Hemorrhagic Presentation in Primary Central Nervous System Lymphoma: A Case Study.

BACKGROUND Primary central nervous system diffuse large B-cell lymphoma (DLBCL) is an extremely aggressive brain disease that rarely affects immunocompetent non-elderly patients, particularly with hemorrhagic presentation. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of this entity, which typically demonstrates restricted diffusion and a T2 hypointense appearance, suggesting hypercellularity. CASE REPORT A 44-year-old man came to the emergency department with a persistent and treatment-resistant bilateral frontal headache that had been bothering him for the past 3 weeks. Upon conducting a neurological assessment, the patient displayed temporal disorientation and incoherent speech, but without any observable motor deficits. A non-contrast enhanced brain computed tomography scan was carried out, revealing a hyperattenuating, space-occupying lesion and hemorrhage in the left hemisphere of the brain. Subsequently, brain MRI demonstrated hypointense signal on T2-weighted images, restricted diffusion, and homogeneous lesional contrast enhancement, suggesting a very cellular expansive lesion with hemorrhage. To establish a definitive diagnosis, a brain biopsy was undertaken, confirming the presence of DLBCL of the primary central nervous system (germinal center phenotype). CONCLUSIONS Hemorrhagic presentation of primary central nervous system DLBCL occurs very rarely, particularly in non-elderly immunocompetent patients. Brain MRI plays an important role in the diagnosis of this entity, which allows differentiation from high-grade glial or other lesions that present more frequently with hemorrhage. Therefore, it is crucial to suspect lymphoma before surgical intervention for appropriate patient management.

CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.

A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.

[Clinical study of 15 cases of primary non-immunodeficient central nervous system lymphoma in children].

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

Analysis and prediction of central nervous system tumor burden in China during 1990-2030.

Central nervous system (CNS) tumors, due to their unique locations, pose a serious threat to human health and present challenges to modern medicine. These tumors exhibit notable epidemiological characteristics across various ethnicities, regions, and age groups. This study investigated the trend of disease burden of CNS tumors in China from 1990-2019 and predicted the incidence and death rate from 2020-2030. Employing data from the 2019 Global Burden of Disease (GBD) database, we utilized key indicators to scrutinize the disease burden associated with CNS tumors in China. The analysis employed the Joinpoint model to track the trend in disease burden, calculating both the annual percentage change (APC) and average annual percentage change (AAPC). Additionally, the Matlab software facilitated the creation of a gray model to forecast the incidence and death rate of CNS tumors in China spanning from 2020 to 2030." In 2019, the age-standardized incidence rate, prevalence rate, death rate, and disability-adjusted life years (DALYs) associated with CNS tumors in China were among the high level in the world. The standardized prevalence rate and DALYs of CNS tumors in China residents showed a stable fluctuation trend with age; however, age-standardized death and incidence rate demonstrated a generally upward trend with age. In China, the age-standardized prevalence and incidence rate of males were lower than those for female residents, while the age-standardized death rate and DALYs among males surpassed those of females. From 1990-2019, the age-standardized prevalence and incidence rate of CNS tumors in China exhibited an increasing trend. The age-standardized death rate and DALYs showed a contrasting trend. According to the gray model's prediction, incidence rate of CNS tumors would continue rising while the death rate is expected to decline in China from 2020-2023. The burden of CNS tumors in China has shown an upward trajectory, posing significant challenges to their treatment. It is necessary to pay attention to tertiary prevention, start from the perspective of high-risk groups and high-risk factors to reduce the burden of disease, and achieve "early detection, early diagnosis, and early treatment".

Cauda equina neuroendocrine tumor: a report of three cases and review of the literature with focus on differential diagnosis and postoperative management.

