Subependymal
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BACKGROUND AND OBJECTIVES: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA. METHODS: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used. RESULTS: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS. CONCLUSION: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.
- MeSH
- astrocytom * chirurgie radioterapie MeSH
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory mozku * chirurgie MeSH
- radiochirurgie * metody MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- MeSH
- astrocytom * genetika patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- MAP kinasový signální systém * fyziologie genetika MeSH
- mutace genetika MeSH
- nádory mozku * genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
In this study, we provide a comprehensive clinical and molecular biological characterization of radiation-induced gliomas (RIG), including a risk assessment for developing gliomas. A cohort of 12 patients who developed RIG 9.5 years (3-31 years) after previous cranial radiotherapy for brain tumors or T-cell acute lymphoblastic leukemia was established. The derived risk of RIG development based on our consecutive cohort of 371 irradiated patients was 1.6% at 10 years and 3.02% at 15 years. Patients with RIG glioma had a dismal prognosis with a median survival of 7.3 months. We described radiology features that might indicate the suspicion of RIG rather than the primary tumor recurrence. Typical molecular features identified by molecular biology examination included the absence of Histon3 mutation, methylation profile of pedHGG-RTK1 and the presence of recurrent PDGFRA amplification and CDKN2A/B deletion. Of the two long-term surviving patients, one had gliomatosis cerebri, and the other had pleomorphic xanthoastrocytoma with BRAF V600E mutation. In summary, our experience highlights the need for tissue diagnostics to allow detailed molecular biological characterization of the tumor, differentiation of the secondary tumor from the recurrence of the primary disease and potentially finding a therapeutic target.
- MeSH
- astrocytom * patologie MeSH
- gliom * genetika radioterapie MeSH
- lidé MeSH
- mutace MeSH
- nádory mozku * genetika radioterapie MeSH
- protoonkogenní proteiny B-Raf genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Neurochirugie je zásadní pro získání histologických vzorků, provádění správných chirurgických výkonů, pro indikace k výkonům a následné pooperační sledování. V posledních letech došlo jak ke zpřesnění indikací neurochirurgických intervencí, tak ke snížení komplikací. Zásadní je použití moderních zobrazovacích, navigačních a elektrofyziologických technik. Péče o pacienty s nádory je však multioborová, proto je nezbytná kooperace s dalšími odbornostmi.
Neurosurgery plays a crutial role in obtaining histological samples, in performance of adequate surgical procedures, in decision about surgical procedures and postoperative follow-up. Indications of neurosurgical procedures has been refined as well as the rate of complications has been reduced. Modern imaging, navigation and eletrophysiological techniques are of utmost importance. Care has to be multidisciplinar, thus cooperation between key care givers is vital.
- MeSH
- astrocytom chirurgie diagnóza patologie MeSH
- chemoradioterapie metody MeSH
- ependymom chirurgie diagnóza patologie MeSH
- glioblastom diagnóza patologie terapie MeSH
- gliom diagnóza klasifikace terapie MeSH
- kraniofaryngeom chirurgie diagnóza MeSH
- lidé MeSH
- lymfom diagnóza patologie terapie MeSH
- meningeom chirurgie diagnóza patologie MeSH
- metastázy nádorů diagnóza terapie MeSH
- nádory centrálního nervového systému * diagnóza klasifikace terapie MeSH
- nádory hypofýzy chirurgie diagnóza patologie MeSH
- nádory míchy diagnóza terapie MeSH
- neurochirurgické výkony metody MeSH
- stupeň nádoru MeSH
- vestibulární schwannom chirurgie diagnóza MeSH
- Check Tag
- lidé MeSH
Pontine gliomas represent difficult to treat entity due to the location and heterogeneous biology varying from indolent low-grade gliomas to aggressive diffuse intrinsic pontine glioma (DIPG). Making the correct tumor diagnosis in the pontine location is thus critical. Here, we report a case study of a 14-month-old patient initially diagnosed as histone H3 wild-type DIPG. Due to the low age of the patient, the MRI appearance of DIPG, and anaplastic astrocytoma histology, intensive chemotherapy based on the HIT-SKK protocol with vinblastine maintenance chemotherapy was administered. Rapid clinical improvement and radiological regression of the tumor were observed with nearly complete remission with durable effect and excellent clinical condition more than 6.5 years after diagnosis. Based on this unexpected therapeutic outcome, genome-wide DNA methylation array was employed and the sample was classified into the methylation class "Low-grade glioma, MYB(L1) altered." Additionally, RT-PCR revealed the presence of MYB::QKI fusion. Taken together, the histopathological classification, molecular-genetic and epigenetic features, clinical behavior, and pontine location have led us to reclassify the tumor as a pontine MYB-altered glioma. Our case demonstrates that more intensive chemotherapy can achieve long-term clinical effect in the treatment of MYB-altered pontine gliomas compared to previously used LGG-based regimens or radiotherapy. It also emphasizes the importance of a biopsy and a thorough molecular investigation of pontine lesions.
