Gliosarcoma is a primary malignant tumor of the central nervous system that contains a mixture of both glioblastoma and sarcoma. Gliosarcoma was first reported by Stroebe as early as 1895, but it was not until 1995 that it was further confirmed and recognized by Feigin and Gross, hence the name Feigin’s tumor. It was named in the 1993 edition of the WHO Classification of Tumors of the Central Nervous System and remains a subtype of glioblastoma in the 2007 edition of the WHO Classification, a WHO grade IV tumor.
Gliosarcoma is a rare malignant CNS tumor, accounting for about 1.8C2.4% of glioblastoma. Among the 162 cases reported before 2007, the age of onset was mostly 50-70 years old, with a mean age of 53 years old and a male-to-female ratio of about 1.9:1, similar to the ratio of glioblastoma. Infants and children have also been reported to develop the disease. Gliosarcoma is most common in the temporal lobe, with other sites in decreasing order: frontal, parietal, occipital and corpus callosum. Most tumors are solitary, but multiple lesions have been reported.
There are three theories about the growth mechanism of gliosarcoma as follows.
1. collision theory, which means that two different tumor components appear simultaneously in the same body.
The induction theory is that one tumor induces the development of another tumor.
The transformation theory is a widely accepted theory that one part of the tumor transforms into another tumor and continues to grow.
Reis et al. used tissue microdissection study and DNA sequential analysis to find p53 and PTEN mutations, p16 deletion and amplification of MDM2 and CDK4 in both the glial and mesenchymal components of the tumor. Another study found the same number of aberrations in chromosomes 10 and 17 in both the glial and mesenchymal components by in situ fluorescence hybridization analysis. These results suggest that both components originate from the same precursor cell population and evolve differently to form malignant cell subpopulations with different morphologies, thus further rejecting the previous hypothesis of collision tumor.
The clinical presentation of gliosarcoma is similar to that of glioblastoma. Clinical symptoms depend on the tumor site and intracranial pressure. Headache, hemiparesis, nausea, seizures, and personality changes are common. Common signs are mild weakness, visual field defects, optic papilloedema and speech difficulties. DSA shows a vascular-rich tumor with irregular vasculature and early peripheral draining veins. Jack et al. found that gliosarcoma may have soft or dural vascular supply and early peripheral venous reflux. In contrast, glioblastoma has no dural blood supply and returns to deep veins, and thus DSA can help differentiate gliosarcoma from glioblastoma.
On CT, the tumor appears as a high-density, well-defined shadow with heterogeneous enhancement or circumferential enhancement and peripheral edema. On MRI, the tumor appears as irregularly shaped long T1 and T2 signal masses, mostly combined with necrosis and cystic lesions, with obvious occupying effects. It shows obvious thick-walled circumferential enhancement, often surrounded by wall nodules of different sizes and obvious enhancement; or long Tl, long T2 signal nodules with clear borders and obvious enhancement. The internal cystic lesions and necrotic areas are often unreinforced, and internal streak-like enhancement is occasionally seen. The surrounding area shows mild to moderate edema.
The pathology of gliosarcoma is a tough, lobulated tumor with poorly defined borders between the tumor and brain tissue, and may involve the cortex and peripheral meninges. The tumor is mostly grayish white in color and may have extensive hemorrhage and necrosis with a brownish red or yellow map-like appearance. Microscopically, a hard, well-defined sarcomatous component is seen within a softer, poorly defined high-grade glioma component. Glial areas tend to be typically glioblastoma-like with varying degrees of interstitial degeneration and GFAP expression, as well as astrocytoma-like or mesenchymal astrocytoma-like manifestations. The sarcoma area is filled with tumor mesenchymal cells with reticulin structures. These cells are spindle-shaped and show increased nuclear anisotropy, mitosis and necrosis. The proliferating sarcomatous component is pleomorphic in nature. As the sarcoma component differentiates, different tissue components are seen within the tumor, mostly fibrosarcoma-like, pleomorphic sarcoma-like, and smooth muscle sarcoma-like. Occasionally, other types of differentiation have been reported, such as bone, cartilage, vascular, smooth muscle, rhabdomyosarcoma, lipomatous tissue, and epithelial tissue.
The histologic criteria for diagnosis were proposed by Meis et al. in 1991.
1, The tumor must consist of two morphologically distinct malignant cells.
2, One component must be astrocytic-like with necrosis, meeting the criteria for glioblastoma.
3, The sarcoma component resembles a spindle cell tumor.
4, and the smallest sarcoma area must fill a medium magnification field of view (10x eyepiece x 10x objective).
The typical lesion of gliosarcoma is a sarcomatous component arranged around a glioma component. Immunohistochemical staining is valuable in the diagnosis of gliosarcoma, which has a positive immunophenotype for glial fibrillary acidic protein (GFAP) in the glial component; reticulofibrillar staining reveals reticulofibrillar richness in the differentiated areas of the sarcoma. The pathological distinction between gliosarcoma and glioblastoma lies in the presence of positive expression of markers of the sarcomatous component in gliosarcoma, but not in glioblastoma. The positive expression of GFAP, on the other hand, helps to differentiate gliosarcoma from malignant meningioma and metastatic carcinoma in the brain.
Similar to most malignant tumors in terms of treatment, gliosarcoma is treated with a combination of surgical resection, supplemented by radiotherapy and chemotherapy. During surgery, the tumor is mostly solid, well-defined and vascularized, so it is easier to achieve total resection. Superficially located tumors are not closely attached to the meninges and can be easily removed. Gliosarcoma with osseous differentiation has a harder texture and is relatively difficult to resect. Postoperative radiation therapy should be routinely administered. The long-term prognosis of radiotherapy patients is better than that of non-radiotherapy patients. The chemotherapy regimen may refer to that of glioblastoma.
The prognosis of gliosarcoma is similar to that of glioblastoma. One study showed that the mean survival for gliosarcoma was 26 weeks after symptom onset and 21 weeks after surgery, with a 6-month survival rate of 75% and a 1-year survival rate of 19%, with a median survival of 6-14.8 months. Survival can be increased by 8-15 weeks after radiotherapy.
In addition to being prone to in situ recurrence, gliosarcoma is also prone to intracranial implant metastases and extracranial metastases in the central nervous system. It has been found that the rate of extracranial metastasis is about 1% for glioblastoma and 11% for gliosarcoma. The reasons for such a huge difference in extracranial metastasis rates are currently believed to be as follows.
1, sarcoma components are prone to hematogenous metastasis.
2. Gliosarcoma mostly occurs in the temporal lobe, near the meninges and large draining venous sinuses, which facilitates hematogenous metastasis. Extracranial metastases mostly involve the lung, liver and lymph nodes. Multiple metastases can be seen. In addition, there are reports of intravascular tumor emboli found at autopsy, further suggesting that hematogenous metastasis is the mechanism of its multiple metastases.