Discussion
To our knowledge, there have not been an published cases reporting the presence of secondary anaplastic medulloblastomas in the pediatric population.
There is another screening protocol for patients with LFS, which recommend annual whole body MRI and brain MRI’s (at 6 months interval), but recommend blood tests every 3-4 months15,16. We followed the LEAD program guidelines, which recommend blood tests, urine tests, and physical exam every 6 months, since it is logistically more feasible to patients and parents10,11. The frequency of visits would not have led to earlier detection of our patient’s secondary medulloblastoma as he was asymptomatic and the frequency of obtaining MRI of brain is similar in the two programs.
Several imaging features of medulloblastomas are helpful in diagnosing the primary tumor and determining its molecular status. Medulloblastomas result in decreased ADC values and hyperintensity on diffusion MRI images13. On T2-weighted images, medulloblastomas can demonstrate heterogenous intensity or isointensity to gray matter (Fig. 1)17. Furthermore, tumor locations are associated with molecular group as SHH tumors are primarily located in the cerebellar periphery which corresponded with a positive predictive value of 94.7%12.
Neuropathological evaluation showed histologic features consistent with large cell/ anaplastic medulloblastoma. Next Generation Sequencing identified genomic alterations that confirmed the diagnosis of SHH-activated anaplastic medulloblastoma14. Additional testing revealed that the tumor was positive for YAP-1 and GAB-1, which further confirmed the diagnosis and ruled out osteosarcoma since osteosarcomas do not express YAP-1 and GAB-1.
The purpose of presenting this case is two-fold: first, to present the previously unreported finding of secondary anaplastic medulloblastoma in a LFS patient and secondly, to emphasize the importance of appropriate cancer surveillance in LFS patients and their families.
Cancer screening for LFS is extremely delicate and complicated as imaging modalities should not include ionizing radiation as these would increase the risk of cancer in the LFS population. Per a prospective and a subsequent 11-year follow-up observational study by Villani et al, the 5 year survival rate of individuals who underwent this screening protocol was 88.8% whereas those who did not undergo screening had 5 year survival rate of 59.6%15, 16.
Although our patient, his mother, and younger brother underwent screening as per LEAD protocol, all three succumbed to their respective malignancies in a short time while his step brother remains cancer free. It is important to emphasize genetic testing in family members of patient’s with LFS and the continued use of a robust screening regimen such as the LEAD program to identify any additional cancers at the earliest stage.
Conflicts of Interest: none
Acknowledgements: none