- MeSH
- astrocytom * diagnostické zobrazování farmakoterapie genetika MeSH
- gliom * diagnostické zobrazování farmakoterapie genetika MeSH
- histony genetika MeSH
- kojenec MeSH
- lidé MeSH
- nádory mozkového kmene * diagnostické zobrazování farmakoterapie genetika MeSH
- pons patologie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Recentní poznatky na poli molekulárně genetických změn difuzních gliomů u dospělých a dětských pacientů iniciovaly významné změny v jejich klasifikaci a diagnostice. Tyto změny předkládá 5. edice klasifikace WHO nádorů centrálního nervového systému zdůrazňující odsun od tradiční kategorizace tumorů na podkladu morfologie k integrované diagnostice inkorporující charakteristické molekulárně-genetické a epigenetické změny s tradičními morfologickými znaky. Tato první část přehledové práce předkládá souhrn jednotek, které jsou zařazeny do skupiny difuzních gliomů dospělého typu, s důrazem na diagnostická kritéria a grading dle 5. edice klasifikace WHO nádorů centrálního nervového systému z roku 2021.
Recent findings in the field of molecular-genetic alterations in diffuse gliomas, encompassing both adult and pediatric types, have initiated significant changes in their classification and diagnostics. These changes are presented in the fifth edition of the WHO Classification of Tumors of the Central Nervous System emphasizing a pivotal shift from the conventional categorization of tumors based on morphology to an integrated diagnostic approach, which incorporates characteristic molecular-genetic and epigenetic alterations alongside traditional morphological features. This review presents a summary of the units that are included in the group of diffuse gliomas of the adult type, with an emphasis on diagnostic criteria and grading according to the fifth edition of the WHO Classification of Tumors of the Central Nervous System, published in 2021.
- MeSH
- astrocytom diagnóza patologie MeSH
- glioblastom patologie MeSH
- gliom * diagnóza genetika klasifikace patologie MeSH
- imunohistochemie MeSH
- lidé MeSH
- mutace MeSH
- oligodendrogliom patologie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Gliomas are the most common central nervous tumors in children and adolescents. However, spinal cord low-grade gliomas (sLGGs) are rare, with scarce information on tumor genomics and epigenomics. To define the molecular landscape of sLGGs, we integrated clinical data, histology, and multi-level genetic and epigenetic analyses on a consecutive cohort of 26 pediatric patients. Driver molecular alteration was found in 92% of patients (24/26). A novel variant of KIAA1549:BRAF fusion (ex10:ex9) was identified using RNA-seq in four cases. Importantly, only one-third of oncogenic drivers could be revealed using standard diagnostic methods, and two-thirds of pediatric patients with sLGGs required extensive molecular examination. The majority (23/24) of detected alterations were potentially druggable targets. Four patients in our cohort received targeted therapy with MEK or NTRK inhibitors. Three of those exhibited clinical improvement (two with trametinib, one with larotrectinib), and two patients achieved partial response. Methylation profiling was implemented to further refine the diagnosis and revealed intertumoral heterogeneity in sLGGs. Although 55% of tumors clustered with pilocytic astrocytoma, other rare entities were identified in this patient population. In particular, diffuse leptomeningeal glioneuronal tumors (n = 3) and high-grade astrocytoma with piloid features (n = 1) and pleomorphic xanthoastrocytoma (n = 1) were present. A proportion of tumors (14%) had no match with the current version of the classifier. Complex molecular genetic sLGGs characterization was invaluable to refine diagnosis, which has proven to be essential in such a rare tumor entity. Moreover, identifying a high proportion of drugable targets in sLGGs opened an opportunity for new treatment modalities.
