ATRT-07. Low-grade diffusely infiltrative tumor, SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC

Autor: Christian Thomas, Aniello Federico, Susanne Bens, Mats Hellström, Olivera Casar-Borota, Uwe Kordes, Julia E Neumann, Matthias Dottermusch, Fausto E Rodriguez, Andrea C Lo, Sylvia Cheng, Glenda Hendson, Juliette Hukin, Christian Hartmann, Arend Koch, David Capper, Reiner Siebert, Werner Paulus, Karolina Nemes, Pascal D Johann, Michael C Frühwald, Marcel Kool, Martin Hasselblatt
Rok vydání: 2022
Předmět:
Zdroj: Neuro-Oncology. 24:i3-i4
ISSN: 1523-5866
1522-8517
DOI: 10.1093/neuonc/noac079.006
Popis: Most atypical teratoid/rhabdoid tumors (ATRTs) occur in infants, but children and adolescents may also be affected. ATRTs occurring in older patients often comprise the molecular subgroup ATRT-MYC. Recently, central nervous system low-grade diffusely infiltrative tumor with INI1 deficiency (CNS LGDIT-INI1) has been described as a rare low-grade lesion (Nobusawa et al. Am J Surg Pathol 2020;44:1459-1468). Little is known on the molecular relationship of CNS LGDIT-INI1 and ATRT. We therefore further explored a series of six CNS LGDIT-INI1. The median age of the four males and two females was 16 years (range: 10-28 years). All tumors were of supratentorial location and showed low to moderate cellularity, diffuse growth of inconspicuous small SMARCB1-deficient tumor cells and reactive pleomorphic neuronal and glial cells with retained SMARCB1-staining in the background. In addition, two cases also displayed a high-grade rhabdoid component. After DNA isolation, purification and bisulfite conversion, samples were subjected to DNA methylation profiling (MethylationEPIC BeadChip array). Using DNA methylation-based classification and the Heidelberg Brain Tumor Classifier (version v11b4), all tumors were classified as ATRT-MYC (median calibrated score: 0.97). On t-SNE analysis, DNA methylation profiles grouped closely together in proximity to ATRT-MYC. Follow-up information was available for four cases (including the two cases with a high-grade component). Patients received heterogeneous treatments (including chemotherapy according to AT/RT protocols) and experienced stable disease or complete remission after an observation time of three to 56 months. In conclusion, CNS LGDIT-INI1 is a clinically and histologically distinct entity with relatively favorable outcome. Nevertheless, epigenetic similarity with ATRT-MYC and the potential of malignant progression warrants close follow-up examinations. In line with recent developments of WHO nomenclature, we propose to refer to these tumors as “low-grade diffusely infiltrative tumor, SMARCB1-mutant”.
Databáze: OpenAIRE
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