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.