Multinodular And Vacuolating Neuronal Tumor Research Articles

Cortically-based Brain Tumors in Children: A Decision-tree Approach in the Radiology Reading Room.

Cortically-based brain tumors in children constitute a unique set of tumors with variably aggressive biological behavior. As radiologists play an integral role on the multidisciplinary medical team, a clinically useful and easy-to-follow flowchart for the differential diagnoses of these complex brain tumors is essential.This proposed algorithm tree provides the latest insights into the typical imaging characteristics and epidemiologic data that differentiate the tumor entities, taking into perspective the 2021 World Health Organization's classification and highlighting classic as well as newly identified pathologic subtypes using current molecular understanding.ABBREVIATIONS: Astroblastoma=AB) Angiocentric glioma (AG) Atypical teratoid rhabdoid tumor (ATRT) Central Nervous System tumor (CNS) CNS neuroblastoma FOXR2-activated (NB-FOXR2) Desmoplastic infantile glioma/astrocytoma (DIG/DIA) Diffuse hemispheric glioma, H3 G34-mutant (DHG) Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) Dysembryoplastic neuroepithelial tumor (DNET) Embryonal Tumors with Multilayered Rosettes (ETMR) Ependymoma (EP) Focal cortical dysplasia (FCD) Ganglioglioma/gangliocytoma (GG) Infant-type hemispheric glioma (IHG) Intracranial pressure (ICP) Long-term epilepsy-associated tumors (LEATs) Pediatric diffuse low-grade gliomas (pLGG) MR spectroscopy (MRS) Multinodular and vacuolating neuronal tumor (MVNT) Overall survival (OS) Pediatric diffuse high-grade gliomas (pHGG).

Bright diffusion sign: A sensitive and specific radiologic biomarker for multinodular and vacuolating neuronal tumor

Background and purposeAccurate differentiation between multinodular and vacuolating neuronal tumor (MVNT) and dysembryoplastic neuroepithelial tumor (DNET) is important for treatment decision-making. We aimed to develop an accurate radiologic diagnostic model for differentiating MVNT from DNET using T2WI and diffusion-weighted imaging (DWI). Materials and methodsA total of 56 patients (mean age, 47.48±17.78 years; 31 women) diagnosed with MVNT (n = 37) or DNET (n = 19) who underwent brain MRI, including T2WI and DWI, were included. Two board-certified neuroradiologists performed qualitative (bubble appearance, cortical involvement, bright diffusion sign, and bright apparent diffusion coefficient [ADC] sign) and quantitative (nDWI and nADC) assessments. A diagnostic tree model was developed with significant and reliable imaging findings using an exhaustive chi-squared Automatic Interaction Detector (CHAID) algorithm. ResultsIn visual assessment, the imaging features that showed high diagnostic accuracy and interobserver reliability were the bright diffusion sign and absence of cortical involvement (bright diffusion sign: accuracy, 94.64 %; sensitivity, 91.89 %; specificity, 100.00 %; interobserver agreement, 1.00; absence of cortical involvement: accuracy, 92.86 %; sensitivity, 89.19 %; specificity, 100.00 %; interobserver agreement, 1.00). In quantitative analysis, nDWI was significantly higher in MVNT than in DENT (1.52 ± 0.34 vs. 0.91 ± 0.27, p < 0.001), but the interobserver agreement was fair (intraclass correlation coefficient = 0.321). The overall diagnostic accuracy of the tree model with visual assessment parameters was 98.21 % (55/56). ConclusionThe bright diffusion sign and absence of cortical involvement are accurate and reliable imaging findings for differentiating MVNT from DNET. By using simple, intuitive, and reliable imaging findings, such as the bright diffusion sign, MVNT can be accurately differentiated from DNET.

Radiological and clinical features of multinodular and vacuolating neuronal tumor (MVNT)

BackgroundTo investigate the imaging findings and clinical features of multinodular and vacuolating neuronal tumor (MVNT).MethodsWe retrospectively sought for cases that have suspicious imaging findings for MVNT through the hospital information system. The patients’ demographics and clinical symptoms were extracted. All available images were re-examined.ResultsHeadache was the most common complaint (n = 7). Other complaints included seizure, stroke-like symptoms and numbness. Conventional MRI revealed that all lesions consisted of tiny, sharply marginated, round or ovoid nodules following the gyral contour. These nodules were hyperintense on T2 and FLAIR WI, hypointense on T1 WI. All lesions were characterized by a lack of enhancement and diffusion restriction. Mass effect and peripheral edema were not observed. MVNT presented as an incidental finding in one case who complained gynecomastia and had pituitary adenoma on pituitary MRI. All lesions were supratentorial—mostly on the right side (10/11)—and located in subcortical white matter. Follow-up MRI was available for 11 patients with a mean of 14.8 months (3–40 months). No change in lesion size and morphology was observed in these follow-up images.ConclusionsRadiological and clinical follow-up data suggest MVNT may exhibit indolent behavior. If asymptomatic, patients can be followed by imaging alone. Surgery should be considered for symptomatic patients.

