Paraganglioma in the Lumbar Spinal Canal Treated by Surgery Assisted by MRI Neuroimaging and 3D Printing Reconstruction: A Case Report and Literature Review

Background: Ganglion cell paraganglioma is a subtype of neuroendocrine tumors, which is rare in clinical practice. Paraganglioma in the spinal area, especially in the spinal canal, is even rarer. Case presentation:The case we reported was a 46-year-old female who was admitted to the hospital due to "physical examination found a mass in the lumbar spinal canal for more than 2 months." After admission, the relevant examinations and preoperative preparations were perfected, and the posterior L2-3 spinal mass resection + spinal decompression + nail rod system internal xation was performed. The patient recovered well after the operation, and there was no tumor recurrence in follow-up. Conclusions:Surgical treatment assisted by MRI neuroimaging and 3D printing reconstruction technology may be an effective way to treat paraganglioma in the lumbar spinal canal. rate and missed diagnosis rate of this disease are extremely high. high. This patient was found in a physical examination. After admission, he was actively improved relevant examinations, performed MRI neuroimaging and 3D printing reconstruction technology, formulated a complete surgical treatment plan before the operation, carefully protected the nerves during the operation, and the patient's tumor was completely removed during the operation, Postoperative neurological function recovered well, and no tumor recurrence was found in follow-up examination.


Introduction to medical records
The patient, female, 46 years old, came to our hospital on February 26, 2019 due to "physical examination found a mass in the lumbar spinal canal for more than 2 months". The patient went to the "First A liated Hospital of Kunming Medical University" in December 2018, and found a mass in the lumbar spinal canal, occasional touch of the left lower extremity, no pain, and no mobility disorders. The patient was admitted to our hospital for further diagnosis and treatment. There is no history of hypertension, no history of exposure to tuberculosis, and no family history of tumors. Physical examination: Physiological curvature of the spine exists, no scoliosis deformity, no tenderness, no percussive pain in the spinous process of cervical, thoracic and lumbar vertebrae, no percussion pain, lumbar spine movement, no obvious abnormalities in muscle strength and muscle tension of both lower limbs, and physiological re exes exist. Pathological re ex is not elicited. DR showed that the density of the soft tissue around the L2 and L2/3 intervertebral space was increased. It is recommended that the lumbar spine be combined with MRI (Fig. 1A, 1B). MRI showed: L2/3 intervertebral disc level intravertebral canal extramedullary intradural round nodules, clear boundaries, size about 1.6cm × 1.5cm × 2.0 cm, T1 is slightly longer T2 signal, enhanced scan is signi cantly enhanced, and the nal The laments are closely related, and the neuroimaging shows better. Consider neurogenic tumors, please combine with the clinical; 2. The shape, structure and signal of the remaining spinal cord are not abnormal; 3. The proximal nerve roots on both sides of the neck, thorax and lumbar are small nodules, Small cystic enlargement changes, long T1 long T2 signal, no obvious enhancement in enhanced scan, observation on neuroimaging images is clearer and more intuitive, the nerve root runs distally, and the shape is not obvious. Consider multiple nerve root sheath cysts. (Fig. 1D-G). The preoperative NSE value was 17.51 µg/L↑ (reference range is 0-16.3 µg/L), and other laboratory tests showed no abnormalities.

Admission to hospital
After admission, complete various preoperative examinations. Under general anesthesia, "L2 and 3 laminectomy decompression + spinal mass removal + nail rod system internal xation", L2 and 3 segments can be seen after L2 and 3 lamina The dural sac is full. After opening the dura, a mass about 2.0cm × 2.0cm × 1.5 cm can be seen. The envelope is intact, dark red, and the surface is smooth. The tumor is connected to the terminal laments. The super cial part of the tumor is connected to the cauda equina Nerve adhesions are mild, the boundary between the tumor and the dural sac is clear, the adhesions are carefully separated, and the tumor is completely removed when the nerve terminal laments are disconnected. Carefully stop the bleeding and suture the dura mater. The internal xation system is installed in the conventional L2 and 3 segments, drainage tube is placed, and suture is layer by layer. On the 7th day, he recovered and was discharged.

