{{Infobox medical condition | name = Gliosarcoma | synonyms = Sarcomatous glioblastoma <ref>{{cite web |title=Gliosarcoma: Genetic and Rare Diseases Information Center (GARD) – an NCATS Program |url=https://rarediseases.info.nih.gov/diseases/5653/index |website=rarediseases.info.nih.gov |access-date=13 July 2019 |archive-date=13 July 2019 |archive-url=https://web.archive.org/web/20190713123334/https://rarediseases.info.nih.gov/diseases/5653/index |url-status=dead }}</ref> | image = Gliosarcoma Histopathology 200x EVG.jpg | caption = Micrograph showing a gliosarcoma. Elastic van Gieson's stain. | pronounce = | field = Neuro-oncology | symptoms = | complications = | onset = Between 40 and 60 years old<ref name="NCI">{{cite web|url=https://www.cancer.gov/rare-brain-spine-tumor/tumors/gliosarcoma|title=Gliosarcoma Diagnosis and Treatment|website=National Cancer Institute|date=17 September 2018 |access-date=March 8, 2023|archive-date=October 11, 2021|archive-url=https://web.archive.org/web/20211011031030/https://www.cancer.gov/rare-brain-spine-tumor/tumors/gliosarcoma|url-status=live}}</ref> | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = Five-year survival rate: 5.6%<ref name="NCI"/> | frequency = ~215 new diagnoses per year (United States)<ref name="NCI"/> | deaths = }} '''Gliosarcoma''' is a rare type of glioma, a cancer of the brain that comes from glial, or supportive, brain cells, as opposed to the neural brain cells. Gliosarcoma is a malignant cancer, and is defined as a glioblastoma consisting of gliomatous and sarcomatous components.<ref name=pmid20415184>{{cite journal | vauthors = Ayadi L, Charfi S, Khabir A, Kalle R, Sellami A, Makni S, Boudawara Z, Sellami-Boudawara T | display-authors = 6 | title = [Cerebral gliosarcoma: clinico-pathologic study of 8 cases] | language = fr | journal = La Tunisie Médicale | volume = 88 | issue = 3 | pages = 142–6 | date = March 2010 | pmid = 20415184 }}</ref> Primary gliosarcoma (PGS) is classified as a grade IV tumor and a subtype of glioblastoma multiforme in the 2007 World Health Organization classification system (GBM).<ref>{{cite journal |vauthors=Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P |title=The 2007 WHO classification of tumours of the central nervous system |journal=Acta Neuropathol |volume=114 |issue=2 |pages=97–109 |date=August 2007 |pmid=17618441 |pmc=1929165 |doi=10.1007/s00401-007-0243-4 }}</ref> Because of a lack of specific and clear diagnostic criteria, the word "gliosarcoma" was frequently used to refer to glial tumours with mesenchymal properties,<ref>{{cite journal |vauthors=Stroebe H |title=Ueber Entstehung und Bau der Gehirnglioma |journal=Beitr Pathol Anat Allg Pathol |volume=19 |pages=405–486 |date=1895 |doi= |url={{GBurl|OB4_AQAAMAAJ|p=405}} }}</ref> such as the ability to make collagen and reticulin.<ref name="Feigin">{{cite journal |vauthors=Feigin IH, Gross SW |title=Sarcoma arising in glioblastoma of the brain |journal=Am J Pathol |volume=31 |issue=4 |pages=633–53 |date=1955 |pmid=14388124 |pmc=1942557 }}</ref>
It is estimated that approximately 2.1% of all glioblastomas are gliosarcomas. Although most gliomas rarely show metastases outside the cerebrum, gliosarcomas have a propensity to do so, most commonly spreading through the blood to the lungs, and also liver and lymph nodes.<ref name="pmid17171442">{{cite journal | vauthors = Beaumont TL, Kupsky WJ, Barger GR, Sloan AE | title = Gliosarcoma with multiple extracranial metastases: case report and review of the literature | journal = Journal of Neuro-Oncology | volume = 83 | issue = 1 | pages = 39–46 | date = May 2007 | pmid = 17171442 | doi = 10.1007/s11060-006-9295-x | s2cid = 13171064 }}</ref>
