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To conclude, we report, for the first time, two embryonal tumors with I PLAG1 i fusions sharing clinico-radiological, histopathological, immunohistochemical, and epigenetic similarities to CNS embryonal tumors with PLAG-family amplification. Central Nervous System (CNS) embryonal tumors with PLAG-family amplification have been isolated by a distinct DNA-methylation profile [[1]]. References 1 Keck M-K, Sill M, Wittmann A, Joshi P, Stichel D, Beck P. Amplification of the PLAG-family genes-PLAGL1 and PLAGL2-is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification. [Extracted from the article]

This article discusses two novel tumors classified as extraventricular neurocytomas (EVN) that were found to have NTRK2 fusions instead of the usual FGFR1 alterations. The first case involved a 23-year-old woman with migraines and epileptic seizures, while the second case involved a 15-year-old girl with intracerebral calcifications. Both cases underwent total removal of the tumors and showed positive staining for synaptophysin and olig2. The study suggests that these findings have implications for diagnosis, therapy, and terminology, and further research is needed to better understand these tumors. [Extracted from the article]

DNA-methylation profiling using the CNS tumor Classifier supported the NB-FOXR2 diagnosis in 9/24 cases (37%), with a calibrated score (> 0.9) for nine of the samples. However, in recent years, thanks to molecular analyses, I forkhead box R2 i ( I FOXR2 i ) alterations have become associated with this tumor type and as a result, the WHO classification renamed the neoplasm "CNS neuroblastoma (NB), I FOXR2- i activated" [[4]]. [Extracted from the article]

Pediatric spinal low-grade glioma (LGG) and glioneuronal tumours are rare, accounting for less 2.8–5.2% of pediatric LGG. New tumour types frequently found in spinal location such as diffuse leptomeningeal glioneuronal tumours (DLGNT) have been added to the World Health Organization (WHO) classification of tumours of the central nervous system since 2016, but their distinction from others gliomas and particularly from pilocytic astrocytoma (PA) are poorly defined. Most large studies on this subject were published before the era of the molecular diagnosis and did not address the differential diagnosis between PAs and DLGNTs in this peculiar location. Our study retrospectively examined a cohort of 28 children with LGGs and glioneuronal intramedullary tumours using detailed radiological, clinico-pathological and molecular analysis. 25% of spinal PAs were reclassified as DLGNTs. PA and DLGNT are nearly indistinguishable in histopathology or neuroradiology. 83% of spinal DLGNTs presented first without leptomeningeal contrast enhancement. Unsupervised t-distributed stochastic neighbor embedding (t-SNE) analysis of DNA methylation profiles showed that spinal PAs formed a unique methylation cluster distinct from reference midline and posterior fossa PAs, whereas spinal DLGNTs clustered with reference DLGNT cohort. FGFR1 alterations were found in 36% of spinal tumours and were restricted to PAs. Spinal PAs affected significantly younger patients (median age 2 years old) than DLGNTs (median age 8.2 years old). Progression-free survival was similar among the two groups. In this location, histopathology and radiology are of limited interest, but molecular data (methyloma, 1p and FGFR1 status) represent important tools differentiating these two mitogen-activated protein kinase (MAPK) altered tumour types, PA and DLGNT. Thus, these molecular alterations should systematically be explored in this type of tumour in a spinal location. [ABSTRACT FROM AUTHOR]

This immunoreactivity is also present in the tumor cells of another neuronal tumor, the MVNT [[3]], which are considered to be neuronal progenitor elements. Case #2: left temporal lobe tumor involving the white matter and the cortex (e, f) showing partial contrast enhancement in the deep part of the tumor (g) and heterogeneous diffusion (restricted in the enhancing portion, increased in the non-enhancing part) (h). All three cases were initially diagnosed as CNS neuroblastoma, I FOXR2 i -activated because of clinical (children with supratentorial tumors), morphological (ganglion-like cells and neurocytic differentiation with signs of malignancy and the co-expression of Olig2 and synaptophysin), and genetic (gain of chromosome 1q in one of our cases) overlaps [[9]]. Among them, three (21%) represent new tumor types [the diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters, the myxoid glioneuronal tumor, and the multinodular and vacuolating neuronal tumor (MVNT)], illustrating the increasing characterization of this group of neoplasms [[5]]. [Extracted from the article]

1:CAS:528:DC%2BC1cXpsV2hu7k%3D. 10.1007/s00401-018-1865-4 6 Navarro RE, Golub D, Hill T, McQuinn MW, William C, Zagzag D. Pediatric midline H3K27M-mutant tumor with disseminated leptomeningeal disease and glioneuronal features: case report and literature review. Gliomas with concomitant mutations of H3K27M and I BRAF/FGFR1 i are supposed to be associated with a better prognosis than other DMG, H3K27-altered according to some publications [[7]]. Arguing for this hypothesis, a previously published monothalamic tumor classified as ganglioglioma, H3K27M- and I BRAF i V600E-mutant presented secondary leptomeningeal dissemination 7 years after the initial diagnosis [[10]]. [Extracted from the article]

