Unusual high-grade features in pediatric diffuse leptomeningeal glioneuronal tumor: comparison with a typical low-grade example

Schwetye, Katherine E.; Kansagra, Akash P.; McEachern, James; Schmidt, Robert E.; Gauvain, Karen; Dahiya, Sonika

doi:10.1016/j.humpath.2017.06.004

Cited by 32 publications

(22 citation statements)

References 15 publications

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“…A summary of characteristics in previous series is given in Table 1. Although most tumors display a slow progression, aggressive cases were occasionally encountered [12,29,31,36]. The largest series with follow-up data of 24 patients showed 9 deaths within 3-21 years [31].…”

Section: Introductionmentioning

confidence: 99%

“…Histologically, DLGNTs have been described as low-to moderate-cellularity lesions consisting of relatively monomorphous oligodendrocyte-like cells with round to oval nuclei, inconspicuous nucleoli and a 'glioneural commitment' [15], embedded in a desmoplastic or myxoid leptomeningeal stroma [29,31]. While a low mitotic activity was most commonly observed, features of anaplasia were also seen in a number of cases [31,36]. Immunohistochemical features of the tumor cells appear to include strong reactivity for OLIG2, MAP2 and S100, with variable expression for GFAP and synaptophysin.…”

Section: Introductionmentioning

confidence: 99%

“…Immunostaining for NeuN, EMA and mutant IDH1 (R132H) was negative [9,29,31,35]. Although typically displaying a low Ki-67 proliferation index, several cases with elevated proliferation were reported [29,31,35,36], with less favorable outcome associated with an index > 4% [31,36]. The wide spectrum of histological and radiological features encountered, as well as its rarity and relatively recent inclusion in the WHO classification, can make this tumor entity difficult to diagnose.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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 14 years, 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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…DLGNT is a very rare entity occurring mostly in children and adolescents. [5][6][7][8][9][10][11][12][13] Several cases in adults have been reported. 3,8,12 Most common symptoms include nausea and vomiting, 2-4,12-14 headache, [2][3][4][5][6][7]9,11,12,14 seizures, 11,12,15 limbs weakness, 2,4,7,9,11 loss of vision, 9,11 and altered mental state (confusion).…”

Section: Discussionmentioning

confidence: 99%

“…DLGNTs are typically positive for S100, Olig2, GFAP, and synaptophysin expression, 3,4,6,7,9 but immunoreactivity can differ between cases. The tumor is becoming increasingly recognized as having BRAF and KIAA1549 genes fusions, 1p deletions 2,6,9,13 and rarely 1p/19q codeletion 7,11 but a significant part of DLGNTs are negative for these markers. 2,3,6,8,10,12,14,16 In the reported case, the tumor showed BRAF and KIAA1549 fusion but without the most common BRAF gene mutations.…”

Section: Discussionmentioning

confidence: 99%

Diffuse Leptomeningeal Glioneuronal Tumor in a 4.5-year-old Girl: A Case Report and Review of the Literature

Gabryś

Kuzaj

Pawełczak

et al. 2020

Journal of Pediatric Neurology

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Diffuse leptomeningeal glioneuronal tumor (DLGNT) is an entity introduced in 2016 World Health Organization classification of tumors of the central nervous system. The tumor occurs very rarely. Due to the lack of specific clinical and radiological features, biopsy is necessary to be performed and histological and immunohistochemical testing is essential to reach the diagnosis. A 4.5-year-old girl presented with a history of headache, vomiting, and right eye convergent squint. Imaging revealed multiple enhancing lesions located supra- and infratentorially and intramedullary. Histopathological examination demonstrated diffused growth of neoplastic cells. Molecular testing revealed KIAA1549-BRAF fusion and the diagnosis of DLGNT was stated.

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A case of diffuse leptomeningeal glioneuronal tumor in a 10‐year‐old boy: First report from Iran

Karimzadeh

Nilipour

Khalili

et al. 2021

Clinical Case Reports

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A 10‐year‐old boy who was referred due to acute hydrocephalus symptoms was diagnosed as the first case of pediatric DLGNT in Iran. The results suggested that using shunting for hydrocephaly and anti‐seizure medicines, as well as chemotherapeutic agents, can be an effective treatment strategy for DLGNT. Although the patient was stable without a tumor recurrence for a limited follow‐up period of 22 months, further studies are expected.

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Unusual high-grade features in pediatric diffuse leptomeningeal glioneuronal tumor: comparison with a typical low-grade example

Cited by 32 publications

References 15 publications

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

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

Diffuse Leptomeningeal Glioneuronal Tumor in a 4.5-year-old Girl: A Case Report and Review of the Literature

A case of diffuse leptomeningeal glioneuronal tumor in a 10‐year‐old boy: First report from Iran

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