Malignant transformation of a polymorphous low grade neuroepithelial tumor of the young (PLNTY)

Bale, Tejus; Sait, Sameer Farouk; Benhamida, Jamal; Ptashkin, Ryan; Haque, Sofia; Villafania, Liliana; Sill, Martin; Sadowska, Justyna; Akhtar, Razia B; Liechty, Benjamin; Juthani, Rupa; Ladanyi, Marc; Fowkes, Mary; Karajannis, Matthias A.; Rosenblum, Marc K.

doi:10.1007/s00401-020-02245-4

Cited by 30 publications

(34 citation statements)

References 10 publications

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“…LGG including PLNTY [19,21,24,44], and one malignant transformation of a PLNTY is on record [44]. Because FGFR3-TACC3 also characterised a subset of malignant diffuse glioma in adults [45], we strongly encourage following carefully patients presenting an…”

Section: Discussionmentioning

confidence: 99%

Low‐grade epilepsy‐associated neuroepithelial tumours with a prominent oligodendroglioma‐like component: The diagnostic challenges

Métais

Appay

Pagès

et al. 2021

Neuropathology Appl Neurobio

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Aims: We searched for recurrent pathological features and molecular alterations in a retrospective series of 72 low-grade epilepsy-associated neuroepithelial tumours (LEATs) with a prominent oligodendroglioma-like component, in order to classify them according to the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumours. Methods: Centralised pathological examination was performed as well as targeted molecular analysis of v-Raf murine sarcoma viral oncogene homologue B (BRAF) and fibroblast growth factor receptor 1 (FGFR1) by multiplexed digital polymerase chain reaction (mdPCR). DNA methylation profiling was performed in cases with sufficient DNA. In cases with no genetic alteration by mdPCR and sufficient material, RNA sequencing was done. Results: We first reclassified our cohort into three groups: ganglioglioma (GG, n = 14), dysembryoplastic neuroepithelial tumours (DNTs, n = 19) and glioneuronal tumours/ paediatric-type low-grade glioma (LGG) not otherwise specified (GNT/PLGG NOS, n = 39). mdPCR found an alteration in 38/72 cases. Subsequent RNA sequencing revealed a fusion transcript involving BRAF, FGFR1/2/3 or neurotrophic tyrosine kinase receptor type 2 [NTRK2] in 9/25 cases. DNA methylation profiling found 12/46 cases with a calibrated score ≥0.9. Unsupervised hierarchical clustering revealed two clusters: Cluster 1 was enriched with cases classified as DNT at histology, belonging to the LGG-DNT methylation class (MC), with haematopoietic progenitor cell antigen (CD34) negativity and FGRF1 alterations; Cluster 2 was enriched with cases classified at histology as GG, belonging to the LGG-GG MC MC, with BRAF V600E mutation and CD34 positivity. The tumours reclassified as GNT/PLGG NOS were equally distributed across both clusters. Interestingly, all polymorphous low-grade neuroepithelial tumour of the young Romain Appay and Mélanie Pagès contributed equally to this study.

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Section: Discussionmentioning

confidence: 99%

Low‐grade epilepsy‐associated neuroepithelial tumours with a prominent oligodendroglioma‐like component: The diagnostic challenges

Métais

Appay

Pagès

et al. 2021

Neuropathology Appl Neurobio

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“…The sole FGFR3:TACC3 fusion positive case in the original series of PLNTY demonstrated no evidence of disease or seizures after gross total resection, with a follow‐up interval of 89 months. However, the malignant transformation of a tumor with an in‐frame fusion involving FGFR3 (exon 18) and TACC3 (exon 11), previously meeting diagnostic criteria for PLNTY, has been reported 89 . This mixed molecular‐genetic background makes PLNTY difficult to stratify into a classification scheme organized by gene driving mutations, highlighting the importance of further studies 4 …”

