Atrt-02. an infantile pineal embryonal tumor showing pathological features of a cns ganglioneuroblastoma in addition to smarca4 mutations and the methylation profiling of an atypical teratoid/rhabdoid tumor

Abstract Embryonal central nervous system tumors require genetic and epigenetic molecular analyses for further classification owing to the pathological, clinical, and molecular heterogeneity among these tumors. Here, we report a case of an infantile pineal tumor showing the pathological features of a CNS ganglioneuroblastoma; however, the specimen also contained SMARCA4 mutations and a methylation signature that is close to an atypical teratoid/rhabdoid tumor. A 2-year-old girl was referred to our hospital because of headache and dizziness presented with a pineal tumor and obstructive hydrocephalus. Radiologically, a large calcification was observed in the mass on head CT. The patient underwent tumor resection, and the pathological diagnosis was CNS ganglioneuroblastoma at that time. The specimen contained a variety of tumor cells, including undifferentiated embryonal cells, neurocytic cells, and ganglion cells embedded in a fibrillary matrix. The patient has been well for 5 years since they received multiagent chemotherapy and local proton irradiation. Subsequent genome-wide DNA methylation analysis revealed that the tumor was molecularly close to a sonic-hedgehog pathway-activated atypical teratoid/rhabdoid tumor. Genetic analysis also revealed SMARCA4 alterations in the splicing region of exons 10 and 34. This report indicates that genetic and epigenetic molecular approaches may facilitate elucidation of the clinical heterogeneity of CNS embryonal tumors, particularly the pathological appearance of CNS ganglioneuroblastomas.