According to the World Health Organization (WHO) classification, the term ependymoma comprises a histologically heterogeneous group of tumours that include cellular, papillary, clear cell and tanycytic subtypes. Ependymoma with lipomatous differentiation [17
], ependymoma with extensive tumour cell vacuolization [8
], melanotic ependymoma [16
], signet-ring cell ependymoma [20
] and GCE are rare variants.
Zec et al. [19
] first described two cases of giant-cell ependymoma of the filum terminale in 1996. They suggested that the absence of perivascular pseudorosettes in GCE might reflect the failure of the neoplastic cells in this tumour to elaborate perivascular processes.
To date eight cases of GCE have been documented in the literature [1
]; only one of these was located in the spinal cord [7
]. Our case is the second example of a cervical spinal cord GCE, and the first with focal calcifications.
Recognizing ependymoma in frozen sections can be difficult, particularly in cases without the characteristic epithelial features and perivascular pseudorosettes. On frozen sections ependymoma often appear distinctly astrocytic because the freezing process exacerbates the fibrillarity and gemistocyte-like appearing of the neoplastic cells.
In the present case the tumour appeared to have a definite cleavage plane for almost its entire extension, a minor area of apparently infiltrating lesion being localized rostrally on the left side. Intra-operatively, in view of both the surgical anatomical features of the mass and the relatively ease of its dissection off the spinal cord, the neoplasm appeared less-infiltrating and less-aggressive. Therefore, given such gross appearance and surgical features, although frozen section analysis suggested a high grade, malignant tumour, the decision to continue debulking the mass until total macroscopic removal was taken. Subsequently, only paraffin sections and immunohistochemical investigations revealed unequivocal evidence of an ependymal tumour with pleomorphic giant cells and focal calcifications.
The histological grading of ependymomas has been a matter of debate, and the wide range in the incidence of anaplastic ependymoma (7–89%) highlights the difficulty in agreeing on a histological grading system [12
]. One of the reasons for such conflicting results are the histopathological criteria currently used to classify an ependymoma as benign or malignant. These are often subjective and not clearly defined. Our case did not satisfy the criteria established by the WHO for anaplastic ependymoma because no significant mitotic activity, microvascular proliferation and pseudopalisading necrosis were present.
Differential diagnosis of GCE includes anaplastic oligodendroglioma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma and giant cell glioblastoma [1
]. GCE has a good prognosis [19
] because, as well as in subependymal giant cell astrocytoma [4
] and pleomorphic xanthoastrocytoma [11
], the presence of pleomorphic giant cells has no correlation with an aggressive behaviour. These histopathological features correlate with the clinical outcome in the present case: at 18-month follow-up progressive neurological improvement has been registered and no signs of tumour recurrence are shown on MRI scan, despite no adjuvant therapy, i.e. radiotherapy, has been administered. The latter should be reserved for tumour recurrences or in cases of partially resected lesions showing evidence of progression over time. We agree with Zec et al. [19
] who attribute cellular pleomorphism to degenerative changes; in fact, in our case, giant cells were strictly observed in association with focal calcifications. And these did not worsen the prognosis, as also reported by Ho et al. [9
]. Ki-67 is an adjunctive prognostic indicator for ependymoma [2
], and the low Ki-67 labelling index in our case has been associated with no disease progression.
The present case highlights the limits of frozen section examination, particularly if a sufficient amount of tissue is not available. It also shows that areas with increased cellularity, increasing variations in nuclear size, in shape, coarseness or dispersion of chromatin, and nucleolar prominence can easily suggest the wrong diagnosis of a malignant, higher-grade neoplasm. Despite possible worrisome histological features, GCE is associated with a relatively good prognosis. It is, hence, important to perform a radical tumour resection in order either to cure the patient or to avoid any further treatment, usually deemed unnecessary for a less aggressive tumour.