Section: Resultsmentioning

confidence: 99%

“…However, the malignant transformation of a tumor with an in-frame fusion involving FGFR3 (exon 18) and TACC3 (exon 11), previously meeting diagnostic criteria for PLNTY, has been reported. 89 This mixed molecular-genetic background makes PLNTY difficult to stratify into a classification scheme organized by gene driving mutations, highlighting the importance of further studies. 4 Altered MAPK pathway in multinodular and vacuolating neuronal tumor (MVNT) At first, MVNT was included in the 2016 WHO Classification of CNS Tumors as a pattern of ganglion cell tumors, 90,91 but it is now recognized as an independent entity in the 2021 WHO Classification.…”

Section: Braf and Fgfr Family Findings In Polymorphous Low-grade Neur...mentioning

confidence: 99%

The landscape of common genetic drivers and DNA methylation in low‐grade (epilepsy‐associated) neuroepithelial tumors: A review

et al. 2022

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Low-grade neuroepithelial tumors (LNETs) represent an important group of central nervous system neoplasms, some of which may be associated to epilepsy. The concept of long-term epilepsy-associated tumors (LEATs) includes a heterogenous group of low-grade, cortically based tumors, associated to drug-resistant epilepsy, often requiring surgical treatment. LEATs entities can sometimes be poorly discriminated by histological features, precluding a confident classification in the absence of additional diagnostic tools. This study aimed to provide an updated review on the genomic findings and DNA methylation profiling advances in LNETs, including histological entities of LEATs. A comprehensive search strategy was conducted on PubMed, Embase, and Web of Science Core Collection. High-quality peer-reviewed original manuscripts and review articles with full-text in English, published between 2003 and 2022, were included. Results were screened based on titles and abstracts to determine suitability for inclusion, and when addressed the topic of the review was screened by full-text reading. Data extraction was performed through a qualitative content analysis approach. Most LNETs appear to be driven mainly by a single genomic abnormality and respective affected signaling pathway, including BRAF p.V600E mutations in ganglioglioma, FGFR1 abnormalities in dysembryoplastic neuroepithelial tumor, MYB alterations in angiocentric glioma, BRAF fusions in pilocytic astrocytoma, PRKCA fusions in papillary glioneuronal tumor, between others. However, these molecular alterations are not exclusive, with some overlap amongst different tumor histologies. Also, clustering analysis of DNA methylation profiles allowed the identification of biologically similar molecular groups that sometimes transcend conventional histopathological classification. The exciting developments on the molecular basis of these tumors reinforce the importance of an integrative histopathological and (epi)genetic classification, which can be translated into precision medicine approaches.

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“…This particular fusion product was present in the only documented case of PLNTY with malignant transformation. 8 The presence of FGFR alterations does not help to distinguish PLNTY from other tumors in the LEAT differential diagnosis, as they have also been reported in many of these tumors.…”

Section: Discussionmentioning

confidence: 97%

Polymorphous low-grade neuroepithelial tumor of the young: Rare tumor and review of the literature

et al. 2022

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Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described low-grade neuroepithelial tumor with an infiltrative growth pattern and oligodendrocyte-like cells that are CD34 immunopositive. Correlating histology and results from molecular testing is critical to correctly diagnosing PLNTY, as its histologic appearance is similar to oligodendrogliomas and shares genetic abnormalities common to other low-grade epilepsy associated tumors (LEATs). In this case report, we describe a 31-year-old female with intractable epilepsy found to have a temporal mass and diagnosed with PLNTY after histopathologic and molecular testing. We describe the radiographic, histologic, and genetic features in relation to the epileptic and oncologic outcomes for this patient. Then, we compare these features and outcomes to other cases of PLNTY described in the literature.

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Malignant transformation of a polymorphous low grade neuroepithelial tumor of the young (PLNTY)

Cited by 30 publications

References 10 publications

Low‐grade epilepsy‐associated neuroepithelial tumours with a prominent oligodendroglioma‐like component: The diagnostic challenges

Low‐grade epilepsy‐associated neuroepithelial tumours with a prominent oligodendroglioma‐like component: The diagnostic challenges

The landscape of common genetic drivers and DNA methylation in low‐grade (epilepsy‐associated) neuroepithelial tumors: A review

Polymorphous low-grade neuroepithelial tumor of the young: Rare tumor and review of the literature

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