ID #855 Pineal Region Group 3/4 Medulloblastoma: Ectopic Disease or a Distinct Molecular Entity?
Omar Chamdine, Giles Robinson, Brent Orr, Soniya Pinto, Paul Klimo, Paul Northcott, Dana TlaisAbstract
Background
Medulloblastoma (MB) is an embryonal tumor (ET) that arises in the posterior fossa (PF). It is molecularly classified into four groups (WNT-activated, SHH-activated, groups 3 and 4) which correlate with tumor biology, anatomic location, and outcome. Pineoblastoma (PB) is a distinct ET originating in the pineal gland with unique molecular characteristics. Here, we report 3 cases of pineal tumors that classified as Group 3/4 MB by methylation profiling.
Case Reports
The patients were male infants aged 12, 13, and 45 months at diagnosis. Clinical presentation included developmental regression, gait disturbance, head tilt, and increased intracranial pressure. Brain magnetic resonance imaging demonstrated hypercellular pineal tumors with obstructive hydrocephalus. None of the patients had evidence of metastatic disease. Diagnostic surgeries consisted of a biopsy in case 1 and a subtotal resection in case 3. Case 2 started treatment without histologic confirmation and subsequently underwent near total resection after 2 cycles of neoadjuvant chemotherapy. Histologically, cases 1 and 3 were classified as ET, whereas case 2 was classified as pineal parenchymal tumor. None of the cases displayed anaplastic features, MYC or MYCN amplification. The tumors classified as MB in the Group 3 and Group 4 family, subgroup 3, with high confidence scores (>0.96). All cases are receiving therapy as per our institutional MB guidelines.
Discussion
Here, we report 3 cases of Group 3/Group 4 MB diagnosed in the pineal region. With the increasing integration of methylation profiling into routine diagnostic practice, it is anticipated that additional cases will be identified. These findings raise important questions: are these tumors ectopic MB, a molecularly overlapping subtype of PB, or a distinct ET entity with epigenetic similarity to MB? The distinction is critical, as tumor classification influences therapeutic decision making, risk stratification, and prognostication. Further studies incorporating larger cohorts are required to address these questions and define the best approach to management.