Primary Extracerebral Meningeal Glioblastoma: Clinical and Pathological Analysis

46 Case Report

Primary Extracerebral Meningeal Glioblastoma: Clinical and Pathological Analysis

Authors

P. Stavrinou1, I. Magras1, L. C. Stavrinou2, T. Zaraboukas1, K. S. Polyzoidis1, P. Selviaridis1

Affiliations

1

Key words ▶ primary meningeal glioma ● ▶ glioblastoma ● ▶ meningioma ● ▶ desmoplasia ● ▶ desmoplastic glioblastoma ●

Abstract &

AHEPA University Hospital, Neurosurgery, Thessaloniki, Greece Evaggelismos General Hospital, Neurosurgery, Athens, Greece

Primary meningeal gliomas are uncommon tumors in the subarachnoid space, their primary characteristic being the absence of any obvious connection to the brain parenchyma. Rarely, they are quite malignant and assume a bulky, well circumscribed appearance rendering the differential diagnosis from other CNS neoplasms difficult. A 53-year-old man presented with a history of persistent headaches and left sided weakness. Magnetic resonance imaging revealed a temporoparietal mass attached to the dura that strongly resembled a meningioma. At surgery, the outer layer of the dura mater was intact and there was a clear brain-tumor interface without obvious pial disruption. Histological examination

Introduction &

Bibliography DOI http://dx.doi/org/ 10.1055/s-0029-1225652 Cent Eur Neurosurg 2010; 71: 46–49 © Georg Thieme Verlag KG Stuttgart · New York ISSN 1868-4904 Correspondence Dr. P. Stavrinou AHEPA University Hospital Neurosurgery St. Kyriakidi 1 54636 Thessaloniki Greece Tel.: + 302310993287 Fax: + 302310993692 [email protected]

Primary meningeal gliomas are rare tumors that arise in the subarachnoid space. They have been reported in the cerebral hemispheres, the cerebellum and the spinal cord [6–8]. Morphologically, they are differentiated into diffuse and solitary gliomas. Both present a diagnostic challenge, since the diffuse form may mimic the clinical manifestation and radiographic appearance of chronic meningitis, while the solitary form may bear a strong histological resemblance to other CNS tumors. We report a case of an intracranial extracerebral tumor with all the radiological and macroscopic features of a meningioma but where histological evaluation revealed intense desmoplasia intermingled with glioblastoma morphology. We describe the histological, radiological and surgical characteristics of this case, together with our course of treatment and discuss the differential diagnosis between a malignant meningioma, an aggressive glioblastoma infiltrating the dura

Stavrinou P et al. Primary Extracerebral Meningeal Glioblastoma … Cent Eur Neurosurg 2010; 71: 46–49

showed a biphasic pattern consisting of benign connective tissue intermingled with bundles of what seemed to be a glioblastoma. The mass demonstrated strong positivity for GFAP and the MIB labeling index focally exceeded 20 %. The tumor was identified as a primary meningeal glioblastoma. The patient was disease-free for 42 months, after which he developed a recurrence for which he was re-operated. This time, the pathological findings of the tumor were those of a typical glioblastoma multiforme. We discuss the origin of the initial neoplasm and also the differential diagnosis that needs to include meningioma, aggressive glioblastoma infiltrating the dura and a recently recognized bimorphic CNS tumor: the desmoplastic glioblastoma.

mater and the recently recognized bimorphic tumor, the desmoplastic glioblastoma.

Case Report & A 53-year-old Caucasian male presented with a 30-day history of increasing headaches. On physical examination mild left-sided weakness was present, with accompanying bilateral papilledema. Past medical history of interest was uneventful. Radiological studies demonstrated a right supratentorial temporoparietal mass that appeared to be extraparenchymal, well circumscribed, 4 cm in diameter, with perifocal edema and inhomogeneous contrast enhancement. The apparent contact with the meninges along with a typical “dural tail sign” appeared to point to a ▶ Fig. 1). diagnosis of meningioma (● At surgery, the outer layer of the dura mater was intact but the inner layer was found to be infiltrated and firmly attached to the neoplasm. The mass itself was whitish-gray, firm, with alterna-

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Case Report 47

months later he presented with a recurrence for which he under▶ Fig. 5). Again, gross total removal was went re-operation (● achieved and chemotherapy with temozolomide was re-initiated. This time the tumor was intraparenchymal, with a macroscopic appearance and pathological findings typical of a ▶ Fig. 6). glioblastoma multiforme (●

Discussion & The present tumor presented a diagnostic and therapeutic challenge. Initial differential diagnosis included meningioma, especially the malignant variant. However, the strong positivity of the neoplastic cells to GFAP indicates their glial lineage [14]. Furthermore, the nuclear atypia, the intense mitotic activity and the presence of clotted neo-vessels and necrosis are all histological characteristic for glioblastoma. Although glioblastomas show all kinds and degrees of invasive growth, the dura mater is a potent collagenous barrier that resists infiltration so that direct and massive infiltration of the pachymeninx is a rare occurrence [9]. Nevertheless, cases of aggressive glioblastomas penetrating the dura mater and even the bone and surrounding tissues have been reported [11, 12]. One could argue that desmoplasia in gliomas is a well recognized process and it comes as no surprise when gliomas, usually high-

Fig. 1 Preoperative contrast-enhanced MRI showing a supratentorial tumor with the radiologic characteristics of a meningioma, including the typical “dura-tail sign”.