INTRODUCTION: Cauda equina neuroendocrine tumors (CENETs), previously described as cauda equina paragangliomas (PGLs) are rare and well-vascularized benign entities which can be often misdiagnosed with other intradural tumors more common in this anatomical site, such as ependymomas and neurinomas. We describe three cases of CENETs observed at our institution with particular focus on differential diagnosis and postoperative management. Since the lack of guidelines, we performed a literature review to identify factors that can predict recurrence and influence postoperative decision making. CASE REPORT AND LITERATURE REVIEW: We report on three patients, two of them presenting with a clinical history of lower back pain and sciatica. In all cases magnetic resonance imaging (MRI) of the lumbosacral spine with and without Gd-DTPA revealed an intradural lesion with strong contrast enhancement, first described as atypical ependymoma or schwannoma. A complete tumor resection was achieved in all cases, the histopathological diagnosis classified the tumors as CENETs. In our literature review, a total of 688 articles were screened and 162 patients were included. Patients demographic data, clinical symptoms, resection and recurrence were recorded. DISCUSSION: Differential diagnosis between CENETs and other more common tumors affecting cauda equina region, such as ependymomas or schwannomas (neurinomas), is still very challenging. Due to the lack of specific clinical or radiological characteristics, a correct preoperative diagnosis is almost impossible. With this paper we want to point out that CENETs must be considered in the differential diagnosis, most of all in case of entities with atypical radiological features. According to the literature, tumor recurrence after gross total resection is unlikely, while a long-term follow-up is recommended in case of subtotal resection or local aggressive behavior.

Letter to editor: C­reactive protein levels, the prognostic nutritional index, and the lactate dehydrogenase­to­lymphocyte ratio are important prognostic factors in primary central nervous system lymphoma: a single­center study of 223 patients.

This critique evaluates a letter to the editor discussing prognostic factors in primary central nervous system lymphoma (PCNSL), focusing on C-reactive protein (CRP) levels, prognostic nutritional index (PNI), and lactate dehydrogenase (LDH)-to-lymphocyte ratio. While the letter provides valuable insights, limitations including reliance on a single-center dataset, lack of consideration for potential confounders, insufficient contextualization within existing literature, and limited discussion of clinical implications are identified. Addressing these limitations is crucial for enhancing the relevance and applicability of the findings in PCNSL management.

BCOR::CREBBP fusion in malignant neuroepithelial tumor of CNS expands the spectrum of methylation class CNS tumor with BCOR/BCOR(L1)-fusion.

Methylation class "CNS tumor with BCOR/BCOR(L1)-fusion" was recently defined based on methylation profiling and tSNE analysis of a series of 21 neuroepithelial tumors with predominant presence of a BCOR fusion and/or characteristic CNV breakpoints at chromosome 22q12.31 and chromosome Xp11.4. Clear diagnostic criteria are still missing for this tumor type, specially that BCOR/BCOR(L1)-fusion is not a consistent finding in these tumors despite being frequent and that none of the Heidelberger classifier versions is able to clearly identify these cases, in particular tumors with alternative fusions other than those involving BCOR, BCORL1, EP300 and CREBBP. In this study, we introduce a BCOR::CREBBP fusion in an adult patient with a right temporomediobasal tumor, for the first time in association with methylation class "CNS tumor with BCOR/BCOR(L1)-fusion" in addition to 35 cases of CNS neuroepithelial tumors with molecular and histopathological characteristics compatible with "CNS tumor with BCOR/BCOR(L1)-fusion" based on a comprehensive literature review and data mining in the repository of 23 published studies on neuroepithelial brain Tumors including 7207 samples of 6761 patients. Based on our index case and the 35 cases found in the literature, we suggest the archetypical histological and molecular features of "CNS tumor with BCOR/BCOR(L1)-fusion". We also present four adult diffuse glioma cases including GBM, IDH-Wildtype and Astrocytoma, IDH-Mutant with CREBBP fusions and describe the necessity of complementary molecular analysis in "CNS tumor with BCOR/BCOR(L1)-alterations for securing a final diagnosis.

Exclusive Breastfeeding Duration and Risk of Childhood Cancers.

