BAP1-deficient meningioma presenting with trabecular architecture and cytokeratin expression: a report of two cases and review of the literature

AimsBRCA (BReast CAncer gene)-associated protein 1 (BAP1), encoded by the BAP1 gene, a tumour suppressor that is lost in several cancers. Importantly, such mutations have been shown to be susceptible to poly (ADP-ribose) polymerase (PARP) inhibition in preclinical studies, offering hope for targeted therapy. While rare, BAP1 loss has been observed in a subset of rhabdoid and papillary meningioma and is associated with earlier recurrence. We seek to add to the literature on this rare disease and advocate for more routine BAP1 testing.MethodsWe present a report of two cases of BAP1-deficient meningioma and review the available literature on this rare entity.ResultsBoth cases present with a distinct trabecular architecture without rhabdoid or papillary features. Interestingly, both also presented with radiographic and histopathological findings unusual for meningioma. While immunohistochemistry and genetic sequencing confirmed BAP1 loss, DNA methylation analysis was required to confirm the final diagnosis.ConclusionsWe suggest that BAP1-deficient meningioma should be considered in the differential diagnosis of extra-axial central nervous system (CNS) tumours with atypical imaging or histopathological features and that BAP1 loss may constitute a clinically important meningioma subtype with opportunities for targeted therapy.

Feasibility on the Use of Radiomics Features of 11[C]-MET PET/CT in Central Nervous System Tumours: Preliminary Results on Potential Grading Discrimination Using a Machine Learning Model

Background/Aim: Nowadays, Machine Learning (ML) algorithms have demonstrated remarkable progress in image-recognition tasks and could be useful for the new concept of precision medicine in order to help physicians in the choice of therapeutic strategies for brain tumours. Previous data suggest that, in the central nervous system (CNS) tumours, amino acid PET may more accurately demarcate the active disease than paramagnetic enhanced MRI, which is currently the standard method of evaluation in brain tumours and helps in the assessment of disease grading, as a fundamental basis for proper clinical patient management. The aim of this study is to evaluate the feasibility of ML on 11[C]-MET PET/CT scan images and to propose a radiomics workflow using a machine-learning method to create a predictive model capable of discriminating between low-grade and high-grade CNS tumours. Materials and Methods: In this retrospective study, fifty-six patients affected by a primary brain tumour who underwent 11[C]-MET PET/CT were selected from January 2016 to December 2019. Pathological examination was available in all patients to confirm the diagnosis and grading of disease. PET/CT acquisition was performed after 10 min from the administration of 11C-Methionine (401–610 MBq) for a time acquisition of 15 min. 11[C]-MET PET/CT images were acquired using two scanners (24 patients on a Siemens scan and 32 patients on a GE scan). Then, LIFEx software was used to delineate brain tumours using two different semi-automatic and user-independent segmentation approaches and to extract 44 radiomics features for each segmentation. A novel mixed descriptive-inferential sequential approach was used to identify a subset of relevant features that correlate with the grading of disease confirmed by pathological examination and clinical outcome. Finally, a machine learning model based on discriminant analysis was used in the evaluation of grading prediction (low grade CNS vs. high-grade CNS) of 11[C]-MET PET/CT. Results: The proposed machine learning model based on (i) two semi-automatic and user-independent segmentation processes, (ii) an innovative feature selection and reduction process, and (iii) the discriminant analysis, showed good performance in the prediction of tumour grade when the volumetric segmentation was used for feature extraction. In this case, the proposed model obtained an accuracy of ~85% (AUC~79%) in the subgroup of patients who underwent Siemens tomography scans, of 80.51% (AUC 65.73%) in patients who underwent GE tomography scans, and of 70.31% (AUC 64.13%) in the whole patients’ dataset (Siemens and GE scans). Conclusions: This preliminary study on the use of an ML model demonstrated to be feasible and able to select radiomics features of 11[C]-MET PET with potential value in prediction of grading of disease. Further studies are needed to improve radiomics algorithms to personalize predictive and prognostic models and potentially support the medical decision process.

