Update: Spinal cord Ependymoma

Ependymomas are the most frequent spinal cord tumors in adult patients.

Some authors believe it is more common in the fourth and fifth decade while others propose a wider distribution spanning between the second and sixth decade of life 1) 2) 3) 4) 5)

In a population-based survey of 467 patients with primary intraspinal neoplasms, intramedullary ependymomas accounted for 34.5% of all ependymomas of the central nervous system. According to the same study, the age-adjusted incidence rate for the primary intraspinal neoplasm is 0.5 in females and 0.3 in males per 100,000 population per year 6).

Spinal ependymomas commonly present as intramedullary tumors in the cervical or thoracic cord or as tumors arising from the conus medullaris or the filum terminale

Sometimes the tumor is located outside of the spinal cord and affects the cauda equina nerve roots.

Classification

Dissemination

Spinal cord ependymomas presenting with regional dissemination along the neuroaxis are rare, with a yet undetermined standard of care.

Diagnosis

Plain radiograph

Plain film features that may be seen with a spinal ependymoma include:

scoliosis

spinal canal widening

vertebral body scalloping

pedicle erosion

laminar thinning

CT

CT may demonstrate:

non-specific canal widening

iso to slightly hyper-attenuating compared with normal spinal cord

intense enhancement with iodinated contrast

large lesions may cause scalloping of the posterior vertebral bodies and neural exit foraminal enlargement

MRI

MRI is the modality of choice for evaluating suspected spinal cord tumours. Features include:

widened spinal cord (as ependymomas arise from ependymal cells lining the central canal, they tend to occupy the central portion of the spinal cord and cause symmetric cord expansion)

although unencapsulated, they are well-circumscribed

tumoral cysts are present in 22%. Non-tumoral cysts are present in 62%.

Syringohydromyelia occurs in 9-50% of cases

In contrast to intracranial ependymomas, calcification is uncommon

average length of four vertebral body segments

Typical signal characteristics:

T1: most are isointense to hypointense; mixed signal lesions are seen if cyst formation, tumour necrosis or haemorrhage has occurred.

T2: hyperintense

peritumoural oedema is seen in 60% of cases

associated haemorrhage leads to the “cap sign” (a hypointense haemosiderin rim on T2 weighed images) in 20-33% of cases.

The cap sign is suggestive of but not pathognomonic for ependymoma as it may also be seen in Spinal cord hemangioblastomas and paragangliomas.

T1 C+ (Gd): virtually all enhance strongly, somewhat inhomogeneously.

Differential diagnosis

Spinal cord astrocytoma

Spinal cord hemangioblastoma

Spinal cord ependymoma is more common in adults.

Scoliosis and bony remodelling more common

Central location in spinal canal

Well-circumscribed

Haemorrhage is common

May rarely present as a subarachnoid haemorrhage

Hemosiderin staining especially at the superior and inferior margins (so-called hemosiderin capping) is common focal, intense homogeneous contrast enhancement more frequent and more prominent cysts (intratumoral and polar).

Ganglioneuroma.

Treatment

Maximal safe resection with Intraoperative neurophysiological monitoring.

Grade II and III intramedullary ependymomas [IME] are circumscribed with a plane of cleavage that should facilitate high gross total resection rates (GTR). Gross total resection of grade II/III IME is superior to subtotal resection (STR) and radiotherapy (RTx) for progression-free and overall survival 7).

Data suggest that it may be necessary to consider tumor features and the type of surgical technique used, particularly when interpreting intraoperative neurophysiologic monitoring profiles of intramedullary spinal cord tumors such as ependymomas and spinal cord hemangioblastomas 8).

A video demonstrates the technique of microsurgical resection of an intramedullary ependymoma through a posterior midline myelotomy. The video can be found here: http://youtu.be/lcHhymSvSqU

9).

Complications

Despite their usually well-defined dissection plane, surgical morbidity has been documented to be considerably higher compared with other intramedullary entities.

