Evolving Treatment Paradigms of Meningiomas; a Precision Medicine Perspective.

Background: Tumors of Central Nervous System constitute approximately 2% of all malignancies. Cancers of the central nervous system (CNS) are considered to be among the most notorious of all cancers. Low-grade cns tumors have been found over time to progress to high grade tumors. CNS is a common site for metastasis from other organs. Due to newer techniques used in radio diagnosis and stereotactic biopsies, more & more CNS tumors are being diagnosed & are being operated upon.
 Aims and objectives: The objective of this article is to provide an overview of intracranial and intraspinal space occupying lesions at a single tertiary care referral center. The aim was to study incidence of various lesions in light of the WHO classification of tumours of the central nervous system, 2016 and to study relevant statistics.
 Material and methods: A total of 124 cases were received between January,2007 & December, 2011 at Bharati Vidyapeeth Deemed University Medical College and Hospital, Pune. Intraoperative diagnosis was desired in 70 cases. The final diagnoses in all the cases were made on Hematoxylin and Eosin stained slides of routinely processed tissue.
 Results: Neoplastic lesions comprised 83.88 %, including metastatic tumors while 16.12 % were nonneoplastic. A wide range of histopathological spectrum of CNS tumors was observed and was classified according to WHO classification of CNS tumors, 2016. The primary CNS tumors were graded from Grade I to IV according to WHO grading system, 2016. Astrocytic tumors constituted the largest category with 33 cases and most of the astrocytomas were grade II at the time of diagnosis. Incidence was more in females than males and maximum number of lesions were seen in fifth and sixth decades of life.
 Conclusion: This study highlights the histological diversity of CNS tumors in both adults and children. The most common destructive but nonneoplastic lesions like, infections/abscesses, infarct and cysts can be diagnosed, by crush cytology and frozen section for the definitive management.

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.

IntroductionContrary to some earlier teachings that central nervous system (CNS) tumours are uncommon in black children, these neoplasms are the fourth most common paediatric tumours in Ibadan. Our centre is the major referral centre for CNS tumours in Nigeria. The last major study of paediatric CNS neoplasms from Ibadan was in 1985. An update of the data on paediatric CNS neoplasms at our centre is presented.MethodsA retrospective review of all histologically diagnosed CNS tumours in children (0-14 years) from January 2001 to December 2010 from the database of the Department of Pathology, University College Hospital, Ibadan, Nigeria was done. The cases were classified using the 2007 WHO Classification of Tumours of the Central Nervous System and were also based on their supratentorial and infratentorial locations.ResultsSeventy-seven tumours, 44 in males, were included in the study. Astrocytic tumour comprised 20 cases, embryonal tumours 15, ependymal tumours 15, germ cell tumours 6, sellar tumours (all craniopharyngiomas) 9 and other histological types- 12 cases. Thirty-seven were WHO Grade 1, eleven Grade 2, ten Grade 3 and nineteen Grade 4 neoplasms. Thirty-six cases were supratentorial and thirty-eight were infratentorial in location. The most common tumours in this series were pilocytic astrocytomas, medulloblastomas, craniopharyngiomas and ependymomas in that order.ConclusionChildhood CNS tumours are being increasingly diagnosed in our centre. This is largely explained by the recent expansion of the available neurosurgical services.

Simple SummaryPrimary brain tumors are rare neoplasms with limited effective systemic treatment options. Recent advances in new molecular techniques have brought about novel information about molecular markers and potential targetable molecular alterations in brain tumors. Targeted therapeutic approaches are already established in several extracranial malignancies and its application is increasingly used and studied in the management of primary brain tumors. The aim of this article is to summarize the latest progress in precision medicine approaches in primary brain tumors.Primary central nervous system (CNS) tumors represent a heterogenous group of tumors. The 2021 fifth edition of the WHO Classification of Tumors of the CNS emphasizes the advanced role of molecular diagnostics with routine implementation of molecular biomarkers in addition to histologic features in the classification of CNS tumors. Thus, novel diagnostic methods such as DNA methylome profiling are increasingly used to provide a more precise diagnostic work-up of CNS tumors. In addition to these diagnostic precision medicine advantages, molecular alterations are also addressed therapeutically with targeted therapies. Like in other tumor entities, precision medicine has therefore also arrived in the treatment of CNS malignancies as the application of targeted therapies has shown promising response rates. Nevertheless, large prospective studies are currently missing as most targeted therapies were evaluated in single arm, basket, or platform trials. In this review, we focus on the current evidence of precision medicine in the treatment of primary CNS tumors in adults. We outline the pathogenic background and prevalence of the most frequent targetable genetic alterations and summarize the existing evidence of precision medicine approaches for the treatment of primary CNS tumors.