New Imaging Features of Multinodular and Vacuolating Neuronal Tumor Revealed by Alcohol and Illicit Drugs Consumption.

It has been almost a decade since the multinodular and vacuolating neuronal tumor (MVNT) was first described. In 2021, WHO classified it as a defined entity, and it is considered one of the glioneuronal and neuronal tumors. Due to its similarities with dysembryoplastic neuroepithelial tumors (DNET), some authors consider it a variant of these, ranking in the category of malformations, but genetic alterations favor a neoplastic origin. We present a 29-year-old male with a generalized onset tonic-clonic seizure after a nightclub party. Imaging studies revealed a right temporal multinodular and vacuolating neuronal tumor confirmed by biopsy. It is considered a nonaggressive, "leave me alone" brain lesion, which does not require biopsy because of well-defined MRI characteristics. Surgery is indicated only in symptomatic cases. We consider that this lesion was revealed by his seizure, most probably provoked (with normal video EEG recording) by the consumption of a lot of alcohol, illicit drugs, and sleep loss after a club party. We recommended close monitoring, but our patient preferred the surgery. Our case added more imaging details corroborated with the histopathology features of MVNT. FLAIR images revealed hypointense nodules surrounded by hyperintense peripheral rings and areas of high signal intensity between the nodules, which correspond to the histopathological architecture. To our knowledge, this is the first case of MVNT with diffusion tensor imaging and fiber tractography imaging studies.

Multinodular and Vacuolating Neuronal Tumor (MVNT) Diagnosed Asymptomatically by Characteristic MRI Findings

Multinodular and Vacuolating Neuronal Tumor (MVNT) Diagnosed Asymptomatically by Characteristic MRI Findings

The 2021 WHO Classification of Tumors of the Central Nervous System: An update on pediatric low-grade gliomas and glioneuronal tumors.

The 2021 5th edition of the WHO Classification of Tumors of the Central Nervous System reflects the discovery of genetic alterations underlying many central nervous system (CNS) neoplasms. Insights gained from technologic advances and novel applications in molecular diagnostics, including next‐generation sequencing and DNA methylation‐based profiling, coupled with the recognition of clinicopathologic correlates, have prompted substantial changes to CNS tumor classification; this is particularly true for pediatric low‐grade gliomas and glioneuronal tumors (pLGG/GNTs). The 2021 WHO now classifies gliomas, glioneuronal tumors and neuronal tumors into 6 families, three of which encompass pLGG/LGNTs: “Pediatric type diffuse low‐grade gliomas,” “circumscribed astrocytic gliomas,” and “glioneuronal and neuronal tumors.” Among these are six newly recognized tumor types: “diffuse astrocytoma, MYB or MYBL1‐altered”; “polymorphous low grade neuroepithelial tumor of the young (PLNTY)”; “diffuse low‐grade glioma‐MAPK altered”; “Diffuse glioneuronal tumor with oligodendroglioma‐like features and nuclear clusters (DGONC)”; “myxoid glioneuronal tumor (MGT)”; and “multinodular and vacuolating neuronal tumor (MVNT).” We review these newly recognized entities in the context of general changes to the WHO schema, discuss implications of the new classification for treatment of pLGG/LGNT, and consider strategies for molecular testing and interpretation.

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 benign entity – cerebral multinodular and vacuolating neuronal tumor

Introduction and aim. Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a rare benign, mixed glial/ neuronal lesion which has been included in the recent (2016) World Health Organization (WHO) Classification of the central nervous system tumors.Most of the reported cases are remarkable with adult onset seizure in the literature.They can also be found incidentally in nonepilepsy patients with or without headache We aimed to present this unique entity with its typical magnetic resonance imaging (MRI) features. Description of the case. A 21-year old man presented with complaint of headache that increased in frequency within the last few months.No relevant seizure or any other signs of note.He was diagnosed with MVNT by imaging andstarted to be followed- up.The repeat MRI 6 months later showed no interval changes. Conclusion. Clinicians should be aware of that it is a do not touch lesion in asymptomatic patients with no need for biopsy or surgery and follow up imaging is sufficient when presented with the typical MRI manifestations. Surgical resection may be required for seizure control and was reported in few cases with no tumoral regrowth in the literature.