They most commonly present in the temporal lobe<ref>{{cite journal |vauthors=Galanis E, Buckner JC, Dinapoli RP, Scheithauer BW, Jenkins RB, Wang CH, O'Fallon JR, Farr G |title=Clinical outcome of gliosarcoma compared with glioblastoma multiforme: North Central Cancer Treatment Group results |journal=J Neurosurg |volume=89 |issue=3 |pages=425–30 |date=September 1998 |pmid=9724117 |doi=10.3171/jns.1998.89.3.0425 }}</ref><ref>{{cite journal |vauthors=Parekh HC, O'Donovan DG, Sharma RR, Keogh AJ |title=Primary cerebral gliosarcoma: report of 17 cases |journal=Br J Neurosurg |volume=9 |issue=2 |pages=171–8 |date=April 1995 |pmid=7632363 |doi=10.1080/02688699550041511 }}</ref> and frontal lobe.<ref>{{cite journal |vauthors=Meis JM, Martz KL, Nelson JS |title=Mixed glioblastoma multiforme and sarcoma. A clinicopathologic study of 26 radiation therapy oncology group cases |journal=Cancer |volume=67 |issue=9 |pages=2342–9 |date=May 1991 |pmid=1849447 |doi=10.1002/1097-0142(19910501)67:9<2342::aid-cncr2820670922>3.0.co;2-b }}</ref>
==Pathogenesis== Early reports claimed that the hyperplastic blood vessels that are frequently present in high grade gliomas underwent neoplastic change to become the sarcomatous components.<ref name="Feigin" /> Feigin's early reports components of perivascular sarcomatous and hyperplastic arteries in gliosarcoma offered evidence for the "collision tumor" hypothesis.<ref>{{cite journal |vauthors=Feigin I, Allen LB, Lipkin L, Gross SW |title=The endothelial hyperplasia of the cerebral blood vessels with brain tumors, and its sarcomatous transformation |journal=Cancer |volume=11 |issue=2 |pages=264–77 |date=1958 |pmid=13511345 |doi=10.1002/1097-0142(195803/04)11:2<264::aid-cncr2820110207>3.0.co;2-d }}</ref> Also, Studies demonstrating the sarcomatous component's histological sensitivity to markers of vascular endothelium such factor CD34, von Willebrand factor, and VIII supported this theory.<ref>{{cite journal |vauthors=McComb RD, Jones TR, Pizzo SV, Bigner DD |title=Immunohistochemical detection of factor VIII/von Willebrand factor in hyperplastic endothelial cells in glioblastoma multiforme and mixed glioma-sarcoma |journal=J Neuropathol Exp Neurol |volume=41 |issue=5 |pages=479–89 |date=September 1982 |doi=10.1097/00005072-198209000-00001 |pmid=6286891 }}</ref><ref>{{cite journal |vauthors=Slowik F, Jellinger K, Gaszó L, Fischer J |title=Gliosarcomas: histological, immunohistochemical, ultrastructural, and tissue culture studies |journal=Acta Neuropathol |volume=67 |issue=3–4 |pages=201–10 |date=1985 |pmid=4050334 |doi=10.1007/BF00687802 }}</ref><ref>{{cite journal |vauthors=Wharton SB, Whittle IR, Collie DA, Bell HS, Ironside JW |title=Gliosarcoma with areas of primitive neuroepithelial differentiation and extracranial metastasis |journal=Clin Neuropathol |volume=20 |issue=5 |pages=212–8 |date=2001 |pmid=11594506 }}</ref> An alternative view that has recently gained support suggests that both gliosarcoma components have a monoclonal origin, with the sarcomatous component deriving from abnormal differentiation of malignant gliomal mesenchyma. First, gliomatous and sarcomatous components were shown to have similar p53 alterations by Biernat and colleagues.