Diffuse Leptomeningeal Glioneuronal Tumor Research Articles

The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population

Pilocytic astrocytoma (PA) is the most common pediatric glioma, arising from a single driver MAPK pathway alteration. Classified as a grade I tumor according to the 2016 WHO classification, prognosis is excellent with a 10-year survival rate > 95% after surgery. However, rare cases present with anaplastic features, including an unexpected high mitotic/proliferative index, thus posing a diagnostic and therapeutic challenge. Based on small histomolecular series and case reports, such tumors arising at the time of diagnosis or recurrence have been designated by many names including pilocytic astrocytoma with anaplastic features (PAAF). Recent DNA methylation-profiling studies performed mainly on adult cases have revealed that PAAF exhibit a specific methylation signature, thus constituting a distinct methylation class from typical PA [methylation class anaplastic astrocytoma with piloid features—(MC-AAP)]. However, the diagnostic and prognostic significance of MC-AAP remains to be determined in children. We performed an integrative work on the largest pediatric cohort of PAAF, defined according to strict criteria: morphology compatible with the diagnosis of PA, with or without necrosis, ≥ 4 mitoses for 2.3 mm2, and MAPK pathway alteration. We subjected 31 tumors to clinical, imaging, morphological and molecular analyses, including DNA methylation profiling. We identified only one tumor belonging to the MC-AAP (3%), the others exhibiting a methylation profile typical for PA (77%), IDH-wild-type glioblastoma (7%), and diffuse leptomeningeal glioneuronal tumor (3%), while three cases (10%) did not match to a known DNA methylation class. No significant outcome differences were observed between PAAF with necrosis versus no necrosis (p = 0.07), or with 4–6 mitoses versus 7 or more mitoses (p = 0.857). Our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting. Further extensive and comprehensive integrative studies are necessary to accurately define this exceptional entity in children.

Characteristics of Diffuse Leptomeningeal Glioneuronal Tumor With First-Episode Headache and Rapid Blindness Misdiagnosed as Viral Meningoencephalitis

Diffuse leptomeningeal glioneuronal tumor has a high degree of malignancy and high mortality. The purpose of this paper is to describe the characteristics of atypical diffuse leptomeningeal glioneuronal tumor and analyze the causes of misdiagnosis as viral meningoencephalitis. An adolescent female patient presented with headache, nausea, vomiting, sharp vision loss and cognitive dysfunction. After poor therapeutic effect of standard antiviral treatment, further inspection found that malignant cells were detected by cerebrospinal fluid (CSF) cytology; and enhanced magnetic resonance imaging (MRI) showed extensive enhancement of the leptomeningeal. In conclusions, when patient with unexplained high intracranial pressure, it is necessary to be alert to the diagnosis of diffuse leptomeningeal glioneuronal tumor. Multiple examinations of fresh CSF are helpful to increase the positive detection rate of tumor cells. Early diagnosis and active treatment are conducive to improving survival rate. J Med Cases. 2019;10(8):241-245 doi: https://doi.org/10.14740/jmc3347

Clinical Features of Diffuse Leptomeningeal Glioneuronal Tumor With the First Symptom of Headache and Decreased Vision Misdiagnosed as Venous Sinus Thrombosis