Multinodular and vacuolating neuronal tumor of the cerebrum: three case reports

Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a seizure-associated rare lesion that currently appears to be a malformative lesion or hamartoma rather than a low-grade neoplastic lesion. MVNT pathognomonic magnetic resonance imaging (MRI) features allow for diagnostic accuracy in the differential diagnosis. Lesions are usually asymptomatic, nonprogressive and incidentally found requiring only imaging monitoring over time. Although uncommon, it is important to be familiar with MVNT clinical presentation and key imaging features. We here present a series of three cases with imaging findings similar to those described in the literature. These patients were followed with serial neuroimaging.

Advanced Magnetic Resonance Imaging Findings of Multinodular and Vacuolating Neuronal Tumor.

To present the magnetic resonance imaging (MRI) findings of a multinodular and vacuolating neuronal tumor (MVNT). The authors identified four patients with MVNT in the hospital between January 2015 and October 2019. Both the clinical and radiological data of the patients were collected for analysis. Three patients complained of non-specific headaches. One patient had vertigo and imbalance. MRI sequences, including spectroscopy, perfusion, and DWI sequences, were retrospectively evaluated. The lesions were located in the subcortical and periventricular white matter of the parietal and temporal lobes, showed confluency, and comprised nodular pattern. The lesions appeared isointense to the cerebral cortex on T1 weighted imaging and hyperintense on T2 weighted and FLAIR sequences. None of the lesions showed diffusion restriction or contrast enhancement. Three of the lesions demonstrated a slight increase in choline peak and a slight decrease in N-acetyl aspartate peak. One lesion showed a noticeable increase in the Cho peak and a decrease in the NAA peak. Radiological features of MVNT are specific. Recognizing the MRI findings would help avoid unnecessary interventions in these patients, who are usually asymptomatic.

BRAF Alteration in Central and Peripheral Nervous System Tumors.

BRAF (alternately referred to as v-raf murine sarcoma viral oncogene homolog B1) is a proto-oncogene involved in the mitogen-activated protein kinase (MAPK) pathway. BRAF alterations are most commonly missense mutations or aberrant fusions. These mutations are observed in numerous primary central nervous system tumors as well as metastases. This review discusses the prevalence of BRAF alteration within select notable CNS tumors, and their prognostic associations. Included are some novel entities such as diffuse leptomeningeal glioneuronal tumor (DLGNT), polymorphous low grade neuroepithelial tumor of the young (PLNTY), and multinodular and vacuolating neuronal tumor (MVNT). Knowledge of this gene’s integrity in CNS and PNS tumors can have profound diagnostic and therapeutic implications. Also reviewed are the current state of targeted therapy against aberrant BRAF as it pertains mostly to the CNS and to a lesser extent in PNS, and certain diagnostic aspects.

Advanced multiparametric magnetic resonance imaging of multinodular and vacuolating neuronal tumor.

Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a rare brain lesion with suggestive imaging features. The aim of our study was to report the largest series of MVNTs so far and to evaluate the utility of advanced multiparametric magnetic resonance (MR) techniques. This multicenter retrospective study was approved by our institutional research ethics board. From July 2014 to May 2019, two radiologists read in consensus the MR examinations of patients presenting with a lesion suggestive of an MVNT. They analyzed the lesions' MR characteristics on structural images and advanced multiparametric MR imaging. A total of 64 patients (29 women and 35 men, mean age 44.2±15.1years) from 25 centers were included. Lesions were all hyperintense on fluid-attenuated inversion recovery and T2-weighted imaging without post-contrast enhancement. The median relative apparent diffusion coefficient on diffusion-weighted imaging was 1.13 [interquartile range (IQR), 0.2]. Perfusion-weighted imaging showed no increase in perfusion, with a relative cerebral blood volume of 1.02 (IQR, 0.05) and a relative cerebral blood flow of 1.01 (IQR, 0.08). MR spectroscopy showed no abnormal peaks. Median follow-up was 2 (IQR, 1.2) years, without any changes in size. A comprehensive characterization protocol including advanced multiparametric magnetic resonance imaging sequences showed no imaging patterns suggestive of malignancy in MVNTs. It might be useful to better characterize MVNTs.

Clinicopathological and molecular analysis of multinodular and vacuolating neuronal tumors of the cerebrum