<ref>{{cite journal |vauthors=Biernat W, Aguzzi A, Sure U, Grant JW, Kleihues P, Hegi ME |title=Identical mutations of the p53 tumor suppressor gene in the gliomatous and the sarcomatous components of gliosarcomas suggest a common origin from glial cells |journal=J Neuropathol Exp Neurol |volume=54 |issue=5 |pages=651–6 |date=September 1995 |pmid=7666053 |doi=10.1097/00005072-199509000-00006 }}</ref> In both tumor regions, Reis and colleagues found similar nuclear accumulation of p53, deletion of p16, mutations of PTEN, and amplifications of CDK4.<ref>{{cite journal |vauthors=Reis RM, Könü-Lebleblicioglu D, Lopes JM, Kleihues P, Ohgaki H |title=Genetic profile of gliosarcomas |journal=Am J Pathol |volume=156 |issue=2 |pages=425–32 |date=February 2000 |pmid=10666371 |pmc=1850048 |doi=10.1016/S0002-9440(10)64746-3 }}</ref> Other scientists then noted that both gliosarcoma components had similar genetic changes and chromosomal abnormalities of the kind often seen in GBM.<ref>{{cite journal |vauthors=Actor B, Cobbers JM, Büschges R, Wolter M, Knobbe CB, Lichter P, Reifenberger G, Weber RG |title=Comprehensive analysis of genomic alterations in gliosarcoma and its two tissue components |journal=Genes Chromosomes Cancer |volume=34 |issue=4 |pages=416–27 |date=August 2002 |pmid=12112531 |doi=10.1002/gcc.10087 }}</ref><ref>{{cite journal |vauthors=Boerman RH, Anderl K, Herath J, Borell T, Johnson N, Schaeffer-Klein J, Kirchhof A, Raap AK, Scheithauer BW, Jenkins RB |title=The glial and mesenchymal elements of gliosarcomas share similar genetic alterations |journal=J Neuropathol Exp Neurol |volume=55 |issue=9 |pages=973–81 |date=September 1996 |pmid=8800093 |doi=10.1097/00005072-199609000-00004 }}</ref>
==Clinical characteristics== Gliosarcoma is rare; incidence ranges from 1.8 to 2.8 percent lower than that of GBMs.<ref name="Lutter">{{cite journal |vauthors=Lutterbach J, Guttenberger R, Pagenstecher A |title=Gliosarcoma: a clinical study |journal=Radiother Oncol |volume=61 |issue=1 |pages=57–64 |date=October 2001 |pmid=11578729 |doi=10.1016/s0167-8140(01)00415-7 }}</ref> PGS affects persons in their 6th to 7th years of life, and it is much more frequent in males than in females (with 1.4–1.8:1 ratio).<ref name="Lutter" /> Depending on where the tumor is located, the reported presenting signs and symptoms, such as aphasia, headaches, hemiparesis, seizures, and cognitive loss, are similar with those of a fast developing intracranial tumor. Many researchers have come to the conclusion that these tumors are clinically identical to GBM due to their clinical similarities.<ref>{{cite journal |vauthors=Machuca TN, Prevedello DM, Pope LZ, Haratz SS, Araújo JC, Torres LF |title=Gliosarcoma: report of four cases with immunohistochemical findings |journal=Arq Neuropsiquiatr |volume=62 |issue=3A |pages=608–12 |date=September 2004 |pmid=15334217 |doi=10.1590/s0004-282x2004000400008 }}</ref>
