Brain Tumor Pathology最新文献

NF2-related schwannomatosis is a tumor predisposition syndrome caused by diverse NF2 alterations, including truncating variants, copy-number changes, and non-truncating variants such as in-frame indels. Molecular and clinical correlations of these variant types remain incompletely defined, particularly for rare deletions. We present two distinct cases highlighting NF2 inactivation spectrum. Case 1 describes a 62-year-old man with a jugular foramen schwannoma harboring a novel somatic NF2 in-frame deletion (c.713_733del, p.Ala238_Tyr244del) resulting in complete Merlin expression loss. Structural modeling predicted FERM-C subdomain destabilization; copy-neutral loss of heterozygosity confirmed biallelic inactivation. Case 2 describes a 55-year-old woman with early-onset bilateral vestibular schwannomas caused by a germline whole-gene NF2 deletion, with additional somatic mutations (splice-site and frameshift) inactivating the second allele. Pedigree analysis demonstrated paternal inheritance, underscoring the relevance of genetic counseling. Both tumors displayed classical schwannoma histology with absent Merlin staining, confirming functional NF2 loss. These cases emphasize the necessity of comprehensive molecular testing-including targeted sequencing, whole-genome sequencing, and multiplex ligation-dependent probe amplification-to detect nucleotide-level and large-scale NF2 alterations; moreover, they expand the NF2 mutation spectrum, illustrate pathogenic mechanisms across germline and somatic contexts, and provide clinically actionable insights for Merlin-deficient tumors.

Rosette-forming glioneuronal tumors (RGNTs) are rare, World Health Organization grade 1 tumors that typically arise around the fourth ventricle. However, cerebral hemisphere RGNTs have recently been reported, with some exhibiting clinical features resembling low-grade epilepsy-associated tumor (LEAT). We report a case of multifocal RGNT in a patient with drug-refractory epilepsy. A 14-year-old woman was incidentally found to have multifocal brain tumor involving the left temporal lobe and bilateral thalamus, she developed drug-resistant epilepsy ten years later and underwent surgery. Partial tumor resection and anterior temporal lobectomy were performed. Histopathology revealed a glioneuronal tumor with oligodendroglia-like cells, neurocytic rosette, and perivascular pseudorosette, exhibiting an infiltrative growth pattern extending into the white matter. Genetic analysis revealed Fibroblast Growth Factor Receptor 1 mutation. The methylation profile analysis matched the low-grade glioneuronal tumor class but did not yield to any subclass category. Finally, the tumor was diagnosed as RGNT-like low-grade glioneuronal tumor with dysembryoplastic neuroepithelial tumor (DNT) features. Cases presenting with a LEAT-like clinical course and exhibiting histopathological features of RGNT are often difficult to definitively distinguish from DNT based on histological and genetic findings. Epilepsy-associated RGNT may harbor genetic profiles distinct from those of prototypical RGNTs, highlighting the need for further investigation.

Tumor Treating Fields (TTFields) are approved for glioblastoma (GBM) treatment, but predictive biomarkers remain unclear. This study evaluates TTFields effectiveness in primary GBM cell cultures and explores miRNA biomarkers in tumor tissue, plasma, and primary cell cultures. TTFields were applied to 21 primary GBM cell cultures for 72 h. Cell viability was assessed pre- and post-treatment, with parallel evaluations in control cultures. Expression levels of miRNAs-21, -26a, -34a, -181c, -181d, and -485-5p were analyzed in tumor tissue, plasma, and untreated/treatment-exposed cultures. Correlation analyses examined TTFields response and miRNA expression. Response rates varied, with a mean cell viability reduction of 48.53%. Expression of miRNA-26a in tumor tissue (p = 0.041, r = 0.502) and miRNAs-21, -26a, and -181c in untreated control cultures (p < 0.05) correlated with increased TTFields effectiveness. Linear correlations were observed for miRNAs-26a and -181c in untreated control cultures ([95% CI: 0.001938-0.01725, p = 0.016; 95% CI: 0.0000003935-0.0001641, p = 0.049). Individual GBM cell cultures respond differently to TTFields. Overexpression of miRNA-26a in native tumor tissue and overexpression of miRNAs-21, -26a and -181c in untreated control cell cultures were positively correlated with increased effectiveness of TTFields treatment.

