Yeon-Lim Suh

Background and Objectives: Diffuse midline glioma (DMG), H3 K27-altered, occurs in children and adults, but age-group differences and their prognostic significance remain uncertain. We examined clinicopathologic and molecular features and survival in H3 K27M-mutant DMG across age groups. Materials and Methods: This retrospective single-center study included 53 patients (18 children and 35 adults). Histologic features, treatment, targeted sequencing results (28 tumors), and overall survival (OS) were analyzed. Results: Thalamic tumors predominated in adults (77.1%) and brainstem tumors in children (66.7%; p < 0.001). Median Ki-67 labeling index (LI) was higher in children (39% vs. 20%; p = 0.032); the estimated age-group difference remained similar after adjustment for location. Treatment regimens differed by age, but no significant age-group differences were found in other histologic features or the genomic alterations examined. At the data cutoff, 48 patients (90.6%) had died. Median OS was 20.3 months, without a significant difference between children and adults (15.2 vs. 21.7 months; p = 0.124). Higher Ki-67 LI remained associated with shorter OS after adjustment for age group, brainstem involvement, necrosis, and upfront radiotherapy (hazard ratio (HR) 1.37 per 10-percentage-point increment; 95% confidence interval (CI), 1.16–1.63; p < 0.001). Necrosis was also independently associated with shorter OS (HR 2.54; 95% CI, 1.29–5.00; p = 0.007). TP53 alteration was associated with shorter OS in univariable analysis but not after adjustment. Conclusions: Age groups differed in anatomical distribution and proliferative activity, but age was not independently associated with OS. Ki-67 LI and necrosis may provide accessible prognostic information, whereas the association of TP53 alteration with outcome requires validation.

Purpose: Dementia imposes a substantial socioeconomic burden in South Korea and has drawn considerable public and political attention. Recent proposals have sought to rename the Korean term for dementia, chimae, to reduce stigma; however, the term remains embedded in medical education, diagnostic systems, and legal frameworks. This study reviews its etymology, international renaming precedents, and the clinical appropriateness of proposed alternatives from a medical perspective.Current concepts: The term derives from Latin dementia and was translated by Japanese physicians in the late 19th century as the Hanja compound 癡呆. Taiwan (2001), Japan (2004), and Hong Kong (2011) adopted alternatives emphasizing cognitive impairment, whereas DSM-5 and ICD-11 retain dementia for specific etiologies or as a core term. South Korea previously renamed epilepsy and schizophrenia through expert-led initiatives, although evidence that renaming reduced stigma or disease concealment remains mixed. Proposed alternatives such as cognitive decline overlap with mild cognitive impairment and may lack diagnostic clarity.Discussion and conclusion: Major medical organizations have opposed renaming the medical diagnostic term, citing diagnostic confusion and the administrative burden of changing approximately 256 dementia care centers nationwide; however, actual costs would depend on the transition strategy. A 2021 survey found no clear majority favoring either renaming or retention, indicating an absence of social consensus. Rather than hastily changing the diagnostic term, a strategic approach would rename administrative and public services using more positive language while preserving medical clarity to support patient dignity and effective care.

Chun MY, et al. J Clin Neurol. 2025 Jul;21(4):315-324. https://doi.org/10.3988/jcn.2024.0526

Jung YH, et al. J Clin Neurol. 2025 May;21(3):190-200. https://doi.org/10.3988/jcn.2024.0517

