Gliosarcoma with Components of Anaplastic Oligodendroglioma and Unclassifiable Spindle Cells - a Case Report

The Korean Journal of Pathology 2008; 42: 45-9

Gliosarcoma with Components of Anaplastic Oligodendroglioma and Unclassifiable Spindle Cells - A Case Report-

Jung-Woo Choi Youngseok Lee Gliosarcoma is a distinct disease entity that is characterized by a biphasic tissue pattern with Jung-Suk An Nam Hee Won alternating areas displaying glial and mesenchymal differentiation. The tumor in our case was Yong-Gu Chung1 Yang Seok Chae a rare morphologic variant of gliosarcoma with components of anaplastic oligodendroglioma and unclassifiable spindle cells. Spindle cells showed CD34 and S-100 protein immunoreactivi- Departments of Pathology and ty, which was possibly related to peripheral nerve sheath differentiation. This unique feature has 1Neurosurgery, College of Medicine, not been described previously and so this case expands the spectrum of possible divergent Korea University, Seoul, Korea mesenchymal differentiation, and it lends support to pluripotential stem cells being the origin of this tumor. Received : February 20, 2007 Accepted : October 4, 2007

Corresponding Author Yang Seok Chae Department of Pathology, Korea University Hospital, 126-1, 5th street Anam-dong, Seongbuk-gu, Seoul 136-705, Korea Tel: 02-920-5352 Fax: 02-920-6576 E-mail: [email protected] Key Words : Gliosarcoma; Anaplastic oligodendroglioma; CD34; S-100 protein

The most recent World Health Organization Classification of CASE REPORT Tumors of the Nervous System defines gliosarcoma as a glioblastoma variant that’s characterized by a biphasic tissue pattern with The patient, a 62-year-old man, was admitted to our hospital alternating areas displaying glial and mesenchymal differentia- with headache and dysarthria. He denied all other symptoms, tion.1 The gliomatous components are nearly always astrocytic and he had no previous significant history of disease or trauma. and they are clearly high grade; most exhibit the features of full- Contrast-enhanced computed tomography and magnetic resonance blown glioblastoma, although examples derived from oligoden- imaging demonstrated a 5.5 cm sized well enhancing mass in drogliomas and subependymomas have been reported.2-4 The the left temporal lobe with a large area of internal necrosis and most common types of differentiation of sarcomatous components moderate to severe peritumoral edema (Fig. 1). The histology are the fibrosarcomatous and malignant fibrous histiocytoma-like of the stereotactic biopsy was consistent with anaplastic oligo- types, but various other lines of mesenchymal differentiation have dendroglioma. The patient underwent subtotal excision of the been described.1,5 We recently experienced an interesting case of tumor with subsequent radiotherapy. He was still free of recur- gliosarcoma with areas of oligodendroglioma in the glial com- rence 4 months after treatment. ponent and there were unclassifiable spindle cells that showed CD34 and S-100 protein immunoreactivity in the sarcomatous Pathologic findings component. To the best of our knowledge, this kind of combi- nation in gliosarcoma has never been reported in the medical Grossly, the tumors were grayish white and firm with areas of literature. hemorrhage without any definite area of necrosis. Microscopic

45 46 Jung-Woo Choi Youngseok Lee Jung-Suk An, et al.

examination of the tumor revealed 2 discrete components that were dendroglioma with increased cellularity, marked cytologic atyp- sometimes intermixed: the one was a typical anaplastic oligo- ia, occasional mitotic activities, and endothelial vascular proliferation (Fig. 2A). Most of the cells that composed the anaplastic oligodendroglioma showed rounded hyperchromatic nuclei, per- inuclear halos, and a few cellular processes reminiscent of oligodendroglial cells. They were diffusely immunoreactive for S-100 protein and CD57 (Leu-7) and, focally positive for glial fibrillary acidic protein (GFAP, Fig. 2B), but they were negative for vimentin, CD31, CD34 (Fig. 2C), smooth muscle actin, desmin, epithelial membrane antigen or epidermal growth factor receptor (EGFR). The MIB-1 labelling was markedly increased (40- 50%). The other component was composed of atypical spindle cells that were mainly centered around proliferating blood vessels and accompanied by collagen deposition and focal necrosis, showing the pattern of spindle cell sarcoma (Fig. 3A, B). Most 10 Cm of these cells showed a spindle cell configuration with thin elon- gated hyperchromatic nuclei, moderate to marked cytologic atypia and occasional mitoses. The cellularity of the hypercellu- lar areas was variable with short interlacing bundles of spindle cells to the hypocellular myxoid areas. The tumor cells were Fig. 1. T2-weighted magnetic resonance imaging demonstrates a well enhancing mass in the left temporal lobe with severe peri- diffusely positive for CD34 (Fig. 3C), S-100 protein (Fig. 3D) tumoral edema. and vimentin immunostaining, but other immunohistochemi-

A B

Fig. 2. The one component is a typical anaplastic oligodendroglioma with increased cellularity, marked cytologic atypia and occasional mitoses (A, H&E stain, ×200). The tumor cells are focally positive for GFAP (B, Immunohistochemistry, ×200) and negative for CD34 C (C, Immunohistochemistry, ×200). Gliosarcoma with Components of Anaplastic Oligodendroglioma and Unclassifiable Spindle Cells 47

