Contributed by Leena Lourduraj, MDFINAL DIAGNOSIS:
DISCUSSION:
According to the new World Health Organization (WHO) classification gliosarcoma is defined as a glioblastoma variant characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation (1).
Gliosarcoma is a relatively rare malignant neoplasm accounting for about 2% of all the Glioblastomas (1). They usually affect the adult population in the fourth to the sixth decade of life. Males are more frequently affected than females (M:F ratio 1.8:1). Gliosarcomas are usually located in the cerebral cortex involving the temporal, frontal, parietal, and occipital lobe in decreasing frequency (1). Invariably the clinical history of the patient is short and the presenting symptoms depend upon the location of the tumor. The etiology of gliosarcoma remains speculative although it is recognized that gliomas can induce sarcomatous transformation in the supporting mesenchymal elements (2) and irradiation of the central nervous system can induce malignant transformation of the brain parenchyma and the meninges predominantly to fibrosarcoma (2).
Grossly Gliosarcoma may be poorly delineated peripheral grayish tumor mass with central yellowish necrosis stippled with red and brown of recent and remote hemorrhage with the sarcomatous component producing firm discrete mass.
The diagnosis of gliosarcoma is based on a biphasic tissue pattern composed of two distinct malignant cell populations, one component being gliomatous (fulfilling the criteria for glioblastoma) and the other with malignant mesenchymal differentiation (fulfilling the criteria for being a sarcoma). Interestingly the sarcomatous component can have varied histological features ranging from a herring bone pattern of fibrosacroma to that of malignant osteiod and cartilaginous differentiation of an osteosarcoma and chondrosarcoma respectively (1). In the above case the sarcomatous component of the tumor showed features of fibrosarcoma with further mesenchymal differentiation to osteogenic sarcoma and chondrosarcoma. Another diagnostic criterion to be fulfilled before a tumor is classified as Gliosarcoma is the demonstration of GFAP through immunohistochemistry in the gliomatous portion and reticulin in the sarcomatous component preferably exhibiting a clear demarcation between the sarcomatous and the glial component. Additional immunohistochemical stains like smooth muscle actin, desmin, cytokeratin etc can be performed to further identify the mesenchymal differentiation.
Although one component of gliosarcoma is clearly of astrocytic origin the histogenesis of the sarcomatous component is still controversial. Feign et al in 1955 described gliosarcoma as glioblastoma in which the proliferating tumor vessels acquired features of a sarcoma (3). This view was widely accepted, given the prominent vascular proliferation found in glioblastoma. Several immunohistochemical studies supported this hypothesis by demonstrating the presence of factor VIII related antigen and Ulex europaeus I agglutinin in the sarcomatous component while other studies failed to confirm these findings (4). Another hypothesis suggested a process of dedifferentiation within the glioma with secondary loss of GFAP _expression and acquisition of mesenchymal characteristics (5). Another school of thought regards gliosarcoma as a spindle cell or desmoplastic variant of glioblastoma (4). However these views have not been supported by recent genetic analysis, which point to a monoclonal origin where p53 mutation, PTEN mutations, p16 (CDKN2A) deletions and coamplification of MDM2 and CDK4 have been identified both in the gliomatous and the sarcomatous component (1).
Gliosarcoma has the same prognosis has Glioblastoma and should be treated identically.
Several criteria have been established for showing a casual relationship between radiation therapy and occurrence of a neoplasm: the latter should be in the irradiated field, there should be a sufficiently long latent period between irradiation and detection of the second tumor, the histology of the second tumor should be different from that of the initial one and a family of tumor diathesis (e.g. Neurofibromatosis or Tuberous sclerosis) must be excluded (6). Our case is unusual in that it not only has a fiborsarcoma component but osteogenic and chondrosarcoma components as well, which are rare findings. The tumor is most likely a primary gliosarcoma. Although the initial biopsy was diagnosed as glioblastoma this may be due to sampling error where only the gliomatous component may have been obtained. The reason it may not be a radiation-induced gliosarcoma is the short time the patient has had radiation therapy and which may not be long enough for transformation of the primary tumor (glioblastoma) to gliosarcoma.
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Contributed by Leena Lourduraj, MD
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