ABSTRACT
PURPOSE: The rarity of IDH2 mutations in supratentorial gliomas has led to gaps in understanding their radiological characteristics, potentially resulting in misdiagnosis based solely on negative IDH1 immunohistochemical staining. We aimed to investigate the clinical and imaging characteristics of IDH2-mutant gliomas. METHODS: We analyzed imaging data from adult patients with pathologically confirmed diffuse lower-grade gliomas and known IDH1/2 alteration and 1p/19q codeletion statuses obtained from the records of our institute (January 2011 to August 2022, Cohort 1) and The Cancer Imaging Archive (TCIA, Cohort 2). Two radiologists evaluated clinical information and radiological findings using standardized methods. Furthermore, we compared the data for IDH2-mutant and IDH-wildtype gliomas. Multivariate logistic regression was used to identify the predictors of IDH2 mutation status, and receiver operating characteristic curve analysis was employed to assess the predictive performance of the model. RESULTS: Of the 20 IDH2-mutant supratentorial gliomas, 95% were in the frontal lobes, with 75% classified as oligodendrogliomas. Age and the T2-FLAIR discordance were independent predictors of IDH2 mutations. Receiver operating characteristic curve analysis for the model using age and T2-FLAIR discordance demonstrated a strong potential for discriminating between IDH2-mutant and IDH-wildtype gliomas, with an area under the curve of 0.96 (95% CI, 0.91-0.98, P = .02). CONCLUSION: A high frequency of oligodendrogliomas with 1p/19q codeletion was observed in IDH2-mutated gliomas. Younger age and the presence of the T2-FLAIR discordance were associated with IDH2 mutations and these findings may help with precise diagnoses and treatment decisions in clinical practice.
Subject(s)
Glioma , Isocitrate Dehydrogenase , Magnetic Resonance Imaging , Mutation , Supratentorial Neoplasms , Humans , Isocitrate Dehydrogenase/genetics , Male , Female , Glioma/genetics , Glioma/diagnostic imaging , Glioma/pathology , Middle Aged , Adult , Supratentorial Neoplasms/genetics , Supratentorial Neoplasms/diagnostic imaging , Supratentorial Neoplasms/pathology , Magnetic Resonance Imaging/methods , Aged , Retrospective StudiesABSTRACT
BACKGROUND: Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas. METHODS: This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis. RESULTS: RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology. CONCLUSION: RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.
Subject(s)
Brain Neoplasms/genetics , Genes, ras/genetics , Glioma/genetics , Mutation , Adolescent , Adult , Aged , Aged, 80 and over , Astrocytoma/genetics , Brain Neoplasms/pathology , Child , Child, Preschool , DNA Methylation , DNA Modification Methylases/metabolism , DNA Mutational Analysis/methods , DNA Repair Enzymes/metabolism , Exons/genetics , Female , Glioblastoma/genetics , Glioma/pathology , Histones/genetics , Humans , Isocitrate Dehydrogenase/genetics , Male , Middle Aged , Oligodendroglioma/genetics , Phenotype , Promoter Regions, Genetic , Telomerase/genetics , Tumor Suppressor Proteins/metabolism , Young AdultABSTRACT
BACKGROUND: Bypass surgery for complex intracranial aneurysms (IAs) results in drastic blood flow changes in intracranial arteries. The aim of the study was to elucidate how vessels adapt to blood flow changes after bypass surgery with phase-contrast magnetic resonance imaging (PC-MRI). METHODS: This is a prospective observational study to assess changes of the blood flow in intracranial arteries after bypass surgery for IAs. Flow rates and vessel diameters were measured with PC-MRI in 52 intracranial arteries of 7 healthy volunteers and 31 arteries of 8 IA patients who underwent bypass surgery. Wall shear stress (WSS) was calculated with the Hagen-Poiseuille formula. In 18 arteries of 5 patients, the same measurement was performed 1, 3, and 12 months after surgery. RESULTS: PC-MRI showed a strong positive correlation between the flow rate and the third power of vessel diameter in both healthy volunteers (r = 0.82, P < 0.0001) and IA patients (r = 0.90, P < 0.0001), indicating the constant WSS. Of the 18 arteries in 5 patients, WSS increased in 7 arteries and decreased in 11 arteries immediately after surgery. In the WSS-increased group, WSS returned to the preoperative value in the third postoperative month. In the WSS-decreased group, WSS increased in the 12th month, but did not return to the preoperative level. CONCLUSIONS: In a physiological state, WSS was constant in intracranial arteries. Changed WSS after bypass surgery tended to return to the preoperative value, suggesting that vessel diameter and flow rate might be controlled so that WSS remains constant.