Meningeal carcinoma has a variety of clinical manifestations and a high mortality and disability rate. Among them, cranial hypertension is one of the important causes of death, which is easy to be missed or misdiagnosed. The purpose of this case report is to describe the clinical features of diffuse leptomeningeal glioneuronal tumor (DNGNT) with the first symptom of headache accompanied by decreased vision misdiagnosed as venous sinus thrombosis. The patient initially suffered from headache and decreased vision, and rapidly developed blindness. According to the clinical manifestations and cerebrospinal fluid (CSF) examination results, the patient was initially misdiagnosed as venous sinus thrombosis, the intracranial pressure was relieved by Ommaya capsule, and the cerebrovascular condition was observed by magnetic resonance venogram (MRV) and digital subtraction angiography (DSA). The degree of meningeal enhancement was observed by enhanced magnetic resonance imaging (MRI), and meningeal cancer cells were found by CSF cytology. The patient was excluded from viral meningitis, tuberculous meningitis, cryptococcal meningitis, optic neuromyelitis, and central nervous system Behcet’s disease by routine examination. Ommaya capsule implantation relieved the intracranial hypertension, and vision was restored after treatment. No venous sinus thrombosis was found in MRV and DSA; brain-enhanced MRI revealed extensive linear enhancement of the meninges, and CSF cytology revealed grotesque, actively dividing tumor cells; she was diagnosed as DLGNT. Meningeal carcinoma cannot be excluded in adolescents without tumor history. When patient has unexplained intracranial hypertension, it is necessary to consider DLGNT; early brain-enhanced MRI and CSF cytology are helpful for early diagnosis. For cranial hypertension, timely placement of Ommaya capsule can improve patient quality of life and save vision in time; molecular targeted therapy as early as possible can prolong survival. J Neurol Res. 2019;9(3):41-47 doi: https://doi.org/10.14740/jnr539

Clinical Features of Diffuse Leptomeningeal Glioneuronal Tumor with Rapid Blindness Misdiagnosed as NMOSD and Literature Review

Diffuse leptomeningeal glioneuronal tumor has various clinical manifestations and is easily misdiagnosed. This article aims to describe the clinical features of a patient with diffuse leptomeningeal glioneuronal tumor misdiagnosed as optic neuromyelitis lineage disease (NMOSD), analyze the causes of misdiagnosis, and identify the disease with similar clinical manifestations. Adolescent women with decreased vision and headache, nausea, and vomiting were initially diagnosed as NMOSD. Immunotherapy was ineffective; enhanced MRI and cerebrospinal fluid cytology examination were completed and compared with classic meningeal carcinoma, NMOSD, multiple sclerosis, and Vogt-Koyanagi-Harada (VKH) syndrome. Diffuse leptomeningeal glioneuronal tumor was finally diagnosed in adolescent women with no history of tumor. Compared with NMOSD: no history of infection, no AQP4, MOG antibody, no spinal segmental abnormalities, immunotherapy was ineffective; compared with multiple sclerosis: no history of infection, no plaque, no oligoclonal antibody, immunotherapy was ineffective; compared with VKH syndrome: no history of infection, no fever, no treatment for immunotherapy; and compared with classic meningeal carcinoma: adolescents, no extracranial tumor lesions, super high protein, more different sugar excess. Patients with acute visual impairment should consider not only NMOSD, but also diffuse leptomeningeal glioneuronal tumor (DLGNT) and other diseases. DLGNT could not be excluded when CSF cytology and MRI plain scan were negative. The positive rate of malignant cells can only be increased by repeatedly sending fresh cerebrospinal fluid for examination; DLGNT needs to be differentiated from NMOSD, multiple sclerosis, VKH syndrome, and other diseases. Early diagnosis and molecular targeted therapy can improve the quality of life and prolong life.

Unusual radiological and histological presentation of a diffuse leptomeningeal glioneuronal tumor (DLGNT) in a 13-year-old girl

Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are newly recognized as an entity in the 2016 revision of the WHO Classification of tumors of the central nervous system. They typically present as diffuse leptomeningeal infiltrates along the neuraxis with focal and superficial involvement of the parenchyma. Here, we report a DLGNT with unusual radiological and histological features. A 13-year-old girl presented with scoliosis and back pain. Magnetic resonance imaging demonstrated a syrinx from C2 to T11 and an intramedullary mass from T6 to T9-10. No leptomeningeal involvement was recognized. Histological examination of the gross total resection specimen revealed a low-grade neuroepithelial neoplasm predominantly infiltrating the spinal cord and only focally involving the leptomeninges. Chromosome microarray identified co-deletion of the short arm of chromosome 1 and the long arm of chromosome 19 as well as fusion of the KIAA1549 and BRAF genes. Next-generation sequencing demonstrated wild-type alleles at the mutational hotspots of IDH1 (R132) and IDH2 (R140 and R172). In contrast to most reported DLGNTs, the tumor described in this manuscript was characterized by a predominant parenchymal component and only minor leptomeningeal involvement both radiographically and histologically. Our case, therefore, expands the spectrum of radiological and histopathological features of this new entity. It also highlights the critical role of molecular genetic testing in establishing the diagnosis of DLGNT in unusual cases.

