Rare Central Nervous System Research Articles

Diagnostic and Dosimetry Features of [64Cu]CuCl2 in High-Grade Paediatric Infiltrative Gliomas.

Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells. Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1h after tracer injection; if the scan was positive, it was repeated 24 and 72h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging. Ten patients were enrolled (median age 9, range 6-16years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose. [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood-brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.

Immune Microenvironment and Lineage Tracing Help to Decipher Rosette-Forming Glioneuronal Tumors: A Multi-Omics Analysis.

Rosette-forming glioneuronal tumors (RGNT) are rare low-grade primary central nervous system (CNS) tumors. The methylation class (MC) RGNT (MC-RGNT) delineates RGNT from other neurocytic CNS tumors with similar histological features. We performed a comprehensive molecular analysis including whole-exome sequencing, RNAseq, and methylome on 9 tumors with similar histology, focusing on the immune microenvironment and cell of origin of RGNT. Three RGNT in this cohort were plotted within the MC-RGNT and characterized by FGFR1 mutation plus PIK3CA or NF1 mutations. RNAseq analysis, validated by immunohistochemistry, identified 2 transcriptomic groups with distinct immune microenvironments. The "cold" group was distinguishable by a low immune infiltration and included the 3 MC-RGNT and 1 MC-pilocytic astrocytoma; the "hot" group included other tumors with a rich immune infiltration. Gene set enrichment analysis showed that the "cold" group had upregulated NOTCH pathway and mainly oligodendrocyte precursor cell and neuronal phenotypes, while the "hot" group exhibited predominantly astrocytic and neural stem cell phenotypes. In silico deconvolution identified the cerebellar granule cell lineage as a putative cell of origin of RGNT. Our study identified distinct tumor biology and immune microenvironments as key features relevant to the pathogenesis and management of RGNT.

Rare embryonic tumor of the central nervous system – neuroblastoma with FOXR2-activation

Introduction. The development of technologies for molecular genetic typing of tumors of the central nervous system (CNS) has significantly increased the specificity of traditional histological and immunohistochemical research methods. As a result, completely new variants of tumors have appeared, as well as improved results of treatment of tumors with a long-term favorable prognosis. Thanks to new biomarkers, among morphologically similar small-cell embryonic CNS tumors, extremely rare tumors have been identified: ETMR (embryonic tumor with multiple rosettes C19MC), CNS NB-FOXR2 (CNS neuroblastoma (NB) with FOXR2-activation), CNS EFT-CIC (tumor of the CNS sarcoma family of sarcoma alteration), CNS HGNET-MN1 (neuroepithelial tumor of the CNS of high grade with MN1 alteration), CNS HGNET-BCOR (neuroepithelial tumor of the CNS of high grade with BCOR alteration).The aim of the study was to assess the historical prerequisites for the emergence of a new rare nosological form “CNS NB with FOXR2- activation”, as well as presentation of own results of diagnostics and treatment of children with this tumor.Materials and methods. The results of diagnosis and treatment of 7 patients with CNS NB with FOXR2-activation were studied. Tumor identification was carried out using a new DNA methylation technique for CNS tumor profiles using the Heidelberg (Germany) brain tumor classifier (www.molecularneuropathology.org), which has recently become available in Russia.Results and discussion. Based on a review of international experience, the evolution of the appearance in the classification of CNS tumors, as well as the clinical and molecular features of CNS neuroblastoma with FOXR2-activation are presented. The authors present their own results of diagnostics and treatment of 7 patients with a rare tumor CNS neuroblastoma with FOXR2-activation.Conclusion. Biomarkers have been proposed for the differential diagnosis of small-cell PNET-like tumors of the CNS in children. Due to the molecular identification of this tumor in children, it became clear that such patients, provided that the treatment protocol is adequately followed, have quite satisfactory long-term survival results.

Targeted Next-Generation Sequencing Reveals Divergent Clonal Evolution in Components of Composite Pleomorphic Xanthoastrocytoma-Ganglioglioma.

Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers. Five PXA-GG were diagnosed in 1 male and 4 female patients ranging from 13 to 25 years in age. Four arose within the cerebral hemispheres; 1 presented in the cerebellar vermis. DNA was sufficient for analysis in 4 PXA components and 3 GG components. Four paired PXA and GG components harbored BRAF p.V600E hotspot mutations. The 4 sequenced PXA components demonstrated CDKN2A homozygous deletion by sequencing with loss of p16 (protein product of CDKN2A) expression by immunohistochemistry, which was intact in all assessed GG components. The PXA components also demonstrated more frequent copy number alterations relative to paired GG components. In one PXA-GG, shared chromosomal copy number alterations were identified in both components. Our findings support divergent evolution of the PXA and GG components from a common BRAF p.V600E-mutant precursor lesion, with additional acquisition of CDKN2A homozygous deletion in the PXA component as is typically seen in conventional PXA.

The First Molecular Genotyping of Naegleria fowleri Causing Primary Amebic Meningoencephalitis in Thailand With Epidemiology and Clinical Case Reviews.

Primary amebic meningoencephalitis (PAM) is a rare and fatal central nervous system infection caused by Naegleria fowleri, a free-living amoeba found in the environment. To date, eight pathogenic N. fowleri genotypes have been reported worldwide. We aimed to explore the genotypes of N. fowleri that cause primary amebic meningoencephalitis in Thailand. In 2021, the 17th PAM case was reported, and a retrospective literature search of PAM cases in Thailand from 1982 through April 2021 was performed. Phylogenetic and genotyping analyses of the two mitochondrial (12S rRNA and 16S rRNA) and nuclear (ITS1 and 5.8s rRNA) genes of N. fowleri were performed on four available clinical isolates. Based on the mitochondrial and nuclear genes, N. fowleri genotype T3 was found to cause PAM in three out of four cases. However, disagreement between the genotype based on the mitochondrial and nuclear genes was found in one of the PAM cases, in which the 12S rRNA locus suggested the causative genotype as T1, while the ITS1 implied genotype T4. The discrepancy between the mitochondrial and nuclear genome was previously observed, which suggests the possible horizontal gene transfer among N. fowleri species. Based on the ITS1 gene, two N. fowleri genotypes, T3 and T4, were found to be the genotypes causing PAM in this study. In addition, N. fowleri genotype T2 was previously reported in a traveler who was infected in Thailand. Thus, at least three genotypes (T2, T3, and T4) of N. fowleri are found to be associated with PAM in Thailand.

Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: A contemporary single-institution experience.

Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity. A single-center, retrospective study was conducted of patients age ≥18 years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses. Fifty-nine patients met criteria, with median age of 25 years (range 18-62 y) and median follow-up of 6.5 years (range 0.7-23.1 y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6 Gy (relative biological effectiveness [RBE]), median total dose was 54.0 Gy (RBE), 80% received proton radiotherapy; 81% received chemotherapy. 5 year PFS and OS were 86.5% and 95.8%, respectively; 10 year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (P = .04). Among eight recurrences, 25% presented after 5 years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (P = .05). Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae.

RARE-27. Treatment and outcomes in atypical choroid plexus papilloma: a single institution experience

