Novel Insights from Clinical Practice Pediatr Neurosurg 2013;49:93–98 DOI: 10.1159/000356931

Received: August 7, 2013 Accepted after revision: October 29, 2013 Published online: December 21, 2013

Extensive Cartilaginous Metaplasia of Recurrent Posterior Fossa Ependymoma: Case Report and Review of the Literature Alexandros Boukas a Abhijit Joshi b Alistair Jenkins a Damian Holliman a Departments of a Neurosurgery and b Neuropathology, Regional Neurosciences Centre, Royal Victoria Infirmary, Newcastle Upon Tyne, UK

Established Facts • Cartilaginous metaplasia is a rare variance of ependymomas with unknown origin. • Surgical excision can prolong survival.

Novel Insights • This is the first report of cartilaginous metaplasia replacing the entirety of the tumour architecture. • Cartilaginous metaplasia can be a late feature after multiple excisions, chemotherapy and radiotherapy, providing us with the opportunity to observe stages of tumour progression. • Ability to achieve gross total resection can be compromised by the cartilaginous/ossified ependymoma.

Key Words Ependymoma · Cartilaginous metaplasia · Chondroid metaplasia · Fourth ventricle

Abstract Cartilaginous metaplasia in ependymomas is extremely rare and only few cases have been reported in the literature. We describe a case of a 5-year-old patient with a 5th recurrence of 4th ventricle ependymoma. He was previously treated with 4 resections, chemotherapy and radiotherapy. Histopa-

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thology revealed well-differentiated chondroid tissue occupying almost the entire lesion. Near total resection was achieved for the 5th time, but the patient died 3 months later achieving a total survival of 48 months, the 3rd longest reported in literature. Multiple resections of tumour recurrence provided a new insight in this very rare tumour, as it gave us the opportunity to observe the progression of tumour aggressiveness from grade II to grade III and finally to chondroid metaplasia. Cartilaginous metaplasia in posterior fossa ependymomas is a very atypical and challenging tumour with poor overall prognosis. © 2013 S. Karger AG, Basel

Alexandros Boukas Neurosurgical Department, Regional Neurosciences Centre Royal Victoria Infirmary, Queen Victoria Road NE1 4LP Newcastle Upon Tyne (UK) E-Mail alexanderboukas @

A 5-year-old boy presented with recurrence of a known posterior fossa ependymoma (fig. 3, 4). He had previously been treated with 4 resections, chemotherapy (between 1st and 2nd resection) and radiotherapy (after 2nd resection). The child was initially diagnosed when 22 months old with signs of raised intracranial pressure. MRI scan showed a large heterogeneous mass filling the 4th ventricle completely (fig.  1). He underwent complete macroscopic resection which revealed a grade II ependymoma. Glial fibrillary acidic protein (GFAP) and S-100 were both positive. Following resection he received chemotherapy, including vincristine, carboplatin, methotrexate, cyclophosphamide and cispla-

tin for 1 year [1]. At 18 months, a 2nd resection for recurrence (fig. 2) demonstrated a more aggressive grade III ependymoma after which he received radiotherapy (54 Gy in total). A 3rd (14 months after the 2nd) and a 4th (17 months after the 3rd) operation were carried out and both times total macroscopic excision was achieved. Histology was consistent as previously with grade III anaplastic ependymoma with hypercellularity, perivascular pseudorosette formation and frequent mitotic activity (4th resection; fig. 6e, f). A further recurrence 2 months later (fig. 3) was initially treated with palliative oral etoposide with poor response. However, the tumour was still felt to be resectable (fig.  5) and as the patient tolerated previous resections well, a 5th operation was performed. No CT scan was performed prior to surgery that could potentially identify the presence of cartilaginous/osseous tissue. The tumour was macroscopically calcified with a cartilaginous appearance (fig.  6a) and difficult to mobilize, leading to near total (>95%) resection. Histological examination of the sample taken during the last resection confirmed the macroscopic findings of well-differentiated cartilaginous tissue which showed mildly increased cellularity containing clusters of chondrocytes, some of which displayed nuclear atypia. The lesion was almost entirely composed of cartilaginous lobules which were well demarcated and separated by thin strands of tissue with mildly increased cellularity composed of scattered spindle cells and macrophages (fig. 6b, c). A small proportion of the spindle cells in the tissue intervening

