An Overview of Intracranial Ependymomas in Adults

Abstract

Ependymomas are rare primary central nervous system tumors. They can form anywhere along the neuraxis, but in adults, these tumors predominantly occur in the spine and less frequently intracranially. Ependymal tumors represent a heterogenous group of gliomas, and the WHO 2016 classification is based essentially on a grading system, with ependymomas classified as grade I, II (classic), or III (anaplastic). In adults, surgery is the primary initial treatment, while radiotherapy is employed as an adjuvant treatment in some cases of grade II and in all cases of anaplastic ependymoma; chemotherapy is reserved for recurrent cases. In recent years, important and interesting advances in the molecular characterization of ependymomas have been made, allowing for the identification of nine molecular subgroups of ependymal tumors and moving toward subgroup-specific patients with improved risk stratification for treatment-decisions and future prospective trials. New targeted agents or immunotherapies for ependymoma patients are being explored for recurrent disease. This review summarizes recent molecular advances in the diagnosis and treatment of intracranial ependymomas including surgery, radiation therapy and systemic therapies.

Keywords: brain tumors; chemotherapy; ependymoma; glioma; radiotherapy.

Figure 1

Histological features of ependymal tumors. (A) Classic ependymomas are well-circumscribed neoplasms with clear-cut vascular pseudorosettes. Immunohistochemically, the neoplastic cells show variable expression for GFAP with characteristic para-nuclear dot-like positivity for EMA. OLIG2 is weak to negative (B) Anaplastic ependymomas are hypercellular tumors with brisk mitotic activity, frequent micro-vascular proliferation, and palisading necrosis. (C) Myxopapillary ependymomas feature well-differentiated cuboidal to elongated tumor cells that are radially oriented around vascularized myxoid cores with a papillary architecture. Endothelial proliferation and cellular atypia are typically absent. (D) Subependymomas consist of small clusters of cells with isomorphic nuclei, scattered throughout a finely fibrillary background with microcysts (H and E and immunoperoxidase stains; original magnification, 10×, 20× and 40×).

Figure 2

Supratentorial (case 1) and infratentorial (case 2) ependymomas. Case 1: a 50-year-old female patient with a lesion in the frontal horn of the right lateral ventricle: a right fronto-parietal transcortical approach was used to remove the tumor whose histology, based on the WHO classification, was A grade I ependymoma). From left to right: pre-operative CT scan; intraoperative image of the tumor under white light microscope illumination; blue light illumination using 5-ALA: in this case the tumor was not fluorescent; and finally, the post-operative CT scan. Case 2: a 29-year-old female patient with an intraventricular lesion in the IV ventricle, with moderate contrast enhancement in T1-weighted MRI scan. The histological diagnosis revealed a grade III ependymoma (WHO 2016).