Background:
Medulloblastoma is a rare embryonal tumor of the cerebellum with an estimated incidence of 0.5 cases per million per year in adults. Patient age and presence of metastases at diagnosis, histological variant, molecular sub-grouping and treatment related sequalae lead to varying survival and quality of life outcomes.
Case Presentation:
A 39-year-old male presented to his GP with progressively worsening occurrences of morning dizzy spells, nausea and vomiting, lethargy and increasing unsteadiness. He is married with two children. He has no other comorbidities or significant medical history.
Investigations:
Magnetic resonance imaging reported a large solid and cystic 4th ventricle mass measuring 37 x 33 x 37mm with surrounding vasogenic oedema in the right cerebellar hemisphere. Histopathology reported a grade 4 medulloblastoma of desmoplastic/nodular sub-type with focal severe anaplasia. Immunohistochemistry confirms SHH pathway activated disease with abnormal p53 expression indicating possible TP53-mutation. Whole spine magnetic resonance imaging showed generalized superficial chord involvement diffusely with larger deposits posteriorly at C6/7 and subtle deposits in the cauda equina region. Cerebrospinal fluid examination showed atypical cells.
Treatment:
Maximal tumor resection was followed by craniospinal radiation with a radiation boost to the tumor bed, posterior fossa and leptomeningeal spread sites. High dose chemotherapy using St Jude hospital SJMB-12 protocol containing cisplatin, vincristine and cyclophosphamide was administered through four cycles. A dose intense regimen with stem cell rescue was utilized, with metastases at diagnosis and likely TP53 mutation indicating high relapse risk. Targeted maintenance therapy was employed through use of the SHH pathway inhibitor sonidegib.
Discussion:
Targeted therapy is a promising treatment option for SHH-activated medulloblastoma however drug access is limited due to cost and availability. Tumor rarity and disease heterogeneity has limited clinical trial utilization to define optimal therapy. Recent imaging has shown disease resolution with no signs of tumor recurrence for this patient.