Importance: Breastfeeding has been suggested to protect against childhood cancers, particularly acute lymphoblastic leukemia (ALL). However, the evidence stems from case-control studies alone. Objective: To investigate whether longer duration of exclusive breastfeeding is associated with decreased risk of childhood ALL and other childhood cancers. Design, Setting, and Participants: This population-based cohort study used administrative data on exclusive breastfeeding duration from the Danish National Child Health Register. All children born in Denmark between January 2005 and December 2018 with available information on duration of exclusive breastfeeding were included. Children were followed up from age 1 year until childhood cancer diagnosis, loss to follow-up or emigration, death, age 15 years, or December 31, 2020. Data were analyzed from March to October 2023. Exposure: Duration of exclusive breastfeeding in infancy. Main Outcomes and Measures: Associations between duration of exclusive breastfeeding and risk of childhood cancer overall and by subtypes were estimated as adjusted hazard ratios (AHRs) with 95% CIs using stratified Cox proportional hazards regression models. Results: A total of 309 473 children were included (51.3% boys). During 1 679 635 person-years of follow-up, 332 children (0.1%) were diagnosed with cancer at ages 1 to 14 years (mean [SD] age at diagnosis, 4.24 [2.67] years; 194 boys [58.4%]). Of these, 124 (37.3%) were diagnosed with hematologic cancers (81 [65.3%] were ALL, 74 [91.4%] of which were B-cell precursor [BCP] ALL), 44 (13.3%) with central nervous system tumors, 80 (24.1%) with solid tumors, and 84 (25.3%) with other and unspecified malignant neoplasms. Compared with exclusive breastfeeding duration of less than 3 months, exclusive breastfeeding for 3 months or longer was associated with a decreased risk of hematologic cancers (AHR, 0.66; 95% CI, 0.46-0.95), which was largely attributable to decreased risk of BCP-ALL (AHR, 0.62; 95% CI, 0.39-0.99), but not with risk of central nervous system tumors (AHR, 0.96; 95% CI, 0.51-1.88) or solid tumors (AHR, 0.87; 95% CI, 0.55-1.41). Conclusions and Relevance: In this cohort study, longer duration of exclusive breastfeeding was associated with reduced risk of childhood BCP-ALL, corroborating results of previous case-control investigations in this field. To inform future preemptive interventions, continued research should focus on the potential biologic mechanisms underlying the observed association.

Peritumoral brain zone in glioblastoma: biological, clinical and mechanical features.

Glioblastoma is a highly aggressive and invasive tumor that affects the central nervous system (CNS). With a five-year survival rate of only 6.9% and a median survival time of eight months, it has the lowest survival rate among CNS tumors. Its treatment consists of surgical resection, subsequent fractionated radiotherapy and concomitant and adjuvant chemotherapy with temozolomide. Despite the implementation of clinical interventions, recurrence is a common occurrence, with over 80% of cases arising at the edge of the resection cavity a few months after treatment. The high recurrence rate and location of glioblastoma indicate the need for a better understanding of the peritumor brain zone (PBZ). In this review, we first describe the main radiological, cellular, molecular and biomechanical tissue features of PBZ; and subsequently, we discuss its current clinical management, potential local therapeutic approaches and future prospects.

Evaluation of Conditions for the Development of Cryogenic Spinal Cord Injury Using a Canine Model: An Experimental Study on the Safety of Cryoablation for Metastatic Spinal Tumors.

