CNSC-74. COMPARATIVE PATHOLOGY OF A RARE <i>MN1::PATZ1</i> -FUSION NEUROEPITHELIAL PRIMARY TUMOR AND RECURRENCE DEMONSTRATING MARKED HETEROGENEITY, POTENTIAL CHANGES IN TUMOR IMMUNE COMPOSITION, AND CELL-STATE TRANSITIONS

Abstract PATZ1-rearranged central nervous system (CNS) tumors are a recently identified subset of primitive neuroepithelial tumors (CNS-PNETs) characterized by significant heterogeneity in histopathologic features, age at presentation, and tumor grade. MN1::PATZ1 fusions are rare alterations with only fourteen cases captured in the literature thus far. Histologically, these tumors may present with characteristics of low-grade, high-grade, and mixed tumors. These tumors can vary significantly immunohistochemically. Clinically, these tumors can be associated with an indolent or even aggressive course. It is unknown whether complete surgical excision is curative for MN1::PATZ1 tumors, but incomplete resection, recurrence, malignant transformation, or metastases may necessitate adjuvant chemotherapy, posing risks. We will present comparative analyses of disease with indolent and aggressive course to better understand the progression of disease and clinical course. We conducted our analysis utilizing bulk transcriptomics, comparative transcriptomics, CIBERSORT, immunohistology, next generation sequencing, DNA methylation, and bioinformatics. We report the first molecular characterization of a paired primary and recurrent MN1::PATZ1 fusion, initially presenting on MRI imaging in a 6-year old female. Neuroimaging revealed a large cystic tumor with ring enhancement. Gross-total resection was completed revealing a neuroepithelial tumor harboring an MN1::PATZ1 fusion mutation via next generation sequencing. Resection was repeated on recurrence. The primary specimen revealed a triphasic tumor with an astrocytic morphology, and oligodendroglial-like morphology, but arranged in ependymoma-like perivascular pseudorosettes and sheets. Individual cell cytology appeared low-grade, but with high-grade architectural features such as necrosis and robust microvascular proliferation. The recurrence retained the appearance of the oligodendroglial-like component, showing monomorphic, round glial cells arranged in sheets with a delicate capillary network and perivascular pseudorosettes. However, the pseudorosettes appeared more astroblastoma-like, evidenced by thicker glial foot processes. Also, portrayed was less microvascular proliferation, no palisading necrosis, and no astrocytic component. Indolent disease course may correlate with loss of astrocytic component, and an increase in CD8+ cytotoxic T cells in these fusions. Considering there is no defined standard of care, targeted immunotherapy should be explored.