Differential patterns of metastatic dissemination across medulloblastoma subgroups

OBJECTIVE Metastatic dissemination is a major treatment challenge and cause of death in patients with medulloblastoma. However, the influence of molecular biology on the pattern of metastatic dissemination at diagnosis is not known. In this study, the authors sought to define the location, pattern, and imaging characteristics of medulloblastoma metastases across subgroups at diagnosis. METHODS A consecutive cohort of patients with metastatic medulloblastoma at The Hospital for Sick Children and the University Hospital Motol, who underwent up-front MRI of the craniospinal axis, was assembled and allocated to subgroups using NanoString limited gene-expression profiling. Radiological characteristics (including location, morphology, size, diffusion restriction, and contrast enhancement) were discerned through a retrospective review. RESULTS Forty metastatic medulloblastomas were identified with up-front neuroimaging of the craniospinal axis: 5 sonic hedgehog (SHH), 16 Group 3, and 19 Group 4 metastases. Significant subgroup-specific differences were observed, particularly with respect to tumor location, size, and morphology. Group 3 metastases were most frequently laminar compared with a more nodular pattern in Group 4 (14 of 16 in Group 3 vs 8 of 19 in Group 4; p = 0.0004). Laminar metastases were not observed in patients with SHH medulloblastoma. Suprasellar metastases are highly specific to Group 4 (p = 0.016). Two of the 5 SHH cases had multifocal lesions in the cerebellum, raising the possibility that these were in fact synchronous primary tumors and not true metastases. A minority of patients with Group 4 metastases harbored metastatic deposits that did not enhance on MRI after contrast administration, often in patients whose primary tumor did not enhance. CONCLUSIONS The location, morphology, and imaging characteristics of metastatic medulloblastoma differ across molecular subgroups, with implications for diagnosis and management. This suggests that the biology of leptomeningeal dissemination differs among medulloblastoma subgroups.