Clinical Features of Diffuse Leptomeningeal Glioneuronal Tumor With the First Symptom of Headache and Decreased Vision Misdiagnosed as Venous Sinus Thrombosis

Meningeal carcinoma has a variety of clinical manifestations and a high mortality and disability rate. Among them, cranial hypertension is one of the important causes of death, which is easy to be missed or misdiagnosed. The purpose of this case report is to describe the clinical features of diffuse leptomeningeal glioneuronal tumor (DNGNT) with the first symptom of headache accompanied by decreased vision misdiagnosed as venous sinus thrombosis. The patient initially suffered from headache and decreased vision, and rapidly developed blindness. According to the clinical manifestations and cerebrospinal fluid (CSF) examination results, the patient was initially misdiagnosed as venous sinus thrombosis, the intracranial pressure was relieved by Ommaya capsule, and the cerebrovascular condition was observed by magnetic resonance venogram (MRV) and digital subtraction angiography (DSA). The degree of meningeal enhancement was observed by enhanced magnetic resonance imaging (MRI), and meningeal cancer cells were found by CSF cytology. The patient was excluded from viral meningitis, tuberculous meningitis, cryptococcal meningitis, optic neuromyelitis, and central nervous system Behcet’s disease by routine examination. Ommaya capsule implantation relieved the intracranial hypertension, and vision was restored after treatment. No venous sinus thrombosis was found in MRV and DSA; brain-enhanced MRI revealed extensive linear enhancement of the meninges, and CSF cytology revealed grotesque, actively dividing tumor cells; she was diagnosed as DLGNT. Meningeal carcinoma cannot be excluded in adolescents without tumor history. When patient has unexplained intracranial hypertension, it is necessary to consider DLGNT; early brain-enhanced MRI and CSF cytology are helpful for early diagnosis. For cranial hypertension, timely placement of Ommaya capsule can improve patient quality of life and save vision in time; molecular targeted therapy as early as possible can prolong survival. J Neurol Res. 2019;9(3):41-47 doi: https://doi.org/10.14740/jnr539

WHO-Klassifikation der Hirntumoren 2016: radiologisch relevante Neuerungen

AbstractRadiologists play a key role in brain tumor diagnosis and management and must stay abreast of developments in the field to advance patient care and communicate with other health care providers. In 2016, the World Health Organization (WHO) released an update to its brain tumor classification system that included numerous significant changes. Several previously recognized brain tumor diagnoses, such as oligoastrocytoma, primitive neuroectodermal tumor, and gliomatosis cerebri, were redefined or eliminated altogether. Conversely, multiple new entities were recognized, including diffuse leptomeningeal glioneuronal tumor and multinodular and vacuolating tumor of the cerebrum. The glioma category has been significantly reorganized, with several infiltrating gliomas in children and adults now defined by genetic features for the first time. These changes were driven by increased understanding of important genetic factors that directly impact tumorigenesis and influence patient care. The increased emphasis on genetic factors in brain tumor diagnosis has important implications for radiology, as we now have tools that allow us to evaluate some of these alterations directly, such as the identification of 2-hydroxyglutarate within infiltrating gliomas harboring mutations in the genes for the isocitrate dehydrogenases. For other tumors, such as medulloblastoma, imaging can demonstrate characteristic patterns that correlate with particular disease subtypes. The purpose of this article is to review the changes to the WHO brain tumor classification system that are most pertinent to radiologists.

Magnetic resonance imaging findings of mixed neuronal-glial tumors with pathologic correlation: a review.

