Fast Evolving Glioblastoma in a Pregnant Woman: Diagnostic and Therapeutic Challenges

Abstract

Background and Clinical Significance: Gliomas diagnosed during pregnancy are rare, and there are no established guidelines for their management. Effective treatment requires a multidisciplinary approach to balance maternal health and pregnancy preservation. Case Presentation: We here present a case of rapidly progressing glioma in a 33-year-old pregnant woman. The patient initially presented with a generalized tonic-clonic seizure at 21 weeks' gestation. Imaging revealed a tumor in the right cerebral lobe, involving both cortical and subcortical structures, while magnetic resonance spectroscopy suggested a low-grade glioma. The patient remained clinically stable for two months but then developed severe headaches; MRI showed a worsening mass effect. At 34 weeks' gestation, an emergency and premature caesarean section was performed under general anesthesia. The patient then underwent a craniotomy for maximal tumor resection, which was histologically and molecularly diagnosed as IDH wild-type glioblastoma (GB). Using qPCR, we found that the GB tissue showed upregulated expression of genes involved in cell structure (GFAP, VIM) and immune response (SSP1, TSPO), as well as increased expression of genes related to potential hormone response (AR, CYP19A1, ESR1, GPER1). After surgery, the patient showed resistance to Stupp protocol therapy, which was substituted with lomustine and bevacizumab combination therapy. Conclusions: This case illustrates that glioma may progress rapidly during pregnancy, but a favorable obstetric outcome is achievable. Management of similar cases should respect both the need for timely treatment and the patient's informed decision.

Keywords: brain cancer; glioblastoma therapy; magnetic resonance spectroscopy; maternal–fetal outcome; pregnancy.

Figure 1

Timeline of major clinical events, from symptom onset during pregnancy to 9 months post-resection. The figure shows timing of key MRI scans (corresponding to Figure 2a–f), seizures, delivery (C-section), surgery, and the start and end of adjuvant treatments. RT—radiotherapy; TMZ –temozolomide; CCNU—chloroethyl-cyclohexyl-nitrosourea (lomustine); BEV—bevacizumab.

Figure 2

Sequential T2-weighted axial brain MRIs over a 12-month period, corresponding to the timeline shown in Figure 1. (a) MRI at 24 weeks of pregnancy showing a hyperintense lesion in the right frontal lobe. (b) MRI at 33 weeks of pregnancy showing significant enlargement of the lesion. (c) Postoperative MRI five weeks after tumor resection. (d) MRI four months after resection showing tumor recurrence and progression despite surgery and radio-chemotherapy (RT + TMZ). (e) MRI seven months after resection, following two cycles of lomustine and four administrations of bevacizumab, demonstrating radiological regression. (f) MRI nine months after resection showing further tumor regression following three cycles of lomustine and nine administrations of bevacizumab, along with six doses of personalized anticancer vaccine administered abroad.

Figure 3

Hematoxylin and eosin staining (a,b) and immunohistochemistry (c,d) of GB, IDH-wild type, CNS WHO grade 4. (a) Hypercellular sheets of anaplastic glial cells. (b) Palisading necrosis and microvascular proliferation with endothelial hyperplasia. (c) GFAP immunoexpression by tumor cells. (d) High Ki-67 proliferation index.

Figure 4

Relative expression of genes associated with cell structure, immune response, and hormone signaling in GB. Expression levels of target genes (GFAP, VIM, SPP1, TSPO, AR, CYP19A1, ESR1, GPER1, and PGR) in tumor tissue are shown relative to the expression of the corresponding gene in peritumor tissue. Tissue samples were collected during surgery and preserved in RNAlater^® RNA Stabilization Solution. Total RNA was extracted with TRIzol reagent. After determining RNA concentrations, reverse transcription was carried out with a High Capacity cDNA Reverse Transcription Kit; qPCR analysis was performed using the QuantStudio™ 3 Real-Time PCR System with SYBR™ Green reagent. All chemicals and equipment were sourced from Thermo Fisher Scientific, Waltham, MA, USA and full methodological details are provided in the Supplementary Materials. The expression levels of target genes were quantified by comparative 2^−ΔCt method, using the hypoxanthine phosphoribosyltransferase gene (HPRT1) as a housekeeping gene. Primer sequences are listed in Supplementary Table S2.