Understanding diffuse leptomeningeal glioneuronal tumors.

INTODUCTION: Diffuse leptomeningeal glioneuronal tumors (DLGNTs) pose a rare and challenging entity within pediatric central nervous system neoplasms. Despite their rarity, DLGNTs exhibit complex clinical presentations and unique molecular characteristics, necessitating a deeper understanding of their diagnostic and therapeutic nuances. METHODS: This review synthesizes contemporary literature on DLGNT, encompassing epidemiology, clinical manifestations, pathological features, treatment strategies, prognostic markers, and future research directions. To compile the existing body of knowledge on DLGNT, a comprehensive search of relevant databases was conducted. RESULTS: DLGNT primarily affects pediatric populations but can manifest across all age groups. Its diagnosis is confounded by nonspecific clinical presentations and overlapping radiological features with other CNS neoplasms. Magnetic resonance imaging (MRI) serves as a cornerstone for DLGNT diagnosis, revealing characteristic leptomeningeal enhancement and intraparenchymal involvement. Histologically, DLGNT presents with low to moderate cellularity and exhibits molecular alterations in the MAPK/ERK signalling pathway. Optimal management of DLGNT necessitates a multidisciplinary approach encompassing surgical resection, chemotherapy, radiotherapy, and emerging targeted therapies directed against specific genetic alterations. Prognostication remains challenging, with factors such as age at diagnosis, histological subtypes, and genetic alterations influencing disease progression and treatment response. Long-term survival data are limited, underscoring the need for collaborative research efforts. CONCLUSION: Advancements in molecular profiling, targeted therapies, and international collaborations hold promise for improving DLGNT outcomes. Harnessing the collective expertise of clinicians, researchers, and patient advocates, can advance the field of DLGNT research and optimize patient care paradigms.

Valproic acid as a radio-sensitizer in glioma: A systematic review and meta-analysis.

Background: Histone deacetylase inhibitors (HDACi) including valproic acid (VPA) have the potential to improve radiotherapy (RT) efficacy and reduce treatment adverse events (AE) via epigenetic modification and radio-sensitization of neoplastic cells. This systematic review and meta-analysis aimed to assess the efficacy and AE associated with HDACi used as radio-sensitizers in adult solid organ malignancy patients. Methods: A systematic review utilized electronic searches of MEDLINE(Ovid), Embase(Ovid), The Cochrane Library, and the International Clinical Trials Registry Platform to identify studies examining the efficacy and AEs associated with HDACi treatment in solid organ malignancy patients undergoing RT. Meta-analysis was performed with overall survival (OS) reported as hazard ratios (HR) as the primary outcome measure. OS reported as median survival difference, and AEs were secondary outcome measures. Results: Ten studies reporting on the efficacy and/or AEs of HDACi in RT-treated solid organ malignancy patients met inclusion criteria. All included studies focused on HDACi valproic acid (VPA) in high-grade glioma patients, of which 9 studies (n = 6138) evaluated OS and 5 studies (n = 1055) examined AEs. The addition of VPA to RT treatment protocols resulted in improved OS (HR = 0.80, 95% CI 0.67-0.96). No studies focusing on non-glioma solid organ malignancy patients, or non-VPA HDACi met the inclusion criteria for this review. Conclusions: This review suggests that glioma patients undergoing RT may experience prolonged survival due to HDACi VPA administration. Further randomized controlled trials are required to validate these findings. Additionally, more research into the use of HDACi radio-adjuvant treatment in non-glioma solid organ malignancies is warranted.

Cytoskeletal Protein Palladin in Adult Gliomas Predicts Disease Incidence, Progression, and Prognosis.

Brain tumors comprise over 100 types of masses, differing in the following: location; patient age; molecular, histological, and immunohistochemical characteristics; and prognosis and treatment. Glioma tumors originate from neuroglia, cells supporting the brain. Palladin, a structural protein widely expressed in mammalian tissues, has a pivotal role in cytoskeletal dynamics and motility in health and disease. Palladin is linked to the progression of breast, pancreatic, and renal cancers. In the central nervous system, palladin is involved in embryonic development, neuronal maturation, the cell cycle, differentiation, and apoptosis. However, the role of palladin in brain tumors is unknown. In this work, we explored palladin's role in glioma. We analyzed clinical data, along with bulk and single-cell gene expression. We then validated our results using IHC staining of tumor samples, together with qRT-PCR of glioma cell lines. We determined that wild-type palladin-4 is overexpressed in adult gliomas and is correlated with a decrease in survival. Palladin expression outperformed clinically used prognostic markers and was most prominent in glioblastoma. Finally, we showed that palladin originates from the malignant cell population. Our findings indicate that palladin expression might be linked to adult glioma progression and is associated with prognosis.