The accurate diagnosis and classification of gliomas are essential for appropriate treatment planning and prognosis prediction. This study aimed to investigate the molecular diagnostics of IDH‐wildtype diffuse astrocytic gliomas and identify potential genetic variants that could differentiate glioblastoma (GBM) from lower‐grade gliomas when DNA methylation analysis is not feasible. In total, 479 H3‐and IDH‐wildtype diffuse astrocytic gliomas were included in this study. All the cases were diagnosed according to the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors. Panel sequencing data were collected, and clinicopathological information was retrieved from medical records. Genetic alterations and histological findings were analyzed to determine their diagnostic utility and prognostic implications. Out of 479 cases, 439 (91.6%) were diagnosed with GBM, including 28 cases that were molecularly diagnosed as GBM. However, 40 (8.4%) cases could not be classified according to the 2021 WHO classification and were diagnosed as lower‐grade diffuse astrocytic glioma, IDH‐wildtype, not elsewhere classified (LGNEC). In addition to the three genetic alterations included in the diagnostic criteria of GBM, PTEN and EGFR mutations were found to be enriched in GBM. Patients harboring mTOR pathway mutations demonstrated a more favorable prognosis and often exhibited morphology resembling subependymal giant cell astrocytoma, along with a high tumor mutational burden. Among patients with mTOR pathway mutations, those lacking molecular diagnostic features of GBM exhibited outstanding survival outcomes, even in the presence of grade 4 histology. Integration of molecular features enhanced the diagnostic accuracy of IDH‐wildtype gliomas. Some molecular alterations enriched in GBM offer valuable insights for molecular diagnosis and glioma classification. Furthermore, high‐grade diffuse astrocytic gliomas featuring mTOR pathway mutations in the absence of molecular diagnostic features of GBM could represent more favorable tumor types distinct from GBM.

The World Health Organization Classification of Tumors of the Central Nervous System recently incorporated histological features, immunophenotypes, and molecular characteristics to improve the accuracy of glioblastoma (GBM) diagnosis. FGFR3::TACC3 (F3T3) fusion has been identified as an oncogenic driver in IDH-wildtype GBMs. Recent studies have demonstrated the potential of using FGFR inhibitors in clinical trials and TACC3-targeting agents in preclinical models for GBM treatment. However, there is limited information on the clinicopathological and genetic features of IDH-wildtype GBMs with F3T3 fusion. The aim of this study was to comprehensively investigate the clinical manifestations, histological features, and mutational profiles of F3T3-positive GBMs. Between September 2017 and February 2023, 25 consecutive cases (5.0%) of F3T3-positive GBM were extracted from 504 cases of IDH-wildtype GBM. Clinicopathological information and targeted sequencing results obtained from 25 primary and 4 recurrent F3T3-positive GBMs were evaluated and compared with those from F3T3-negative GBMs. The provisional grades determined by histology only were distributed as follows: 4 (26/29; 89.7%), 3 (2/29; 6.9%), and 2 (1/29; 3.4%). Grade 2–3 tumors were ultimately diagnosed as grade 4 GBMs based on the identification of the TERT promoter mutation and the combined gain of chromosome 7 and loss of chromosome 10 (7+/10−). F3T3-positive GBMs predominantly affected women (2.6 females per male). The mean age of patients with an F3T3-positive GBM at initial diagnosis was 62 years. F3T3-positive GBMs occurred more frequently in the cortical locations compared to F3T3-negative GBMs. Imaging studies revealed that more than one-third (12/29; 41.4%) of F3T3-positive GBMs displayed a circumscribed tumor border. Seven of the seventeen patients (41.2%) whose follow-up periods exceeded 20 months died of the disease. Histologically, F3T3-positive GBMs more frequently showed curvilinear capillary proliferation, palisading nuclei, and calcification compared to F3T3-negative GBMs. Molecularly, the most common alterations observed in F3T3-positive GBMs were TERT promoter mutations and 7+/10−, whereas amplifications of EGFR, PDGFRA, and KIT were not detected at all. Other genetic alterations included CDKN2A/B deletion, PTEN mutation, TP53 mutation, CDK4 amplification, and MDM2 amplification. Our observations suggest that F3T3-positive GBM is a distinct molecular subgroup of the IDH-wildtype GBM. Both clinicians and pathologists should consider this rare entity in the differential diagnosis of diffuse astrocytic glioma to make an accurate diagnosis and to ensure appropriate therapeutic management.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia encompasses hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented orthochromatic leukodystrophy. We describe the clinicopathological and genetic findings of three patients with this disorder. All patients presented with dysarthria, with or without cognitive decline. The first and second patients were siblings who died of the disease at ages 42 and 54, respectively, while the third patient has been bedridden. Brain magnetic resonance imaging revealed T2 hyperintensities in the subcortical and periventricular white matter. Pathological diagnosis was established by brain autopsy in cases 1 and 2, and a stereotactic brain biopsy in case 3, followed by genetic analysis of colony stimulating factor-1 receptor gene. A heterozygous c.2345G > A (p.R782H) variant was identified in the autopsy-proven cases, and a c.1765G > A (p.G589R) variant in the biopsy-proven case. Postmortem examination revealed severe white matter degeneration involving the bilateral frontoparietal lobes, but sparing the subcortical U-fibers. All cases revealed widespread loss of myelinated axons in the white matter lesions; however, axonal spheroids and pigmented macrophages were abundant in cases 1 and 3 and much less in case 2. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia should be considered in patients with presenile dementia and diffuse white matter lesions.