BACKGROUND: Atypical choroid plexus papillomas (aCPP) are rare central nervous system (CNS) tumors often occurring in very young children. While surgical resection has been a mainstay of therapy, there is no consensus and limited data on the treatment of relapsed or metastatic tumors. METHODS: Retrospective review of the treatment and outcome of patients diagnosed with aCPP since 2011 was performed. RESULTS: Of the seven patients, 4 were male and 3 were female with a median age of 3 years at diagnosis (range: antenatal to 18 years old). All non-metastatic patients (six) were treated with surgery and all achieved gross total resection. Two patients had diffuse leptomeningeal contrast enhancement on diagnosis MRI that resolved after resection of primary tumor alone. One patient developed local relapse underwent re-resection with a GTR then was treated with 4 cycles of chemotherapy based on CPT-SIOP-2000 protocol (carboplatin, etoposide) and has not had further relapse in 24 months. One patient had metastatic disease at the time of diagnosis. They were treated with adjuvant chemotherapy, which stabilized disease for 36 months until they had progression. Additional four cycles were given and has again stabilized disease now 8 months from completion of that therapy. One non-metastatic patient died of unknown causes 28 months from diagnosis. CONCLUSIONS: Surgical resection remains the standard of care for patients with aCPP. However, chemotherapy based on the SIOP backbone may be useful to reduce the need for or to delay radiation therapy in select patients in the relapsed or metastatic setting.

RARE-25. Primary Intracranial Ewing Sarcoma in a Child: Case Report

Ewing sarcoma is a rare childhood tumor which accounts for 3% of all pediatric malignancies. More so, primary intracranial involvement with meningeal attachment is even rarer, accounting for only 1% of all Ewing sarcoma. We report a case of a 5-year-old boy who presented with headache, vomiting, and left-sided weakness that rapidly progressed over a period of three months. Cranial MRI showed a 7.1 x 6.7 x 8.6 cm multilobulated, heterogeneously enhancing, mixed solid and cystic extra-axial tumor compressing the frontoparietal lobe and causing significant midline shift. It was attached to the falx and infiltrated the middle third of the superior sagittal sinus. We performed a large right frontoparietal craniotomy to excise the tumor. Because of massive bleeding from the tumor, only a subtotal resection was possible. The bone flap was left out. The patient was discharged fully awake but with right hemiplegia on the fourteenth post-op day. Histopathologic examination revealed a spindle cell neoplasm that exhibited diffuse membranous staining for CD99. Fluorescence in-situ hybridization confirmed EWSR1 gene rearrangement, consistent with Ewing sarcoma. Three months after his surgery, the patient subsequently received 56 Gy of radiation therapy. At twelve months post-op, he remains fully awake and is back in school. He has residual left hemiparesis, but with antigravity movement. A multidisciplinary team involving Pediatric Oncology, Pediatric Neurology, Neurosurgery, Pathology, Radiation Oncology, and Rehabilitation Medicine is essential for patients with rare central nervous system tumors, to maximize effective treatment strategies despite limited resources.

RARE-20. Retrospective analysis of 9 pineoblastoma

BACKGROUND: Pineoblastomas (PBs) are rare, supratentorial, primitive neuroectodermal tumors. Little is known with the clinical features and outcomes of PBs. METHODS: We retrospectively analyzed consecutive patients with PBs who were treated in Guangdong Sanjiu Brain Hospital between December 2006 to May 2020. RESULTS: A total of 9 patients (7 males and 2 females) with PBs were treated in our hospital with a median age of 9 yrs (range: 1-36 yrs) at diagnosis. Total or near-total resection was achieved in 3 patients (33%), partially resection in 4 (44.4%),and biopsy in 2(22.2%). There were 4 patients have spinal cord metastasis at diagnosis. Five patients received craniospinal irradiation (CSI), with concurrent or adjuvant chemotherapy. The average total dose of CSI was 34.80±2.683Gy, and the average dose to local tumor bed was 56.08±6.41Gy. Two patients younger than 3 years old only received chemotherapy, while 1 patient did not receive any postoperative treatment, and 1 patients was unknown. The median followed up time is ? months(range:3-39 months). At the last follow up, 5 patients were died, 3 patients were survived, and 1 was lost to follow-up. The median OS was 31 months (95%CI 1.782-60.281). Disease progression occurred in 5 patients during the follow-up period, and the median PFS was 19 months. CONCLUSION: Pineoblastoma is a rare central nervous system malignancy with a tendency for disseminated disease. Comprehensive therapies such as surgical resection, radiation and chemo therapy are effective therapies for PBs.

