Fatal Postpartum Hemorrhage in Diffuse Midline Glioma with H3-K27M Mutation

Abstract

Management of pregnant women with brain tumors necessitates difficult decision-making especially for estimating or preventing its intratumoral hemorrhage. A 26-year-old, 19-week pregnant woman complaining of headache and vomiting was admitted to our hospital. Magnetic resonance imaging (MRI) revealed hydrocephalus and a mass lesion without contrast enhancement extending from the left thalamus. To resolve severe symptoms, a ventriculoperitoneal shunt was inserted, and a biopsy was taken via the right ventricle. Pathological examination suggested diffuse or pilocytic astrocytoma, but subsequent genetic analysis revealed the diagnosis of midline glioma with H3-K27M mutation. The patient opted not to terminate the pregnancy, and MRIs conducted every four weeks revealed no change in tumor aspect. The patient delivered a healthy baby by cesarean section, and postpartum day 1 was uneventful. However, she was found in a coma due to a massive intratumoral hemorrhage on postpartum day 2 and died 3 weeks after the hemorrhage. This is the first case report of diffuse midline glioma with H3-K27M mutation in a pregnant woman followed by fatal hemorrhage. It highlights the necessity of careful clinical management and frequent neuroimaging during the entire perinatal period, even if the tumor has hypovascularity or low proliferative potential on radiological or pathological findings.

Figure 1

CT imaging revealed hydrocephalus and an iso-density mass lesion at the left thalamus (A). MRI revealed imaging revealed a poorly circumscribed mass lesion in the left thalamus, extending to both the midbrain and the right thalamus. The signal patterns were T1-low (B), T2-high (C), T2^∗-high (D), diffusion weighted image-slight high (E), T1 Gadrinium-nonenhanced (F), and fluid attenuation inversion recovery-high (G; axial, H; coronal, I; sagittal), respectively. MRA showed no obvious vascular abnormalities (H).

Figure 2

Hematoxylin-Eosin (H&E) staining revealed proliferation of various palisading cells with bipolar nature and no obvious findings of Rosenthal fiber (A, B). The immunohistochemical status of IDH1 showed wildtype IDH1 (C) and the Ki-67 labeling index was approximately 4% (D). CD34 staining suggested low microvascular proliferation (E). The optical magnification ratio of photomicrographs is 200-fold except for (B) (400-fold). The histone H3-K27M mutation was detected by Sanger sequencing (F).

Figure 3

Follow-up MRIs conducted every 4 weeks revealed fluid attenuation inversion recovery and no change in tumor size and pattern of intensity ((A); shortly after surgery, (B); 4 weeks later, (C); 8 weeks later).

Figure 4

The emergency head CT on postpartum day 2 revealed cerebral herniation due to massive intratumoral hemorrhage ((A); axial view, (B); coronal view).