A Challenge in Diagnosis of Cerebellar Hemangioblastoma.

Hemangioblastomas are benign neoplasms, which are highly vascularized and have a slow-growing rate that typically affect the central nervous system; they account for about 1-2.5% of all intracranial tumors and for approximately 2-3% of all intramedullary neoplasms. We present a clinical case of cerebellar hemangioblastoma with six years of evolution, which illustrates the diagnostic difficulties that often arise, especially when the clinical and imaging characteristics escape those usually described and when other clinical findings appear as confounding factors. A 17-year-old female was initially admitted to the emergency department (ED) with a holocranial headache, gait imbalance, and vomiting. A brain magnetic resonance imaging (MRI) was done and a rounded lesion was detected in the left cerebellar hemisphere, hypointense in T1 and hyperintense in T2, with annular contrast enhancement. Several hypotheses for diagnosis were made, and the patient was subjected to several therapies, with periods of remission of symptoms interleaved with periods of worsening. After imaging suggestive of hemangioblastoma on routine brain MRI, the tumor was excised surgically and the histopathology confirmed the diagnosis. In the control brain MRI exams performed six and 24 months after surgery, no evidence of tumor recurrence was detected, and the patient remained asymptomatic. In conclusion, although these are rare neoplasms, it is essential to always consider hemangioblastomas in the differential diagnosis of cases with compatible clinical and radiological findings. A wrong or late diagnosis may lead to the use of unnecessary and harmful therapies as well as the appearance of potentially preventable complications if these tumors are handled correctly and timely.

Clinical Trial Enrollment Among Adolescent and Young Adults with Primary Central Nervous System Tumors Treated at the Dana-Farber Cancer Institute.

Purpose: In recent decades, the survival outcomes among adolescent and young adults (AYAs, 15-39 years) have not improved substantially, especially among AYAs with primary central nervous system (CNS) tumors. While this is likely multifactorial, low participation in clinical trials among AYAs is thought to be a critical contributing factor. In this study, we describe the pattern of clinical trial enrollment among AYAs with primary CNS tumors at our institution. Methods: We performed a retrospective, IRB-approved chart review of AYAs with CNS tumors treated at the Dana-Farber Cancer Institute (DFCI) between January 2009 and December 2018. We used logistic regression analyses and descriptive statistics to analyze this sample and determine the clinical trial enrollment at the pediatric affiliate (Dana-Farber/Boston Children's Cancer and Blood Disorders Center) and adult affiliate (Dana-Farber/Brigham and Women's Cancer Center). Results: Ninety-three AYA patients with primary CNS tumors were treated at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, while 507 patients with primary CNS gliomas were treated at the Dana-Farber/Brigham and Women's Cancer Center. At the pediatric affiliate, 35.4% (33/93) of AYAs were enrolled in a therapeutic clinical trial, while at the adult affiliate, 15.8% (80/507) of AYAs were enrolled in a clinical trial. High-grade gliomas were associated with significantly higher rates of enrollment in the adult affiliate. Conclusions: Clinical trial enrollment remains poor among AYAs with CNS tumors, and clinical trial enrollment participation is modestly higher in the pediatric setting. Our study demonstrates the continued need to evaluate and address factors associated with clinical trial enrollment among AYAs with CNS tumors.

Marginal zone lymphoma of the dura - two case reports with long-term follow-up.

Primary MALT lymphoma arising at the dura is a rare circumstance with no categorical therapeutic plan in literature. There are few reports available with different treatment courses. Here, we report two cases with a long-term follow-up after the same pattern of management and review the literature.

Primary diffuse large B-cell lymphoma of the CNS, with a "Lymphomatosis cerebri" pattern.

We describe an unusual case of lymphomatosis cerebri in a middle-aged lady presenting with rapid-onset dementia. The lymphomatous infiltrate, instead of forming mass lesions, percolated throughout the brain parenchyma, which is often missed on a stereotactic biopsy and hence warrants caution and awareness about this entity. The nonspecific symptoms at presentation and a variable picture at imaging make this entity diagnostically challenging.

Imaging Mimics of Brain Tumors.