Although surgery was once reserved for diagnosis alone, the evolution of surgical practices has elevated resection to the treatment of choice for these lesions. While technological advances continue to improve the capacity for gross-total resections and thus decrease the risk of recurrence, ependymoma spinal surgery still contains a variety of potential complications. The presence of neurological deficits and deterioration are not uncommonly associated with spinal cord ependymoma surgery, including sensory loss, dorsal column dysfunction, dysesthetic syndrome, and bowel and bladder dysfunction, particularly in the immediate postoperative period. Surgical treatment may also lead to wound complications and CSF leaks, with increased risk when radiotherapy has been involved. Radiation therapy may also predispose patients to radiation myelopathy and ultimately result in neurological damage. Additionally, resections of spinal ependymomas have been associated with postoperative spinal instability and deformities, particularly in the pediatric population. Despite the advances in microsurgical techniques and intraoperative cord monitoring modalities, there remain a number of serious complications related to the treatment of spinal ependymoma tumors. Identification and acknowledgment of these potential problems may assist in their prevention, early detection, and increased quality of life for patients afflicted with this disease 10).

Outcome

While resection can often achieve favorable outcomes in the treatment of spinal ependymoma, more research on the unique molecular, genetic, chromosomal and epigenetic traits must be conducted in order to tailor treatment and intervention for those patients for whom total resection is not possible 11).

There have been anecdotal reports of radiographic response of spinal ependymomas in neurofibromatosis type 2 (NF2) patients being treated for progressive vestibular schwannomas with bevacizumab.

Neurofibromatosis 1 (NF1) and ependymoma

Ependymoma with Neurofibromatosis type 1 (NF1) has rarely been reported. To date, only four cases have been reported in English literature.

Case series

 2016

Seventeen patients were identified: 16 grade II and one grade 3. GTR was 94.12%. Factors that correlated with a decline in MCC were longitudinal extension of the tumour (p = 0.0238) and presentation with motor signs and symptoms (p = 0.0223). There was no statistical difference between preoperative factors that influence post-operative outcomes in the current study when compared with other published series. There was no statistical difference between preoperative and postoperative MCC scores between our series and other published series.

The current series with a GTR of 94.12% compares favourably with other published series with GTRs of 55.8-84% with no significant difference in functional outcomes. Series with low GTRs should examine their operative strategy or false-positive alarm rates which may lead to higher STRs. This series should be viewed as a unique opportunity to benchmark GTRs of circumscribed intramedullary tumours 12).


Keil et al., assessed the outcome of 61 consecutive cases of spinal ependymoma in a single centre over a 20year period using a variety of outcome measures. Sex distribution was equal, with a mean age at surgery of 43.6years (range 5-76years). Overall, most tumours occurred in the lumbosacral region (70.5%), with fewer in the thoracic (27.9%) and cervical regions (18.0%). Myxopapillary features were seen in 41.0% of tumours, and were more common when occurring in the lumbar region (51.2%). Gross total resection was achieved in 52.5%, subtotal resection in 37.7% and biopsy alone in 9.8% of patients and 31.1% received adjuvant radiotherapy. Two-thirds of patients achieved an excellent post-operative neurological outcome (Frankel grade E). Tumour recurrence was rare. Gross total resection and good preoperative neurological condition were most strongly predictive of good outcome. Post-operative radiotherapy did not seem to confer survival benefit in this case series, even in cases of incomplete resection, leading us to question its utility for all cases of spinal cord ependymoma 13).


Farschtschi et al conducted a retrospective review of all patients with NF2 treated with bevacizumab for symptomatic ependymoma at three NF2 specialty centers. Tumor size was evaluated by linear measurements; radiographic response was defined as >20% reduction in tumor size. We also performed immunohistochemical evaluation of NF2-associated symptomatic ependymomas from five patients, including two from this clinical series.

Eight patients with NF2 and symptomatic ependymoma were treated with bevacizumab. All patients had subjective clinical improvement with bevacizumab, although only five of eight patients evaluated had radiographic response. All tumors expressed VEGF-R2. Four of five evaluated ependymomas expressed VEGF-R1; one without VEGF-R1 expression was from a patient who showed clinical but not radiographic response.

