Intracranial myxoid mesenchymal tumour with EWSR1-ATF1 fusion mimicking high grade glioma

Aims Molecular profiling is increasingly used in the diagnosis of CNS and non-CNS neoplasms. More than a quarter of all soft tissue tumours are characterized by specific recurrent chromosomal translocations which can be used as molecular signatures. With increasing frequency, EWSR1 rearrangements are found on both mesenchymal tumours and primary glial/neuronal tumours. Here we present a case of intracranial myxoid mesenchymal tumour (IMMT), a rare tumour which is becoming more recognised in recent years, affecting mainly children and young adults, and rarely older adults. It can be found in intraaxial and extraaxial location, with frequent dural connection. The tumour is defined by the genetic hallmark of EWSR1-CREB family gene fusion. Including our case, 16 intracranial tumours with this gene fusion have been reported to date. Our goal is to contribute further to the characterisation of the morphological spectrum, fusion partners and biological behaviour of rare EWSR1-CREB (non-ETS)-rearranged tumours of the CNS. Method Case: The patient is a 27 year old woman with a frontal lobe lesion, radiologically described as a tumour with dural attachment. She underwent surgical debulking, and tumour tissue was histologically examined with conventional immunohistochemistry. Additional genetic testing included targeted mutation screening, FISH, EPIC (Illumina BeadChip) methylation array and next generation sequencing. Histology showed a mitotically active neoplasm with relatively uniform cells, round nuclei and oligodendroglioma-like clear cell change, but no myxoid change. Glomeruloid microvascular proliferation and large areas of tumour necrosis were present. Immunohistochemistry was focally positive for GFAP, and negative or normal for synaptophysin, IDH1 R132H mutation, ATRX and p53. The ki-67 index reached ~20%. Sequencing of IDH1 and IDH2 did not reveal rare IDH mutations, and FISH did not show 1p19q codeletion. Testing for BRAF V600 mutation was negative. Results Although the histology initially suggested a diagnosis of oligodendroglioma, the integrated diagnosis was compatible with glioblastoma, IDH wildtype. Methylation array analysis by EPIC array did not result in classification of currently known entities, neither confirming glioblastoma, nor providing a new diagnosis, when analysed on both brain tumour and sarcoma classifier. This suggested a novel tumour entity not yet represented in the classifier algorithm. Additional testing including next generation sequencing revealed EWSR1 gene rearrangement with fusion partner ATF1 (EWSR1-ATF1 fusion). Based on this, the diagnosis was revised to the emerging new entity of ‘intracranial myxoid mesenchymal tumor’ (IMMT) characterised by EWSR1 fusion with members of the cAMP response element binding protein (CREB) family (ATF1, CREB1 and CREM). Subsequent immunohistochemistry demonstrated positive staining for CD99 and EMA but not desmin. The patient underwent various oncological treatments and is recurrence-free 3 years after initial diagnosis. Conclusion Histologically, IMMT demonstrates a spectrum of features that overlaps with other tumours, but often displays circumscribed growth, uniform cellularity, cytoplasmic clearing and variable myxoid change. The clinical behaviour of these tumours is not fully understood, however provisionally considered intermediate grade. EWSR1-CREB family fusion is not specific but shared with a diverse group of extracranial tumours including soft tissue, salivary gland, odontogenic and myoepithelial tumours. Therefore, clinico-radiologico-pathological correlation is essential to achieve the final diagnosis, and ensure the absence of a primary tumour elsewhere. Familiarisation with IMMT, its characteristic genetic profile and its as yet underreported natural course is crucial, as it can clinically mimic other intracranial tumours such as malignant meningioma or glioma but appears to behave less aggressively than high grade glioma. It is also important to further our understanding of its optimal treatment through review of larger case series and global comparison of patient management.

Medulloblastoma in Adulthood

Defined as a tumour with increased malignancy potential in childhood, medulloblastoma was first reported in the literature by Percival Bailey and Harvey Cushing in 1925. Scientific studies over the years have shown that this type of tumour represents about 20% of all intracranial tumours encountered in childhood, their percentage decreasing with advancing age. The genetic factor plays an important part in the appearance of medulloblastoma; there are certain diseases, in the patient’s history, that can be associated with this type of tumour. Here, we can specify Turcot syndrome (an autosomal recessive disease, rarely encountered) or basal cell carcinoma syndrome. This article presents the case of a young patient (41-year-old) suffering from a cerebellar tumour formation that turned out to be, after histopathological examination, a medulloblastoma. In practice we can find several types of medulloblastoma (desmoplastic or nodular, anaplastic, classical or undifferentiated). In what follows I will try to highlight a few aspects of a classic medulloblastoma.

