Discussion
The vast majority of cases of synchronous and metachronous brain tumors
occurred in adults. There are many reported cases in the literature as
early as the 19th century2.
Histopathologically, the vast majority are constituted of meningiomas
and astrocytomas and are more common in patients with known underlying
genetic syndromes or after radiation therapy for previous brain
tumors3. We performed a comprehensive literature
review and identified a total of twelve pediatric cases with
synchronous/ metachronous brain tumors (table 1).
The origin of gliomas remains a matter of investigation. Evidence from
mouse models of glioma and human clinical data have provided some clues
about proposed cell types in initiating oncogenic mutations that drive
gliomagenesis. Some suggested neural stem cells, progenitor cells or
differentiated progeny as the cell of origin of different glioma
subtypes. The cell of origin is thought to be of neuroglial in lineage
and differs from the “brain tumor stem cells” which initiates tumor
formation and helps tumor survival and virulence.4 The
link between these cell types is still not discovered. In our patients
the presence of synchronous/ metachronous brain tumors may support this
former theory of a common stem cell of origin of gliomas. These stem
cells may migrate to different brain locations and thrive in a different
microenvironment leading to a specific type of
glioma4. Cohnheim suggested that embryonic residual
cells could evolve into different primary brain lesions5.
In this report, we describe two rare cases of children with multiple
brain tumors exhibiting different histologic subtypes and occurring
simultaneously in the same patient. To the best of our knowledge,
case#1 is the first report of a child with both, a ST anaplastic EPN
and a cerebellar PA. One study reported a case of an 8-month-old girl
suffering from a frontal lobe ependymoma in association with a
cerebellopontine angle meningioma without any genetic predisposition3. Upon review of the adult literature, two cases of
concurrent meningiomas and EPN were detected 6,7.
While MT is frequent in adults (accounting for 50-90% of high grade
glioma cases)8,9 it is rare in children. The long-term
risk of MT in children is estimated to be less than 10%
(2.9-10%).1,10 Although our second patient did not
have histologic confirmation at diagnosis, the clinical and radiologic
pictures highly suggested that the original tumor in the left frontal
lobe was a LGG that later underwent MT.
Genetic predisposition syndromes tend to be linked to the histogenesis
of different intra axial and extra-axial tumors, hence increases the
risk of simultaneous neoplasms 11. Previous RT
exposure also predisposes to the occurrence of different primary tumors
within the same individual 12,13, but is otherwise
rare 3,14. Five out of the 12 reported pediatric cases
(41.6%) developed the second tumor 6 to 21 years following RT to the
first tumor. RT was focal in 2 cases, craniospinal in 2 cases, and whole
brain in 1 case 3,5,15–20. Case#1 did not have a
genetic predisposition syndrome and both cases were not exposed to
either radiation of chemotherapy at the time of diagnosis.
Outcome of relapsed anaplastic EPN is unfavorable. Available treatment
options include surgical resection and/ or RT (focal or craniospinal).
Chemotherapy is usually ineffective21. We elected to
treat our patient with metronomic therapy based on a published
experience. 22 Up to date, the tumor growth of this
tumor is well controlled. Therapy resulted in a significant decrease in
the tumor vascularity, thus facilitating gross total resection without
major morbidity. Although the risk of recurrence is high, the patient
remains alive and has regained her baseline quality of life.
Conclusion
Histopathologic analysis and molecular interrogation of each lesion in
synchronous and or metachronous brain tumors is highly recommended. This
will enable the oncologists to offer individualized and tailored therapy
and avoid under or over treatment. A high index of suspicion should be
present for genetic predisposition in such cases.