April Issue.indd

1Department of Neurosurgery, Royal Liverpool Children’s NHS Trust and Walton Centre for Neurology and Neurosurgery NHS Trust, Liverpool, UK

Correspondence to: D. F. O’Brien, Department of Neurosurgery, Royal Liverpool Children’s NHS Trust, Alder Hey, Eaton Road, Liverpool, L12 2AP, UK Email: dfobstl@hotmail.com

Introduction

A 26-year-old man presented with left leg pain and progressive paraparesis. Imaging revealed a large intradural tumour compressing the cauda equina. The lesion was radically resected and histological analysis revealed it to be a paraganglioma. The clinical features of this rare tumour are described with a review of the literature

Paragangliomas of the cauda equina were first described in 1970 and are generally found in the middle-aged population, ranging from 13 to 71 years.^2,8 Although morphologically similar to adrenal tumours of this type, paragangliomas of the cauda equina differ in that the vast majority (97%) do not secrete catecholamines.^1-3 As they are relatively uncommon and their diagnosis often unexpected, we illustrate a case of a cauda equina paraganglioma. We also highlight the biochemical and clinical features peculiar to other paraganglioma cases.

A 26-year-old gentleman presented with a two-year history of progressive weakness and pain in his left lower limb. He was unable to walk or stand unaided. Examination of his lower limbs revealed left-sided proximal muscle power of 2/5 and there was no power in the anterior tibialis or extensor hallucis longus. Right lower limb proximal muscle power was 4+/5 with normal distal power. His knee and ankle jerks were absent bilaterally. Sensation was decreased to light touch and pin-prick in his left lower limb, particularly in the fourth and fifth lumbar dermatomes. Neurological examination was otherwise normal.

Figure 1a: Showing a large contrast enhancing tumour filling the spinal canal. Axial view.

Figure 1b: Sagittal MRI of lumbar spine showing the extent in cross-section of the lesion.

Magnetic resonance imaging (MRI) of the lumbar spine revealed a large intradural mass in the spinal canal, extending from the second to the fourth lumbar vertebrae (Figures 1a and 1b). The tumour was multilobulated, predominantly low signal on T1, intermediate signal on T2 and enhanced avidly following the administration of dimeglumine gadopentetate (magnevist). The lesion had caused scalloping of the posterior aspect of the L3 vertebral body and had eroded its pedicles. It extended into the exit foraminae of the L2/3 and the L3/4 interspaces bilaterally.

On the day following admission, an L1-L5 bilateral laminectomy was performed. A vascular tumour was seen penetrating through a large dural defect. Frozen section revealed it to be a paraganglioma. Nerve root bundles were seen at L2 entering the tumour mass on the left and right hand sides and continuing caudally on both sides of it. Initially, the tumour bulk was internally decompressed with the ultrasonic aspirator and the remainder was resected using sharp micro-dissection.

Figure 2a: Sagittal MRI following surgery showing complete resection of the tumour.

Figure 2b: Axial image showing the nerve root bundles at the periphery of the spinal canal bilaterally.

Following resection, two nerve root bundle masses were seen in continuity in the lateral recesses of the spinal canal. The dural defect was repaired with an absorbable synthetic dural patch and a lumbar drain was left in situ for five days. Post-operatively, the patient’s lower limb weakness gradually improved and at discharge, ten days later, he was walking with the aid of a walking stick.

Imaging at three months post-resection revealed no residual tumour (Figures 2a and 2b). Currently, two years post-surgery, he has returned to his previous occupation.

Paragangliomas are generally non-secreting (nonchromaffin) tumours that arise from neural ectoderm. They are thought to arise from autonomic ganglionic tissue. The incidence of catacholine secretion is of the order of 1-3%.

They are typified by the glomus jugulare and carotid body tumours.^4,10,13 They can occur in many diverse and unusual sites, such as the orbit, maxilla, larynx, thyroid gland, mediastinum, lung, para-aortic and retroperitoneal region.^2,5,13 Within the spine, paragangliomas are most frequently located in the intradural, extramedullary compartment at the level of the cauda equina.⁴ Other spinal levels are far less commonly affected.⁸

Paragangliomas of the cauda equina more commonly present with symptoms due to cauda equina or selective nerve root compression.^1-3 The typical patient presents with lower back pain of months to years in duration.^4,12,13 Sciatica is also a common feature, along with other neurological features such as paresis, dysaesthesia and sphincter disturbances.^6,8,12,13 Due to the difficulty in distinguishing these neoplasms from benign degenerative conditions of the lumbar spine they tend to be diagnosed at an advanced stage of growth.⁷

T-1 weighted MRI with contrast agent is currently the most effective way of imaging these tumours.^1,2,12 Paragangliomas in this region are indistinguishable on MRI from myxopapillary ependymomas, a common tumour of the cauda equina.⁴ Other tumours occurring here include schwannomas, dermoid lesions, lipomas associated with spinal dysraphism and metastatic lesions. Radiolabelled metaiodobenzylguanidine (mIBG) scanning may be helpful in delineating small paragangliomas not readily seen on MRI. Metaiodobenzylguanidine, a noradrenaline analogue, allows visualisation of the adrenal medulla and biochemically-related tumours including paragangliomas. As the uptake of mIBG is not related to catecholamine secretion, it allows for identification of tumours without endocrine activity.¹