==Imaging== On CT imaging, the lesions might show as Well-defined high-density lesion edges and homogeneous enhancement, replicating the meningioma appearance, or as lesions with large necrotic regions and GBM-like heterogeneous contrast enhancement.<ref>{{cite journal |vauthors=Lee YY, Castillo M, Nauert C, Moser RP |title=Computed tomography of gliosarcoma |journal=AJNR Am J Neuroradiol |volume=6 |issue=4 |pages=527–31 |date=1985 |pmid=3927668 |pmc=8335194 }}</ref><ref>{{cite journal |vauthors=Maiuri F, Stella L, Benvenuti D, Giamundo A, Pettinato G |title=Cerebral gliosarcomas: correlation of computed tomographic findings, surgical aspect, pathological features, and prognosis |journal=Neurosurgery |volume=26 |issue=2 |pages=261–7 |date=February 1990 |doi=10.1227/00006123-199002000-00013 |pmid=2308674 }}</ref> Marked peritumoral edema is a characteristic and frequent hallmark of gliosarcomas observed on MRI.<ref name="Lutter" />
==Metastasis== GBM and other cerebral gliomas rarely metastasize outside the brain. Numerous authors described incidences of metastatic foci that mixed gliomatous and sarcomatous components,<ref>{{cite journal |vauthors=Ehrenreich T, Devlin JF |title=A complex of glioblastoma and spindle-cell sarcoma with pulmonary metastasis |journal=AMA Arch Pathol |volume=66 |issue=4 |pages=536–49 |date=October 1958 |pmid=13582394 }}</ref><ref>{{cite journal |vauthors=Garret R |title=Glioblastoma and fibrosarcoma of the brain with extracranial metastases |journal=Cancer |volume=11 |issue=5 |pages=888–94 |date=1958 |pmid=13585341 |doi=10.1002/1097-0142(195809/10)11:5<888::aid-cncr2820110504>3.0.co;2-t }}</ref> while others reported metastatic foci that were entirely composed of the sarcomatous component.<ref>{{cite journal |vauthors=Smith DR, Hardman JM, Earle KM |title=Contiguous glioblastoma multiforme and fibrosarcoma with extracranial metastasis |journal=Cancer |volume=24 |issue=2 |pages=270–6 |date=August 1969 |pmid=4307749 |doi=10.1002/1097-0142(196908)24:2<270::aid-cncr2820240210>3.0.co;2-5 }}</ref><ref>{{cite journal |vauthors=Gjerdrum LM, Bojsen-Møller M |title=October 1998--61 year old male with brain tumor and oral, lung, and palpebral masses |journal=Brain Pathol |volume=9 |issue=2 |pages=421–2 |date=April 1999 |pmid=10219754 }}</ref><ref>{{cite journal |vauthors=Ojeda VJ, Sterrett GF |title=Cerebral gliosarcoma, pulmonary adenoid-cystic carcinoma, and pulmonary metastatic gliosarcoma: report of an untreated case |journal=Pathology |volume=16 |issue=2 |pages=217–21 |date=April 1984 |pmid=6087260 |doi=10.3109/00313028409059108 }}</ref> Most gliosarcoma extracranial metastases are found in the lung and liver, but there have been reports of metastases elsewhere as well,<ref>{{cite journal |vauthors=Weaver D, Vandenberg S, Park TS, Jane JA |title=Selective peripancreatic sarcoma metastases from primary gliosarcoma. Case report |journal=J Neurosurg |volume=61 |issue=3 |pages=599–601 |date=September 1984 |pmid=6747700 |doi=10.3171/jns.1984.61.3.0599 }}</ref><ref>{{cite journal |vauthors=Cerame MA, Guthikonda M, Kohli CM |title=Extraneural metastases in gliosarcoma: a case report and review of the literature |journal=Neurosurgery |volume=17 |issue=3 |pages=413–8 |date=September 1985 |pmid=4047352 |doi=10.1227/00006123-198509000-00003 }}</ref><ref>{{cite journal |vauthors=Slowik F, Balogh I |title=Extracranial spreading of glioblastoma multiforme |journal=Zentralbl Neurochir |volume=41 |issue=1 |pages=57–68 |date=1980 |pmid=6258355 |doi= }}</ref><ref>{{cite journal |vauthors=Matsuyama J, Mori T, Hori S, Nakano T, Yamada A |title=[Gliosarcoma with multiple extracranial metastases. Case report] |language=Japanese |journal=Neurol Med Chir (Tokyo) |volume=29 |issue=10 |pages=938–43 |date=October 1989 |pmid=2482946 |doi=10.2176/nmc.29.938 }}</ref><ref>{{cite journal |vauthors=Yokoyama H, Ono H, Mori K, Kishikawa M, Kihara M |title=Extracranial metastasis of glioblastoma with sarcomatous component |journal=Surg Neurol |volume=24 |issue=6 |pages=641–5 |date=December 1985 |pmid=2997942 |doi=10.1016/0090-3019(85)90122-3 }}</ref> including evidence of intramedullary metastases to the cervical spine.