Primary Leptomeningeal Spread of Glioblastoma : A Rare Case Report

Abstract

Background : Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults and is classified as a CNS WHO grade 4 diffuse astrocytic tumor. Leptomeningeal spread (LMS) represents one of its most severe complications, occurring in up to two-thirds of patients when assessed using advanced imaging or autopsy. However, clinically symptomatic LMS is reported in only 2–4% of cases and is often underrecognized due to overlapping symptoms with tumor progression. Primary, or de novo, LMS at the initial presentation of GBM is exceedingly rare and poses significant diagnostic challenges, particularly because early manifestations may mimic infectious or inflammatory meningoencephalitis. Advances in MRI techniques have improved the early detection of leptomeningeal involvement.

Case Presentation: A woman in her 40s presented with an unknown-onset tonic–clonic seizure and a 10-month history of recurrent seizures despite antiepileptic therapy. Her symptoms had progressed to chronic headaches, left-sided weakness, dysarthria, and declining consciousness. Neurological examination revealed papilledema, left central facial palsy, and left hemiparesis. CT imaging demonstrated a heterogeneous right parietal mass, while advanced MRI with spectroscopy identified an extra-axial enhancing lesion with cystic components suggestive of high-grade glioma with possible leptomeningeal involvement. Gross total tumor resection was performed. Histology revealed hypercellularity, pleomorphic anaplastic glial cells, palisading necrosis, and microvascular proliferation, while immunohistochemistry showed IDH-1 positivity, ATRX loss, and negative p53, confirming Astrocytoma, IDH-1 mutant, CNS WHO grade 4. Five days postoperatively, the patient developed worsening consciousness without radiologic evidence of hemorrhage or increased intracranial pressure. Her condition continued to decline, and she passed away one month later due to multiorgan failure following a septic infection.

Conclusion: This case demonstrates the rare occurrence of primary LMS as the initial manifestation of GBM. Early leptomeningeal involvement should be considered in patients presenting with multifocal neurological deficits or rapidly progressive symptoms. Advanced MRI techniques are essential for early detection, particularly when clinical findings overlap with other intracranial pathologies. Although IDH mutation is often associated with improved prognosis, this advantage may diminish in grade 4 astrocytomas, which can still exhibit highly aggressive behavior. Prompt recognition and comprehensive management are critical, although overall prognosis remains poor.