Neuroimaging of thalamic tumors in children

Colosimo, Cesare; Lella, Giuseppe Maria Di; Tartaglione, Tommaso; Riccardi, Riccardo

doi:10.1007/s00381-002-0607-y

Cited by 38 publications

(29 citation statements)

References 20 publications

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“…However, we showed that children with GC commonly have involvement of deeper brain structures, including the thalami. Furthermore, similar to other studies in children [1, 5, 6], we showed that more than 25 % of our patients had symmetrical bithalamic involvement as a prominent feature of GC. Because only 4 of our 9 patients with GC and a symmetrical bithalamic involvement had molecular data available, the possibility that a H3F3A p.K27M mutation could be found in pediatric GC cannot be entirely excluded.…”

Section: Discussionsupporting

confidence: 92%

Gliomatosis cerebri in children shares molecular characteristics with other pediatric gliomas

et al. 2016

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Gliomatosis cerebri (GC), a rare and deadly CNS neoplasm characterized by involvement of at least three cerebral lobes, predominantly affects adults. While a few small series have reported its occurrence in children, little is known about the molecular characteristics of pediatric GC. We reviewed clinical, radiological, and histological features of pediatric patients with primary GC treated at our institution over 15 years. Targeted sequencing of mutational hotspots in H3F3A, IDH1/2, and BRAF, and genome-wide analysis of DNA methylation and copy number abnormalities was performed in available tumors. Thirty-two patients [23 (72 %) with type 1 and 9 (28 %) with type 2 GC] were identified. Median age at diagnosis was 10.2 years (range 1.5–19.1). A median of 4 cerebral lobes (range 3–8) was affected at diagnosis. In addition, symmetrical bithalamic involvement was observed in 9 (28 %) patients. Twenty-two patients (69 %) had an anaplastic astrocytoma. Despite aggressive therapy, only two patients younger than 3 years at diagnosis are long-term survivors. Clustering analysis of methylation array data from 18 cases classified tumors as IDH (n = 3, 17 %), G34 (n = 4, 22 %), mesenchymal (n 3, 17= %), and RTK I ‘PDGFRA’ (n = 8, 44 %). No tumors were classified as K27 subgroup. PDGFRA was the most commonly amplified oncogene in 4 of 22 tumors (18 %). H3F3A p.G34 occurred in all cases classified as G34. Two of 3 cases in the IDH subgroup had IDH1 p.R132H. No H3F3A p.K27 M, IDH2 p.R172, or BRAF p.V600E mutations were observed. There was a trend towards improved survival in the IDH subgroup (P = 0.056). Patients with bithalamic involvement had worse outcomes (P = 0.019). Despite some overlap, the molecular features of pediatric GC are distinct from its adult counterpart. Like in adults, the similarity of genetic and epigenetic characteristics with other infiltrative high-grade gliomas suggests that pediatric GC does not represent a distinct molecular entity.

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Section: Discussionsupporting

confidence: 92%

Gliomatosis cerebri in children shares molecular characteristics with other pediatric gliomas

et al. 2016

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“…It has been hypothesized that these symptoms arise due to the impairment of the dorsomedial nuclei, which have connections to the amygdala, the temporal neocortex, and the prefrontal region [24]. Most cases of bilateral thalamic astrocytomas occur in children [25]. These patients nearly always need a shunt because of compression of the third ventricle caused by the tumor (Figure 7).…”

Section: Tumormentioning

confidence: 99%

“…Bilateral diffuse thalamic gliomas on MRS show an elevated creatinine peak compared to choline [20]; however, whether this finding is characteristic of the bilateral manifestation is still controversial [21]. An increase in choline can itself serve as a measure of the proliferation activity of the tumor, since it correlates with the membrane metabolism [25].…”

Section: Tumormentioning

confidence: 99%

Differential Diagnosis of Bilateral Thalamic Lesions

Linn

Danek

Hoffmann³

et al. 2007

Clin Neuroradiol

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“…At present, tumours arising in the brainstem, known as diffuse intrinsic pontine glioma (DIPG), have been extensively investigated and stratified into disease subtypes [6, 20]. Whereas DIPG is heavily researched, thalamic tumours, accounting for approximately 5 % of all paediatric brain neoplasms, are largely unexplored [8–10, 14, 27, 28]. Currently, the outcome of patients with thalamic tumours is predicted based on the histological grade and the potential for surgical resection of the tumour.…”

Section: Introductionmentioning

confidence: 99%

Targeted detection of genetic alterations reveal the prognostic impact of H3K27M and MAPK pathway aberrations in paediatric thalamic glioma

Ryall

Krishnatry

Arnoldo

et al. 2016

acta neuropathol commun

102

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Paediatric brain tumours arising in the thalamus present significant diagnostic and therapeutic challenges to physicians due to their sensitive midline location. As such, genetic analysis for biomarkers to aid in the diagnosis, prognosis and treatment of these tumours is needed. Here, we identified 64 thalamic gliomas with clinical follow-up and characterized targeted genomic alterations using newly optimized droplet digital and NanoString-based assays. The median age at diagnosis was 9.25 years (range, 0.63–17.55) and median survival was 6.43 (range, 0.01–27.63) years. Our cohort contained 42 and 22 tumours reviewed as low and high grade gliomas, respectively. Five (12 %) low grade and 11 (50 %) high grade gliomas were positive for the H3F3A/HIST1H3B K27M (H3K27M) mutation. Kaplan-Meier survival analysis revealed significantly worse overall survival for patients harbouring the H3K27M mutation versus H3F3A/HIST1H3B wild type (H3WT) samples (log-rank p < 0.0001) with a median survival of 1.02 vs. 9.12 years. Mitogen-activated protein kinase (MAPK) pathway activation via BRAF or FGFR1 hotspot mutations or fusion events were detected in 44 % of patients, and was associated with long-term survival in the absence of H3K27M (log-rank p < 0.0001). Multivariate analysis demonstrated H3K27M status and high grade histology to be the most significant independent predictors of poor overall survival with hazard ratios of 6.945 and 7.721 (p < 0.0001), respectively. In contrast, MAPK pathway activation is a predictor of favourable patient outcome, although not independent of other clinical factors. Importantly, we show that low grade malignancies may harbour H3K27M mutations and that these tumours show a dismal survival compared to low grade H3WT cases. Our data strongly supports the inclusion of targeted genetic testing in childhood thalamic tumours to most accurately stratify patients into appropriate risk groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0353-0) contains supplementary material, which is available to authorized users.

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Neuroimaging of thalamic tumors in children

Cited by 38 publications

References 20 publications

Gliomatosis cerebri in children shares molecular characteristics with other pediatric gliomas

Gliomatosis cerebri in children shares molecular characteristics with other pediatric gliomas

Differential Diagnosis of Bilateral Thalamic Lesions

Targeted detection of genetic alterations reveal the prognostic impact of H3K27M and MAPK pathway aberrations in paediatric thalamic glioma

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