Subject(s)
Cerebral Revascularization/adverse effects , Intracranial Aneurysm/surgery , Postoperative Complications/pathology , Adult , Cerebral Arteries/pathology , Cerebral Revascularization/methods , Female , Hemodynamics , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Stress, MechanicalABSTRACT
Mixed pial-dural arteriovenous malformation(AVM) is currently defined as a malformation fed by both the pial and meningeal arteries. Although many cases of mixed pial-dural AVM have been reported, few papers have addressed its pathological locations. The authors report a case of a 43-year-old male patient with mixed pial-dural AVM in the occipital lobe, consisting of two distinct nidi located on the tentorium and in the cerebral parenchyma respectively. The lesions were surgically resected, and the pathological examination confirmed that both were indeed AVM. The authors discuss this rare type of AVM, focusing on the possible pathogenic mechanism thereof.
Subject(s)
Dura Mater/blood supply , Intracranial Arteriovenous Malformations/surgery , Pia Mater/blood supply , Adult , Humans , Intracranial Arteriovenous Malformations/pathology , MaleABSTRACT
BACKGROUND: Spinal cord diffuse midline glioma (DMG) is a relatively rare disease with a poor prognosis and no effective treatment. OBSERVATIONS: A 45-year-old man presented with rapidly progressive paraplegia in both lower extremities, along with bladder and bowel disturbance. Spinal magnetic resonance imaging (MRI) showed a heterogeneously contrast-enhanced mass at the T1-4 levels. A biopsy via T1-4 decompressive laminectomy with expansive duraplasty was performed. The histopathological diagnosis was DMG, H3K27-altered, World Health Organization grade 4. Radiation plus concomitant temozolomide was started; however, follow-up MRI showed tumor progression. Additional hypofractionated radiotherapy (HFRT; 24 Gy/5 fractions) was performed, with bevacizumab (BEV) plus low-dose ifosfamide-carboplatin-etoposide (ICE) as second-line treatment. One month later, MRI showed tumor regression with significant improvement in the peritumoral edema. The chemotherapy regimen was repeated every 4-6 weeks, and the patient remained stable. After 13 courses of chemotherapy, the size of the spinal DMG increased markedly, with dissemination to the temporal lobe. The patient died approximately 21 months after the initial diagnosis. LESSONS: Spinal DMG is a malignant tumor with a poor prognosis. However, treatment with additional HFRT combined with BEV plus low-dose ICE may inhibit tumor progression to prolong the progression-free period and survival. https://thejns.org/doi/10.3171/CASE2464.
ABSTRACT
BACKGROUND: The prognosis for cancer patients has been improved because of the development of molecularly targeted drugs. Treatment of intracranial tumors must be personalized while prioritizing the treatment of comorbid cancers. OBSERVATIONS: A 38-year-old man presented with bloody sputum, bilateral multiple nodules, and a mass in the lower lobe of his right lung. Bronchoscopy revealed stage IV lung adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation. Screening head magnetic resonance imaging revealed a 38-mm-diameter mass in the left petroclival area. Because the patient was neurologically intact, the treatment of lung adenocarcinoma was prioritized, and the third-generation EGFR-tyrosine kinase inhibitor osimertinib was used. Although nodules in the lung began to shrink, the intracranial lesion expanded and caused hydrocephalus, necessitating a ventriculoperitoneal shunt. The tumor also caused diplopia, dysarthria, and gait abnormalities. A left anterior transpetrosal approach was used to remove the tumor derived from the trochlear nerve. The pathological examination revealed schwannoma. Neurological symptoms improved following surgery. Osimertinib was continued during the perioperative period. LESSONS: Osimertinib was effective for lung adenocarcinoma but not for trochlear nerve schwannoma, which required surgical intervention. It is necessary to tailor the treatment of benign brain tumors in patients with concurrent malignant cancers. https://thejns.org/doi/10.3171/CASE24144.
