Case report
Paraganglioma of the lumbar spinal canal – case report

Communicating author:
Jerzy Słowiński, MD, Department of Neurosurgery and Neurotraumatology, Al. Legionów 10, 41-902 Bytom, Poland. Tel. +48 32 281 02 71,
fax +48 32 281 02 70, e-mail: slovy@mp.pl





Introduction
Extraadrenal paragangliomas are benign lesions of neuroendocrine origin. They are derived from chemoreceptors’ cells, and observed usually in the carotic body and glomus jugulare [3,9]. Their location in the spinal canal is rare, and usually confined to the cauda equina and filum terminale. Spinal paragangliomas are encountered in adolescents and adults, with the peak incidence in the fifth decade [7,13]. We present a case of spinal root paraganglioma which developed in the lumbar segment of the spine.
Case report
A 46-year-old woman was admitted to the Department of Neurosurgery in Bytom, Poland with a history of right-sided lumboischialgia. The patient had L4-L5 fenestration on the right side four years earlier because of intervertebral disc hernia, diagnosed in computerized tomography scan. Preoperative magnetic resonance imaging (MRI) study showed recurrent L4-L5 hernia and intradural tumour located medially at the L3 level. The tumour, 7x6x6 mm in diameter, adhered to the dorsal aspect of the dura and spinal root and enhanced homogenously after gadolinium (Fig. 1 A-C). The L3 laminectomy was performed and the total removal of intradurally located tumour was achieved. The tumour was soft, round, bluish in colour, and contiguous with the spinal root. The L4-L5 intervertebral disc hernia was removed by refenestration at the same time. The lumboischialgia disappeared soon after the operation. In the two years follow-up the patient has no neurological or radiological signs of tumour or hernia recurrence (Fig. 1 D). Histological examination showed a typical picture of paraganglioma, composed of cells balls (zellballen) formed by nests of chief cells, separated from each other by fibrovascular septa (Fig. 2 A, B). Closely packed chief cells had regular, round to oval nuclei and abundant, eosinophilic cytoplasm. Some tumour regions showed extensive areas of hyalinization and fibrosis with secondary trabecular arrangement of tumour cells. There were no mitotic figures.
For immunohistochemistry, paraffin 3? m-thick tissue sections were used. The primary antisera (all from DAKO, Denmark) against the following antigens were used: neurofilament proteins (cat. no N1591), chromogranin A (N1535), neuronal specific enolase (N1557), S-100 protein (N1519), synaptophysin (N1566), cytokeratin (M0821), glial fibrillary acidic protein (GFAP) (N1506) and Ki-67 (N1633). The anti–cytokeratin antibody was diluted 1:50, remaining antisera were obtained pre-diluted from the manufacturer. Antibody binding was visualized by the labelled streptavidin-biotin complex technique with LSAB+ kit (DAKO, K0690) for detection of cytokeratin and LSAB (DAKO, K0675) for detection of other antigens, using diaminobenzidine as a chromogen. The sections were counterstained with Mayer’s hematoxylin solution.
The chief cells were immunopositive for chromogranin A (CHR), neuronal specific enolase (NSE), synaptophysin (SF), and cytokeratin (CK) (Fig. 3A) and negative for neurofilament proteins (NF). Sustentacular cells, with their elongated processes encompassing nests of chief cells, were positive for S-100 protein, some of them were also GFAP-positive (Fig. 3 B). The tumour cells showed no proliferative activity (Ki-67 labelling index = 0%).

Discussion
Paragangliomas are neuroectodermal tumours of the autonomic paraganglia, derived from the chromaffin cells of neural crest origin [10]. Their location within the central nervous system is unusual. Intracranially, paragangliomas were encountered in the sellar, pineal and petrous ridge regions [3]. Spinal paragangliomas are rare, most of the single reported cases occured in the cauda equina and filum terminale region [1,5,10,11-13]. Interestingly, a series of 30 spinal paragangliomas reported by Moran et al. [7] consisted of nineteen tumours located in the lumbar segment of the spine, six in the cauda equina, two in filum terminale, two in the thoracic and the remaining two in the cervical region of the spinal canal.
Spinal paragangliomas are presumably derived from ganglionic cells, normal paraganglions associated with blood vessels or from residual peripheral neuroblasts, which can give rise to either chemoreceptor or ganglion cells [5,10].
Spinal paragangliomas are benign, slowly growing tumours with low proliferative activity [1,8,9]. They may be associated with syringomyelia [10] or intramedullary cyst [3]. Clinically relevant secretory activity of spinal paraganglioma cells (e. g. release of catecholamines) is a rare phenomenon and can be induced by surgical manipulations of the tumour [12].
Histologically, spinal paragangliomas are generally identical to paragangliomas in other locations. Some variants of classic paraganglioma, including oncocytic metaplasia, the presence of spindle cell component, melanin pigment and ganglion cells have been observed in spinal paragangliomas [7].
The histological picture of the presented case, with alveolar „zellballen” pattern is typical of paraganglioma located elsewhere in the body.
Immunopositivity for neuroendocrine markers – chromogranin A, synaptophysin and neuronal specific enolase in chief cells and positive reaction for S-100 protein in sustentacular cells supported the histological diagnosis in the presented case. These markers are useful in the differential diagnosis of paragangliomas [7,8,9,13]. Positive reaction for NSE, CHR and SF was found by Moran et al. [7] in 100%, 91% and 91% of thirty spinal paragangliomas, and thus are the most consistent immunohistochemical findings in these tumours. Differential diagnosis of spinal paragangliomas should first of all include myxopapillary ependymomas and neurinomas. These last two entities are negative for neuroendocrine markers, furthermore, ependymomas are usually strongly GFAP and S-100 protein reactive [7,13]. Other antigens, less frequently detected in spinal paragangliomas, include leu-enkephalin, somatostatin, cytokeratin, neurofilament proteins and ACTH [7].
Another valuable tool in the diagnosis of paragangliomas is the electron microscopy. The presence of membrane-bound, electron dense neurosecretory granules in the cytoplasm, supports the diagnosis of neuroendocrine tumour [1,5,13].
Neuroradiological picture of the spinal paragangliomas usually consists of the intradural mass, isointense with spinal cord [3] and enhancing with gadolinium-DTPA [6,10].
In most cases of spinal paragangliomas surgical cure can be achieved, provided that total resection was accomplished [9,11], however, recurrencies with progression of the disease [11] and even metastasizing outside the spinal canal [2,7] have been reported. On the other hand, vertebral metastases with spinal cord compression from carotid body [6] and retroperitoneal [4] paragangliomas were reported.
In the presented case a small paraganglioma, located intradurally at the L3 level was probably asymptomatic and diagnosed incidentally only thanks to the follow-up MRI examination, performed in the patient with a history of previous lumbar disc surgery. This explains that, to our knowledge, it is the smallest spinal paraganglioma reported in the literature. Yoshida et al. [13] reviewed 69 spinal paraganglioma cases and found that they measured from 15 to 100 mm in the greatest diameter, tumours in a series of Moran et al. [7], encompassing 30 cases, measured from 10 to 50 mm.
The radicular pain in our patient was most likely caused by recurrent L4-L5 disc hernia. Nevertheless, the presented case supports the value of MRI study in the early diagnosis of spinal tumours and prompts to include paraganglioma in the differential diagnosis of extramedullary lesions.

Acknowledgements
This work was partly supported by grant NN-5-432/04 from the Medical University of Silesia in Katowice, Poland.

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