Introduction

Paragangliomas are usually benign tumors which can occur in many sites of the body, from the base of the skull down to the pelvic floor. They are derived from the neural crest cells. Although uncommon, paragangliomas are known to affect the central nervous system most commonly the glomus jugulare and filum terminale [1]. Those that arise in the sellar region are extremely rare [2]. Here we report a case of sellar Paraganglioma.

Case description

A 17-year-old male presented to us with history of mild headache of 2 months, blurring of vision in both eyes of 15 days, and diplopia of 10 days in October 2005. General physical examination did not reveal any abnormality. Visual acuity was 6/6 in both eyes. Visual fields were normal in both eyes. There was diplopia on looking toward left side. Other cranial nerves were within normal limits. There was no motor or sensory deficit. Contrast-enhanced MRI of the brain was ordered which showed a well-defined mass in the sellar and parasellar region of size 2.7 × 2.8 × 2.5 cm. The mass was isointense on T1 and hypointense on T2 weighted images (Figs. 1, 2). A provisional diagnosis of pituitary adenoma was made. Serum prolactin, growth hormone, T3, T4, and TSH were within normal range.

Fig. 1
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Sagittal MRI cut showing mass in the sella

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Fig. 2
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Axial MRI slice at the level of sella showing a well-defined mass in the sella

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He then underwent trans-nasal trans-sphenoid biopsy from the mass in November 2005. Per-operatively it was a highly vascular firm to hard tumor. On histopathologic examination, the tumor tissue, present in multiple fragments, showed cells arranged in a nested pattern with a richly vascularized delicate connective stroma around the nests. The cells displayed round to oval nuclei with vesicular chromatin and prominent centrally placed nucleoli with moderate to abundant eosinophilic cytoplasm. Nuclear pleomorphism was of a moderate degree and no areas of necrosis were evident and mitotic figures were rare (Fig. 3a). The reticulin stain (Fig. 3b) shows the classic Zellballen pattern. Immunohistochemically, the tumor cells were positive for chromogranin A (CGA) (Fig. 4), neuron specific enolase (NSE) (Fig. 5), and synaptophysin. They were negative for cytokeratin, vimentin, glial fibrillary acidic protein (GFAP), Prolactin, growth hormone, ACTH, TSH, FSH, LH, S-100, and EMA. MIB1 proliferation index is ∼5% in the highest labeled area. Based on these morphologic and immunohistochemical features, a final diagnosis of paraganglioma was offered. Twenty-four-hour Urine 5-Hydroxy indole acetic acid, epinephrine, and nor-epinephrine were within the normal range. Metastatic work up including CECT of chest and abdomen and bone scan revealed no abnormality.

Fig. 3
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(a) H&E photomicrograph. Tumor cells arranged in a ‘Zellballen’ pattern, with intervening dilated vascular channels. (b) Reticulin staining showing the classic ‘Zellballen’ pattern

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Fig. 4
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The tumor cells are positive for chromagranin A

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Fig. 5
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The tumor cells are positive neuron-specific enolase

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He received postoperative radiotherapy by Stereotactic radiotherapy 50 Gy/25 Fractions over 5 weeks. He completed his radiotherapy in Feb 2006. Patient showed much improvement symptomatically. Headache resolved but diplopia remained static. Four months after treatment, the patient came back to us with a swelling on the right side of head. Local examination showed a bony hard mass of size 3 × 3 cm in the right parietal region. There were no swellings anywhere else in the body. Bone scan was repeated which showed extensive skeletal metastases to skull, right acetabulum, and right femur. Incisional biopsy from the skull lesion showed metastatic paraganglioma. CECT of chest and abdomen was repeated which revealed normal lungs, adrenals, and liver. Twenty-four-hour urinary 5-Hydroxy indole acetic acid was 16.2 mg (normal range: 2–6 mg). Twenty-four-hour urinary epinephrine level was 3.48 μg (normal range: <20 μg) and nor-epinephrine was 13.63 μg (normal range: <90 μg). 1-131 MIBG scan was normal. He received palliative radiotherapy for his bone metastases. Patient was offered zoledronic acid for bone strengthening and palliative chemo with Carboplatin and Etoposide.

Discussion

Paragangliomas are tumors derived from neural crest cells. About 90% of them arise from the adrenal medulla which has the largest collection of chromaffin cells. These tumors in this location are called pheochromocytoma. The remaining 10% arise from extra adrenal sites [3]. Glomus tumors, chemodectomas, nonchromaffin tumors, carotid body tumors, etc are the different synonyms given to these tumors that are seen in the Head and neck region. They are very rare in the central nervous system. Sellar and supra sellar ones are confined to case reports only. Till date only 11 cases of sellar paraganglioma have been reported in literature [1, 4–12].

Generally the adrenal paragangliomas secrete catecholamines. Extra adrenal ones are generally nonfunctional [13]. In our case it was nonsecretory in the beginning, but once the disease had spread the catecholamine levels were elevated. Paragangliomas are usually benign and vascular tumors. They are slow growing. About 3% cases are malignant [14]. The reported cases of Sellar and suprasellar paragangliomas were all benign ones. Our case is exceptional as it is highly malignant and has metastasized within a span of 4 months.

Clinical history, physical examination, radiographic investigation, as well as intraoperative gross observation are the same as any other mass lesion in the sella-like meningioma or pituitary adenoma. Histologically they are composed of two types of cells—the chief cells and sustentacular cells (modified Schwann cells). They are characteristically arranged in a Zellballen pattern. They generally function as chemo receptors [15]. Immunohistochemistry, using neuroendocrine markers and electron microscopy are the two definitive diagnostic methods to differentiate paragangliomas from pituitary adenomas and meningiomas. Meningiomas express EMA, pituitary adenomas usually express pituitary hormones, Paragangliomas are positive for chromogranin and synaptophysin stains [16].

Surgical removal of these tumors is difficult, and the trans-sphenoidal approach usually results in limited resection. Most authors who published reports on this tumor recommended radiation therapy after partial removal of the tumor. The role of postoperative radiotherapy in a completely resected case is a matter of debate. Taking into account the risk of radiation-induced endocrine insufficiency and optic neuropathy; some authors reserve postoperative adjuvant therapy only if the symptoms or signs of cranial nerve compression persist following maximal tumor removal, or if there is evidence of subsequent growth of residual tumor. Due to scarcity of cases it is difficult to come to a solid conclusion in this matter. We feel that Surgery followed by postoperative radiotherapy would be the ideal treatment in these cases. Anyway in our case only biopsy was possible so radiotherapy was indicated.

Our case is exceptional from the other reported cases since it has metastasized to bone. We could not find even a single case of sellar paraganglioma with bone metastasis in the literature. A detailed literature review did not reveal bone metastases or metastases to other areas in any of the reported 11 cases. All were locally confined, while some did recur locally. Paragangliomas without sustentacular cells or lacking S-100 reactivity are considered more aggressive than those without. This is certainly exemplified by our case. Once the disease has metastasized there is only role for palliative treatment.