Fig. 1. T1-weighted sagittal and axial MR images with contrast (presenting scan) showing a large soft tissue mass with heterogeneous enhancement filling the body of the 4th ventricle, extending

through the foramina of Magendie and Luschka. There is prominent mass effect with obstructive hydrocephalus and crowding at the foramen magnum.


Cartilaginous metaplasia with or without bone formation in ependymomas is an extremely uncommon phenomenon. We report a case in a 5-year-old patient with multiple recurrent 4th ventricle ependymoma (fig.  1–5). The tumour was macroscopically calcified and histopathology revealed cartilaginous metaplasia throughout. Case Report


Pediatr Neurosurg 2013;49:93–98 DOI: 10.1159/000356931


between the cartilaginous lobules showed weak-to-moderate GFAP staining. GFAP immunoreactivity was mainly within chondrocytes (fig. 6d), which were also S-100 positive. Ki-67 labelling was generally very low within the cartilaginous lobules as well as the intervening tissue. In contrast to the previous resections, there was no definite morphological evidence of a neoplastic ependymal element within the specimen.


Cartilaginous metaplasia of paediatric ependymomas was first described by Mackay [2] in 1935 and since then only 14 cases have been reported [2, 3]. Mean age was 20 years (1–61), and this is only the 3rd case that was originally diagnosed under the age of 3 [3–5]. The most com-

Fig. 2. T1-weighted axial with contrast axial and T2-weighted FLAIR sagittal MR images (1st recurrence, 14 months after surgery, end of chemotherapy) showing a 6-mm nodule of high signal within/just projecting into the 4th ventricle to the left of midline. There is no enhancement after contrast.

Fig. 3. T1-weighted axial and sagittal MR

images with contrast (5 months after 4th excision, on oral chemotherapy) showing an enhancing lesion within the 4th ventricle. Post-surgical changes of the left cerebellopontine angle (4th resection) with no abnormal enhancement seen.

Cartilaginous Metaplasia of Ependymoma

Pediatr Neurosurg 2013;49:93–98 DOI: 10.1159/000356931


Fig. 4. T1-weighted axial and sagittal MR images with contrast showing the extent of recurrent 4th ventricle ependymoma before 5th resection was attempted.

Fig. 5. T1-weighted axial and sagittal MR images with contrast (2 months after excision of cartilaginous tumour) showing significant recurrence of disease with increase in size of the enhancing tumour in the 4th ventricle, extending into the medulla, with mass effect and surrounding oedema in the cerebellum and up to the pons.


Pediatr Neurosurg 2013;49:93–98 DOI: 10.1159/000356931


Color version available online







Fig. 6. a–d Macroscopic and microscopic appearance of cartilaginous metaplasia of posterior fossa ependymoma during the 5th (last) attempted resection. a Pale grey-white lobulated tissue with a cartilaginous appearance. b Well-differentiated cartilaginous lobules. HE. Low magnification. c Well-differentiated cartilaginous lobules. HE. Higher magnification. d GFAP expression with-

in chondrocytic cells. GFAP immunohistochemistry. e, f Microscopic appearance of anaplastic ependymoma (4th resection). e Anaplastic ependymoma with perivascular pseudorosettes. HE. Low magnification. f Anaplastic ependymoma with frequent mitotic activity. HE. High magnification.

