Background

Anaplastic ependymomas classified as WHO Grade III neoplasms are featured by high grade histopathological changes such as increased mitotic activity, necrosis, and vascular endothelial hyperplasia. These tumors are considered clinically more aggressive associated with higher risk of recurrence and drop metastasis. Intracranial extra-axial ependymomas, which could be defined as an extraparenchymal, extraventricular ependymoma usually located between the dura mater and pia mater without involving the cortex. These tumors are extremely rare, with only 19 cases reported with undefined surgical outcomes (Hanchey, 1976; Cosgrove, 1985; Winer, 1989; Hayashi, 1994; Fukui, 1997; Donich, 1999; Youkilis, 2001; Goto, 2003; Torun, 2005; Kasliwal, 2007; Park, 2010; Salunke, 2011; Ma, 2012; Singh, 2012; Seo, 2013; Yang, 2014; Gill, 2015). This report documents a case of anaplastic ependymoma with an extra-axial origin and growing directly into the CPA and is contributory to understanding this rare neoplasm. To the best of our knowledge, this is the first case report of anaplastic ependymoma involving CPA region.

1 Case Report

1.1 Clinical history

A 42-year-old woman developed a headache that was associated with left hearing loss for 20 years. 6 months before, she presented with the increased severity in hearing loss and abnormal gait and was admitted to our hospital. MRI scans detected a large tumor at left CPA space and the patient was referred to our neurosurgical division for surgical treatment.

1.2 MRI findings

MRI demonstrated a solid irregular mass centered at left CPA space with mixed intense signal in T1 and T2-weighted images, and heterogeneously bright enhancement. Although the mass displaced the brain stem and the fourth ventricle, it had not invaded into these structures, and no apparent perilesional brain edema was observed. On the basis of the radiographic features, the diagnosis of a solid hemangioblastoma or meningioma was considered.

Figure 1 MRI findings of different sequences at axial, sagittal and coronary plane: (A) An axial and (C) A sagittal T1-weighted image demonstrating a hypointense tumor and heterogeneous lesion with compression and deviation of the brain stem and fourth ventricle. (B) An axial hyperintense lesion on T2-weighted image and (D) axial and (E) coronary T1-weighted gadolinium-enhanced scan showing significant and heterogeneous enhancement and brain stem compression.

1.3 Surgical procedure and histopathological findings

Intraoperatively, the reddish lobulated lesion was found to be poor demarcated from cerebellum, and intensely vascularized. The lesion was seen encasing vestibular and posterior cranial nerves and extending into the fourth ventricle. Histopathology was performed by 2 independent neuropathologists and revealed that the tumor was typical of an anaplastic ependymoma (World Health Organization grade III).

2 Discussion

2.1 Pathogenesis

Accounting for approximately 3% of all primary central nervous system neoplasms, ependymal tumors are rare neoplasms of neuroectodermal origin arising from ependymal cells in the obliterated central canal of the spinal cord, the filum terminale, choroid plexus or white matter adjacent to the highly angulated ventricular surface (Patel, 2012; Yang, 2016). Additionally, ependymal tumors can be found in the brain parenchyma as a result of fetal ependymal cell rests migrating from periventricular areas. One hypothesis regarding oncogenesis of intracranial extra-axial epedymomas has been proposed and favored by most studies on the basis of the relationship between the lesion and subarachnoid space: intracranial extra-axial epedymomas derive from ectopic ependymal nests that result from migration disorders of the germinal matrix. According to the 2016 WHO classification of CNS neoplasms, ependymal tumors are being classified as WHO grade I: myxopapillary ependymoma (occurring almost exclusively in the conus-cauda-filum terminale region) and subependymoma, a benign, slowly growing intraventricular lesion with a very favourable prognosis, WHO grade II ependymoma and WHO grade III anaplastic ependymoma (Chen, 2017). Although most ependymal tumors are benign, Grade III ependymomas are characterised by hypercellularity, cellular and nuclear pleomorphism, frequent mitosis, pseudopalisading necrosis and endothelial proliferation an associated with higher risk of recurrence, or drop metastasis (Trivedi, 2017; Ferris, 2017; Sun, 2017; Takeda, 2017). Extra-CNS metastasis, although extremely rare, have been described in isolated works of the literature (Marsecano, 2017). The present case, which belongs to WHO Grade III shows an extra-axial origin and grows directly into the CPA region.

