MBCL-40. UNFAVORABLE CLINICAL COURSE OF A WNT-ACTIVATED MEDULLOBLASTOMA. Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Haberler, Christine; Peyrl, Andreas; Czech, Thomas; Kool, Marcel; Slavc, Irene
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i125
• Page End: i126
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.436
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Prognostic risk factors in medulloblastomas currently comprise extent of resection, M-staging at diagnosis, histopathological subtype and genetic aberrations (MYC/N status, CTNNB1 mutation). The majority of medulloblastomas with WNT activation (WNT-MB) are characterized by CTNNB1 mutation and associated with a particular good prognosis in children up to 16 years of age. Tumor recurrence and death of disease are exceptional in children having WNT-MB, therefore they are considered as low risk tumors and treated with a decreased chemotherapy protocol in the European PNET5 therapy trial. We report a female patient from Georgia who presented at the age of 9 years with a cerebellar midline tumor. The tumor was completely resected and diagnosed as medulloblastoma. She was treated with RTX and CTX. 5 years after diagnosis a local recurrence occurred and a reoperation was performed. Histopathology revealed a classic medulloblastoma, a CTNNB1 mutation was detected by Sanger sequencing and WNT subgroup confirmed by methylation array. Re-evaluation of the primary tumor confirmed the diagnosis of a classic medulloblastoma, however no CTNNB1 mutation could be detected. Despite gross total resection of the recurrence followed by antiangiogenic metronomic treatment the tumor progressed after one year, and the patient succumbed to her disease. Postmortem analysis revealed a highly anaplastic medulloblastoma with focal myogenic differentiation (medullomyoblastoma) and CTNNB1 mutation. In conclusion, the absence of a detectable CTNNB1 mutation in the primary tumor could indicate its presence only in a small subclone and shows that a WNT-MB with a classic subtype may occasionally evolve into a highly anaplastic MB.