The epidemiology and current treatment of pediatric choroid plexus carcinoma: An analysis of the national cancer database.

e14024 Background: Choroid Plexus Carcinoma (CPC), a subtype of choroid plexus tumors (CPT), is a rare central nervous system neoplasm mostly affecting the pediatric population. The epidemiology of CPC is poorly understood due to the rarity of the disease. By analyzing the National Cancer Database (NCDB), we describe the demographic and social factors that influence the risk and current treatment of the cancer. Methods: We conducted a retrospective cohort analysis utilizing the 2018 National Cancer Database (NCDB) and included patients with Choroid Plexus Carcinoma with a histology-confirmed WHO grade III tumor, between ages 0-99 years (N = 202). Analysis was completed for the frequency of cases, types of treatment received, and overall survival within the pediatric population (age &lt; 18 years, N = 139) and the adult population. Demographic factors were analyzed using Pearson Chi-squared tests, and survival was estimated using Kaplan-Meier curves. Results: The majority of the cases analyzed were white (55.4%), male (54%), and pediatric patients (66.8%, mean age at diagnosis = 15.17 years) with an average Charlson-Deyo Score of 0.24. The mean age at diagnosis of the pediatric population was 2.34 years (min = less than 1 years old/diagnosed in utero, max = 16, std. deviation = 3.84) while the mean age at diagnosis of the adult population was 43.49 years (min = 18, max = 84, std. deviation = 18.23.) The most common primary site for CPC was malignant neoplasm of the cerebral ventricle (87.6%) followed by malignant neoplasm of the brain stem (5.9%). Surgical procedure of the primary site was performed in 92.6% of cases including local excision, subtotal resection, resection, radical resection, partial resection of a lobe of brain, lobectomy, and surgery NOS. Radiation was not used 71.3% of the time, but was more than three times as likely to be used in the adult population after surgery than in the pediatric population after surgery (44.4% vs 14.4%, p value &lt; 0.001). Most patients received chemotherapy (53%) with the administration of chemotherapy higher in the cohort less than 18 years old (69.8% versus 15.9%, p value &lt; 0.001). Multiagent chemotherapy was administered as the first course of therapy as the top chemotherapeutic choice (86%) especially among the pediatric population (88.6%) compared to the adult population (60%) Palliative care was not provided in any of the cases. There was no statistical significance difference between the general survival of CPC between the pediatric and adult population. Conclusions: Historically, CPC is known as a pediatric cancer, but this NCDB study suggests that the frequency of the adult population affected is not negligible (31.2%). There is a difference regarding the current treatment of CPC in the pediatric versus adult population. Further study is needed to determine the impact of treatment and the importance of socioeconomic factors on the survival of CPC.

Recent Molecular and Genetic Findings in Intramedullary Spinal Cord Tumors.

The study of genetic alterations and molecular biology in central nervous system (CNS) tumors has improved the accuracy of estimations of patient prognosis and tumor categorization. Therefore, the updated 2021 World Health Organization (WHO) classification includes various diagnostic genes, molecules, and pathways for diagnosis, as well as histological findings. These findings are expected both to have diagnostic applications and to facilitate new targeted therapies that target tumor-specific genetic changes and molecular biology. Intramedullary spinal cord tumors (IMSCTs) are rare CNS tumors that are difficult to treat because they occur in eloquent areas. Although the genetic underpinnings of IMSCTs remain unclear compared to their intracranial counterparts, the genetic characteristics of these tumors are gradually being revealed. Here, we describe the major changes in the new 2021 WHO classification and review the major types of IMSCTs, with an emphasis on their clinical features and genetic alterations.

