Embryonal Malignant Neuroepithelial Tumors of the Cerebellum with No Neuroblastic Differentiation: Medulloblastoma Variant or Different Entity?
Benjamin Ellezam, Vidya Mehta, Girard R Courteau, Adekunle M Adesina. Texas Children's Hospital, Baylor College of Medicine, Houston
Background: Medulloblastomas are embryonal small blue cell tumors with predominantly neuroblastic differentiation. Distinction from small cell variants of other tumor types is dependent on immunophenotype and ultrastructural characteristics. A minor subset of embryonal malignant neuroepithelial tumors occur in the cerebellum and show no demonstrable neuroblastic, glial or epithelial differentiation. These tumors remain poorly characterized and their relationship to classic medulloblastoma and variants in terms of tumor biology and prognosis is unclear.
Design: Surgical pathology records of patients operated at Texas Children's Hospital between 1995 and 2010 were searched for embryonal cerebellar tumors with small cell morphology. Medulloepitheliomas, small cell glioblastomas and ATRTs were not included in this study. Malignant embryonal neuroepithelial tumors with no evidence of neuroblastic differentiation by histology, immunohistochemistry and electron microscopy were identifed and processed for additional molecular studies as well as review of outcome. Analysis for copy number aberrations were done by array CGH and FISH. Results were compared to those previously reported for medulloblastoma and other embryonal cerebellar tumors.
Results: A total of 98 small blue cell cerebellar tumors were identified with only 2 cases meeting the defined criteria for undifferentiated malignant embryonal neuroepithelial tumors. Treatment included gross total resection of primary tumor, followed by chemotherapy and craniospinal radiation therapy, as per protocol for standard high-risk medulloblastomas. FISH analysis did not reveal amplification of C-MYC, N-MYC, EGFR or OTX2. No deletion of INI1/HSNF5 locus or monosomy 22 was identified. Array CGH revealed multiple loci and gene-specific copy number aberrations that did not mimic those previously described for medulloblastoma. No isochromosome 17q was identified. In spite of dissemination at presentation, one patient is alive and well after four years and the other has only had a soft tissue surgical site recurrence which was successfully excised one year after initial surgery.
Conclusions: Cerebellar embryonal malignant neuroepithelial tumors with no neuroblastic differentiation show differing molecular signatures from those of medulloblastoma with implications for possible differing tumor biology and prognosis.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 236, Tuesday Afternoon