2.2 Clinical characteristics

Of the previously reported 5 CPA ependymal tumors comprising 3 males and 2 females with a mean age of 52.8 years, (range from 22-78 years) seen in Table 1; whereas, of the 4 intracranial extra-axial anaplastic ependymoma cases compromising 3 males and 1 females with a mean age of 32.3 years, (range from 17-47 years) seen in Table 2. Preoperative symptoms were associated with headache, vomiting and seizure due to intracranial hypertension or neurologic focal deficits with a mean symptom duration of 3.4 months (range 3 days – 6 months) and 26.7 months (range 3 weeks – 80 months) respectively. From Yang Yang et al’ s review of these 17 extra-axial ependymal cases, there were no data correlating the duration of symptoms with the lesion size (Yang, 2016). Our present case developed nonspecific symptoms for 20 years. This finding is different from data in previous report by Reni, M., et al. that has found more rapid signs and symptoms for anaplastic ependymomas. CPA lesions most commonly present with symptoms related to the brainstem or cranial nerves compressed by or involved with the lesion (Reni, 2007). Clinical presentation is non-specific, and depends on the size, location and malignancy of the tumor. Therefore, CPA ependymomal tumors are difficult to be discriminated from other neoplasms based on their nonspecific clinical presentations alone.

Ependymal tumors are more commonly infratentorial (60%), particularly in the fourth ventricle, and in 50% of cases can extend into the subarachnoid space of the cisterna magna or the CPA space, or involve the medulla and upper cervical cord. However, anaplastic ependymomas are extremely rare, particularly regarding CPA space. To date, only 19 cases of intracranial extra-axial ependymomas have been reported in English literarture since 1976 when first reported by Hanchey et al (Hanchey, 1976). 8 of these cases were infratentorial (5 out of 8 cases at CPA space), and the other 11 cases were supratentorial. 4 of these 19 cases were anaplastic ependymomas, but none of them involved CPA region (Yang, 2016). To the best of our knowledge, here is the first case report of CPA anaplastic ependymoma in the literature. Of these 19 previously reported cases, intracranial extra-axial ependymal tumors appear more commonly in adults. With respect to anaplastic epedymomas, these 4 cases present with a young adult predominance. Due to the paucity of data regarding intracranial extra-axial ependymomas, particularly anaplastic ependymomas in the literature, there are no symptoms or radiographic features that are pathognomonic for this spectrum of neoplasms. Therefore, more cases are expected to be collected for further study.

2.3 MRI findings

In terms of radiological findings, most published documents about ependymal tumors focus more on ependymomas due to the relative common cases. The imaging features of intracranial extra-axial ependymomas need to be accumulated. Magnetic resonance imaging is thought to be the imaging modality of choice for showing the internal features of the lesion and superior soft tissue contrast. Because of calcification, necrosis, hemorrhage, or cystic components (Table 1), most cases were mixed-intensity on both T1- (hypointense to isointense) and T2- (isointense to hyperintense) weighted images, as similarly detected in out case; however, 2 out of 4 anaplastic ependymomas showed isointense on both T1- and T2-weighted images (Table 2), and most lesions had heterogeneous enhancement. Similarly, perilesional edema, which occurred infrequently, was not detected in present case. Although there is no consensus on imaging, absence of perilesional edema has been reported common and more easily discerned radiologically for ependymal tumors. Ma Reni et al suggested more pronounced contrast enhancement in anaplastic tumors. This finding is consistent with present case. Owing to the paucity of radiographic appearances, there is no consensus regarding the radiological diagnosis.

It is worth to note that Grade III ependymomas are characterised by hypercellularity, cellular and nuclear pleomorphism, frequent mitosis, pseudopalisading necrosis and endothelial proliferation associated with higher risk of recurrence, or drop metastasis through CSF and spine, which accounts for 8-33%, particularly detected in infratentorial lesions. Therefore, imaging protocols including intracranial and spinal MR examination are essential before operation.

Notably, MR-spectroscopy is noted for its priority in providing additional biochemical information in which intense signals of myo-inositol are observed in ependymomas compared with conventional MRI sequences (T1- and T2-weighted MRI, contrast T1-weighted MRI) (Yang, 2016). Moreover, MRS is considered of importance for optimal treatment strategies. Radio surgical resection is recommended for ependymomas aiming for recurrences; while radical resection is considered optimal treatment for other tumors such as meningiomas. It was unfortunate that MR- spectroscopy was not performed in either of the cases reported here.