Aim: Rosette‐forming glioneuronal tumour (RGNT) is a rare central nervous system (CNS) World Health Organization (WHO) grade 1 brain neoplasm. According to the WHO 2021, essential diagnostic criteria are a 'biphasic histomorphology with neurocytic and a glial component, and uniform neurocytes forming rosettes and/or perivascular pseudorosettes associated with synaptophysin expression' and/or DNA methylation profile of RGNT whereas 'FGFR1 mutation with co‐occurring PIK3CA and/or NF1 mutation' are desirable criteria. Material and methods: We report a series of 46 cases fulfilling the essential pathological diagnostic criteria for RGNT. FGFR1 and PIK3CA hotspot mutations were searched for by multiplexed digital PCR in all cases, whereas DNA methylation profiling and/or PIK3R1 and NF1 alterations were analysed in a subset of cases. Results: Three groups were observed. The first one included 21 intracranial midline tumours demonstrating FGFR1 mutation associated with PIK3CA or PIK3R1 (n = 19) or NF1 (n = 1) or PIK3CA and NF1 (n = 1) mutation. By DNA methylation profiling, eight cases were classified as RGNT (they demonstrated FGFR1 and PIK3CA or PIK3R1 mutations). Group 2 comprised 11 cases associated with one single FGFR1 mutation. Group 3 included six cases classified as low‐grade glioma (LGG) other than RGNT (one‐sixth showed FGFR1 mutation and one a FGFR1 and NF1 mutation) and eight cases without FGFR1 mutation. Groups 2 and 3 were enriched in lateral and spinal cases. Conclusions: We suggest adding FGFR1 mutation and intracranial midline location as essential diagnostic criteria. When DNA methylation profiling is not available, a RGNT diagnosis remains certain in cases demonstrating characteristic pathological features and FGFR1 mutation associated with either PIK3CA or PIK3R1 mutation. [ABSTRACT FROM AUTHOR]

The article presents case studies of patients who developed paediatric glial and glioneuronal tumours due to BRAF V600E and H3F3A K27M mutations. The first patient had a large tumour in the pons and cerebellar hemisphere, the second patient had a large pineal tumour while the third patient had a glioma located in the brainstem.

Primary sinonasal intestinal-type adenocarcinomas (ITAC) are defined on the basis of their morphological similarities to colorectal adenocarcinomas (CRA). Thus, differential diagnosis with sinonasal metastasis of CRA could be a real challenge. Neuroendocrine differentiation has been variably described in several types of adenocarcinomas and notably in ITACs and CRAs. In a series of 25 ITACs and 25 lymph node metastasis of CRAs (nmCRA), we analysed neuroendocrine differentiation by immunohistochemistry with antichromogranin A and synaptophysin antibodies. Neuroendocrine differentiation (chromogranin A and/or synaptophysin positivity) was significantly different (p=0.0002) in ITACs (72%) and in nmCRAs (20%). In conclusion, presence of neuroendocrine cells seems more in favour of a sinonasal intestinal-type adenocarcinoma, than metastatic CRA. This immunohistochemical study could be useful in difficult cases and should be an interesting complement in a clinical discussion. [ABSTRACT FROM AUTHOR]

Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations). To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively. At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD. Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD. [ABSTRACT FROM AUTHOR]

Cytologic pleomorphism has been described in a limited number of benign pineal tumors, namely pineocytoma (PC) and pineal parenchymal tumors (PPTs) of intermediate differentiation (PPTID). We examined the clinicopathologic features in a retrospective series of 14 cases (seven females and seven males aged from 10 to 65 years) of pleomorphic PPT. Seven cases were PC, with no mitoses and with areas of tumoral cells forming large pineocytomatous rosettes and other areas with giant cells containing hyperchromatic nuclei. The other seven were PPTID, presenting few mitoses (≤2), a Ki67 proliferation index between 3% and 7%, and predominantly composed of small neoplastic cells and scattered giant cells, sometimes multinucleated. In the 14 tumors, the proportion of pleomorphic areas was variable. Most tumoral cells showed extensive neuronal differentiation with strong expression of neuron-specific enolase, synaptophysin and neurofilaments. Some of the neoplastic cells expressed S100 protein. The follow-up period ranged from 1.2 to 13 years and only one PC and one PPTID progressed after stereotactic biopsy or incomplete resection. The lack of invasiveness and the low proliferation index of these tumors suggest a benign clinical course despite the marked pleomorphism, the latter of which can lead to upgrading. [ABSTRACT FROM AUTHOR]