Paragangliomas are neuroendocrine tumors, usually originating from the adrenal gland. They are usually benign and nonfunctioning[1–3] and rarely observed in the central nervous system. More than 90% of central nervous system paragangliomas manifest as carotid and glomus jugulare tumors. Spinal paragangliomas (SPs) are quite rare[1–5] and were first defined by Miller and Torack and Lerman et al. Clinical findings of SPs generally include nonspecific spinal cord pressure findings. The diagnosis of an SP is based on histopathological findings due to the absence of specific clinical and radiological findings.[3,7]
Herein, we describe surgical treatment and follow-up outcomes of 8 patients with a prediagnosis of a spinal intradural mass lesion who underwent surgery between 2011 and 2017. All the patients were diagnosed with a paraganglioma histopathologically.
2 Material and methods
This study is a retrospective analysis of the files of patients with a prediagnosis of a spinal intradural tumor who underwent surgery between 2011 and 2017. All the patients were subsequently diagnosed with a paraganglioma. Patients whose files were incomplete were excluded from the study. Patients were evaluated with regard to age, sex, tumor location, complaints on admission, neurological examination findings (Frankel classification), spinal computed tomography (CT) findings, spinal magnetic resonance imaging findings, duration of follow-up, and recurrence (Table 1).
In total, 8 patients (4 females, 4 males) were included in the study. The mean age of the patients was 51.1 years (28–64 years). The mean duration to admission was 6.5 months (3 weeks to 24 months). The main complaints were lumbar pain, lower back pain, and leg pain. Some patients also had hypoesthesia, neurogenic claudication, and motor deficits.
When the patients’ files were evaluated, it was determined that radiographic diagnosis could not be performed as part of the preliminary diagnosis process. With the exception of 1 subject diagnosed with recurrent paraganglioma, surgeries were conducted on the basis of a prediagnosis of schwannoma, meningioma, and ependymoma. It was determined that the radiologic diagnosis could not be made in the preliminary diagnosis of all patients, when evaluated on the basis of the patients’ files. Apart from a patient diagnosed with recurrent paraganglioma, others were operated on based on the presumption of schwannoma, meningioma, and ependymoma. The patients underwent general anesthesia and neuromonitoring with microsurgical techniques. Pathological results revealed spinal intradural extramedullary paraganglioma. Vanil-mandelic acid was negative in the patients’ urine, and their abdominal ultrasonography and CT of the whole abdomen and thorax were considered normal. No multiple paragangliomas were found by clinical investigation.
Total surgery was performed in 7 patients. One patient had undergone subtotal resection at another center in 2005 but underwent surgery again in 2014 due to recurrence of complaints. However, residue was left due to common nerve adhesion.
The neurological examination was evaluated according to the Frankel classification system. During the postoperative period, a 1-stage improvement was observed in 2 patients. No differences were observed in the other 6 patients (as 5 patients did not have deficits, and postoperative deterioration was not observed).
The mean duration of follow-up was 46 months (8–80 months). Recurrence did not occur in 7 patients. One patient with a residual tumor continues to be followed (Table 1 and Figs. 1–3).
Tumors usually had a well-circumscribed nodular appearance. For example, the macroscopic examination of case 4 showed a well-circumscribed tumor with nodular appearance (size: 5.5 × 2.5 × 1.5 cm). Microscopic examination revealed an invasive tumoral lesion with local zellballen nests across a large section and with solid pattern. Tumor cells displayed hyperchromatic nuclei showing small round pleomorphisms with eosinophilic cytoplasm locally. Diffuse positive staining was observed in tumor cells with cluster differentiation 56 and chromogranin (neuroendocrine differentiation markers). No staining was observed with epithelial membrane antigen. Sustentacular cells were stained with S100 (Fig. 4).
According to the World Health Organization (WHO) classification, paragangliomas are grade 1 tumors which develop from neural crest cells. They may be secretory, although the vast majority is nonsecretory. Although paragangliomas mainly originate from sympathetic system cells, 80% to 90% of paragangliomas are located in the carotid and glomus jugulare regions and are of parasympathetic system origin. Secretory paragangliomas usually do not lead to clinical findings, although they produce excessive amounts of catecholamines.[3,4,8,9] They are usually benign and grow slowly. The rate of malignant transformation was reported to be 2.4% to 14% in the literature.
