Extensive anaplastic multi-centric ependymoma in a young adult: case report and literature review

Abstract

Background

Ependymoma is a rare adult tumor that originates from ependymal cells of the ventricles and the spinal cord. The diagnosis and management can be very challenging. This study aims to bring out the hypothalamus as an atypical location of ependymoma and to underline the consequences of treatment delay in anaplastic ependymomas through a concrete case.

Case presentation

We present a case of 20 years with no previous medical history, suffering from progressive intracranial hypertension syndrome, tetraparesis, cerebellar ataxia, and a weight loss of 3 kg in 4 months. Cerebral and medullar Magnetic Resonance Imaging showed multiple processes including the temporal region, the cerebellum, the 4th ventricular floor, the interpeduncular cistern, the hypothalamus, and almost the entire spinal cord, in addition to a posterior intradural lesion. The hypothalamic localization was very suggestive of neurohistiocytosis. A stereotactic biopsy and immunohistochemical study confirmed the diagnosis of anaplastic ependymoma. Total resection was impossible and radiotherapy was delayed by inconclusive dosimetric scans. The patient's outcome was unfortunately quickly fatal.

Conclusions

Ependymomas should be evoked whatever the location in the central nervous system. Radiotherapy must be quickly discussed and started when the gross total resection is impossible. The locations, as well as the doses of irradiation, are now well-established and any delay in initiating radiotherapy only darkens the prognosis.

Background

Ependymoma is a glial neoplasm that originates from the ependymal cells lining the brain ventricles and the central canal of the spinal cord. There is a clear predominance in infants compared to the adult population. It also remains clinically silent for a long time and appears very heterogeneous on imaging [1, 2].

Many atypical origins and extensive locations of this tumor have been described in the literature and many theories have been proposed to explain them.

This paper aims to point out the atypia, and extensibility and the consequences of treatment delay of anaplastic ependymomas through a concrete case and a review of the literature.

Case presentation

Authors present 20 years, right handed man, a university student with no personal or familiar medical past. He complained of neurological symptoms, which appeared 4 months before the admission and included intracranial hypertension syndrome (headache, vomiting, and blurred vision), progressive tetraparesis, and balance deficit, all in addition to polydipsia, polyuria, and a weight loss of three kilograms in 4 months. We noticed an underweight patient (BMI = 16.5) with asymmetric tetraparesis scored between 3 and 4/5, cerebellar ataxia, and no papillary edema.

Encephalic and spinal cord Magnetic Resonance Imaging MRI (SIEMENS Healthineers, MAGNETOM Aera 1.5 T, Germany) showed multiple intra and extra-axial, supra and infratentorial processes of different sizes and heterogeneous compounds.

The most voluminous supratentorial lesion was located in the temporal lobe. It was spherical, measuring 11 mm, and with no enhancement after Gadolinium injection (Fig. 1).

Fig. 1

MRI of the brain shows a spherical temporal lesion, measuring 11 mm, unchanged after gadolinium injection (arrows)

Infratentorial lesions involved the cerebellum (Fig. 2), the 4th ventricular floor, and the interpeduncular cistern (Fig. 3). These lesions appeared as T1-hyposignal, T2-hypersignal and included tissue and liquid signals.

Fig. 2

Axial MRI of the brain shows multiple lesions of cerebellum appearing as T1-hyposignal, T2-hypersignal with certain liquid signals (arrows)

Fig. 3

Axial and sagittal MRI of the brain shows lesions of the 4th ventricular floor and the interpeduncular cistern appearing as T1-hyposignal, T2-hypersignal with certain liquid signals (arrows)

The hypothalamic region was the seat of a voluminous lesion of 21 × 22 mm, T1-isosignal, T2-hyperintense with an obvious enhancement after Gadolinium. It comes into contact with the optic chiasm and internal carotid arteries and compresses the pituitary stem, pushed back (Fig. 4).

