Rhabdoid phenotype and loss of SMARCB1 expression in a brain tumor are characteristic features of atypical teratoid/rhabdoid tumors (ATRT). Rare non-rhabdoid brain tumors showing cribriform growth pattern and SMARCB1 loss have been designated cribriform neuroepithelial tumor (CRINET). Small case series suggest that CRINETs may have a relatively favorable prognosis. However, the long-term outcome is unclear and it remains uncertain whether CRINET represents a distinct entity or a variant of ATRT. Therefore, 10 CRINETs were clinically and molecularly characterized and compared with 10 ATRTs of each of three recently described molecular subgroups (i.e. ATRT-TYR, ATRT-SHH and ATRT-MYC) using Illumina Infinium HumanMethylation450 arrays, FISH, MLPA, and sequencing. Furthermore, outcome was compared to a larger cohort of 27 children with ATRT-TYR. Median age of the 6 boys and 4 girls harboring a CRINET was 20 months. On histopathological examination, all CRINETs demonstrated a cribriform growth pattern and distinct tyrosinase staining. On unsupervised cluster analysis of methylation data, all CRINETs examined exclusively clustered within the ATRT-TYR molecular subgroup. As ATRT-TYR, CRINETs mainly showed large heterozygous 22q deletions (9/10) and SMARCB1 mutations of the other allele. In two patients, SMARCB1 mutations were also present in the germline. Estimated mean overall survival in patients with CRINETs was 125 months (95% confidence interval 100-151 months) as compared to only 53 (33-74) months in patients with ATRTs of the ATRT-TYR subgroup (Log-Rank P < 0.05). In conclusion, CRINET represents a SMARCB1-deficient non-rhabdoid tumor, which shares molecular similarities with the ATRT-TYR subgroup but has distinct histopathological features and favorable long-term outcome.

2nd Department of Pediatrics Semmelweis University Budapest Hungary

Clinical Cooperation Unit Neuropathology German Cancer Research Center Heidelberg Germany

Department of Laboratory Medicine and Pathology Division of Anatomical Pathology Neuropathology Specialty Group University of Alberta Edmonton Canada

Department of Laboratory Medicine and Pathology Princess Margaret Cancer Centre University Health Network Toronto Canada

Department of Neuropathology Burdenko Neurosurgical Institute Moscow Russia

Department of Neuropathology University Hospital Heidelberg Heidelberg Germany

Department of Pathology and Laboratory Medicine Nationwide Children's Hospital and Department of Pathology and Division of Anatomy Ohio State University Columbus OH

Department of Pathology Keimyung University Dongsan Medical Center Daegu Korea

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 Germany

Department of Pediatric Oncology and Hematology University Hospital Heidelberg Heidelberg Germany

Department of Pediatric Oncology Oslo University Hospital Oslo Norway

Division of Molecular Genetics German Cancer Research Center Heidelberg Germany

Division of Pathology The Hospital for Sick Children Toronto Canada

Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany

German Cancer Consortium Core Center Heidelberg Heidelberg Germany

Institute of Human Genetics University Ulm Ulm Germany

Institute of Neuropathology University Hospital Münster Münster Germany

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

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