scholarly journals PATH-44. AN UNUSUAL PRESENTATION OF A PEDIATRIC MIDLINE H3K27M-MUTANT TUMOR WITH DISSEMINATED CRANIOSPINAL LEPTOMENINGEAL DISEASE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii174-ii174
Author(s):  
Ralph Navarro ◽  
Danielle Golub ◽  
Travis Hill ◽  
Michelle McQuinn ◽  
Nora Kim ◽  
...  
Keyword(s):  
Treatment Response ◽  
Molecular Signature ◽  
Proliferation Index ◽  
Glioneuronal Tumor ◽  
Leptomeningeal Disease ◽  
Extensive Literature ◽  
Thalamic Lesion ◽  
Leptomeningeal Spread ◽  
Local Progression ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

Abstract BACKGROUND H3K27M-mutant midline lesions were recently reclassified by the WHO as “Diffuse Midline Glioma” (DMG) based on their molecular signature. DMG is one of the most common and most lethal pediatric brain tumors; terminal progression is typically caused by local progression or secondary leptomeningeal dissemination. H3K27M mutations have also been infrequently associated with a histologically diverse set of lesions, particularly spinal masses with early leptomeningeal spread, but the role of H3K27M in these atypical lesions remains poorly understood. CASE PRESENTATION A 15-year-old girl was found to have a T2/FLAIR-hyperintense and heterogeneously contrast-enhancing thalamic mass accompanied by severe leptomeningeal enhancement along the entire neuraxis. Initial infectious workup was negative, and open intracranial biopsy was inconclusive. Follow-up spinal arachnoid biopsy was diagnostic for H3K27M neuroepithelial tumor, thereafter classified as DMG. Biopsy also showed focal p53 immunopositivity, variable immunoreactivity for GFAP and synaptophysin, and an increased proliferation index, altogether suggestive of a glioneuronal origin. She received craniospinal irradiation (CSI) to 41.4Gy with a boost to the thalamic lesion to 54Gy. Imaging 1-month post-radiation demonstrated significant treatment response only with residual enhancement at the conus. CONCLUSIONS This case report describes the unique presentation of an H3K27M-mutant midline lesion with significant craniospinal leptomeningeal spread on admission and atypical glioneuronal histopathological markers. Given her avid leptomeningeal disease, spinal dural biopsy could have been considered earlier given its diagnostic yield in classifying the lesion as DMG. This lesion, however, additionally demonstrated synaptophysin positivity. Per extensive literature review, this histopathology is also potentially consistent with diffuse leptomeningeal glioneuronal tumor (DLGNT). This patient’s uniquely marked treatment response to CSI is also not typically observed in DMG, further supporting the possibility of an alternative molecular identity. In atypical DMG cases, particularly with early leptomeningeal spread, additional consideration of clinical and histopathological context is warranted for accurate diagnosis and prognostication.

scholarly journals HGG-06. REMARKABLE RESPONSE TO BRAF INHIBITOR IN AN INFANT WITH DISSEMINATED DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR (DLGNT)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii345-iii345
Author(s):  
Le Le Aung
Keyword(s):  
Braf Inhibitor ◽  
Braf V600e ◽  
Proliferation Index ◽  
Glioneuronal Tumor ◽  
Low Grade ◽  
Braf Inhibitors ◽  
Visual Contact ◽  
Ki 67 ◽  
Low Grade Gliomas ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

Abstract INTRODUCTION Diffuse Leptomeningeal Glioneuronal Tumor (DLGNT) are rare CNS tumors and in infants, they can be lethal. There are several anecdotal reports in infants with low grade gliomas (LGG) with treated with BRAF inhibitors. METHODS A six-month old baby girl presented with a 2-week history of absent visual contact and vomiting. Imaging revealed a large 4.7 X 4.2 X 2.8 cm suprasellar charismatic region mass and multiple small extra-axial plaques in spinal canal. The child developed significant ascites post VP shunt requiring shunt externalization, extensive protein infusion support and hospitalization for six weeks. Immunohisto-chemical staining revealed Olig-2 and S-100, GFAP and synaptophysin positive. EMA showed patchy cytroplasmic reactivity in stromal cells and CD99 showed diffuse reactivity in stromal and lesional cells. INI-1, IDH-1, and CD117 were negative. Ki-67 proliferation index was 8–10%. PCR for BRAF V600E/E2/D was detected and KIAA1549-BRAF fusion as negative. This was confirmed by Genome Wide Next Generation Sequencing. While waiting for GNS testing results, the baby received one dose of Vinblastine. However, within seven days of initiating Debrafenib, significant clinical and radiological responses were observed. CONCLUSION The baby continues safely on Debrafenib with continued dramatic radiological response. This suggest that there may be a role in early initiation of targeted therapy such as BRAF inhibitors rather than giving standard chemotherapy such as Vinblastine or Carboplatin-Vincristine in extremely ill infants with low grade gliomas.

