Gliosarcoma with direct involvement of the oculomotor nerve: Case report and literature review

Gliosarcoma is a rare malignant brain tumor, characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation. We first report a case of temporo-mesial gliosarcoma, extended to the crural and ambient cisterns, with direct involvement of the ipsilateral third cranial nerve and encasement of anterior choroidal, posterior communicant and posterior cerebral arteries, presenting without symptoms of peripheral neuropathy. A 61-year-old woman with 1-month history of intense bilateral frontal-temporal headache resistant to pharmacological therapy and paresis of the left lower midface underwent surgical resection, through pterional trans-sylvian approach, of a right temporo-mesial gliosarcoma which directly involved the ipsilateral oculomotor nerve. Reported cases of gliomas with direct involvement of a cranial nerve, from the third to the twelfth, are very rare, whit no cases of gliosarcoma described. Because of its rarity, sometimes this entity is not considered as diagnostic hypothesis and is misdiagnosed, both during preoperative diagnostic evaluation and during the surgery. Gliosarcoma is a strong challenge for neurosurgeons and neurooncologists because of low incidence, poor prognosis and limited reported cases on literature. This case shows unique features for localization, pattern of growth and clinical presentation.


Introduction
Gliosarcoma, a variant of IDH-wildtype glioblastoma, is a rare malignant brain tumor (incidence 2%-8% of all glioblastoma), characterized by a biphasic tissue pattern with alternating ar-✩ Competing Interests: The authors have declared that no competing interests exist. * Corresponding author. S. Corvino.
eas displaying glial and mesenchymal differentiation [1] . It displays slight prevalence for sex male and the mean age of affected patients ranges from fifth to seventh decade [ 1 ,2 ]. It more frequently affects the cerebral hemispheres, with a predilection for the temporal lobes [2][3][4][5][6][7][8][9] , followed by the rarer localizations at the posterior cranial fossa and spinal cord.   direct involvement of a cranial nerve by gliomas is very rare [ 10 ,11 ], and no cases of gliosarcoma are described. We first report a case of temporo-mesial gliosarcoma, with extension to the crural and ambient cisterns, with direct involvement of the ipsilateral third cranial nerve and encasement of the anterior choroidal, posterior communicant and posterior cerebral arteries, presenting without symptoms of peripheral neuropathy.

Case report
A 61-year-old woman with 1-month history of intense bilateral frontal-temporal headache resistant to pharmacological therapy and paresis of the left lower midface was observed. The brain computed tomography ( Fig. 1A ) showed a right temporal cortico-subcortical area of heterogeneous and slight hypodensity; a brain MRI detected a right temporal infiltrating mass, hypointense in T1, hyperintense in T2, with intense and heterogeneous enhancement after contrast administration, with irregular shape and extended from the temporal pole, anteriorly, to the atrium of the lateral ventricle, posteriorly, and through the para-hippocampal gyrus and uncus, to the ambiens and parasellar cisterns medially, with involvement of the homolateral third cranial nerve in its intracis-  The patient underwent right pterional trans-sylvian approach. Firstly, the surgical removal was addressed to the tumoral component involving the temporal pole, which appeared as a soft, greyish-pink mass, with central necrotic yellowish area, moderately vascularized; then, once sylvian fissure was opened, the neoplastic component involving the medial part of the temporal lobe and extending to the ambiens and crural cisterns was exposed: it appeared as a firm greyish mass with a small yellowish central core. This last component was strongly adherent to the cisternal part of third cranial nerve and encompassed the anterior choroidal, the posterior communicant and the posterior cerebral arteries, thus the complete resection was not possible.
Postoperative course was characterized by transient right ptosis and mydriasis, which disappeared on the POD 3, and by improvement of the central paresis signs of contralateral midface. Post-contrast brain MRI performed 48 hours after surgical procedure showed a satisfactory tumor removal, with a small residual area of contrast enhancement.
The histological and immunohistochemical studies ( Fig. 2A ) reported a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation; the immunophenotypic characterization revealed GFAP positive expression in glial, and negative in mesenchymal component, whereas p53 was positive in both; all these findings were consistent for the diagnosis of gliosarcoma; genetic profile ( Fig. 2B ) showed lack of mutations in IDH1 and IDH2 genes, absence of 1p/19q co-deletion, absence of MGMT methylation, EGFR amplification, gain of 7 chromosome and loss of 10, con- firming the definitive diagnosis of mesenchymal glioblastoma ( Fig. 3 ).
At discharge, the patient was addressed to the oncological team for the Stupp protocol administration.
No progression-disease was detected on brain MRI with contrast performed 3 months after surgery.

Discussion
Reported cases of gliomas with direct involvement of a cranial nerve, from the third to the twelfth, were very rare [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ( Table 1 ); among them the glioblastoma (WHO grade IV) was the most common (11 cases [ 10 ,11 ,14 ,22-24 ]), followed by the low-grade gliomas; no cases of gliosarcoma were described. The anatomical region and the cranial nerves more often affected were the cerebellopontine angle and trigeminal and vestibulocochlear nerves, while the oculomotor nerve was involved only 2 times. In most of the cases clinical symptoms related to the cranial nerve directly involved were present; only 5 cases of high-grade temporal glioma associated to isolated third cranial nerve palsy were reported in the literature [ 11 ,25-28 ]. We first report a case of temporomesial gliosarcoma, with exophytic pattern of growth to the ambient and crural cisterns and with sleeve involvement of the ipsilateral third cranial nerve, with encasement of the anterior choroidal, posterior communicant and posterior cerebral arteries, presenting without symptoms of peripheral neuropathy.
Because of the small number of cases reported in the literature due to the low incidence of GBM with direct cranial nerve involvement and no cases of gliosarcoma, sometimes this kind of lesion is not considered and is misdiagnosed, both during preoperative diagnostic evaluation and during the surgery, hypothesizing the tumor origin from the nerve with secondary extension to the near brain parenchyma, or from heterotopic neuroglial cell dissemination from leptomeningeal gliomas or gliomatosis [29] , or from primary brainstem GBM with extension along adjacent cranial nerve.
Concerning the macroscopic features, based on sarcomatous component amount, gliosarcoma with high connective tissue percentage have the appearance of a firm, wellcircumscribed mass, which can be mistaken for a metastasis or, when attached to the dura, for a meningioma, whereas lesions less rich in connective tissue may have features more similar to a glioblastoma. Concerning imaging features, gliosarcoma usually presents as a well-demarcated solid mass, often on peripheral location, with heterogeneous enhancement, moderate or marked surrounding edema and abutting dura [ 2 ,6 ,7 ,30-34 ], but without dural attachment or invasion.
The pattern of growth shows a rate of extracranial metastases upon 11% for gliosarcoma [35] , while it is under 2% for conventional glioblastoma [ 36 ,37 ].
Glioblastoma and gliosarcoma are similar in terms of clinical behavior, treatment and prognosis [2] , while they differ for some features which are unique of gliosarcoma, including major propensity to extracranial metastases, intraoperative findings similar to aggressive meningioma, predilection for temporal lobe location and infrequency EGFR mutation [2] . For the diagnosis, immunohistochemical and molecular studies are crucial.

Conclusion
Gliosarcoma is a strong challenge for neurosurgeons and neurooncologists because of its low incidence, poor prognosis and limited reported cases on literature. This case shows unique features for localization, pattern of growth and clinical presentation.

Patient consent
Informed consent was obtained from the patient involved in this case.