Multinodular and vacuolating neuronal tumor (MVNT) of the cerebrum is a recently recognized rare neuronal tumor, and its pathogenesis is unclear. We analyzed 7 cases of histologically typical MVNT: 6 were adults (mean age, 43.0 years [range, 23-56 years]) and 1 was a child (age, 10 years). The most common symptoms were seizures (n = 4) and headache (n = 2). The tumors were supratentorial (temporal, 5; frontal lobes, 2) in origin as reported. Vacuolated tumor cells were robustly positive for α-INA and Olig2 and at least partly positive for synaptophysin and MAP2, but negative for Neu-N, nestin and CD34. GFAP and vimentin were expressed in reactive astrocytes but not in tumor cells. Negative results were obtained for p53, IDH-1, BRAFV600E, H3 K27M, EGFR, Lin28A, and L1CAM. ATRX, BRG1, INI-1, and TMHH were retained. The Ki-67 labeling index was very low (<1%), and pHH3 revealed no mitotic figure. Ultrastructural features of tumor cells were comparable with those of immature neuronal cells, with several intracytoplasmic myelin-like autophagosomes and pericellular vacuolization. No IDH1/IDH2 and BRAFV600E mutations were found upon direct sequencing. Whole-exome sequencing revealed FGFR2-ZMYND11 gene fusion in 1 case. After gross total resection, all patients were alive without seizures. There was no tumor recurrence during an average period of 68 months (range, 23-101 months). The analysis of 7 typical cases of MVNT suggested that these lesions may be clonal tumors because FGFR2-ZMYND11 fusion was found (1 case).

A 36-year-old patient with a multinodular lesion in the left temporal lobe

A 36-year-old female patient was referred to our hospital for a six-months clinical history of episodes of right-sided focal motor seizures and absence. MRI scan showed a multi-nodular lesion in the subcortical white matter of left superior temporal gyrus. After a complete resection, the neuropathological examination revealed a lesion with marked cell vacuolation which was composed of neuroepithelial cells ranging from small to medium sized elements to larger, neuron-like cells, occasionally bi-nucleated. The neuropathological features of the lesion were compatible with the diagnosis of multinodular and vacuolating neuronal tumor (MVNT) of the CNS. MVNT is very rare, recently described entity among the large spectrum of glioneuronal tumors. It is characterized by benign clinical behavior and neurosurgical resection usually provide control of disease.

Multinodular and vacuolating neuronal tumors in epilepsy: dysplasia or neoplasia?

Multinodular and vacuolating neuronal tumor (MVNT) is a new pattern of neuronal tumour included in the recently revised WHO 2016 classification of tumors of the CNS. There are 15 reports in the literature to date. They are typically associated with late onset epilepsy and a neoplastic vs. malformative biology has been questioned. We present a series of ten cases and compare their pathological and genetic features to better characterized epilepsy‐associated malformations including focal cortical dysplasia type II (FCDII) and low‐grade epilepsy‐associated tumors (LEAT). Clinical and neuroradiology data were reviewed and a broad immunohistochemistry panel was applied to explore neuronal and glial differentiation, interneuronal populations, mTOR pathway activation and neurodegenerative changes. Next generation sequencing was performed for targeted multi‐gene analysis to identify mutations common to epilepsy lesions including FCDII and LEAT. All of the surgical cases in this series presented with seizures, and were located in the temporal lobe. There was a lack of any progressive changes on serial pre‐operative MRI and a mean age at surgery of 45 years. The vacuolated cells of the lesion expressed mature neuronal markers (neurofilament/SMI32, MAP2, synaptophysin). Prominent labelling of the lesional cells for developmentally regulated proteins (OTX1, TBR1, SOX2, MAP1b, CD34, GFAPδ) and oligodendroglial lineage markers (OLIG2, SMI94) was observed. No mutations were detected in the mTOR pathway genes, BRAF, FGFR1 or MYB. Clinical, pathological and genetic data could indicate that MVNT aligns more with a malformative lesion than a true neoplasm with origin from a progenitor neuro‐glial cell type showing aberrant maturation.

Natural history of lesions with the MR imaging appearance of multinodular and vacuolating neuronal tumor.

Multinodular and vacuolating neuronal tumor (MVNT) have been recently added to the WHO classification of CNS tumors and has not been extensively reported upon in the radiological literature. We report the first radiological and the largest series of cases, aiming to highlight the natural history of lesions with the imaging appearance of MVNT with long follow-up time. In this retrospective study, we collected cases with the imaging appearance of MVNT. All lesions were evaluated by using routine MR imaging, with follow-up of up to 93months. Patient demographics, clinical course, and MRI features of the lesions were recorded. Twenty-four subjects were enrolled, f/m=16:8, age range 24-59years, with a median age of 45years. The patients' symptoms were often episodic and most frequently due to headaches in 12 (50%), visual symptoms in 6 (25%), seizures in 5±1 (20-25%), paresthesia in 4 (~17%), cognitive difficulties in 4 (~17%), in addition to other variable neurological symptoms, or incidental. A total of 30 lesions identified, 77% of the lesions had gadolinium-enhanced MRI and only 13% showed enhancement. A 6.7% of the lesions that had MRI followed up showed progression, while the rest remained stable up to 93months interval. All patients had intact neurological examinations (except one case that was diagnosed with optic neuritis), were managed conservatively, and did well. The natural history of lesions with imaging features of MVNT is overall stable from a clinical and imaging appearance over time.