Gliosarcoma is a highly aggressive primary brain tumour. It is a relatively rare tumour and comprises of two histological components, glial and sarcomatous. Gliosarcomas carry a poorer prognosis than that of Glioblastoma Multiforme (GBM). The current review highlights important histological and radiological features of gliosarcoma in the light of recent literature, and also touches upon the treatment options and outcomes of various types of gliosarcoma

Bari, Muhammad Ehsan

Hashmi, Fauzan Alam

Salim, Adnan

Shamim, Muhammad Shahzad

English

eCommons@AKU

eCommons@AKUSection of Neurosurgery Department of SurgeryAugust 2018Biological characteristics and outcomes ofgliosarcomaFauzan Alam HashmiAga Khan University, fauzan.alam@aku.eduAdnan SalimAga Khan UniversityMuhammad Shahzad ShamimAga Khan University, shahzad.shamim@aku.eduMuhammad Ehsan BariAga Khan University, ehsan.bari@aku.eduFollow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurgRecommended CitationHashmi, F. A., Salim, A., Shamim, M., Bari, M. (2018). Biological characteristics and outcomes of gliosarcoma. Journal of the PakistanMedical Association, 68(8), 1273-1275.Available at: https://ecommons.aku.edu/pakistan_fhs_mc_surg_neurosurg/152AbstractGliosarcoma is a highly aggressive primary brain tumour. It isa relatively rare tumour and comprises of two histologicalcomponents, glial and sarcomatous. Gliosarcomas carry apoorer prognosis than that of Glioblastoma Multiforme(GBM). The current review highlights important histologicaland radiological features of gliosarcoma in the light of recentliterature, and also touches upon the treatment options andoutcomes of various types of gliosarcoma.Keywords:Glioma, Sarcoma, Brain tumour.Review of EvidenceGliosarcoma is a rare primary brain tumour with prevalencevarying from 1.5-8% in different studies, and accounts for0.48% of all intra-cranial tumours.1 It can be further sub-classified into primary gliosarcoma (PGS) and secondarygliosarcoma (SGS), and whereas PGS occurs de novo, SGS isbelieved to occur as a recurrence or progression ofGlioblastoma Multiforme (GBM), or as a consequence ofradiation therapy.2The current accepted definition of gliosarcoma is 'a well-circumscribed lesion with clearly identifiable biphasic glial andmetaplastic mesenchymal components'.3,4 The glialcomponent resembles GBM and is richly positive for glialfibrillary acidic protein (GFAP),while the sarcomatouscomponent resembles fibrosarcoma, but may also resembleosteosarcoma, chondrosarcoma, angiosarcoma,orrhabdomyosarcoma,5,6 and is rich in reticulin and poor in GFAPexpression. Reis et al., observed that P53 mutation is seen in23% of gliosarcomas as compared to 11% of primary GBM, andepidermal growth factor receptor (EGFR) amplification, is foundin only 4% of gliosarcomas compared to 35% of GBM. Smalldifferences are also noted in Phosphatase and Tensin homolog(PTEN) mutation and cyclin-dependent kinase (CDK)amplification.7 Cases of radiation induced gliosarcoma includeependymoma, oligodendroglioma, anaplastic astrocytoma,meningioma, pituitary adenoma, acute lymphoblasticleukaemia and choriocarcinoma. Extracranial metastasis can beseen in patients with SGS.2,8,9Radiologically, Zhang et al., reported gliosarcomas as irregularmasses on both CT and MRI, with a smooth external wall, welldemarcated from the surrounding brain parenchyma, andsignificant surrounding oedema. Furthermore, they describedthat gliosarcomas occur more commonly in the temporal lobe,and can appear similar to meningiomas on gross morphology.10Han et al.,3 described it as generally large lesions that are hypo-intense on T1-weighted images and hyper-intense on T2-weighted images, with areas of necrosis and central calcification(characterized by heterogenous contrast enhancement), andintense peripheral or irregular enhancement and shift of midlinestructures. Diffusion and mass diffusion coefficient are usuallyheterogeneous and MR spectroscopy may show choline (Cho)peak, with normal creatinine (Cr) and low N-acetyl-aspartate(NAA), although these findings are non-specific.11 Despite smalldifferences, gliosarcoma is largely indistinguishable from GBMin most cases as they share identical radiological and clinicalcharacteristics, and their definitive differentiation is based onlyon histopathology.4,12The treatment is on the same lines as GBM, with maximal saferesection as the cornerstone, followed by ConcomitantChemotherapy and Radiation Therapy (CCRT).13 Castelli et al.,reported their management of gliosarcoma patients with12-months median follow up (2-71 months), and reported Grosstotal resection (GTR) in 59% patients. Temozolamide basedCCRT was administered in 64% patients while 15% patientsreceived adjuvant chemotherapy regimens based onplatinum, fotemustine and vincristine. Treatment atrecurrence included chemotherapy in 80% of patients, repeatsurgery in 17% and chemo-radiotherapy in 2% of thepatients.14 They report a median Overall Survival (OS) of 13months, and a median Progression Free Survival (PFS) of 7months. Although it is difficult to conclude as such but CCRTand adjuvant chemotherapy did not improve OS comparedto radiotherapy alone. High dose of Radiation Therapy (RT)and salvage treatment appeared to increase OS.14Cachia