ABSTRACT
PURPOSE: The telomerase reverse transcriptase promoter (TERTp) mutation is an unfavorable prognostic factor in isocitrate dehydrogenase-wildtype (IDHwt) histologically lower-grade astrocytoma (LGA), which was incorporated as a key component in the WHO 2021 classification of IDHwt LGA, replacing histologic grades in the WHO 2016 classification. The purpose of this study was to identify the imaging characteristics predictive of TERTp mutations in IDHwt LGA. METHODS: This retrospective study was approved by our institutional review board. This single-center study retrospectively included 59 patients with pathologically confirmed IDHwt LGA with known TERTp mutation status. In addition to clinical information and morphological characteristics, semi-quantitative imaging biomarkers such as the tumor-to-normal ratio (T/N ratio) on 18F-FDG-PET, normalized apparent diffusion coefficient (nADC), and histogram parameters from normalized relative cerebral blood volume (nrCBV) maps were compared between (a) TERTp-wildtype and TERTp-mutant tumors or (b) grade II and grade III astrocytoma. A p value < 0.05 was considered significant. RESULTS: There were no significant differences in the conventional imaging findings, T/N ratio on FDG-PET, nrCBV or ADC histogram metrics between IDHwt LGA with TERTp mutations and those without. Grade III IDHwt astrocytomas exhibited significantly higher nrCBV values, T/N ratio and lower ADC parameters than grade II IDHwt astrocytoma. CONCLUSIONS: In patients with IDHwt LGA, T/N ratio, nrCBV values and nADC may be surrogate markers for predicting histologic grade, but are not useful for predicting TERTp mutations.
Subject(s)
Astrocytoma , Brain Neoplasms , Glioma , Telomerase , Humans , Astrocytoma/diagnostic imaging , Astrocytoma/genetics , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Fluorodeoxyglucose F18 , Glioma/diagnostic imaging , Glioma/genetics , Glioma/pathology , Isocitrate Dehydrogenase/genetics , Mutation , Perfusion , Retrospective Studies , Telomerase/geneticsABSTRACT
Intradural extramedullary (IDEM) ependymoma except for tumors originated from the filum terminale or conus medullaris is rare. The present study showed a case of IDEM ependymoma. A 16-year-old boy was referred to our hospital with a complaint of right hypochondriac pain and motor weakness in his right leg. MRI revealed a solitary intradural tumor at Th5-8 level with syringomyelia at Th2-4 level. Microscopic total tumor resection was performed with right hemi-laminectomy of Th4-9. Histological diagnosis was ependymoma (WHO grade 2). Although his leg weakness was worsened transiently, he showed improvement in leg weakness being able to go up and down the stairs 1 month after the surgery. There was no tumor recurrence until now, 7 years after the surgery, without any adjunctive therapies. A total of 44 cases of IDEM ependymoma had been reported in the past literatures. They are thought to arise from ependymal cells which remained during the process of neural tube closure. Like intramedullary ependymomas, most of the IDEM ependymomas have clear border to surrounding tissue and often removed completely. However, a small number of recurrences and malignant transformations had been reported after complete resections despite benign histological features tumors. In the case of totally resected low grade IDEM ependymoma, it is thought to be reasonable to perform long-term periodical radiographic follow-up without postoperative adjunctive therapy.