Nonneoplastic entities may closely resemble the imaging findings of primary or metastatic intracranial neoplasia, posing diagnostic challenges for the referring provider and radiologist. Prospective identification of brain tumor mimics is an opportunity for the radiologist to add value to patient care by decreasing time to diagnosis and avoiding unnecessary surgical procedures and medical therapies, but requires familiarity with mimic entities and a high degree of suspicion on the part of the interpreting radiologist. This article provides a framework for the radiologist to identify "brain tumor mimics," highlighting imaging and laboratory pearls and pitfalls, and illustrating unique and frequently encountered lesions.

Primary diffuse large B-cell lymphoma of the CNS, with a "Lymphomatosis cerebri" pattern

We describe an unusual case of lymphomatosis cerebri in a middle-aged lady presenting with rapid-onset dementia. The lymphomatous infiltrate, instead of forming mass lesions, percolated throughout the brain parenchyma, which is often missed on a stereotactic biopsy and hence warrants caution and awareness about this entity. The nonspecific symptoms at presentation and a variable picture at imaging make this entity diagnostically challenging.

Adjuvant Radiotherapy Did Not Reduce Recurrence of World Health Organization Grade I Meningiomas with Venous Sinus Involvement: A Propensity Score Adjusted Analysis and Literature Review.

BACKGROUND: Most meningiomas are classified as World Health Organization (WHO) grade I. Adjuvant radiation therapy (RT) is commonly recommended for subtotal resections with documented progressive regrowth of lesions with venous sinus involvement. We investigated if recurrence of WHO grade I meningiomas was influenced by adjuvant RT. METHODS: From 2000 to 2014, patients with grade I meningiomas with at least one venous sinus involvement and at least 4 years of follow-up were included. Demographics, venous sinus involvement, histology, and extent of resection (EOR) were characterized. Because patients undergoing RT tend to differ from those for whom adjuvant therapy was not prescribed, we used propensity scores to adjust for confounding variables. RESULTS: Sixty-two patients were included; of these, 18 (29.0%) had recurrences. The mean age was 52.8 ± 12.3 years, and 79.0% were women. A total of 34 cases (54.8%) were submitted to adjuvant RT. Adjuvant RT was more frequent in those who had tumor recurrence (77.8% vs. 45.5%, P = 0.020). RT was more frequent in superior sagittal sinus (SSS) invasion (76.5% vs. 50.0%, P = 0.030) and less prevalent after gross total resection (GTR) (32.4% vs. 67.9%, P = 0.005). Propensity score adjusted analysis suggested no adjuvant RT benefit (odds ratio [OR], 2.51; 95% confidence interval [CI], 0.68-9.28; P = 0.167), independent of the EOR. SSS involvement increased recurrence risk (OR, 12.69; 95% CI, 1.46-110.27; P = 0.021), whereas GTR tended to decrease it (OR, 0.26; 95% CI, 0.06-1.09; P = 0.065). CONCLUSIONS: Adjuvant RT does not seem to be a pivotal criterion to reduce the recurrence rate in patients with grade I meningioma, even when venous sinuses are involved.

The relationship of study and authorship characteristics on trial sponsorship and self-reported conflicts of interest among neuro-oncology clinical trials.

PROPOSE: To examine the association between trial sponsorship sources, self-reported conflicts of interest (COI), and study and author characteristics in central nervous system (CNS) oncology clinical trials (CT). METHODS: MEDLINE search was performed for original CT on "Central Nervous System Neoplasms"[Mesh]. The investigators assessed for relationships between funding source (industry, academic or cooperative, none, not described), COI (presented, none, or not reported), CT, and author characteristics. RESULTS: From 2010 to 2015, 319 CT were considered eligible. The majority of the studies involved primary gliomas (55.2%) and were Phase II CT (59.2%). Drug therapy was investigated in 83.0% of the CT. The remaining studies investigated surgery or radiotherapy. A minority of papers were published in journals with impact factor (IF) higher than > 10 (16%) or in regions other than North America and Europe (20.4%). Overall, 83.1% of studies disclosed funding sources: 32.6% from industry alone, 33.9% from an academic or cooperative group, and 10.7% from a mixed funding model. COI data was reported by 85.9% of trials, of which 56.2% reported no COI and 43.8% reported a related COI. Significant predictors for sponsorship (industry and/or academia) on univariate analysis were study design, type of intervention, journal impact factor, study conclusion, transparency of COI and presence of COI. On multivariate analysis, type of intervention, (P < 0.001), journal impact factor (IF) (P = 0.003), presence of COI (P < 0.001) and study conclusion (P = 0.003) remained significant predictors of sponsorship. For predicting COI, significant variables on univariate analysis were disease type, type of intervention, journal IF, funding source, and intervention arm being related to sponsor. On multivariate analysis, disease type (P = 0.003), journal IF (P < 0.001), type of intervention (P = 0.001), and funding source (P = 0.008) remained significant. CONCLUSIONS: The majority of CNS CT reported some external funding sources and non-related COI. We identified that drug trials, higher IF, presence of COI, and a neutral or negative study conclusion are associated with external funding. Likewise drug trials, higher IF, and glioma trials are associated with presence of COI.

