Primary spinal glioblastoma multiforme: a case report

INTRODUCTION

Spinal cord tumours in adults mostly occur at the extramedullary space.¹ Out of the intramedullary tumours, the most common is astrocytoma.² This is in contrast to that seen in children where ependymomas are much more prevalent.²

Spinal cord glioblastoma multiforme (GBM) is a unique tumour type which accounts for a small percentage of all tumours of the spinal cord.³ Defined by world health organisation (WHO) as a grade IV astrocytoma, is a highly malignant central nervous system (CNS) tumour that is histologically, genetically, and clinically heterogeneous.³

According to our literature review, less than 200 cases of primary GBM have been reported. Based on these, the tumour is regarded more prevalent in young men and occurs more commonly in the cervical and thoracic area.⁴ For establishing a diagnosis, MRI, IHC and HPE are indispensably required.⁵ Clinical manifestations are dependent almost entirely upon the location and extent othethe tumour.⁶

Currently the most recommended management is similar to that of its intracranial counterpart, which consists of surgical excision along with adjuvant temozolamide and RT.⁷ However, despite prompt intervention it has an aggressive course and an invariably dreadful prognosis such that the median survival is estimated at just ~11 months.⁴

CASE REPORT

A 35 year female, with no known comorbidities presented to our institute with a complaint of lower back pain for 1 month. The pain was insidious in onset, mild in severity, intermittent in nature and radiated to bilateral thighs. It was also associated with tingling sensation and numbness over both feet (right>left). She also had a history of loss of bladder control. Around 2 months earlier, the patient was evaluated elsewhere and managed as a case of myxopapillary ependymoma, with laminectomy and micro-surgical excision revealing tumour at conus medullaris and surrounding the filum terminale.

At our institute, the patient was conscious, oriented and had a GCS score of 15. She had normal power across all joints in all 4 limbs. She had reduced sensory perception for all the modalities below L1 level. Her DTR was brisk in the lower limb. Upper limbs and cranial nerve examination was within normal limits. Routine blood investigations were unremarkable.

MRI lumbosacral spine with contrast revealed a well-defined rounded intradural hyperintense lesion at the level of L1-L2 vertebrae that was consistent with a residual tumour.

Given this, the patient underwent re-surgery under general anaesthesia. L1-L2 re-exploration and near total excision of the mass was performed. On opening dura, a fibrous band (probably tumorous) was seen entering into the subarachnoid space, which was continuous with the residual tumour. The Tumour was soft, partly fibrous, which was amenable to cavitron ultrasonic surgical aspirator (CUSA). It had a very poor plane with adjacent nerve roots and conus medullaris. Near-total resection could be achieved with bits of tumorous tissue left at the upper pole where it was indistinguishable from conus medullaris.

HPE and IHC were used and the diagnosis of GBM Grade IV was formulated in accordance with the WHO criteria. IHC showed positivity for ATRX, p53 and negativity for EMA, D240. Malignancy also exhibited an elevated MIB-1 labelling index ranging ~8-10%.

Postoperatively, Karnofsky performance status (KPS) score was 80%. Preoperative complaints showed improvement. An MRI (plain and enhanced) of the head disclosed no abnormalities. Lumbar puncture was performed, which was again normal. The cerebral spinal fluid (CSF) showed no malignant cells. Subsequently, patient received conformal external beam RT to postoperative site on 6 MV LINAC for 50.4 Gy in 28 fractions with concurrent temozolamide followed by 6 cycles of adjuvant temozolamide.

MRI lumbosacral spine showed a heterogeneously enhancing intradural lesion at L1-L2. The patient came for follow-up 12 months after surgery, with headache secondary to increased intracranial pressure (ICP). Computed tomography (CT) of head showed blunting of sulcal subarachnoid spaces and brain surface. Her fundus examination revealed gross papilledema and diagnosis of benign intracranial hypertension was made. In view of this, she underwent right ventriculo-peritoneal shunting. Despite ventriculo-peritoneal shunting patient had only transient improvement for a few days and the patient had progressive worsening of vision and drop in sensorium.

Given the disease progression, further treatment was not deemed appropriate and the patient succumbed to the illness a few months later.

DISCUSSION

Spinal cord GBM is a unique tumour type which accounts for a small percentage of all tumours of the spinal cord.³ Less than ~5.5% of these originate in the conus medullaris making our case even more unique.⁸ However, some authors claim that the tumour location has no impact on the overall survival rate.⁹ At the time of diagnosis, the majority of spinal GBM cases exhibit severe disability.¹⁰ Consequently, an early diagnosis becomes essential for increasing the survival rate.¹⁷

The gold standard for establishing a spinal GBM diagnosis is MRI.¹¹ Most lesions arise as expansile and infiltrative masses with high T2 signal and demonstrate heterogeneous enhancement on post-contrast T1-weighted sequences.¹² Nevertheless, distinguishing spinal GBM from other spinal tumours is challenging. For tumours with vague MRI traits, F-18 fluoride deoxyglucose positron emission tomography (FDG PET) can be done.⁴ A newer modality that may assist in the diagnosis is diffusion tensor imaging and perfusion which shows decreased fractional anisotropy and increased relative cerebral blood volume for its cranial counterpart.¹³

Surgical intervention continues to deliver a definitive diagnosis via HPE, and at the same time is also therapeutic.⁵ The histological characteristics of this tumour are comparable to cerebral GBM, illustrating marked hypercellularity, nuclear atypia, microvascular proliferation and necrosis.¹⁴

IHC staining of most tumours shows a prominent expression of the p53 gene, positivity for GFAP and negativity for EMA.¹⁵ Some tumours also demonstrate overexpression of EGFR protein.¹⁵

Pathology

WHO grading of astrocytoma^19- Grade I: Pilocytic Astrocytoma, grade II: Low-grade Diffuse Astrocytomas, grade III: Anaplastic Astrocytomas and grade IV: Glioblastoma

Treatment

The conventional treatment for spinal GBM includes maximal resection, followed by RT given concomitantly with temozolamide followed by adjuvant temozolamide.⁷ Gross-total resection (no residual enhancement) is preferred, but near-total resection (thin rim of enhancement) is reasonable when margin between tumour and normal tissue is not precise.¹⁷ The most radical surgical technique is cordectomy which is reserved for lumbar or sacral tumours.¹⁸

Lately, targeted drug therapy is also being used to gain maximum survival benefit. Bevacizumab (BEV) a humanised monoclonal antibody against vascular endothelial growth factor A (VEGF-A) has potential benefits.¹⁹ Some authors have proposed an intrathecal regime of interferon-β via an ommaya reservoir.¹³

Prognosis is determined by CSF involvement, intracranial seeding and the use of adjuvant RT and temozolamide.²⁰ Thus, regular follow up is advocated.

CONCLUSION

Spinal cord GBM is an extremely unique tumour with a dismal prognosis. Aggressive management is required which includes maximal resection, followed by RT given concomitantly with temozolamide followed by adjuvant temozolamide. Regular follow up of CSF cytology and spinal MRI is advised. Further, a central registry and treatment trials are required to interpret this disease and improve survival.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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