Fig. 2 Macroscopic appearance of tumor sections that strongly resembled a meningioma intraoperatively (1st operation).

Fig. 3 a Diffuse islets and bundles of neoplastic cells within an abundant, thick, fibrous substrate. Inset: clotted tumor vessel. b Strong positivity for glial fibrillary acidic protein (GFAP).

Stavrinou P et al. Primary Extracerebral Meningeal Glioblastoma … Cent Eur Neurosurg 2010; 71: 46–49

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▶ Fig. 2). There tions between vascular and avascular areas (● was a clear brain-tumor plane, without pial disruption, and the mass could be easily separated from the surrounding brain parenchyma, giving the impression of a meningioma. Gross complete resection was accomplished, with removal of the infiltrated dura and placement of a synthetic dura substitute, comparable to a Simpson-I resection. No frozen sections were obtained. Pathological examination excluded the diagnosis of a meningioma, disclosing a biphasic pattern consisting of islets and bundles of neoplastic cells clearly separated by broad strands of thick connective tissue with no sign of malignancy. The tumor cells were mostly spindle-shaped, with marked nuclear atypia and dense mitotic figures. In places they were larger, with eccentric nuclei, assuming a gemistocytic character. A small number of multinucleated giant cells could also be identified. The tumor showed clotted vessels and necrosis as in a glioblastoma. Focally, the MIB-1 labeling index exceeded 20 %. The margin of the tumor showed a clear brain-tumor interface. Immunohistochemical studies demonstrated strong positivity for GFAP and vimentin ▶ Fig. 3a, b). The diagnosis of meningeal glioblastoma was (● made. Due to a lack of experience with such rare tumors the patient was treated as if suffering from a typical glioblastoma. Subsequently, he received 60 Gy of whole brain radiation and he was started on temozolomide, every day for 42 days with six additional 5-day cycles. The patient was followed-up closely with ▶ Fig. 4). Forty-two MRI control studies at 6-month intervals (●

grade, have access to the meninges [12]. The presence of a duratail sign, as in this case, could only underscore the intimacy in which the dura was recruited to respond. The above argumentation however shows some serious plot-holes: in cases of dura infiltration by aggressive gliomas, the desmoplasia is usually temperate (not massive and profound as in our case), confining itself around the point of tumor dura contact [12]. In a case of a dura-infiltrating glioma reported by Shuangshoti et al. where there was a desmoplastic reaction, the fibrous tissue was reported to be “absent in most of the neoplasm, except in the

Fig. 4 Postoperative control MRI at 12 months showing complete resection and no tumor recurrence.

Fig. 5 MRI showing the tumor recurrence.

region where the dura mater was invaded”. In cases where highgrade gliomas grow per continuitatem, destroying the surrounding bone and dura, they still conserve their primary histological, macroscopic and radiological appearance – that of a glioblastoma multiforme – at their remote initial intracerebral site [1, 2, 12]. The tumor presented herein had an unvarying morphology throughout. Finally, we find it very hard to believe that – had our tumor been an aggressive glioblastoma – it could have caused such a massive reaction by merely infiltrating the inner layer while respecting the outer layer of the pachymeninx. A differential diagnosis should also include the recently recognized bimorphic CNS tumors [13]. Probably the most distinctive example of such a neoplasm is the gliosarcoma in which both the glial and the mesenchymal component are malignant. In our case, the mesenchymal component was completely benign excluding gliosarcoma as a possible diagnosis. Cerda-Nicolas and Kepes in their review suggest that the term desmoplastic glioblastoma should be used for mixed tumors where the mesenchymal component is benign but the glial population has the outright appearance of a glioblastoma, with the production of connective tissue emanating from the basal lamina of the glial cells themselves [4]. The fact that after dura removal the tumor recurred as a classic glioblastoma gave us a useful insight, and corroborated our suspicion that the cancerous glial nests did not have an intrinsic capability to produce fibrous tissue [5]. We speculate that our patient’s solitary extracerebral glioblastoma arose from cancerous transformation of heterotopic glial tissue sometimes found in the leptomeninges [10]. To our knowledge, the only leptomeningeal glioblastoma recruiting the dura and resembling a meningioma was reported by Bailey in a 39year-old patient with a sizeable frontoparietal mass, who died thirteen months after diagnosis [3]. At thirteen months after the second operation our patient is still alive and the tumor has already recurred as a classic cerebral glioblastoma. We cannot prove definitively that our case is indeed a primary menigneal glioma and not an intracerebral glioblastoma that seeded the subarachnoid space. Nevertheless, the above arguments, and especially the fact that intraoperatively there was no impression of pial breach, are evidence that it was the primary tumor which seeded the parenchyma and not the other way around. Retrospectively, we believe that not obtaining frozen sections of the tumor was poor judgment. But it would not have altered our surgical strategy since we would have still aimed at total resection, including removal of the dura. Primary meningeal glioblastoma is a very rare entity that should be considered in the differential diagnosis of malignant desmoplastic glial tumors. The definite diagnosis can only be made by histological examination and the strong impression of the surgeon that he is operating on a meningioma should not bias the pathologist when making the correct diagnosis.

Conflict of interest: None References

Fig. 6

Glioblastoma multiforme. Severe cellularity and nuclear atypia.

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Stavrinou P et al. Primary Extracerebral Meningeal Glioblastoma … Cent Eur Neurosurg 2010; 71: 46–49