Abstract
Supratentorial extraventricular anaplastic ependymoma is a rare entity, often resulting in diagnostic delays and rapid recurrence that complicate management. We report a case in a 67-year-old woman, emphasizing the need for broad immunohistochemical and molecular evaluation. A 67-year-old female presented with two weeks of progressive left-sided hemiparesis. Brain magnetic resonance imaging revealed a ring-enhancing lesion with central necrosis and extensive perilesional edema in the right frontal lobe. She underwent right frontal craniotomy with gross total resection. Initial pathology (May 1, 2025) demonstrated poorly differentiated malignant cells, prominent necrosis, microvascular proliferation, and up to eight mitoses per ten high-power fields. Immunohistochemistry showed strong perinuclear dot-like CD99 expression, focal CD56 positivity, focal weak somatostatin receptor 2a positivity, very weak GFAP, and focal CD138 positivity. EMA, TTF-1, panCK, MUM1, CD3, CD79a, kappa, lambda, and EBV in situ hybridization were negative. The Ki-67 proliferation index was 80%. Integrated findings supported a diagnosis of anaplastic supratentorial ependymoma (WHO grade III). Six weeks later (June 15, 2025), the patient returned with worsened left hemiparesis. MRI demonstrated a 1.5–2.0 cm nodular recurrence adjacent to the resection cavity with associated necrosis and edema. Repeat gross total resection was performed. Second pathology revealed similar poorly differentiated, necrosis and microvascular proliferation. Immunohistochemistry again showed strong perinuclear CD99 expression, with GFAP and EMA remaining negative. Initial “cancer panel” next-generation sequencing (NGS) was negative; “sarcoma panel” NGS for EWSR1, SYT-SSX, STAT6, HEY1-NCOA2, and MDM2 is pending. The rarity of extraventricular anaplastic ependymoma and overlapping immunoprofiles can lead to misclassification and delayed treatment, facilitating rapid recurrence. Persistent CD99 positivity without GFAP or EMA expression raises suspicion for a non-neuroglial round cell sarcoma. Negative results from a standard glial NGS panel underscore the limitations of routine testing. Early comprehensive immunohistochemical profiling combined with timely sarcoma-targeted NGS is essential to avoid misdiagnosis and guide appropriate therapy. A multidisciplinary approach integrating pathology, immunophenotyping, and molecular data is critical for accurate classification and personalized treatment.