|Year : 2015 | Volume
| Issue : 3 | Page : 651
Long-term survival in gliosarcoma with radiation-induced meningeal sarcomas: Case report and molecular features
Zhen Wang, Qing-Tao Kong, Xin-Hu Wu, Xi-Xu Zhu
Department of Radiation Oncology, Jinling Hosp, Nanjing Univ Sch Med, Nanjing, China
|Date of Web Publication||9-Oct-2015|
Department of Radiation Oncology, Jinling Hosp, Nanjing Univ, Sch Med, Nanjing 210002
Source of Support: None, Conflict of Interest: None
Gliosarcoma is a rare primary malignant tumor of the central nervous system with poor prognosis. The median survival time of this disease ranges from 6 months to 14.8 months. However, a computer literature search indicated few long-term survivors. We investigated a case of a survivor of gliosarcoma with radiation-induced meningeal sarcomas, who showed no indication of recurrence for more than 9 years. A battery of molecular studies was performed to develop a molecular profile of this unique patient. We also reviewed the distinct clinical and molecular features of the tumor.
Keywords: Gliosarcoma, long-term survival, meningeal sarcomas, molecular profile, radiation
|How to cite this article:|
Wang Z, Kong QT, Wu XH, Zhu XX. Long-term survival in gliosarcoma with radiation-induced meningeal sarcomas: Case report and molecular features. J Can Res Ther 2015;11:651
|How to cite this URL:|
Wang Z, Kong QT, Wu XH, Zhu XX. Long-term survival in gliosarcoma with radiation-induced meningeal sarcomas: Case report and molecular features. J Can Res Ther [serial online] 2015 [cited 2019 Nov 17];11:651. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/651/137995
| > Introduction|| |
Gliosarcoma (GSM) is a primary tumor of the central nervous system composed of both malignant glial and sarcomatous components. They account for 2% to 8% of all glioblastoma multiforme (GBM) and 0.48% of all intracranial tumors.  Historical data showed that the median survival time of GSM is 6 months to 14.8 months, despite multidisciplinary treatment with extensive surgical resection and adjuvant therapies, such as molecular-targeted therapies.  An unusually long overall survival (OS) of more than 2 years exists after diagnosis of GSM [Table 1]. This study reports the clinical and molecular features of a long-term survivor of GSM. To our knowledge, this subject is the first reported case of a long-term survival of a GSM patient who developed radiation-induced meningeal sarcomas.
|Table 1: Clinico-pathologic characteristics of patients who lived more than 2 years after diagnosis of gliosarcoma|
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| > Case report|| |
The patient was a 21-year-old male with unremarkable family history and without significant past medical history. He was in stable health until the summer of 2003 (age 21), during which he developed gradually progressive headaches. He was diagnosed with a brain tumor after a CT scan at a local hospital. In August 2003, he visited our hospital for treatment. A cranial MRI scan showed a well-defined lesion measuring 4 × 3 × 3 cm with mixed signals in both T1- and T2-weighted MR images of the right frontal lobe [Figure 1]a and b. On September 15, 2003, the patient underwent craniotomy and complete resection of the mass. The histopathologic diagnosis was GSM (WHO grade IV). Immunohistochemical studies were negative for CKAE1, CEAE3, and CD34, but positive for vimentin and glial fibrillary acidic protein (GFAP) [Figure 2]. The patient subsequently received local radiotherapy with a total dose of 60 Gy directed to the surgical cavity and a 2 cm margin on the estimated volume. The radiation therapy was completed on November 18, 2003 and well-tolerated, with the usual short-term side effects of fatigue and hair loss. The patient was well until November 2012, when he presented with a 1 month history of increasing frontoparietal painless mass for treatment. A homogeneous lesion was found in the right frontoparietal lobe on cranial MRI [Figure 1]c. On December 18, 2012, surgical resection of the tumor was performed. The tumor was histopathologically diagnosed as meningeal sarcoma, which was mainly osteosarcoma [Figure 3]. The patient then received local radiation therapy with a total dose of 60 Gy/30 fx. The patient has been alive for 10 years until now, without any indication of recurrence.
