ct images of children with brain tumours

Imaging features of tumors with BRD4::LEUTX fusion. Case #3 shown: Large right supratentorial brain tumor, mostly solid, with associated mass effect, midline shift (open black arrow) and hydrocephalus (white asterisk). Intense heterogeneous contrast enhancement, cystic change (thick white arrow), marked restriction on ADC map (white star) and hemosiderin deposition (thin white arrow) are also observed.

Image source: Andreiuolo, F et al., Acta Neuropathologica Communications 2024 (CC BY 4.0)

News • Neuropathology

Technology offers new insights into pediatric brain tumors

Next-generation molecular sequencing and DNA methylation profile analysis allow the characterization of rare brain tumors

The research results were recently published in the journal Acta Neuropathologica Communications.

Embryonal tumors of the central nervous system (CNS) are a class of malignant tumors composed of embryonal neuroepithelial cells predominantly found in children. Recent updates by the World Health Organization (WHO) classification included several new subtypes of these tumors, highlighting the increasing importance of epigenetic studies in defining these subcategories. Epigenetic studies, particularly DNA methylation profiling, have an increasing importance in the classification of brain tumors and new tumor types delineation. The technique application allowed the identification of a particular group of cases where genetic analysis revealed a specific molecular alteration (fusion involving the BRD4 and LEUTX genes).

Radiological findings demonstrating response to chemotherapy. Case #4 shown. A A small foci of calcification is depicted on CT scan and susceptibility-weighted imaging MRI (short white arrow). Supratentorial obstructive hydrocephalus and macrocrania are also observed. A, B Heterogeneous tectal and pineal region solid cystic mass, with intense heterogeneous enhancement and rapid overgrowth within two months. B The solid component is highly cellular with marked restriction on ADC map (white star). A rim of increased blood flow on ASL perfusion map is observed in the periphery of the mass (long white arrows), possibly related to neovascularization. Leptomeningeal enhancement is also observed (open black arrow). C Significant shrinkage of the tectal and pineal region mass after chemotherapy was observed, with nearly complete resolution of the intracranial leptomeningeal enhancement.

Image source: Andreiuolo, F et al., Acta Neuropathologica Communications 2024 (CC BY 4.0)

The BRD4 gene (Bromodomain Containing 4) acts in transcriptional regulation and development, as well as maintaining the pluripotency of stem cells, and its dysregulation has been associated with different types of cancer, as it contributes to cell proliferation and tumor progression. On the other hand, the LEUTX gene (Leucine Twenty Homeobox) plays a role in embryonic development and regulation of early cell differentiation.

In this study, careful analysis of four new cases with these molecular alterations and five other cases described individually in the literature revealed similar clinical, radiological, and histopathological characteristics, indicating that they are most likely a specific type of tumor. All patients were children up to 4 years old, with bulky tumors, rapid growth, and aggressive clinical behavior. However, some cases responded well to chemotherapy.

Although the sample size is small, preliminary results indicated that these tumors are clinically aggressive, requiring personalized treatment strategies that combine chemotherapy with total surgical removal of the tumor. It is worth noting that small molecule BRD4 inhibitors and BRD4 degraders have shown promising results in preliminary studies in hematological and solid malignancies and may represent a future therapeutic avenue for these aggressive CNS tumors.

Source: D'Or Institute for Research and Education

31.05.2024