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.