Mixed neuronal-glial tumors are rare, and MRI diagnosis of them presents a challenge. In this review, we discuss the MRI findings of ganglioglioma, anaplastic ganglioglioma, desmoplastic infantile ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, and primary diffuse leptomeningeal glioneuronal tumor with clinicopathologic correlation. There is overlap of imaging features both with each other and some other tumors, which complicates diagnosis. The combination of imaging findings and the age, location, and appropriate clinical picture should allow the radiologist and the clinicians to raise a provisional diagnosis of a mixed neuronal glial tumor, and guide patient management.

Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features.

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80% of cases. In the DLGNT-MC-1 group, age at diagnosis was significantly lower (median 5 vs 14years, p < 0.01) and clinical course less aggressive (5-year OS 100, vs 43% in DLGNT-MC-2). Our study proposes an additional molecular layer to the current histopathological classification of DLGNT, of particular use for cases without typical morphological or radiological characteristics, such as diffuse growth and radiologic leptomeningeal dissemination. Recurrent 1p deletion and MAPK/ERK pathway activation represent diagnostic biomarkers and therapeutic targets, respectively-laying the foundation for future clinical trials with, e.g., MEK inhibitors that may improve the clinical outcome of patients with DLGNT.

2016 Updates to the WHO Brain Tumor Classification System: What the Radiologist Needs to Know.

Radiologists play a key role in brain tumor diagnosis and management and must stay abreast of developments in the field to advance patient care and communicate with other health care providers. In 2016, the World Health Organization (WHO) released an update to its brain tumor classification system that included numerous significant changes. Several previously recognized brain tumor diagnoses, such as oligoastrocytoma, primitive neuroectodermal tumor, and gliomatosis cerebri, were redefined or eliminated altogether. Conversely, multiple new entities were recognized, including diffuse leptomeningeal glioneuronal tumor and multinodular and vacuolating tumor of the cerebrum. The glioma category has been significantly reorganized, with several infiltrating gliomas in children and adults now defined by genetic features for the first time. These changes were driven by increased understanding of important genetic factors that directly impact tumorigenesis and influence patient care. The increased emphasis on genetic factors in brain tumor diagnosis has important implications for radiology, as we now have tools that allow us to evaluate some of these alterations directly, such as the identification of 2-hydroxyglutarate within infiltrating gliomas harboring mutations in the genes for the isocitrate dehydrogenases. For other tumors, such as medulloblastoma, imaging can demonstrate characteristic patterns that correlate with particular disease subtypes. The purpose of this article is to review the changes to the WHO brain tumor classification system that are most pertinent to radiologists. ©RSNA, 2017.

P21.03 Efficacy of bevacizumab in a primary diffuse leptomeningeal glioneuronal tumor of the adult

P21.03 Efficacy of bevacizumab in a primary diffuse leptomeningeal glioneuronal tumor of the adult

Newly Identified Characteristics and Suggestions for Diagnosis and Treatment of Diffuse Leptomeningeal Glioneuronal/Neuroepithelial Tumors: A Case Report and Review of the Literature.

Diffuse leptomeningeal glioneuronal tumor is unique for communicating hydrocephalus, diffuse leptomeningeal enhancement, cystic changes, absence of tumor cells in cerebral spinal fluid, and a cell population of both glial and neuronal copositivity. It has likely been misdiagnosed as mixed glioneuronal tumors, oligodendrogliomas, and neuroepithelial tumors. Children with signs of this tumor are often worked up for infection, rheumatologic disease, or disseminated primary malignancy, resulting in unnecessary testing and treatment. We describe a 14-year-old female with recurrent headaches, hydrocephalus, and diffuse leptomeningeal enhancement discovered to be neoplastic 1 year after initial presentation, owing to extensive and unrevealing infectious and immunologic workups. Biopsies revealed atypical cells with markers of both glial and neuronal cells, positivity for OLIG-2, and focal p53 positivity. Great response was seen with temozolomide and craniospinal irradiation. Additionally, we postulate additional diagnostic indicators that may aid in earlier diagnosis and treatment decisions.