Discussion
Myxopapillary ependymomas are rare in children. Though MPEs are WHO Grade 1 tumors and are thought to have an indolent course, the natural history of these tumors as well as the management remains unpredictable and unclear in the pediatric population.
Reduced H3K27me3 expression has been described in pediatric posterior fossa “Group A” ependymomas. 19 The retained expression of H3K27me3 in all cases of this series suggests that this is likely not a driver mechanism in the tumorigenesis of myxopapillary ependymomas. The molecular basis of pediatric MPE behavior remains to be determined.
The copy number gains observed in the cases tested in our series indicate chromosomal instability (CIN). CIN is a feature of myxopapillary ependymomas, for which the oncogenic driver is currently unknown. 19 The pattern of copy number gain in these specimens suggests intermediate ploidy, which has been seen in myxopapillary ependymomas, as well as in posterior fossa “Group B” ependymoma, which harbor large genomic aberrations.20-22 The prognostic significance of these alterations in myxopapillary ependymoma remains to be determined.
There is no clear treatment consensus for the management of pediatric MPEs with anaplastic features. Surgery remains the mainstay of treatment with adjuvant radiation therapy a consideration in some clinical situations. Moreover, the management of pediatric MPEs showing increased mitotic activity and presence of necrosis is even less studied.
A Surveillance, Epidemiology, and End Results (SEER) database study that looked at 122 cases of primary spinal MPE in the pediatric population (ages 21 years and under) showed patients who received gross total resection (GTR, surgery alone) had a 5-year overall survival rate of 100 %, while those who received subtotal resection (STR) plus radiation had a 5-year overall survival of 91 %, suggesting GTR whenever feasible is the best treatment option. This study did not have information on presence/absence of ‘anaplastic features’. 6
A large pediatric MPE study which included 18 patients showed patients with disseminated disease trended towards inferior event free survival (EFS) compared to those with localized disease. Nine patients had disseminated disease. Three of the 18 patients who did not undergo a gross total resection received radiation at diagnosis (of which one patient had disseminated disease). No patient received adjuvant chemotherapy at diagnosis. Though the study had patients with atypical histopathologic features including vascular proliferation, atypia and necrosis, the association of these features with dissemination, management and outcomes was not elucidated in this study. Also, the small number of patients that received adjuvant radiation therapy precluded any further analysis. 7
To date, there are 13 cases of pediatric myxopapillary ependymomas (MPE) with “anaplastic features” described in the literature.12-17 Our study adds 5 additional cases with increased mitotic activity, 3 of which also demonstrated necrosis. Among the three patients with both increased mitotic activity and necrosis, two had disseminated disease and had disease recurrence. Our findings are similar to previous studies that demonstrated more aggressive clinical behavior, particularly in pediatric patients, when at least 2 of the following criteria suggesting anaplasia: ≥5 mitoses per 10 HPF, Ki-67 labeling index of >10%, necrosis, and microvascular proliferation were present. 14 Similar to our cohort, with the previous 12 pediatric cases reported, the primary treatment modality was surgical resection. In some patients, radiation therapy was administered either at diagnosis if the patients presented with disseminated disease or at first recurrence. 12-17
Our findings and available literature suggests that in pediatric patients with MPE, the concurrent presence of elevated mitotic activity and necrosis may be associated with a more aggressive clinical course and may help identify patients at higher risk for recurrence and progression. Although prior to our cohort there were only 13 cases reported in the literature, given that we identified 5 additional patients in our cohort suggests that there may be underreporting or lack of recognition of the clinical importance of these histologic features. Patients with such findings may warrant closer surveillance, as well as consideration of adjuvant therapies such as radiation, especially in the setting of disseminated disease at presentation.
Further studies including more cases of MPE with these features are needed to help create management guidelines in the subset of patients that demonstrate anaplastic features.