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.

Department of Neuropathology Institute of Pathology Hannover Medical School

Department of Neurosurgery International Neuroscience Institute Hannover Germany

Department of Pediatric Hematology and Oncology University Hospital Motol Charles University 2nd Medical School Prague Czech Republic

Department of Pediatric Hematology and Oncology University Medical Center Hamburg Eppendorf Hamburg

Division of Pediatric Neuro oncology German Cancer Research Center Heidelberg

Gerhard Domagk Institute of Pathology University Hospital Münster Münster

Hopp Children's Cancer Center

Institute of Human Genetics University of Ulm and Ulm University Hospital Ulm

Institute of Neuropathology

Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands

Swabian Childrens' Cancer Center University Childrens' Hospital Augsburg and EU RHAB Registry Augsburg

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