BACKGROUND AND PURPOSE: Although the application of cryoablation to metastatic spinal tumors has been attempted, spinal cryoablation has the unique complication of cryogenic spinal cord injury. This study aimed to elucidate the conditions for the development of cryogenic spinal cord injury. MATERIALS AND METHODS: Fifteen canines were used in this study. A metal probe was inserted into the 13th thoracic vertebral body. Cryoablation was performed for 10 minutes by freezing the probe in liquid nitrogen. The control canine underwent probe insertion only. Spinal cord monitoring, epidural temperature measurement, motor function assessment, and pathologic examination of the spinal cord were performed. RESULTS: During the 10 minutes of cryoablation, the epidural temperature decreased and reached the lowest epidural temperature (LET) at the end of cryoablation. The LETs (degrees celsius [°C]) of each canine were -37, -30, -27, -8, -3, -2, 0, 1, 4, 8, 16, 18, 20, and 25, respectively. As the epidural temperature decreased, waveform amplitudes also decreased. At the end of cryoablation (10 minutes after the start of cryoablation), abnormal waves were observed in 92.9% (13/14) of canines. With epidural rewarming, the amplitude of the waveforms tended to recover. After epidural rewarming (2 hours after the start of cryoablation), abnormal waves were observed in 28.6% (4/14) of canines. The LETs (°C) of the canines with abnormal waves after epidural rewarming were -37, -30, -27, and -8. None of the canines with normal waves after epidural rewarming had any motor impairment. In contrast, all canines with remaining abnormal waves after epidural rewarming had motor impairment. In the pathologic assessment, cryogenic changes were found in canines with LETs (°C) of -37 -30, -27, -8, 0, and 1. CONCLUSIONS: This study showed that 10-minute spinal cryoablation with LETs (°C) of -37, -30, -27, -8, 0, and 1 caused cryogenic spinal cord injury. There was no evidence of cryogenic spinal cord injury in canines with LET of ≥4°C. The epidural temperature threshold for cryogenic spinal cord injury is between 1 and 4°C, suggesting that the epidural temperature should be maintained above at least 4°C to prevent cryogenic spinal cord injury.

Imaging of supratentorial intraventricular masses in children:a pictorial review- part 1.

PURPOSE: This article is the first in a two-part series designed to provide a comprehensive overview of the range of supratentorial intraventricular masses observed in children. Our primary objective is to discuss the diverse types of intraventricular masses that originate not only from cells within the choroid plexus but also from other sources. METHODS: In this article, we review relevant epidemiological data, the current genetics/molecular classification as outlined in the fifth edition of the World Health Organization's Classification of tumours of the Central Nervous System and noteworthy imaging findings. We conduct an exhaustive analysis of primary choroid plexus tumours as well as other conditions such as choroid plexus hyperplasia, choroid plexus cyst, choroid plexus xanthogranuloma, atypical teratoid rhabdoid tumour, meningioma, arteriovenous malformation and metastasis. RESULTS: We comprehensively evaluated each supratentorial intraventricular mass, providing an in-depth analysis of their unique clinical and histological characteristics. The fifth edition of the World Health Organization Classification of Tumours of the Central Nervous System introduces major modifications. These important changes could potentially have a profound impact on the management strategies and subsequent outcomes of these tumours. CONCLUSION: Intraventricular masses in children can arise from various sources. Surgical intervention is key for certain supratentorial intraventricular masses in paediatric patients, with preoperative neuroimaging essential to decide the best treatment approach, surgical or otherwise, as some cases may not require surgery.

Survival of European adolescents and young adults diagnosed with cancer in 2010-2014.

BACKGROUND: We used the comprehensive definition of AYA (age 15 to 39 years) to update 5-year relative survival (RS) estimates for AYAs in Europe and across countries and to evaluate improvements in survival over time. METHODS: We used data from EUROCARE-6. We analysed 700,000 AYAs with cancer diagnosed in 2000-2013 (follow-up to 2014). We focused the analyses on the 12 most common cancers in AYA. We used period analysis to estimate 5-year RS in Europe and 5-year RS differences in 29 countries (2010-2014 period estimate) and over time (2004-06 vs. 2010-14 period estimates). FINDINGS: 5-year RS for all AYA tumours was 84%, ranging from 70% to 90% for most of the 12 tumours analysed. The exceptions were acute lymphoblastic leukaemia, acute myeloid leukaemia, and central nervous system tumours, presenting survival of 59%, 61%, and 62%, respectively. Differences in survival were observed among European countries for all cancers, except thyroid cancers and ovarian germ-cell tumours. Survival improved over time for most cancers in the 15- to 39-year-old age group, but for fewer cancers in adolescents and 20- to 29-year-olds. INTERPRETATION: This is the most comprehensive study to report the survival of 12 cancers in AYAs in 29 European countries. We showed variability in survival among countries most likely due to differences in stage at diagnosis, access to treatment, and lack of referral to expert centres. Survival has improved especially for haematological cancers. Further efforts are needed to improve survival for other cancers as well, especially in adolescents.

Factors associated with overall survival in breast cancer patients with leptomeningeal disease (LMD): a single institutional retrospective review.

