Radiation-Induced High-Grade Glioma in a Long-Term Survivor of Medulloblastoma: A Case Report
Year: 2026
Type: preprint
Study design: Case Report
Abstract: Background Advances in multimodal therapy have significantly improved survival in medulloblastoma, but long-term survivors remain at risk of secondary malignancies. We describe a rare case of radiation-induced high-grade glioma developing after a disease-free interval of approximately seven years, and nearly nine years following initial treatment. Case Presentation A 19-year-old male with a history of classical medulloblastoma (CNS WHO grade 4) presented nine years after his initial diagnosis with worsening headaches and fatigue. His primary tumor was treated with multiple surgical resections followed by high-dose craniospinal irradiation and adjuvant chemotherapy, after which he remained under surveillance. Seven years after completing treatment, he came in with a four-week history of weight loss and fatigue. One week before admission, he developed drowsiness, followed by a 10-day history of right focal seizures and increasing right-sided weakness. On neurological examination, he was obtunded with a Glasgow Coma Scale score of 9/15 and showed right-sided spastic hemiparesis with impaired verbal responsiveness. Magnetic resonance imaging revealed multiple supratentorial lesions associated with extensive vasogenic edema and mild midline shift, raising concern for a secondary malignant neoplasm. A left frontal burr-hole biopsy was subsequently performed. Histopathological examination demonstrated a highly cellular glial neoplasm composed of pleomorphic, hyperchromatic tumor cells embedded within a fibrillary background. Prominent microvascular proliferation and frequent mitotic activity were identified, consistent with a high-grade infiltrating glioma. Immunohistochemical analysis showed diffuse glial fibrillary acidic protein (GFAP) positivity, absence of IDH1 R132H expression, retained ATRX nuclear staining, and a Ki-67 proliferation index of 15–20%. Tumor cells were negative for H3K27M, and mismatch repair protein expression was preserved. Based on the histopathological and immunophenotypic findings, a diagnosis of high-grade glioma, favoring astrocytoma, NOS, CNS WHO grade 4, was established. Given the patient's previous exposure to craniospinal radiotherapy and the prolonged latency period of nine years between treatment of the primary medulloblastoma and development of the high grade glioma, the lesion was highly suggestive of radiation-induced high-grade glioma. Despite supportive management, the patient's clinical condition deteriorated rapidly, and he succumbed to the disease one month after diagnosis. Conclusion This case illustrates the development of a secondary high-grade glioma in a long-term survivor of medulloblastoma, most likely representing a radiation-induced malignancy. It highlights the critical importance of lifelong surveillance in survivors of pediatric brain tumors, as early detection of secondary central nervous system neoplasms may allow timely intervention. Despite the limited therapeutic options available for these aggressive tumors, prompt recognition remains essential to optimize patient management and outcomes.
Source: Research Square
Institution: Aga Khan University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221473887