scholarly journals Frequent FGFR1 hotspot alterations in driver-unknown low-grade glioma and mixed neuronal-glial tumors

2022 ◽  
Author(s):  
Sophie Engelhardt ◽  
Felix Behling ◽  
Rudi Beschorner ◽  
Franziska Eckert ◽  
Patricia Kohlhof ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Mapk Pathway ◽  
Glioneuronal Tumor ◽  
Dysembryoplastic Neuroepithelial Tumor ◽  
Low Grade ◽  
Sequencing Analysis ◽  
Diffuse Astrocytoma ◽  
Glial Tumors ◽  
Hotspot Mutations ◽  
Fgfr1 Mutation

Abstract Purpose Low-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations. Oncogenic fibroblast growth factor receptor 1 (FGFR1) tyrosinase kinase domain has been reported in brain tumors of various histologies. We sought to determine the frequency of FGFR1 hotspot mutations N546 and K656 in driver-unknown LGG/MNGT and examined FGFR1 immunohistochemistry as a potential tool to detect those alterations. Methods We analyzed 476 LGG/MNGT tumors for KIAA-1549-BRAF fusion, IDH1/2, TERT promotor, NF1, H3F3A and the remaining cases for FGFR1 mutation frequency and correlated FGFR1 immunohistochemistry in 106 cases. Results 368 of 476 LGG/MNGT tumors contained non-FGFR1 alterations. We identified 9 FGFR1 p.N546K and 4 FGFR1 p.K656E mutations among the 108 remaining driver-unknown samples. Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells, but not with age or tumor location. FGFR1 immunohistochemical expression was observed in 92 cases. FGFR1 immunoreactivity score was higher in PA and DNT compared to diffuse astrocytoma, but no correlation between FGFR1 mutation in tumors and FGFR1 expression level was observed. Conclusion FGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases.

scholarly journals LGG-26. DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT) IN CHILDREN: DIFFERENT CLINICAL PRESENTATIONS AND OUTCOMES

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii371-iii371
Author(s):  
Andge Valiakhmetova ◽  
Ludmila Papusha ◽  
Ludmila Yasko ◽  
Alexander Druy ◽  
Alexander Karachunsky ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Braf Inhibitor ◽  
Complete Response ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Conventional Chemotherapy ◽  
Diffuse Leptomeningeal Glioneuronal Tumor ◽  
Braf Fusion

Abstract Diffuse leptomeningeal glioneuronal tumor (DLGNT) is an extremely rare disease, newly recognized in the 2016 WHO classification of tumors of the CNS. Most DLGNTs are low-grade neuroepithelial tumors with variable elements of neuronal/neurocytic and glial differentiation, have diffuse leptomeningeal enhancement on MRI, and typically harbor KIAA1549-BRAF fusions. Other alterations, such as the BRAF V600E substitution, are less common. Here, we present three cases of DLGNT with different presentations and outcomes. The first patient is a 2yr-old male with KIAA1549-BRAF fusion, and was treated with Carbo/VCR chemotherapy after a biopsy, with resultant ongoing stable disease for 3.5 years. The second patient, an 8yr-old male had the BRAF V600E point mutation and was treated with conventional chemotherapy (VCR/carboplatin). On progression, he received the BRAF inhibitor vemurafenib, achieving a complete response which last 14 month. The third patient, a 27 month old male, harbored a KIAA1549-BRAF fusion and was treated at diagnosis with the MEK inhibitor trametinib. The tumor has been radiographically stable in the context of clinical improvement for 21 months since the treatment initiation, ongoing 24 month. In summary, we present further evidence of MAPK pathway alterations in children with DLGNT. We describe a range of molecular presentations and clinical outcomes, including one patient treated with conventional chemotherapy with further stabilization of disease during 3.5 years and two patients who were successfully treated with targeted therapy.

Selumetinib in patients with tumors with MAPK pathway alterations: Results from Arm E of the NCI-COG pediatric MATCH trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10008-10008
Author(s):  
Carl E. Allen ◽  
Olive Eckstein ◽  
Paul M. Williams ◽  
Sinchita Roy-Chowdhuri ◽  
David R Patton ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stable Disease ◽  
Thromboembolic Event ◽  
Mapk Pathway ◽  
Low Grade Glioma ◽  
Braf V600e ◽  
Low Grade ◽  
Match Trial ◽  
Hotspot Mutations ◽  
Clinical Trial Information