Fig. 4

T1 sagittal MRI of the brain showing a voluminous lesion of the hypothalamus, measuring 21 × 22 mm, T1-isosignal and T2-hyperintense, with an obvious enhancement after injection of Gadolinium, close to the optic chiasm and the internal carotid arteries and compresses the pituitary stem pushed back (arrows)

The spinal MRI showed an almost total infiltration of the spinal cord by cystic and tissue lesions, in addition to a posterior intradural lesion of 11 mm, at T4–T5 disc level, compressing the spinal cord, reduced to 4 mm of transversal diameter (Fig. 5).

Fig. 5

Sagittal MRI of the spine showing an almost total infiltration of the spinal cord by cystic and tissue lesions, in addition to a posterior intradural lesion of 11 mm (arrow), at T4–T5 disc level, compressing the spinal cord reduced to 4 mm

Clinical and radiological correlation, in this case, was very suggestive of neurohistiocytosis and neurosarcoidosis particularly due to hypothalamic localization. The rapid evolution and the extensive appearance on the MRI were not very suggestive of a tumor, an ependymoma, for example.

The case was discussed in a multidisciplinary meeting and an agreement was found about a biopsy of the dorsal intradural lesion (Fig. 6). The anatomopathological and immunohistochemical evaluation of the tumor samples concluded with anaplastic ependymoma WHO grade III (Fig. 7).

Fig. 6

Biopsy of the dorsal intradural lesion at T4–T5 disc level

Fig. 7

A Histology of an anaplastic ependymoma grade III. Immunohistochemical staining showing expression of anti-GFAP; Glial Fibrillary Acidic Protein (B), anti-EMA; Epithelial Membrane Antigen (C) and anti-Ki67 (D) in anaplastic ependymoma grade III

Because of the rapid deterioration of the neurological state of our patient, dosimetry and, therefore, radiotherapy were delayed. The patient's outcome was unfortunately quickly fatal.

Ependymomas are very rare and especially affect children [1, 2, 3]. Different statistics have been published. The variability of reported epidemiologic results can be attributed to the heterogeneity of the patients (age) and tumors’ characteristics (location) [3, 4, 5]. Ependymoma originates from the ependymal cells of the central nervous system. Therefore, it is typically located in the ventricles and the spinal cord.

In regards to intracranial ependymoma, the average age of onset is very heterogeneous. It is 16 ± 1 years in the Maghreb series [6, 7], 46.1 ± 16 years in a French series of 121 cases [8], and 42.2 years in an American meta-analysis of 183 cases (based on 56 studies) [9]. The neoplasm is compressive rather than infiltrative. It remains clinically silent for months or even years [9]. These two data argue for the onset of this neoplasm at a very early age in our patient, with progressive volume gain and extensibility. Headache and vomiting are the most common presenting signs followed by cerebellar syndrome [6–9]. Schwartz and colleagues, in a study of supratentorial ependymomas in adult patients, noted that only one-quarter of ependymomas involve the brain in adults, in contrast to 90% in children [10]. It fits with the results of Sayegh and colleagues’ meta-analysis. Indeed, Sayegh reported that about 61% of ependymomas were supratentorial. However, the French and Tunisian series found a predominance of infratentorial localization, which represented, respectively, 60.1% and 77.4% of intracranial ependymomas. In addition, it has been noted that an extraventricular location is more common than an intraventricular one in the subgroup of supratentorial ependymomas [9].

Intraspinal ependymomas are the most prevalent primary intramedullary spinal tumor in adults [11]. The reported mean age at diagnosis was around 32.4 (Australia), 35.2 ± 17.8 (China), 41.8 (France), and 43.5 (USA) years [5, 12–14]. Pain, neurological deficit, and paresthesia are the main revealing symptoms [13, 15]. Cervical localization is not only recognized as the most common but also as a good prognostic factor of survival. In addition, intramedullary ependymoma often occurs centrally in the spinal cord [16]. Contrariwise, intraspinal extramedullary ependymoma is very unusual. Lars Gardner established a summary table of 18 cases of intraspinal extramedullary ependymomas published from 1951 to 2013 [17]. We noted that this subgroup of intraspinal ependymoma preferentially affects young women (13/18) and the thoracic floor (12/18) and that resection was complete in all cases.

