LAUSR

Medulloblastoma (MB) is the most common malignant central nervous system (CNS) cancer diagnosed in childhood and is divided into four subtypes: WNT-activated, SHH-activated, Group 3 (Non-WNT, Non-SHH), and Group 4 (Non-WNT, Non-SHH). Non-WNT/Non-SHH make up roughly two-thirds of MB and have the least understood pathogenesis with substantial intratumoral heterogeneity. Therapeutic targets and treatment strategies for Group 3 and 4 patients therefore remain unclear. In this report we present a 16-year-old patient with standard risk Group 4 medulloblastoma and multiple midline defects. The patient’s medical history was remarkable for a cleft lip (which healed in utero), a notable heart murmur, an inguinal hernia repair at 3 months of age, and significant pectus excavatum. This patient was diagnosed at age 12 with a MB. Tumor cells were negative for GAB-1, p53 stain was positive for approximately 1–2% of tumor cells, no evidence on monosomy 6, MYC or MYCN amplification. The family history is significant for paternal biliary cancer. The patient was treated as per ACNS0331 and is approximately 36 months off-therapy. This case presents an interesting instance of a CNS tumor arising within the microenvironment of wide-spread dysregulated development. Single cases do not provide any substantiative evidence. However, they do give insight on factors which may drive oncogenesis and may provide an indication as to whether we should continue to pursue targeted therapy for Group 3/4 uniformly or move towards personalized therapy strategies in this group patients.