BACKGROUND: Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center from 2011 to 2020, to determine the changing incidence of BC-LMD, factors which are associated with the progression of BC CNS metastasis to BC-LMD, and factors which are associated with OS for patients with BC-LMD. METHODS: Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS. RESULTS: 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016 and 2020 when compared to 2011-2015. Patients with HR+ or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) was associated with prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC were associated with a delayed BC-CNS metastasis to LMD progression. Lapatinib treatment was associated with a delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT was associated with prolonged survival for all patients. Lapatinib and trastuzumab therapy was associated with improved OS in patients with HER2 + BC-LMD. CONCLUSIONS: Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Prospective trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.

Recurrence Patterns and Surveillance Imaging in Pediatric Brain Tumor Survivors.

Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in pediatric central nervous system (CNS) tumors. The frequency of neuroimaging surveillance varies without a standardized approach. A single-institutional retrospective cohort study evaluated the frequency of recurrences. This study included 476 patients with the majority diagnosed with low-grade glioma (LGG) (n=138, 29%), high-grade glioma (HGG) (n=77, 16%), ependymoma (n=70, 15%), or medulloblastoma (n=61, 13%). LGG, HGG, and ependymoma patients more commonly had multiply recurrent disease ( P =0.08), with ependymoma patients demonstrating ≥2 relapses in 47% of cases. Recurrent disease was identified by imaging more often than clinical symptoms (65% vs. 32%; P =<0.01). Patients diagnosed with meningioma demonstrated the longest mean time to first relapse (74.7 mo) whereas those with atypical teratoid rhabdoid tumor and choroid plexus carcinoma tended to have the shortest time to relapse (8.9 and 9 mo, respectively). Overall, 22 patients sustained first relapse >10 years from initial diagnosis. With a higher tendency toward detection of tumor recurrence/progression on MRI surveillance in comparison to clinical progression, surveillance imaging is necessary in routine follow up of pediatric CNS tumor survivors. With some relapses >10 years from initial diagnosis, imaging beyond this time point may be useful in particular tumor types. While the study is limited in outcome analysis, earlier detection of recurrence would lead to earlier initiation of treatment and implementation of salvage treatment regimens which can impact survival and quality of life.

Diagnostic significance of cerebrospinal fluid flow cytometry in Chinese children with B lineage acute lymphoblastic leukemia.

BACKGROUND: Central nervous system leukemia (CNSL) is one of the major causes of the poor prognosis of childhood leukemia. We aimed to compare the sensitivity of cytomorphology (CM) and flow cytometry (FCM) in diagnosing CNSL, emphasizing the importance of FCM in the diagnosis process. METHODS: One-hundred-sixty-five children with newly diagnosed B-cell Acute Lymphoblastic Leukemia (B-cell ALL) were included in this study. Cerebrospinal fluid (CSF) samples were taken for routine CSF analysis, CM analysis, and FCM examination. Computed tomography scans and/or magnetic resonance imaging were performed at diagnosis. Patients with CNS2, CNS3, and traumatic lumbar puncture (TLP) at diagnosis received two additional courses of triple intrathecal injections during induction treatment. We compared the sensitivity of FCM and CM in the diagnosis of children with CNSL. RESULTS: One hundred and twenty-eight (77.58%) CSF samples were negative by either CM or FCM (CM-/FCM-), four (2.42%) were positive by both CM and FCM (CM+/FCM+), and thirty-three (20%) displayed a single positive finding by FCM (CM-/FCM+) (p = 0.044). By adding two intrathecal injections in the induction treatment, ten children with TLP+ had no CNS relapse, like those with TLP-. However, compared to CNS1 and TLP, the event-free survival (EFS) did not significantly improve in patients with CNS2 and CNS3. Moreover, CNSL status was associated with worse 3-year EFS (p < 0.05). CONCLUSIONS: We have validated that FCM is more accurate in stratifying the status of the CNS compared to CM analysis. However, to improve the EFS rate of childhood leukemia, it is necessary to combine CM examination, FCM, and cranial imaging for the early diagnosis of CNSL.