<ref>{{cite journal |vauthors=Witwer BP, Salamat MS, Resnick DK |title=Gliosarcoma metastatic to the cervical spinal cord: case report and review of the literature |journal=Surg Neurol |volume=54 |issue=5 |pages=373–8; discusiion 378–9 |date=November 2000 |pmid=11165614 |doi=10.1016/s0090-3019(00)00315-3 }}</ref>
==Treatment== Tumor removal, postoperative radiation treatment, and chemotherapy with nitrosureas, misonidazole, dacarbazine, temozolomide, doxorubicin, vincristine, cisplatin, mithramycin, ametophterin, thalidomide, or irinotecan have all been recorded as treatment options for gliosarcoma<ref>{{cite journal |vauthors=Rodriguez FJ, Scheithauer BW, Jenkins R, Burger PC, Rudzinskiy P, Vlodavsky E, Schooley A, Landolfi J |title=Gliosarcoma arising in oligodendroglial tumors ("oligosarcoma"): a clinicopathologic study |journal=Am J Surg Pathol |volume=31 |issue=3 |pages=351–62 |date=March 2007 |pmid=17325476 |doi=10.1097/01.pas.0000213378.94547.ae }}</ref> and radiotherapy with temozolomide.<ref>{{cite journal |vauthors=Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO |title=Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma |journal=N Engl J Med |volume=352 |issue=10 |pages=987–96 |date=March 2005 |pmid=15758009 |doi=10.1056/NEJMoa043330 }}</ref>
==Prognosis== PGS has a poor prognosis,<ref>{{cite journal |vauthors=Kozak KR, Mahadevan A, Moody JS |title=Adult gliosarcoma: epidemiology, natural history, and factors associated with outcome |journal=Neuro Oncol |volume=11 |issue=2 |pages=183–91 |date=April 2009 |pmid=18780813 |pmc=2718990 |doi=10.1215/15228517-2008-076 }}</ref> a prognosis of median survival of 4 months in untreated individuals.<ref>{{cite journal |vauthors=Morantz RA, Feigin I, Ransohoff J |title=Clinical and pathological study of 24 cases of gliosarcoma |journal=J Neurosurg |volume=45 |issue=4 |pages=398–408 |date=October 1976 |pmid=956876 |doi=10.3171/jns.1976.45.4.0398 }}</ref> The National Cancer Institute states that the relative five-year survival rate of gliosarcoma is only 5.6%.<ref name="NCI"/>
== References == {{Reflist}}
== External links == {{Medical resources | DiseasesDB = | ICD10 = G71.9 | ICD9 = | ICDO = {{ICDO|9442|3}} | OMIM = | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeshID = | Orphanet = 251576 | SNOMED CT = 35262004 }} * [http://www.cancer.gov/dictionary?CdrID=45701 Gliosarcoma] {{Webarchive|url=https://web.archive.org/web/20150428143257/http://www.cancer.gov/dictionary?cdrid=45701 |date=2015-04-28 }} entry in the public domain NCI Dictionary of Cancer Terms *[https://www.cancer.gov/rare-brain-spine-tumor/tumors/gliosarcoma Gliosarcoma - National Cancer Institute] {{Webarchive|url=https://web.archive.org/web/20211011031030/https://www.cancer.gov/rare-brain-spine-tumor/tumors/gliosarcoma |date=2021-10-11 }}
{{NCI-cancer-dict}}
{{Central nervous system tumors}}
Category:Rare cancers Category:Brain tumor