A B

C D

Fig. 3. The other component is composed of cellular areas of spindle cells forming short fascicles (A, H&E stain, ×100) and showing perivas- cular arrangement of plump and spindle-shaped tumor cells (B, H&E stain, ×100). Most of the tumor cells are diffusely positive for CD34 (C, Immunohistochemistry, ×200) and S-100 protein (D, Immunohistochemistry, ×200). cal markers, including GFAP, CD31, smooth muscle actin, and nonglial compartments of gliosarcoma bear the same genet- desmin, CD68, epithelial membrane antigen, and EGFR, were ic abnormalities, thus showing evidence of their common origin, negative. Immunostaining for p53 was positive in about 10% which is probably from pluripotential stem cells.9,10 of these tumor cells and the MIB-1 labeling was focally increased Morphologically, this case should be differentiated from oligo- (5-10%). These two discrete components were occasionally inti- dendroglial tumor that invades the meninges and causes a promi- mately admixed with each other (Fig. 4A), in which only the nent desmoplastic reaction. However, the formation of separate oligodendroglial component shows focal immunoreactivity for nodules that are predominantly composed of spindle cells apart GFAP (Fig. 4B). The biphasic nature of the tumor was clearly from the oligodendroglial component, and the frequent arrange- emphasized by vimentin (Fig. 4C) immunostaining, which de- ment of these tumor cells around proliferating blood vessels is monstrated positivity only in the sarcomatous area. highly suggestive of their neoplastic nature rather than a reac- tive stromal reaction around infiltrating oligodendroglial cells. In addition, the different immunohistochemical staining pattern DISCUSSION and the deposition of abundant collagen and reticulin fibers in these spindle cell components confirmed the diagnosis of a gliosar- The histogenesis of gliosarcoma continues to be a subject of coma. debate. However, although the previous morphologic studies have Unlike the previously reported gliosarcomas, there are two un- suggested an evolution of the sarcomatous component from mi- usual pathologic features that make our case noteworthy. First, the crovascular proliferation within a highly malignant glioblastoma,6-8 occurrence of a sarcoma within an oligodendroglioma remains the recent genetic studies have demonstrated that both the glial highly exceptional and this was rarely mentioned by Feigin et al.2 48 Jung-Woo Choi Youngseok Lee Jung-Suk An, et al.

A B

Fig. 4. Occasionally, glioma and sarcomatous components inti- mately admixed each other (A, H&E stain, ×100). GFAP stain (B, immunohistochemistry, ×100) shows focal immunoreactivity only in the oligodendroglial component, which is well contrasted with diffuse positive staining for vimentin (C, immunohistochemistry, C ×100) in the sarcomatous area. in 1976 and by Pasquier et al.4 in 1978, and there have been no dle cells and the deposition of collagen fibers in the sarcomatous additional reports thereafter. The case reported by Feigin et al.2 component may suggest the possible peripheral nerve sheath di- was histologically composed of an anaplastic oligodendroglioma fferentiation.12 This can be further supported by the fact that sev- combined with a sarcomatous component that probably had a eral reports have described nerve sheath tumors within the CNS vascular origin, and the case by Pasquier et al.4 was a typical oli- parenchyma that are unrelated to the cranial nerves and a benign godendroglioma with mixed fibrosarcomatous and angiosarco- “glioneurofibroma” composed of astrocytes and schwann cells in matous components. Due to the extreme rarity of sarcomas aris- children, although these type of tumors are extremely rare.13,14 ing in oligodendroglioma, the response to conventional therapy In conclusion, the tumor in our case was a rare morphologic and the behavior of these tumors still remain to be determined. variant of gliosarcoma with components of anaplastic oligoden- Second, the sarcomatous components in this case show diffuse droglioma combined with unclassifiable spindle cells showing immunoreactivity for CD34 and S-100 protein. Several attempts CD34 and S-100 protein immunoreactivity, and this was possibly have failed to demonstrate the direct participation of endotheli- related with peripheral nerve sheath differentiation. This unique um in the formation of the sarcomatous component and a CD34- feature has not been described previously and so this case expands positive gliosarcoma has never been reported in the English medi- the spectrum of possible divergent mesenchymal differentiation, cal literature.5,11 However, considering a relatively reduced speci- and it support the tumor’s origin from pluripotential stem cells. ficity of CD34 immunostaining for defining the endothelial origin of tumor cells and the negative immunostaining result for CD31, which is the other well-known vascular endothelium-relat- REFERENCES ed marker, CD34 immunoreactivity alone in this case does not necessarily indicate the endothelial origin of the sarcomatous 1. Ohgaki H, Reis R, Hegi M, Kleihues P. Gliosarcoma. In: Kleihues P, component. Instead, the presence of S-100 protein positive spin- Cavenee WK. Pathology and genetics of tumours of the nervous sys- Gliosarcoma with Components of Anaplastic Oligodendroglioma and Unclassifiable Spindle Cells 49

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