A rare case of cauda equina paraganglioma histologically simulating ependymoma

Abstract

Background:

Paragangliomas of the cauda equina are rare neuroendocrine tumors that can mimic ependymomas on imaging and histology, creating diagnostic challenges and influencing surgical planning.

Case Description:

A 41-year-old man presented with progressive low back pain and bilateral leg numbness. MRI showed a well-circumscribed, enhancing intradural extramedullary mass at L3. He underwent L3–L4 laminectomy with gross-total microsurgical excision. Histopathology revealed pseudorosettes and uniform tumor cells, initially suggesting ependymoma; however, immunohistochemistry demonstrated strong synaptophysin and S100 positivity with negative GFAP and EMA, confirming a cauda equina paraganglioma. Postoperatively, the patient recovered fully and remained asymptomatic at 1-year follow-up.

Conclusion:

Paragangliomas can closely resemble ependymomas, and accurate diagnosis requires immunohistochemistry. Complete surgical excision yields excellent outcomes, and individualized long-term imaging follow-up is recommended because recurrence, although uncommon, can occur.

INTRODUCTION

Paragangliomas (PGs) are neuroendocrine tumors that arise from neural crest cells within the lateral autonomic or segmental ganglia.[22] Although they can develop in various anatomical locations, primary PGs of the spine are exceedingly rare and typically involve the cauda equina and filum terminale regions.[20] These tumors are classified as World Health Organization (WHO) Grade I,[1,23] in contrast to ependymomas – which are frequently observed in the cauda equina region and are typically WHO Grade II/III.[23] Despite their differing biological behaviors, PGs may exhibit histological features that closely resemble those of ependymomas, posing a significant diagnostic challenge.[5] Accurate differentiation between these entities is critical for appropriate clinical management. We present a rare case of a benign PG of the cauda equina that histologically mimicked an ependymoma, with the final diagnosis confirmed using immunohistochemistry (IHC).

CASE PRESENTATION

Clinical history

A 41-year-old male with a known history of back pain presented on December 6, 2023, with worsening pain and a change in its character. The pain was gradual in onset, progressive in nature, localized to the lower back, and radiated bilaterally to the legs. It was associated with numbness in both legs. The patient reported experiencing back pain for approximately 4–5 years, during which it occurred only after physical exertion, particularly after playing football. However, he now complained of constant pain, including at rest, with significant nocturnal discomfort that disrupts his sleep.

On clinical examination

The patient was fully conscious and alert, with a Glasgow Coma Scale score of 15/15. His vital signs, including blood pressure, heart rate, respiratory rate, oxygen saturation, and oral temperature, were within normal limits. His calculated body mass index was 28, and no associated injuries were noted.

Neurological examination revealed normal-shaped pupils (3 × 3 mm) that were reactive to light. Muscle tone was normal, and muscle strength was 5/5 in all limbs bilaterally. The straight leg raising test and inverted Lasegue sign were negative. Reflexes were intact and within normal limits, while pain, touch, and proprioception sensations were preserved. Cranial nerve examination was unremarkable.

Laboratory investigations

Laboratory tests showed a normal white blood cell count, hemoglobin, hematocrit, and platelet count. Renal and liver function tests were also within normal parameters.

Radiological investigations

Magnetic resonance imaging (MRI) of the lumbosacral spine revealed a well-defined, ovoid soft-tissue lesion within the spinal canal at the lower aspect of the L3 vertebral body. The lesion was intradural and extramedullary, causing splaying and displacement of the cauda equina nerve roots at this level. It measured approximately 20 × 15 × 14 mm and demonstrated heterogeneously high signal intensity on T2-weighted images (T2WI), intermediate signal intensity on T1-weighted images (T1WI), and avid homogeneous enhancement on post-contrast series. The findings were highly suggestive of a primary tumor, most likely meningioma. Sagittal T1- and T2WIs show the craniocaudal extent of the lesion and its intradural, extramedullary location, while axial T2WIs at the L3–4 and L4–5 levels demonstrate the lesion’s relationship with the surrounding cauda equina nerve roots and confirm displacement of the neural elements within the spinal canal [Figure 1].

Figure 1:

Magnetic resonance images showing a well-defined, ovoid soft-tissue lesion within the spinal canal at the lower aspect of the L3 vertebral body (arrows in A, B, C, D). The lesion is intradural, extra-medullary, and causes splaying of the cauda equina nerve roots at this level. It measures approximately 20 × 15 × 14 mm. (A) Sagittal T2-weighted image (T2WI). (B) Coronal T2WI. (C and D) Post-gadolinium-diethylenetriamine pentaacetic acid contrast-enhanced T1-WI in coronal and sagittal planes, respectively. (E and F) Axial T2WI.

Management

The patient was admitted and started on intravenous analgesics and antibiotics. A microscope-assisted procedure was performed, including a complete L3 laminectomy and a partial L4 laminectomy.

The dura was opened at the midline and retracted laterally using 6–0 nylon sutures, followed by the opening of the arachnoid mater. On exposure, the tumor was identified at the midline and extending to the right side, located between the nerve roots. It appeared as a firm, capsulated, reddish-gray mass, round in shape, positioned posterior to the L3 vertebra and attached to a small nerve root. In addition, three calcified spots were noted above the tumor level, with the first located at its rostral pole. These calcifications appeared sheet-like, not attached to the tumor, and were positioned horizontally within the subarachnoid space.

Piecemeal debulking inside the capsule was performed while continuous intraoperative somatosensory and motor monitoring was utilized. At the final stage, the capsule was carefully dissected out from the surrounding nerve roots and completely removed. Electrical somatosensory and motor stimulation was applied to the small nerve root attached to the interior aspect of the tumor, with no response observed. The three calcified pieces were also removed.

