A pediatric H3K27-altered diffuse midline glioma with suspected systemic lymphatic dissemination complicated by bilateral pleural effusion: a case report

H3K27-altered diffuse midline glioma (DMG) is a highly malignant pediatric central nervous system (CNS) tumor with an extremely poor prognosis. Extraneural metastases are rare, and systemic dissemination accompanied by pleural effusion is even more uncommon, with limited clinical evidence reported to date. We report an 8-year-old female with brainstem-origin H3K27-altered DMG who achieved 2-year local control of the primary lesion after radical radiotherapy. The lesion first metastasized to the spinal epidural space, followed by widespread systemic dissemination characterized by bilateral pleural effusion and extensive lymphadenopathy. Pathological and genetic testing confirmed the metastatic lesions were consistent with the primary DMG, with H3F3A p.K28M missense mutation identified. This case challenges the conventional understanding of limited metastatic potential of H3K27-altered DMG, suggesting prolonged survival may facilitate systemic spread, with lymphatic drainage as a hypothesized dissemination pathway that lacks direct pathological validation. The unique metastatic pattern provides new insights into the biological behavior of this tumor. This case enriches the clinical spectrum of H3K27-altered DMG, highlighting the necessity of long-term systemic surveillance for long-surviving patients and further investigation of systemic anti-tumor therapies; the hypothesized lymphatic metastatic route requires additional pathological verification in future cohorts.