A case of disseminated spinal astroblastoma harboring a MAMLD1::BEND2 fusion.

Astroblastoma, MN1-altered, is a rare neoplasm of the central nervous system (CNS). This malignancy shares similar histopathological features with other CNS tumors, including ependymomas, making it challenging to diagnose. DNA methylation profiling is a new and robust technique that may be used to overcome this diagnostic hurdle. We report the case of a now 25-year-old female diagnosed with what was initially called an ependymoma located in the cervical spine at the age of 2 years old. After initial resection, the tumor recurred multiple times and within 2 years of diagnosis had disseminated disease throughout the brain and spinal cord. She has now undergone over two decades of treatment, including multiple surgical resections, radiation therapy, and administration of numerous chemotherapeutic agents. In 2021, the patient presented to our institution with lumbosacral radicular symptoms due to enlarging lesions within the lumbosacral spine. Reexamination of formalin-fixed, paraffin-embedded material from the patient's tumor using genomic DNA methylation profiling resulted in a diagnostic change from grade III anaplastic ependymoma to astroblastoma, MN1-altered. This work describes another confirmed case of astroblastoma, MN1-altered, to the growing body of literature.

Glioblastoma may evade immune surveillance through primary cilia-dependent signaling in an IL-6 dependent manner.

Glioblastoma is the most common, malignant primary brain tumor in adults and remains universally fatal. While immunotherapy has vastly improved the treatment of several solid cancers, efficacy in glioblastoma is limited. These challenges are due in part to the propensity of glioblastoma to recruit tumor-suppressive immune cells, which act in conjunction with tumor cells to create a pro-tumor immune microenvironment through secretion of several soluble factors. Glioblastoma-derived EVs induce myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs) from myeloid precursors leading to systemic and local immunosuppression. This process is mediated by IL-6 which contributes to the recruitment of tumor-associated macrophages of the M2 immunosuppressive subtype, which in turn, upregulates anti-inflammatory cytokines including IL-10 and TGF-ß. Primary cilia are highly conserved organelles involved in signal transduction and play critical roles in glioblastoma proliferation, invasion, angiogenesis, and chemoradiation resistance. In this perspectives article, we provide preliminary evidence that primary cilia regulate intracellular release of IL-6. This ties primary cilia mechanistically to tumor-mediated immunosuppression in glioblastomas and potentially, in additional neoplasms which have a shared mechanism for cancer-mediated immunosuppression. We propose potentially testable hypotheses of the cellular mechanisms behind this finding.