Brain Pathology Case of the Month - September 2003



The differential diagnoses base on clinical history included malignant meningioma and metastatic breast carcinoma. The histologic findings of biphasic patterns, with areas displaying high grade astrocytic and unequivocal areas of mesenchymal differentiation with a reticulin network but without GFAP immunoreactivity were diagnostic of gliosarcoma. The findings of rare EMA immunoreactivity and negative cytokeratin immunoreactivity were helpful to exclude malignant meningioma and metastatic breast carcinoma.

Gliosarcomas comprise approximately 2% of all high grade gliomas (2, 11) and are characterized by a biphasic tissue pattern, with areas displaying definitive glial and mesenchymal differentiation (1, 7). The term gliosarcoma was described in 1898 by Stroebe (13). In 1958, Feigin et al defined gliosarcoma as a glioblastoma subtype and the term "Feigin tumor" denotes gliosarcomas in which proliferating vessels had acquired the features of sarcoma (3). Some studies showed expression of monohistiocytic markers, indicating that gliosarcomas develop from histiocytes whereas others suggested an origin from fibroblasts, pluripotent mesenchymal cells of the perivascular adventitia or perivascular spaces (5, 8). More recent publications suggested a common origin of for the two components; the sarcomatous areas result from advanced glioma progression with acquisition of a mesenchymal phenotype (6, 10). This idea is strongly supported by many investigators. Reis et al. showed that gliosarcomas exhibit clinical features and a genetic profile similar to primary (de novo) glioblastoma, i.e. advanced patient age, short clinical history, and frequent p16 deletions and PTEN mutations (12). The presence of identical genetic alterations in both gliomatous and sarcomatous components strongly supports the concept of monoclonal origins of gliosarcomas.

It has been suggested that gliosarcomas carry a somewhat more favorable prognosis (12) than glioblastoma multiforme but large clinical trials have not succeeded in revealing a significant difference in outcome (4, 11).


  1. Ohgaki H, Biernat W, Reis R, Hegi M, Kleihues P (2000): in Gliosarcoma: Pathology and Genetics of Tumours of the Nervous System, Kleihues P, Cavenee WK (eds), pp. 42-44, Lyon International Agency for Research on Cancer.
  2. Burger PC, Scheithauer BW (1994): Tumors of the Central Nervous System. Washington, pp 68, Armed Forces Institute of Pathology, Washington, D.C.
  3. Feigin IH, Gross SW (1958): Sarcoma arising in glioblastoma of the brain. Am J Pathol 33: 633-653.
  4. Galanis E, Buckner JC, Dinapoli RP, Scheithauer BW, Jenkin RB, Wang CH, O' Fallon JR Farr G Jr (1998): Clinical outcome of gliosarcoma compared with glioblastoma multiforme. North Central Cancer Treatment Group results. J Neurosurg 89: 425-430.
  5. Grant JW, Steart PV, Aguzzi A, Jone DB, Gallagher PJ (1989): Gliosarcoma: an immunohistochemical study. Acta Neuropathol (Berl) 73: 305-309.
  6. Jones H, Steart PV, Weller RO (1994): Spindle-cell glioblastoma or gliosarcoma? Neuropathol Appl Neurobiol 17: 177-187.
  7. Kleihues P, Burger PC, Scheithauer BW (1993): The WHO classification of brain tumors. Brain Pathol 3: 255-268.
  8. Kochi N, Budka H (1987): Contribution of histiocytic cells to sarcomatous development of the gliosarcoma. An immunohistochemical study. Acta Neuropathol (Berl) 73: 124-130.
  9. Maiuri F, Stella L, Benvenuti D, Giamundo A, Pettinato G (1990): Cerebral gliosarcomas: correlation of computed tomographic findings, surgical aspect, pathological features, and prognosis. Neurosurgery 26: 261-267.
  10. Meis JM, Ho KL, Nelson JS (1990): Gliosarcoma: a histologic and immunohistochemical reaffirmation. Mo Pathol 3: 19-24.
  11. Meis JM, Martz KL, Nelson JS (1991): Mixed glioblastoma multiforme and sarcoma. A clinicopathologic study of 26 radiation therapy oncology group cases. Cancer 67: 2342- 2349.
  12. Reis RM, KöNü-Leblebiicioglu D, Lopes JM, Kleihues P, Ohgaki H (2000): Genetic profile of gliosarcomas. Am J Pathol 156: 425-432.
  13. Stroebe H (1895): Uber Entstehung und Bau der Hirrngliome. Beitr Pathol Anat 18: 405-486

Contributed by Paisit Paueksakon, MD, Jerry B Blacklock, MD, Suzanne Z Powell, MD, J Clay Goodman, MD

International Society of Neuropathology