Ependymal Tumors: Overview of the Recent World Health Organization Histopathologic and Genetic Updates with an Imaging Characteristic

Supratentorial ependymoma, “not otherwise specified” (NOS), in a 1-year-old girl. Solid-cystic heterogeneous T2 signal (A and B) mass in the left frontoparietal lobe with a peripheral rim of nodular contrast enhancement (C) and severe mass effect. Gross total resection was performed with histopathology (D), revealing supratentorial ependymoma, CNS WHO grade III, with high cellularity and increased mitotic activity (up to 14 mitoses per 10 high-powered fields) along with necrosis, supporting an anaplastic designation. The tumor was classified as anaplastic ependymoma at an outside institution with unfeasible molecular testing available. Final integrated diagnosis was supratentorial ependymoma, NOS, given the lack of molecular analysis.

Supratentorial ependymoma, ZFTA fusion–positive, in a 12-year-old girl. Solid-cystic heterogeneous T2 signal (A) mass with T2-FLAIR hyperintense fluid contents (B) with increased ADC values (C, arrow). There is enhancement of the solid component and peripheral walls (D, arrow) with increased vascularity within the solid enhancing component on the CBV maps (E, arrow). Gross-total resection was performed with histopathology revealing fibrillary perivascular pseudorosettes (F, arrows), a hallmark of ependymoma. Molecular testing was performed by a solid tumor fusion analysis, next-generation sequencing (NGS), and DNA methylation profiling. By solid tumor fusion analysis, a ZFTA:RELA fusion was identified. NGS revealed a PIK3CA (p.R88Q) mutation and an approximately 2MB gain on chromosome 11, encompassing ZFTA and RELA, whole arm gain of chromosome 1q, and loss of chromosome 9. By DNA methylation profiling, the tumor matched to methylation class ependymoma, RELA fusion. Overall, the histologic, immunohistochemical, and molecular findings were consistent with supratentorial ependymoma, ZFTA fusion–positive (CNS WHO grade II).

PFA ependymoma in a 17-year-old boy. Predominantly solid, heterogeneous T2 signal (A and B, arrows) mass centered in the right cerebellomedullary cisterns, extending into the fourth ventricle with obstructive hydrocephalus. Lesion shows restricted diffusion (C, arrow) and reveals solid pattern of contrast enhancement (D) with mass effect upon the lower brainstem. Central calcification is seen within the mass on CT (E, arrow). Gross total resection and histopathology revealed posterior fossa ependymoma with high cellularity, elevated mitotic activity (up to 7 mitoses in a single high-power field), microvascular proliferation, and foci of necrosis, corresponding to CNS WHO grade III designation. Widespread loss of nuclear H3-K27me3 expression noted across neoplastic nuclei (E), consistent with the group A molecular group.

Posterior fossa group B (PFB) ependymoma in a 23-year-old man. Solid midline intraventricular mass centered in the fourth ventricle with hyperattenuated hemorrhagic foci on CT (A, arrow). Lesion shows heterogeneous T2 signal (B, arrow) with SWI signal drop-out (C, black arrow) confirming hemorrhagic changes. Lesion appears isointense on T1-weighted image (D, arrow) with moderate contrast enhancement (E, arrow). Tumor resection showed an ependymoma with moderate to high cellularity, moderate proliferative activity (up to 4 mitoses per 10 high power field) and with multiple areas of bland necrosis. There was no evidence of microvascular proliferation, and the histopathologic features were consistent with a CNS WHO grade II ependymoma. The tumor cells showed retained expression of H3K27me3 on immunohistochemical stains (F) consistent with a PFB ependymoma. This finding was confirmed by a whole genome methylation analysis performed. Next-generation sequencing studies were performed that did not disclose the presence of significant mutations and/or fusion.

Multifocal spinal ependymoma, NOS, in a 42-year-old woman. Multifocal T2 hyperintense (A) enhancing (B and C) neoplasms throughout the spinal cord in the central region. Neoplasm shows perivascular pseudorosettes on H&E stains (D) with scattered mitotic activity (up to 3 mitoses per 10 high-power fields) and no microvascular proliferation or necrosis, suggesting a low-grade designation. Genomic alterations include gain of chromosomes 5 and 9, and loss of chromosomes 13 and 22. The tumor lacked features of myxopapillary ependymoma or subependymoma, and testing for MYCN amplification was negative. Despite the absence of vestibular schwannoma and any significant family history, the pattern of alterations was consistent with NF-2. Given the absence of MYCN amplification, these tumors are now classified under spinal ependymoma, NOS.

Multifocal spinal ependymoma, MYCN-amplified, in a 29-year-old man. Sagittal (A and B) and axial (C) postcontrast MR images reveal few intramedullary (A, white arrow) and multiple extramedullary (A, black arrows) tumors of varying sizes throughout the thoracic cord and cauda equina nerve roots (A–C). Immunohistochemistry shows many tumor cells expressing GFAP (D) in perivascular radiating processes (pseudorosettes). Tumor revealed high-grade anaplastic histopathologic features, including high mitotic activity, and microvascular proliferation. Chromosomal microarray analysis revealed genomic alterations, including amplification of 2p24.3 (including MYCN), loss of chromosome 17, and gain of chromosomes 4, 7, 8. 9. The pattern of alterations was consistent with spinal ependymoma, with amplification of MYCN.