Intracranial Lesions Presenting as Bony Swellings of Scalp – An Observational Study of 13 Cases at King George Hospital, Visakhapatnam, A Tertiary Care Government Hospital

BACKGROUND The purpose of this study was to evaluate the intracranial lesions eroding the calvarium and presenting as bony swellings of the scalp. This kind of presentation is usually rare. This is because intracranial tumours usually manifest early with focal neurological deficits, seizures or features of raised intracranial pressure. Only a few patients, in whom the intracranial lesions, despite being present for a long duration, do not have neurological manifestations but erode the overlying bone and may present as bony swellings of the scalp. We studied the clinical presentation of such lesions, analysed their radiological and histological characteristics. METHODS This is an observational study from October 2018 to September 2020. A total of thirteen cases were studied in the Department of Neurosurgery, Andhra Medical College, Visakhapatnam, Andhra Pradesh. After clinical examination, an appropriate diagnostic workup was done, and all the cases were taken up for surgery. The clinical behaviour and histopathological features of the lesions were analysed. RESULTS In our study of thirteen cases, the most common cause of an intracranial lesion presenting as bony scalp swelling is meningioma which comprised almost 53.8 %, the second most common lesion is secondaries. Others included fibrous dysplasia and malignant small blue round cell tumour. CONCLUSIONS Intracranial lesions eroding the bone and presenting as scalp swellings are rare. In our study, the spectrum of these scalp swellings has ranged from benign lesions like meningioma to malignant lesions like secondary deposits. KEYWORDS Bony Scalp Lesions, Intracranial Tumours with Bony Erosion, Dumbbell Brain Tumours

Neuroophthalmic Manifestations of Intracranial Tumours in Children

Background. All children between 0 and 16 years presenting with brain tumours confirmed by Magnetic Resonance Imaging (MRI) and treated surgically in our institute were included in this study. Objective. The aim of this study is to evaluate the neuroophthalmic and clinical characteristics of intracranial space occupying lesions in children. Methods. Neuroophthalmic manifestations along with location of the tumour by contrast-enhanced MRI, type of surgical intervention, and postoperative histopathological diagnosis were evaluated. Results. In pediatric brain tumours, male preponderance was seen and supratentorial location was more common in general, while in older children, infratentorial tumours were more common than supratentorial tumours. Headache, vomiting, and cerebellar signs were the commonest neurological features. Diminution of vision, diplopia, and strabismus were the commonest ophthalmic symptoms. Papilledema, ophthalmoparesis, and nystagmus were the most frequent ophthalmological signs. Neurological manifestations of seizures, altered sensorium and motor deficits were more frequently seen in supratentorial tumours, while cranial nerve involvement and ataxia were seen in infratentorial tumours. Ophthalmological manifestations including diplopia, strabismus, ophthalmoparesis, and nystagmus were more frequently seen in infratentorial tumours. Astrocytoma was the most frequent histopathological diagnosis followed by medulloblastoma. Conclusion. Diagnosis of pediatric intracranial tumours is complex and requires a multidisciplinary approach for prompt management. An ophthalmologist should have a high index of suspicion for brain tumours especially in patients presenting with common ocular symptoms like diminution of vision, diplopia, and strabismus without any neurological symptoms.

CovidNeuroOnc: a UK multi-centre, prospective cohort study of the impact of the COVID-19 pandemic on the neuro-oncology service

Background The COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumours. Methods We performed a multi-centre prospective study of all adult patients discussed in weekly neuro-oncology and skull base multidisciplinary team meetings who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumour between 01 April and 31 May 2020. All patients had at least 30-day follow-up data. Descriptive statistical reporting was used. Results There were 1357 referrals for newly diagnosed or recurrent intracranial tumours across fifteen neuro-oncology centres. Of centres with all intracranial tumours, a change in initial management was reported in 8.6% of cases (n=104/1210). Decisions to change the management plan reduced over time from a peak of 19% referrals at the start of the study to 0% by the end of the study period. Changes in management were reported in 16% (n=75/466) of cases previously recommended for surgery and 28% of cases previously recommended for chemotherapy (n=20/72). The reported SARS-CoV-2 infection rate was similar in surgical and non-surgical patients (2.6% vs. 2.4%, p>0.9). Conclusions Disruption to neuro-oncology services in the UK caused by the COVID-19 pandemic was most marked in the first month, affecting all diagnoses. Patients considered for chemotherapy were most affected. In those recommended surgical treatment this was successfully completed. Longer-term outcome data will evaluate oncological treatments received by these patients and overall survival.

Intracranial chondroma of the falx-cerebi: a clinical case

Intracranial chondroma is a rare pathology with the occurrence of 0.1 % to 0.5 % of all primary intracranial tumours. The mechanism of tumour formation outside cartilaginous tissue is controversial. The majority of data point at a very diverse cellular composition of the Dura mater and the tumour may emerge as a result of fi broblast activation. Frequently, the tumour is a manifestation of multiple enchodromatosis (Ollier’s disease) or Maff ucci syndrome. Clinical manifestations of the disease are unspecifi c and generalised. Diff erential diagnosis of the tumour is complicated due to the absence of pathognomonic neurovisualisation characteristics. Th erefore, it is only possible to verify the diagnosis via pathomorphological examination. Chondroma is a benign neoplasm and its complete resection is essential for the positive outcome and longer life duration of the patients. Th e article presents a clinical case of successful surgical treatment of a patient with intracranial chondroma of falxcerebri.