Postoperative pathology and review
Postoperative pathological examination showed that the epithelioid cells constitute the tumor parenchyma, the cell morphology is uniform, the cytoplasm is abundant, the nucleolus is not obvious, the mitoses are rare, and the arrangement is acinar; the interstitial is sinusoidal and a little brous (Fig. 3A). Immunohistochemistry showed that the tumor cells were strongly positive for CgA, NSE, and Syn (Fig. 3BCD). Pathological diagnosis: Paraganglioma in L2 and 3 spinal canal. Postoperative DR showed that the physiological curvature of the lumbar spine became at, and the lumbar 1-3 vertebral and paravertebral metal internal xation were in normal position ( Fig. 2C-F). The postoperative function recovered well, and no tumor recurrence was found in the 14-month follow-up.

Literature Review
In order to review the cases of paraganglioma in the spinal canal at home and abroad, we use the keywords "spinal cannal' and 'paraganglioma' to search for cases in Medline for nearly 40 years. Using this strategy, we found 26 articles and 47 cases were reported. The reported case and the age of onset, location, clinical characteristics and follow-up of this case are summarized in Table 1.

Discussion
Paragangliiocytoma originates from sympathetic nerve sheath cells, 85%~90% occurs in the adrenal gland, about 10% occurs outside the adrenal gland, such as carotid body, jugular bulb, heart, retroperitoneum, bladder, hepatic portal, thoracic cavity [28][29] , Pick named pheochromocytoma that occurred in the adrenal gland in 1912, and named paraganglioma that occurred outside the adrenal gland. There are no accessory ganglia in the normal spinal canal and vertebral body, so the paraganglioma in the spinal canal and vertebral body is very rare, the incidence is about 0.07/1,000,000. The origin of paraganglioma in the spine has not been determined. Some scholars believe that it originated from the sympathetic cells of the lateral spinal cord of the thoracolumbar segment or the ectopic sympathetic trunk branches [30] , which mainly occurred in the dura mater of the spinal canal. It is rare to occur in the epidural. Paraganglioma can synthesize, store, and secrete catecholamines. Some tumors have neuroendocrine function. Few cases that occur in the spinal area are accompanied by neuroendocrine function. There are reports in the literature that may be associated with hypertension [31] , most of which are concentrated in In the lumbosacral area, cauda equina, and terminal laments in the spinal canal [32][33] , and non-functional tumors account for the vast majority. The prevalence of this disease is about 50 years old. Because most tumors have no functional lesions, non-speci c symptoms caused by tumor compression are the rst symptoms in clinical practice. Therefore, the misdiagnosis rate and missed diagnosis rate of this disease are extremely high.
MRI is currently the best examination method for the diagnosis of paraganglioma in the spinal canal [34] . It is mainly manifested as soft tissue masses with clear boundaries, T1WI and other signals, T2WI high signals, abundant internal nourishing blood vessels, and a few tumors have spotted hemorrhage, The tumor is obviously strengthened on the enhanced scan, and there are often thick "empty blood vessels" around it, and the enhanced scan shows vascular-like enhancement. Mainly differential diagnosis with neurogenic tumors in the spinal canal, epidermoid cysts in the spinal canal and other rare diseases [35][36] . Hemosiderin deposits can be seen at the edge of the tumor, which is helpful to prompt diagnosis. Hemosiderin deposits are mainly seen in vascular-rich lesions [37] . Preoperative MRI neuroimaging and 3D reconstruction in this patient have important guiding signi cance for the diagnosis of tumor, the formulation of surgical plan and the recovery of postoperative nerve function.
Pathological examination is the only way to diagnose paraganglioma. The tumor's main cells are uniform in size, round or almost round, with nuclei located in the center, chromatin punctiform, thinner, and nucleoli are usually inconspicuous. They are distributed in nests and look normal. Paraganglia: Sertoli cells arranged in a single layer around the nest, fusiform or cylindrical, sometimes di cult to identify under light microscope. The nested principal cell and surrounding supporting cells constitute a typical "Zellballen" structure [21] ; Immunohistochemistry is mainly used to distinguish it from other neuroendocrine tumors. Chroma n A (CgA), synapse protein (Syn), neuron-speci c enolase (NSE), S-100 protein, glial brillary acidic protein (GFAP) and keratin (CK), etc. To a certain degree of diagnostic signi cance, the expression of Syn, CgA, and NSE among these indicators in this patient was positive.
Total surgical resection is the rst choice for treatment of paraganglioma in the spinal canal, and most patients have a good prognosis. The surgery uses the posterior median approach of the vertebral body segment where the tumor is located, and the lamina and dura must be opened. Paraganglioma is located in the subdural epimedullary, mostly closely related to nerve tissue, and has abundant blood supply [38] . Paraganglioma has a rich blood supply and shares a large and deformed blood supply vessel with the conus medullaris. Disconnection of this blood vessel may cause abnormal blood supply to the conus medulla [42] . It is often seen in literature reports that patients have complications such as urinary incontinence after surgery. The possible reasons are not only the damage of the cauda equina during the operation, but also the in uence of the blood supply of the conus medullarius after the vessel is broken. Therefore, the blood supply artery should be blocked during surgical resection. In order to reduce bleeding and reduce the tumor volume; the priority is to separate the tumor from the adhering nerve roots, if the nerve roots cannot be separated, then perform a total resection; then strictly stop the bleeding, close the dura mater, and x the lamina.
Paraganglioma in the spinal canal is a benign tumor, but there are still a few reports of malignant metastasis of the tumor after surgery [39] .
Surgery may have a curative effect, but the spread of the tumor limits the chance of radical resection [41] . A small number of tumors that cannot be completely removed may have cerebrospinal uid dissemination and metastasis. For patients whose tumors are not completely removed, reoperation and combined treatment with radiotherapy and chemotherapy are feasible [33] . According to reports, there are still a few reports that pathological examinations cannot determine the benign and malignant tumors, so long-term follow-up is very important for the prognosis of patients [40] . This patient underwent complete tumor resection during the operation. Thanks to preoperative neuroimaging and 3D reconstruction technology, no important nerves were injured during the operation. The patient's neurological function recovered well after the operation. The postoperative patient needs to review B-ultrasound, DR, CT, etc. regularly. To better assess the local recurrence. The patient has been followed up for 1 year and 7 months with good internal xation and no signs of tumor recurrence and metastasis. The follow-up is still ongoing.
Although neuroendocrine markers such as CgA, Syn, S-100 protein, NSE positive and epithelial-derived markers such as CK, EMA and other negative are helpful to distinguish ependymoma, schwannoma, meningioma, chordoma, etc. Pathological examination is still di cult to judge the benign and malignant tumors. It should be judged according to its biological behavior. If lymph node metastasis or/and distant metastasis occurs, it can be considered as malignant paraganglioma. Therefore, long-term follow-up is of great signi cance in determining the prognosis of patients.