Growth hormone deficiency due to a rare central nervous system tumor

Growth hormone deficiency due to a rare central nervous system tumor

Tuberculous Meningitis in Which Inflammation Cannot Be Adequately Suppressed by Standard Therapy: Treatment-Resistant Tuberculous Meningitis

To understand tuberculous meningitis (TBM), its clinical features and standard therapy were briefly reviewed. In addition, to determine the therapeutic strategies for treatment-resistant TBM, several clinical cases, including those with paradoxical reaction, ventriculitis, cerebral tuberculoma, and human immunodeficiency virus (HIV) co-infection, are presented. Steroid pulse therapy and intrathecal isoniazid administration are discussed as specific therapeutic strategies. Immune reconstitution inflammatory syndrome in patients with TBM suffering from HIV co-infection and alternative drug selection for drug-resistant TBM cases are also introduced. Although TMB is a rare central nervous system infection, it remains a serious disease with high rates of mortality and neurological sequelae. Knowing therapeutic strategies for treatment-resistant TBM is necessary to prevent a devastating prognosis.

Rare central nervous system lymphomas.

Central nervous system (CNS) lymphomas are rare malignancies characterised by lymphoid infiltration into the brain, spinal cord, cranial nerves, meninges and/or eyes in the presence or absence of previous or concurrent systemic disease. Most CNS lymphomas are of the diffuse large B‐cell lymphoma (DLBCL) subtype for which treatment strategies, particularly the use of high‐dose methotrexate‐based protocols and consolidation with autologous stem cell transplantation, are well established. Other histopathological subtypes of CNS lymphoma are comparatively less common with published data on these rare lymphomas dominated by smaller case series and retrospective reports. Consequently, there exists little clinical consensus on the optimal methods to diagnose and manage these clinically and biologically heterogeneous CNS lymphomas. In this review article, we focus on rarer CNS lymphomas, summarising the available clinical data on incidence, context, diagnostic features, reported management strategies, and clinical outcomes.

Gliosarcoma: Report of Four Cases and Review of Literature

Gliosarcoma (GSM) is a rare central nervous system malignancy; it represents less than 0.5% of all intracranial tumors. GSM usually affects often male in their fifth to sixth decade of life with supratentorial location especially in temporal lobes. The management of GS is extrapolated from glioblastoma with maximal gross total resection, and adjuvant radiotherapy with/without temozolomide. The prognosis is poor with median survival ranged from 06 to 14.8 months. The optimal treatment of GSM is unclear because of the lack of prospective studies. We report 04 cases (three cases of primary GSM and one case of secondary GSM) treated in our department of radiotherapy. Unfortunately, this publication confirmed the poor prognosis and the aggressive behavior of GSM tumors.

Emerging glioneuronal and neuronal tumors: case-based review

Glioneuronal and neuronal tumors (GNTs) are rare heterogeneous central nervous system tumors characterized by slow growth and favorable outcomes, but are often associated with diagnostic difficulties. A thorough analysis of three rare and recently recognized GNTs was performed in the context of clinicopathological features and molecular genetic characterization. The current spinal diffuse leptomeningeal glioneuronal tumor (DLGNT) was characterized with oligodendroglioma-like tumor with chromosome 1p/19q codeletion without IDH mutations and KIAA1549:BRAF fusion. The current occipital multinodular and vacuolating neuronal tumor (MVNT) was characteristic of the variable-sized vague nodules consisted of gangliocytic tumor cells with intracytoplasmic and pericellular vacuolation and the next-generation sequencing (NGS) revealed MAP2K1 p.Q56_V60del. A diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) of the amygdala was characterized by oligodendroglia-like cells and nuclear clusters, and monosomy 14. From the current cases and literature review, we found that DLGNT commonly occurs in the spinal cord and can make mass and more commonly have KIAA1549:BRAF fusion; MVNT is a neoplasm rather than malformation and MAP2K1 deletion is one of the hallmarks of this tumor; although DGONC may require a methylation profile, we can reach a diagnosis through its unique histology, monosomy 14, and exclusion diagnosis without a methylation profile.