10008 Background: The NCI-Children’s Oncology Group (COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial assigns patients age 1 to 21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase 2 treatment arms of molecularly-targeted therapies based on genetic alterations detected in their tumor. Arm E evaluated the MEK inhibitor selumetinib (ARRY-142886) in patients whose tumors harbored activating alterations in the MAPK pathway ( ARAF, BRAF, HRAS, KRAS, NRAS, MAP2K1, GNA11, GNAQ hotspot mutations; NF1 inactivating mutations; BRAF fusions). Methods: Patients received selumetinib 25 mg/m2/dose (max 75 mg/dose) PO BID for 28-day cycles until disease progression or intolerable toxicity with response assessments obtained every 2-3 cycles. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS). Patients with low grade glioma were excluded. Results: A total of 21 patients (median age 14 years; range 5-21) were enrolled between 10/2017 and 8/2019, with 20 patients evaluable for response. Diagnoses were high grade glioma (HGG; n = 8), rhabdomyosarcoma (n = 7), adenocarcinoma (n = 2), and one each of MPNST, endodermal sinus/yolk sac tumor, plexiform neurofibroma (PN), and neuroblastoma. MAPK pathway alterations detected consisted of inactivating NF1 mutations (n = 8), hotspot mutations in KRAS (n = 8), NRAS (n = 3), and HRAS (n = 1), and BRAF V600E (n = 2). No objective responses were observed. Three patients had a best response of stable disease (HGG with NF1 mutation, 6 cycles; HGG with KRAS mutation, 12 cycles; PN with NF1 mutation, 13 cycles prior to removal for dose-limiting toxicity). Six-month PFS was 15% (95% CI: 4%, 34%). Adverse events that were deemed possibly, probably, or definitely attributable to study drug included one case each of grade 3 uveitis, lymphopenia, and thromboembolic event; one grade 4 CPK elevation; and one grade 5 thromboembolic event. Conclusions: Selumetinib did not result in tumor regression in this cohort of children and young adults with treatment-refractory tumors with activating MAPK pathway alterations. Of note, two patients with HGG initially had stable disease, but ultimately progressed after 6 and 12 cycles, respectively. Selumetinib has previously demonstrated activity in low grade glioma and PN and is now FDA-approved for PN. The results of our study indicate that MAPK pathway mutation status alone is insufficient to predict response to selumetinib monotherapy. It is likely that selumetinib and other MEK inhibitors will require combination with targeted or cytotoxic agents for optimal efficacy in children with persistent or progressive cancers after front-line chemotherapy. Clinical trial information: NCT03213691. Clinical trial information: NCT03155620.

scholarly journals Risk stratification in pediatric low-grade glioma and glioneuronal tumor treated with radiation therapy: an integrated clinicopathologic and molecular analysis

2020 ◽  
Vol 22 (8) ◽  
pp. 1203-1213 ◽  
Author(s):  
Sahaja Acharya ◽  
Jo-Fen Liu ◽  
Ruth G Tatevossian ◽  
Jason Chiang ◽  
Ibrahim Qaddoumi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Groups ◽  
Low Risk ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Prognostic Features

Abstract Background Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset. Methods Children with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation. Results One hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%–98.4% vs 59.3%–87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P < 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021). Conclusion A high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation.

scholarly journals Dynamic Contrast Enhanced MRI in Glioma Diagnosis

2017 ◽  
pp. 88-96
Author(s):  
E. A. Nechipay ◽  
M. B. Dolgushin ◽  
A. I. Pronin ◽  
E. A. Kobyakova ◽  
L. M. Fadeeva
Keyword(s):  
Differential Diagnosis ◽  
Brain Tumors ◽  
Surgical Removal ◽  
Low Grade ◽  
Glial Tumors ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Informative Parameters ◽  
Contrast Enhanced ◽  
Grade Iii

The aim: to examine the possibility of using dynamic contrast  enhanced magnetic resonance imaging (DCE MRI) in clarifying the  diagnosis of glial brain tumors and the differentiation between them  on the basis of the malignancy degree. In this regard, the authors  evaluated the effectiveness of perfusion parameters (Ktrans, Kep, Ve and iAUC).Materials and methods.The study included examination of 54  patients with an established presence of brain glial tumors. Glioma  Grade I–II diagnosed in 13 (24.1%) and glioma Grade III–IV in 41  (75.9%) cases. Morphological verification of the diagnosis obtained  as a result of either surgical removal of the tumor or stereotactic biopsy was achieved in 31 (57.4%) patients: glial tumors Grade I–II  identified in 6 (19.4%), and glioma Grade III–IV – 25 (80.6%) cases. Results. According to DCE increasing of the malignancy degree of  glial tumors is followed by increasing of all perfusion parameters:  thus, the lowest values of Ktrans, Kep, Ve and iAUC were identified  in low grade gliomas (0.026 min−1, 0.845 min−1, 0.024 and 1.757,  respectively), the highest in gliomas Grade III–IV (0.052 min−1  1.083 min−1, 0.06 and 2.694, respectively). The most informative parameters with sensi tivity 90% and specificity 100% in the  differential diagnosis of gliomas Grade I-II and Grade III-IV are  Ktrans (cut-off = 0.16 min−1) and Ve (cut-off = 0.13).Conclusion.DCE MRI can be used in differential diagnosis of glial brain tumors of different malignancy grade.