Jeon YH, et al. J Korean Med Sci. 2023 Mar;38(10):e78. https://doi.org/10.3346/jkms.2023.38.e78

A late-onset treatment-related changes (TRCs), which represent radiographic radiation necrosis (RN), frequently occur after stereotactic radiosurgery (SRS) for brain metastases and often need surgical treatment. This study aimed to validate the true pathology and investigate clinical implication of surgically resected TRCs on advanced magnetic resonance imaging (MRI). Retrospective analyses of 86 patients who underwent surgical resection after radiosurgery of brain metastases were performed. Fifty-four patients displayed TRCs on preoperative MRI, comprising pure RN in 19 patients (TRC-RN group) and mixed viable tumor cells in 35 patients (TRC-PD group). Thirty-two patients revealed the consistent diagnosis of progressive disease in both MRI and histopathology (PD–PD group). The TRC-PD group showed larger prescription isodose volume (9.4 cm³) than the TRC-RN (4.06 cm³, p = 0.014) group and a shorter time interval from SRS to preoperative MRI diagnosis (median 4.07 months) than the PD–PD group (median 8.77 months, p = 0.004). Progression-free survival was significantly different among the three groups (p < 0.001), but not between TRC-RN and TRC-PD (post hoc test, p = 1.00), while no difference was observed in overall survival (p = 0.067). Brain metastases featured as TRCs after SRS frequently contained viable tumor cells. However, this histologic heterogeneity had a minor impact on benign local prognosis of TRCs after surgical resection.

Purpose Detection of telomerase reverse transcriptase (TERT) promoter mutations is a crucial process in the integrated diagnosis of glioblastomas. However, the TERT promoter region is difficult to amplify because of its high guanine-cytosine (GC) content (> 80%). This study aimed to analyze the capturing of TERT mutations by targeted next-generation sequencing (NGS) using formalin-fixed paraffin-embedded tissues.Materials and Methods We compared the detection rate of TERT mutations between targeted NGS and Sanger sequencing in 25 cases of isocitrate dehydrgenase (IDH)-wildtype glioblastomas and 10 cases of non-neoplastic gastric tissues. Our customized panel consisted of 232 essential glioma-associated genes.Results Sanger sequencing detected TERT mutations in 17 out of 25 glioblastomas, but all TERT mutations were missed by targeted NGS. After the manual visualization of the NGS data using an integrative genomics viewer, 16 cases showed a TERT mutation with a very low read depth (mean, 21.59; median, 25), which revealed false-negative results using auto-filtering. We optimized our customized panel by extending the length of oligonucleotide baits and increasing the number of baits spanning the coverage of the TERT promoter, which did not amplify well due to the high GC content.Conclusion Our study confirmed that it is crucial to consider the recognition of molecular bias and to carefully interpret NGS data.