mon location is the 4th ventricle (12 cases, 73.3%); 1 was prepontine extending to the suprasellar region and 2 were supratentorial (temporo-occipital, frontal lobes) [3–6]. Histopathological examination in all cases revealed classic ependymoma features with pleomorphic fibrillary cells arranged in perivascular pseudo- and ependymal rosettes. Metaplastic tissue was surrounded by ependymoma cells with low pleomorphism and low mitotic activity. The extent of the metaplasia, occupying almost the entire tumour, makes our case unique. At the time of the diagnosis, 2 patients were WHO grade I, 4 were grade II and 6 grade III. In 3 reports no official grading was mentioned [2, 3, 7, 8]. Ghosal et al. [9] described a patient that was initially diagnosed as a grade II ependymoma with chondroid metaplasia, which progressed to grade III 12 months after resection. In our case the tumour progressed from grade II to grade III between the first 2 resections and a course of chemotherapy (18 months later). Cartilaginous tissue was found only in the last operation, 27 months later.

Cartilaginous metaplasia was found on the initial operation in 7 cases (64%), on the 2nd operation following adjuvant radiotherapy in 1 (9%) and on the 3rd operation following radiotherapy in 2 (18%) [3–5, 10]. Our patient was the only one to have 5 resections in total and histological findings progressed from a grade II to more aggressive grade III anaplastic ependymoma following a year of chemotherapy and then, after a course of radiotherapy, to ependymoma with cartilaginous metaplasia. Immunohistochemically, GFAP was positive in all cases that were tested and also positive in the cartilaginous metaplastic tumour cells in 92% of cases. Of 12 cases that were tested for epithelial membrane antigen 58% were found positive, and all 7 cases tested for S-100 protein were positive [3–5]. The origin of cartilaginous metaplasia is unknown. Kepes et al. [7] noticed the presence of morphological transition from ependymoma to GFAP-positive chondrocytes which implies glial origin of the cartilaginous

Cartilaginous Metaplasia of Ependymoma

Pediatr Neurosurg 2013;49:93–98 DOI: 10.1159/000356931


components of the tumour. Those cells possibly secrete basement membrane material and mucopolysaccharides which gradually concede to a form of chondroid ground substance. During the same period the glial cells transform into functional chondrocytes [4, 6, 7, 9, 11, 12]. Mathews and Moossy [13] described 4 cases of gliomas with fibrous capsules and GFAP-negative cartilaginous metaplasia and hypothesized that it originates from connective tissue cells (fibroblasts). This has also been supported by other cases of glial tumours, but not in ependymomas. Moreover, the consistency of GFAP positivity (92%) in all ependymomas makes it a less likely hypothesis [11]. Other hypotheses, not widely accepted, include fibroblastic origin of chondrocytes, mixed mesenchymal-neuroepithelial nature of cartilaginous areas, heteroplasia, and ossification of mucoid degeneration matrix [7, 11]. There is no consensus about the causes that lead to this rare phenomenon. Kepes et al. [7] and Feyza et al. [11] hypothesized that previous radiotherapy could have attributed to the metaplastic changes. This type of mesenchymal metaplasia in (neuro) epithelial tumour is very rare. Previous reports include squamous metaplasia following radiotherapy in pituitary adenomas [14] and pros-

tate gland [15]. The mean time between radiotherapy and appearance of cartilaginous tissue was 46 months (5–111) in mixed infra- and supratentorial cases. In 4 cases (36%), including ours, chondroid tissue was not present in the initial resection and appeared following radiotherapy [8, 10, 11]. The combination of radiotherapy and consequent chemotherapy before the appearance of cartilaginous metaplasia has never been reported before. It could be considered whether either of the treatment modalities contributed to such a pathological change.


Cartilaginous metaplasia in paediatric ependymoma is rare and remains poorly understood. We present a case in which repeated resections gave us the opportunity to observe the tumour progression from grade II to III and then to cartilaginous metaplasia.

Disclosure Statement The authors declare that they have no conflict of interest.

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Extensive cartilaginous metaplasia of recurrent posterior fossa ependymoma: case report and review of the literature.

Cartilaginous metaplasia in ependymomas is extremely rare and only few cases have been reported in the literature. We describe a case of a 5-year-old ...
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