scholarly journals Low-Grade Gliomas in Patients with Noonan Syndrome: Case-Based Review of the Literature

Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 582
Author(s):  
Mariachiara Lodi ◽  
Luigi Boccuto ◽  
Andrea Carai ◽  
Antonella Cacchione ◽  
Evelina Miele ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Noonan Syndrome ◽  
Positive Outcome ◽  
Point Of View ◽  
Optic Pathway Glioma ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Solid Malignancies

Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher risk for leukemia and solid malignancies, including brain tumors, is related to NS. A review of the published literature concerning low grade gliomas (LGGs) in NS is presented. We described also a 13-year-old girl with NS associated with a recurrent mutation in PTPN11, who developed three different types of brain tumors, i.e., an optic pathway glioma, a glioneuronal neoplasm of the left temporal lobe and a cerebellar pilocytic astrocytoma. Molecular characterization of the glioneuronal tumor allowed to detect high levels of phosphorylated MTOR (pMTOR); therefore, a therapeutic approach based on an mTOR inhibitor (everolimus) was elected. The treatment was well tolerated and proved to be effective, leading to a stabilization of the tumor, which was surgical removed. The positive outcome of the present case suggests considering this approach for patients with RASopathies and brain tumors with hyperactivated MTOR signaling.

scholarly journals TB-9 An attempt to establish a patient-derived brain tumor culture model by organoid culture method

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi7-vi7
Author(s):  
Hideki Kuroda ◽  
Noriyuki Kijima ◽  
Tomoyoshi Nakagawa ◽  
Ryuichi Hirayama ◽  
Yoshiko Okita ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Tumor Resection ◽  
Culture Method ◽  
Molecular Heterogeneity ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
True Nature ◽  
Culture Models ◽  
Establishment Rate

Abstract Background: Molecular heterogeneity among and within tumors are one of the reasons for the poor survival rate of brain tumors even with the current standard therapy. However, monolayer culture and neuro-sphere culture (NS) use exogenous growth factors, so may not show the true nature of the tumor. And the culture establishment rate is low, especially low-grade tumors. Therefore, we used the glioblastoma organoid (GBO) culture method showed by Fadi to create culture models of various brain tumors and investigated their characteristics. Methods: We examined the establishment rate in pathological and genotypic types of 56 patients who underwent brain tumor resection at our hospital between January 2020 and June 2021 and were cultured with GBO or NS. If tumor cells are increased visually at 1 month after culture, we defined establishment. Results: There were 15 cases of glioblastoma, 7 cases of anaplastic astrocytoma, 7 cases of diffuse astrocytoma, 3 cases of diffuse midline glioma, 2 cases of anaplastic oligodendroglioma, 5 cases of oligodendroglioma, and 16 cases of others. The establishment rate was 76.5% by the GBO method and 40% by the N S method. By histological type, GBO: 80% in glioblastoma, NS: 58.3% in glioblastoma, GBO: 83.3% in AA, NS: 40% in AA, and GBO: 100% in DA. The IDH mutation and pTERT mutation were investigated in GBO: IDHwt/TERT+ 87.5%, IDHwt/TERT- 64.3%, IDHmt/TERT- 100%, and in NS: IDHwt/TERT+ 75%, IDHwt/TERT- 33.3%, IDHmt/ TERT- 20% in NS. In addition, establishment was observed in GBO 2 case in medulloblastoma, 1 case in ependymoma. Discussion and Conclusion: This suggest that GBO can be used to establish culture models for low-grade tumors. In addition, GBO can establish culture earlier, so it is expected to be applicable to personalized therapies such as preclinical drug efficacy studies tailored to individual patients.