With regard to the demographic characteristics of patients, paragangliomas are generally seen in individuals aged 9 to 74 years, with a slight male predominance (male:female ratio of 1.4:1). The most common complaints upon admission include lower back pain and leg pain, sometimes with urinary incontinence and paraparesis.
According to the literature, paragangliomas rarely occur in the orbits, larynx, vagal nerve, gastrointestinal tract, urinary tract, or thyroid gland. Intraspinal paragangliomas are quite rare.[3,4] The incidence of SPs is unknown. In the literature, SPs were reported to be mainly located in the lumbar and sacral regions.[5,10] In all of our cases, the lesion was located in the lumbar region.
Clinical manifestations of SPs are nonspecific. Patients are usually admitted with lower back pain, leg pain, hypoesthesia at various levels, neurogenic claudication, and incontinence due to cord pressure. Secretory-type paragangliomas may present with hypertension, palpitation, tremor, vomiting, and weight loss.[3,4] None of our patients had clinical findings of secretory-type paragangliomas.
According to the literature, SPs do not have specific radiological findings and do not lead to bone erosion and destruction. The lesion is observed as a mildly calcified homogenous mass, with an intense vasculature and foraminal enlargement on spinal CT.[9,11,12] They appear as hypo-isointense on T1W1 spinal magnetic resonance imaging images and as iso-hyperintense homogenously contrasting masses on T2W1 images.[9,10] SPs are difficult to distinguish from neuromas and ependymomas radiologically. In the present series, the radiological images were consistent with those in the literature. However, they could not be distinguished from other tumors (Table 2).[13–17]
Histologically, paragangliomas are composed of balls of cells (zellballen), which are usually well encapsulated, very rich in vascular stroma, and supported by vascular sinusoids. Immunohistochemically, the main cells are stained with neuron specific enolase, chromogranin, and synaptofizin, and fusiform sustentacular cells are stained with S-100 protein and glial fibrillary acidic protein.[3,4] It is difficult to discriminate between benign and malignant paragangliomas, as there is relatively little invasion of neighboring tissues. Metastasis has been reported in 7% of malignant paragangliomas. Therefore, the histopathological assessment should include not only a microscopic examination. In the present series, the histopathology results were benign in all cases.
Primary treatment of a paraganglioma involves total excision, as the tumor is well encapsulated. The prognosis following total surgical resection is very good in cases of benign paragangliomas. In their review, Gelabert-Gonzales reported a local recurrence rate of 2.2% in cases of total excision and 5.4% to 10.5% in cases of subtotal excision. In a study by Yin et al of SPs in 18 patients, they observed recurrence in only one patient. Mishra et al reported no recurrence in eight patients with SPs. The role of postoperative radiotherapy or chemotherapy in cases of paragangliomas is controversial. It is recommended for patients who do not undergo surgery.[3,4,21,22] In the present series, total excision was performed in seven patients. Adjuvant therapy was required and relapse occurred in no patients. Residual tissue was left in 1 patient due to widespread adhesions. This patient was re-operated on due to recurrence. This patient continues to be followed.
SPs are relatively rare and usually benign tumors. The prediagnoses include neuromas, schwannomas, and ependymomas due to the difficulty in making a diagnosis based on radiologic findings. Total resection is important at the time of surgery to prevent recurrence and ensure progression-free survival. Primary treatment includes total surgical resection. Chemotherapy and radiotherapy are supportive treatments, but their use is controversial. The current consensus is that they are not effective. The patient's prognosis depends on a correct diagnosis prior to surgery and total resection.
We consider that long-term follow-up is important in cases of paragangliomas. Early recognition of malignant transformation may improve the success of treatment in patients who are not diagnosed based on histopathological findings. Such early recognition can improve the quality of life of patients.
Conceptualization: Okan Turk.
Data curation: Okan Turk, Can Yaldız.
Formal analysis: Okan Turk, Can Yaldız, Veysel Antar, Sebnem Batur, Nuriye Guzin Ozdemir.
Funding acquisition: Can Yaldız, Veysel Antar, Nail Demirel, Nuriye Guzin Ozdemir.
Investigation: Can Yaldız, Nail Demirel, Nuriye Guzin Ozdemir.
Resources: Veysel Antar, Sebnem Batur, Burak Atci.
Software: Burak Atci.
Supervision: Ayhan Kocak.
Visualization: Ayhan Kocak.
Writing – original draft: Can Yaldız, Okan Turk, Sebnem Batur.
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