|Figure 1: Representative images of radiological imaging. Axial (a) and (b) sagittal post-contrast T1-WI show thin ring-like marked enhancement and an enhanced mural nodule. Coronal (c) T1-weighted MR scans demonstrate extra-epidural lesions with notable contrast enhancement|
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|Figure 2: Pathological features from primary resection. Histopathology shows diffusely distributed tumor cells. The presence of polygonal or fusiform cells is consistent with high-grade gliosarcoma. (H and E staining, A ×100, B ×400). Immunostaining for glial fibrillary acidic protein (C ×400) and vimentin (D ×400) is present in tumor cells|
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|Figure 3: Pathological features from second resection. Microscopic examination shows diffuse tumor cell infiltration within the leptomeningeal spaces, with areas of highly cellular undifferentiated tumor manifestation (H and E staining, A ×100, B ×400)|
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A battery of molecular studies was performed on the specimen on January 2013 in the Department of Pathology at our hospital. Quantitative real-time PCR measured the expression of phosphatase and tensin homolog (PTEN) in the tumor samples. Direct DNA sequencing detected the status of isocitrate dehydrogenase 1 gene (IDH1), isocitrate dehydrogenase 2 gene (IDH2), and methylguanine methyltransferase (MGMT).
The results showed the following: PTEN mRNA, 29% positive; methylated MGMT; and unmutated IDH1 codon 132 and IDH2 codon 172.
| > Discussion|| |
Gliosarcoma contain malignant glial and mesenchymal tissue elements. The median age of patients with GSMs is 51 years (range, 11 years to 84 years).  Compared with GBM, GSM has an apparent proclivity for the temporal lobe, and metastases are more likely to occur with GSMs than glioblastoma.  Multimodality treatment, which includes radical surgical resection, adjuvant irradiation, and chemotherapy, is the treatment of choice for these tumors. However, the prognosis of GSM patients using this approach remains poor with a median survival between 6.25 months and 11.5 months.  Longer survival times up to 2 years are rarely reported [Table 1]. Among these patients, 8 are males and 5 are females (M: F = 1.6:1) with an age range of 10 years to 63 years. Nearly 70% of the patients are younger than 50 years old. Presenting symptoms included seizures, headaches, and other symptoms related to increased intra-cranial pressure. The most common tumor location is the temporal lobe (five cases, 38.5%), followed by the frontal (23.1%) and parietal lobes (15.4%). All patients are treated with gross total resection and adjuvant radiation.
Several factors are associated with overall survival in GBM patients, including clinical and genetic parameters. Based on the available literature,  clinical parameters, such as young age, predominance of female sex, aggressive surgical resection, and adjuvant RT in GBM, are generally associated with better prognosis. Similarly, these clinical factors affect GSM survival. Patients diagnosed with GSM prior to 50 years of age have a median survival of 15 months compared with 7 months for those diagnosed after age 50. Patients treated with gross total resection and adjuvant radiation have a significantly higher median survival rate.  In addition, a number of molecular factors are associated with a favorable prognosis in GSM patients. These factors include MGMT promoter methylation, EGFR, and PTEN protein expression. , MGMT promoter methylation in glioma is associated with tumor regression as well as prolonged overall and disease-free survival.  MGMT methylation increases efficacy of temozolomide by inhibiting MGMT gene expression. Based on these results, temozolomide was prescribed as maintenance therapy. EGFR amplification in glioma is associated with tumor invasiveness, angiogenesis, poor survival, and resistance to radiation therapy.  EGFR amplification is common in glioblastoma, and the rate of EGFR amplification is much lower in GSM, barely accounting for 0% to 8% of cases.  Our patient was EGFR-negative. Recent investigations demonstrated that IDH1 and IDH2 mutations are associated with prolonged GBM survival.  The prognostic significance of IDH1 or IDH2 mutations to GSM remains unknown, which we hypothesize to be associated with the low mutation rate.
In conclusion, we report a case of a GSM patient who developed radiation-induced meningeal sarcomas and survived for more than 9 years. Factors associated with long-term survival in our case may include hypermethylation of MGMT promoter methylation, PTEN positivity, and clinical characteristics (younger than 50 years old, GTR, and adjuvant RT) of the patient. Further research is needed to confirm whether this molecular profile is prognostic of prolonged survival. Molecular genetics will determine future treatment and prognosis in GSM.
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[Figure 1], [Figure 2], [Figure 3]