Histopathological examination of the biopsy specimen revealed a cellular tumor with circumscribed borders, consisting of monomorphic columnar to oval cells with speckled chromatin, perivascular pseudorosettes, and true ependymal rosettes with lumina. No necrosis was observed, and a sclerotic stroma with bone fragments was present. Few mitotic figures were noted. The biopsy findings were initially suggestive of ependymoma, but IHC showed the lesion to be positive for synaptophysin and S100, and negative for glial fibrillary acidic protein and epithelial membrane antigen, confirming the final diagnosis of a well-encapsulated PG with no necrosis or pleomorphism.

After 1 year follow-up, the patient appeared to be completely fine with no concerns or return of symptoms.

DISCUSSION

PG is a tumor that arises from the neuroendocrine system. It originates from the neural crest cells from the lateral autonomic or the segmental ganglia.[22] It can affect multiple sites of the human body including retroperitoneum and mediastinum.[8] More than 90% of extra-adrenal PGs occur in the head and neck.[4] However, primary PGs of the spine are rare and typically involve filum terminale and cauda equina.[20] PG tumors are classified as WHO grade 1.[1]

The most common symptom of lumbosacral PGs is lower back pain accompanied by radiculopathy.[20] Moreover, studies have reported that combined motor and sensory deficits are seen in 35% of cases, sensory deficits only in 13%, and bowel/bladder dysfunction in 6% of cases.[21] Along with these symptoms, sexual dysfunction has been reported also in other studies.[7,15,23] Extradural PGs can compress the spine and present with paraparesis.[6] These tumors rarely exhibit functional hormonal activity, despite their neuroendocrine origin. Due to their nonspecific nature of symptoms, the presentation and diagnosis are commonly delayed for months and years.[20]

Despite their rarity, PGs must be considered in the differential diagnosis of spinal tumors. They share clinical, radiological, and histopathological features with other spinal tumors making their diagnosis challenging. If they are not functional tumors causing catecholamine hypersecretion syndrome, which are extremely rare, there is no specific investigation to diagnose PGs preoperatively.[20] MRI is the diagnostic modality of choice for PGs. They appear as well circumscribed masses that are isoechoic or hypoechoic to the spinal cord on T1WI, and hyperintense on T2WI. Cystic areas may sometimes be found within the mass.[25] A unique “salt and pepper” pattern may be seen on T2WI resulting from rich vascularity of the tumor. Serpentine, congested and ectatic vessels and “cap sign,” which is a low intensity rim of peripheral hemosiderin may sometimes be identified on T2WI.[19,25] However, these MRI findings are not specific for these lesions. The MRI appearance overlaps and might be indistinguishable from other spinal tumors such as schwannomas, hemangiomas, meningiomas, and ependymomas.[3] Due to this reason, PGs are frequently misdiagnosed as other tumors such as ependymoma and schwannoma on MRI preoperatively.[12,20]

Grossly, PGs appear as encapsulated, oval masses with a reddish brown cut surface and are soft in consistency.[1] On histological examination of the tumor, two main types of cells are identified, chief and sustentacular cells. The predominant cells are the chief cells that are polygonal to round in shape and have oval nuclei with finely dispersed chromatin (“salt and pepper” appearance). These cells have a finely granular eosinophilic cytoplasm. The second cell type is the sustentacular or supporting cells, which are spindle shaped and are placed around the chief cells. The tumor parenchymal cells are arranged in characteristic nests or lobular structures called “zellballen” within stroma composed of multiple thin-walled small blood vessels.[18] Sometimes, the tumor cells can mimic ependymomas and can form pseudorosettes (perivascular radial arrangement of the cells).[5] Rarely, PGs may have ependymoma-like features, the presence of ependymal tubules.[9,27]

Since histopathology is not unequivocal in making the accurate diagnosis, and given the similarity of histological features between other spinal tumors, immunochemistry is essential in making the exact diagnosis. All PG tumors express S-100, especially the sustentacular cells although ependymomas may express this marker too.[5,9,11] The chief cells express chromogranin A and synaptophysin because they are of neuroendocrine origin.[24] Another antibody crucial in differentiating between PGs with ependymoma-like features on histology and actual ependymomas is the glial fibrillary acid protein (GFAP), which is not expressed in PGs. There is positive expression of GFAP in ependymomas.[9,14,17] PGs can be differentiated from other types of neuroendocrine tumors because they do not express cytokeratin.[2]

Ependymomas are growths that are very commonly seen in the lumbar area, particularly in the cauda equina region. They are classified as WHO grade 2, whereas PGs are classified as WHO grade 1.[1] Therefore, differentiating PGs from ependymomas which is noted to be more aggressive is crucial.[23]

Total surgical excision is the treatment of choice for PGs spinal tumors. If total removal of the tumor is not possible, radiotherapy is advocated.[13,26] These tumors have an excellent prognosis after surgical resection with local recurrence only observed in 4% of the cases and metastasis being rare.[16] Radiation therapy is unlikely to reduce the recurrence rate which is more commonly observed in patients who receive incomplete surgical excision.[10]

Most recent practice recommends following up the patient in clinic with an initial MRI scan typically in 3–6 months. Although most of the cases do not recur after total surgical excision which is confirmed by the follow-up scans, duration of follow-up must be determined individually and according to the surgeon’s clinical judgment.[2]

CONCLUSION

This case highlights the diagnostic challenge of differentiating benign PGs of the cauda equina from ependymomas due to their overlapping histopathological features. IHC plays a pivotal role in establishing an accurate diagnosis, which is essential given the differences in the WHO grading and management strategies between these tumors. Total surgical excision remains the treatment of choice, offering an excellent prognosis. Continued long-term follow-up is recommended to monitor for potential recurrence.

Ethical approval:

The Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

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