gms | German Medical Science

Objective: Recent reports on medulloblastoma (MB) in adults suggest different risk stratification based on biological findings as well as prognostic expectations. We intend to illustrate that this seemingly rare entity requires new clinical trials to establish the prognostic impact and expected clinical outcome for adult patients with MB based on molecular investigations.

Methods: Neuropathological analysis of the tumor samples included conventional stains, immunohistochemistry and genome-wide DNA methylation profiling using an 850k Illumina EPIC array and classified by the DKFZ brain tumor classifier. Clinical records were examined concerning age at diagnosis, clinical symptoms, MRI-studies, surgical procedures and adjuvant therapy.

Results: We show the data of 5 adults diagnosed with MB in 2019 at our medical center. The median age at diagnosis was 38.2 years. The main clinical feature was hydrocephalus in all cases, headache, nausea, gait disturbance and walking disorder. MRI scans revealed a tumor in the posterior fossa, in one case associated meningeosis and spinal metastasis. All patients underwent surgery. Gross total resection was performed in 4 patients, in one patient only a stereotactic biopsy seemed reasonable. Histology showed 3 cases of sonic hedgehog (SHH), all of desmoplastic subtype, whereof 2 indicated TP53 wt and 2 cases of wingless (WNT) MB with just one TP53 wt. None of the tumors showed N-MYC or C-MYC gene amplification. The MGMT Promoter was found unmethylated in all cases. All patients receive adjuvant radiochemotherapy accordingly NOA 07 with slight individualized modification after stem cell mobilization in 4 cases.

Conclusion: These cases of MB in adults correspond to the adult MB series reported to date but display an epigenetic profile differing from the widely understood childhood counterparts. Moreover, these cases illustrate that the development of detailed molecular analyses and the molecular understanding of rare entities provided nowadays enable detailed planning and coordination of upfront clinical trials to evaluate treatment options particularly in respect to chemotherapy regimen.