Treatment using bevacizumab improved symptoms related to NF2-associated ependymomas, often without concurrent radiographic response. This treatment effect may be related to VEGF-R1 expression in NF2-associated ependymoma 14).

2015

One hundred patients with intramedullary ependymomas underwent 102 operations. Mean age was 44 ± 15 years (range 8-74 years). Patients were followed by outpatient visits and questionnaires, with a mean follow-up of 77 ± 91 months. Short-term results were determined for individual symptoms and the McCormick Scale, whereas tumor recurrence rates were calculated with Kaplan-Meier statistics.

Compared with cervical ependymomas, those of the thoracic spine were associated with more severe motor deficits and gait problems at presentation. A total of 86.3% of patients with intramedullary ependymomas underwent gross-total resection (GTR). A low preoperative McCormick grade and first surgery were the strongest predictors for a GTR. Postoperatively, 67.6% of patients demonstrated a worse neurological state at discharge from the hospital. This deterioration was transient for 40.1% of the patients and permanent for 27.5%. In the long term, the McCormick grade remained unchanged from the preoperative grade in 74.5% of patients, while it was improved in 5.9% of patients and increased after surgery in 19.6% of patients. According to a multivariate analysis, the risk of permanent morbidity increased with a thoracic level of the ependymoma, advanced age, a long clinical history, presence of a tumor hemorrhage, and surgery on a recurrent tumor. In the long term, tumor recurrence rates correlated significantly with the amount of resection (4.2% and 18.5% in 20 years after GTR and partial resections, respectively). Postoperative neuropathic pain syndromes affected 37.0% of patients, whereas 4% demonstrated a postoperative myelopathy related to cord tethering at the level of surgery.

Intramedullary ependymomas are tumors best treated surgically. A complete resection indicates cure for the overwhelming majority of these patients. Surgery should be performed early by neurosurgeons who deal with these lesions on a regular basis to achieve high GTR rates. Permanent surgical morbidity varies most according to tumor location and patient age 15).


53 adult patients over the span of 15years were analyzed for OS, PFS, and the effects of plane of dissection (POD) and gross total resection (GTR) on functional and long term outcomes. The mean age was 45 years and median follow-up was 54 months. The follow-up neurological outcome and modified McCormick scale were used to determine the functional outcome. Kaplan-Meier curves were used to calculate progression and survival. The overall ability to achieve GTR was significantly correlated to identification of an intraoperative POD (p<0.001). There was a trend towards increased PFS with the ability to achieve a GTR. There was no significant difference in the pre- and postoperative functional outcome scores. The ability to achieve a GTR is strongly correlated to the identification of a POD in ependymomas. There is a trend towards an increased probability of PFS in intramedullary spinal cord tumors when GTR is achieved. The resection of these tumors is likely to halt, but not reverse, neurological deterioration 16).

2014

Between 2002 and 2012, 16 patients with regionally metastatic spinal ependymomas were diagnosed and treated. The patients were retrospectively divided into two groups according to tumor grading and histological features. Nine patients were diagnosed with myxopapillary ependymomas (MPE), and seven patients were diagnosed with other low-grade ependymomas.

With a median follow-up of 46.4 months, 13 out of 16 patients had no postsurgical recurrence/progression of the disease. In three patients, the disease recurred/progressed, leading to death in one patient. There was no correlation between gross total removal (GTR) of the main tumor, or resection of the main lesion and the metastatic foci and increased progression free survival in patients of the MPE group. There was an advantage for patients diagnosed with other low-grade ependymomas. Adjuvant radiotherapy did not prove beneficial.

Spinal ependymoma with regional metastases SERMP has a relatively benign course. Achieving GTR of both the main lesion and the metastases is preferable, but should not be achieved at any cost, especially in MPE interfering with the conus medullaris. The benefit of adjuvant radiotherapy remains unproven 17).

1999

Thirty-six consecutive patients who underwent surgical removal of an intramedullary spinal cord ependymoma between September 1980 and June 1998 were studied retrospectively. This series includes 19 women and 17 men between the age of 12 and 67 years (mean age, 41.2 yr). The location of the tumors was cervical in 24 cases, cervicothoracic in 3 cases, thoracic in 7 cases, and conus in 2 cases. At surgery, complete removal was achieved in 34 patients and subtotal removal was performed in the remaining 2.

