Uncommon pattern of H3 К27М-mutant diffuse midline glioma progression in children after open tumor biopsy: clinical cases

Background. The lack of progress in the treatment of diffuse midline gliomas (DMG) has led to the increased use of biopsies with molecular genetic testing of tumor tissue to search for new therapeutic options. However, the consequences of frequent biopsies are not fully established. aim of the study: to demonstrate an atypical progression of brainstem DMG in children after open biopsy.

Material and Methods. A retrospective analysis of data from 138 patients treated for DMG between 2020 and 2024 was performed. Of the 138 patients included in this analysis, 38 patients with diffuse pontine glioma underwent open biopsy with exophytic component resection or cyst evacuation. In terms of the age and gender distribution, these 38 patients did not differ statistically from the rest of the patients. Biopsy samples were subjected to histological and molecular genetic examination. All 138 patients received radiotherapy to the tumor and chemotherapy, if indicated. Follow-up was based on the assessment of neurological status and contrast-enhanced MRI of the central nervous system.

Results. Immunohistochemical analysis of surgical specimens revealed K27M mutation in the H3F3A gene in 19 patients (50 % of 38 who underwent biopsy). Atypical progression of DMG manifested as metastasis along the brain’s ventricular system was found in 6 out of 38 (15 %) patients within 2 to 5 months (median 4.5 months) after radiation therapy. In the remaining patients of the study cohort, who did not undergo a biopsy, a similar pattern of progression was not observed (p<0.002): they, as a rule, had continued tumor growth (96 patients); leptomeningeal metastasis along the spinal cord was diagnosed in 4 patients.

Conclusion. Thus, we identified cases of atypical progression of DMG manifested as metastasis along the ventricular system in children after open tumor biopsy. There is reason to believe that biopsy could contribute to the dissemination of DMG throughout the liquor spaces. It is necessary to search for alternative methods for assessing the molecular genetic characteristics of DMGs.

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