Infantile Astrocytoma Research Articles

CDC42BPA::BRAF represents a novel fusion in desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytoma.

Summary Desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytoma (DIG/DIA) are low-grade glial/glioneuronal tumors occurring predominantly in the cerebral hemispheres of infants. DIG/DIA exhibit BRAF or RAF1 alterations leading to oncogenic mitogen-activated protein kinase (MAPK) pathway activation. Here, we report the discovery of the novel CDC42BPA::BRAF fusion in a three-month-old patient with left frontotemporal DIA using DNA sequencing. Independent validation was performed through RNA sequencing. This fusion joins the kinase domains of BRAF and CDC42BPA, potentially constitutively activating both. It marks the first report of a fusion involving the actomyosin regulatory kinase CDC42BPA/MRCKα in brain tumors, suggesting potential involvement of actin remodeling defects in DIG/DIA. Surgical excision is curative for DIG/DIA, but incomplete resection, recurrence, malignant transformation, or metastases may necessitate adjuvant chemotherapy, posing risks. Identifying and excluding molecular alterations is crucial for selecting targeted therapies, such as BRAF and MEK inhibitors. These options present potential treatments with lower toxicity compared to conventional chemotherapy.

PATH-54. CDC42BPA::BRAF REPRESENTS A NOVEL FUSION IN DESMOPLASTIC INFANTILE GLIOMA

Abstract Desmoplastic infantile ganglioglioma/desmoplastic infantile astrocytomas (DIG/DIA), although rare, are low-grade glioneuronal tumors that typically affect patients < 1 year old, and generally carry a good prognosis. Often successfully cured with surgical excision, DIG/DIA still carry the potential for malignant transformation or recurrence. Whilst pediatric low grade glioma (LGG) survival rates are >95%, tumor grade does not correlate well with outcomes in infant LGG (iLGG), thus highlighting the need for investigation into molecular mechanisms of tumor progression. We describe a novel CDC42BPA-BRAF fusion in a DIA in a three-month old patient, and its detection via Next Generation Sequencing. Future studies will investigate whether this novel fusion can function as a target for BRAF and MAPK pathway inhibitors, which have recently been FDA-approved for pLGG.

Two cases of desmoplastic non⁃infantile astrocytoma with review of the literature

Objective To investigate clinical pathological characteristics, diagnosis and differentiation of desmoplastic non ⁃ infantile astrocytoma (DNIA). Methods & Results Two female patients with DNIA aged 5 and 10 years old, respectively. The patient of case 1 had repeated unconsciousness with limbs twitch, MR image showed a mass in the inner part of the left temporal horn, the tumor was located in the underside of cortex of temporal lobe, about 3.00 cm × 3.50 cm × 3.50 cm in size with yellow in color and medium blood supply, the boundaries of the tumor were fairly clear and the mass was completely dissected. The patient of case 2 had recurrent headache with vomiting, MR image showed a large cystic solid mass in the right frontal temporal lobe⁃lateral ventricle. The tumor was located at 1 cm under the subcortex and drew off yellow cyst fluid about 80 ml. The tumor was about 11.00 cm × 10.00 cm × 10.00 cm in size with yellow in color and brittle texture and abundant blood supply, adhesion to the brain tissue and was completely dissected. Histology showed obvious interstitial fibrosis associated with neoplastic astrocytes with primary neuroepithelium. Immunohistochemical staining indicated that the expression of both tumor cells was positive for vimentin, GFAP, S⁃100, Nestin, and negative for CK, EMA, NeuN, the expression of primary cells was positive for Syn; Ki ⁃ 67 labeling index was 6% and 10% , respectively. Histochemical staining showed that the tumor cells were surrounded by reticular fibers. Patients were followed up for 18 and 52 months, respectively, both had no recurrence and metastasis. Conclusion DNIA is a rare supratentorial neuroepithelial tumor. The prognosis is generally good. It needs to be differentiated from other tumors, especially malignant glioma. DOI：10.3969/j.issn.1672⁃6731.2012.03.015

Human herpesvirus‐6 associated encephalitis with subsequent infantile spasms and cerebellar astrocytoma

A 14‐month‐old girl presented after 3 days of fever, floppiness, and diffuse urticarial exanthem. She developed encephalitis and carditis and 1 week later, intractable seizures. Initial CT and MRI showed no changes in the brain parenchyma. On days 14 and 34 after the onset of symptoms, a human herpesvirus‐6 (HHV‐6) genome in cerebrospinal fluid was identified by polymerase chain reaction (PCR). Convulsions became more frequent and 11 weeks from the onset, they changed to typical infantile spasms with hypsarrhythmic electroencephalogram. She gradually lost her social contact and ability to walk and sit. Eleven months after the primary infection, a repeated MRI of the brain revealed a cystic tumour of 2 cm in diameter near the vermis. The tumour was surgically removed, and shown to be a pilocytic astrocytoma on histopathological examination. HHV‐6 DNA was detected by PCR in new tumour tissue. This is the first reported case of HHV‐6 encephalitis associated with carditis, infantile spasms, and a subsequent brain tumour containing the HHV‐6 genome.