- MeSH
- astrocytom * genetika MeSH
- dítě MeSH
- genomika MeSH
- gliom * genetika patologie MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy kinas MeSH
- mladiství MeSH
- nádory míchy * genetika MeSH
- nádory mozku * genetika MeSH
- protoonkogenní proteiny B-raf genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVES: Multiple factors have been found to contribute to the high risk of epilepsy in infants with tuberous sclerosis complex (TSC), including evolution of EEG abnormalities, TSC gene variant, and MRI characteristics. The aim of this prospective multicenter study was to identify early MRI biomarkers of epilepsy in infants with TSC aged <6 months and before seizure onset, and associate these MRI biomarkers with neurodevelopmental outcomes at 2 years of age. The study was part of the EPISTOP project. METHODS: We evaluated brain MRIs performed in infants younger than 6 months with TSC. We used harmonized MRI protocols across centers and children were monitored closely with neuropsychological evaluation and serial video EEG. MRI characteristics, defined as tubers, radial migration lines, white matter abnormalities, cysts, calcifications, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA), were visually evaluated and lesions were detected semiautomatically. Lesion to brain volume ratios were calculated and associated with epilepsy and neurodevelopmental outcomes at 2 years. RESULTS: Lesions were assessed on MRIs from 77 infants with TSC; 62 MRIs were sufficient for volume analysis. The presence of tubers and higher tuber-brain ratios were associated with the development of clinical seizures, independently of TSC gene variation and preventive treatment. Furthermore, higher tuber-brain ratios were associated with lower cognitive and motor development quotients at 2 years, independently of TSC gene variation and presence of epilepsy. DISCUSSION: In infants with TSC, there is a significant association between characteristic TSC lesions detected on early brain MRI and development of clinical seizures, as well as neurodevelopmental outcomes in the first 2 years of life. According to our results, early brain MRI findings may guide clinical care for young children with TSC. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in infants with TSC, there is a significant association between characteristic TSC lesions on early brain MRI and the development of clinical seizures and neurodevelopmental outcomes in the first 2 years of life.
- MeSH
- dítě MeSH
- epilepsie * komplikace etiologie MeSH
- kojenec MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- tuberózní skleróza * komplikace diagnostické zobrazování genetika MeSH
- záchvaty komplikace MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system tumor predominantly occurring in infants that may also arise in older children and adults. Rare secondary AT/RT developing from other tumors such as pleomorphic xanthoastrocytoma (PXA) are on record, but AT/RT presenting with molecular features of PXA have not been described. Here, we report 3 malignant central nervous system tumors in children (10, 13, and 18 y old). All tumors were located in the temporal lobe. In 2 cases, there was no history of a low-grade precursor lesion; in 1 case anaplastic PXA had been diagnosed 3 months earlier. Histopathologically, all tumors were composed of RT cells and showed frank signs of malignancy as well as loss of nuclear SMARCB1/INI1 protein expression. Two cases displayed homozygous deletions of the SMARCB1 region while the third case showed an exon 7 mutation (c.849_850delGT; p.Met283Ilefs*77). Of note, DNA methylation profiles did not group with AT/RT or other tumor entities using the Heidelberg Brain Tumor Classifier (version v11b4). By unsupervised t-distributed stochastic neighbor embedding analysis and hierarchical clustering analysis, however, all tumors clearly grouped with PXA. Genome-wide copy number analysis revealed homozygous CDNK2A/B deletions and gains of whole chromosome 7. BRAF V600E mutations could be demonstrated in all cases. In conclusion, the possibility of AT/RT with molecular features of PXA needs to be taken into account and warrants molecular characterization of AT/RT especially in older children. Since treatments targeting mutated BRAF are available, identification of such cases may also have therapeutic consequences.
- MeSH
- astrocytom genetika MeSH
- dítě MeSH
- gen SMARCB1 genetika MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- nádory mozku genetika MeSH
- protoonkogenní proteiny B-raf genetika MeSH
- rhabdoidní nádor genetika MeSH
- teratom genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