Through the literature review, we noticed that many atypical localizations have been reported (Table 1) [18–22]. The extra-axial cerebral localization, the cerebellopontine angle, the pineal region, and the sella turcica are the most recent. The hypothalamus is the one never described as far as we know. This exceptional localization was very suggestive of neurohistiocytosis and neurosarcoidosis. Larsen and colleagues, trying to resolve the enigma of the pituitary fossa ependymomas, suggested that it is the consequence of neoplastic transformation of heterotopic ependymal cells or embryological remnants of the ependymal cells lining in the infundibular process [23]. Our patient presented a very extensive ependymoma at the time of diagnosis, with supratentorial cerebral localization (extra-axial and hypothalamic), subtentorial and intraspinal; intra and extramedullary development.

Table 1 Overview of the published cases of atypical ependymomas localization

Extra-cranial and extra-spinal ependymomas are extremely rare [24]. They mainly occur in children and young adults. Sacrum, mediastinum and ovarium are the most frequent. Over a 25-year period, Yust Katz and colleagues [24] published a paper of 8 cases of which five were sacral. The proximity of the sacrum to the spinal cord may explain why it is, indeed, the most frequent location of ependymomas arising outside the central nervous system. Since 1988, only 10 cases of mediastinal ependymoma have been reported. All patients were women with a median age of 44 years. They suffered from back pain and/or dyspnea and had atypical imaging aspects [25]. Ovary, board ligament, and mediastinum are the most reported extra-neurological ependymomas in women. These localizations support the germinal cell theory.

If the tumor location is very variable in ependymomas, the imaging is even more heterogeneous. In CT (Computed Tomography), ependymoma appears iso, hypo, or hyperdense, with heterogeneous enhancement after contrast product injection [7]. CT scan is superior to MRI in highlighting intralesional calcification. However, MRI remains the gold standard in ependymoma imaging [26]. Ependymomas demonstrate low T1, high T2, and intermediate to high Flair signal, with Cystic formation, calcifications, hemorrhage, and necrosis [16, 26]. Diffusion-weighted imaging, Perfusion MRI, and MRI spectroscopy are increasingly used sequences that orient the tumor nature of a suspicious MRI lesion [26]. The diagnosis of ependymoma is based on pathology and immunohistochemistry. The diagnosis of an intracranial ependymoma requires a complement by medullary MRI ± a study of the CSF (cerebrospinal fluid) in search of medullary dissemination, to guide the therapeutic approach [7].

The management of ependymoma is based on surgery and radiotherapy [27, 28]. Maximal safe resection and relief of obstructive hydrocephalus are the targets of surgery [29]. Indeed, whatever the intracranial or medullary seat of the tumor, the surgical resection must be total whenever feasible [27]. A second-look surgery is only recommended for intracranial ependymoma when postoperative MRI shows an unsatisfactory resection [28]. Postoperative conformal radiotherapy is recommended for patients with WHO grade III (anaplastic) ependymomas (Table 2), regardless of the extent of resection, and for patients with WHO grade II ependymomas following incomplete resection [28]. The use of chemotherapy in newly diagnosed ependymomas remains very controversial [16]. However, chemotherapy might be warranted in patients with recurrent ependymomas, who are no longer eligible for local treatments [28].

Table 2 Recommendations for the treatment of intracranial and spinal grades II and III ependymomas in adults [28]

Conclusions

The diagnosis of ependymoma is very challenging because of its atypical origins, its extensive sites and its heterogeneous MRI aspects. Consequently, ependymoma should be evoked whatever the location; in the central nervous system and even outside of it, especially the sacrum. Indeed, it should be considered a differential diagnosis of tumors in pineal, intrasellar and hypothalamus regions. Only biopsy and immunohistochemistry study can confirm the tumor nature. The optimal management is gross total resection and radiotherapy. If maximal safe resection if impossible, as the case of CSF or spinal dissemination, craniospinal irradiation is recommended and must be carried out quickly.