A patient with granulomatous amoebic encephalitis caused by Balamuthia mandrillaris survived with two excisions and medication

BackgroundGranulomatous amoebic encephalitis (GAE) is a rare central nervous system infection caused by the Balamuthia mandrillaris or Acanthamoeba species. Diagnosis is challenging because of the non-specific clinical presentation, cerebrospinal fluid analysis, and radiological features. There is no effective treatment for GAE to date.Case presentationA 54-year-old male was admitted to hospital after experiencing acute onset of numbness and weakness on his left limb. Due to the initial consideration of intracranial tumor, surgical removal of the right parietal lesion was performed. However, the patient had a headache accompanied by diplopia, difficulty walking and a new lesion was found in the left occipital-parietal lobe two weeks after the first operation. High-throughput next-generation sequencing (NGS) detected the presence of high copy reads of the B. mandrillaris genome sequence in the patient’s blood, cerebral spinal fluid (CSF), and brain tissue. Pathological investigation of the brain tissue showed granulomatous changes and amoebic trophozoite scattered around blood vessels under high magnification. The patient was re-operated due to developing progressive confusion caused by subfalcine herniation of the left cerebral hemisphere. The lesions of the right parietal lobe were obviously decreasing in size after the first surgery, and the lesions of the left occipital lobe and the sunfalcine herniation didn’t ameliorate two months after the second surgery. The patient was transferred to local hospital for continuous treatment with sulfamethoxazole and azithromycin. After five months of the second surgery, the patient showed good recovery with mild headache.ConclusionsThis is the first report of a patient with B. mandrillaris encephalitis initially confirmed by NGS and have experienced two excisions, responding favorably to the combination of surgeries and medications. Early surgical resection of intracranial lesions combined with drug treatment may offer the chance of a cure.

The biology of ependymomas andemerging novel therapies.

Ependymomas are rare central nervous system tumours that can arise in the brain's supratentorial region or posterior fossa, or in the spinal cord. In 1924, Percival Bailey published the first comprehensive study of ependymomas. Since then, and especially over the past 10 years, our understanding of ependymomas has grown exponentially. In this Review, we discuss the evolution in knowledge regarding ependymoma subgroups and the resultant clinical implications. We also discuss key oncogenic and tumour suppressor signalling pathways that regulate tumour growth, the role of epigenetic dysregulation in the biology of ependymomas, and the various biological features of ependymoma tumorigenesis, including cell immortalization, stem cell-like properties, the tumour microenvironment and metastasis. We further review the limitations of current therapies such as relapse, radiation-induced cognitive deficits and chemotherapy resistance. Finally, we highlight next-generation therapies that are actively being explored, including tyrosine kinase inhibitors, telomerase inhibitors, anti-angiogenesis agents and immunotherapy.

Rare central nervous system tumors in adults: a population-based study of ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors.

BackgroundEpendymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors occur relative frequently in children, but are rare central nervous system (CNS) tumors in adults. In this population-based survey, we established incidence, treatment, and survival patterns for these tumors diagnosed in adult patients (≥18 years) over a 30-year period (1989–2018).MethodsData on 1384 ependymomas, 454 pilocytic astrocytomas, 205 medulloblastomas, and 112 intracranial germ cell tumors were obtained from the Netherlands Cancer Registry (NCR) on the basis of a histopathological diagnosis. For each tumor type, age-standardized incidence rates and estimated annual percentage change were calculated. Trends in incidence and main treatment modalities were reported per 5-year periods. Overall survival was calculated using the Kaplan–Meier method, and relative survival rates were estimated using the Pohar-Perme estimator.ResultsIncidence and survival rates remained generally stable for pilocytic astrocytomas, medulloblastomas, and germ cell tumors. Increasing incidence was observed for spinal ependymomas, mostly for myxopapillary ependymomas, and survival improved over time for grade II ependymomas (P < .01). Treatment patterns varied over time with shifting roles for surgery in ependymomas and for chemotherapy and radiation in medulloblastomas and germinomas.ConclusionsThe study provides baseline information for highly needed national and international standard treatment protocols, and thus for further improving patient outcomes in these rare CNS tumors.

