Atypical Teratoid/Rhabdoid Tumor (AT/RT) With Molecular Features of Pleomorphic Xanthoastrocytoma

TY - JOUR

T1 - Atypical Teratoid/Rhabdoid Tumor (AT/RT) With Molecular Features of Pleomorphic Xanthoastrocytoma

AU - Thomas, Christian

AU - Federico, Aniello

AU - Sill, Martin

AU - Bens, Susanne

AU - Oyen, Florian

AU - Nemes, Karolina

AU - Johann, Pascal D

AU - Hartmann, Christian

AU - Hartmann, Wolfgang

AU - Sumerauer, David

AU - Paterno, Vincenzo

AU - Samii, Amir

AU - Kordes, Uwe

AU - Siebert, Reiner

AU - Frühwald, Michael C

AU - Paulus, Werner

AU - Kool, Marcel

AU - Hasselblatt, Martin

N1 - Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system tumor predominantly occurring in infants that may also arise in older children and adults. Rare secondary AT/RT developing from other tumors such as pleomorphic xanthoastrocytoma (PXA) are on record, but AT/RT presenting with molecular features of PXA have not been described. Here, we report 3 malignant central nervous system tumors in children (10, 13, and 18 y old). All tumors were located in the temporal lobe. In 2 cases, there was no history of a low-grade precursor lesion; in 1 case anaplastic PXA had been diagnosed 3 months earlier. Histopathologically, all tumors were composed of RT cells and showed frank signs of malignancy as well as loss of nuclear SMARCB1/INI1 protein expression. Two cases displayed homozygous deletions of the SMARCB1 region while the third case showed an exon 7 mutation (c.849_850delGT; p.Met283Ilefs*77). Of note, DNA methylation profiles did not group with AT/RT or other tumor entities using the Heidelberg Brain Tumor Classifier (version v11b4). By unsupervised t-distributed stochastic neighbor embedding analysis and hierarchical clustering analysis, however, all tumors clearly grouped with PXA. Genome-wide copy number analysis revealed homozygous CDNK2A/B deletions and gains of whole chromosome 7. BRAF V600E mutations could be demonstrated in all cases. In conclusion, the possibility of AT/RT with molecular features of PXA needs to be taken into account and warrants molecular characterization of AT/RT especially in older children. Since treatments targeting mutated BRAF are available, identification of such cases may also have therapeutic consequences.

AB - Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system tumor predominantly occurring in infants that may also arise in older children and adults. Rare secondary AT/RT developing from other tumors such as pleomorphic xanthoastrocytoma (PXA) are on record, but AT/RT presenting with molecular features of PXA have not been described. Here, we report 3 malignant central nervous system tumors in children (10, 13, and 18 y old). All tumors were located in the temporal lobe. In 2 cases, there was no history of a low-grade precursor lesion; in 1 case anaplastic PXA had been diagnosed 3 months earlier. Histopathologically, all tumors were composed of RT cells and showed frank signs of malignancy as well as loss of nuclear SMARCB1/INI1 protein expression. Two cases displayed homozygous deletions of the SMARCB1 region while the third case showed an exon 7 mutation (c.849_850delGT; p.Met283Ilefs*77). Of note, DNA methylation profiles did not group with AT/RT or other tumor entities using the Heidelberg Brain Tumor Classifier (version v11b4). By unsupervised t-distributed stochastic neighbor embedding analysis and hierarchical clustering analysis, however, all tumors clearly grouped with PXA. Genome-wide copy number analysis revealed homozygous CDNK2A/B deletions and gains of whole chromosome 7. BRAF V600E mutations could be demonstrated in all cases. In conclusion, the possibility of AT/RT with molecular features of PXA needs to be taken into account and warrants molecular characterization of AT/RT especially in older children. Since treatments targeting mutated BRAF are available, identification of such cases may also have therapeutic consequences.

KW - Adolescent

KW - Astrocytoma/genetics

KW - Brain Neoplasms/genetics

KW - Child

KW - Female

KW - Humans

KW - Mutation

KW - Proto-Oncogene Proteins B-raf/genetics

KW - Rhabdoid Tumor/genetics

KW - SMARCB1 Protein/genetics

KW - Teratoma/genetics

U2 - 10.1097/PAS.0000000000001694

DO - 10.1097/PAS.0000000000001694

M3 - SCORING: Journal article

C2 - 33739782

VL - 45

SP - 1228

EP - 1234

JO - AM J SURG PATHOL

JF - AM J SURG PATHOL

SN - 0147-5185

IS - 9

ER -