Multicentric spinal cord and brain glioblastoma without previous craniotomy.

BACKGROUND: Glioblastoma multiforme (GBS) is a highly malignant glioma that rarely presents as an infratentorial tumor. Multicentric gliomas lesions are widely separated in site and/or time and its incidence has been reported between 0.15 and 10%. Multicentric gliomas involving supratentorial and infratentorial region are even more rare. In most cases, infratentorial disease is seen after surgical manipulation or radiation therapy and is usually located in the cerebellum or cervical region. CASE REPORT: We present a rare case of symptomatic multicentric glioma in the brain, fourth ventricle, cervical as well as lumbar glioblastoma in an adult without previous therapeutic intervention. We also review the literature of this rare presentation.
CONCLUSIONS: This report suggests that GBM is a diffuse disease; the more extended the disease, the worse prognosis it has. The management still remains controversial and further studies are required to understand the prognosis factors of dissemination.

INTRODUCTION

Glioblastoma multiforme (GBM) is a highly malignant glioma that rarely presents as an infratentorial tumor. The tumor is called multicentric glioma when the lesions are widely separated in site and/or time; its incidence has been reported between 0.15% in small series to 10%.[512] Multicentric gliomas involving supratentorial and infratentorial region are exceptional. In most reported cases, infratentorial disease occurs after surgical manipulation or radiation therapy and is placed in the cerebellum or cervical spine.

We present a rare case of symptomatic multicentric glioma in the brain, fourth ventricle, cervical as well as lumbar glioblastoma in an adult without previous therapeutic intervention and review the literature of this rare presentation.

CASE REPORT

An 83-year-old woman presented with a 3-week history of progressive bilateral low back pain on admission. She had associated numbness in the left leg. On neurological examination, the patient presented global motor deficit of 4+/5 in the left inferior extremity, without sensitive deficit. A dorsolumbar magnetic resonance imaging (MRI) was performed, revealing a D12-L1 intramedullary mass, with necrosis and irregular contrast enhancement [Figure 1]. She underwent subtotal surgical resection after lumbar laminectomy. An intramedullary infiltrative lesion inside the piamatter, with thrombotic vessels and necrosis were found. Histopathological examination confirmed that the lesion was a GBS [Figure 2]. After surgery, the patient presented cerebrospinal fluid (CSF) fistula, and a continuous lumbar drainage was placed.

Figure 1

T1 Sagittal magnetic resonance imaging (MRI) with contrast (a) and T1 axial MRI (b) without demonstrating intradural extramedullary compressive lesion in D12-L1

Figure 2

Dense cell proliferation is observed, with areas of spindle cell pattern (a: H&E), with some areas of pleomorphism, lots of mitosis, some of them atypical, and karyomegaly and nuclear irregularity (b: H&E). This neoplastic lesión was negative for cytokeratin (c: CkAE1/AE3) and intense and diffuse positivity form vimentin (d). Cell proliferation rate was high, about 30% (e: Ki67), showing glial fibrillary acid protein positive (f)

Considering the diagnosis, a craneocervical MRI was performed. An enhancing necrotic mass in the left atrium, with an increase of Cholina value related to N-acetyl aspartate and high concentration of lactate was observed, corresponding to high grade glioma. A third enhancing mass was diagnosed in fourth ventricle [Figure 3]. In cervical spine, an extramedular, intradural C7-D1 enhancing mass was diagnosed as a fourth implant. Two weeks after the surgery, the patient experienced worsening of her neurological and general status and finally died.

Figure 3

(a) T1 axial magnetic resonance imaging (MRI) with contrast revealing an enhancing mass in the left atrium. (b) T1 sagittal MRI with contrast showing an enhancing mass in fourth ventricle

DISCUSSION

We report a case of multicentric GBM involving the supratentorial and spine region in an adult without previous surgery. Multicentric glial tumors are rare, accounting for 0.15–10% of glial tumors.[2512] To our knowledge, 11 cases have been documented of multicentric supra and infratentorial glioblastomas,[13] even though all these cases had supratentorial and a concomitant cerebellar or brainstem disease; this is the first case that reach the lumbar spinal section.

Many cases have also been described of cranial and spinal metastasis after surgery or radiotherapy in low[1] and high grade gliomas.[7] However, only 2 cases have been described before with spinal glioblastoma without history of craniotomy or radiotherapy.[910] There are no differences in age at presentation between single or multiple glioblastomas, radiological findings, or biology.[15]

The reasons of leptomeningeal spread without surgical procedure are unknown. Although nothing is known about the pathogenesis of these multicentric gliomas, multicentric and multiple gliomas could be a distinct disease. Multiple gliomas are thought to spread along CSF, white matter pathways, and local invasion. The patient presented a CSF fistula and a continuous lumbar drainage was placed. This could produce a high flow of CSF that could benefit the diffusion of tumoral cells. However, this was placed 2 days after surgery and the diagnosis was made 1 week after surgery, hence this is highly unlikely. In addition, with respect to CSF spread, metastases should be placed on the surface, which is unlikely in an intramedullary tumor. However, our case, according to 2 previously cases published,[910] presented a tumor in the atrium, possibly infiltrating the occipital horn of the lateral ventricle. Nevertheless, no abnormal cells were found in CSF cytology. The subventricular zone harbors cell with proliferative potential and has been described as an area which can result in multiple and multicentric GBM, with the expression of metalloproteinase and mesenchymal markers associated with poor prognosis and related to tumor spread as IDH1 or YKL40.[1314] Conversely, it has been described different histopathological grades in multicentric glioblastomas.[25] This may support the hypothesis that multicentric gliomas are low grade malignancy,[5] and that they arise from separate focus of the brain and spine, which would support the fact that GBS is a diffuse disease. Furthermore, the presence of tumoral cells have been seen even 3 cm away from neuroimaging enhancement area, which also suggests the same.[34] The diffuse nature makes treatment for glioblastoma treatment a challenge. The treatment should combine surgery, radiotherapy involving a safe margin, and chemotherapy. New immunological techniques can also play an important role.

Treatment options are still open to debate. An aggressive approach is recommended by some authors,[16] although others recommends biopsy because extent resection of multicentric lesions have obviously more technical difficulty and poor prognosis.[812] Regarding radiotherapy treatment, some studies support that craniospinal radiotherapy is reasonable when CFS dissemination occurs.[611] No significant differences were found in the median time to progression or survival time between conformal radiotherapy and whole brain radiotherapy.[14]

To our knowledge, our case is the first case report in the literature presenting with a multicentric brain, cervical and lumbar glioblastoma, without previous therapeutic intervention. This confirms that GBM is a diffuse disease, and the more extended it is the worse prognosis it has. The management remains still controversial and further studies are required to know prognosis factors of dissemination.

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Conflicts of interest

There are no conflicts of interest.