INTRODUCTION: Gliomas are currently classified based on the 2007 WHO Classification of Tumours of the Central Nervous System, which uses histological features to classify and grade these heterogeneous tumors. With recent advances in the development of clinically relevant molecular signatures, there is an interest to incorporate appropriate molecular markers in to the classification. The views of the neuro-oncology community on such changes would be informative for advising this process. METHODS: A survey with 8 questions regarding molecular markers in tumor classification was sent to an email list of SNO members and attendees of prior meetings (n = 5065). There were 403 respondents. Analysis was performed using whole group response and based on self-reported subspecialty. RESULTS: Survey results among all respondents show support for incorporating our molecular knowledge of brain tumors into the WHO classification. Across all seven subspecialty groups, 370% of respondents agreed to this integration. Interestingly, despite support in the majority of questions, neuropathologists were more inclined to disagree that molecular markers should be included in the WHO classification (25% for neuropathologists versus 13% overall). This is in contrast to radiation oncologists who were less inclined (3%) to disagree with this statement. Additionally, neuropathologists were more inclined to state there was no need to change the structure of diagnosis into a “layered” format (17% versus 6% overall) or to agree that pediatric diffuse gliomas should be classified differently from adult tumors despite different molecular features (23% versus 5% overall). CONCLUSION: Based on a survey provided to SNO membership, we report strong support for the integration of molecular markers into the WHO classification of brain tumors, as well as for using an integrated “layered” diagnostic format. While membership from each specialty showed support, there was variation by specialty in enthusiasm regarding proposed changes.

Advances in the understanding of the molecular biology of central nervous system (CNS) tumors have prompted a new WHO classification of brain and spinal cord tumors in 2021 and integration it in routine clinical practice. Nowadays accurate diagnosis verification consists not only of the histological tumor type, but also includes its molecular-genetic characteristics. Differences in the genetic features of a tumor, even within the same histological type, will determine differences in the prognosis of the disease, and in the tactics of anticancer therapy. The introduced changes necessitate a comprehensive diagnosis of CNS tumors, thereby placing the responsibility for formulating the final diagnosis not only on pathologists. New approaches to classification make it possible to personalize anticancer treatment, as well as including new methods of targeted and immunotherapy, which today seems to be a key aspect of improving the survival of this category of patients.

Introduction to 2021 WHO Classification of Thoracic Tumors

In 2021, the WHO classification of tumors of the central nervous system (CNS) was published, which drastically changed the diagnostic approach to tumors in the CNS. In the diagnosis of most subtypes of CNS tumors, especially in gliomas, the genetic test became critical in the latest version of the classification, meanwhile analyzing genetic alterations in routine practice is still quite difficult in most of the hospitals in Japan because of the accessibility of the genetic analysis. In Kyoto University Hospital (KUHP), around 80 tumors in CNS are newly diagnosed every year, half of which are gliomas with a few challenging cases on the histopathological diagnosis. The diagnostic approach to CNS tumors in KUHP can be divided into two steps: the clinical phase and the academic phase. The clinical phase includes a pre-operative conference with neurosurgeons, radiologists, and pathologists, and classical histopathological analysis on formalin-fixed and paraffin-embedded tissues with H&E staining, immunohistochemistry on p53, IDH1 R132H, and ATRX, fluorescence in situ hybridization on 1p/19q co-deletion, and consultation to the experts of the CNS tumors. Some cases are further analyzed by clinical cancer genome sequencing. When the tumors are expected to be glioma during the pre-operative conference, after the surgery, the tumor tissue gets frozen to be submitted to the academic phase. The academic phase includes analysis of genetic alterations with Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) assay on the representative glioma-associated genes. In some cases, the tumors are further analyzed by methylome assay and/or mRNA sequencing (PMID: 35900258), to identify novel genetic alterations. Most of the neuropathologists in Japan today are suffering in diagnosing gliomas because of the novel, sophisticated, and complicated WHO classification. In this presentation, we want to share our diagnostic approach to the diagnosis of CNS tumors and shed light on it.

The introduction of molecular methods into the diagnostics of central nervous system (CNS) tumours and the subsequent deciphering of their molecular heterogeneity has resulted in a significant impact on paediatric neurooncology. Particularly in the field of rare embryonal and sarcomatous CNS tumours, novel tumour types have been delineated and introduced in the recent 5th edition of the WHO classification of CNS tumours. The rarity and novelty of these tumour types result in diagnostic and therapeutic challenges. Apart from distinct histopathological and molecular features, these tumour types exhibit characteristic clinical properties and require different therapeutic approaches for optimal patient management. However, based on the limited availability of clinical data, current therapeutic recommendations have to be based on data from small, predominantly retrospective patient cohorts. Within this article, we provide guidance for diagnostic work-up and clinical management of rare CNS embryonal tumours (‘embryonal tumour with multi-layered rosettes’, ETMR; ‘CNS neuroblastoma, FOXR2-activated’, CNS NB-FOXR2; ‘CNS tumour with BCOR-ITD, CNS BCOR-ITD) and rare CNS sarcomatous tumours (‘primary intracranial sarcoma, DICER1-mutant’, CNS DICER1; ‘CIC-rearranged sarcoma’, CNS CIC). By emphasizing the significant consequences on patient management in paediatric CNS tumours, we want to encourage wide implementation of comprehensive molecular diagnostics and stress the importance for joint international efforts to further collect and study these rare tumour types.