Allergic conditions and risk of glioma and meningioma in the CERENAT case-control study.

Inverse association between allergic conditions and glioma risk has been consistently reported in epidemiological studies with little attention paid to potential environmental confounders; the association with meningioma risk is less consistent. We examined the association between allergy history and risk of glioma and meningioma in adults using data from the CERENAT (CEREbral tumors: a NATional study) multicenter case-control study carried out in 4 areas in France in 2004-2010. Participants' histories of doctor-diagnosed allergic asthma, eczema, rhinitis/hay fever and other allergic conditions were collected at onset through a detailed questionnaire delivered in a face-to-face interview. Conditional logistic regression for matched sets was adjusted for participants' educational level and mobile phone use. A total of 273 glioma cases, 218 meningioma cases and 982 matched controls selected from the local electoral rolls were analyzed. A significant inverse association was found between glioma and a history of any allergy (OR 0.52, 95% CI 0.36-0.75), with a dose-effect relationship with the number of allergic conditions reported (p-trend = 0.001) and a particularly strong association with hay fever/allergic rhinitis (OR 0.46, 95% CI 0.30-0.72). Interestingly, associations with glioma risk were more pronounced in women. For meningioma, no association was observed with overall or specific allergic conditions. Our findings confirmed the inverse association between allergic conditions and glioma risk but questioned the role of allergy in meningioma risk. Future research is needed to clarify the biological mechanism of overall allergy and allergic rhinitis on glioma and to confirm the different effect by gender.

Interstitial pneumonitis during rituximab-containing chemotherapy for primary central nervous system lymphomas: a case report and review of literature.

BACKGROUND: Primary central nervous system lymphoma(PCNSL) is a rare kind of non-Hodgkin lymphoma. Rituximab combined with high-dose methotrexate, cytarabine and dexamethasone (R-MAD regimen) were reported effective for PCNSL patients. Rituximab can cause several side effects, including fever, chills and rigors. CASE PRESENTATION: In this case report, we demonstrate rituximab-induced interstitial pneumonitis in a PCNSL patient who has been treated with R-MAD regimen. The patient recovered after treatment and she remains complete remission after following consolidation chemotherapy. CONCLUSIONS: Here is no report of potential fatal complications of Rituximab like interstitial pneumonitis nowadays in PCNSL patients. As Rituximab is widely used, physicians should raise their awareness of this rare complication and detect RTX-ILD in early stage.

Funding source, conflict of interest and positive conclusions in neuro-oncology clinical trials.

We aimed to test any association between authors' conclusions and self-reported COI or funding sources in central nervous system (CNS) studies. A review was performed for CNS malignancy clinical trials published in the last 5 years. Two investigators independently classified study conclusions according to authors' endorsement of the experimental therapy. Statistical models were used to test for associations between positive conclusions and trials characteristics. From February 2010 to February 2015, 1256 articles were retrieved; 319 were considered eligible trials. Positive conclusions were reported in 56.8% of trials with industry-only, 55.6% with academia-only, 44.1% with academia and industry, 77.8% with none, and 76.4% with not described funding source (p = 0.011). Positive conclusions were reported in 60.4% of trials with unrelated COI, 60% with related COI, and 60% with no COI reported (p = 0.997). Factors that were significantly associated with the presence of positive conclusion included trials design (phase 1) [OR 11.64 (95 CI 4.66-29.09), p < 0.001], geographic location (outside North America or Europe) [OR 1.96 (95 CI 1.05-3.79), P = 0.025], primary outcomes (non-overall or progression free survival) [OR 3.74 (95 CI 2.27-6.18), p < 0.001], and failure to disclose funding source [OR 2.45 (95 CI 1.22-5.22), p = 0.011]. In a multivariable regression model, all these factors remained significantly associated with trial's positive conclusion. Funding source and self-reported COI did not appear to influence the CNS trials conclusion. Funding source information and COI disclosure were under-reported in 14.1 and 17.2% of the CNS trials. Continued efforts are needed to increase rates of both COI and funding source reporting.