scholarly journals SEIZURES IN CHILDREN WITH LOW GRADE GLIOMA

2021 ◽  
Vol 7 (1) ◽  
pp. 60-65
Author(s):  
Piyush Ostwal ◽  
Shanbhag Nandan
Keyword(s):  
Brain Tumors ◽  
Pediatric Brain Tumors ◽  
Dysembryoplastic Neuroepithelial Tumor ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
Tumor Type ◽  
Low Grade Gliomas ◽  
Primary Treatment Modality ◽  
Antiepileptic Medications ◽  
Pediatric Brain

Seizures are a common presentation of pediatric brain tumors. The incidence of pediatric brain tumor (Age 0-19 years) ranges from 1.12–5.26 cases per 100,000 persons. Low grade gliomas are an important subgroup of pediatric brain tumors causing epilepsy. Low-grade gliomas are largely slow-growing tumors and the manifestations are dependent on age, location, tumor type, size of tumor and rate of tumor growth. Seizures have been reported in up to 38 % of children with supratentorial tumors. The tumors are identified when work up of patients for epilepsy includes electrophysiological and imaging studies. The primary treatment modality remains surgical excision. Antiepileptic medications are used for control of seizures. Subsequent histopathological diagnosis is important for prognostication. The tumors commonly associated with long-term epilepsy in various studies were ganglioglioma, dysembryoplastic neuroepithelial tumor, pilocytic astrocytoma and pilocytic xanthoastrocytoma. The outcome of surgery with regards to seizure control is generally good. Though concomitantly antiepileptic medications will be needed for most of them. An attempt is made in this review to summarize the epidemiology, clinical features, pathology and treatment aspects of pediatric low grade gliomas presenting with seizures.

scholarly journals Epilepsy outcome following resection of low-grade brain tumors in children

2019 ◽  
Vol 23 (6) ◽  
pp. 726-731
Author(s):  
Arvind C. Mohan ◽  
Howard L. Weiner ◽  
Carrie A. Mohila ◽  
Adekunle Adesina ◽  
Murali Chintagumpala ◽  
...  
Keyword(s):  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Class I ◽  
Gross Total Resection ◽  
Subtotal Resection ◽  
Dysembryoplastic Neuroepithelial Tumor ◽  
Low Grade ◽  
Total Resection ◽  
Glial Tumors

OBJECTIVEThe indication for and timing of surgery for epilepsy associated with low-grade mixed neuronal-glial tumors may be controversial. The purpose of this study was to evaluate the effect of resection and associated variables on epilepsy and on progression-free survival (PFS).METHODSA retrospective chart review of patients treated between 1992 and 2016 was conducted to identify individuals with epilepsy and low-grade gliomas or neuronal-glial tumors who underwent resective surgery. Data analyzed included age at epilepsy onset, age at surgery, extent of resection, use of electrocorticography, the number of antiepileptic drugs (AEDs) before and after surgery, the presence of dysplasia, Engel class, histological findings, and PFS. The institutional review board protocol was specifically approved to conduct this study.RESULTSA total of 107 patients were identified. The median follow-up was 4.9 years. The most common pathology was dysembryoplastic neuroepithelial tumor (36.4%), followed by ganglioglioma (31.8%). Eighty-four percent of patients had Engel class I outcomes following surgery. Gross-total resection was associated with a higher likelihood of an Engel class I outcome (90%) as compared to subtotal resection (58%) (p = 0.0005). Surgery reduced the AED burden, with 40% of patients requiring no AEDs after surgery (p < 0.0001). Children with neurodevelopmental comorbidities (n = 5) uniformly did not experience seizure improvement following resection (0% vs 83% overall; p < 0.0001). Electrocorticography was used in 33% of cases and did not significantly increase class I outcomes. PFS was 90% at 5 years. Eleven percent of tumors recurred, with subtotal resection more likely to result in recurrence (hazard ratio 5.3, p = 0.02). Histological subtype showed no significant impact on recurrence.CONCLUSIONSGross-total resection was strongly associated with Engel class I outcome and longer PFS. Further studies are needed to elucidate the suitable time for surgery and to identify factors associated with oncological transformation.

scholarly journals PATH-38. ROSETTE-FORMING GLIONEURONAL TUMOR IS DEFINED BY FGFR1 ACTIVATING ALTERATIONS WITH FREQUENT ACCOMPANYING PI3K AND MAPK PATHWAY MUTATIONS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi151-vi152
Author(s):  
Lucas Calixto-Hope ◽  
Julieann Lee ◽  
Emily Sloan ◽  
Jeffrey Hofmann ◽  
Jessica Van Ziffle ◽  
...  
Keyword(s):  
Map Kinase ◽  
Fourth Ventricle ◽  
Mapk Pathway ◽  
Pik3ca Mutation ◽  
Kinase Domain ◽  
Pi3 Kinase ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Map Kinase Pathway ◽  
Kinase Pathway

