spot-Light amplification probes from Zymed® Laboratories Inc., South San Francisco, CA, USA) and immunohistochemistry (anti-EGFR polyclonal antibody, dilution 1:100, clone 31G7, Zymed® Laboratories Inc., San Francisco, CA, USA), respectively.[] The meningioma and primary gliosarcoma were negative for EGFR protein expression [ and ]. EGFR immunohistochemistry showed a focal region with strong immunoreactivity in the recurrent gliosarcoma. In both meningioma and primary gliosarcoma, it was observed the presence of 2 signals per neoplastic cell, representing absence of EGFR gene copy number alterations [ and ]. EGFR gene amplification, represented by clusters of more than 5 signals per neoplastic cell, was observed only in the recurrent gliosarcoma, in the same region with strong focal positivity for EGFR protein [ and ].\nFinally, we studied the expression of COX-2 by immunohistochemistry, using the anti-COX-2 monoclonal antibody (dilution 1:50, clone SP21, Neomarkers, Fremont, CA, USA).[] We observed positivity only in meningioma lesion []. Both gliosarcomas (primary and recurrent) were negative for COX-2 expression [ and ].