Masson's tumor revealed by an intracerebral hematoma. Case report and a review of the literature.

We report the case of a 56-year-old woman who underwent total resection of a Masson's tumor or intravascular papillary endothelial hyperplasia (IPEH), which was discovered due to a left temporal intracerebral hematoma revealed by aphasia. IPEH is more often localized on cutaneous and subcutaneous locations, intracranial IPEH are rare and only approximately twenty cases have been published to date. These tumors are a benign vascular lesion composed of papillary intravascular proliferation of epithelial cellular associated thrombosis with fibrin deposits responsible for vascular lumen obliteration. Differential diagnoses of neurological locations of IPEH are more often an angiosarcoma, or meningioma, and metastasis. Magnetic Resonance imaging (MRI) and CT-scan are not specific. On CT-scan the lesion is hypodense without calcification with a peripheral enhancement and on MRI a hyposignal T1 with homogeneous enhancement and a hypersignal T2. Arteriography may reveal a tumoral blush and arterio-venous shunt or arterial pedicles which can be embolized. The age of discovery is between 12 and 70 with a female predominance. IPEH are often localized close to the venous sinus or can be developed in a vascular malformation, thrombus or aneurysm. The curative treatment is total resection but recurrence has been reported, long-term follow-up with MRI is recommended.

Alveolar soft part sarcoma with brain metastases.

Metastatic tumors are the most common mass lesions in the brain. This case reports a rare form of sarcoma with metastasis to the brain. The appropriate management of a patient with metastatic alveolar soft part sarcoma to the brain is discussed. Author describes a 32-year-old gentleman diagnosed with primary tumor at gluteus and distant metastases at lower lobe of right lung and the brain. Histopathology proves diagnosis as alveolar soft part sarcoma. Craniotomy with excision of brain lesion was done. Repeated magnetic resonance imaging of the brain after 2 months showed rapidly growing new lesions. The next step of management was made by the oncology team as recurrence rate was high and due to multi-systemic involvement. Patient was planned for palliative chemotherapy and to be reassessed later. This case report discusses the appropriate approach to any form of brain metastases and the role of early follow-up especially after surgery for better outcome and choice of post operative management such as radiotherapy or chemotherapy or both for malignant tumors. Based on this report, it was concluded that every brain tumor patient should be frequently monitored even in the outpatient setting as most of them are metastatic and rapidly spreading. The patient should be considered for radiotherapy or chemotherapy or both after surgery if the histopathology result is suggestive of malignancy.

(18)F-Flourodeoxy-Glucose PET/Computed Tomography in Brain Tumors: Value to Patient Management and Survival Outcomes.

(18)F-flourodeoxy-glucose (FDG) PET/computed tomography (CT) is most useful in the evaluation of primary central nervous system (CNS) lymphoma, important in diagnosis, pretherapy prognosis, and therapy response evaluation. Utility in working up gliomas is less effective, and FDG PET/CT is most helpful when MR imaging is unclear. FDG avidity correlates with the grade of gliomas. FDG PET/CT can be used to noninvasively identify malignant transformation. Establishing this change in the disease process has significant effects on patient management and survival outcome.

An enigmatic brainstem posterior fossa ganglioglioma in an adult.

Ganglioglioma is a rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occurs in the pediatric population with an incidence of 7.6%. These tumors are usually slow-growing and well-circumscribed solid or cystic lesions. Gangliogliomatosis infrequently occurs in the frontal lobe, pineal gland, basal ganglia, hypothalamus, and optic chiasm, with very few reports of brainstem ganglioglioma. We report a case of a 35-year-old female who initially presented with headache, vertigo, ataxia, saccadic dysfunction, dysarthria, and dysmetria for several years due to an unknown etiology. Her brain imaging showed multiple lesions in the pons and the cerebellum with cystic changes and size reduction and enlargement over the next few years while her neurological symptoms continued to worsen. The patient received courses of steroid treatment that improved her neurological symptoms, suggesting an inflammatory component of her disease. Extensive workup for an inflammatory or infectious etiology was unfruitful and two brain biopsies were inconclusive. A third biopsy showed atypical glial nuclei, binucleated cells, and Rosenthal fibers and the presence of BRAF V600E mutation was detected. The diagnosis of gangliogliomatosis was consequently established. This case illustrates that gangliogliomatosis may present with the waxing-and-waning neurological signs and symptoms. It can masquerade inflammatory processes in the central nervous system on brain imaging and deserves careful consideration in the diagnosis of patients with an indolent course of neurological deterioration.