• MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell genetics   MeSH
• DNA-Directed DNA Polymerase genetics   metabolism   MeSH
• DNA Primase genetics   metabolism   MeSH
• Extracellular Matrix metabolism   pathology   MeSH
• Genes, p53 genetics   MeSH
• Glioblastoma metabolism   pathology   MeSH
• Pericytes metabolism   pathology   MeSH
• BRCA1 Protein genetics   metabolism   MeSH
• Publication type
• Overall MeSH

• Keywords
• Chirurgie, ortopedie, traumatologie,
• MeSH
• Neurosurgery MeSH

• NML Fields
• neurochirurgie

• MeSH
• Astrocytoma * genetics   pathology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• MAP Kinase Signaling System * physiology   genetics   MeSH
• Mutation genetics   MeSH
• Brain Neoplasms * genetics   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Letter MeSH

Precizní onkologie představuje nové pojetí onkologické péče, které umožňuje co možná nejlepší individualizaci léčby pro konkrétního pacienta a konkrétní tumor. Toho je dosaženo s využitím výsledků pokročilých molekulárně­‐genetických diagnostických metod, které umožňují detailní molekulární profilování nádorové choroby a zjištění potenciálních cílů moderní protinádorové terapie, tzv. cílené léčby. Toto sdělení pojednává o postupných změnách v klasifikaci nádorů centrálního nervového systému, které byly nutné právě vzhledem k enormnímu rozvoji poznání o molekulárních mechanismech onkogeneze v posledních letech. Součástí jsou také některé důležité příklady využití přístupů precizní onkologie u nádorů centrálního nervového systému s podrobným zaměřením na difuzní gliomy.

Precision oncology represents a new concept of cancer care that allows the best possible individualization of treatment for a particular patient and a particular tumour. This is achieved by using the results of advanced molecular-genetic diagnostic methods which enable detailed tumour molecular profiling and identification of potential targets of modern anticancer treatment, i.e. targeted therapy. The present article deals with gradual changes in the classification of central nervous system tumours which were necessary given the enormous development of knowledge on molecular mechanisms of oncogenesis in recent years. Also included are some important examples of using precision oncology approaches in central nervous system tumours, with a detailed focus on diffuse gliomas.

• MeSH
• Molecular Targeted Therapy methods   MeSH
• Glioblastoma genetics   pathology   therapy   MeSH
• Glioma classification   pathology   therapy   MeSH
• Precision Medicine methods   MeSH
• Carcinogenesis genetics   MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Central Nervous System Neoplasms * classification   pathology   therapy   MeSH
• Antineoplastic Agents, Immunological therapeutic use   MeSH
• Antineoplastic Agents pharmacology   therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Check Tag
• Humans MeSH

Diffusion-weighted imaging (DWI) and its numerical expression via apparent diffusion coefficient (ADC) values are commonly utilized in non-invasive assessment of various brain pathologies. Although numerous studies have confirmed that ADC values could be pathognomic for various ring-enhancing lesions (RELs), their true potential is yet to be exploited in full. The article was designed to introduce an image analysis method allowing REL recognition independently of either absolute ADC values or specifically defined regions of interest within the evaluated image. For this purpose, the line of interest (LOI) was marked on each ADC map to cross all of the RELs' compartments. Using a machine learning approach, we analyzed the LOI between two representatives of the RELs, namely, brain abscess and glioblastoma (GBM). The diagnostic ability of the selected parameters as predictors for the machine learning algorithms was assessed using two models, the k-NN model and the SVM model with a Gaussian kernel. With the k-NN machine learning method, 80% of the abscesses and 100% of the GBM were classified correctly at high accuracy. Similar results were obtained via the SVM method. The proposed assessment of the LOI offers a new approach for evaluating ADC maps obtained from different RELs and contributing to the standardization of the ADC map assessment.

• MeSH
• Brain Abscess * pathology   MeSH
• Diffusion Magnetic Resonance Imaging methods   MeSH
• Glioblastoma * diagnostic imaging   pathology   MeSH
• Humans MeSH
• Brain diagnostic imaging   pathology   MeSH
• Cross-Sectional Studies MeSH
• Machine Learning MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article 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
• Astrocytoma * diagnostic imaging   drug therapy   genetics   MeSH
• Glioma * diagnostic imaging   drug therapy   genetics   MeSH
• Histones genetics   MeSH
• Infant MeSH
• Humans MeSH
• Brain Stem Neoplasms * diagnostic imaging   drug therapy   genetics   MeSH
• Pons pathology   MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH

• Publication type
• Overall 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
• Astrocytoma diagnosis   pathology   MeSH
• Glioblastoma pathology   MeSH
• Glioma * diagnosis   genetics   classification   pathology   MeSH
• Immunohistochemistry MeSH
• Humans MeSH
• Mutation MeSH
• Oligodendroglioma pathology   MeSH
• Severity of Illness Index MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Cíl: Cílem této práce bylo vyhodnocení bezpečnosti supracerebellárního transtentoriálního přístupu na našem souboru pacientů. Jedná se o technicky náročný přístup, který jsme využili při operacích zadní a střední mediotemporální oblasti, laterálního mezencefala a posteromediálního talamu. Soubor a metodika: Jedná se vyhodnocení souboru našich 8 pacientů operovaných supracerebellárním transtentoriálním přístupem v letech 2013–2021. V jednom případě se jednalo o anaplastický astrocytom, 3× o primooperaci glioblastoma multiforme, 1× difuzního středočárového H3K27M gliomu, 1× o operaci recidivy glioblastoma multiforme, 1× o operaci nízkostupňového gliomu a jednou jsme tímto přístupem operovali akutně prokrvácený kavernom lemniskálního trigona mesencefali. Všichni naši pacienti byli operováni v poloze v polosedě. Výsledky: 30denní mortalita v našem souboru je nulová. U pacientky s difuzním středočárovým H3K27M gliomem primárně operované v neurologicky těžkém stavu jsme museli provést časnou reoperaci stejným přístupem z důvodu prokrvácení rezidua tumoru. U našeho prvního pacienta s rozsáhlým mediotemporálním anaplastickým astrocytomem jsme museli po první době časně doplnit subokcipitální přístup ke zvýšení radikality resekce, po operaci měl horní kvadrantanopsii. U jednoho pacienta došlo k ischemii okcipitálního laloku z důvodu peroperačně pozorovatelné léze arteria cerebri posterior obklopené glioblastomem. Klinicky byla po operaci přítomna hemianopsie. Závěr: Jedná se o technicky náročný, přitom ale o bezpečný přístup. U lézí postihujících mediotemporální oblast je výhodný pro její střední a zadní část, ale při resekci lze dosáhnout anteriorně až k uncu a amygdale. Předpokládanou podmínkou je precizní znalost anatomie, na našem pracovišti pro tento přístup preferujeme polohu v polosedě. Důležitá je dostatečná likvorová dekomprese vypuštěním moku z cisterna magna ze separátní durální incize a šetrná manipulace s cévními strukturami tentoriální incisury.

Aim: The aim of this work was a retrospective evaluation of the safety of the supracerebellar transtentorial approach in our patient series. It represents a technically challenging approach, which we used during surgeries of the posterior and medial mediotemporal area, lateral mesencephalon and posteromedial thalamus. Materials and methods: We evaluate the series of our 8 patients, which we operated on using the supracerebellar transtentorial approach during 2013–2021. In one case, we dealt with anaplastic astrocytoma, 3× with glioblastoma multiforme primary surgery, 1× with diffuse midline H3K27M glioma, 1× with glioblastoma multiforme recurrence surgery, 1× with low-grade glioma surgery and once we operated using this approach an acutely bleeding cavernoma of the lemniscal trigone of the mesencephalon. All our patients were operated on in a semisitting position. Results: The thirty-day mortality rate of our series is zero. In case of a patient with diffuse midline H3K27M glioma which was primarily operated on in a bad neurological condition, we had to perform early revision surgery using the same approach due to residual tumor hemorrhage. In case of our first patient with extensive mediotemporal anaplastic astrocytoma, we had to add the suboccipital approach for resection radicality increase early after the first phase of surgery; after the surgery, he had superior quadrantanopsia. In one patient’s case, ischemia of the occipital lobe occurred due to an intraoperatively visible lesion of the posterior cerebral artery inside the glioblastoma. After surgery, hemianopsia was present. Conclusion: The approach poses a technically challenging, but concurrently safe surgical trajectory. In case of the lesions affecting the mediotemporal area, it is advantageous for its medial and posterior part, but during the resection it is possible to reach as far as the uncus and amygdala. The prerequisite condition is accurate anatomical knowledge; in our department, we prefer the semisitting position for this approach. It is important to have a sufficient cerebrospinal fluid decompression by releasing the fluid from the cisterna magna from a separate dural incision and a gentle manipulation of the vascular structures of the tentorial incisura.

• Keywords
• supracerebellární transteritoriální přístup,
• MeSH
• Adult MeSH
• Glioma surgery   MeSH
• Hippocampus surgery   MeSH
• Craniotomy methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Microsurgery * methods   MeSH
• Brain Neoplasms * surgery   MeSH
• Neurosurgical Procedures methods   MeSH
• Temporal Lobe surgery   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't 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
• Astrocytoma * genetics   MeSH
• Child MeSH
• Genomics MeSH
• Glioma * genetics   pathology   MeSH
• Humans MeSH
• Mitogen-Activated Protein Kinase Kinases MeSH
• Adolescent MeSH
• Spinal Cord Neoplasms * genetics   MeSH
• Brain Neoplasms * genetics   MeSH
• Proto-Oncogene Proteins B-raf genetics   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Journal Article MeSH