An Overview of Central Nervous System Tumours

Central nervous system (CNS) tumours refer to tumours that occur in the tissues of the brain and/or spinal cord. These tumours arise as a result of abnormal growth of cells and may begin in different parts of the brain or spinal cord. There are many types of CNS tumours, which are further divided into subtypes. Despite decades of research conducted, CNS tumours remain among the deadliest of all cancers. It is most often challenging to treat these tumours, due to the risks involved, and biological characteristics associated with them. The classification, grading, and characterisation of CNS tumour plays a pivotal role in the management thereof. The current review provides an overview of CNS tumours, classification, grading and treatment, as well as their characterisation with specific focus on gliomas, ependymomas, oligodendrogliomas, meningiomas, medulloblastomas, schwannomas, gangliogliomas, and craniopharyngiomas. Doi: 10.28991/SciMedJ-2021-0304-8 Full Text: PDF

PATH-47. THE 2016 WHO CLASSIFICATION AND IT'S CLINICAL IMPACT: THE LEEDS TEACHING HOSPITALS NHS TRUST EXPERIENCE

INTRODUCTION In 2016 the WHO Classification of Tumours of the Central Nervous System was updated to include molecular testing, in addition to the previous standard histological methods; producing a final integrated diagnosis. Although molecular information can guide treatment and aid in prognostication, it adds a significant workload to pathology and genetic testing services. Delayed diagnosis can also add anxiety to patients, at an already traumatic time. AIMS: To determine if final integrated diagnoses, for patients undergoing neurosurgery for CNS tumours, is being provided in an appropriate time frame, and whether it changes clinical management. METHODS All patients >16 years at the time of surgery with a histopathologically-confirmed CNS tumour were identified from 2016-2020. A retrospective analysis of the time taken to produce an integrated histological diagnosis took place, using the date of surgery and date of verified final integrated report being the first and last data points respectively. Data were collected by accessing electronic and paper health records, and local databases. Changes in clinical management between the initial histology result and the final integrated diagnosis were classified as no change or a major change. RESULTS 1390 surgical procedures for CNS pathology were identified between 2016-2020, producing 361 final integrated diagnosis reports. 64 (18%) of these reports resulted in a major change in clinical management when compared to the initial histology report. The turn-around time for initial histology from date of surgery was a mean of 9 days and a mean of 34 days for the final integrated diagnosis. CONCLUSIONS The integrated diagnosis is essential for providing the gold standard of treatment for patients, although for the majority of patients it does not change their clinical management. Further study and discussion is required about the role of the final integrated diagnosis in the management of patients with CNS tumours.

EPID-20. THE RISING INCIDENCE AND PREVALENCE OF BRAIN TUMOURS: A CANADIAN EPIDEMIOLOGICAL STUDY

BACKGROUND Primary malignant brain tumours account for over one third of all brain tumours and are associated with high morbidity and mortality. The purpose of this paper is to estimate the rate and trends of incidence and prevalence for primary malignant CNS tumours in Canada from 1992 to 2017. METHODS An epidemiological study using publicly available data from Statistics Canada: Canadian Cancer Registry (CCR) from 1992 to 2017 for all of Canada was conducted. Incidence and prevalence per 100,000, age-standardized incidence, and age-standardized prevalence per 100,000 person-years of primary malignant CNS tumours were calculated and stratified by sex and age: pediatric (0-19), adult (20-64), and elderly ( >64) populations. RESULTS During the study period, incidence and prevalence increased by 27.3% and 28.8%, respectively. Males accounted for 56% of all diagnoses and experienced decreased survival compared to females one year after diagnosis (p-value = 0.04). Age-standardized rates of incidence and prevalence were highest in elderly populations. CONCLUSIONS Overall, the incidence of primary malignant CNS tumours has increased from 1992 to 2017 with males and the elderly disproportionately affected. Increased healthcare resources and awareness are needed to better identify and deliver evidence-based care for these patients.

P.164 The Rising Incidence and Prevalence of Brain Tumours: a Canadian epidemiological study

Background: Primary malignant brain tumours account for over one third of all brain tumours and are associated with high morbidity and mortality. The purpose of this paper is to estimate the rate and trends of incidence and prevalence for primary malignant CNS tumours in Canada from 1992 to 2017. Methods: An epidemiological study using publicly available data from Statistics Canada: Canadian Cancer Registry (CCR) from 1992 to 2017 for all of Canada was conducted. Incidence and prevalence per 100,000, age-standardized incidence, and age-standardized prevalence per 100,000 person-years of primary malignant CNS tumours were calculated and stratified by sex and age: pediatric (0-19), adult (20-64), and elderly (>64) populations. Results: During the study period, incidence and prevalence increased by 27.3% and 28.8%, respectively. Males accounted for 56% of all diagnoses and experienced decreased survival compared to females one year after diagnosis (p-value = 0.04). Age-standardized rates of incidence and prevalence were highest in elderly populations. Conclusions: Overall, the incidence of primary malignant CNS tumours has increased from 1992 to 2017 with males and the elderly disproportionately affected. Increased healthcare resources and awareness are needed to better identify and deliver evidence-based care for these patients.

Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours

Central nervous system (CNS) tumours comprise 25% of the paediatric cancer diagnoses and are the leading cause of cancer-related death in children. Current treatments for paediatric CNS tumours are far from optimal and fail for those that relapsed or are refractory to treatment. Besides, long-term sequelae in the developing brain make it mandatory to find new innovative approaches. Chimeric antigen receptor T cell (CAR T) therapy has increased survival in patients with B-cell malignancies, but the intrinsic biological characteristics of CNS tumours hamper their success. The location, heterogeneous antigen expression, limited infiltration of T cells into the tumour, the selective trafficking provided by the blood–brain barrier, and the immunosuppressive tumour microenvironment have emerged as the main hurdles that need to be overcome for the success of CAR T cell therapy. In this review, we will focus mainly on the characteristics of the deadliest high-grade CNS paediatric tumours (medulloblastoma, ependymoma, and high-grade gliomas) and the potential of CAR T cell therapy to increase survival and patients’ quality of life.

Diffuse leptomeningeal glioneuronal tumour (DLGNT) in children: the emerging role of genomic analysis

Diffuse leptomeningeal glioneuronal tumours (DLGNT) represent rare enigmatic CNS tumours of childhood. Most patients with this disease share common radiological and histopathological features but the clinical course of this disease is variable. A radiological hallmark of this disease is widespread leptomeningeal enhancement that may involve the entire neuroaxis with predilection for the posterior fossa and spine. The classic pathologic features include low- to moderate-density cellular lesions with OLIG2 expression and evidence of ‘oligodendroglioma-like’ appearance. The MAPK/ERK signaling pathway has recently been reported as a potential driver of tumourigenesis in up to 80% of DLGNT with KIAA1549:BRAF fusions being the most common event seen. Until now, limited analysis of the biological drivers of tumourigenesis has been undertaken via targeted profiling, chromosomal analysis and immunohistochemistry. Our study represents the first examples of comprehensive genomic sequencing in DLGNT and shows that it is not only feasible but crucial to our understanding of this rare disease. Moreover, we demonstrate that DLGNT may be more genomically complex than single-event MAPK/ERK signaling pathway tumours.

Clinicopathological Study of Primary Central Nervous System Tumours - A Descriptive Study in a Tertiary Care Center Hospital of Dakshina Kannada

BACKGROUND The central nervous system (CNS) consisting of brain and spinal cord is a delicate and a complex organ. Even a minor lesion within the central nervous system can significantly affect the higher functions and the voluntary and involuntary systems of the body. The CNS tumours have become one among the leading cause of cancer death in the present days. Early diagnosis and proper grading of these tumours can significantly improve the patient outcome. This study was conducted with an objective of correlating the clinical features with histomorphological characteristics of the primary CNS tumours and to grade the primary CNS tumors based on World Health Organization (WHO) classification. METHODS This was a descriptive observational study. A total of 117 cases of primary CNS tumours were collected from January 2012 to June 2017 at the central diagnostic laboratory of A.J Institute of Medical Sciences and Research Centre, Mangalore belonging to the Dakshina Kannada district of Karnataka, India. Out of 117 cases, 35 cases were retrieved from the files and remaining 82 were fresh cases. The tissues were fixed in 10 % buffered formalin and routinely processed. The tissue sections were stained with haematoxylin and eosin and were classified based on WHO classification. Special stain like reticulin was done in selected cases to establish the diagnosis. Patient details including the complete clinical history was collected to correlate with the histological findings. RESULTS Meningeal tumours were the maximum (37.6 %) among the central nervous system tumours in present study. Clinically, most of them (40.9 %) presented with headache and seizures. The commonest clinical presentation of central nervous system tumours observed in the present study was seizures (31.6 %). Middle cranial fossa was the preferred site for the CNS tumours (35 %). The study showed a female preponderance for CNS tumour with a male to female ratio of 1 : 1.3. The mean age for primary CNS tumours observed in the present study was 43.94 years. CONCLUSIONS In the present study, a systematic analysis of primary central nervous system tumour has been done giving due importance to the clinical features. The present study also showed a significant correlation with that of other studies. Despite of having modern imaging technique, the histopathological examination remains as the gold standard in diagnosing CNS tumours. KEY WORDS CNS Tumours, Neuroepithelial Tumours, Meningioma, Astrocytoma, Schwannoma.