Cerebrospinal fluid tumor-derived DNA analysis aids in the diagnosis of postpartum diffuse midline glioma.

Abstract

Background: Gliomas diagnosed during pregnancy or postpartum pose diagnostic and management challenges. Neurologic symptoms may be attributed to physiological changes of pregnancy or the postpartum state, possibly delaying evaluation. When lesions arise in high-risk locations, such as the brainstem, tissue biopsy is frequently infeasible, further complicating the diagnostic process.

Patient presentation: A 28-year-old woman developed dysphagia during pregnancy, which persisted and gradually worsened after delivery. Postpartum evaluation identified a right thyroid nodule, subsequently diagnosed as papillary thyroid carcinoma following hemithyroidectomy. Eight months postpartum, the patient experienced progressive dysphagia, headaches, and dizziness. Magnetic resonance imaging revealed an expansile medullary lesion concerning for a high-grade primary brainstem tumor. Due to the brainstem location, biopsy was infeasible, and empiric chemoradiation was initiated for presumed high-grade glioma.

Molecular findings: Cerebrospinal fluid (CSF) tumor-derived nucleic acid analysis using Summit 2.0 identified an H3-3A K28M alteration, along with co-occurring pathogenic alterations in NF1 and TP53. In conjunction with the clinical and radiographic findings, these molecular results supported classification of the tumor as diffuse midline glioma, H3 K27-altered.

Management and outcome: Following completion of chemoradiation, dordaviprone therapy was initiated. At the most recent documented follow-up in January 2026, brain MRI demonstrated decreased size and enhancement of the medullary lesion, accompanied by improvement in dysphagia, headaches, dystonic movements, balance, and overall performance status.

Conclusions: This case demonstrates that cerebrospinal fluid-based genomic profiling can provide clinically meaningful molecular information when tissue diagnosis is contraindicated and can inform treatment planning for patients with anatomically inaccessible central nervous system tumors. It also highlights the significance of ongoing evaluation of persistent neurologic symptoms during pregnancy and the postpartum period.