49 research outputs found
Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions
Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors
Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature
Pediatric neoplasms in the central nervous system (CNS) show extensive clinical and molecular heterogeneity and are fundamentally different from those occurring in adults. Molecular genetic testing contributes to accurate diagnosis and enables an optimal clinical management of affected children. Here, we investigated a rare, molecularly distinct type of pediatric high-grade neuroepithelial tumor (n = 18), that was identified through unsupervised visualization of genome-wide DNA methylation array data, together with copy number profiling, targeted next-generation DNA sequencing, and RNA transcriptome sequencing. DNA and/or RNA sequencing revealed recurrent fusions involving the capicua transcriptional repressor (CIC) gene in 10/10 tumor samples analyzed, with the most common fusion being CIC::LEUTX (n = 9). In addition, a CIC::NUTM1 fusion was detected in one of the tumors. Apart from the detected fusion events, no additional oncogenic alteration was identified in these tumors. The histopathological review demonstrated a morphologically heterogeneous group of high-grade neuroepithelial tumors with positive immunostaining for markers of glial differentiation in combination with weak and focal expression of synaptophysin, CD56 and CD99. All tumors were located in the supratentorial compartment, occurred during childhood (median age 8.5 years) and typically showed early relapses. In summary, we expand the spectrum of pediatric-type tumors of the CNS by reporting a previously uncharacterized group of rare high-grade neuroepithelial tumors that share a common DNA methylation signature and recurrent gene fusions involving the transcriptional repressor CIC. Downstream functional consequences of the fusion protein CIC::LEUTX and potential therapeutic implications need to be further investigated
Une localisation parotidienne bilatérale d’un carcinome épithélial myoépithélial
International audienceWe report the case of a 52-year-old man, who was admitted in the department of otorhinolaryngology for a mass of the right parotid gland. The radiological and clinical hypothesis was a squamous cell carcinoma. Histopathological examination revealed a biphasic proliferation composed of epithelial cells arranged in a tubular pattern stained with cytokeratins 5-6 and 7 and EMA surrounded by clear myoepithelial cells stained with smooth muscle actin and p63. Ki-67 labeling index was low. The diagnosis of epithelial myoepithelial carcinoma was proposed. One year after, the patient noticed a centimetric mass of the left parotid gland. The radiological hypothesis was the presence of an intraparotidian lymph node. Histopathological examination showed a second epithelial myoepithelial carcinoma. This is an uncommon neoplasm comprising approximately 1% of all salivary gland tumours, affecting mainly the parotid gland. It is occurring preferably in patients older than 60years old. This is a low-grade malignant tumour with tendency to local recurrence and lymph node metastatic potential. We describe an exceptional bilateral epithelial myoepithelial carcinoma of the parotid gland
La classification de l’OMS 2021 des tumeurs du système nerveux central
Rapid technical advances in molecular biology allowed for the identification of key genetic alterations in central nervous system (CNS) tumors. Our ever-expanding knowledge of brain tumor genetics and the development of new technologies, such as DNA-methylation profiling, required an update of the 2016 fourth edition of the WHO classification of CNS tumors. Updates were regularly published by the Consortium to Inform Molecular Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (c-IMPACT-NOW) until the publication of the fifth edition of the WHO classification of CNS tumors in 2021. In that edition, new types and subtypes are introduced and criteria for histo-molecular diagnostic and grading are refined, especially for diffuse gliomas. The definition of a broad category "diffuse glioma, pediatric subtype" (low or high grade) is a major improvement of the classification. Moreover, the nomenclature was simplified and aligned with that of other blue books. The 2021 edition truly advances the role of molecular diagnostics in CNS tumor classification. Methyloma profiling may become a cornerstone of CNS tumor diagnostic. The new WHO classification will lead to better management of brain tumor patients
Gliome de bas grade avec altération de MYBL1 : observation d’une nouvelle entité tumorale pédiatrique
International audienceDiffuse gliomas with MYB or MYBL1 alterations are rare tumours mostly affecting children or young adults with long-term epilepsy. This category of glioma includes two morphological subtypes. The angiocentric subtype is characterized by an angiocentric pattern of growth and a frequent MYB:QKI fusion. The isomorphic subtype corresponds to a highly differentiated astrocytic glioma with low cellularity, low proliferation and no specific microscopic features. The diagnosis is based on the imaging, demonstrating a supratentorial tumor, associated with the confirmation of a MYB or MYBL1 rearrangement. Here, we report the case of a 7-year-old child who presented a right frontal brain lesion corresponding to an isomorphic diffuse glioma with MYBL1 alteration
Multifocal cutaneous phaeohyphomycosis caused by Paraconiothyrium cyclothyrioides in an immunocompromised patient: A case report
International audienc
Refinement of diagnostic criteria for pediatric-type diffuse high-grade glioma, IDH- and H3-wildtype, MYCN-subtype including histopathology, TP53, MYCN and ID2 status
NF2 and ZFTA evaluation in the diagnostic algorithm of pediatric posterior fossa ependymoma with H3K27ME3 retained expression
International audienc