2.4 Differential diagnosis

Housing 6-10% of all intracranial tumors, CPA represents a space comprising neuroglia tissue, cranial nerve sheaths, meninges and embryo reminant. A wide spectrum of lesions occurs in the space of the CPA. In adults, benign tumors are more common including vestibular schwannomas (70-80%), meningiomas (10-15%) and epidermoid cysts (3-7%) (Patel, 2012). Vestibular schwannomas are the most common lesion within the CPA space, typically arising from the inferior vestibular portion of the VIII cranial nerve. Most of vestibular schwannomas originate from the VIII cranial nerve in the lateral third of the internal auditory canal, where they grow medially along the line of least resistance, remodeling and expanding the canal and extending into the CPA. In 90% of patients, the initial presenting symptoms entail unilateral sensorineural hearing loss, tinnitus, and imbalance. Radiologically, vestibular schwannomas are round or oval lesions that show isointensity on T1WI compared with parenchyma, and variable signals intensities on T2WI owing to its components such as Antonio A/B. After contrast administration, intense enhancement detected. Bony changes including widening of the canal caused by the lesion are usually demonstrated on Computed tomography (CT). However, overall radiologic findings are nonspecific for vestibular schwannomas.

Meningiomas that occupy the CPA are usually based at the posterior surface of the petrous bone or the petrotentorial junction where the arachnoid villi are predominately found. Owing to the diverse anatomic location from vestibular schwannomas, meningiomas are more likely to present with hearing loss later in the disease process and involve other cranial nerves more frequently. Radiologically, CT scan may demonstrates homogeneous masses showing its higher tendency for bony destruction or hyperostosis. The presence of calcification and dural tails may be helpful in differential diagnosis. Meningiomas usually show isointensity on both T1WI and T2WI, or variable signal intensity on T2WI, with bright enhancement. The similar MRI manifestations make radiologic differentiation of the two lesions difficult at times. Most reported IEAEs and present case were misdiagnosed as meningiomas. In a recent study, Yang Yang et al found it useful to apply MRS in differential diagnosis between meningioma and ependymoma, and helpful for making treatment decisions. intrascranial extral-axial ependymoma case showed choline and myo-inositol/glycine peaks, rather than alanine glutamate/glutamine peaks commonly dected in meningioma; however, the conclusion is made based on very rare data.

The remaining abnormalities found at CPA space account for less than 1% of all lesions in this region (Patel, 2012). Such as CPP, although exceedingly rare, needs to be taken into account. CPP shows iso to homogeneous hyperintensity on T1WI and T2WI, with 20% showing calcifications; whereas, calcification is rare in ependymal tumors.

However, these above neoplasms are rarely seen in children. For children, ependymal tumors usually arise from the fourth ventricle (the roof, floor, lateral medullary velum) and its lateral recess and extend into the CPA or subarachnoid space through the foramen of Luschka by means of exophytic growth. No case of CPA anaplastic ependymoma in children has been reported yet.

3 Conclusion

We describe a rare case of WHO Grade III anaplastic ependymoma in CPA region. Cerebellopontine angle (CPA) lesions can mimic more common tumors through nonspecific symptoms and radiologic findings. Conventional MRI sequences (T1- and T2-weighted MRI, contrast T1-weighted MRI) and information on lesion intensity, size, shape, boundary, multi-lobular growth, and surrounding edema) have not identified any pathognomonic radiologic features for the diagnosis of this entity; MR-spectroscopy provides additional biochemical information in which intense signals of myo-inositol are observed in ependymomas. However, due to the rarity of this entity, an accurate preoperative diagnosis remains difficult. This report documents a case of CPA anaplastic ependymoma and is contributory to understanding this rare neoplasm.

Authors’ contributions

Liang Zong-hui conceived and designed the work that led to the submission. Dou Ya-fang and Liang Zong-hui evaluated images and analyzed data. Dou Ya-fang completed the writing of the article. Liang Zong-hui revised the paper. All authors participated in paper writing and approved the final manuscript.

Acknowledgments

This work was supported by the Shanghai Jing’an District Health System talent training Plan discipline leader, project number JWRC2014D04.

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