Conclusion
Paraganglioma of the spine is a subtype of neuroendocrine tumors and is clinically rare. Because most tumors have no functional lesions, non-speci c symptoms caused by tumor compression are the rst symptoms in clinical practice. Therefore, the misdiagnosis rate and missed diagnosis rate of this disease are extremely high. high. This patient was found in a physical examination. After admission, he was actively improved relevant examinations, performed MRI neuroimaging and 3D printing reconstruction technology, formulated a complete surgical treatment plan before the operation, carefully protected the nerves during the operation, and the patient's tumor was completely removed during the operation, Postoperative neurological function recovered well, and no tumor recurrence was found in follow-up examination. The patient and family members agreed that the case was reported and signed an informed consent form. The scanned copy of the informed consent form can be sent to the publishing house.

Con ict of interest
The authors declare that they have no competing interests.  A: HE staining showed that the epithelioid cells constitute the tumor parenchyma, the cell morphology is uniform, the cytoplasm is more, the nucleolus is not obvious, the mitoses are rare, and the arrangement is acinar; the interstitial is sinusoidal and a little brous; B: CgA immunohistochemical results showed strong positive; C: NSE immunohistochemical results showed strong positive; D: Syn immunohistochemical results showed strong positive; E: Ki67 immunohistochemical expression was positive (about 5%) ; F: CK immunohistochemistry result showed negative; G: CD34 immunohistochemistry result showed negative; H: S-100 immunohistochemistry result showed negative. 3 Postoperative pathological pictures