Luteinizing hormone-releasing hormone (LHRH) agonists are widely used for androgen-deprivation therapy in prostate cancer. Recent reports have raised concern that LHRH may influence the biological behavior of LHRH receptor-expressing intracranial tumors, including meningiomas; however, clinical evidence remains limited. We describe two cases of rapidly progressive meningioma temporally associated with the initiation of leuprorelin acetate. Case 1 was a 67-year-old man with a left cerebellopontine angle meningioma that had demonstrated gradual enlargement over 26 months. Following the initiation of leuprorelin acetate, the tumor exhibited accelerated growth, necessitating surgical resection. Pathology confirmed a fibrous meningioma with LHRH and its receptor positive. Case 2 was a 72-year-old man previously treated with subtotal resection and radiotherapy for an atypical meningioma. After 6 years of radiographic stability, the tumor rapidly regrew soon after leuprorelin acetate initiation and required re-resection. Both the primary and recurrent tumors were LHRH- and LHRH receptor-positive. Freshly resected tumor tissue cultured ex vivo demonstrated a dose-dependent increase in cell viability following 7-day exposure to leuprorelin acetate. These findings suggest that LHRH agonists may be associated with increased cell viability in a subset of receptor-positive meningiomas. Caution is warranted when initiating LHRH agonist therapy in patients with known or suspected meningiomas.
TERT promoter (TERTp) mutations are among the most frequent molecular alterations in isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM), yet the molecular profiles and prognostic implications associated with TERTp status remain incompletely characterized. This study aimed to delineate differences in molecular characteristics and prognostic factors according to TERTp status in histologically defined, IDH wild-type GBM. Clinical and molecular characteristics and survival outcomes were retrospectively assessed according to TERTp status. Among 112 patients, 70 (62.5
Ependymoma-like tumor with mesenchymal differentiation (ELTMD) is a recently proposed, but not yet formally defined, entity that is not recognized in the 2021 World Health Organization (WHO) classification of central nervous system tumors. Although it shares molecular features, such as ZFTA fusion, with ependymomas, it exhibits distinct histopathological and epigenetic profiles. Herein, we report the case of a 5-year-old girl with a supratentorial tumor harboring the ZFTA::NCOA2 fusion. Histopathology revealed atypical features including mesenchymal and undifferentiated components, which overlapped with those of ependymomas. DNA methylation profiling using two independent classifiers (DKFZ and NIH) yielded no matches, indicating that the tumor did not belong to any recognized CNS class. The failure of subclass assignment by both classifiers suggests that ELTMD represents a potentially epigenetically distinct subgroup. Despite being unclassifiable by the current WHO criteria, the tumor shared features with previously reported ELTMDs, supporting its recognition as an emerging tumor. This highlights the need for additional cases to refine the diagnosis, classification, and future therapeutic strategies.
Glioblastoma (GBM) is a highly lethal brain tumor resistant to immunotherapy such as immune checkpoint inhibitors, partly because of an immunosuppressive tumor microenvironment and blood-brain barrier (BBB) dysfunction. Although bevacizumab can remodel the tumor vasculature, the relationship between BBB-related vascular changes and immune cell infiltration in GBM remains poorly understood. We analyzed human isocitrate dehydrogenase (IDH)-wildtype GBM tissues obtained after bevacizumab administration. Immunohistochemistry was performed for CD34 and plasmalemma vesicle-associated protein (PLVAP/PV-1), an endothelial marker associated with BBB disruption. Infiltrating T cells (CD3, CD8) and tumor-associated macrophages/microglia (TAMs; CD163) were also examined. PLVAP was broadly expressed in tumor vessels of untreated GBM and significantly reduced after bevacizumab administration, with marked downregulation in 3 of 10 treated cases. Among the 10 treated cases, significant increases in T-cell and cytotoxic T-lymphocyte infiltration were seen in PLVAP-low GBM compared with PLVAP-high GBM. TAM density did not differ significantly between groups but tended to be higher in the PLVAP-low group. These findings suggest that the bevacizumab-associated reduction of PLVAP expression is linked to increased T-cell infiltration in a subset of GBM cases. PLVAP may serve as an auxiliary histological marker for evaluating bevacizumab-related vascular/BBB remodeling in clinical specimens.