Abstract BACKGROUND Rosette-forming glioneuronal tumor (RGNT) is an uncommon CNS tumor originally described in the fourth ventricle characterized by a low-grade glial neoplasm admixed with a rosette-forming neurocytic component. METHODS We reviewed clinicopathologic features of 42 patients with RGNT. Targeted next-generation sequencing was performed, and genome-wide methylation profiling is underway. RESULTS The 20 male and 22 female patients had a mean age of 25 years (range 3–47) at time of diagnosis. Tumors were located within or adjacent to the lateral ventricle (n=16), fourth ventricle (15), third ventricle (9), and spinal cord (2). All 31 tumors assessed to date contained FGFR1 activating alterations, either in-frame gene fusion, kinase domain tandem duplication, or hotspot missense mutation in the kinase domain (p.N546 or p.K656). While 7 of these 31 tumors harbored FGFR1 alterations as the solitary pathogenic event, 24 contained additional pathogenic alterations within PI3-kinase or MAP kinase pathway genes: 5 with additional PIK3CA and NF1 mutations, 4 with PIK3CA mutation, 3 with PIK3R1 mutation (one of which also contained focal RAF1 amplification), 5 with PTPN11 mutation (one with additional PIK3R1 mutation), and 2 with NF1 deletion. The other 5 cases demonstrated anaplastic features including hypercellularity and increased mitotic activity. Among these anaplastic cases, 3 harbored inactivating ATRX mutations and two harbored CDKN2A homozygous deletion, in addition to the FGFR1 alterations plus other PI3-kinase and MAP kinase gene mutations seen in those RGNT without anaplasia. CONCLUSION Independent of ventricular location, RGNT is defined by FGFR1 activating mutations or rearrangements, which are frequently accompanied by mutations involving PIK3CA, PIK3R1, PTPN11, NF1, and KRAS. Whereas pilocytic astrocytoma and ganglioglioma are characterized by solitary activating MAP kinase pathway alterations (e.g. BRAF fusion or mutation), RGNT are genetically more complex with dual PI3K-Akt-mTOR and Ras-Raf-MAPK pathway activation. Rare anaplastic examples may show additional ATRX and/or CDKN2A inactivation.

scholarly journals RARE-48. CHARACTERISTICS AND OUTCOME OF DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT): A SINGLE INSTITUTION EXPERIENCE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii452-iii452
Author(s):  
Emily Owens Pickle ◽  
Ana Aguilar-Bonilla ◽  
Amy Smith
Keyword(s):  
Mapk Pathway ◽  
Clinical History ◽  
Mek Inhibitor ◽  
Glioneuronal Tumor ◽  
Unknown Etiology ◽  
Leptomeningeal Disease ◽  
Low Grade ◽  
Diffuse Leptomeningeal Glioneuronal Tumor ◽  
Braf Fusion ◽  
Chemotherapy Patients

Abstract Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare with an unknown etiology and unestablished incidence. Most frequently reported genetic alteration is KIAA1549-BRAF fusion. We present four DLGNT cases diagnosed between 2005–2018. Patient 1 is a female who presented with a 2-year history of back pain subsequently diagnosed with pilocytic astrocytoma. Re-imaging 3 months post-resection revealed a low grade glioneuronal tumor with BRAF duplication. Patient 2 is a female who presented with recurrent vomiting, dizziness, and hydrocephalus. The patient underwent biopsy which was consistent with oligodendrogliomatosis; no genetic analysis was done. Patient 3 is a male who presented with worsening headaches and intermittent vomiting. Approximately 5 months after resection, imaging showed leptomeningeal disease and further testing revealed KIAA1549-BRAF fusion and 1p deletion. Patient 4 is a male who presented with hydrocephalus. Imaging showed disseminated leptomeningeal enhancement without a dominant mass lesion; biopsy and clinical history confirmed the diagnosis. All four patients received chemotherapy, Patients 1 and 3 underwent radiation therapy, and Patient 3 received a MEK-inhibitor to which he had a great response. However, the patient was non-compliant and had PD which continued despite re-starting therapy. Patients 1, 2, and 3 have died of progressive disease; survival was Patient 1, 276 days, Patient 2, approximately 7 years and 8 months, and Patient 3, 2 years and 11 months. Patient 4 remains alive with disease 4.5 years from diagnosis. There is much to be learned about this rare, poorly understood disease but hope for improvement through therapeutic targeting of the MAPK pathway.

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