Background
Myxopapillary ependymomas (MPE) are slow growing glial neoplasms,
corresponding to a Grade I designation per the 2016 WHO Classification
of CNS Tumors. MPEs typically arise in the conus medullaris, cauda
equine, and filum terminale, and account for the majority of
intramedullary tumors in this region.1 MPEs have been
noted to arise in other locations, including the cervical or thoracic
spinal cord, the fourth and lateral ventricles, brain parenchyma, and
less commonly subcutaneously in the sacrococcygeal or presacral
regions.1 Overall, MPEs represent 9-13% of all
ependymomas.1 Although rare, distant metastasis and
brain parenchymal metastasis has been reported in both adult and
pediatric patients.2
MPEs arise in both the adult and pediatric patients, with an average of
36 years of age at presentation.1 The presenting
symptom is often chronic back pain.1 Although WHO
Grade I classification implies an indolent clinical course and good
prognosis, it has been documented that pediatric cases may behave more
aggressively, with a higher rate of disease recurrence, even after gross
total resection. 1-2 Additionally, pediatric patients
demonstrate higher rates of treatment failure, and often present with
disseminated disease. 1-5 It has been suggested that
age is the strongest predictor of recurrence and overall prognosis.1 Additional adverse predictors of prognosis include
surgical treatment alone and subtotal resection. 6Indication for adjuvant therapy in pediatric patients with disseminated
disease at diagnosis remains unclear, although a recent study evaluating
18 pediatric patients suggested improvement in local control of disease
with post-surgical radiation. 7
Molecularly, MPEs are characterized by polyploidy, with gains in various
chromosomes. 1 In particular, copy number alterations
in chromosome 7 have been described. 8 Other studies
have suggested overexpression in HOXB13 , NEFL , andPDGFRA . 9 One study has suggested that MPEs may
have a “Warburg” metabolic phenotype, i.e. elevated glycolysis and
possible accumulation of lactate, due to increased protein expression ofHIF-1α, HK2, PDK1 , and phosphorylation of PDHE1A .10 Studies have demonstrated a distinct DNA
methylation profile for MPEs, with chromosomal gains and losses across
large regions. 11
To date, 13 pediatric MPEs have been reported in the literature to show
“anaplastic features”, including necrosis, microvascular
proliferation, an elevated Ki-67 labeling index, and increased mitotic
activity (≥5 mitoses per 10 high-power fields). 12-17However, there currently are no consensus criteria for classifying MPEs
as histologically anaplastic and more importantly, clear treatment
guidelines for this sub-group. Here, we present our institutional
experience with pediatric MPEs, with detailed evaluation of their
clinical and pathological features, and chromosomal microarray analysis,
in order to help identify features associated with adverse outcomes
among this patient population.