ABSTRACT
The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear. According to cIMPACT-NOW update 3, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+ 7/- 10), and/or EGFR amplification, and/or TERT promoter (TERTp) mutation. Multiplex ligation-dependent probe amplification (MLPA) can detect copy number alterations at reasonable cost. The purpose of this study was to identify a precise, cost-effective method for stratifying the prognosis of IDH-wild-type astrocytoma. Sanger sequencing, MLPA, and quantitative methylation-specific PCR were performed for 42 IDH-wild-type lower-grade astrocytomas surgically treated at Kyoto University Hospital, and overall survival was analysed for 40 patients who underwent first surgery. Of the 42 IDH-wild-type astrocytomas, 21 were classified as grade 4 using cIMPACT-NOW update 3 criteria and all had either TERTp mutation or EGFR amplification. Kaplan-Meier analysis confirmed the prognostic significance of cIMPACT-NOW criteria, and World Health Organization grade was also prognostic. Cox regression hazard model identified independent significant prognostic indicators of PTEN loss (risk ratio, 9.75; p < 0.001) and PDGFRA amplification (risk ratio, 13.9; p = 0.002). The classification recommended by cIMPACT-NOW update 3 could be completed using Sanger sequencing and MLPA. Survival analysis revealed PTEN and PDGFRA were significant prognostic factors for IDH-wild-type lower-grade astrocytoma.
Subject(s)
Astrocytoma , DNA Copy Number Variations , Adult , Glioma , Humans , Kaplan-Meier Estimate , Male , Middle Aged , PrognosisABSTRACT
The most recurrent fusion of central nervous system high-grade neuroepithelial tumor with MN1 alteration (HGNET-MN1) is MN1 rearrangement. Here, we report the case of a 36-year-old man with spinal cord astroblastoma showing Ewing Sarcoma breakpoint region 1/EWS RNA-binding protein 1 (EWSR1)-BEN domain-containing 2 (BEND2) fusion. The patient presented with back pain, gait disturbance and dysesthesia in the lower extremities and trunk. Magnetic resonance imaging showed an intramedullary tumor at the T3-5 level, displaying homogeneous gadolinium enhancement. Partial tumor removal was performed with laminectomy. Histological examinations demonstrated solid growth of epithelioid tumor cells showing high cellularity, a pseudopapillary structure, intervening hyalinized fibrous stroma, and some mitoses. Astroblastoma was diagnosed, classified as HGNET-MN1 by the German Cancer Research Center methylation classifier. MN1 alteration was not detected by fluorescence in situ hybridization (FISH), but EWSR1-BEND2 fusion was detected by FISH and RNA sequencing. Previously, a child with EWSR1-BEND2 fusion-positive spinal astroblastoma classified as HGNET-MN1 was reported. In conjunction with that, the present case provides evidence that EWSR1-BEND2 fusion is identified in the entity of HGNET-MN1. Taken together, the BEND2 alteration rather than MN1 may determine the biology of a subset of the central nervous system HGNET-MN1 subclass.
Subject(s)
Contrast Media , Neoplasms, Neuroepithelial , Adult , Gadolinium , Humans , In Situ Hybridization, Fluorescence , Male , Methylation , Neoplasms, Neuroepithelial/genetics , Neoplasms, Neuroepithelial/surgery , RNA-Binding Protein EWS/genetics , Spinal Cord , Trans-Activators/genetics , Tumor Suppressor Proteins/geneticsABSTRACT
BACKGROUND: Arachnoid cysts originating from the velum interpositum are very rare, and their existence as a clinicopathologic entity remains controversial. We report a case of a patient with an arachnoid cyst of the velum interpositum presenting with memory disturbance, focusing on the anatomical origin of the lesion and the physiological mechanisms causing memory disturbance. CASE DESCRIPTION: A 65-year-old man with a large cystic lesion in the velum interpositum experienced progressive memory disturbance and enlargement of the lesion 6 months before referral to our institution. Neuropsychological evaluation on admission demonstrated severe memory disturbance. Radiological examination did not reveal hydrocephalus, but the bilateral fornices and thalami were compressed by the cyst. The patient underwent endoscopic cystoventriculostomy via the frontal horn of the right lateral ventricle through a frontal burr hole. Histopathology of the sample was consistent with that of an arachnoid cyst, and the endoscopic findings suggested that the cyst originated from the tela choroidea, which covers the velum interpositum. The symptoms resolved after surgery with significant improvement in neuropsychological test scores. CONCLUSION: Arachnoid cysts of the velum interpositum are rare but distinct clinicopathologic entities that originate from the tela choroidea. The lesions can cause memory disturbance without hydrocephalus due to compression of the fornices and thalami, but this can be reversed by surgery.