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.