Extraventricular neurocytoma.

Neurocytoma is a rare central nervous system neoplasm that usually arises in an intraventricular location (so-called Central Neurocytoma), but also exists in an extraventricular location (defined as Extraventricular Neurocytoma: EVN). Clinically EVN manifests as headache, nausea, vomiting, complex partial seizures or focal neurological deficits. In some cases, atypical signs characterizing an aggressive clinical behavior may be present. Topographically, EVN most frequently occurs as intrahemispheric (particularly in the frontal lobes), followed by the spinal cord. However, rarer sites have been described.1 Radiologically, EVN is a well-circumscribed, slow-growing neoplasm, usually hyperintense on T2-weighted MRI and isointense/hypointense with no contrast enhancement on T1-weighted MRI.2 Microscopically, EVN consists of small, round cells that show neuronal differentiation, without marked atypia and/or pleomorphism, without vascular endothelial proliferation and/or necrosis and with low mitotic and proliferation indexes. The 2016 World Health Organization classification of tumors of the central nervous system (WHO2016) assigns to EVN histological grade II.3 Immunohistochemically, the main marker to identify the neuronal nature of the neoplasm is Synaptophysin, but immunohistochemical positivity for Synaptophysin alone is not sufficient to conclude a diagnosis of EVN. In fact, there are other central nervous system tumors that may express it, including mainly: pilocytic astrocytoma, disembryoplastic neuroepithelial tumor, ganglioglioma, glioneuronal papillary tumor, some oligodendrogliomas and diffuse leptomeningeal glioneuronal tumor. For this reason, the immunohistochemistry of Synaptophysin should be supplemented with immunohistochemistry for OLIG2 (expression of this marker is usually incompatible with EVN) and molecular investigations to look for IDH mutations (in EVN, IDH must be non-mutated) and/or to look for co-deletion of chromosomes 1p and 19q (AVN must be 1p/19q non-codeleted).3 The pictures above refer to the case of an 86-year-old woman who was found unconscious on the ground at her home for no apparent reason. When she was taken to hospital, a febrile state set in but, before further investigation, she died. An autopsy was therefore carried out, which revealed acute pneumonia as the main cause of death. However, careful macroscopic examination of the formalin-fixed brain, after isolating the vessels of the polygon of Willis, revealed the presence of a 1.2 cm roundish mass at the bifurcation of the two anterior cerebral arteries (Figure1A). Figure 1 A – Macroscopic view of the Willis polygon with a mass at the emergence of the anterior cerebral arteries (arrow); B – Photomicrograph of the well- circumscribed nodular lesion with some micro calcifications (arrows) (H&E, 4x); C – High power field of the nodular lesion showing round cells, sometimes with evident nucleoli, without significant atypia and without mitosis (H&E; 60x); D – Immunohistochemistry, showing positivity for Synaptophysin.: Histological examination of this lesion showed a nodular proliferation of small, uniform round cells, sometimes with cleared cytoplasm (oligodendroglioma-like appearance), in the absence of mitosis, endothelial proliferation and/or necrosis (Figures 1B, 1C), expressing a neuronal-like immunohistochemical profile: widespread immunohistochemical positivity for S100, Synaptophysin (Figure 1D) and Neuron-specific Enolase (NSE) were detected; the proliferation index, assessed by Ki67, was less than 1%. Immunohistochemical staining was negative for: cytokeratins AE1/AE3; EMA; GFAP; OLIG2; Chromogranin; GH; Prolactin; ACTH; TSH; LH; FSH; TTF1; CD31 and CD34. Finally, also the immunohistochemical staining for R132-mutant IDH1 protein was negative. The molecular testing (FISH) for 1p/19q deletion status was not performed. The results were overall consistent with a low-grade neuronal neoplasm of the central nervous system and in particular - although the exceptional site - with an extraventricular neurocytoma.