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