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.

scholarly journals Diffuse leptomeningeal glioneuronal tumor with high-grade features masquerading as tubercular meningitis—a case report

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Sameer Peer ◽  
Vivek Murumkar ◽  
Karthik Kulanthaivelu ◽  
Chandrajit Prasad ◽  
Shilpa Rao ◽  
...  
Keyword(s):  
Case Report ◽  
Early Diagnosis ◽  
Histopathological Examination ◽  
Glioneuronal Tumor ◽  
Communicating Hydrocephalus ◽  
High Grade ◽  
Endemic Region ◽  
Tubercular Meningitis ◽  
Leptomeningeal Enhancement ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

Abstract Background Diffuse leptomeningeal glioneuronal tumor (DLGNT) has been recently described in the literature. The complete neuroimaging spectrum and histopathological characteristics of this entity are yet to be elucidated. In an endemic region, diffuse leptomeningeal enhancement on neuroimaging with associated communicating hydrocephalus is usually suggestive of infective meningitis and the patients are started on empirical anti-microbial therapy. However, it is important to consider other differential diagnosis of leptomeningeal enhancement in such cases, particularly if the clinical condition does not improve on anti-microbial therapy. An early diagnosis of a neoplastic etiology may be of particular importance as the treatment regimens vary considerably depending on the underlying disease condition. Case presentation In this case report, we describe a case of DLGNT with high-grade histopathological features which was initially managed as tubercular meningitis based on the initial neuroimaging findings. Due to worsening of the clinical course and subsequent imaging findings at follow-up, a diagnosis of DLGNT was considered and subsequently proven to be DLGNT with features of anaplasia on histopathological examination of leptomeningeal biopsy specimen. Conclusion This case highlights the importance of recognizing certain subtle finding on MRI which may help in an early diagnosis of DLGNT which is crucial for appropriate treatment.

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.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) mimicking Whipple’s disease: a case report and literature review

2017 ◽  
Vol 33 (8) ◽  
pp. 1411-1414 ◽  
Author(s):  
Vega Karlowee ◽  
Manish Kolakshyapati ◽  
Vishwa Jeet Amatya ◽  
Takeshi Takayasu ◽  
Ryo Nosaka ◽  
...  
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Glioneuronal Tumor ◽  
Whipple’S Disease ◽  
Whipple's Disease ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR IN CHILDREN: MR CHARACTERISTICS, CLINICAL FEATURES AND OUTCOME. FOUR CLINICAL CASES

2021 ◽  
Vol 20 (1) ◽  
pp. 42-55
Author(s):  
A. F. Valiakhmetova ◽  
L. I. Papusha ◽  
A. V. Artemov ◽  
G. V. Tereshchenko ◽  
E. A. Sal’nikova ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Molecular Genetic ◽  
Complete Response ◽  
Mek Inhibitor ◽  
Braf V600e ◽  
Glioneuronal Tumor ◽  
Molecular Testing ◽  
Genetic Characteristics ◽  
Diffuse Leptomeningeal Glioneuronal Tumor ◽  
Braf Fusion

Background. Diffuse leptomeningeal glioneuronal tumor (DLGNT) is an extremely rare entity first officially recognized in 2016 WHO classification of tumors of the central nervous system. Magnetic resonance imaging (MRI) of this tumor usually visualizes diffuse meningeal infiltration with contrast enhancement, with the presence of multiple small contrast‑negative cysts, visible mainly in the T2 images. The main molecular markers of DLGNTs include the KIAA1549-BRAF fusion gene, BRAF V600E substitution is less common.The aim of this work is to describe the manifestation of DLGNT, its neuroimaging and molecular genetic characteristics, the experience of using anti‑BRAF and anti‑MEK therapy.Materials and methods. In this article are described four cases of DLGNT. The first patient with the presence of the KIAA1549-BRAF fusion in the tumor tissue received a full course of SIOP‑LGG / 2004 chemotherapy (carbo‑ platin and vincristine), the stabilization of the disease on the MRI remains for 4 years after completion of treatment. Second patient with KIAA1549-BRAF fusion gene in tumour tissue received MEK inhibitor trametinib as first line of treatment with the stabilization of the disease on control MRI which last for 2 years. A third patient with a mutation in the BRAF V600E gene. After disease progression on standard chemotherapy (carboplatin and vincristine) according to the SIOP‑LGG / 2004 protocol, anti‑BRAF therapy with vemurafenib was prescribed. After 10 months on MRI a complete response was recorded, which persists during the drug intake for 2.5 years. In the fourth patient, no molecular genetic aberrations were detected; a refractory / progressive course of the dis‑ ease was noted. To date, the stabilization of the disease is recorded on the fourth line of chemotherapy (everoli‑ mus and temozolomide).Conclusion. Given the rarity of this tumor and the lack of consensus about therapy, despite the limited number of observations, our experience allows us to recommend molecular testing of DLGNT to detect activating events in the BRAF gene, as well as consideration of anti‑BRAF / MEK therapy if either the BRAF V600E mutation is de‑ tected or KIAA1549-BRAF fusion.

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

2019 ◽  
Vol 35 (9) ◽  
pp. 1609-1614 ◽  
Author(s):  
Nishant Tiwari ◽  
Benita Tamrazi ◽  
Nathan Robison ◽  
Mark Krieger ◽  
Jianling Ji ◽  
...  
Keyword(s):  
Glioneuronal Tumor ◽  
Diffuse Leptomeningeal Glioneuronal Tumor

scholarly journals Spinal Cord Glioneuronal Tumor with Rosetted Neuropil-Like Islands in Pediatric Age Group

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Nil Comunoglu ◽  
Ozgur Kilickesmez ◽  
Buge Oz
Keyword(s):  
Spinal Cord ◽  
Urinary Incontinence ◽  
Proliferation Index ◽  
Glioneuronal Tumor ◽  
Age Group ◽  
Pediatric Age ◽  
Ki 67 ◽  
Rare Tumors ◽  
Pediatric Age Group

Glioneuronal neoplasms are rare tumors. Recently, an unusual glioneuronal tumor histologically showing neuropil-like islands has been described. Here, we present such a tumor originating from spinal cord of a 14-year-old girl, who has scoliosis and urinary incontinence. Microscopically, the glial component was chiefly fibrillary astrocytic, punctuated by neuropil-like islands. Immunohistochemically, glial tissue was GFAP positive, and neuropil-like areas and big neurons were synaptophysin reactive. For astrocytic component Ki-67 proliferation index was 1% and p53 was immunonegative. This case is unique in that in the literature it is the second reported case in pediatric age group that is located at spinal cord.

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