There has been no tumor recurrence in any patient except one who had an anaplastic ependymoma after a mean follow-up period of 56 months. The surgery improved neurological status in 14 of the 36 patients (39%). However, five patients (14%) experienced persistent deteriorations in clinical grade caused by surgery. Four of the five patients harbored benign ependymomas in the thoracic cord and characteristically demonstrated arachnoid scarring and cord atrophy at surgery, indicating that tumors had been present for a long time.

Surgical removal of intramedullary ependymomas is beneficial to patients. However, the thoracic cord may be susceptible to surgical manipulations for intramedullary ependymomas. In addition, intraoperative findings of arachnoid scarring and cord atrophy are ominous for surgical morbidity 18).

Case reports

 2016

Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to be a cause of acute neurological deficit. A 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia 19).

2015

Cheng et al., report an intramedullary spinal tumor consisting of an ependymoma and a hemangioblastoma (HB). A 37-year-old woman presented with progressive bilateral lower limb sensory and motor deficits. Magnetic resonance imaging showed a single intramedullary mass in the thoracic cord (T4-T6 level). Clinically, the patient had no von Hippel-Lindau disease and neurofibromatosis type 2. Metastatic carcinomas including renal cell carcinoma were altogether negative. Complete surgical resection was performed. Histologically, the tumor consisted of a mixed ependymoma and HB. Tumor cells of ependymoma displayed a rather uniform appearance with round to oval nuclei having salt-and-pepper-like chromatin, forming perivascular pseudorosette structures with radially arranged, tapering cell processes extending to intratumoral blood vessels. Stromal cells of HB had vacuolated or homogeneously eosinophilic cytoplasm and variable sized hyperchromatic nuclei within a background of capillaries. Immunohistochemically, tumor cells of ependymoma were strongly positive for glial fibrillary acidic protein (GFAP), focally positive for epithelial membrane antigen (EMA) and D2-40 in a dot-like or ring-like pattern. Stromal cells of HB showed immunoreactivity for S100, vimentin, inhibin-α, D2-40, EMA and cytokeratins (CK: AE1/AE3, CK19). A review of the literature, in conjunction with the present case, shows that ependymomas and HBs may have a close relationship with each other. 20).

2013

A 36-year-old woman presented with headache, multiple cranial nerve palsies, visual hallucinations, confusion, hemiparesis, hemihipoestesia, episodes of disconnection, and toxic syndrome. Magnetic resonance imaging and positron emission tomography scan revealed leptomeningeal carcinomatosis in the brainstem, the cerebellum, and along the whole spinal cord. Various nodular, intradural extramedullary lesions were present at multiple dorsal and lumbar levels. Metastatic bone disease affected all the vertebral bodies and various extraspinal bones. An intradural and bone biopsy was performed at L4, providing the diagnosis of anaplastic ependymoma (World Health Organization grade III) with focal neuronal differentiation. Despite chemotherapy, the patient’s symptoms quickly progressed, and she died 7 weeks after diagnosis.

There are no previous descriptions of ependymomas with this extensive leptomeningeal, spinal, intracranial, and extraneural dissemination at clinical onset. Bone metastases in spinal ependymoma have not been previously reported 21).

2006

A 33-year-old male presented to a chiropractic clinic complaining of chronic, recurrent low back pain. Subtle signs of muscle atrophy were noted in the left hand during the history taking. This muscle atrophy was reported as having a gradual onset spanning the past six months without any precipitating event. Cervical, thoracic and lumbar spinal radiographs were deemed unremarkable. Due to the progressive nature of the neurological deficit, the patient was referred for a neurological consultation. A magnetic resonance imaging (MRI) study was performed and revealed an expansive intramedullary lesion between C6 and T1 suggesting a differential diagnosis of spinal cord ependymoma or astrocytoma. The patient underwent surgical excision of the tumour. Pathological report confirmed a diagnosis of ependymoma 22).


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