Gliosarcomas account for approximately 2% of all glioblastomas. The cellular origin of the sarcomatous component in gliosarcomas remains unclear. Originally gliosarcoma was thought to be a collision tumor with a separate astrocytic component and independent development of the sarcomatous portion from the proliferating vessels, but some studies have supported another hypothesis that the sarcomatous differentiation results from a phenotypic change in the glioblastoma cells rather than an indication of the coincidental development of two separate neoplasms[1,5]. Despite the inconclusive pathogenesis of sarcomatous component, the proliferating vessels are commonly seen in gliosarcomas and become predominant in the angiosarcomatous component of gliosarcomas.
There is another rare entity of primary central nervous system (CNS) angiosarcoma that should be diagnosed in the absence of glial component, in addition to secondary CNS angiosarcomas. The primary CNS angiosarcoma are originating from endothelial cells of the blood vessels, and arising from the cerebral parenchyma in most reported cases or meninges in a few other cases. The clinicopathological features and properties of primary cerebral angiosarcomas are similar to those of the angiosarcomatous component in gliosarcomas. As the majority of reported CNS angiosarcomas present with hemorrhage, it is expected that an angiosarcomatous component in gliosarcomas is associated with hemorrhagic propensity. In our present case, MR images of the tumor demonstrated avid enhancement, restricted diffusion, prominent flow voids, and significant peritumoral edema, which are all features of high-grade glioma typically with rich vascularity. In addition, the preoperative MR perfusion not only helped to identify the tumor progression but also demonstrated increased CBV of the tumor, which is also suggestive of increased vascularity. However, the MR perfusion study may have underestimated the degree of vascularity of the tumor, compared to the intraoperative and pathological findings.
Angiosarcomatous features have been reported exceptionally in other primary brain tumors including a case of oligodendroglioma with mixed fibrosarcomatous and angiosarcomatous features and another case of recurrent subependymoma with angiosarcoma-like overgrowth. So far, there has been only one reported case of gliosarcoma with frankly angiosarcomatous features. That tumor was described as a T1-isointense and T2-hyperintense lesion with a large cystic space and heterogeneous contrast enhancement; it was severely bleeding during the tumor resection. In contrast, the tumor in our present case demonstrated characteristic features such as asymmetrically thick wall, prominent flow voids, rim-like enhancement as well as multiple enhancing intratumoral strips and nodular components. The characteristic enhancing intratumoral strip and nodular components have been described in less than half of gliosarcomas without frank angiosarcomatous features and likely correspond to abundant vascular proliferation within the tumor. In our present case, the tumor hemorrhage was seen during and after the first and second resections.
Unlike infiltrative glioblastomas, gliosarcomas are usually well-circumscribed, rim-enhancing lesions with intratumoral paliform and nodular components on neuroimaging. The differential diagnosis for a gliosarcoma with angiosarcomatous component includes other glioblastoma variants with hypervascular features, metastatic tumors, brain abscess, and some vascular lesions[2–4,8–9]. Gliosarcomas with an angiosarcomatous components may be radiologically distinguishable from these entities by characteristic features including peripheral location, well-demarcated margin, as well as characteristic intratumoral strips and nodular enhancing components. Nevertheless, the pathological examination of a reasonable tissue sample is the key to diagnose the angiosarcomatous component in gliosarcomas.
Gliosarcomas are usually treated with surgical resections followed by radiotherapy with or without chemotherapy, so are primary CNS angiosarcomas. With the treatment of surgical resection followed by radiotherapy and chemotherapy, the generally poor prognosis despite considerable variation is noted in both primary CNS angiosarcomas (with the median survival of 8 months) and gliosarcomas (with the median overall survival of 13.9 and 7.9 months, respectively, in two recently published studies[10–11]; the median progression-free survival 7.9 months in the former study). The previously reported patient with an angiosarcomatous component in a gliosarcoma was free from recurrence during a 7-month follow-up after the same treatment. Our present patient was free from recurrence for 8 months but had the tumor recurrence at 9 months when the second resection was required. Therefore, it seems that gliosarcomas with an angiosarcomatous component are prognostically of no significant difference from other gliosarcomas although the angiosarcomatous component is commonly associated with intraoperative and/or postoperative hemorrhage. A recent study by Smith et al showed that in the rat in vivo model of 9L orthotopic gliosarcomas, overall survival was significantly prolonged with neurosurgical delivery of etoposide and temozolomide into the surgical resection cavity. This approach may play an important role in the future treatment of gliosarcomas including those with angiosarcomatous features.
In conclusion, awareness of perplexing radiographically heterogeneity of gliosarcoma and the increased hemorrhage risk of an angiosarcomatous component in gliosarcoma is important for the patient's preoperative diagnosis and surgical management.