Meningiomas, the most common primary benign intracranial tumors, may recur and, in some cases, undergo WHO grade progression, acquiring more aggressive clinical behavior. The molecular mechanisms underlying such progression, particularly following stereotactic radiosurgery (SRS), remain poorly understood. We report a 70-year-old woman with a gradually enlarging tentorial meningioma treated with SRS as primary therapy. The irradiated lesion remained stable on serial MRI for 30 months following treatment. Subsequently, a rapidly enlarging marginal progression was detected posterior to the original tumor site. Surgical resection revealed two distinct pathological components: the anterior, irradiated lesion was a fibrous meningioma whereas the posterior, marginally progressed lesion was diagnosed as an anaplastic meningioma (WHO grade 3). Whole-exome sequencing identified shared NF2 mutations and losses at 1p and 18p in both components, while the marginally progressed lesion harbored additional high-risk alterations, including homozygous CDKN2A/B deletion and loss of the X chromosome. Despite re-irradiation and further surgical resections, the patient succumbed to tumor progression and disseminated disease 8 months after the marginal progression. These findings suggest that a subset of tumor cells may have acquired genetic alterations driving WHO grade progression, ultimately leading to marginal progression after SRS.

While tumor-associated macrophages (TAMs) have been extensively studied, the role of tumor-associated astrocytes (TAAs) in glioma progression is less explored. Astrocytes are crucial in maintaining lipid homeostasis by synthesizing cholesterol and apolipoprotein E (APOE) in the brain. However, the contribution of astrocytes in supporting the metabolic needs of tumor cells within the tumor microenvironment (TME) is still poorly understood. This study aims to investigate how astrocytes contribute to the unique brain TME by examining the spatial distribution of APOE and its correlation with glial cells. This study examined the spatial distribution of APOE in gliomas with two murine brain tumor models: ALTS1C1 and GL261. To validate astrocyte APOE secretion, in situ hybridization (ISH) for APOE mRNA and immunofluorescence (IF) staining for GFAP were performed. Immunofluorescence (IF) staining showed that APOE was accumulated at the tumor edge. ISH analysis confirmed that activated astrocytes were the primary cells responsible for the increased APOE in this region. Flow cytometry and IF staining demonstrated that TAMs were also associated with increased APOE expression in the tumor core. This study provides the first evidence that astrocytes at the tumor edge are activated and upregulated for APOE secretion. These brain tumor edge-associated astrocytes are responsible for the accumulation of APOE in this region and create a unique metabolic environment, which may contribute to brain tumor invasion and resistance to therapy.

A limited number of cases involving non-midline lesions have been documented in diffuse midline glioma (DMG), H3K27-altered, for which a definitive classification has yet to be developed. Additionally, no studies have investigated the temporal evolution of imaging features in diffuse non-midline gliomas. We herein report a case of DMG, H3K27-altered, initially presenting with a gliomatosis cerebri-like appearance, cystic lesions in the right frontal lobe, and progression toward the brainstem. Histopathological analysis and comprehensive genomic profiling indicated glioblastoma (GBM) or DMG, H3K27-altered. The patient was diagnosed with GBM because of imaging characteristics atypical for DMG; however, 9 months after the initial diagnosis, a pontine glioma emerged. This case indicates that DMG, H3K27-altered, may exhibit atypical characteristics, including non-midline cystic lesions, that can subsequently progress to pontine gliomas. Considering the limited therapeutic options available for this malignancy, the early recognition of such atypical presentations is crucial for achieving a timely and accurate diagnosis of DMG, H3K27-altered.