Functional paragangliomas secrete norepinephrine and epinephrine producing symptoms similar to phaeochromocytoma. Their metabolites vanillylmandelic acid (VMA) and metanephrine act as tumour markers. These may be obtained as a pre-interventional base line, with future samples being taken as a guide to the success of therapy.⁷

When viewed histologically, the majority of extra-adrenal paragangliomas resemble the normal adrenal gland, although the neoplastic cells are frequently larger and more irregular in shape than typical adrenal cells.1 They appear as a highly vascular uniform proliferation of polygonal or rounded cells, arranged in clusters, referred to as Zellballen.^1,10 The principal cell types are chief cells (type 1 cells) and sustentacular cells (type 2 cells).1 The relationship between these two cell populations is interesting in that there is a correlation between more active tumours and decreased numbers of sustentacular cells.^1,2

Where paragangliomas occur as familial cases (more common in males), the mode of inheritance is thought to be autosomal dominant, with partial penetrance.^2,5,14 To date, however, there have been no reports of familial cauda equina paragangliomas.8 While the exact pathogenesis of this is unknown, the presence of the mdm2 protoncogene, which produces a protein inhibiting the function of the p53 and Rb proteins, may play a significant role in the proliferation of these tumours.⁹

Where possible, the treatment of choice for paragangliomas is surgical excision.^2,5,7 However, in some cases, this is not possible due to adherence of and traversing of nerve roots, local invasion through the dura and prominent tumour vascularity. Although endocrine activity is uncommon,2 the importance of pre-operative evaluation of urinary VMA and metanephrines levels must be stressed, as intraoperative hypertensive crises may result from manipulation of the tumour.^2,3,5,8

Surgery followed by adjunctive radiotherapy, has been found to be more effective than surgery alone in the treatment of large tumours where gross total resection is not possible.¹¹ Results with chemotherapy have been disappointing and its use alone, or as an adjuvant to the surgical treatment of these neoplasms has shown no consistent benefit.^5,10 In patients with unresectable tumours, the use of radioiodine labelled mIBG therapy could prove valuable as a non-surgical therapeutic agent. The general response to I-131 mIBG has been interuption of disease progression, improvement in patient symptoms and a remission rate of at least three years.¹

The most effective combination therapy for metastatic paragangliomas causing spinal cord compression is a surgical decompression followed by a course of radiotherapy, with radiotherapy alone an alternative to surgery for effecting local control in candidates unsuitable for surgery.^2,10

A patient presenting with backache and sciatica may infrequently have a tumour compressing the cauda equina. Paraganglioma is a rare example of one such tumour. Patients with a paraganglioma of the cauda equina do well following a complete resection.

1. Noorda JP, Wuisman PIJM, Kummer AJ, Winters HA, Rauwerda JA, Egeler-Peerdeman SM. Nonfunctioning malignant paraganglioma of the posterior mediastinum with spinal cord compression. A case report. Spine 1996;14:1703-1709.

2. DeVita TV, Hellman S, Rosenberg SA. Cancer of the head and neck. In: DeVita TV, Hellman S, Rosenberg SA, editors. Cancer: Principles and practice of oncology. Philadelphia: Lippincott-Raven; 2001. p. 841-46.

3. Wiley C. Unusual tumours of the mediastinum. In: Williams CJ, Keikorian JG, Green MR, Raghavan D, editors. Textbook of Uncommon Cancer. Oxford: Wiley and Sons; 1998. p. 437-39.

4. Sundgren P, Annertz M, Englund E, Stromblad L, Holtas S. Paragangliomas of the spinal canal. Neuroradiology 1999;41:788-94.

5. Blades DA, Hardy RW, Cohen M. Cervical paraganglioma with subsequent intracranial and intraspinal metastases. Case Report. J Neurosurg 1991;75:320-23.

6. Cybulski GR, Nijensohn E, Brody BA, Meyer PR, Cohen B. Spinal cord compression from a thoracic paraganglioma: A case report. Neurosurgery 1991;28:306-309.

7. Wang CC. Paraganglioma of the Head and Neck. In: Williams CJ, Keikorian JG, Green MR, Raghavan D, editors. Textbook of Uncommon Cancer. Oxford: Wiley and Sons; 1998. p. 725-29.

8. Soffer D, Scheithauer B. Paraganglioma. Pathology and genetics of tumours of the nervous system. In: Kleihues P, Cavenee WK, editors. World Health Organisation classification of tumours. Lyon: IARC Press; 2000. p. 12-114.

9. Lam KY, Wat NMS, Luk JM, Lam KSL. The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas. J Clin Path 2001;54:443-48.

10. Brodkey JA, Brodkey JS, Watridge CB. Metastatic paraganglioma causing spinal cord compression. Spine 1995;20:367-72.

11. North CA, Zinreich ES, Christensen WN, North RB. Multiple spinal metastases from paraganglioma. Cancer 1990;66:2224-28.

12. Haslbeck KM, Eberhardt KE, Nissen U, Tomandl BF, Stefan H, Neundorfer B, Erbguth F. Intracranial hypertension as a clinical manifestation of cauda equina paraganglioma. Neurology 1999;52:1297-98.

13. Taxy BJ. Paraganglioma of the cauda equine. Report of a rare tumour. Cancer 1983; 51:1904-1906.

14. Chew SL. Paraganglioma Genes. Clinical Endocrinology 2001; 54: 573-74.

Paraganglioma of the cauda equina: A case report and literature review