et al., in their series reported GTR in 53 % patients andCCRT in 70% of patients. Bevacuzimab based regimens wereused in 47% of patients, with half receiving single agent andhalf another agent in combination.8 Patients with GTR had abetter Overall Survival (OS) (24.7 vs. 10.1 months), althoughthis did not reach statistical significance. Overall, patientstreated with bevacizumab had a PFS of 4.2 months and an OSof 8.7 months from initiation of treatment. Patients with PGShad the same outcomes, however, SGS patients treated withJ Pak Med Assoc1276EVIDENCE BASED NEURO-ONCOLOGYBiological characteristics and outcomes of GliosarcomaFauzan Alam Hashmi, Adnan Salim, Muhammad Shahzad Shamim, Muhammad Ehsan BariAga Khan University Hospital, Karachi, Pakistan.Correspondence:Muhammad Shahzad Shamim.Email: shahzad.shamim@aku.edubevacizumab, had a OS of 7.3 months and PFS of 3.8 months.8Treatment with bevacuzimab along with temozolamidebased CCRT did not show any benefit in OS of patients withSGS.8Kozak et al., also reported a median OS of 9 months. Age atpresentation, extent of resection, and adjuvant RT weresignificantly associated with better survival.15 SGS patientswere defined as those with a prior history of GBM, and in thissub-group PFS was 3.1 months from the time of sarcomatoustransformation.8 Twenty-one percent of patients developedtumour metastases and 15% showed leptomeningealdissemination. Extra-axial spread occurred to theinfratemporal region outside the temporal bone, cervicallymph nodes, and temporal bone. The cumulative OS of PGSand SGS was 17.5 months and PFS was 6.5 months. There appears a wide variation in reported OS for gliosarcomapatients, from 4-11.5 months.3,5 Interestingly, the OS for SGSis 25 months, and is the same as PGS if measured from thetime of first diagnosis of GBM.ConclusionGliosarcoma is a rare tumour that is difficult to differentiatefrom GBM on clinical or radiological information although canbe differentiated on histopathology. GTR followed bytemozolamide based CCRT may provide the best outcome.References1. Galanis E, Buckner JC, Dinapoli RP, Scheithauer BW, Jenkins RB, WangCH, et al. Clinical outcome of gliosarcoma compared withglioblastoma multiforme: North Central Cancer Treatment Groupresults. J Neurosurg. 1998; 89: 425-30.2. Han SJ, Yang I, Tihan T, Chang SM, Parsa AT. Secondary gliosarcoma: areview of clinical features and pathological diagnosis: Clinical article. JNeurosurg 2010; 112: 26-32. 3. Han SJ, Yang I, Ahn BJ, Otero JJ, Tihan T, McDermott MW, et al. Clinicalcharacteristics and outcomes for a modern series of primarygliosarcoma patients. Cancer 2010; 116: 1358-66.4. Miller CR, Perry A. Morphologic and molecular genetic diversity. ArchPathol Lab Med. 2007; 131: 397-406.5. Damodaran O, van Heerden J, Nowak AK, Bynevelt M, Mcdonald K,Marsh J, et al. Clinical management and survival outcomes ofgliosarcomas in the era of multimodality therapy. J Clin Neurosci.2014; 21: 478-81.6. Kumar P, Singh S, Kumar P, Krishnani N, Datta NR. Gliosarcoma: anaudit from a singleinstitution in India of 24 post-irradiated cases over15 years. J Can Res Ther 2008; 4: 164.7. Reis RM, Könü-Lebleblicioglu D, Lopes JM, Kleihues P, Ohgaki H.Genetic profile of gliosarcomas.  Am J Pathol. 2000; 156: 425-32.8. Cachia D, Kamiya-Matsuoka C, Mandel JJ, Olar A, Cykowski MD,Armstrong TS, et al. Primary and secondary gliosarcomas: clinical,molecular and survival characteristics. ?J. Neuro-Oncol 2015; 125: 401-10.9. Dawar R, Fabiano AJ, Qiu J, Khushalani NI. Secondary gliosarcoma withextra-cranialmetastases: a report and review of the literature.  ClinNeurol Neurosurg.. 2013; 115: 375-80.10. Zhang B-Y, Chen H, Geng D-Y, Yin B, Li Y-X, Zhong P, et al. Computedtomography and magnetic resonance features of gliosarcoma: a studyof 54 cases. J Comput Assist Tomogr. 2011; 35: 667-73.11. Romero-Rojas AE, Diaz-Perez JA, Ariza-Serrano LM, Amaro D, Lozano-Castillo A. Primary gliosarcoma of the brain:radiologic andhistopathologic features.Neuroradiol J..2013; 26: 639-48.12. Fukuda T, Yasumichi K, Suzuki T. Immunohistochemistry ofgliosarcoma with liposarcomatous differentiation. Pathol.Int. 2008; 58:396-401.13. Choudry UK, Shaikh HI, Nisar A, Khan SA, Shamim MS. Role of extent ofresection on quality of life in patients with newly diagnosed GBM. JPak Med Assoc 2018; 68: 142-144.14. Castelli J, Feuvret L, Haoming Q, Biau J, Jouglar E, Berger A, et al.Prognostic and therapeutic factors of gliosarcoma from a multi-institutional series. Journal of Neuro-oncology. 2016; 129: 85-92.15. Kozak KR, Mahadevan A, Moody JS. Adult gliosarcoma: epidemiology,natural history, and factors associated with outcome. J Neuro-Oncol2009; 11: 183-91.Vol. 68, No. 8, August 2018Relationship of the angiographic extent of peripheral arterial disease with coronary artery involvement 1277Figure: a) T1WI showing iso-hypo-intense lesion in left parieto-temporal region. b) T2WI showing hyper-intense lesion in left parieto-temporal region. c) T1- contrast enhanced imageshowing heterogenous enhancement.

Biological characteristics and outcomes of gliosarcoma

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Biological characteristics and outcomes of gliosarcoma

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