The 2021 WHO classification of tumors of the central nervous system, 5th edition (WHO CNS 5) is built on the previous, revised 4th edition, published in 2016, which incorporated molecular information into the diagnosis of brain tumors for the first time, breaking with the century-old histogenetic classification. WHO CNS 5 also adopted a series of recommendations of "the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT)" that facilitates a consensus review of novel diagnostically relevant data and determines how such information can be fit into future CNS tumor classifications. In WHO CNS 5, the grading system was reformed to "grading within tumor types," and the tumor groups, especially diffuse gliomas, have been significantly restructured; the diffuse gliomas have been divided into the adult type and the pediatric type, the latter being subdivided into low-grade and high-grade gliomas. Based on molecular alterations, 22 novel tumor types are recognized, and some nomenclature has also been revised. The integrated, layered diagnosis of combining histology, grading, and molecular information was recommended to provide clinically relevant information.

The 2021 WHO Classification of Tumors of the Heart

Report two adult cases of high-grade neuroepithelial neoplasm harbouring EP300::BCOR fusions with comprehensive molecular detection.

The 2021 5th edition of the WHO Classification of Tumors of the Central Nervous System reflects the discovery of genetic alterations underlying many central nervous system (CNS) neoplasms. Insights gained from technologic advances and novel applications in molecular diagnostics, including next‐generation sequencing and DNA methylation‐based profiling, coupled with the recognition of clinicopathologic correlates, have prompted substantial changes to CNS tumor classification; this is particularly true for pediatric low‐grade gliomas and glioneuronal tumors (pLGG/GNTs). The 2021 WHO now classifies gliomas, glioneuronal tumors and neuronal tumors into 6 families, three of which encompass pLGG/LGNTs: “Pediatric type diffuse low‐grade gliomas,” “circumscribed astrocytic gliomas,” and “glioneuronal and neuronal tumors.” Among these are six newly recognized tumor types: “diffuse astrocytoma, MYB or MYBL1‐altered”; “polymorphous low grade neuroepithelial tumor of the young (PLNTY)”; “diffuse low‐grade glioma‐MAPK altered”; “Diffuse glioneuronal tumor with oligodendroglioma‐like features and nuclear clusters (DGONC)”; “myxoid glioneuronal tumor (MGT)”; and “multinodular and vacuolating neuronal tumor (MVNT).” We review these newly recognized entities in the context of general changes to the WHO schema, discuss implications of the new classification for treatment of pLGG/LGNT, and consider strategies for molecular testing and interpretation.

Histopathologic classifications of primary central nervous system lymphoma(PCNSL)are covered by two WHO classifications; WHO classification of Tumors: Central Nervous System Tumours(WHO-CNS)and WHO classification of Tumors: Haematolymphoid Tumours(WHO-HAEM). The International Consensus Classification(ICC)is another recent comprehensive classification of hematolymphoid tumors that covers these disease entities. While these classifications mainly share the same principles for categorizing these tumors, there are several differences that should be noted owing to the nature of WHO-CNS(which covers only the lymphomas manifesting in the CNS, and the anatomic sites are described in the titles of some entities)and the introduction of new entities in the latest version(5th)of the WHO-HAEM(WHO-HAEM5). In the WHO-HAEM5, two novel entities related to the perception of PCNSLs are introduced: primary large B-cell lymphoma of immune-privileged sites and lymphomas arising in immune deficiency/dysregulation. These entities are largely based on the underlying biology shared by lymphomas that arise from different sites, including the central nervous system, and they combine and re-classify several types that had been defined separately according to their sites and etiologies in previous versions. Classifications of PCNSLs in future revisions of the WHO-CNS might be described as parts of these novel entities, and nomenclatures of some diagnostic entities may be subject to change accordingly. This review will mainly focus on the classification of lymphomas described in the 5th edition of WHO-CNS, along with its comparison with WHO-HAEM and ICC.

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, established new approaches to both CNS tumor nomenclature and grading, emphasizing the importance of integrated diagnoses and layered reports. This edition increased the role of molecular diagnostics in CNS tumor classification while still relying on other established approaches such as histology and immunohistochemistry. Moreover, it introduced new tumor types and subtypes based on novel diagnostic technologies such as DNA methylome profiling. Over the past decade, molecular techniques identified numerous key genetic alterations in CSN tumors, with important implications regarding the understanding of pathogenesis but also for prognosis and the development and application of effective molecularly targeted therapies. This review summarizes the major changes in the 2021 fifth edition classification of pediatric CNS tumors, highlighting for each entity the molecular alterations and other information that are relevant for diagnostic, prognostic, or therapeutic purposes and that patients’ and oncologists’ need from a pathology report.